Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation.
Fructose consumption induces metabolic syndrome to increase cardiovascular disease risk. Cinnamaldehyde and allopurinol possess anti-oxidative and anti-inflammatory activity to relieve heart injury in metabolic syndrome. But the mechanisms of fructose-induced cardiac injury, and cardioprotective effects of cinnamaldehyde and allopurinol are not completely understood. In this study, fructose-fed rats displayed metabolic syndrome with elevated serum ox-LDL, cardiac oxidative stress, inflammation and fibrosis. Scavenger receptor CD36, Toll-like receptor 4 (TLR4), TLR6, IL-1R-associated kinase 4/1 (IRAK4/1), nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, interleukin-1β, transforming growth factor-β (TGF-β), drosophila mothers against DPP homolog (Smad) 2/3 phosphorylation and Smad4 were increased in animal and H9c2 cell models. These pathological processes were further evaluated in ox-LDL or fructose-exposed H9c2 cells pretreated with ROS scavenger and CD36 specific inhibitor, or IRAK1/4 inhibitor, and transfected with CD36, NLRP3, or IRAK4/1 siRNA, demonstrating that NLPR3 inflammasome activation through CD36-mediated TLR4/6-IRAK4/1 signaling may promote cardiac inflammation and fibrosis. Cinnamaldehyde and allopurinol reduced cardiac oxidative stress to suppress NLPR3 inflammasome activation and TGF-β/Smads signaling by inhibiting CD36-mediated TLR4/6-IRAK4/1 signaling under fructose induction. These results suggest that the blockage of CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation by cinnamaldehyde and allopurinol may protect against fructose-induced cardiac inflammation and fibrosis.


Elevated amylase levels as a result of self-induced hypersalivation.
A patient with recurrent vomiting, abdominal pain, and elevated serum amylase activity may have pancreatitis. Although elevated serum amylase levels are a sensitive indicator for acute pancreatitis, this test is not highly specific for pancreatic disease. A patient is described who illustrates the need for specific laboratory, historical, and occasional psychological evaluation in pediatric patients with elevated amylase values.


Racism Is Not a Factor in Door-to-electrocardiogram Times of Patients With Symptoms of Acute Coronary Syndrome: A Prospective, Observational Study.
Investigators have identified important racial identity/ethnicity-based differences in some aspects of acute coronary syndrome (ACS) care and outcomes (time to presentation, symptoms, receipt of coronary angiography/revascularization, repeat revascularization, mortality). Patient-based differences such as pathophysiology and treatment-seeking behavior account only partly for these outcome differences. We sought to investigate whether there are racial identity/ethnicity-based variations in the initial emergency department (ED) triage and care of patients with suspected ACS in Canadian hospitals. We prospectively enrolled ED patients with suspected ACS from one university-affiliated and two community hospitals. Trained research assistants administered a standardized interview to gather data on symptoms, treatment-seeking patterns, and self-reported racial/ethnic identity: "white," South Asian" (SA), "Asian," or "Other." Clinical parameters were obtained through chart review. The primary outcome was door-to-electrocardiogram (D2ECG) time. ECG times were log-transformed and two linear regression models, controlling for important demographic, system, and clinical factors, were fit. Of 448 participants, 214 (48%) reported white identity, 115 (26%) SA, 83 (19%) Asian, and 36 (8%) "Other." Asian respondents were younger and more likely to report initial discomfort as "low" and be accompanied by family; respondents identifying as "Other" were more likely to report initial discomfort as "high." There was no difference in D2ECG time between white participants and all other groups, but there were statistically significant differences by sex: women had longer D2ECG times than men. Exploring more specific racial identities revealed similar findings: no significant differences between the white, SA, Asian, and other groups, while sex (women had 13.4% [95% confidence interval, 0.81%-27.57%] longer D2ECG times) remained statistically significantly different in the adjusted models. Although racial/ethnicity-based differences in aspects of ACS care have been previously identified, we found no differences in the current study of early ED care in a Canadian urban setting. However, female patients experience longer D2ECG times, and this may be a target for process improvements.


