[Correlation between changes in lungs caused by industrial dusts and the composition of amino acids in blood plasma. I. Experimental animal studies].
Animals, used for experiments, were intoxicated intratracheally with a suspension of grinding, ceramic or welding dust, in a NaCl solution. These studies demonstrated that the ceramic and welding dusts, used in the experiment, showed a rather great biological activity. This has been proved by the increased weight of dried lungs, and increased total content of some aminoacids in lungs, e.g. hydroxyproline, which is thought to be a reliable index of fibrosis of the pulmonary tissue, as well as of the change in the morphological structure of lungs. Parrallel to the mentioned changes of the lungs, the content of free aminoacids in the animals blood plasma has been remarkably reduced. The results described in this paper prove that there is a dependence between the content of aminoacids in the blood plasma and the changes in lungs caused by dust.


Thickening of the gastric wall on transabdominal sonography: a sign of gastric cancer.
To determine the value of a thickened gastric wall detected during transabdominal sonography (TAS) in the diagnosis of gastric cancer. This prospective study comprised 312 patients who underwent both TAS and endoscopy. Transverse TAS scanning was performed using a 3.5-MHz curved transducer to measure gastric wall thickness in the antrum and body of the stomach. Based on endoscopic and histologic findings, we classified the patients into 3 groups: normal or benign disease (BD), early gastric cancer (EGC), and advanced gastric cancer (AGC). TAS findings were then compared. The thickness of the gastric wall was 4.9 +/- 1.6 mm in 262 patients with BD, 5.6 +/- 2.4 mm in 21patients with EGC, and 10.3 +/- 4.7 mm in 29 patients with AGC (p < 0.01). A gastric wall thickness of greater than 7 mm had a 75.0% sensitivity, 92.6% specificity, 50.0% positive predictive value, and 97.4% negative predictive value in the diagnosis of AGC. Although not suitable as a screening method for gastric cancer, a thickening of the gastric wall of >7 mm may be a marker for AGC.


Sensitivity study in vivo: glass-ionomer versus zinc-phosphate bases beneath amalgam restorations.
This study in vivo evaluated the sensitivity of class 1 and 2 amalgam restorations which had bases of either zinc phosphate or an admix, silver-reinforced glass ionomer. The evaluation of sensitivity was done by providing the patient with five postcard questionnaires to be mailed to the clinic over a period of time from one to 28 days. Teeth restored with amalgam and silver-reinforced glass ionomer were significantly less sensitive to cold than those restored with amalgam and zinc phosphate.


Gentiopicroside alleviated epileptogenesis in immature rats through inactivation of NLRP3 inflammasome by inhibiting P2X7R expression.
This study aimed to elucidate the effects of Gentiopicroside (Gent) on epileptogenesis and underlying mechanisms. The status epilepticus (SE) model was established by intraperitoneal (i.p.) injection of lithium chloride (127 mg/kg) and pilocarpine (50 mg/kg) in immature rats. HAPI microglial cellular inflammation model was induced by lipopolysaccharide (LPS, 1 μg/ml) and adenosine triphosphate (ATP, 5 mM). The differential concentrations of Gent were used to pretreat animal (200, 400, and 800 mg/kg) and model cells (50, 100, and 200 μM). Epileptic discharges were assessed by electroencephalography (EEG) and Racine scale. Changes in spatial memory function were measured using the Morris water maze task test. Nissl and FJB staining were employed to assess the damage to hippocampus tissues. ELISA was used to detect the production of IL-1β, IL-18, and TNF-α. The expressions of P2X7R and NLRP3 were detected by q-PCR, immunofluorescence staining, and Western blot, and cell viability was determined by cell counting kit-8 (CCK-8). Lithium chloride and pilocarpine (LICL-PILO) induced abnormal EEG activities, behavioral alterations, brain damage, and inflammatory responses in immature rats. However, Gent pretreatment significantly reduced the neuronal damage and spatial memory dysfunction induced by LICL-PILO. Additionally, Gent suppressed the production of inflammatory cytokines and inhibited the expression of P2X7R, NLRP3, ASC, and Caspase-1 in LPS/ATP-induced HAPI microglial cells. Gent intervention could improve epileptogenesis in immature rats partially due to suppressing P2X7R and NLRP3 inflammasome.


4-Dihydromethyltrisporate dehydrogenase, an enzyme of the sex hormone pathway in Mucor mucedo, is constitutively transcribed but its activity is differently regulated in (+) and (-) mating types.
4-Dihydromethyltrisporate dehydrogenase (TDH) converts the (+) mating type sex pheromone 4-dihydromethyltrisporate into methyltrisporate. In Mucor mucedo, this conversion is required only in the (-) mating type. Expression of the TDH encoding TSP1 gene was analyzed qualitatively using reverse-transcribed PCR. TSP1 is constitutively transcribed in the (+) and in the (-) mating type, irrespective of the mating situation. By immunodetection, the translation product is also formed constitutively. In contrast to gene expression, TDH enzyme activity depends on the sexual status of the mycelium. Activity is restricted to the sexually stimulated (-) mating type. Non-stimulated (-), as well as stimulated and non-stimulated (+) mycelia exhibit no activity and do not influence activity in stimulated (-) mycelia. Time course analysis shows strongly increased enzyme activity at 80 min after stimulation. Low activity exists from the onset of stimulation, indicating that additional regulation mechanisms are involved in TDH function.


Concomitant ventricular septal rupture and interventricular septal aneurysm in neglected inferior myocardial infarction misdiagnosed with congenital ventricular septal defect: A case report.
This study emphasizes that VSD should not be immediately diagnosed as a congenital disorder; instead, regional wall motion abnormalities in the left ventricle should also be taken into account since it may result from mechanical complications of neglected myocardial infarction.


The Action of TAAR1 Agonist RO5263397 on Executive Functions in Rats.
Trace amine-associated receptor 1 (TAAR1) is a widely recognized new perspective target for the neuropsychiatric pharmacological treatment. Despite a growing number of studies investigating TAAR1 role in the animal models of different pathologies, information of TAAR1 agonists impact on executive cognitive functions is limited. The goal of the present study was to evaluate the activity of highly selective partial TAAR1 agonist RO5263397 on various executive cognitive functions. The results of the present study demonstrated that the pretreatment with RO5263397 was able to increase attention and decrease cognitive flexibility in rats. The analysis of the RO5263397 action on impulsivity demonstrated that the TAAR1 activation failed to affect premature responding but was able to slightly modify impulsive choice. Problem solving was resistant to the pharmacological intervention.


Pulse oximetry and transcutaneous oxygen tension for detection of hypoxemia in critically ill infants and children.
We tested the performance of transcutaneous oxygen monitoring (TcPO2) and pulse oximetry (tcSaO2) in detecting hypoxia in critically ill neonatal and pediatric patients. In 54 patients (178 data sets) with a mean age of 2.4 years (range 1 to 19 years), arterial saturation (SaO2) ranged from 9.5 to 100%, and arterial oxygen tension (PaO2) from 16.4 to 128 mmHg. Linear correlation analysis of pulse oximetry vs measured SaO2 revealed an r value of 0.95 (p less than 0.001) with an equation of y = 21.1 + 0.749x, while PaO2 vs tcPO2 showed a correlation coefficient of r = 0.95 (p less than 0.001) with an equation of y = -1.04 + 0.876x. The mean difference between measured SaO2 and tcSaO2 was -2.74 +/- 7.69% (range +14 to - 29%) and the mean difference between PaO2 and tcPO2 was +7.43 +/- 8.57 mmHg (range -14 to +49 mmHg). Pulse oximetry was reliable at values above 65%, but was inaccurate and overestimated the arterial SaO2 at lower values. TcPO2 tended to underestimate the arterial value with increasing PaO2. Pulse oximetry had the best sensitivity to specificity ratio for hypoxia between 65 and 90% SaO2; for tcPO2 the best results were obtained between 35 and 55 mmHg PaO2.


A synthetic prostaglandin E1 analog, alprostadil alfadex, relaxes sphincter of Oddi in humans.
It is well established that prostaglandins (PGs) exert potent pharmacological actions on vascular and nonvascular smooth muscle, although their effects on the sphincter of Oddi (SO) remain to be elucidated. The aim of this study was to investigate the effect of PGE1 on motility of the human SO. Twenty patients appearing for routine endoscopic retrograde cholangiopancreatography (ERCP) examination were studied. Each patient was randomly allocated to receive an intravenous infusion of normal saline (six patients), or alprostadil alfadex, a synthetic PGE1 analog, at a dose of either 0.05 or 0.1 microg/kg/min (seven patients for each condition). Endoscopic biliary manometry was done with a recording of basal SO pressure, amplitude of SO phasic contractions, and phasic contractile frequency before and 5 min after intravenous infusions, using a 4-French microtransducer catheter. There was no significant change in SO motor variables following application of normal saline. Alprostadil alfadex significantly decreased basal SO pressure at a dose of 0.05 microg/kg/min, and significantly decreased all parameters at a dose of 0.1 microg/kg/min. A synthetic PGE1 analog, alprostadil alfadex, effectively inhibits motility of the human SO. This drug may be of clinical application as a SO-relaxing agent.


Deletion of poly(ADP‑ribose) polymerase-1 changes the composition of the microbiome in the gut.
Poly(adenosine diphosphate‑ribose) polymerase (PARP)‑1 is the prototypical PARP enzyme well known for its role in DNA repair and as a pro‑inflammatory protein. Since PARP1 is an important co‑factor of several other pro‑inflammatory proteins, in the present study the possible changes in microbial flora of PARP1 knockout mice were investigated. Samples from the duodenum, cecum and feces from wild type and PARP1 knockout C57BL/6J male mice were collected and 16S ribosomal RNA genes were sequenced. Based on the sequencing results, the microbiome and compared samples throughout the lower part of the gastrointestinal system were reconstructed. The present results demonstrated that the lack of PARP1 enzyme only disturbed the microbial flora of the duodenum, where the biodiversity increased in the knockout animals on the species level but decreased on the order level. The most prominent change was the overwhelming abundance of the family Porphyromonadaceae in the duodenum of PARP1‑/‑ animals, which disappeared in the cecum and feces where families were spread out more evenly than in the wild type animals. The findings of the present study may improve current understanding of the role of PARP1 in chronic inflammatory diseases.


