Glomerular C3 receptors in human renal disease.
The relationship between glomerular C3 receptor activity and intraglomerular C3 deposition was studied in 73 cases of various forms of renal disease. C3 receptor activity was measured by enumeration of complement-coated sheep red blood cells (IgM EAC) that adhered to glomeruli in frozen sections and expressed as a percentage of the mean number present in control kidneys. Adjacent sections were studied for the presence and distribution of C3 deposits. The precise location of corresponding dense deposits was determined through 1-mu sections or electron micrographs. Marked depression of C3 receptor activity was found in most cases in which there was accumulation of C3 along the glomerular basement membrane, irrespective of whether the deposits were in a subepithelial, intramembranous, or subendothelial location. In contrast, when C3 was not detectable or was found exclusively in the mesangium, C3 receptor activity was affected only moderately, if at all. These data are consistent with the hypothesis that the interaction of C3 with podocytes is a major determinant in the loss of C3 receptor activity in glomerular disease, but do not exclude the possibility that interaction with mesangial or endothelial cells may also influence C3 receptor activity.


The CBS-H2S axis promotes liver metastasis of colon cancer by upregulating VEGF through AP-1 activation.
The main therapy for colon cancer with liver metastasis is chemotherapy based on 5-fluorouracil combined with targeted drugs. However, acquired drug resistance and severe adverse reactions limit patients' benefit from standard chemotherapy. Here, we investigate the involvement of endogenous hydrogen sulfide (H2S) in liver metastasis of colon cancer and its potential value as a novel therapeutic target. We used the CRISPR/Cas9 system to knockdown CBS gene expression in colon cancer cell lines. PCR arrays and proteome arrays were applied to detect the transcription and protein expression levels, respectively, of angiogenesis-related genes after knockdown. The molecular mechanism was investigated by western blot analysis, RT-qPCR, immunofluorescence staining, ChIP assays and dual-luciferase reporter assays. A liver metastasis mouse model was adopted to investigate the effect of targeting CBS on tumour metastasis in vivo. Knockdown of CBS decreased the metastasis and invasion of colon cancer cells and inhibited angiogenesis both in vivo and in vitro. Tissue microarray analysis showed a positive correlation between CBS and VEGF expression in colon cancer tissues. Further analysis at the molecular level validated a positive feedback loop between the CBS-H2S axis and VEGF. Endogenous H2S promotes angiogenesis and metastasis in colon cancer, and targeting the positive feedback loop between the CBS-H2S axis and VEGF can effectively intervene in liver metastasis of colon cancer.


Lead content in household paints in India.
Lead and its compounds are used in paints not only to impart colour but also to make it durable, corrosion resistant and to improve drying. Adverse health impacts of lead especially on children have led countries to restrict or ban its use in paints. While U.S. and other developed countries instituted measures to limit the use of lead in paints, some developing countries including India have failed to regulate their lead content. The present study was undertaken to determine the levels of lead in new latex (water-based) and enamel paints (oil-based) intended for residential use in India. A total of 69 paint samples (38 latex and 31 enamel samples) from six of the most popular brands were analysed for lead concentrations. While all latex paint samples contained low levels of lead, (i.e., well below 600 ppm as regulated by United States' Consumer Products Safety Commission) the enamel paint samples of all but one brand contained significant concentrations of lead, ranging up to 140,000 ppm. In fact 84% of the enamel paints tested exceeded 600 ppm whereas only 38 % of all samples (including latex and enamel types) exceeded this regulatory level.


Effects of ginsenoside Rg1 on postimplantation rat and mouse embryos cultured in vitro.
GRg1 is one of the most important active agents extracted from ginseng. Although there are numerous reports in the medical literature concerning the beneficial effects of GRg1, little is known about its effects on embryonic development. In our study, whole embryo culture was applied to explore the effects of GRg1 on SD rat and ICR mouse embryos during their critical period of organogenesis. All embryos were exposed to different concentrations of GRg1, and scored for their growth and differentiation at the end of the 48-h culture period. Total morphological score decreased significantly at the concentration of GRg1 of 50 microg/ml to mice and at 30 microg/ml to rats. The whole embryonic growth was affected, represented as reduced crown-rump length and head length, and decreased number of somites from 10 microg/ml both in mice and rats. Morphological development was influenced relatively late. To rats, the scores of flexion, forelimb bud and hindlimb bud were significantly reduced at 30 microg/ml, and heart was among the affected organs. However, the effect on heart was not observed in mice, and flexion and limb buds were influenced at 50 microg/ml. These results demonstrate that GRg1 has embryotoxicity during both rat and mouse organogenetic period and rats might be more sensitive than mice. We suggest that pregnant women of first trimester should use ginseng with caution before the exact conclusion is obtained.


Simple scoring system for prediction of mortality in Fournier's gangrene.
To create new scoring system for prediction of hospital mortality for patients with Fournier's gangrene(FG). In total, 84 patients with FG were enrolled into this study. The demographic and clinical characteristics of patients were analyzed retrospectively. The mortality rate was 11.9 %. On multivariate analyses, age >60 years, BUN >40 mg/dl, RDW >14.95 %, albumin level <20 mg/dl and presence of sepsis were significant and independent predictors of mortality. The predictive value of our score for mortality was 95.1 %. Our scoring system shows adequate discriminatory function for prediction of mortality in patients with FG. Further larger scale studies can improve the performance of our score.


Comparative efficacy of ciprofloxacin, ceftazidime and gentamicin, given alone or in combination, in a model of experimental septicemia due to Klebsiella pneumoniae in neutropenic mice.
The therapeutic efficacy of ciprofloxacin, used alone and in combination with either ceftazidime or gentamicin, was evaluated in a model of experimental Klebsiella pneumoniae septicemia in neutropenic mice. Therapeutic results were compared to those achieved by treatment with ceftazidime or gentamicin alone, as well as their combination. Infections were induced by i.v. injection of two strains of K. pneumoniae. Therapy with i.m. antibiotics was performed in 8 h intervals for a total of 13 doses, and survival rates were recorded at the end of treatment as well as seven days later. Ciprofloxacin alone proved to be significantly more effective than ceftazidime and gentamicin, producing survival rates similar to the combination of ceftazidime plus gentamicin. Bacterial counts of spleens and blood confirmed the superior bactericidal activity of ciprofloxacin. Except for the combination of ciprofloxacin with ceftazidime, there was no apparent advantage of combinations of ciprofloxacin with the other agents compared to ciprofloxacin alone. These data suggest a high in vivo activity of ciprofloxacin in systemic infection due to K. pneumoniae.


Study of the evolution of acute phase reactants and of thromboxane and prostacyclin during calcium pyrophosphate-induced pleurisy in the rat.
By using a clearly defined model of acute inflammation in rats, CaPP-induced pleurisy, we compared the evolution of four APR levels (Hp, HpX, alpha 2M, SAP) at a local and peripheral site. At the same time we studied thromboxane and prostacyclin concentrations in pleural exudate. The levels of APR have shown a progressive increase up to 24 h. For alpha 2M, Hp, HpX the increase in serum concentration was more rapid than in exudate, whereas the evolution of SAP level was parallel in the intra and extra-vascular compartments. On the other hand the levels of albumin and transferrin which are not APR remained constant in serum and also in exudate from 6 h to 24 h. Thromboxane and prostacyclin levels reached a peak during the first two hours of the inflammatory reaction followed by a rapid decreased. These prostanoids may be considered as early and transient mediators of acute inflammation, whereas the acute phase proteins studied have a more prolonged role in the inflammatory reaction.


Low miR-182-5p Expressing Extracellular Vesicles Derived From Human Bone Marrow Stromal Cells of Subjects With Steroid-Induced Osteonecrosis of the Femoral Head Aggravate Disease Progression.
Steroid-induced osteonecrosis of the femoral head (SONFH) is a refractory, progressive disease. However, the underlying mechanisms that aggravate femoral head necrosis remain unclear. Extracellular vesicles (EVs) act as molecular carriers in intercellular communication. We hypothesize that EVs derived from human (h) bone marrow stromal cells (BMSC) resident in SONFH lesion areas promote the pathogenesis of SONFH. In the present study, we determined the modulatory effects of SONFH-hBMSCs-derived EVs on the pathogenesis of SONFH in vitro and in vivo. We found that the expression of hsa-miR-182-5p was downregulated in SONFH-hBMSCs and EVs isolated from those hBMSCs. After tail vein injection, EVs isolated from hBMSCs transfected with hsa-miR-182-5p inhibitor aggravated femoral head necrosis in the SONFH mouse model. We conclude that miR-182-5p regulates bone turnover in the SONFH mouse model via targeting MYD88 and subsequent upregulation of RUNX2 expression. We further assume that EVs derived from hBMSCs resident in SONFH lesion areas aggravate femoral head necrosis by downregulating miR-182-5p secreted from hBMSC located outside these lesions. We suggest that miR-182-5p could provide a novel target for future therapeutic approaches to treat or prevent SONFH. © 2023 American Society for Bone and Mineral Research (ASBMR).


High-Resolution Genomic Profiling of Disseminated Tumor Cells in Prostate Cancer.
Circulating tumor cells and disseminated tumor cells (DTCs) are of great interest because they provide a minimally invasive window for assessing aspects of cancer biology, including tumor heterogeneity, a means to discover biomarkers of disease behavior, and a way to identify and prioritize therapeutic targets in the emerging era of precision oncology. However, the rarity of circulating tumor cells and DTCs poses a substantial challenge to the consistent success in analyzing their molecular features, including genomic aberrations. Herein, we describe optimized and robust methods to reproducibly detect genomic copy number alterations in samples of 2 to 40 cells after whole-genome amplification with the use of a high-resolution single-nuclear polymorphism-array platform and refined computational algorithms. We have determined the limit of detection for heterogeneity within a sample as 50% and also demonstrated success in analyzing single cells. We validated the genes in genomic regions that are frequently amplified or deleted by real-time quantitative PCR and nCounter copy number quantification. We further applied these methods to DTCs isolated from individuals with advanced prostate cancer to confirm their highly aberrant nature. We compared copy number alterations of DTCs with matched metastatic tumors isolated from the same individual to gain biological insight. These developments provide high-resolution genomic profiling of single and rare cell populations and should be applicable to a wide-range of sample sources.