Systematic review of antenatal dietary and lifestyle interventions in women with a normal body mass index.
Women who commence pregnancy with a normal body mass index (BMI) are at the greatest risk of excessive gestational weight gain, impacting on infant birthweight, pregnancy-related complications and postpartum weight retention. Our aim was to review systematically the effect of antenatal dietary and lifestyle interventions in pregnant women with a normal BMI on maternal and infant outcomes. We searched the Cochrane Controlled Trials Register, PubMed, Medline, and the Australian and International Clinical Trials Registry with the date of the last search in July 2015. We included all published, unpublished and ongoing randomized trials recruiting women of a normal BMI, comparing dietary and/or lifestyle interventions with standard antenatal care. Twelve randomized controlled trials were identified, involving a total of 2713 pregnant women, with five studies reporting clinical data for 714 women with a normal BMI. Women who received a dietary and lifestyle intervention were less likely to experience gestational weight gain [four studies, 446 women; mean difference -1.25 kg; 95% confidence interval (CI) -2.39 to -0.11], weight gain above the Institute of Medicine guidelines (four studies, 446 women; risk ratio 0.66; 95% CI 0.53-0.83) and hypertension (two studies; 243 women; risk ratio 0.34; 95% CI 0.13-0.91). There were no statistically significant differences in the occurrence of gestational diabetes, cesarean section or birthweight greater than 4 kg. While providing an antenatal dietary and lifestyle intervention for pregnant women of normal BMI appears to reduce gestational weight gain, the review was limited by the relatively small available sample size. Further well-designed randomized controlled trials are required.


Muscarinic acetylcholine receptors in Torpedo electric organ: effect of guanine nucleotides.
The effect of guanine nucleotides on the binding properties of presynaptic muscarinic receptors has been studied in a membrane preparation from the electric organ of Torpedo marmorata by measuring the competitive displacement of the radiolabelled antagonist, [3H]quinuclidinyl benzilate, by nonradioactive muscarinic ligands. The binding of the antagonists, atropine, scopolamine and pirenzepine was to a single class of sites [slope factors (pseudo Hill coefficients) close to 1] and was unaffected by 0.1 mM GTP. The binding of the N-methylated antagonists, N-methylatropine and N-methyl-scopolamine was more complex (slope factors less than 1) but also insensitive (N-methylatropine) to 0.1 mM GTP. Agonist binding was complex and could be resolved into two binding sites with relatively high and low affinities. The proportion of high-affinity sites varied with the nature of the agonist (15-80%). Agonist binding was depressed by 0.1 mM GTP, and the order of sensitivity was oxotremorine-M greater than carbamoylcholine greater than muscarine greater than acetylcholine greater than arecoline greater than oxotremorine. The binding of pilocarpine, a partial agonist, was unaffected by GTP. With carbamoylcholine as a test ligand the GTP effect on agonist binding was half-maximal at 12 microM. GDP and guanylylimidodiphosphate produced comparable inhibition of carbamoylcholine binding, but GMP and cyclic GMP were ineffective, as were various adenine nucleotides. Analysis of agonist binding in terms of a two-site model indicates that the predominant effect of guanine nucleotides is to reduce the number of sites of higher affinity.


Role of primary anterior cruciate ligament repair with or without augmentation.
Primary ACL repair with or without extra-articular augmentation can be functionally and statically successful based on our experience in high-performance athletes. Proper surgical technique, appropriate rehabilitation, and excellent quality of the tissue being repaired are required to achieve these results. Several notable improvements in diagnostic imaging, physical examination, surgical technique, and rehabilitation protocol have led to excellent results. The notchplasty, multiple loop suture technique, and improved meniscal repair are key factors. Moreover, we believe that one of the prime enhancements is to provide the highly stable extra-articular lateral capsular ligament reconstruction described previously. Laboratory findings have shown that this procedure provides excellent support against anterior subluxation immediately after surgery. It appears that release of the iliotibial band tissue proximally prevents stretching and failure of this extra-articular procedure. Rehabilitation unquestionably is a critical factor in the success of this surgical procedure. Immediate motion and appropriate biomechanical stresses on the repaired ligament have proved compatible with good functional and objective results. Even though intra-articular reconstruction of the torn ACL continues to be considered the gold standard, we remain convinced that primary repair of the ACL with appropriate extra-articular augmentation should not be ruled out in many cases. This procedure clearly is a viable, successful, and acceptable alternative to intra-articular reconstruction in selected cases.