Life-course trajectories of employment quality and health in the U.S.: A multichannel sequence analysis.
The organization of employment in the U.S. has changed dramatically since the 1970s, causing decreased power and security for workers across many dimensions of the employment relationship. Multidimensional employment-quality (EQ) measures can be used to capture these changes and test their association with health. However, most public-health EQ studies have used cross-sectional, unidimensional data. We addressed these limitations using a longitudinal, multidimensional EQ measure and data on 2779 1985-2017 Panel Study of Income Dynamics respondents. First, using a multichannel sequence-analysis approach, we identified gender-specific clusters of mid-career (ages 29-50) EQ trajectories based on respondents' employment stability, material rewards, working-time arrangements, collective organization, and power relations. Next, we examined cross-cluster variation in respondent characteristics. Finally, we estimated the gender-specific associations between cluster-membership and post-sequence-analysis-period prevalence of poor/fair self-rated health (SRH) and moderate mental illness (Kessler-K6≥5). We identified five clusters among women and seven among men. Respondents in poor-EQ clusters were disproportionately people of color and less-educated; they also tended to report worse health. For example, among women, the prevalence of poor/fair SRH and moderate mental illness was lowest among standard-employment-relationship-like-non-union workers and the becoming self-employed, and greatest among minimally-attached, returning-to-the-labor-force, and precariously-employed workers. Meanwhile, among men, the prevalence of the outcomes was lowest among stably-high-wage workers and the wealthy self-employed, and greatest among exiting-the-labor-force and precariously-employed workers. Given the potential role of EQ in health inequities, researchers and practitioners should consider EQ in their work.


Heterogeneity of cancer-associated fibroblasts: Opportunities for precision medicine.
Despite marked development in cancer therapies during recent decades, the prognosis for advanced cancer remains poor. The conventional tumor-cell-centric view of cancer can only explain part of cancer progression, and thus a thorough understanding of the tumor microenvironment (TME) is crucial. Among cells within the TME, cancer-associated fibroblasts (CAFs) are attracting attention as a target for cancer therapy. However, CAFs present a heterogeneous population of cells and more detailed classification of CAFs and investigation of functions of each subset is needed to develop novel CAF-targeted therapies. In this context, application of newly developed approaches to single-cell analysis has already made an impact on our understanding of the heterogeneity of CAFs. Here, we review the recent literature on CAF heterogeneity and function, and discuss the possibility of novel therapies targeting CAF subsets.


Targetome profiling, pathway analysis and genetic association study implicate miR-202 in lymphomagenesis.
miRNAs have been implicated in numerous tumorigenic pathways, and previous studies have associated miR-202 dysregulation with various cancer types, including follicular lymphoma. The miR-202 targetome was identified by ribonucleoprotein immunoprecipitation-microarray (RIP-Chip), and functional interactions among identified targets were investigated using the Ingenuity Pathway Analysis tool. We also conducted a population-based genetic association study of a polymorphism within the miR-202 stem-loop sequence and risk of non-Hodgkin lymphoma. In vitro gain-of-function experiments were further conducted to elucidate the functional significance of the variant. A total of 141 potential members of the miR-202 targetome were identified by a transcriptome-wide RIP-Chip assay. Functional interactions among identified targets suggested that miR-202-regulated genes are involved in biologic pathways relevant for hematologic function and cancer. Consistent with this, a genetic association analysis using human blood samples revealed a significant association between a germline mutation (rs12355840) in the miR-202 precursor sequence and follicular lymphoma risk. An in vitro functional assay further showed that the variant allele resulted in diminished miR-202 levels, possibly by altering precursor-processing efficiency. Taken together, our findings suggest that miR-202 is involved in follicular lymphomagenesis. These findings implicate miR-202 as a potential tumor suppressor in follicular lymphoma and warrant the investigation of miR-202 as a novel biomarker of follicular lymphoma risk.


Spectroflurimetric estimation of the new antiviral agent ledipasvir in presence of sofosbuvir.
A spectroflurimetric method has been developed and validated for the selective quantitative determination of ledipasvir in presence of sofosbuvir. In this method the native fluorescence of ledipasvir in ethanol at 405nm was measured after excitation at 340nm. The proposed method was validated according to ICH guidelines and show high sensitivity, accuracy and precision. Furthermore this method was successfully applied to the analysis of ledipasvir in pharmaceutical dosage form without interference from sofosbuvir and other additives and the results were statistically compared to a reported method and found no significant difference.


The relationship between pitch velocity and shoulder distraction force and elbow valgus torque in collegiate and high school pitchers.
The relationship between pitch velocity, shoulder distraction force, and elbow valgus torque is not well understood. The purpose of this study was to (1) determine the association between baseball pitch velocity and shoulder distraction force and (2) determine the association between baseball pitch velocity and elbow valgus torque. A subpurpose was to determine these same associations within subgroups of college baseball and high school baseball pitchers. Collegiate and high school baseball pitchers were biomechanically analyzed; variables extracted from the pitching reports included fastball pitch velocity, shoulder distraction force, and elbow valgus torque. Linear regression was performed to analyze the relationship between fastball velocity and shoulder and elbow kinetics. Subgroup analyses were then performed for college and high school pitches. Coefficients and 95% confidence intervals (95% CI) were calculated, with R squared (r2) used to assess model fit. A total of 70 pitchers (college: n = 23; high school: n = 47) were included in this study. There was a positive weak linear relationship between pitch velocity and shoulder distraction force (3.24 %body weight [BW] [95% CI: 2.07, 4.40], r2 = 0.32, P < .001) and elbow valgus torque (0.16 %body weight × height [BW × H] [95% CI: 0.11, 0.20], r2 = 0.44, P < .001). College pitchers did not exhibit a relationship between pitch velocity and shoulder distraction force (1.44 %BW [95% CI: -2.50, 5.38], r2 = 0.02, P < .001), whereas high school pitchers did exhibit a weak positive linear relationship between pitch velocity and shoulder distraction force (3.69 %BW [95% CI: 2.25, 5.14], r2 = 0.36, P < .001). Both college and high school pitchers exhibited a weak positive relationship between pitch velocity and elbow valgus torque (college: 0.15 %BW × H [95% CI: 0.05, 0.25], r2 = 0.29, P < .001; high school: 0.16 %BW × H [95% CI: 0.09, 0.22], r2 = 0.36, P < .001). Pitching velocity exhibited a weak positive linear relationship with both shoulder distraction force and elbow valgus torque. However, only high school pitchers were observed to have a weak positive linear relationship between pitch velocity and shoulder distraction force, whereas both college and high school pitchers exhibited a weak positive relationship between pitch velocity and elbow valgus torque. These findings suggest that older pitchers may attenuate shoulder forces with increased pitch velocity due to physical maturity or increased pitching mechanical skill in comparison with younger pitchers.


Synthesis of sialyl Lewis X mimetics using the Ugi four-component reaction.
Application of the Ugi four-component condensation to rapidly synthesize a library of glycopeptide mimics of the tetrasaccharide SLe(x) as inhibitors of E- and P-selectin, and to study the effect of varied functionality in mimics on the inhibition is described.


A survey of fumonisins (B1, B2, B3) in Indonesian corn-based food and feed samples.
In this paper a survey is described for determination of contamination level of fumonisins (B(1), B(2), B(3)) in Indonesian cornbased feed and food samples. The survey was conducted from February to May 2001. Foodstuffs, which are consumed directly such as snacks and other products, were investigated for fumonisin contamination. Of 105 food and feed samples purchased from local retail stores and local poultry shops around Yogyakarta, Java, Indonesia were analyzed using ELISA. Results indicate that 74.3% of samples analyzed were contaminated in a large range of 10.0 - 3307 μg/kg, and the concentration of fumonisins depends on the type of samples. Detection limit of the method used was 9 μg/kg.From eight food samples of maize flour, and corn-based beverages and cereals, none was contaminated (below detection limit). For food samples of industrial products (19 samples), 13 were contaminated in the range of 22.8 - 105 μg/kg and 19 of 20 samples from home made products were contaminated between 12.9 - 234 μg/kg. The food samples contaminated in highest level occurred in corn. Of ten samples, 6 were contaminated from 68.0 - 2471 μg/kg. For feed samples, 17 corn samples were evaluated. Of those samples, 16 contained in a large range of 17.6 - 3306 μg/kg.


Tetrazolium-based colorimetric assays underestimat the direct antitumor effects of anti-VEGF agent bevacizumab.
The direct antitumor effect of bevacizumab (BEV) has long been debated. Assessment of the direct cytotoxic activities of drugs is usually conducted via in vitro experiments, of which tetrazolium-based colorimetric assays are widely employed to measure the direct antitumor activity of BEV. This study aimed to investigate whether tetrazolium-based colorimetric assays are applicable when evaluating the cytotoxicity of BEV against tumor cells. Our results showed that BEV significantly augmented tumor-cell mitochondrial metabolism. Enhanced mitochondrial metabolism caused changes in cellular oxidation-and-reduction environment and upregulated succinate dehydrogenase, which in turn promoted the reduction of tetrazolium to produce formazan. Increased formazan formation resulted in underestimation of the in vitro direct antitumor effect of BEV. Furthermore, inhibition of mitochondrial hypermetabolism partially corrected the underestimation of colorimetric assays in evaluating the direct antitumor activity of BEV. Our findings suggest that tetrazolium-based colorimetric assays are unsuitable for accurately assessing the in vitro cytotoxicity of anti-VEGF drugs and may be the methodological reason for the controversial direct antitumor effect of BEV.


Developmental changes in cerebrospinal fluid pressure and resistance to absorption in rats.
Cerebrospinal fluid (c.s.f.) pressure and resistance to absorption have been studied in exteriorized fetuses (18 to 21 days gestation) from pregnant rats anaesthetised with pentobarbitone and in similarly anaesthetised postnatal rats at 1, 5, 10 and 30 days after birth and in adults. The resting c.s.f. pressure was low in fetuses (17-21 mm H2O) and it rose to 26-27 mm H2O at 1 and 5 days after birth. By 10 days after birth the pressure was 34 mm H2O after which time there was no further change. The plateau pressure response to different infusion rates was linear, but only up to pressures around 7-fold higher than the resting c.s.f. pressure. Hence, resistance to absorption was calculated for plateau pressures up to 140 mm H2O in fetuses, to 200 mm H2O in 1- and 5-day rats and to 240 mm H2O for 10-day, 30-day and adult rats. Resistance to absorption was not significantly different for the two measurement sites (lateral ventricle and subarachnoid space) at any age studied, showing that fluid can move freely through the ventricular system in young rats. The resistance to absorption was low in the fetuses, 10.8 and 16.3 mm H2O min/microliters at 18-19 and 20-21 days gestation, respectively. There was a sharp increase in resistance to 39.2 mm H2O min/microliters at 1 day after birth and thereafter there was a decrease to 6.8 mm H2O min/microliters at 30 days and this was similar to adult values. This decrease in outflow resistance from the first day after birth may be related to the increase in c.s.f. pressure and secretion rate that occur after birth in the rat.