Comparison of microbial communities during anaerobic digestion of kitchen waste: Effect of substrate sources and temperatures.
In this study, batch experiments were conducted to compare the effect of temperature and substrate source on microbial communities in the anaerobic digestion of kitchen waste. The results showed that the microbial communities of anaerobic digestion were not sensitive to varied sources of waste, but shifted with the change in operating temperatures. In the reactors operated at mesophilic conditions, Levilinea, Syntrophomonas, Methanothrix, and Methanosphaerula, etc. were the dominant microbes during the process. While in thermophilic reactors, Levilinea, Ornatilinea, Methanosphaerula and Methanomassiliicoccus, etc. prevailed. Meanwhile, an enrichment in Coprothermobacter, Defluviitoga, Defluviitalea, Tepidimicrobium, Lutispora and Fonticella were observed as the temperature changed from mesophilic to thermophilic, suggesting these genera could be selectively enriched at thermophilic conditions. The results provided fundamental understanding of the microbiology that could support the scale up of food waste anaerobic digestion.


Risk factors for postoperative sepsis in laparoscopic gastric bypass.
Postoperative sepsis is a rare but serious complication following elective surgery. The purpose of this study was to identify the rate of postoperative sepsis following elective laparoscopic gastric bypass (LGBP) and to identify patients' modifiable, preoperative risk factors. The American College of Surgeons National Surgical Quality Improvement Program database was queried from 2005 to 2013 for factors associated with the development of postoperative sepsis following elective LGBP. Patients who developed sepsis were compared to those who did not. Results were analyzed using the Chi-square test for categorical variables and Wilcoxon two-sample test for continuous variables. A multivariate logistic regression analysis was utilized to calculate adjusted odds ratios for factors contributing to sepsis. During the study period, 66,838 patients underwent LGBP. Of those, 546 patients developed postoperative sepsis (0.82%). The development of sepsis was associated with increased operative time (161 ± 77.8 vs. 135.10 ± 56.5 min; p < 0.0001) and a greater number of preoperative comorbidities, including diabetes (39.6 vs. 30.6%; p < 0.0001), hypertension requiring medication (65.2 vs. 54%; p < 0.0001), current tobacco use (16.7 vs. 11.5%; p = 0.0002), and increased pack-year history of smoking (8.6 ± 18.3 vs. 5.6 ± 14.2; p = 0.0006), and the Charlson Comorbidity Index (0.51 ± 0.74 vs. 0.35 ± 0.57, p < 0.0001). Sepsis resulted in an increased length of stay (10.1 ± 14.4 vs. 2.4 ± 4.8 days; p < 0.0001) and a 30 times greater chance of 30-day mortality (4.03 vs. 0.11%, p < 0.0001). Multivariate logistic regression analysis showed that current smokers had a 63% greater chance of developing sepsis compared to non-smokers, controlling for age, race, gender, BMI, and CCI score (OR 1.63, 95% CI 1.23-2.14; p = 0.0006). Laparoscopic gastric bypass is uncommonly associated with postoperative sepsis. When it occurs, it portends a 30 times increased risk of death. A patient history of diabetes, hypertension, and increasing pack-years of smoking portend an increased risk of sepsis. Current smoking status, a preoperative modifiable risk factor, is independently associated with the chance of postoperative sepsis. Preoperative patient optimization and risk reduction should be a priority for elective surgery, and patients should be encouraged to stop smoking prior to gastric bypass.


Improving the validity of global ratings.
To examine the effects of behavior sampling on global ratings, four groups of 10 teachers each received varying amounts of observation training, practice, and feedback. Teachers viewed a series of seven videotapes depicting two, boys whose percentage of distractible behavior was systematically manipulated. Ratings of distractibility were obtained for each taped vignette. Results showed that teachers who received observation training and who routinely collected data in their own classroom submitted ratings which corresponded to actual levels of distractible behavior. Teachers who received no training, or who were trained but did not practice, submitted ratings that were significantly less accurate.


Expression of dentin matrix protein 1 in tumors causing oncogenic osteomalacia.
Oncogenic osteomalacia, which is characterized by renal phosphate wasting, low serum 1, 25-dihydroxyvitamin D, and osteomalacia, is caused by mesenchymal neoplasms that are termed phosphaturic mesenchymal tumors (PMTs). As PMTs are usually small and lack specific histological features, the pathological identification of PMTs is difficult. Dentin matrix protein 1 (DMP1) is an acidic phosphoprotein expressed in mineralized tissues including bone, tooth, and hypertrophic cartilage. Increased expression of DMP1 gene in PMTs has been reported by using differential cDNA screening. In the present study, DMP1 expression in PMTs and other soft tissue tumors was analyzed immunohistochemically to verify its utility in the differential diagnosis of PMTs. Anti-DMP1 polyclonal antibody was raised against the C-terminal sequence of DMP1. Three cases with PMTs and 11 other soft tissue tumors (two malignant hemangiopericytomas, three solitary fibrous tumors, three synovial sarcomas, and three malignant peripheral nerve sheath tumors) were analyzed for DMP1 expression. DMP1 expression was observed in all of the three cases with PMTs, but never found in other soft tissue tumors examined. DMP1 was detected in the extracellular matrix with myxomatous features or around capillary vessels, and in dystrophic calcified sites. Paranuclear DMP1 staining in the tumor cells was also observed. These findings indicate that DMP1 immunohistochemistry is a useful tool for identifying PMTs.


A ferrofluidic hydrophobic deep eutectic solvent for the extraction of doxycycline from urine, blood plasma and milk samples prior to its determination by high-performance liquid chromatography-ultraviolet.
The ferrofluid phase was prepared according to mixing magnetic nanoparticle and the hydrophobic deep eutectic solvent as a green microextraction solvent. This new composite was applied for vortex-assisted dispersive liquid-liquid microextraction (VA-HDES-ferrofluid-DLLME) of doxycycline (DOC) residual extraction and determined through high-performance liquid chromatography-ultraviolet (HPLC-UV). The characterization of magnetic nanoparticle was investigated by XRD, TEM and FESEM. The dependency of DOC microextraction to main variables and their interaction and find optimum points were undertaken using response surface methodology with either central composite design (CCD). Thus, the optimum pH, ionic strength, ferrofluid volume and vortex time for DOC extraction are determined to be 3.0, 4%w/v, 150 μL and 7 min, respectively. According to this condition, linear response is found to be greater than 10-400 ng mL-1, with a correlation coefficient of 0.983. The detection and quantification limits are 3.6 and 8.5 ng mL-1, while the repeatability and reproducibility as precision criteria (RSD%) are 3.74% and 4.15%, respectively. The DOC recoveries in all of the urine, blood plasma and milk samples are between 86.70 and 97.48%, with RSD% lower than 5.72%.


Malignant pericardial effusion as a primary manifestation of metastatic colon cancer: a case report.
Pericardial neoplastic involvement is rarely related to primary tumors of the pericardium and is most often caused by spread from other primary sites, such as lung and breast carcinomas, hematological malignancies (lymphoma and leukemia), and melanoma. Although pericardial metastasis from infradiaphragmatic tumors (such as colon cancers) are rare and poorly described in literature, any neoplasm has the potential to metastasize to the pericardium and heart by either contiguity, lymphatic, or hematological spread. A 44-year-old previously healthy male Causasian patient had a sudden onset of dyspnea and wheezing. During investigation with echocardiogram, computed tomography and repeated pericardiocentesis, the cause of malignant pericardial effusion was confirmed as primary manifestation of metastatic colon cancer. The patient was treated with appropriate chemotherapy and presented satisfactory disease control. This report emphasizes the importance of considering the diagnostic hypothesis of occult neoplasia in a patient with pericardial effusion.


Assessment of calcinosis in Portuguese patients with systemic sclerosis - a multicenter study.
The study aims to define the clinical and subclinical calcinosis prevalence, the sensitivity of radiographed site and clinical method for its diagnosis, and the phenotype of Portuguese systemic sclerosis (SSc) patients with calcinosis. A cross-sectional multicenter study was conducted with SSc patients fulfilling Leroy/Medsger 2001 or ACR/EULAR 2013 classification criteria, registered in the Reuma.pt. Calcinosis was assessed through clinical examination and radiographs of hands, elbows, knees, and feet. Independent parametric or non-parametric tests, multivariate logistic regression, and sensitivity calculation of radiographed site and clinical method for calcinosis detection were performed. We included 226 patients. Clinical calcinosis was described in 63 (28.1%) and radiological calcinosis in 91 (40.3%) patients, of which 37 (40.7%) were subclinical. The most sensitive location to detect calcinosis was the hand (74.7%). Sensitivity of the clinical method was 58.2%. Calcinosis patients were more often female (p = 0.008) and older (p < 0.001) and had more frequently longer disease duration (p < 0.001), limited SSc (p = 0.017), telangiectasia (p = 0.039), digital ulcers (p = 0.001), esophageal (p < 0.001) and intestinal (p = 0.003) involvements, osteoporosis (p = 0.028), and late capillaroscopic pattern (p < 0.001). In multivariate analysis, digital ulcers (OR 2.63, 95% CI 1.02-6.78, p = 0.045) predicted overall calcinosis, esophageal involvement (OR 3.52, 95% CI 1.28-9.67, p = 0.015) and osteoporosis (OR 4.1, 95% CI 1.2-14.2, p = 0.027) predicted hand calcinosis, and late capillaroscopic pattern (OR 7.6, 95% CI 1.7-34.9, p = 0.009) predicted knee calcinosis. Anti-nuclear antibody positivity was associated with less knee calcinosis (OR 0.021, 95% CI 0.001-0477, p = 0.015). Subclinical calcinosis high prevalence suggests that calcinosis is underdiagnosed and radiographic screening might be relevant. Multifactorial pathogenesis may explain calcinosis predictors' variability. Key Points • Prevalence of subclinical calcinosis in SSc patients is substantial. • Hand radiographs are more sensitive to detect calcinosis than other locations or clinical method. • Digital ulcers were associated with overall calcinosis, esophageal involvement and osteoporosis were associated with hand calcinosis, and late sclerodermic pattern in nailfold capillaroscopy was associated with knee calcinosis. • Anti-nuclear antibody positivity may be a protective factor for knee calcinosis.


Hemostasis in Orbital Surgery.
This article highlights the major vascular supply of the orbit and structures supplied by these vessels. Key anatomic principles are then reviewed as they pertain to endoscopic orbital surgery in order to avoid serious orbital hemorrhages. Next, preoperative planning and patient education are outlined as well as description of orbital compartment syndrome. This is followed by discussion of various techniques for managing orbital hemorrhage in the intraoperative and postoperative setting.