Large-Conductance Calcium-Activated Potassium Channel Opener, NS1619, Protects Against Mesenteric Artery Remodeling Induced by Agonistic Autoantibodies Against the Angiotensin II Type 1 Receptor.
Background Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AAs) extensively exist in patients with hypertensive diseases and have been demonstrated to play crucial roles in the pathophysiological process of vascular remodeling. However, the treatment options are limited. The large-conductance calcium-activated potassium (BK) channel is a critical regulator and potential therapeutic target of vascular tone and architecture. We have previously observed that AT1-AAs have an inhibitory effect on BK channels. However, whether BK channel dysfunction is involved in AT1-AAs-induced vascular remodeling and the therapeutic effect of BK channel opener is unclear. Methods and Results In our study, mesenteric arteries from AT1-AAs-positive rats exhibited increased wall thickness, narrowing of the arteriolar lumen, and increased collagen accumulation. Patch clamp test results showed that the voltage sensitivity of BK channel declined in mesenteric arteriolar smooth muscle cells from AT1-AAs-positive rats. Experiments with freshly isolated mesenteric arteriolar smooth muscle cells showed that AT1-AAs reduced the opening probability, open levels, open dwell time, and calcium sensitivity of BK channel. Experiments with HEK293T cells transfected with GFP-ZERO-BK α-subunit plasmids suggested a BK channel α-subunit-dependent mechanism. BK channel α-subunit deficient, namely KCNMA1-/- rats showed a phenotype of mesenteric artery remodeling. The administration of NS1619, a specific BK channel opener targeting the α-subunit, reversed the phenotypic transition and migration induced by AT1-AAs in cultured mesenteric arteriolar smooth muscle cells. Finally, perfusion of NS1619 significantly relieved the pathological effects induced by AT1-AAs in vivo. Conclusions In summary, we provide compelling evidence that BK channel α-subunit dysfunction mediates AT1-AAs-induced mesenteric artery remodeling. Preservation of BK channel activity may serve as a potential strategy for the treatment of AT1-AAs-induced maladaptive resistance artery remodeling.


Identification of robust and generalizable biomarkers for microbiome-based stratification in lifestyle interventions.
A growing body of evidence suggests that the gut microbiota is strongly linked to general human health. Microbiome-directed interventions, such as diet and exercise, are acknowledged as a viable and achievable strategy for preventing disorders and improving human health. However, due to the significant inter-individual diversity of the gut microbiota between subjects, lifestyle recommendations are expected to have distinct and highly variable impacts to the microbiome structure. Here, through a large-scale meta-analysis including 1448 shotgun metagenomics samples obtained longitudinally from 396 individuals during lifestyle studies, we revealed Bacteroides stercoris, Prevotella copri, and Bacteroides vulgatus as biomarkers of microbiota's resistance to structural changes, and aromatic and non-aromatic amino acid biosynthesis as important regulator of microbiome dynamics. We established criteria for distinguishing between significant compositional changes from normal microbiota fluctuation and classified individuals based on their level of response. We further developed a machine learning model for predicting "responders" and "non-responders" independently of the type of intervention with an area under the curve of up to 0.86 in external validation cohorts of different ethnicities. We propose here that microbiome-based stratification is possible for identifying individuals with highly plastic or highly resistant microbial structures. Identifying subjects that will not respond to generalized lifestyle therapeutic interventions targeting the restructuring of gut microbiota is important to ensure that primary end-points of clinical studies are reached. Video Abstract.