Pharmacokinetic behaviour and anthelmintic efficacy of 1-n-butyl carbamoyl oxfendazole given by intramuscular injection.
Oxfendazole (OFZ) was chemically modified to 1-n-butyl carbamoyl OFZ (C4-OFZ) in an attempt to improve the solubility of OFZ and enable it to be administered by injection. After intramuscular injection to sheep and cattle, C4-OFZ was metabolised to OFZ which resulted in higher plasma OFZ concentrations that persisted for a considerably longer period than those observed following administration of OFZ orally. The anthelmintic efficacy of injected C4-OFZ was tested, in sheep, against strains of Trichostrongylus colubriformis, Haemonchus contortus and Ostertagia circumcincta, which were highly resistant to benzimidazoles. In all cases, the C4-OFZ treatment showed a significant improvement in efficacy over the conventional oral OFZ drench.


Health related quality of life in patients treated with multimodal therapy for prostate cancer.
Patients with prostate cancer and high risk disease characteristics may benefit from multimodal therapy. However, the effects of multimodal therapy on health related quality of life have not been comprehensively described. We further characterized health related quality of life in patients treated with multimodal therapy. Patient data were obtained from the CaPSURE database, a national disease registry of men with prostate cancer. Included patients received active primary therapy (ie surgery or various forms of radiation) for prostate cancer with or without adjuvant or neoadjuvant therapy, and had complete clinical data, including health related quality of life assessments at baseline and through 2 years after treatment. The association between health related quality of life outcomes and different primary therapies with and without adjuvant or neoadjuvant therapy over time was analyzed using a repeated measures mixed model for each primary therapy. A total of 2,204 men met the study criteria. As primary therapy 1,427 patients received radical prostatectomy, 267 received external beam radiation therapy and 510 received brachytherapy. When androgen deprivation therapy was included with radical prostatectomy, brachytherapy or external beam radiation therapy, there was a transient loss of sexual function that improved within 9 months postoperatively. When external beam radiation therapy was given with brachytherapy there was continuous worsening of urinary function and bother through 21 months. Multimodal therapy may lead to declines in health related quality of life especially in the domains of urinary function, urinary bother and sexual function. These effects must be considered and patients must be counseled appropriately before initiation of multimodal therapy.


Effects of two different hydrocortisone doses on human peripheral blood lymphocyte nucleologram.
The effect of 200 and 500 mg of hydrocortisone hemisuccinate given i.v. on the circulating lymphocyte nucleologram was studied in 12 healthy volunteers. Transient lymphopenia was observed in all treated subjects, with the nadir at 3 to 9 h after drug administration. An evaluation of the lymphocyte nucleologram, at this time, showed a statistically significant decrease in mono- and binucleolated lymphocytes. By 24-36 h, the number of total lymphocytes and the nucleologram had returned to baseline values. No differences were revealed among the two groups of subjects. The role of lymphocyte redistribution and of lymphocytolysis to explain the lymphocytopenia and the behaviour of lymphocyte nucleologram is discussed.


Overview of the regulation of S-phase in Xenopus egg extracts.
Recently, several components required for nuclear DNA replication and involved in the regulation of S-phase within the cell cycle have been identified. Though detailed models of these events are not available, we focus on recent developments arisen from analysis in Xenopus egg extracts.


[Vitamin K epoxide reductase complex 1 gene polymorphism and warfarin dose requirement in Chinese patients].
To investigate the possible relationship between vitamin K epoxide reductase complex 1 (VKORC1) gene polymorphism and warfarin dose requirements in Chinese patients. Genotyping for the C1173T polymorphism in the VKORC1 gene was performed using a restriction enzyme digestion of PCR-amplified DNA in 102 Chinese patients treated with warfarin. TT genotype was found in 83 patients (81.4%), CT genotype in 16 patients (15.7%) and CC genotype in 3 patients (2.9%). To achieve similar target INR range (1.5 - 2.5), the warfarin dose requirement was significantly lower in patients with TT genotype than that in patients with CT/CC genotypes (P < 0.01). C1173T polymorphism in the VKORC1 gene might be one important determinant for warfarin dose requirement in Chinese patients.


Parallel gradualistic evolution of Ordovician trilobites.
There are very few high-resolution studies of the fossil record from which to assess the relative frequency of gradualistic and punctuated evolution. Here I report some of the first detailed evidence of phyletic gradualism in benthic macroinvertebrates, based on a study of approximately 15,000 trilobites from central Wales. Over a period of about three million years, as many as eight lineages underwent a net increase in the number of pygidial ribs, a species-diagnostic character. The end members of most lineages have previously been assigned to different species and, in one case, to different genera. In view of intermediate morphologies and temporary trend reversals, however, practical taxonomic subdivision of each lineage proved impossible. The apparent success of earlier Linnean nomenclature (with its implications of discrete species) could easily have been misinterpreted as evidence of punctuation and stasis, and it is probable that detection of many other gradualistic patterns has been hindered by ready application of binominal taxonomy to fossils.


Retracted: Exploring Online Teaching Design of Curriculum Politics by Deep Learning and Visual Sensing Technology.
[This retracts the article DOI: 10.1155/2022/1283256.].


Mefatinib as first-line treatment of patients with advanced EGFR-mutant non-small-cell lung cancer: a phase Ib/II efficacy and biomarker study.
EGFR inhibitors have revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC). Mefatinib is a novel, bioavailable, second-generation, irreversible pan-EGFR inhibitor. This phase Ib/II open-label, single-arm, multi-center study investigated the efficacy, safety, biomarker, and resistance mechanisms of mefatinib in the first-line treatment of patients with advanced EGFR-mutant NSCLC. This study included 106 patients with EGFR-mutant stage IIIB-IV NSCLC who received first-line mefatinib at a daily dose of either 60 mg (n = 51) or 80 mg (n = 55). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The cohort achieved an ORR of 84.9% and DCR of 97.2%. The median PFS was 15.4 months and the median OS was 31.6 months. Brain metastasis was detected in 29% of patients (n = 31) at diagnosis and demonstrated an ORR of 87.1%, PFS of 12.8 months, and OS of 25.2 months. Adverse events primarily involved skin and gastrointestinal toxicities, which were well-tolerated and manageable. Analyses of mutation profiles were performed using targeted sequencing of plasma samples at baseline, first follow-up 6 weeks from starting mefatinib therapy (F1), and at progression. Patients with concurrent TP53 mutations had comparable PFS as wild-type TP53 (14.0 vs 15.4 months; p = 0.315). Furthermore, circulating tumor DNA clearance was associated with longer PFS (p = 0.040) and OS (p = 0.002). EGFR T790M was the predominant molecular mechanism of mefatinib resistance (42.1%, 16/38). First-line mefatinib provides durable PFS and an acceptable toxicity profile in patients with advanced EGFR-mutant NSCLC.


Allergy and asthma.
An increased prevalence of sensitization to inhalants in asthmatic children is well known. Bronchial hyperresponsiveness is regarded as a major characteristic of bronchial asthma and is partly acquired during life as a result of a permanent airway irritation to inhaled allergens. We investigated 704 schoolchildren of two different climate areas for existing bronchial hyperreactivity (cumulative carbachol test) and sensitization to ten common aeroallergens (by skin prick test). Additional information on residential factors, passive smoking, and clinical symptoms for asthma was obtained by a standardized interview and compared with the clinical results. Among 35 of 704 children who were considered as asthmatics, 83% demonstrated a sensitization to one or more allergens. On the contrary, only one third of the nonasthmatic population (n = 669) showed sensitization in the skin test. The relative risk for allergy in children with bronchial hyperreactivity was increased (odds ratio 3.0). Therefore we regard sensitization to common inhalants as an important predictor of asthma in childhood.


Antigen based detection of cystic echinococcosis in buffaloes using ELISA and Dot-EIA.
Cystic echinococcosis is caused by the larval stage of the dog tapeworm, Echinococcus granulosus. The disease is recognized as one of the world's major zoonoses affecting human beings and domestic animals apart from its economic and public health importance. Development of the cysts in the intermediate host such as buffaloes occurs in the lungs, liver and other organs. In this study, detection of circulating antigen in the diagnosis of cystic echinococcosis in buffaloes was done using enzyme linked immunosorbent assay and Dot-Enzyme immunoassay (Dot-EIA). The sensitivity and specificity were determined as 89 and 92 % respectively, whereas those of Dot-EIA were determined as 94 and 96 %.


Diabetes Associated Markers After Bariatric Surgery: Fetuin-A, but Not Matrix Metalloproteinase-7, Is Reduced.
Recent studies showed that fetuin-A and matrix metalloproteinase-7 (MMP-7) are type 2 diabetes mellitus (T2DM)-associated markers. Bariatric surgery not only reduces body weight but also improves T2DM. This study aimed to investigate the changes of fetuin-A and MMP-7 in obese subjects with and without T2DM after bariatric surgery. We enrolled 130 obese subjects that received bariatric surgery, including 41 Roux-en-Y gastric bypass (RYGB), 67 mini-gastric bypass (MGB), and 22 sleeve gastrectomy (SG) patients. Forty-three patients suffered from T2DM prior to surgery. The fasting serum fetuin-A and MMP-7 levels were measured before and 1 year after surgery. Only five of 43 patients remained diabetic after surgery. Preoperative T2DM patients had higher fetuin-A and MMP-7 levels than non-T2DM subjects. RYGB, MGB, and SG all decreased the fetuin-A levels 1 year after the operation. The MMP-7 levels were not changed after RYGB, MGB, or SG. In multivariate analyses, the preoperative fetuin-A was significantly related to the diastolic blood pressure (DBP) and glycosylated hemoglobin (HbA1c), while the postoperative fetuin-A was independently related to the waist-to-hip ratio and HbA1c. Moreover, the preoperative MMP-7 level was significantly related to age, DBP, aspartate transaminase, alanine transaminase, and gamma-glutamyl transferase (rGT), while the postoperative MMP-7 level was independently related to age and rGT. The fetuin-A and MMP-7 levels are both higher in obese T2DM than non-T2DM subjects. The level of fetuin-A is reduced after RYGB, MGB, and SG, but the level of MMP-7 remains unchanged.