A contemporary cost analysis of postoperative morbidity after coronary artery bypass grafting with and without concomitant aortic valve replacement to improve patient quality and cost-effective care.
The financial burden of postoperative morbidity after cardiac operations remains ill defined. This study evaluated the costs associated with the performance of coronary artery bypass grafting (CABG) with and without aortic valve replacement (AVR) and determined the incremental costs associated with major postoperative complications. A total of 65,534 regional patients undergoing CABG (n = 55,167) ± AVR (n = 10,367) were evaluated from 2001 to 2011. Patient-related, hospital-related, and procedure-related cost data were analyzed by use of Medicare-based cost reports. Hierarchical multivariable regression modeling was used to estimate risk-adjusted incremental cost differences in postoperative complications. The mean age was 64 years, and women accounted for 31% of patients. CABG + AVR patients had higher rates of overall complication (40% vs 35%, p < 0.001) and operative mortality (5% vs 3%, p < 0.001) than did CABG patients. CABG + AVR patients also accrued increased median postoperative lengths of stay (7 vs 5 days, p < 0.001) and total costs ($26,527 vs $24,475, p < 0.001). After mortality risk adjustment, significant positive relationships existed between total costs and major postoperative complications. Interestingly, the highest incremental costs among CABG patients included newly instituted hemodialysis ($71,833), deep sternal wound infection ($56,003), and pneumonia ($50,025). Among CABG + AVR patients, these complications along with perioperative myocardial infarction ($68,917) dominated costs. Postoperative complications after CABG ± AVR are associated with significantly increased incremental costs. The most costly complications include newly instituted hemodialysis, infectious complications, and perioperative myocardial infarction. Identification of the most common and the most costly complications provides opportunities to target improvement in patient quality and the delivery of cost-effective care.


Acute osteomyelitis of index finger caused by dog bite.
A forty-seven-year-old man was bitten by a dog on his left index finger. Despite initial antibiotic treatment, he developed acute osteomyelitis of the middle phalanx over the next three weeks. Pasteurella multocida and Bacteroides were isolated from the necrotic bone. Subsequently the infection was successfully treated by debridement and Tetracycline.


The biomechanical design of a walking appliance for a paraplegic adult.
One of the major requirements of the medical consultant treating paraplegic patients is to have them upright for at least a few hours a day associated, if possible with some physical exercise. This paper deals with the construction and operation of an appliance which makes this possible.


Neonatal near miss and mortality and associated factors: cohort study of births in the city of Rio de Janeiro, RJ, Brazil.
The aim of this study was to investigate factors associated with neonatal near miss and mortality of the live birth cohort in the city of Rio de Janeiro, Brazil, in 2015. Population-based retrospective cohort of live births (LB) of single pregnancy with 0-27 days of follow-up. Data were obtained from the Brazilian Live Birth and Mortality Information Systems. Logistic regressions with the analytical strategy of hierarchical determination were used for cases of near miss and deaths separately. The cohort was composed of 85,850 LB. For every one thousand LB, about 16 were cases of near miss and six died. Maternal level of education, skin color, and age and adequacy of prenatal care were associated with neonatal near miss; for deaths, presentation of LB at delivery, birth weight, gestational age, and five-minute Apgar score are added. Besides confirming the effect of low birth weight, prematurity, and asphyxia on neonatal death, socioeconomic vulnerability markers - low education level and brown or black skin colors - were associated with neonatal death and near miss. Absent or inadequate prenatal care showed a strong association with both outcomes, being stronger for neonatal death. Investments in the quality of prenatal care and reduction of disparities in health care are necessary in Rio de Janeiro.


A novel method of utilizing permeable reactive kiddle (PRK) for the remediation of acid mine drainage.
Numerous technologies have been developed and applied to remediate AMD, but each has specific drawbacks. To overcome the limitations of existing methods and improve their effectiveness, we propose a novel method utilizing permeable reactive kiddle (PRK). This manuscript explores the performance of the PRK method. In line with the concept of green technology, the PRK method recycles industrial waste, such as steel slag and waste cast iron. Our results demonstrate that the PRK method can be applied to remediate AMD under optimal operational conditions. Especially, this method allows for simple installation and cheap expenditure, compared with established technologies.


[Aspects of treatment of hypertrophic obstructive cardiomyopathy with emphasis on the role of percutaneous transluminal ablation of the myocardial septum].
The prevalence of hypertrophic cardiomyopathy is approximately 0.2% whereby the obstructive form accounts for one quarter. The basic treatment involves administration of negatively inotropic drugs (beta-blockers and/or verapamil), which reduce the intraventricular pressure gradient and have a positive impact on the symptomatology. In patients refractory or intolerant to medicamentous treatment surgical or catheterization is used. Percutaneous transluminal septal myocardial ablation reduces significantly the symptomatology of dyspnoea and stenocardia, increases load tolerance and improves the left ventricular diastolic function. In none of the mentioned therapeutic approaches so far a favourable effect on the prognosis of patients with a risk profile associated with hypertrophic obstructivel cardiomyopathy was proved.


Genetic analysis of the mitotic transmission of minichromosomes.
The fidelity of the mitotic transmission of minichromosomes in S. cerevisiae is monitored by a novel visual assay that allows one to detect changes in plasmid copy number in individual mitotic divisions. This assay is used to investigate the mitotic transmission of a plasmid containing a putative yeast origin of replication (ARS 1) and a centromere (CEN3). The rate of improper segregation for the minichromosome is 200-fold higher than observed for a normal chromosome. However, the replication of the minichromosome is stringently controlled; it overreplicates less than once per one thousand mitotic divisions. We also use this assay to isolate and characterize mutations in ARS 1 and CEN3. The mutations in ARS 1 define a new domain required for its optimal activity, and the mutations in CEN3 suggest that the integrity of element II is not essential for centromere function. Finally, the phenotypes of the mutations in ARS 1 and CEN3 are consistent with their function in replication and segregation, respectively.


Evaluation of morphogenic regulatory activity of farnesoic acid and its derivatives against Candida albicans dimorphism.
A series of farnesoic acid derivatives was prepared and their morphogenic regulatory activities were evaluated. Their inhibitory activities against yeast cell growth and yeast-to-hypha transition examined in Candida albicans cells are dependent upon the chain length as well as the substitution patterns on the isoprenoid template. The preliminary structure-activity relationship of these compounds is described to elucidate the essential structural requirements.


Tight and loose shapes in flat entangled dense polymers.
We investigate the effects of topological constraints (entanglements) on two-dimensional polymer loops in the dense phase, and at the collapse transition (theta-point). Previous studies have shown that in the dilute phase the entangled region becomes tight, and is thus localised on a small portion of the polymer. We find that the entropic force favouring tightness is considerably weaker in dense polymers. While the simple figure-eight structure, created by a single crossing in the polymer loop, localises weakly, the trefoil knot and all other prime knots are loosely spread out over the entire chain. In both the dense and theta conditions, the uncontracted-knot configuration is the most likely shape within a scaling analysis. By contrast, a strongly localised figure-eight is the most likely shape for dilute prime knots. Our findings are compared to recent simulations.


Effect of stress on fasting-induced ghrelin, orexin and galanin secretion in male rats fed different levels of their energy requirement.
Ghrelin, orexin, and galanin are orexigenic factors in rodents and humans which participate in adaptive response to weight loss. On the other hand, weight loss and fasting is accompanied by increased levels of epinephrine (Ep) and cortisol (Cor). In this study, we investigated the effects of Ep and Cor on fasting-induced ghrelin, orexin, and galanin secretion in rats fed different levels of their energy requirements. Forty five male Wistar rats (300-350 g, 15 per group) were fed a diet containing 100, 50, and 25% of their energy requirement for 10 days followed by 2 days of fasting. Animals were then anesthetized for carotid artery cannulation for injections and blood samplings. Rats received either 3 µg Ep/kg body weight (BW), 3 µg Cor/kg BW, or a combination of those two (0.1 mg in 1 ml of phosphate-buffered saline). Blood samples were collected before, 30, 60, and 120 min after injection. In normal and 50% food restricted groups, fasting ghrelin levels fell after Ep and combination of Ep and Cor injection (P ≤ 0.05), whereas, orexin were decreased by combination of Ep and Cor injection in rats fed 100% of their needs and Ep alone in rats fed 50%. Galanin just fell after combination of Ep and Cor injection in both starved (50%) and normal rats. In contrast, all groups whit 25% fed ad libitum did not response to any injections (P > 0.05). These results indicate that Ep suppresses starvation-induced secretion of ghrelin, orexin, and galanin in normal (100%) and starved (50%) rats and their response to Ep might be affected by weight loss.


[Birth of an IPA collective within a hospital].
Since 2020, the Charles-Perrens Hospital Center in Bordeaux has been supporting the implementation of advanced practice nursing. The formation of a group of five advanced practice nurses (APNs) has enabled the deployment of numerous missions consistent with the APN model. With a view to developing the nursing discipline and enriching the healthcare offer, they are developing direct clinical missions or missions addressed to professionals and the healthcare system. The collective represents a major lever for implementation, and allows this new professional identity to be positioned within the hospital institution.


A global increase in tree cover extends the growing season length as observed from satellite records.
Plant phenology provides information on the seasonal dynamics of plants, and changes herein are important for understanding the impact of climate change and human management on the biosphere. Land surface phenology is the study of plant phenology across large spatial scales estimated by satellite observations. However, satellite observations (pixels) are often composed of a mixture of vegetation types, like woody vegetation and herbaceous vegetation, having different phenological characteristics. Therefore, any changes in tree cover presumably impact land surface phenology, as trees usually have a different seasonal cycle compared to herbaceous vegetation. On the other hand, changes in land surface phenology are often interpreted as a result of climate change-induced impacts on the photosynthetic activity of vegetation. Therefore, it is important to better understand the role of changes in vegetation cover (here, the proportion between tree and short vegetation cover) in satellite-derived land surface phenology analysis. We studied the impact of changes in tree cover on satellite observed land surface phenology at a global scale over the past three decades. We found an extension of the growing season length in 36.6% of the areas where tree cover increased, whereas only 20.1% of the areas where tree cover decreased showed an increase in growing season length. Furthermore, the ratio between tree cover and short vegetation cover was found to affect changes in the length of the growing season, with the denser tree cover showing a more pronounced extension of the growing season length (especially in boreal forests). These results highlight the importance of changes in tree cover when analyzing the impact of climate change on vegetation phenology. Our study thereby addresses a critical knowledge gap for an improved understanding of changes in land surface phenology during recent decades in the context of climate and human-induced global land cover change.


Trigeminal and facial nerve involvement in Charcot-Marie-Tooth disease. An electrodiagnostic study.
The electrically and optically elicited orbicularis oculi reflex (OOR) and facial nerve latency were investigated in eight patients from three families. Each had autosomal dominant peroneal muscular atrophy. In a family with the dominantly inherited hypertrophic type markedly delayed latencies of the early reflex component of the OOR were found while the facial nerve had remained unaffected. These findings were interpreted as an indicator for supraorbital nerve involvement. In the other two investigated families of hypertrophic and neuronal type, a prolonged facial nerve latency was demonstrable. In these cases the latency of the optically evoked blink reflex was also delayed, while the latency of the early reflex component of the OOR was within normal limits or only slightly delayed. It is assumed that the different degree of cranial nerve involvement in these families is the expression of their genetically determined peculiarities.