Human antral damage induced by alcohol is potentiated by enprostil.
Enprostil, a synthetic analogue of prostaglandin E2, has been shown to protect the human gastroduodenal mucosa from aspirin injury. This study was designed to determine if enprostil protected against alcohol damage. A double-blind, randomized, cross-over study was performed on eight healthy adult men. After an overnight fast, a gastroscope was inserted and the antral mucosa was sprayed with a 10-mL test solution containing either enprostil (70 micrograms) or its vehicle (control). After 15 minutes, mucosal injury was scored (0-5), and the mucosa was sprayed with 100 mL 80% ethanol. Mucosal injury was scored after a further 15, 20, 25, and 30 minutes. The entire experiment was recorded on video film, which a second endoscopist used to score the damage independently. The two experiments were separated by an interval of 1 week. There was close agreement between the two endoscopists (r = 0.9385), and their scores were averaged. Using Friedman's two-way analysis of variance, a highly significant (P less than 0.00004) increase in injury was demonstrated following enprostil pretreatment. The Wilcoxin signed rank test showed the differences to be significant (P less than 0.05) at every time point. We conclude that enprostil, rather than protecting the human antral mucosa from alcohol injury, appears to potentiate this injury and may itself be damaging in therapeutic concentrations. This unexpected result cannot yet be explained but demands caution in the clinical use of enprostil.


[Clinicopathological study of colorectal cancer in young adults including a case of cancer family syndrome].
During the last 6 years, we examined 402 cases (including 5 cases in their 20's and 17 cases in their 30's) of colorectal cancer. We compared three groups (cases in their 20's, cases in their 30's, and cases over 40 years old), and had the following results. Cases in their 20's had a higher rate of familial history of colorectal cancer, and the cancer was located mainly in the proximal colon. Well differentiated and moderately differentiated adenocarcinoma was dominant in the cases in their 30's and in those over 40 years old. On the other hand mucinous adenocarcinoma and signet ring cell carcinoma was dominant in the cases in their 20's. A case of cancer family syndrome is also presented.


Control of dual-specificity phosphatase-1 expression in activated macrophages by IL-10.
Ligation of Toll-like receptors (TLR) on macrophages induces cytokines and mediators important for the control of pathogens. Macrophage activation has to be tightly controlled to prevent hyper-inflammation. Accordingly, the hallmarks of TLR-triggered signaling, nuclear translocation of NF-kappaB and phosphorylation of mitogen-activated protein kinases (MAPK), are transient events. We have mined microarray datasets for changes in the expression of phosphatases in resting and TLR-activated macrophages. Several members of the dual-specificity phosphatases (DUSP) were induced upon triggering TLR4 with LPS. Up-regulation of DUSP1 mRNA was transient after stimulation with LPS alone, but addition of the immunosuppressive cytokine IL-10 resulted in robust, continued DUSP1 expression. IL-10 also synergized with the anti-inflammatory glucocorticoid dexamethasone in the induction of DUSP1 mRNA expression in activated macrophages, as well as in the inhibition of IL-6 and IL-12 production. Increased expression of DUSP1 in IL-10-treated activated macrophages was correlated with a faster down-regulation of p38 MAPK activation. Thus, these data suggest an operational link between IL-10 and inhibition of p38 MAPK via sustained expression of DUSP1.


Quantitative Evaluation of Mitral Regurgitation Secondary to Mitral Valve Prolapse by Magnetic Resonance Imaging and Echocardiography.
The present prospective study was designed to evaluate the accuracy of quantitative assessment of mitral regurgitant fraction (MRF) by echocardiography and cardiac magnetic resonance imaging (cMRI) in the modern era using as reference method the blinded multiparametric integrative assessment of mitral regurgitation (MR) severity. 2-Dimensional (2D) and 3-dimensional (3D) MRF by echocardiography (2D echo MRF and 3D echo MRF) were obtained by measuring the difference in left ventricular (LV) total stroke volume (obtained from either 2D or 3D acquisition) and aortic forward stroke volume normalized to LV total stroke volume. MRF was calculated by cMRI using either (1) (LV stroke volume - systolic aortic outflow volume by phase contrast)/LV stroke volume (cMRI MRF [volumetric]) or (2) (mitral inflow volume - systolic aortic outflow volume)/mitral inflow volume (cMRI MRF [phase contrast]). Six patients had 1 + MR, 6 patients had 2 + MR, 12 patients had 3 + MR, and 10 had 4 + MR. A significant correlation was observed between MR grading and 2D echo MRF (r = 0.60, p <0.0001) and 3D echo MRF (r = 0.79, p <0.0001), cMRI MRF (volumetric) (r = 0.87, p <0.0001), and cMRI MRF (phase contrast r = 0.72, p <0.001). The accuracy of MRF for the diagnosis of MR ≥3+ or 4+ was the highest with cMRI MRF (volumetric) (area under the receiver-operating characteristic curve [AUC] = 0.98), followed by 3D echo MRF (AUC = 0.96), 2D echo MRF (AUC = 0.90), and cMRI MRF (phase contrast; AUC = 0.83). In conclusion, MRF by cMRI (volumetric method) and 3D echo MRF had the highest diagnostic value to detect significant MR, whereas the diagnostic value of 2D echo MRF and cMRI MRF (phase contrast) was lower. Hence, the present study suggests that both cMRI (volumetric method) and 3D echo represent best approaches for calculating MRF.