Molecular pharmacological basis of the YiSui ShenXu Granule in beta-thalassemia therapy.
To study the molecular pharmacological basis of the YiSui ShenXu Granule, a complex prescription of the Chinese traditional medicine used to treat beta-thalassemia. Real-time quantitative PCR method had been applied to analyze the genes expression: gamma-globin, Ckit, EpoR, Spi, FKLF, GATA1 and GATA2 in K562 cell treated and untreated with this complex prescription and its each single herbal medicine. The results showed that this complex prescription increased the gamma-globin, EpoR, Spi and FKLF expression and decreased the Ckit, GATA1 and GATA2 expression. And all single herbal medicines of this complex prescription could change some of those gene expressions, but not the same as the complex prescription. Even that, this study results indicated that the YiSui ShenXu Granule has its molecular pharmacological basis in treating beta-thalassemia.


Practicing preventive medicine: a national survey of general preventive medicine residency graduates--United States, 1991.
We conducted a national survey of all physicians who graduated from preventive medicine residency (PMR) programs between 1979 and 1989. We mailed a self-administered questionnaire to all PMR graduates of the 43 U.S. programs in General Preventive Medicine and Public Health, requesting information on their current professional activities. Out of 1,070 PMR graduates, 797 (75%) responded to the survey. Overall, graduates were distinguished from other physicians by both work setting and work activities. PMR graduates worked predominantly in institutional settings: in federal or state health agencies, academia, or hospitals/clinics. In addition to maintaining their involvement in clinical medicine, PMR graduates were heavily involved in epidemiologic research and program management. This unique blend of organizational skills, expertise in population-based research, and clinical experience makes PMR graduates an increasingly important human resource as health care reform increases the population of patients being cared for in a managed care setting.


Plasma Concentrations and Safety of Lopinavir/Ritonavir in COVID-19 Patients.
Although the efficacy of lopinavir/ritonavir has not been proven, it has been proposed as an off-label treatment for COVID-19. Previously, it has been reported that the plasma concentrations of lopinavir significantly increase in inflammatory settings. As COVID-19 may be associated with major inflammation, assessing the plasma concentrations and safety of lopinavir in COVID-19 patients is essential. Real-world COVID-19 data based on a retrospective study. Among the 31 COVID-19 patients treated with lopinavir/ritonavir between March 18, 2020 and April 1, 2020, higher lopinavir plasma concentrations were observed, which increased by 4.6-fold (interquartile range: 3.6-6.2), compared with the average plasma concentrations in HIV. Lopinavir concentrations in all except one patient were above the upper limit of the concentration range of HIV treatment. Approximately one to 5 patients prematurely stopped treatment mainly because of an ADR related to hepatic or gastrointestinal disorders. Lopinavir plasma concentrations in patients with moderate-to-severe COVID-19 were higher than expected, and they were associated with the occurrence of hepatic or gastrointestinal adverse drug reactions. However, a high plasma concentration may be required for in vivo antiviral activity against SARS-CoV-2, as suggested by previous studies. Therefore, in the absence of adverse drug reaction, lopinavir dosage should not be reduced. Caution is essential because off-label use can be associated with a new drug safety profile.


Ex vivo study of manual and rotary instrumentation techniques in human primary teeth.
This study aimed to evaluate, ex vivo, time and dentin removal by manual and rotary instrumentation in human primary teeth. Eighty primary teeth were divided into 2 groups, embedded in resin, and sectioned for evaluation before and after instrumentation. For manual technique, teeth were prepared using K-type files and rotary preparation was performed with Hero 642. All root canals were prepared up to size 40, and the instrumentation time was recorded. Dentin removal was calculated using digital image software. Data was statistically analyzed using chi-squared, Mann-Whitney, and t tests. Manual instrumentation removed more dentin in all groups compared with rotary instrumentation (P < .05). In some specimens, root perforations were observed in areas coinciding with largest root resorption. Rotary technique showed the shortest instrumentation time (P < .05). Deciduous teeth, without significant root resorption, have enough root structure for instrumentation up to size 40. Rotary technique required less time and generated less dentin removal.


Follow-up of the sagittal spine by optical technique.
Report the use of an optical technique for individual monitoring of the sagittal morphology of the spine in an upright position while avoid irradiation. The series consists of 15 asymptomatic subjects and 326 cases with spinal disorders. Sagittal analysis is expressed by the global trunk tilt (GTT), the intensity of the curves and their level of inflection. The confidence interval is 2 to 3° and 3 to 6mm according to the parameters. A significant correlation was observed for the global axis measured by optical or radiological techniques. Variations in intensity and proportion of thoracic and lumbar sagittal curves were observed according to the disease, as well as their evolution over a period of 5 to 30 months. Various "strategies" of adaptation have been observed during repeated examinations. This non-radiating technique allows to be repeated after initial X-rays, for regular monitoring of a disturbance or a therapeutic effect. Its understandable imaging allows the patient to be aware of his situation. This optical technique is reliable and safe for monitoring the sagittal balance while helping further therapeutic target.


The influence of imipramine on dopamine-induced ganglionic inhibition and neurogenic vasodilatation in the dog.
Imipramine potentiates the dopamine-induced inhibition in the paravertebral lumbar ganglia of the dog. Potentiation by imipramine of the dopamine-induced neurogenic vasodilatation in the isolated perfused gracilis muscle, is seen in cross-circulation preparations only, where imipramine is injected into the perfusion circuit of an isolated perfused gracilis muscle, it antagonizes the dopamine-induced neurogenic vasodilatation. When imipramine is injected intravenously into a dog with an autoperfused gracilis muscle, the peripheral antagonism masks the potentiating effect at the ganglionic level, and the dopamine-induced neurogenic vasodilatation is abolished.


The intracellular location of pyruvate carboxylase, citrate synthase and 3-hydroxyacyl-CoA dehydrogenase in lactating rat mammary gland.
The intracellular location of pyruvate carboxylase (EC 188.8.131.52), citrate synthase (EC 126.96.36.199) and 3-hydroxyacyl-CoA dehydrogenase (EC 220.127.116.11) in rat mammary gland was investigated by using a fractional-extraction technique. The results indicate a mitochondrial location for all three enzymes.


Adenocarcinoma within anorectal fistulae: different clinicopathological characteristics between Crohn's disease-associated type and the usual type.
Adenocarcinoma within anorectal fistulae is rare and is sometimes associated with Crohn's disease. Crohn's disease-associated adenocarcinoma within anorectal fistulae has a poor prognosis; however, little is known about the clinicopathological differences between Crohn's disease-associated adenocarcinoma within anorectal fistulae and usual adenocarcinoma within anorectal fistulae. We retrospectively searched patients' charts and pathology archives at Tokyo Yamate Medical Center and Tokyo Medical and Dental University Hospital for adenocarcinoma within anorectal fistulae. Clinical and pathological data were collected and immunohistochemical examinations were conducted. Overall survival rate was estimated using the Kaplan-Meier method. Prognostic factors of overall survival were assessed using univariate and multivariate Cox regression analyses. We examined 82 cases of adenocarcinoma within anorectal fistulae. Fifty-nine of 82 cases (72%) had usual adenocarcinoma within anorectal fistulae, while the remaining 23 cases (28%) had Crohn's disease-associated adenocarcinoma within anorectal fistulae. Patients with Crohn's disease-associated adenocarcinoma within anorectal fistulae were diagnosed at a younger age and at a more advanced stage than those with usual adenocarcinoma within anorectal fistulae. Macroscopic and histological types were also different between usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae. Crohn's disease-associated adenocarcinoma within anorectal fistulae included more ulcerative types and high-grade adenocarcinomas. The rate of lymphovascular invasion was higher in Crohn's disease-associated adenocarcinoma within anorectal fistulae. Immunohistochemically, the expression of E-cadherin, p53, and MUC5AC differed between usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae. Patients with Crohn's disease-associated adenocarcinoma within anorectal fistulae exhibited worse overall survival than those with usual adenocarcinoma within anorectal fistulae, and vascular invasion was the strongest significant independent predictor of overall survival in patients with adenocarcinoma within anorectal fistulae. In conclusion, usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae have different clinicopathological characteristics and should be considered separate clinical entities.


A smoothing neural network for minimization l1-lp in sparse signal reconstruction with measurement noises.
This paper investigates a smoothing neural network (SNN) to solve a robust sparse signal reconstruction in compressed sensing (CS), where the objective function is nonsmooth l1-norm and the feasible set satisfies an inequality of lp-norm 2≥p≥1 which is used for measuring residual errors. With a smoothing approximate technique, the non-smooth and non-Lipschitz continuous issues of the l1-norm and the gradient of lp-norm can be solved efficiently. We propose a SNN which is modeled by a differential equation and give its circuit implementation. In this case, we prove the proposed SNN converges to the optimal of considered problem. Simulation results are discussed to demonstrate the efficiency of the proposed algorithm.


Release of prostacyclin from the dog saphenous vein by 5-hydroxytryptamine.
5-Hydroxytryptamine (5-HT) stimulated the release of prostacyclin (PGI2) from strips of the dog saphenous vein. This stimulation was maintained after mechanical removal of the endothelium. The effect of 5-HT was mimicked by alpha-methyl-5-hydroxytryptamine (alpha-CH3-5-HT) but not by 5-carboxamidotryptamine (5-CT) and it was inhibited by ritanserin. It is concluded that, in the dog saphenous vein, the stimulation of PGI2 release by 5-HT involves 5-HT2 receptors distinct from the '5-HT1-like' receptors that mediate contraction of the vessel.


[The relationship between lymph node size and metastasis and extracapsular spread in squamous cell carcinoma of the larynx, orohypopharynx, and oral cavity].
We examined the relationship between lymph node size and metastasis and extracapsular spread (ECS) in patients who underwent neck dissection for squamous cell carcinoma of the larynx, orohypopharynx, or oral cavity. We retrospectively evaluated a total of 200 neck dissections performed in 128 patients (107 males, 21 females; mean age 56+/-11 years; range 26 to 81 years) with squamous cell carcinoma of the larynx, orohypopharynx, or oral cavity, and having complete clinical and pathologic data. Along with 442 metastatic lymph nodes (139 with ECS), the greatest axial diameter of the biggest benign lymph node obtained from each patient was measured. Lymph nodes were classified according to the neck zone and size, and the relationship of lymph node size with metastasis and ECS was examined. Lymph nodes with metastasis and ECS were often 11 to 30 mm in size and the highest rates of metastasis and ECS were seen in lymph nodes measuring 31 to 60 mm. However, approximately 40% and 25% of lymph nodes with metastasis and ECS, respectively, were in the range of 1 to 10 mm, which is not clinically accepted as pathologic. In larynx, orohypopharynx, and oral cavity squamous cell carcinomas, the clinical assessment of the size of neck lymph nodes is usually not a predictor for lymph node metastasis or ECS. Thus, until methods like sentinel lymph node biopsy become standard to determine occult metastasis, the importance of elective neck dissections is still valid in clinically N0 necks.