Effect of different methods for decontaminating tooth enamel after contact with blood before bonding orthodontic buttons.
To evaluate the best method for decontaminating tooth enamel contaminated by contact with blood before bonding orthodontic buttons. The labial surfaces of 195 bovine incisors initially received prophylaxis, followed by 37% phosphoric acid etching, adhesive application, and light polymerization. After this, the labial surfaces of all teeth were contaminated with blood. The teeth were then randomly divided into 13 groups (n = 15), comprising the control group (treated according to the manufacturer's recommendations) and 12 experimental groups treated by the following decontamination methods: group 1, no decontamination; group 2, washing with distilled water; group 3, washing with physiologic solution; group 4, jets of air; group 5, gauze; group 6, cotton wool; group 7, distilled water plus jets of air; group 8, distilled water plus gauze; group 9, distilled water plus cotton wool; group 10, physiologic solution plus jets of air; group 11, physiologic solution plus gauze; and group 12, physiologic solution plus cotton wool. No statistical differences were shown between the control group and groups 4, 7, 10, and 11 (P > .05). The lowest bond strength values were shown in group 1, in which no decontamination was performed, and groups 6 and 12, which were decontaminated with cotton wool and physiologic solution plus cotton wool, respectively. The best method of decontaminating enamel contaminated with blood is washing with physiologic solution, followed by drying with jets of air and gauze or drying with jets of air only.


[Construction and evaluation of hepatitis C virus (HCV) DNA vaccine containing E2-gAD fusion gene].
To rational design HCV DNA vaccine candidates and evaluate their specific We design to construct two DNA vaccine candidates, one consists of immunity to HCV in mice. We design to construct two DNA vaccine candidates, one consists of E2 (the envelope glycoprotein 2 of HCV) gene only, the second consists of E2-gAD (Globular Domain of Human Adiponectin) fusion gene via overlapping PCR. Confirm the expression of the DNA vaccines by Western blotting, and then vaccinated by injection of DNA vaccines with gene electrotransfer (GET) in BALB/c mice. The immune response was measured by IFN-gamma ELISPOT. The DNA vaccine candidate consists of E2-gAD could effectively express in vitro , and it could induced a higher anti-HCV T cell response in mice than the one consists of E2 only. The HCV DNA vaccine consists of E2-gAD fusion can increase the immunity of the E, to some extend, and the research paved a way to develop and optimize the novel HCV DNA vaccine.


Sudden-onset trochlear nerve palsy: clinical characteristics and treatment implications.
To identify clinical characteristics, etiologies, and treatment implications of sudden-onset, acquired cases of superior oblique palsy. The medical records of patients diagnosed with trochlear nerve palsy between January 2010 and January 2018 were reviewed retrospectively to identify cases of acquired trochlear nerve palsy with a specific date of onset of acute symptoms or specific causative incident. Patients with congenital palsies or an uncertain date of onset, history of other strabismus, concomitant oculomotor or abducens nerve palsies, or history of strabismus surgery were excluded. Of 214 patients with superior oblique palsy, 23 had sudden-onset, acquired palsies. There were 14 cases of unilateral palsy and 9 cases of bilateral palsy. Patients with unilateral palsy presented with vertical diplopia, while those with bilateral palsy complained of either torsional (4/9 patients) or vertical (5/9 patients) diplopia. The most common etiologies were severe trauma associated with traumatic brain injury, followed by central nervous system neoplasm and stroke. Fifteen patients underwent surgical intervention, 3 of whom required more than one surgery. Patients with acute superior oblique palsy invariably complain of vertical and/or torsional diplopia. Neuroimaging should be considered in cases of acquired superior oblique palsy without a known traumatic cause. Bilateral cases of acquired superior oblique palsy are more challenging to manage surgically because of symptomatic torsional diplopia.


Life-threatening cryptosporidiosis in immunocompetent infants.
Cryptosporidium infection in immunocompetent patients has been described as a mild self-limiting diarrhoea. We describe two immunocompetent infants presented with life-threatening protracted diarrhoea. These two cases expand on the clinical spectrum of cryptosporidiosis in normal hosts.


Clinical Usefulness of an Echo-Doppler Model in Predicting Elevated Pulmonary Capillary Wedge Pressure in Patients With Heart Failure.
Although several tissue-Doppler imaging (TDI) models for pulmonary capillary wedge pressure (PCWP) estimation have been reported, their reliability remains uncertain. Our previous theoretical and experimental analyses suggest that right atrial pressure (RAP) corrected by tissue-Doppler imaging tricuspid/mitral annular peak systolic velocities (ST/SM) (RAP × ST/SM) reliably predicts elevated PCWP. We sought to investigate its clinical usefulness for predicting elevated PCWP in heart failure (HF) patients. Ninety-eight patients admitted with HF who underwent right heart catheterization were prospectively studied. RAP and PCWP were measured by right heart catheterization. Simultaneously, ST/SM, early diastolic transmitral flow velocity to mitral annular velocity ratio (E/Ea), and diameter of inferior vena cava at inspiration (IVCDi), a noninvasive surrogate for RAP, were measured by echocardiography. RAP correlated with IVCDi (R2 = 0.57). A significantly stronger correlation was observed between IVCDi corrected by ST/SM (IVCDi × ST/SM) and PCWP than between E/Ea and PCWP (R2 = 0.47 vs 0.18). Receiver-operating characteristic analyses indicated that IVCDi × ST/SM >16 mm predicted PCWP >18 mm Hg with 90% sensitivity and 77% specificity, and the area under the curve was 0.86, which was significantly larger than that of E/Ea (area under the curve=0.72). In conclusions, IVCDi × ST/SM is a new useful noninvasive model to predict elevated PCWP in HF patients.


Antibacterial activity and spectral studies of trivalent chromium, manganese, iron macrocyclic complexes derived from oxalyldihydrazide and glyoxal.
A new series of complexes is synthesized by template condensation of oxalyldihydrazide and glyoxal in methanolic medium in the presence of trivalent chromium, manganese and iron salts forming complexes of the type: [M(C(8)H(8)N(8)O(4))X]X(2) where M = Cr(III), Mn(III), Fe(III) and X = Cl(-1), NO(-1)(3), CH(3)COO(-1). The complexes have been characterized with the help of elemental analyses, conductance measurements, magnetic susceptibility measurements, electronic, NMR, infrared and far infrared spectral studies. On the basis of these studies, a five coordinate square pyramidal geometry for these complexes has been proposed. The biological activities of the metal complexes were tested in vitro against a number of pathogenic bacteria and some of the complexes exhibited remarkable antibacterial activities.


Quality of prostate carcinoma care in a statewide public assistance program.
The authors evaluated the feasibility of measuring quality of care in a statewide public assistance program for men with prostate carcinoma. The sample consisted of 84 men who were followed for > or = 6 months after receiving primary treatment for early-stage prostate carcinoma (55 received radical prostatectomy and 29 received radiotherapy) through a free public program for low-income, uninsured men. Quality was assessed by chart review with 16 indicators previously developed and validated at the RAND Corporation, as well as by telephone and mail surveys that included the University of California at Los Angeles Prostate Cancer Index short form. Quality of care measurement was feasible for 13 (81%) indicators from electronic chart abstraction, administrative documents, and patient questionnaires. Communication between specialist and primary physician was better for men treated with radiotherapy than with surgery (84% vs. 45%, P = 0.004). Subjects treated in private institutions were more likely than those treated in public institutions to have > or = 2 follow-up visits with the treating physician or institution within 1 year of treatment (93% vs. 63%, P = 0.003) and to have documentation of communication with the primary care physician (90% vs. 40%, P << 0.0001). Disease-specific, health-related quality of life 6 months after treatment did not appear to differ between public and private facilities. The authors found the application of quality of care indicators to be feasible in a statewide public assistance program, but with some differences between public and private providers. These quality of care indicators identified target areas for improvement.


Rhabdoid tumors in patients conceived following ART: is there an association?
In children affected by rhabdoid tumors (RT), are there clinical, therapeutic, and/or (epi-)genetic differences between those conceived following ART compared to those conceived without ART? We detected a significantly elevated female predominance, and a lower median age at diagnosis, of children with RT conceived following ART (RT_ART) as compared to other children with RT. Anecdotal evidence suggests an association of ART with RT. This was a multi-institutional retrospective survey. Children with RT conceived by ART were identified in our EU-RHAB database (n = 11/311 children diagnosed between January 2010 and January 2018) and outside the EU-RHAB database (n = 3) from nine different countries. A population-representative German EU-RHAB control cohort of children with RTs conceived without ART (n = 211) (EU-RHAB control cohort) during the same time period was used as a control cohort for clinical, therapeutic, and survival analyses. The median follow-up time was 11.5 months (range 0-120 months) for children with RT_ART and 18.5 months (range 0-153 months) for the EU-RHAB control cohort. We analyzed 14 children with RT_ART diagnosed from January 2010 to January 2018. We examined tumors and matching blood samples for SMARCB1 mutations and copy number alterations using FISH, multiplex ligation-dependent probe amplification, and DNA sequencing. DNA methylation profiling of tumor and/or blood samples was performed using DNA methylation arrays and compared to respective control cohorts of similar age (n = 53 tumors of children with RT conceived without ART, and n = 38 blood samples of children with no tumor born small for gestational age). The median age at diagnosis of 14 individuals with RT_ART was 9 months (range 0-66 months), significantly lower than the median age of patients with RT (n = 211) in the EU-RHAB control cohort (16 months (range 0-253), P = 0.03). A significant female predominance was observed in the RT_ART cohort (M:F ratio: 2:12 versus 116:95 in EU-RHAB control cohort, P = 0.004). Eight of 14 RT_ART patients were diagnosed with atypical teratoid rhabdoid tumor, three with extracranial, extrarenal malignant rhabdoid tumor, one with rhabdoid tumor of the kidney and two with synchronous tumors. The location of primary tumors did not differ significantly in the EU-RHAB control cohort (P = 0.27). Six of 14 RT_ART patients presented with metastases at diagnosis. Metastatic stage was not significantly different from that within the EU-RHAB control cohort (6/14 vs 88/211, P = 1). The incidence of pathogenic germline variants was five of the 12 tested RT_ART patients and, thus, not significantly different from the EU-RHAB control cohort (5/12 versus 36/183 tested, P = 0.35). The 5-year overall survival (OS) and event free survival (EFS) rates of RT_ART patients were 42.9 ± 13.2% and 21.4 ± 11%, respectively, and thus comparable to the EU-RHAB control cohort (OS 41.1 ± 3.5% and EFS 32.1 ± 3.3). We did not find other clinical, therapeutic, outcome factors distinguishing patients with RT_ART from children with RTs conceived without ART (EU-RHAB control cohort). DNA methylation analyses of 10 tumors (atypical teratoid RT = 6, extracranial, extrarenal malignant RT = 4) and six blood samples from RT_ART patients showed neither evidence of a general DNA methylation difference nor underlying imprinting defects, respectively, when compared to a control group (n = 53 RT samples of patients without ART, P = 0.51, n = 38 blood samples of patients born small for gestational age, P = 0.1205). RTs are very rare malignancies and our results are based on a small number of children with RT_ART. This cohort of patients with RT_ART demonstrated a marked female predominance, and a rather low median age at diagnosis even for RTs. Other clinical, treatment, outcome, and molecular factors did not differ from those conceived without ART (EU-RHAB control cohort) or reported in other series, and there was no evidence for imprinting defects. Long-term survival is achievable even in cases with pathogenic germline variants, metastatic disease at diagnosis, or relapse. The female preponderance among RT_ART patients is not yet understood and needs to be evaluated, ideally in larger international series. M.C.F. is supported by the 'Deutsche Kinderkrebsstiftung' DKS 2020.10, by the 'Deutsche Forschungsgemeinschaft' DFG FR 1516/4-1 and by the Deutsche Krebshilfe 70113981. R.S. received grant support by Deutsche Krebshilfe 70114040 and for infrastructure by the KinderKrebsInitiative Buchholz/Holm-Seppensen. P.D.J. is supported by the Else-Kroener-Fresenius Stiftung and receives a Max-Eder scholarship from the Deutsche Krebshilfe. M.H. is supported by DFG (HA 3060/8-1) and IZKF Münster (Ha3/017/20). BB is supported by the 'Deutsche Kinderkrebsstiftung' DKS 2020.05. We declare no competing interests. N/A.