Identification of ceRNA and candidate genes related to fertility conversion of TCMS line YS3038 in wheat.
Previous studies have indicated that noncoding RNAs are important factors in gene functions. To explore the mechanism of male sterility of YS3038, the sterile genes were mapped, and based on previous work, the expression of long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and their target genes was studied. Weighted gene coexpression network analysis (WGCNA) and competitive endogenous RNA (ceRNA) analysis were further performed for differentially expressed noncoding RNAs and target genes. At last, the candidate genes were silenced by barley stripe mosaic virus-induced gene silencing (BSMV-VIGS) to prove their function. The sterile genes were mapped on chromosomes 1B and 6B based on chip mix pool analysis, and one major effect QTL (27.3190% variation) was found based on SSR primers. The WGCNA analysis revealed that the dark turquoise and steel blue modules were highly correlated with anther development and fertility conversion, respectively. The ceRNA analysis showed that a total of 184 RNAs interacted with each other, including 115 mRNAs, 55 microRNAs (miRNAs), eight circRNAs, and six lncRNAs. Finally, the seed setting rate of the plant was significantly decreased after fatty acyl-CoA reductase 5 silencing. This study provides breeders with a new option for the development of thermosensitive cytoplasmic male-sterile (TCMS) wheat lines, which will favor the sustainable development of two-line hybrid wheat.


Child maltreatment and adult violent offending: population-based twin study addressing the 'cycle of violence' hypothesis.
Associations between child maltreatment and adult violence, often termed the 'cycle of violence', are well documented. However, the nature of such links after appropriate control for confounding remains uncertain. We aimed to determine whether child maltreatment causes adult violent offending or whether suggested links are due to genetic or family environment confounding. A total of 18 083 20- to 47-year-old twins from the Swedish population-based Study of Twin Adults: Genes and Environment (STAGE) participated. We linked information on self-reported child maltreatment with national register data on convictions for adult crime. We used a case-control design to elucidate associations among unrelated individuals and also conducted within-discordant twin pair analyses to estimate the influence of familial confounding on this association. The odds ratio (OR), adjusted for age, sex and education, for violent offending in maltreated children grown up versus unrelated controls was 1.98 [95% confidence interval (CI) 1.52-2.57]. However, the association decreased to 1.18 (95% CI 0.62-2.25) when maltreated children were compared to their non-maltreated twins, suggesting substantial confounding by genetic or family environmental factors (within-twin OR<1.98) and a weak, non-significant causal effect (within-twin OR>1.00). Familial confounding was also pronounced for the association between child maltreatment and any offending. Childhood maltreatment was found to be a weak causal risk factor for adult violent offending; hence, reducing maltreatment might decrease violent crime less than previously expected. Instead, considerable familial confounding of the link between child maltreatment and adult violent offending suggests that prevention strategies need to address overlapping genetic and/or family environmental liability for abusive and violent behavior.