Metabolic and clinical considerations in an unusual patient with 35% BSA deep partial-thickness thermal injury.
The treatment of a moderately large burn usually require blood and its products to restore circulating blood volume, achieve metabolic stabilization, and promote wound healing. This case study demonstrates the remarkable metabolic response to injury in a patient refusing blood products administration. Specific management considerations are discussed.


Electron microscopy analysis of femtosecond laser-assisted capsulotomy before and after lens fragmentation.
Studying anterior lens capsule cutting edge profiles from femtosecond laser-assisted capsulotomy procedures performed before and after lens fragmentation. Twenty eyes (10 patients) with age-related cataract underwent femtosecond laser-assisted surgery (FLACS) using the Ziemer Z8 platform. First step of laser surgery was either capsulotomy (group first) or fragmentation (group second). One eye of each patient was assigned randomly, the second eye treated with the different sequence of procedures. After anterior capsule removal, tissue was fixed in cacodylate-buffered solution and cutting-edge profiles were analysed using scanning electron microscopy (SEM). All cases had cataract grade 2 and 3 based on LOCS III grading. SEM analysis showed more smooth edges in the first group, especially in cases with pseudoexfoliation (P = 0.037); more tags and bridges and a significant number of staggered cutting patterns (7 out of 10 cases) in the second group. All cases evolved the same microgroves with "valleys and mountains " as signs of the photodisruption process. Femtosecond laser capsulotomy should be performed before lens fragmentation minimizing the rate of cutting errors. Especially in eyes with advanced cataract, as intracapsular pressure may increase due to lens fragmentation without anterior capsular opening.


Histochemistry of ventricular heavy-chain myosins in cardiomyopathic Syrian hamsters treated with D-600.
Monoclonal antibodies (MAb) have been used to study the distribution of ventricular heavy-chain (HC) myosins in cardiomyopathic UM-X7.1 Syrian hamsters. The Ab were identified as alpha and beta anti-HC myosins because of their ability to cross-react with ventricular V1 and V3 myosins, respectively. Cryostat frozen sections from the midventricle region of normal and myopathic hearts were processed for demonstration of these isomyosins by indirect immunofluorescence. In myopathic hearts, there was a shift of predominant alpha myosin toward the beta isoform with the time course of the hamster cardiomyopathy. A D-600 treatment while preventing cardiac necrotic lesions had little or no effect on the beta isomyosin conversion. It is inferred that the isomyosin shift during the progression of the hamster cardiomyopathy is unrelated to the necrotizing process and merely reflects the hypokynetism of the cardiomyocytes.


Streptococcus pneumoniae Surface Adhesin PfbA Exhibits Host Specificity by Binding to Human Serum Albumin but Not Bovine, Rabbit and Porcine Serum Albumins.
PfbA (Plasmin(ogen) and Fibronectin Binding protein A) is an adhesin present on the surface of Streptococcus pneumoniae. Initial studies characterized PfbA as plasmin(ogen) and fibronectin binding protein and later it was found that it binds with many other proteins of the extracellular matrix such as fibrinogen, collagen and laminin. It also binds to blood protein human serum albumin (HSA). Interestingly, PfbA exhibits no binding with serum albumins of bovine (BSA), rabbit (RSA) and porcine (PSA) which are sequentially and structurally homologous to HSA. This suggests that PfbA is likely involved in host specificity. Therefore, to get more insights into this aspect, a detailed analysis, which includes the interaction of rPfbA with HSA/BSA/RSA/PSA at different pHs by bio-layer interferometry, comparison of sequences and surface electrostatic potential of HSA/BSA/RSA/PSA, lysine modification of HSA by succinylation and subsequent interaction analysis of succinylated HSA with rPfbA and the secondary structural content estimation by FT-IR spectroscopy was carried out. Since large protrusions are another important geometric feature of protein surfaces, the property was also analyzed for HSA/BSA/RSA/PSA. The results of the above studies clearly suggest that the rPfbA exhibits host specificity by selectively binding only to HSA and not with its homologous BSA/RSA/PSA. Since the three dimensional structures of these albumins are highly similar, it is likely that rPfbA utilizes the differences in the surface electrostatic charge in combination with surface protrusions of HSA/BSA/RSA/PSA for the selective molecular recognition process and this feature may be important in the pathogenesis of pneumococcal infection.


Promoter methylation of AREG, HOXA11, hMLH1, NDRG2, NPTX2 and Tes genes in glioblastoma.
Epigenetic alterations alone or in combination with genetic mechanisms play a key role in brain tumorigenesis. Glioblastoma is one of the most common, lethal and poor clinical outcome primary brain tumors with extraordinarily miscellaneous epigenetic alterations profile. The aim of this study was to investigate new potential prognostic epigenetic markers such as AREG, HOXA11, hMLH1, NDRG2, NTPX2 and Tes genes promoter methylation, frequency and value for patients outcome. We examined the promoter methylation status using methylation-specific polymerase chain reaction in 100 glioblastoma tissue samples. The value for clinical outcome was calculated using Kaplan-Meier estimation with log-rank test. DNA promoter methylation was frequent event appearing more than 45 % for gene. AREG and HOXA11 methylation status was significantly associated with patient age. HOXA11 showed the tendency to be associated with patient outcome in glioblastomas. AREG gene promoter methylation showed significant correlation with poor patient outcome. AREG methylation remained significantly associated with patient survival in a Cox multivariate model including MGMT promoter methylation status. This study of new epigenetic targets has shown considerably high level of analyzed genes promoter methylation variability in glioblastoma tissue. AREG gene might be valuable marker for glioblastoma patient survival prognosis, however further analysis is needed to clarify the independence and appropriateness of the marker.


Heparan sulfate levels in mucopolysaccharidoses and mucolipidoses.
Glycosaminoglycans are accumulated in both mucopolysaccharidoses (MPS) and mucolipidoses (ML). MPS I, II, III and VII and ML II and ML III patients cannot properly degrade heparan sulphate (HS). In spite of the importance of HS storage in the metabolic pathway in these diseases, blood and urine HS levels have not been determined systematically using a simple and economical method. Using a new ELISA method using anti-HS antibodies, HS concentrations in blood and urine were determined in MPS and ML II and ML III patients. HS concentrations were determined in 156 plasma samples from MPS I (n = 23), MPS II (n = 26), MPS III (n = 24), MPS IV (n = 62), MPS VI (n = 5), MPS VII (n = 5), ML II (n = 8) and ML III (n = 3), and 205 urine samples from MPS I (n = 33), MPS II (n = 33), MPS III (n = 30), MPS IV (n = 82), MPS VI (n = 7), MPS VII (n = 9), ML II (n = 8) and ML III (n = 3). The ELISA method used monoclonal antibodies against HS. MPS I, II, III and VII and ML II and III patients had significant elevation in plasma HS, compared to the age-matched controls (p < 0.0001). Eighty-three out of 89 (93.3%) of individual values in the above MPS types and ML were above the mean +2SD of the controls. In urine samples, 75% of individual values in patients with those types were above the mean +2SD of the controls. In contrast to the previous understanding of the HS metabolic pathway, plasma HS levels in all five MPS VI and 15% of MPS IV patients were elevated above the mean +2SD of the controls. These findings suggest that HS concentration determined by ELISA, especially in plasma, could be a helpful marker for detection of the most severe MPS I, II, III, VI and VII and ML II, distinguishing them from normal populations.


Health Related Quality of Life of Caregivers of Children and Adolescents With Phenylketonuria: A Systematic Review.
Introduction. Caregivers of children with chronic illness are at risk of having impairment in their quality of life (QOL). We systematically reviewed the available literature related to the Health Related Quality Of Life (HRQOL) of caregivers of children with Phenylketonuria (PKU). Methods. We comprehensively searched in electronic databases including Scopus, Science Direct, CINAHL, Medline, PubMed, Google scholar, and ProQuest. The search criteria included studies with samples more than one, children suffering from PKU, exploring parents or primary caregiver's HRQOL, published from 2010 to 2020, full article available for download and published in English. Eight studies including 5 cross sectional studies, 1 open label trial, and 2 surveys were systematically reviewed. Results. Seven out of 8 studies have established a negative correlation between PKU and parent's HRQOL in at least 1 of the domains. In one study, the HRQOL of parents is higher than their population norms. Conclusion. Most of the caregivers had poor to moderate HRQOL. More studies are required to explore HRQOL of caregivers of children with PKU using similar tools and outcome measures addressing all the domains of HRQOL in order to have more clarity on the impact of PKU on caregiver's HRQOL. Interventional studies might help in improving the HRQOL of caregivers.


Comparison of echocardiographic and fluoroscopic sizing of the left atrial appendage prior to percutaneous closure.
Sizing of the left atrial appendage (LAA) ostium prior to occlusion (LAAO) is routinely performed with transesophageal echocardiography (TEE). We sought to compare the utility of sizing via fluoroscopy to TEE for percutaneous LAAO. We retrospectively evaluated all patients undergoing percutaneous LAAO at our institution from April 2015 through January 2018 (n = 195). We evaluated baseline characteristics, maximum measured ostium size (for both TEE and fluoroscopy), and differences in measured size to device size for both techniques. Of the total cohort, 185 (95%) had both intraoperative TEE and fluoroscopic images available for analysis and were included in the final analysis. The mean age was 74 years and 64% were male. Hypertension was present in 89%, diabetes in 30%, and stroke in 32% of patients. The mean ejection fraction was 51%. The most common LAA morphology was "wind sock" (52%). Measured ostial diameter on fluoroscopy was larger compared with TEE (2.04 ± 3.43 mm larger on fluoroscopy, p < 0.001). Ostium diameter on TEE was more closely correlated to the size of the device implanted compared with fluoroscopy (0.76 vs. 0.61, p = 0.001). Fluoroscopy results in larger estimated LAA ostium diameter compared with TEE. Despite this, TEE was more strongly correlated to operator choice in device sizing, which may reflect practice patterns. Because compression of the ostium on the device is necessary for long-term procedural success, under-sizing may lead to a higher rate of leaks. Prospective evaluation of the utility of routine fluoroscopic sizing compared with TEE is warranted.