Investigation of the active site of human placenta glutathione transferase pi by means of a spin-labelled glutathione analogue.
A spin-labelled analogue of glutathione (sl-glutathione) has been used in order to characterize the active site of human placenta glutathione transferase pi. The sl-glutathione shows a competitive inhibition towards glutathione (Ki = 14 microM). Binding of sl-glutathione to the enzyme, followed by electron paramagnetic resonance spectroscopy, gives a Kd of 3 microM and two identical binding sites for dimeric unit. Inhibition of the enzyme, by modification of the Cys-47 residue, completely prevents the binding of sl-glutathione. The same results are obtained by monitoring the binding of glutathione by means of fluorescence spectroscopy. It is concluded that integrity of the thiolate of Cys-47 is necessary to maintain an active conformation of the enzyme able to efficiently bind glutathione into the active site.


Contaminant pulse following wildfire is associated with shifts in estuarine benthic communities.
Novel combinations of climatic conditions due to climate change and prolonged fire seasons have contributed to an increased occurrence of "megafires". Such large-scale fires pose an unknown threat to biodiversity due to the increased extent and severity of burn. Assessments of wildfires often focus on terrestrial ecosystems and effects on aquatic habitats are less documented, particularly in coastal environments. In a novel application of eDNA techniques, we assessed the impacts of the 2019-2020 Australian wildfires on the diversity of estuarine benthic sediment communities in six estuaries in NSW, Australia, before and after the fires. Estuaries differed in area of catchment burnt (0-92%) and amount of vegetative buffer that remained post-fire between burnt areas and waterways. We found greater dissimilarities in the composition and abundance of eukaryotic and bacterial sediment communities in estuaries from burnt catchments with no buffer compared to those with an intact buffer or from unburnt catchments. Shifts in composition in highly burnt catchments were associated with increased concentrations of nutrients, carbon, including fire-derived pyrogenic carbon, and copper, which was representative of multiple highly correlated trace metals. Changes in the relative abundances of certain taxonomic groups, such as sulfate-reducing and nitrifying bacterial groups, in the most impacted estuaries indicate potential consequences for the functioning of sediment communities. These results provide a unique demonstration of the use of eDNA to identify wildfire impacts on ecological communities and emphasize the importance of vegetative buffers in limiting wildfire-associated impacts.


Electroelution of nucleic acids from polyacrylamide gels: a custom-made, agarose-based electroeluter.
Polyacrylamide electrophoresis is routinely used for small-scale preparative and analytical separations. The incomparably high-resolution separations achieved by this technique, however, have not been widely exploited to the large-scale preparative isolation of biological molecules from contaminants, mainly because of difficulties in the recovery of the desired molecule from the gel matrix. Electroelution is an effective procedure applied for this purpose. However, commercially available, high-cost electroeluters are required for achieving high recovery yields. Here, we describe a custom-made electroeluter that combines low-cost, high-recovery yields, short times of electroelution, and convenience in the manipulation of sensitive samples.


Cell adhesion and neurite outgrowth are promoted by neurofascin NF155 and inhibited by NF186.
Neurofascin (NF) is a neural cell adhesion molecule in the L1-family containing six Ig domains and multiple fibronectin type III (FnIII) repeats in its extracellular region. NF has many splicing variants and two of these are exemplars that have different cellular patterns of expression during development. NF186, which is expressed on neurons, contains an unusual mucin-like region and NF155, which is expressed on glia, contains a unique FnIII repeat with an RGD motif. Analysis of Fc fusion proteins representing different extracellular regions of NF indicate that NF186 inhibits cell adhesion and neurite outgrowth, and the inhibition is associated with the region containing the mucin-like domain. NF155 promotes neural cell adhesion and neurite outgrowth, and the RGD motif in its third FnIII repeat is critical for cell spreading and neurite outgrowth. The results suggest that different splicing variants of NF expressed on neurons and glia play distinct roles during neural development.


The prevalence of locally-synthesized virus antibodies in various forms of multiple sclerosis.
In 125 patients with multiple sclerosis, intrathecally synthesized antibodies against measles, rubella and zoster viruses were determined with an ELISA. 70% of patients with chronic progressive disease synthesized measles antibodies in comparison to 50% with a relapsing course. Women suffering from chronic progressive multiple sclerosis exhibited zoster antibodies 3 times as frequent as the other patients. These data indicate that relapsing and chronic progressive forms of multiple sclerosis exhibit different antiviral responses within the central nervous system which remain stable during the course of the disease.


Cyclic DNA remethylation following active demethylation at euchromatic regions in mouse embryonic stem cells.
DNA methylation is an essential epigenetic mark that regulates normal mammalian embryonic development. DNA methylation profiles are not always static, especially during germline development. In zygotes, DNA is typically highly methylated but, during preimplantation, DNA methylation is erased globally. Then, at the start of post-implantation development in mouse embryos, DNA again becomes dramatically hypermethylated. Chromatin structure regulates the accessibility of DNA-modifying enzymes to target DNA. Beyond that, however, our understanding of the pathway by which chromatin regulation initiates changes in global DNA methylation during mouse embryonic development remains incomplete. To analyse the relationship between global regulation of DNA methylation and chromatin status, we examined 5-methylcytosine (5mC), modified by the DNA methyltransferase DNMT, and the oxidative derivative 5-hydroxymethylation (5hmC), converted from 5mC by TET-family enzymes, by means of immunofluorescence staining of mitotic chromosomes in mouse embryonic stem cells (ESCs). Our comparison of immunostaining patterns for those epigenetic modifications in wild-type, DNMT-deficient, and TET-deficient ESCs allowed us to visualise cell cycle-mediated DNA methylation changes, especially in euchromatic regions. Our findings suggest that DNA methylation patterns in undifferentiated mouse ESCs are stochastically balanced by the opposing effects of two activities: demethylation by TET and subsequent remethylation by DNMT.


Cancer genetics and the cardiotoxicity of the therapeutics.
Cancer genomics has focused on the discovery of mutations and chromosomal structural rearrangements that either increase susceptibility to cancer or support the cancer phenotype. Protein kinases are the most frequently mutated genes in the cancer genome, making them attractive therapeutic targets for drug design. However, the use of some of the kinase inhibitors (KIs) has been associated with toxicities to the heart and vasculature, including acute coronary syndromes and heart failure. Herein we discuss the genetic basis of cancer, focusing on mutations in the kinase genome (kinome) that lead to tumorigenesis. This will allow an understanding of the real and potential power of modern cancer therapeutics. The underlying mechanisms that drive the cardiotoxicity of the KIs are also examined. The preclinical models for predicting cardiotoxicity, including induced pluripotent stem cells and zebrafish, are reviewed, with the hope of eventually being able to identify problematic agents before their use in patients. Finally, the use of biomarkers in the clinic is discussed, and newer strategies (i.e., metabolomics and enhanced imaging strategies) that may allow earlier and more accurate detection of cardiotoxicity are reviewed.


The structural relationship between job satisfaction and organizational commitment of beauty industry employees.
Based on the analysis results that can further enhance organizational satisfaction and response to changes in the employment environment of cosmetic employees and workers through organizational commitment and turnover intention of cosmetic. This research paper empirically analyzed changes in employment environment due to coronavirus disease-19 (COVID-19) pandemic and 4th industrial revolution and the effect of employees and job satisfaction on turnover intention in the cosmetic industry, and sought measures necessary for conflict management in industrial sites. A self-report questionnaire was conducted on 508 cosmetic implementers. Statistical processing of the data collected by the data analysis method was analyzed using the Statistical Package for Social Science (SPSS) WIN23.0 statistical package program through data coding and data organizing process. Changes in the employment environment were found to have a significant effect on job satisfaction (t = -11.728, p < 0.05). Changes in the employment environment were found to have a significant effect on organizational commitment, which is a dependent variable (t = -9.476, p < 0.05). Changes in the employment environment and job satisfaction were found to have a significant effect on organizational commitment, and this regression model was found to be statistically significant (F = 67.703, p < 0.05). Job satisfaction showed a significant positive (+) effect on organizational commitment rather than the employment environment (t = 6.235, p < 0.05). As a result, it was found that the organizational commitment and job satisfaction of cosmetic employees and workers affected their turnover intentions due to changes in the employment environment due to the 4th industrial revolution and the COVID-19 pandemic. This study focused on the relationship between employment environment changes in the cosmetic industry due to the recent 4th industrial revolution and the COVID-19 pandemic, and the effects of job satisfaction and organizational commitment of cosmetic employees on turnover intention. Based on the results of the analysis that can further increase the organizational commitment and search for job satisfaction of cosmetic employers and workers, we intend to establish the identity of cosmetic industry organizations nationwide and raise community awareness. This study will help the development and growth of the cosmetic industry by providing basic data that can be reborn as a better cosmetic service organization.


Establishing confidence in the output of qualitative research synthesis: the ConQual approach.
The importance of findings derived from syntheses of qualitative research has been increasingly acknowledged. Findings that arise from qualitative syntheses inform questions of practice and policy in their own right and are commonly used to complement findings from quantitative research syntheses. The GRADE approach has been widely adopted by international organisations to rate the quality and confidence of the findings of quantitative systematic reviews. To date, there has been no widely accepted corresponding approach to assist health care professionals and policy makers in establishing confidence in the synthesised findings of qualitative systematic reviews. A methodological group was formed develop a process to assess the confidence in synthesised qualitative research findings and develop a Summary of Findings tables for meta-aggregative qualitative systematic reviews. Dependability and credibility are two elements considered by the methodological group to influence the confidence of qualitative synthesised findings. A set of critical appraisal questions are proposed to establish dependability, whilst credibility can be ranked according to the goodness of fit between the author's interpretation and the original data. By following the processes outlined in this article, an overall ranking can be assigned to rate the confidence of synthesised qualitative findings, a system we have labelled ConQual. The development and use of the ConQual approach will assist users of qualitative systematic reviews to establish confidence in the evidence produced in these types of reviews and can serve as a practical tool to assist in decision making.


Common management of primary rectal carcinoma in patients with stage IV disease at the diagnosis.
Rectal cancer is one of the more common neoplasms of Western countries. It is commonly diagnosed at a precocious stage but, because of local relapse and/or metastatic disease, only half of radically resected patients can be considered free of disease. In patients presenting at diagnosis with stage IV disease the best treatment is still unknown. If the patient is a candidate for surgical resection, the primary tumor should be treated as in a patient without metastatic disease. If metastases are unresectable, the treatment of the primary lesion is palliative and, according to the patients' symptoms, it is usually represented by a chemotherapy approach. It is still unclear whether to reserve radiotherapy only for the symptomatic cases. This paper examines the factors pertinent to clinical trials designed for stage IV rectal cancer with resectable and unresectable metastases and reviews the existing data supporting palliative therapy for symptomatic and asymptomatic primary tumors.


Sepsis and hypothermia in the newborn infant: value of gastric aspirate examination.
Bacteriologic examination of blood, urine, CSF, and gastric aspirate was performed in 88 babies admitted with hypothermia (rectal temperature less than 35 degrees C) during the neonatal period. Infection was common in infants older than 3 days (late-onset hypothermia). In 36 of the 44 (81.8%) infected babies, the gastric aspirate was abnormal, whereas it was abnormal in only three of the 23 (13%) not infected. Infection was much less common in babies younger than 3 days (early-onset hypothermia), and in these the gastric aspirate was mostly normal. Two babies had RDS-like symptoms, and streptococci were cultured from the gastric aspirate. Examination of the gastric aspirate is a quick, efficient method of diagnosing severe infection, not only immediately after birth but throughout the neonatal period.


Effects of TGF-β1 on the Proliferation and Apoptosis of Human Cervical Cancer Hela Cells In Vitro.
To investigate the effects of TGF-β1 on the proliferation and apoptosis of cervical cancer Hela cells in vitro. Human cervical cancer Hela cells were cultured in vitro and divided into the experimental and control groups. In the experimental groups, Hela cells were stimulated with different concentrations of TGF-β1 (0.01, 0.1, 1, and 10 ng/mL), while Hela cells cultured in serum-free medium without TGF-β1 were used as controls. The CCK8 method was adopted to detect the effect of TGF-β1 on Hela cell proliferation, and flow cytometry was used to determine cell apoptosis 72 h after TGF-β1 treatment. Compared with the control group, the CCK-8 tests showed that different concentrations of TGF-β1 had no obvious effect on Hela cell proliferation 24 h after treatment (P > 0.05). However, upon 48 or 72 h of treatment, TGF-β1 significantly inhibited the proliferation of Hela cells in a time- and dose-dependent manner (P < 0.05). The flow cytometry results indicated that TGF-β1 influenced the apoptosis of human cervical cancer Hela cells in a dose-dependent manner after 72 h of treatment (P < 0.05). TGF-β1 significantly inhibited the growth and induced the apoptosis of human cervical Hela cells in vitro.


Real world utilization of Andexanet alfa in the management of oral factor Xa inhibitor-associated gastrointestinal bleeding.
Andexanet alfa (AA) is approved for reversal of factor Xa inhibitor (FXaI) bleeds; however, there are limited reports of its use for gastrointestinal bleeding (GIB) in real-world populations. The objective of this study was to report real-world utilization and evaluation of the effectiveness of AA for FXaI-associated GIB. This retrospective cohort study including consecutive patients receiving AA for FXaI-associated GIB (7/2018-2/2021). Demographics, blood product administration, hemostatic efficacy, rebleeding, thrombosis, and mortality rates were collected. Hemostatic efficacy (HE), based on corrected hemoglobin at 12 h compared to baseline, was categorized as excellent (<10% decrease), good (≤ 20% decrease), or poor (>20% decrease, > 2 units of additional coagulation intervention or death prior to repeat hemoglobin). Comparative transfusion requirements between efficacy groups was assessed by Wilcoxon-Rank test. Twenty-two patients were included (64% male, median (IQR) age 76 years (67, 80). Most patients (59%, n = 13) were on apixaban, and the primary anticoagulation indication was atrial fibrillation (64%, n = 14). Median initial hemoglobin was 7.5 g/dL (IQR 6.4, 8.8) and 50% (n = 11) were upper GIB. Hemostatic efficacy was excellent in 46% (n = 10), good in 23% (n = 5), and poor in 32% (n = 7). There was no statistically significant difference in red blood cells (RBCs) received between those with excellent/good hemostasis (median 2, IQR 1 to 2) and those with poor hemostasis (median 4, IQR 1.5 to 4.5). Two patients (9%) had arterial thrombotic events within 30 days of reversal. In this multicenter, single arm, real-world observational analysis of patients with factor Xa inhibitor associated GIB most patients achieved good hemostasis following administration of AA. There was a 9% 30-day thrombotic event rate. The lack of a control group limits the strength of the conclusions that can be drawn from this study.


Outcomes following transcatheter closure or surgical repair of coronary-left ventricular fistula: A single-center study with 10-year experience.
Coronary arteries drain into the left ventricle, known as coronary-left ventricular fistula (CLVF), an extremely rare anomalous coronary artery disease. Little is known about the outcomes following transcatheter closure (TC) or surgical closure (SC) of CLVF. This was a single-center retrospective study including 42 consecutive patients who underwent either the TC or SC procedure from January 2011 to December 2021. The baseline and anatomic characteristics of the fistulas, procedural outcomes, and late outcomes were summarized and analyzed. The mean age was 31.6 ± 16.2 years, with 28 male patients (66.7%). Fifteen patients underwent SC group and the remaining received TC group. There were no differences in age, comorbidities, clinical presentations, and anatomic characteristics between the 2 groups. The procedural success rate was similar (93.3% vs. 85.2%, P = 0.639) without operative and in-hospital mortality in both groups. Notably, patients who underwent TC had a significantly shorter postoperative in-hospital length of stay (2.11 ± 1.49 vs. 7.73 ± 2.37 days, P<0.001). The median follow-up time was 4.6 years (2.5-5.7 years, TC group) and 3.98 years (0.42-7.15 years, SC group), respectively. No difference was observed in the incidence of recanalization of the fistula (7.4% vs. 6.7%, P = 1) and myocardial infarction (0% vs. 0%). Cerebral infarction due to discontinuation of anticoagulants happened to two patients in the TC group. Importantly, thrombotic occlusion of the fistulous tract with patent parent coronary artery was found in 7 patients of the TC group. Both transcatheter and SC are safe and effective for patients with CLVF. Thrombotic occlusion is a noteworthy late complication, and its presence indicates the use of anticoagulants lifelong.


Antisera specific for the oligoribonucleotide sequences AAU and A2U2 and their recognition of oligonucleotide conformation.
Antisera specific for two synthetic oligoribonucleotide sequences, AAU and A2U2, were elicited in rabbits. The oligonucleotides were synthesized using polynucleotide phosphorylase under high salt conditions. Each oligomer was isolated by ion exchange chromatography, and was conjugated to bovine serum albumin, and injected into rabbits as an emulsion with complete Freund's adjuvant. The specificities of the resulting sera were analyzed using a modified Farr-type radioimmunoassay employing homologous oligonucleotide-protein conjugates radiolabeled with [3H]acetic anhydride and unlabeled free oligonucleotides as inhibitors. The antiserum elicited by AAU-BSA reacted well with AAU-RSA but a major fraction of the antibodies was directed to determinants of the conjugate that were not present on the free hapten. With respect to the haptenic determinants, AAU was a better inhibitor than any of the constituent mono- or dinucleotides, implying that features of the entire trinucleotide were being recognized. The other members of the A2Un family reacted to about the same extent as AAU, while other trinucleotides required an up to 21-fold higher concn in order to achieve similar inhibition. The most striking aspect of this antiserum was its failure to bind free ApA, although it could bind the ApA-containing oligonucleotides A3, AAG, AAC and A2Un. It seems likely that the ApA sequence in solution does not contain a significant proportion of a conformation present to a great extent in the ApA-containing oligomers. The antiserum elicited by A2U2-BSA was like anti-AAU-BSA in that some of the antibodies were directed against determinants not present on the free hapten. The most striking result of the inhibition experiments was the specificity of the antiserum for members of the A2Un series. When the A2Un series was compared with AA, AMP or any member of the Un series, approximately four orders of magnitude separated the inhibition curves. The poor binding of component mono- and dinucleotides implies that the conformation recognized by the antibody is present only to a significant extent in the trimeric sequence; the equality of binding of AAU with A2U2, A2U3 and A2U4 suggests that this conformation of the triplet is preserved in the longer sequences. These studies demonstrate the utility of immunochemical procedures for the study of oligonucleotide conformation in solution.


A high involvement of O2- possibly generated in inner membranes for iron-induced microsomal lipid peroxidation.
The lipid peroxidation of and the O2- generation by rat liver microsomes in the presence of NADPH or both NADPH and Fe3+ were determined by thiobarbituric acid-reacting substance formation and by chemiluminescence intensities with a cypridina luciferin analog, 2-methyl-6-(p-methoxyphenyl)-3, 7-dihydroimidazo[1,2-a]pyrazin-3-one(MCLA), as a chemiluminescence probe. Judging from the experiments with various inhibitors on the O2- generation and the lipid peroxidation, O2- generated, at intramembranous site, by cytochrome P-450 system is considered to be highly involved in the iron-induced lipid peroxidation.