Features for medically serious suicide attempters who do not have a strong intent to die: a cross-sectional study in rural China.
Previous studies have implied that there were many Chinese suicide attempters who did not want to die by suicide. In the current study, we explored the factors which were associated with low levels of suicide intent. We also examined features for medically serious suicide attempters who do not have a strong intent to die in rural china. Cross-sectional study. The interviews occurred between May 2012 and July 2013 in 13 rural counties in Shandong and Hunan provinces, China. Subjects were 791 medically serious suicide attempters whose injury and wounds were so serious they required hospitalisation or immediate medical care. The results supported that less years of education (β=-0.11, p=0.037), religious beliefs (β=1.20, p=0.005), living alone (β=1.92, p=0.017), negative life events (β=0.29, p=0.003), low levels of impulsivity (β=-0.10, p=0.013) and mental disorders (β=2.82, p<0.001) were associated with higher levels of suicide intent. Results imply that there are some medically serious suicide attempters with a higher education and/or exhibit impulsivity who do not want to die by suicide. These findings can inform practice to prevent suicide in rural China.


Clinical characteristics of pregnancies complicated by intrapartum fetal asphyxia.
The clinical characteristics of 124 pregnancies complicated by intrapartum fetal asphyxia have been reviewed. The evidence of fetal asphyxia tends to appear earlier in patients with maternal medical and obstetric complications than in those with labor complications. Evidence of clinical fetal distress was present in 36 per cent and was not related to the severity of the asphyxia. Low Apgar scores occurred in 40 per cent of infants with moderate asphyxia and in 80 per cent of infants with severe asphyxia at delivery. In the newborn infants, clinical evidence of cerebral abnormality was observed in 3 per cent, and evidence of the respiratory distress syndrome was seen in 3 per cent of the study group.


A modification to the Walch classification of the glenoid in primary glenohumeral osteoarthritis using three-dimensional imaging.
Since Walch and colleagues originally classified glenoid morphology in the setting of glenohumeral osteoarthritis, several authors have reported varying levels of interobserver and intraobserver reliability. We propose several modifications to the Walch classification that we hypothesize will increase interobserver and intraobserver reliability. We propose the addition of the B3 and D glenoids and a more precise definition of the A2 glenoid. The B3 glenoid is monoconcave and worn preferentially in its posterior aspect, leading to pathologic retroversion of at least 15° or subluxation of 70%, or both. The D glenoid is defined by glenoid anteversion or anterior humeral head subluxation. The A2 glenoid has a line connecting the anterior and posterior native glenoid rims that transects the humeral head. Using 3-dimensional computed tomography glenoid reconstructions, 3 evaluators used the original Walch classification and the modified Walch classification to classify 129 nonconsecutive glenoids on 4 separate occasions. Reliabilities were assessed by calculating κ coefficients. Interobserver reliabilities improved from an average of 0.391 (indicating fair agreement) using the original classification to an average of 0.703 (substantial agreement) using the modified classification. Intraobserver reliabilities improved from an average of 0.605 (moderate agreement) to an average of 0.882 (nearly perfect agreement). When 3-dimensional glenoid reconstructions and the modified Walch classification described herein are used, improved interobserver and intraobserver reliabilities are obtained.


The bilaminar and banded distribution of the callosal terminals in the posterior neocortex of the rat.
After callosal sectioning, the callosal connections of the posterior neocortex of the rat cerebral hemisphere were demonstrated using the Fink-Heimer technique. Serial frozen sections of the whole brains were cut in transverse, horizontal, and tangential planes. In tissue sections, degenerating terminals were concentrated in two distinct laminae within the depth of the cortex. In addition the terminals had a patchy distribution. The degeneration was marked on projection drawings of serially arranged sections, and subsequent reconstruction showed the terminal degeneration to be distributed in bands. Five dorsoventrally oriented bands of terminals were present in areas 39, 41 and 36 collectively, and a rostrocaudal band in area 20. In area 17 terminations were apparently absent except at its borders with areas 18, 18a and 7. The degenerating callosal terminals within these areas produced a circumferential band around area 17. The findings are discussed with respect to the significance of these patterns of corticocortical connections.


Glaucoma patients have an increased level of trimethylamine, a toxic product of gut bacteria, in the aqueous humor: a pilot study.
Animal studies suggest that gut bacteria metabolites are involved in regulation of intraocular pressure or development of glaucoma. However, clinical data are lacking. Here, we wanted to compare level of trimethylamine (TMA), an uremic toxin produced by gut bacteria, along with betaine and trimethylamine N-oxide (TMAO), a substrate and a product of its metabolism, in the aqueous humor and in plasma of patients with glaucoma and their controls. Twenty patients were selected for cataract phacoemulsification, and 20 patients selected for phacotrabeculectomy were enrolled in the study. Patients were matched with controls on systemic diseases and estimated glomerular filtration rate. Blood samples were collected in the preoperative suite, whereas aqueous humor samples were collected as the first step of both procedures. Subsequently, level of betaine, TMA and TMAO was analyzed by means of chromatography. In the aqueous humor, level of TMA, but not betaine or TMAO, was significantly higher in the phacotrabeculectomy group than in the phacoemulsification group. Plasma level of betaine, TMA and TMAO was similar between groups. In both groups, level of betaine and TMA, but not TMAO, was significantly higher in plasma than in the aqueous humor. TMA, but not TMAO or betaine level, is increased in the aqueous humor of patients with glaucoma. TMA might play a role in pathogenesis of glaucoma; however, prospective studies are needed to confirm our findings.


[Liberation of inorganic phosphates in the coronary sinus as an indicator of human myocardial ischemia].
The effects of atrial pacing (A.P.) on the myocardial balance of inorganic phosphate (Pi) were studied in 11 patients with coronary atherosclerosis and pacing-induced angina (Group C) and in 5 normal subjects (Group N). During A.P. in group C 64% of patients had myocardial loss of Pi, statistically significant (p less than 0,025) always with concomitant reduced myocardial extraction or production of lactate, but only 70% of patients with reduced myocardial extraction or production of lactate had myocardial loss of Pi. In only 1 p. of group N myocardial loss of Pi with normal lactate extraction was observed. These data show that during pacing-induced ischemia there is a negative myocardial balance of Pi, that can be used as a metabolic indicator of ischemia, but less reliable than lactate reduced extraction or production.


Comparison of Early Fatigue Failure of the TFNa and Gamma 3 Cephalomedullary Nails in the United States From 2015 to 2019.
To compare reports of implant fatigue failure submitted to the FDA of 2 commonly used cephalomedullary nails. In total, 2724 medical device reports from the FDA's MAUDE database from Jan 2015 to Oct 2019 were reviewed for the Trochanteric Femoral Nail-Advanced (TFNa) and Gamma 3 implants. Data from 342 implant failures included in the MAUDE database were analyzed. TFNa and Gamma 3 had 183 and 159 reported fatigue failures, respectively. All failed implants fractured in the same location through the proximal screw aperture. Time from implantation to failure was on average 2 months shorter for TFNa implants that were reported fractured than for Gamma 3 implants reported, a difference that was statistically significant (P < 0.05). In total, 100 implants were reported to have failed within the first 4 months (53 and 47 for TFNa and Gamma 3, respectively). For Gamma 3 implants that failed in the first 4 months, almost all of the available manufacturers' inspection reports revealed implant notches at the point of failure from drilling. For TFNa implants that failed early, only one reported notch was noted in the available inspection reports. In contrast to other studies regarding fatigue failure, reported failures in both TFNa and Gamma 3 occurred earlier than can be attributed to delayed or nonunion. The reported failures of the TFNa in the MAUDE database occurred earlier than did those of the Gamma 3. Early failures of the Gamma 3 seemed to be the result of iatrogenic implant notching. Therapeutic Level III. See instructions for authors for a complete description of levels of evidence.


Blood pressure and metabolic effects of ACTH in anephric sheep.
1. ACTH (80--100 iu/day) was administered to seven sheep for 3--5 days following bilateral nephrectomy. 2. ACTH treatment produced rises in mean arterial pressure in anephric sheep similar to those observed in intact animals. Following withdrawal of ACTH, blood pressure declined over the following 72 h. 3. ACTH produced a transient fall in plasma potassium and anephric sheep, suggesting an internal redistribution mechanism for this ion. 4. These studies demonstrate that adrenal steroid hormones can modify blood pressure in the absence of the kidney.


The role of non-directiveness in genetic counseling.
When the complete human genome has been sequenced, everyone of us will become a potential candidate for genetic counseling and testing. Within a short period of time everyone will obtain his personal genetic passport identifying deleterious and susceptibility genes. With the availability of presymptomatic tests for late-onset disorders and the possibilities of prevention and treatment, the conflict between directiveness and nondirectiveness will dominate the counseling setting. Despite general consent on providing genetic information in a nondirective fashion to preserve value neutrality and enhance client's autonomy, there is no accepted common definition of what non-directiveness really is or ought to be. The article tries to elaborate some aspects which might be fruitful and clarifying in the complex issues involved in the black box of genetic counseling.


LIX1-mediated changes in mitochondrial metabolism control the fate of digestive mesenchyme-derived cells.
YAP1 and TAZ are transcriptional co-activator proteins that play fundamental roles in many biological processes, from cell proliferation and cell lineage fate determination to tumorigenesis. We previously demonstrated that Limb Expression 1 (LIX1) regulates YAP1 and TAZ activity and controls digestive mesenchymal progenitor proliferation. However, LIX1 mode of action remains elusive. Here, we found that endogenous LIX1 is localized in mitochondria and is anchored to the outer mitochondrial membrane through S-palmitoylation of cysteine 84, a residue conserved in all LIX1 orthologs. LIX1 downregulation altered the mitochondrial ultrastructure, resulting in a significantly decreased respiration and attenuated production of mitochondrial reactive oxygen species (mtROS). Mechanistically, LIX1 knock-down impaired the stability of the mitochondrial proteins PHB2 and OPA1 that are found in complexes with mitochondrial-specific phospholipids and are required for cristae organization. Supplementation with unsaturated fatty acids counteracted the effects of LIX1 knock-down on mitochondrial morphology and ultrastructure and restored YAP1/TAZ signaling. Collectively, our data demonstrate that LIX1 is a key regulator of cristae organization, modulating mtROS level and subsequently regulating the signaling cascades that control fate commitment of digestive mesenchyme-derived cells.