Cardioprotective effects of dipeptidyl peptidase-4 inhibitors versus sulfonylureas in addition to metformin: A nationwide cohort study of patients with type 2 diabetes.
Cardiovascular effects of dipeptidyl peptidase-4 inhibitors (DPP4i) versus sulfonylureas (SU) remain controversial in observational studies. This study aimed to evaluate the influence of DPP4i on major adverse cardiovascular events (MACEs), including acute myocardial infarction, cerebrovascular disease, heart failure, cardiogenic shock, malignant dysrhythmia, and revascularisation. We conducted a nationwide cohort study using claims data from the National Health Insurance in Taiwan from 2007 to 2013. We enrolled type 2 diabetes patients who received DPP4i or SU in addition to metformin. DPP4i users were matched to SU users using propensity scores at a ratio of 1:1. The study outcomes were hospitalisation for MACE, heart failure, acute myocardial infarction, cerebrovascular disease, coronary revascularisation, and hypoglycaemia. There were 37,317 matched pairs of DPP4i and SU users with a mean follow-up of 2.1 years. Compared with SU users, DPP4i users showed a significantly lower risk of hospitalisation for MACE (HR 0.79 [95% CI 0.75-0.82]), heart failure (0.86 [0.79-0.93]), acute myocardial infarction (0.76 [0.68-0.92]), and cerebrovascular disease (0.72 [0.67-0.77]). Both sitagliptin (0.89 [0.85-0.94]) and vildagliptin ([0.77 [0.60-0.99]) showed a significantly lower risk of hospitalisation for MACE, but saxagliptin showed a borderline significantly higher risk of hospitalisation for heart failure (1.59 [1.00-2.55]). DPP4i showed better cardioprotective effects than SU, especially among patients receiving sitagliptin or vildagliptin.


Effects and Safe Inclusion of Narbonne Vetch (Vicia narbonensis) in Rainbow Trout (Oncorhynchus mykiss) Diets: Towards a More Sustainable Aquaculture.
Aquaculture's sustainability deeply relies on the identification and inclusion of alternative raw materials. Although meals from insects and/or byproducts from different industries are being recently tested, the meal from terrestrial vegetable species is still the main substitution candidate for fish meal. Here the effects of 0% (Control), 10% (A10) and 30% (A30) inclusion of Narbonne vetch (Vicia narbonensis; ZV-156 strain) meal in rainbow trout (Oncorhynchus mykiss) diets was assessed in a 63-day feeding trial by means of growth performance, histopathological, nutritional value of the fish fillet and blood biochemistry analyses. A dose-response trial was conducted in triplicate with 25 rainbow trout juveniles (20 g average body weight) per 500 L tank. Narbonne vetch meal decreased total intestine protease activity in vitro (from 26.81% to 48% inhibition), although high temperature partially inhibited the action of antinutritional factors (ANFs). No differences in fish growth performance and no severe histopathological alterations on the proximal intestine were observed between 10% Narbonne vetch inclusion and Control groups. In contrast, high inclusion (30%) of Narbonne vetch led to poor growth performance (30% reduction on final growth) and severe histopathological alterations (e.g., loss of brush border integrity, high number of villi fusion, reduced goblet cells density as well as reduced width of submucosa, muscular and serosa layers). Furthermore, while the A30 diet decreased docosahexaenoic fatty acid (FA) content in fish fillets, the A10 diet improved monounsaturated FA content when compared to that of the Control group. No altered levels of cholesterol, glucose or triglycerides in blood plasma and/or histopathological effects on the liver were observed among fish fed the different experimental diets. Although further research efforts (e.g., identifying potential enzymatic treatments to decrease the action of ANFs from Narbonne vetch meal) might be required, present results show that a low inclusion (10%) of Narbonne vetch in rainbow trout diets is possible. The inclusion of locally produced legumes such a Narbonne vetch might be an interesting approach to reduce carbon footprint in European aquaculture and the dependency on other alternative raw materials such as soybean (Glycine max) imported from third countries.


Comparison of four stains and a urease test for rapid detection of Helicobacter pylori in gastric biopsies.
Gastric biopsies were obtained from 125 subjects to compare detection of Helicobacter pylori by culture, a rapid urease test and histopathologic examination using haematoxylin-eosin, Gram, Giemsa, Warthin-Starry silver and acridine orange stains. Helicobacter pylori was isolated from 39 specimens. Acridine orange and Giemsa were the most sensitive stains, detecting 85% and 79% of positive specimens respectively. All stains showed high specificity (97-100%). The sensitivity and specificity of the rapid urease test was 62% and 100% respectively. These stains or the rapid urease test may be useful for rapid detection of Helicobacter pylori in gastric biopsies.


[Mediterranean boutonneuse fever. Apropos of cases observed in Sousse].
We report 5 confirmed cases of boutonneuse fever. All patients presented fever with a generalised maculopapular rash, and the tache noire at the site of the tick bite. Trimethoprim sulfamethoxazole failed to cure one patient. Treatment with oral oxytetracycline was effective in all cases.


Chemical hair relaxers have adverse effects a myth or reality.
Hair plays an important role in one's personality and builds confidence. Now-a-days, chemical hair relaxers are used very commonly in the society. We document the adverse effects reported by the sample that have used any one of the professional chemical hair relaxers. To study the adverse effects reported by the sample who underwent repeated chemical hair relaxing. Cross-sectional questionnaire based study done on a sample taken from a medical college and hospital campus in Mangalore. The sample was restricted to females and to those who underwent it more than once. A questionnaire was given to a sample of 90, which matched our criteria. SPSS software 17. Adverse effects reported by the sample after undergoing the procedure were found to be a high 95.56%, out of which the following are the common adverse effects reported; frizzy hair in 67%, dandruff in 61%, hair loss in 47%, thinning and weakening of hair in 40%, greying of hair 22%, and split ends in only 17%. Very few studies have been conducted on the adverse effects of hair straightening products in India. From our study, it can be stated that most of the samples had adverse effects, which was as high as 95.56%. Hence from the details elicited from this study, we can conclude that, usage of chemical hair relaxers does cause adverse effects and is "not a myth." Thus, it is necessary to make available a less harmful chemical hair relaxer to the society.


Sequential parametric optimization of lipase production by a mutant strain Rhizopus sp. BTNT-2.
Lipase production by the mutant strain Rhizopus sp. BTNT-2 was optimized in submerged fermentation. Different chemical and physical parameters such as carbon sources, nitrogen sources, oils, inoculum level, pH, incubation time, incubation temperature and aeration have been extensively studied to increase lipase productivity. Potato starch (1.25% w/v) as a carbon source, corn steep liquor (1.5% w/v) as a nitrogen source and olive oil (0.5% v/v) as lipid source were found to be optimal for lipase production. The optimal levels of other parameters are 4 ml of inoculum (2.6x10(8) spores/ml), initial pH of 5.5, incubation time of 48 hours, incubation temperature of 28 degrees C and aeration rate of 120 rpm. With the optimized parameters, the highest production of lipase was 59.2 U/ml while an yield of only 28.7 U/ml was obtained before optimization resulting in 206% increase in the productivity.


Listeria monocytogenes infection in caspase-11-deficient mice.
Caspase-11 (Cas11) is a cysteine protease involved in programmed cell death and cytokine maturation. Through activation of Cas1 (interleukin-1beta [IL-1beta]-converting enzyme), Cas11 is directly involved in the maturation of IL-1beta and IL-18. Apoptosis is mediated through Cas3. Given the role of apoptosis and cytokine signaling during the innate immune response in intracellular infection, we examined Cas11-deficient (Cas11(-/-)) mice during infection with Listeria monocytogenes. Cas11(-/-) and wild-type C57BL/6 mice were equally susceptible to intravenous infection with L. monocytogenes, resulting in similar bacterial burdens in tissue and similar survival rates. By contrast, enhanced susceptibility was observed in control mice on a mixed genetic 129/C57BL/DBA2 background. Cas11(-/-) and wild-type mice infected with Listeria had similar hepatic microabscess formation in terms of histologic appearance, size, and number. Apoptosis of L. monocytogenes-infected hepatocytes in vivo and in vitro in primary culture was not altered by the absence of Cas11. Serum IL-18 and IL-1beta levels were similar in Cas11(-/-) mice and controls. Endotoxin (lipopolysaccharide [LPS])-challenged Cas11(-/-) mice were deficient in the production of gamma interferon. IL-1beta responses in Cas11(-/-) were normal with intravenous administration of LPS but decreased with intraperitoneal administration. Our findings suggest that Cas11 deficiency does not impair the immune response to infection with L. monocytogenes. Apoptosis and maturation of IL-18 and IL-1beta were normal despite Cas11 deficiency. LPS-induced proinflammatory pathways are altered by the absence of Cas11. While Cas11-mediated Cas1 and Cas3 activation is crucial for cytokine maturation and apoptosis during inflammation, alternative pathways allow normal inflammatory and apoptotic responses during infection with L. monocytogenes.


Alopecia areata susceptibility variant in MHC region impacts expressions of genes contributing to hair keratinization and is involved in hair loss.
Alopecia areata (AA) is considered a highly heritable, T-cell-mediated autoimmune disease of the hair follicle. However, no convincing susceptibility gene has yet been pinpointed in the major histocompatibility complex (MHC), a genome region known to be associated with AA as compared to other regions. We engineered mice carrying AA risk allele identified by haplotype sequencing for the MHC region using allele-specific genome editing with the CRISPR/Cas9 system. Finally, we performed functional evaluations in the mice and AA patients with and without the risk allele. We identified a variant (rs142986308, p.Arg587Trp) in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene as the only non-synonymous variant in the AA risk haplotype. Furthermore, mice engineered to carry the risk allele displayed a hair loss phenotype. Transcriptomics further identified CCHCR1 as a novel component interacting with hair cortex keratin in hair shafts. Both, these alopecic mice and AA patients with the risk allele displayed morphologically impaired hair and comparable differential expression of hair-related genes, including hair keratin and keratin-associated proteins (KRTAPs). Our results implicate CCHCR1 with the risk allele in a previously unidentified subtype of AA based on aberrant keratinization in addition to autoimmune events. This work was supported by JSPS KAKENHI (JP16K10177) and the NIHR UCLH Biomedical Research center (BRC84/CN/SB/5984).