Transforming growth factor β receptor signaling restrains growth of pancreatic carcinoma cells.
Pancreatic ductal adenocarcinoma (PDAC) is extremely malignant. Efficient control of cancer growth may substantially improve the survival of PDAC patients. However, no efficient treatments are so far available. Here, we inhibited transforming growth factor β (TGFβ) receptor signaling by overexpression of a key inhibitor of this pathway, SMAD7, in the mouse pancreas, using a recently developed intraductal infusion method. Overexpression of SMAD7 significantly increased growth of both implanted PDAC and PDAC by K-ras modification. Our data thus suggest that TGFβ receptor signaling restrains growth of PDAC, and modulation of TGFβ receptor signaling may be an effective treatment for PDAC.


Long-term physical and neurodevelopmental outcomes after antenatal betamethasone administration for congenital heart block prevention.
Congenital heart block (CHB) is associated with a mortality rate of 20% and requires a pacemaker in 70% of cases. Steroids can reduce morbidity and prevent the onset of CHB but may have adverse effects on growth and neurodevelopment. This study aimed to clarify the long-term effects of antenatal betamethasone administration on growth and neurodevelopment. The subjects were children with a high risk of CHB due to a high level of maternal anti-SSA/Ro antibody or a maternal history of a previous delivery of a offspring with CHB to whom antenatal betamethasone was administered. Data on body weight, height, and blood pressure were collected as physical outcomes. The Wechsler Intelligence Scale for Children (fourth edition) or the Kyoto Scale of Psychological Development and the Pervasive Developmental Disorders Autism Society Japan Rating Scale was administered to assess the neurodevelopmental outcome. Fourteen children were enrolled. The body weight and height were within normal range in all children. All children had normal intelligence, and none had autism. Our study suggested that antenatal betamethasone administration has no negative effects on long-term physical and neurodevelopmental outcomes.


Advancing nursing science in vulnerable populations: measurement issues.
This study examined measurement practices of researchers in relation to vulnerable population research published in four general nursing research journals in 2004. The purpose was to identify issues and imperatives in the measurement of research variables with vulnerable populations that warrant attention. A total of 133 articles were eligible for inclusion in the study, and 428 measurement instruments were used in the studies. A content analysis of the 133 eligible articles indicated that most samples included to a greater extent more Whites than predominantly minority populations, and more adults than children. Most of the articles did not specify socioeconomic status of samples. Of the 133 eligible articles, 83 (62.4%) included samples that were comprised of a majority of racial and ethnic minorities; however, percentages of studies that focused predominately on a specific minority group were below 10% in more than 80% of studies. Major findings related to measurement practices indicated inadequate specification of the measurement framework employed; lack of adequate specification of the conceptual base of measurement tools; and, a heavy reliance on the use of self-report data, attitudinal and perceptual measures, and the use of questionnaires and rating scales. There was also inadequate attention to the metric qualities of laboratory physiological measures, and to reliability and validity in general. It was concluded that inadequate attention is given to measurement practices by researchers when studying vulnerable populations.


Evidence for significant quantities of creatine kinase MM isoenzyme in human brain.
The isoenzymes of creatine kinase (ATP: creatine N-phosphotransferase, EC 126.96.36.199) in human brain were studied. Approx. 30% of total creatine kinase activity is due to the MM isoenzyme. The identity of this isoenzyme was confirmed by several techniques and shown not to be of mitochondrial origin.


The Irish cattle population structured by enterprise type: overview, trade & trends.
The cattle sector is the most important economic production unit of the Irish farming and agri-food sector. Despite its relevance, there has been limited quantitative information about the structure of differing cattle production types and of the connections between them. This paper addresses this gap by providing, for the first time, an overview of the Irish cattle population structured by enterprise type. METHODS & RESULTS: We collected data from the cattle register for the period 2015 to 2019 and assigned registered herds to one of 18 different herd types using a recently published herd type classification approach. This allows, for the first time, to exploring changes in enterprise types and subtypes over time, and describing the movements between these subtypes and from these subtypes to slaughter. The overview and associated classification presented in this study will form the basis for a number of future comparative studies, including cross-sectoral assessments of profitability, estimation of the extent of animal health losses on Irish cattle farms or structural analysis of Greenhouse Gas (GHG) emissions across production systems.


Is there an association between the nutritional and functional parameters and congestive heart failure severity?
The association between markers of nutritional status (handgrip strength [HGS] and adductor pollicis muscle thickness [APMT]) and clinical markers of congestive heart failure (CHF) severity is currently unclear. The objective of this study was to evaluate the association between HGS, APMT, as markers of nutritional status and CHF severity. APMT and muscle strength was measured in 500 CHF patients bilaterally. Nutritional status was assessed by Subjective Global Assessment (SGA). Functional classification was performed according to guidelines provided by the New York Heart Association (NYHA) and ejection fraction (EF) was measured to classify CHF severity. Poisson regression, adjusted for sex and age, was performed to verify the association between nutritional factors and CHF severity markers. The majority of patients (75.8%) were ≥60 years old and 53.6% were either overweight or obese. SGA identified 42.2% of the patients as malnourished, 12.6% with low APMT, and 29.0% with low HGS. Most of the patients were classified as NYHA III/IV (56.8%) and almost one third of patients (31.1%) had EF ≤ 40%. HGS and APMT were significantly lower in malnourished male patients and in male patients with a lower EF or worse NYHA classification. Even after controlling for the EF, malnourished patients showed a 2.5-fold increased risk of CHF severity by NYHA classification and for each kilogram of increase in the HGS, there was a significant decrease of 2% in the risk (RR: 0.98 p < 0.001). Malnourished patients presented a 52% higher risk (RR: 1.52 p = 0.016) of having a low EF, whereas for each APMT increase, there was a 5% decrease in the risk (RR: 0.95 p < 0.001), even after controlling for NYHA classification. Malnutrition is highly prevalent among patients with CHF and it is associated with the functional class and the severity of the disease. Objective markers of strength (HGS) and muscle (APMT) are independently associated with the CHF severity, assessed by NYHA classification and EF, respectively, even after adjustment for other confounding variables. Thus, the implementation of these nutritional assessment methods in hospital routines, either by SGA or by objective methods, such as HGS and APMT, can configure effective measurements for early detection of malnutrition in patients at higher risk, and possibly a way to avoid their further functional decline.


The export of hazardous factories to developing nations.
The export of hazardous industrial plants to developing nations is examined for a number of industries. As hazardous and polluting industries come under increasing regulation in industrial nations, some of the affected processes are exported, without improvements to make them less hazardous, to nonregulating countries where cheap and uninformed labor is abundant. "Runaway shops" then market their products in industrial nations with the competitive advantage of not having had to comply with costly workplace and pollution-control regulations. The international trade impacts of hazard export include: export of jobs from regulating to nonregulating countries; shift of international balance of payments in favor of nonregulating countries; export of mortal health hazards and environmental destruction to workers and communities in nonregulating nations, in order to produce goods for consumption by the regulating countries; weakened competitive position of reputable manufacturers who incur control costs and complete in domestic and would markets against less scrupulous companies; prolonged widespread use of discredited, extremely hazardous technologies, arising from the continuing "subsidy" of certain industries by workers and communities exposed to uncontrolled, well-recognized, mortal health hazards; and aggravated international relations resulting from developing nations' awareness and concern over becoming dumping grounds for hazard export from industrial nations.


Diffuse and severe ischemic injury of the extremities: a complication of umbilical vein catheterization.
We report a case of severe, peripheral, and diffuse tissue ischemia after umbilical vein catheterization (UVC) in a preterm newborn born to a preeclamptic mother. Nitroglycerin ointment was used to treat lesions. The recovery was good but partial loss of the distal phalange of one finger and one toe occurred. This is the first report of peripheral vasospasm occurring after UVC. Topical nitroglycerin, traditionally used to treat peripheral artery catheter-induced ischemic injury, may be useful to treat the same lesions occurring after UVC.


Expanding access to non-medicalized community-based rapid testing to men who have sex with men: an urgent HIV prevention intervention (the ANRS-DRAG study).
Little is known about the public health benefits of community-based, non-medicalized rapid HIV testing offers (CBOffer) specifically targeting men who have sex with men (MSM), compared with the standard medicalized HIV testing offer (SMOffer) in France. This study aimed to verify whether such a CBOffer, implemented in voluntary counselling and testing centres, could improve access to less recently HIV-tested MSM who present a risk behaviour profile similar to or higher than MSM tested with the SMOffer. This multisite study enrolled MSM attending voluntary counselling and testing centres' during opening hours in the SMOffer. CBOffer enrolees voluntarily came to the centres outside of opening hours, following a communication campaign in gay venues. A self-administered questionnaire was used to investigate HIV testing history and sexual behaviours including inconsistent condom use and risk reduction behaviours (in particular, a score of "intentional avoidance" for various at-risk situations was calculated). A mixed logistic regression identified factors associated with access to the CBOffer. Among the 330 participants, 64% attended the CBOffer. Percentages of inconsistent condom use in both offers were similar (51% CBOffer, 50% SMOffer). In multivariate analyses, those attending the CBOffer had only one or no test in the previous two years, had a lower intentional avoidance score, and met more casual partners in saunas and backrooms than SMOffer enrolees. This specific rapid CBOffer attracted MSM less recently HIV-tested, who presented similar inconsistent condom use rates to SMOffer enrolees but who exposed themselves more to HIV-associated risks. Increasing entry points for HIV testing using community and non-medicalized tests is a priority to reach MSM who are still excluded.


A study on the clinical characteristics of treating nevus of Ota by Q-switched Nd:YAG laser.
The purpose of this study was to retrospectively analyze the clinical characteristics of treating nevus of Ota by Q-switched Nd:YAG laser in Laser Cosmetology Center of Department of Dermatology, the Second Hospital, Xi'an Jiaotong University. The data of 1168 patients of nevus of Ota were analyzed retrospectively, which included the correlation among lesion color, treatment sessions, sex, age, lesion types, and effect. The Q-switched (QS) Nd:YAG laser system had a higher number of treatment sessions which were positively associated with a better response to treatment. Other variables, including gender, age, the categorization of the lesion according to Tanino's classification, and the color of the lesion, were not associated with the response to treatment. The treatment of nevus of Ota with QS Nd:YAG laser is safe and effective, with rare complications.