Functional end-plate recovery in long-term botulinum toxin therapy of hemifacial spasm: a nerve conduction study.
Botulinum toxin type-A is currently thought to be effective and safe for hemifacial spasm (HFS). The pre-synaptic block of acetylcholine release at the neuromuscular junction induces depression of orbicularis oculi muscle compound motor action potential (CMAP). The aim of our study was to evaluate at what extent end-plate functional recovery is possible even in botulinum toxin treatments lasting up to 15 years. We examined 81 outpatients with primary HFS (mean treatment duration = 7.2 ± 4.2 years) who underwent neurophysiologic study, once clinical effect of the previous treatment had vanished. The mean CMAP amplitude, mean rectified amplitude of response 1 (R1) of the blink reflex and area of response 2 (R2) of treated orbicularis oculi muscle were measured in comparison to the controlateral side. Mean amplitude of the above mentioned parameters was slightly lower (about 20%; p < 0.001) in the treated side at the end of the follow-up period (4.7 ± 1.7 months). The CMAP amplitude reduction weakly correlated with the interval from last treatment, while other neurophysiologic parameters did not change due to treatment duration or total toxin amount. Our study demonstrates that botulinum toxin affects compound motor action potential and blink-reflex responses for at least 4-5 months in HFS patients. The residual block is slight and does not increase with repeated injections after several years of treatment. Our study, beside confirming the long-term efficacy of botulinum toxin treatment for HFS, provides neurophysiologic evidence that therapeutic effect may be obtained without hindering the regenerative potential of the nerve-muscle complex.


Designing an eHealth Breastfeeding Resource With Young Mothers Using a Participatory Design.
Breastfeeding rates among young mothers are low and do not meet recommendations from health authorities, putting the health of young mothers and their infants at risk. Young mothers require breastfeeding support that meets their learning needs and preferred mode for accessing information. The objective of this study was to work collaboratively with young mothers in order to cocreate an eHealth breastfeeding resource. A three-phase exploratory study was conducted in Ontario, Canada. In Phases I and II, young mothers and health care providers (HCPs) were recruited and preferences for an eHealth breastfeeding resource were explored. In Phase III, feedback from young mothers and HCPs about the new resource was collected. Participants found the breastfeeding eHealth resource visually appealing, engaging, and informative. Cocreating a tailored breastfeeding eHealth resource with young mothers and HCPs using a participatory approach ensured that the resource design and content met the learning needs of young mothers.


Influence of the Silver Nanocrystal Shape on the Luminous Efficiency of Blue-Emitting Polymer Light-Emitting Diodes.
Truncated silver nanodecahedrons (TAgNDs) and truncated silver nanoplates (TAgNPs) fabricated via chemical reduction and photochemical methods were added to poly[3,4-ethylenedioxythiophene]:poly[styrenesulfonate] (PEDOT:PSS) as dopants to promote the luminous efficiency of blue-emitting polymer light-emitting diodes (PLEDs). The differences in shape between TAgNDs and TAgNPs result in better dispersion of TAgNDs in PEDOT:PSS. Therefore, at an optimal doping concentration (the distributed density in the light-emitting region is 6.88 μg cm-2 for TAgNDs and 5.16 μg cm-2 for TAgNPs), the average current efficacy and maximum electroluminescence intensity enhancement factor for TAgND-doped PLEDs were 4.18 cd A-1 and 420%, respectively, which are much higher than those for TAgNP-doped PLEDs (1.83 cd A-1 and 200%) at a luminescence wavelength of 440 nm.


Relative quantity judgments in the beluga whale (Delphinapterus leucas) and the bottlenose dolphin (Tursiops truncatus).
Numerous studies have documented the ability of many species to make relative quantity judgments using an analogue magnitude system. We investigated whether one beluga whale, Delphinapterus leucas, and three bottlenose dolphins, Tursiops truncatus, were capable of selecting the larger of two sets of quantities, and analyzed if their performance matched predictions from the object file model versus the analog accumulator model. In Experiment 1, the two sets were presented simultaneously, under water, and they were visually (condition 1) or echoically (condition 2) available at the time of choice. In experiment 2, the two sets were presented above the water, successively (condition 1) or sequentially, item-by-item (condition 2), so that they were not visually available at the time of choice (condition 1) or at any time throughout the experiment (condition 2). We analyzed the effect of the ratio between quantities, the difference between quantities, and the total number of items presented on the subjects' choices. All subjects selected the larger of the two sets of quantities above chance levels in all conditions. However, unlike most previous studies, the subjects' choices did not match the predictions from the accumulator model. Whether these findings reflect interspecies differences in the mechanisms which underpin relative quantity judgments remains to be determined.


Prevalence of sarcocysts of Sarcocystis capracanis in oesophagus and tail muscles of naturally infected goats.
The prevalence of sarcocysts of Sarcocystis capracanis in oesophagus and tail muscles of 76 goats slaughtered at Jabalpur, India, was found to be 67.10 and 46.05%, respectively. A total of 79.3% of oesophagi and 72.4% of tails had sarcocysts in older goats (greater than 1 year), but their prevalence in younger animals (less than 1 year) was 40.0% in oesophagi and none in tails. Therefore examination by biopsy of the tail muscles can be used to monitor the development of Sarcocystis sarcocysts in experimental infection without killing the animal.


Crystal structure of the Al8Cr5-type inter-metallic Al7.85Cr5.16.
An aluminium-deficient Al8Cr5-type inter-metallic with formula Al7.85Cr5.16 (octa-aluminium penta-chromium) was uncovered when high-pressure sinter-ing of a mixture with composition Al11Cr4 was carried out. Structure analysis reveals that there are three co-occupied positions with refined occupancy factors for Al atoms being 0.958, 0.772 and 1/2. The present phase is confirmed to be isotypic with the previously reported rhombohedral Al8Cr5 ordered phase [Bradley & Lu (1937). Z. Kristallogr. 96, 20-37] and structurally closely related to the disordered phases of rhombohedral Al16Cr9.5 and cubic Al8Cr5.


Dietary administration of chitooligosaccharides to enhance growth, innate immune response and disease resistance of Trachinotus ovatus.
The present study was conducted to investigate the effects of dietary chitooligosaccharides (COS) supplementation on the innate immune response and protection against Vibrio harveyi infection in Trachinotus ovatus. A basal diet was supplemented with 0.0 (control), 2.0, 4.0 and 6.0 g COS kg(-1) to formulate four experimental diets. Each diet was randomly allocated to triplicate groups of fish in floating sea cages (1.5 × 1.0 × 2.0 m), and each cage was stocked with 80 fish (initial average weight 10.8 ± 0.05 g). After 8 weeks of feeding trial, Both the final weight and specific growth rate (SGR) significantly increased with increasing dietary COS levels up to 4.0 g kg(-1), whereas there were no significant differences for COS levels from 4.0 to 6.0 g kg(-1). A decreased feed conversion ratio (FCR) was observed with increasing dietary COS levels. The total leukocyte counts (WBC), differential leukocyte counts, respiratory burst activity, lysozyme and superoxide dismutase (SOD) activity were significantly increased with the increased levels of dietary COS (P < 0.05), and reached a maximum at level of 4.0 g kg(-1) COS. There were no significant differences in those immunological parameters between 4.0 and 6.0 g kg(-1) COS. Moreover, the dietary COS supplementation groups also exhibited a decrease in the cumulative symptom rates compared to the controls when challenged with V. harveyi. These results indicated that dietary intake containing COS could enhance the immune responses of fish and improve its resistance to infection by V. harveyi. Especially supplementation with 4.0 g kg(-1) COS to the fish for 56 days showed considerable improvement in the growth, survival and immune response of the fish.


Psychological Factors Affecting the Willingness to Accept a Possible Tyrosine Kinase Inhibitor (TKI) Discontinuation in Chronic Myeloid Leukaemia (CML) Patients.
Patients with chronic myeloid leukemia (CML) who present a sustained deep molecular response (DMR) for a stable period of time might benefit from discontinuing tyrosine kinase inhibitors (TKIs). A significant number of patients seem able to reach this stage due to the availability of TKIs. However, many patients remain reluctant about TKI discontinuation and may refuse treatment interruption. The purpose of this study was to explore the clinical and psycho-cognitive factors that may influence the decision to discontinue TKI therapy, thereby gaining a better understanding of patients' viewpoints on TKI discontinuation. One hundred and nineteen patients diagnosed with CML aged between 34 and 69 were enrolled (67 males and 52 females). Different clinical information and psycho-cognitive aspects such as attitude toward risk behaviours, risk preferences, need for cognitive closure, and tendency to resist to changes were assessed through the administration of a battery of questionnaires. A higher tendency toward risk behaviours and the tendency to focus on possible gain in the short term rather than on losses might represent important predictors for the willingness to accept TKI discontinuation. Possible relapses following interruption of the therapy are the most common reason for concern. Furthermore, lower levels of resistance to change and having previously experienced the desire to interrupt the therapy might lead patients to accept a higher probability of relapse risk when facing such a decision. TKI discontinuation appears appealing and challenging at the same time for many CML patients, and different factors may influence this decision. Psychology plays a crucial role in assisting physician-patient communication and informed decision-making.


Safe screening rules for multi-view support vector machines.
Multi-view learning aims to make use of the advantages of different views to complement each other and fully mines the potential information in the data. However, the complexity of multi-view learning algorithm is much higher than that of single view learning algorithm. Based on the optimality conditions of two classical multi-view models: SVM-2K and multi-view twin support vector machine (MvTwSVM), this paper analyzes the corresponding relationship between dual variables and samples, and derives their safe screening rules for the first time, termed as SSR-SVM-2K and SSR-MvTwSVM. It can assign or delete four groups of different dual variables in advance before solving the optimization problem, so as to greatly reduce the scale of the optimization problem and improve the solution speed. More importantly, the safe screening criterion is "safe", that is, the solution of the reduced optimization problem is the same as that of the original problem before screening. In addition, we further give a sequence screening rule to speed up the parameter optimization process, and analyze its properties, including the similarities and differences of safe screening rules between multi-view SVMs and single-view SVMs, the computational complexity, and the relationship between the parameter interval and screening rate. Numerical experiments verify the effectiveness of the proposed methods.


Iatrogenic Keratectasia after Refractive Surgery - Causes, Prophylaxis, Therapy.
Iatrogenic keratectasia is induced thinning and protrusion of the cornea after laser refractive surgery. Known risk factors include an excessively thin postoperative residual stromal bed, a thicker flap, or preoperatively undetected evidence of preexisting subclinical keratoconus. The rate of post-refractive ectasia in eyes without identifiable preoperative risk factors is 20 per 100 000 eyes for photorefractive keratectomy, 90 per 100 000 eyes for laser in situ keratomileusis, and 11 per 100 000 eyes for small incision lenticule extraction. Traditional screening tools for preoperative risk include the ectasia risk score system and percentage of tissue alteration. More recent methods include corneal elastography and epithelial mapping, in addition to Artificial Intelligence methods for data analysis. Therapy includes contact lenses, cross-linking, implantation of intracorneal ring segments, penetrating or lamellar keratoplasty, and, in early studies, implantation of corneal lenticules.