Comparison of the calcium- and magnesium-induced structural changes of troponin--C. A proton magnetic resonance study.
Previous proton magnetic resonance studies of the effects of Ca(II) on the structure of rabbit skeletal muscle troponin--C have shown that Ca(II) binding to the two high affinity sites of troponin--C both directs and stabilizes the folding of much of the structure. Ca(II) binding by the two low affinity sites of troponin--C causes changes in the environment of largely hydrophobic residues. We have now examined the structural changes caused by Mg(II) and by Ca(II) in the presence of excess Mg(II). Successive addition of Mg(II) to metal-free troponin--C leads to broadly similar, but not identical, structural changes to those previously assigned to Ca(II) binding at the high affinity sites. None of the changes previously assigned to Ca(II) binding to the low affinity sites was observed. Since Mg(II) does not bind to the low affinity sites, these results confirm the previous assignments. The spectral differences between Mg(II) and Ca(II) show that the degree of backbone folding and interactions between a group of hydrophobic residues (one or more Val, Leu, Ile; two or more Phe) are different for the two cations. In the presence of excess Mg(II), at a molar ratio that may exist in vivo (approx. 40 : 1 mol ratio Mg(II): Ca(II), titration with Ca(II) leads to a displacement of Mg(II) and to all the structural changes previously observed for Ca(II) alone. However, in the presence of Mg(II) the distinction between high and low affinity sites is blurred as judged by the overlap of the spectral changes associated with each of the binding sites. This result, together with the observation that Mg(II) promotes structural changes different from Ca(II), suggests a structural basis for the observation that the Ca(II) threshold for the activation of tension in some myofibrils is increased in the presence of high Mg(II) concentrations.


Genus-wide Bacillus species identification through proper artificial neural network experiments on fatty acid profiles.
Gas chromatographic fatty acid methyl ester analysis of bacteria is an easy, cheap and fast-automated identification tool routinely used in microbiological research. This paper reports on the application of artificial neural networks for genus-wide FAME-based identification of Bacillus species. Using 1,071 FAME profiles covering a genus-wide spectrum of 477 strains and 82 species, different balanced and imbalanced data sets have been created according to different validation methods and model parameters. Following training and validation, each classifier was evaluated on its ability to identify the profiles of a test set. Comparison of the classifiers showed a good identification rate favoring the imbalanced data sets. The presence of the Bacillus cereus and Bacillus subtilis groups made clear that it is of great importance to take into account the limitations of FAME analysis resolution for the construction of identification models. Indeed, as members of such a group cannot easily be distinguished from one another based upon FAME data alone, identification models built upon this data can neither be successful at keeping them apart. Comparison of the different experimental setups ultimately led to a few general recommendations. With respect to the routinely used commercial Sherlock Microbial Identification System (MIS, Microbial ID, Inc. (MIDI), Newark, Delaware, USA), the artificial neural network test results showed a significant improvement in Bacillus species identification. These results indicate that machine learning techniques such as artificial neural networks are most promising tools for FAME-based classification and identification of bacterial species.


Removal of focal atheromatous lesions by angioscopically guided high-speed rotary atherectomy. Preliminary experimental observations.
A new high-speed rotary atherectomy device, inserted over a guide wire and directed with an angioscope, offers the potential of restoring patency of outflow vessels by "boring out" the atheromatous lesion of the orifices of runoff vessels. The device was tested on 68 cadaver arteries with atheromatous lesions involving the superficial femoral, popliteal, and tibial arteries. This was performed with either free segments or in situ with the device placed through a popliteal arteriotomy. The gross results of rotary atherectomy were assessed by angioscopy, angiography, or both. The luminal surfaces were studied with scanning electron microscopy and transverse sections of vessels were studied with light microscopy. The pulverized atheroma, in colloidal suspension, was analyzed for particle size by Coulter counter. The effect of a colloidal suspension of atheromatous particles on distal capillary circulation was measured in animal experiments. Obstructive lesions were successfully removed in 36 of 37 stenotic arteries (97%) and 18 of 31 completely occluded arteries (58%), an overall efficacy of 54 of 68 (79%). In successfully atherectomized arteries, angioscopy and angiography demonstrated a widely patent, smooth, polished surface. Light microscopy demonstrated removal of the diseased intima with maintenance of the outer media and adventitia. The pulverized atheroma particles were generally smaller than red blood cells and injection of the colloidal atheroma into canine femoral arteries failed to produce local tissue injury. We conclude that in the human cadaver this atherectomy device effectively enlarges and recanalizes obstructed superficial femoral, popliteal, and tibial arteries.(ABSTRACT TRUNCATED AT 250 WORDS)


Proapoptotic activity and ABCC1-related multidrug resistance reduction ability of semisynthetic oleanolic acid derivatives DIOXOL and HIMOXOL in human acute promyelocytic leukemia cells.
One of the main problems of present-day oncology is the ability of neoplastic cells to develop different mechanisms of resistance to chemotherapeutic agent. A natural compound oleanolic acid (OA) was found to be active against many types of neoplastic cells. This paper examines the influence of eight semisynthetic oleanolic acid derivatives on drug-sensitive human acute promyelocytic leukemia cell line HL-60 and its multidrug resistant subline ABCC1 overexpressing HL-60/AR. Viability inhibition, proapoptotic activity, as well as influence on the ABCC1 gene expression level, ability to inhibit the transport function of multidrug resistance associated protein 1 (ABCC1) and to alter its level by the tested compounds, were evaluated. The most potent compounds were DIOXOL (methyl 3,11-dioxoolean-12-en-28-oate) and HIMOXOL (methyl 3-hydroxyimino-11-oxoolean-12-en-28-oate). DIOXOL was most efficient in inducing apoptosis of HL-60 cells. It activated both intrinsic and extrinsic pathways of apoptotic cell death. Proapoptotic properties of DIOXOL were probably related to the significant decrease of p65 NFκB level and inhibition of its translocation to the nucleus. In turn, HIMOXOL was the most potent compound against resistant HL-60/AR cells. It inhibited ABCC1 transport function (short time response) and decreased the level of ABCC1 protein (long time response) as a result of reduction of ABCC1 expression.


Influence of sex on the pharmacokinetic interaction of fleroxacin and ciprofloxacin with caffeine.
Previous pharmacokinetic studies have shown that a number of the quinolones inhibit the metabolism of caffeine. To evaluate the effect of sex on the interaction between two quinolones and caffeine. Multiple-dose, double-blind, randomised, three-period crossover study. Twelve male and twelve female healthy volunteers. Subjects received by mouth either fleroxacin 400 mg once daily and caffeine 100 mg three times daily, ciprofloxacin 500 mg twice daily and caffeine 100 mg three times daily, or caffeine alone, for 3 days. Subjects received each of the other regimens after 12-day washout periods. Plasma and urine concentrations were determined by validated high-performance liquid chromatography procedures and the data were analysed by noncompartmental linear pharmacokinetic methods. Analysis of the interaction by sex revealed that females showed a significant difference in caffeine pharmacokinetics in the presence of ciprofloxacin (area under the concentration-time curve [AUC], peak plasma concentration [C(max)], time to C(max) [t(max)] and apparent total body clearance [CL/F]) and fleroxacin (AUC and CL/F) when compared with males. Significant differences between sexes were also observed in the pharmacokinetics of ciprofloxacin (AUC, elimination rate constant [beta] and CL/F) and fleroxacin (C(max) and beta) in the presence of caffeine. However, these significant differences disappeared when AUC and C(max) were normalised to 70 kg bodyweight and CL/F was expressed as per kg bodyweight. The effect of quinolones on the pharmacokinetics of caffeine, and the reciprocal effect, are different between the sexes, due in part to different bodyweights.


An efficient way to achieve stable and high-rate ferrous ion-dependent nitrate removal (FeNiR): Batch sludge replacement.
Ferrous ion can be used as electron donor for denitrification in the ferrous ion-dependent nitrate removal (FeNiR). To prevent the FeNiR performance decrease caused by iron encrustation, a modified FeNiR process with batch sludge replacement was developed. Based on the decay kinetics of sludge mass and sludge activity, the sludge retention time (SRT) was determined as 40 days in the modified FeNiR process. To keep the FeNiR rate at 0.70 kg-N/(m3·d), the sludge replacement amount was 25% of total sludge every 10 days. The FeNiR efficiency stabilized around 70%. The batch sludge replacement could be an effective method to offset the active sludge decay caused by iron encrustation, and therefore led to the good FeNiR performance. The wasted FeNiR sludge was found to adsorb phosphate at a rate of 0.9 mg-P/(g VS min). The modified FeNiR process was proposed to be coupled with phosphate removal, achieving the co-removal of nitrate and phosphate. The coupled technology is promising due to the less consumption of resources and energy, as well as the less production of excessive sludge.


Behavioral Sciences in the Promotion of Oral Health.
The importance and value of behavioral sciences in dentistry have long been recognized, and their contribution to dental education, research, clinical practice, and oral health policy has been significant over the past half century. Over time behavioral sciences have expanded our understanding of oral health beyond "disease" to a broader biopsychosocial concept of oral health. This in turn has led dentistry away from a focus of "treatment" to oral health "care," notably in the new millennium. Key oral health behaviors have been identified for more than half a century: the importance of diet, oral hygiene, dental services, and other factors. Various behavioral models and theories have been proposed, particularly since the 1970s, providing useful frameworks with sound psychological basis to help understand the paths of oral health behaviors. These models draw on theories of self-efficacy, motivation, counseling, and "behavior change." Since the 1980s, there has been a greater understanding that these behaviors often share a common pathway with the etiology of other diseases (common risk factors). Furthermore, the relationship between individual factors and the broader environmental factors has been increasingly emphasized since the 1990s, leading to a united call for action in addressing oral health inequalities. Within the past decade, there are useful examples of models, frameworks, and techniques of behavior change with respect to oral health, involving planning, prompting, encouraging, goal setting, and/or motivating. In particular, there is a growing interest and use of motivational interviewing. Likewise, behavioral therapies, such as cognitive behavioral therapy, are increasingly being employed in dental practice in the management of dental anxiety, pain, and psychosomatic dental and oral problems, with promising results. Recommendations are outlined for future directions for behavioral sciences in the promotion of oral health.


Gestational hypertension and "severe" disease: time for a change.
Our understanding and management of gestational hypertension and its variants are substantially hindered by a reliance on antiquated terminology and on practice recommendations based largely on tradition rather than outcomes-based evidence. Unsurprisingly, gestational hypertension remains a major contributor to maternal and neonatal morbidity and mortality rates, with little improvement seen over the past half century except as it relates to better newborn care. Reliance on a binary classification of vastly disparate types and degrees of organ dysfunction (severe or not severe) and the use of nonphysiological and largely arbitrary gestational age cutoffs are particularly problematic. If this situation is to improve, it will be necessary to abandon current misleading terminology and non-evidence-based traditional practice patterns and start again, building on management approaches validated by outcomes-based data.