Surgery Grand Rounds: Perspectives of the 21st Century Attendee.
Grand rounds is an important and traditional academic medical institution. With generational changes in learning and the advancement of technology, it is difficult to know if the current method of grand rounds remains relevant and is meeting its audience's needs. Furthermore, surgeons may have different educational needs for grand rounds than other fields of healthcare. This study evaluates the needs of attendees and their attitudes toward modern surgical grand rounds through focus groups. Independent focus groups were conducted in the department of surgery at a large academic institution. In total, 19 individuals (five professors, three associate professors, three assistant professors, seven senior residents, and one junior resident) participated in the focus groups. Thematic analysis was conducted through a process of independent coding and defining of themes followed by joint revision until consensus was reached. Four major themes arose from the discussion: current design and format of grand rounds, audience attitudes and needs, perceived barriers to meaningful grand rounds, and suggestions and improvements to grand rounds. Further subthemes also emerged. These themes were present in both faculty and resident responses, with 115 individual data pieces coded in total. Grand rounds is an opportunity for social interaction, networking, professional and personal identity formation, and learning meaningful and relevant content. Audience diversity, desire for more audience engagement, and changes in the modern learning environment provide the largest challenges to meaningful grand rounds. This first and interesting research into surgery grand rounds provides insight on how to best meet attendee needs in the 21st century.


The arginine-stimulated insulin response is impaired in congenital duck hepatitis B virus infection.
Duck hepatitis B virus (DHBV) infects both A (glucagon-containing) and B (insulin-containing) islet cells. To examine the effect of this infection on islet cell function, baseline and secretagogue-augmented plasma insulin and glucagon levels as well as the pancreatic content of insulin and glucagon were compared in congenitally DHBV- and noninfected ducks. No difference in baseline plasma levels or the pancreatic content of insulin or glucagon was detected. However, the magnitude of the second phase of the biphasic arginine-stimulated insulin response was markedly diminished in infected ducks.


Prediction of the therapeutic effects of anticoagulation for recent portal vein thrombosis: a novel approach with contrast-enhanced ultrasound.
To examine whether intra-thrombus enhancement on contrast-enhanced sonograms can predict the recanalization by anticoagulation for recent portal thrombosis. This prospective study included 10 patients with a recent portal thrombosis and 20 controls (10 cirrhosis patients and 10 healthy subjects, all without thrombosis). The diagnosis of thrombosis was based on clinical and ultrasound findings. Pre-anticoagulation intra-thrombus enhancement on the contrast-enhanced sonogram was examined with respect to the post-anticoagulation results or portal enhancement in controls. Complete recanalization was obtained in 4 patients with positive intra-thrombus enhancement. However, in 4 other patients who had a thrombosis showing positive enhancement concurrent with one showing negative enhancement, anticoagulation recanalized the former and failed to recanalize the latter. Mean onset time of contrast enhancement measured from the beginning of hepatic arterial enhancement was significantly longer in the thrombus (6.6 ± 4.3 s, 3-16 s) than in the portal vein of controls (cirrhosis, 4.3 ± 1.4 s, 2-8 s, P = 0.0035; healthy subjects, 2.4 ± 0.6 s, 1-3 s, P < 0.0001). Anticoagulation failed to achieve recanalization in 2 patients with negative intra-thrombus enhancement. Sensitivity and specificity of contrast enhancement for the prediction of post-treatment recanalization was 100%. Intra-thrombus positive enhancement demonstrated on contrast-enhanced sonograms has promise as a successful predictor of recanalization for the recent portal thrombosis.


Inhibiting DNA methylation alters olfactory extinction but not acquisition learning in Apis cerana and Apis mellifera.
DNA methylation plays a key role in invertebrate acquisition and extinction memory. Honey bees have excellent olfactory learning, but the role of DNA methylation in memory formation has, to date, only been studied in Apis mellifera. We inhibited DNA methylation by inhibiting DNA methyltransferase (DNMT) with zebularine (zeb) and studied the resulting effects upon olfactory acquisition and extinction memory in two honey bee species, Apis cerana and A. mellifera. We used the proboscis extension reflex (PER) assay to measure memory. We provide the first demonstration that DNA methylation is also important in the olfactory extinction learning of A. cerana. DNMT did not reduce acquisition learning in either species. However, zeb bidirectionally and differentially altered extinction learning in both species. In particular, zeb provided 1h before acquisition learning improved extinction memory retention in A. mellifera, but reduced extinction memory retention in A. cerana. The reasons for these differences are unclear, but provide a basis for future studies to explore species-specific differences in the effects of methylation on memory formation.


Left ventricular hypertrophy and diastolic dysfunction in healthy pregnant women.
The purpose of this study was to examine which hemodynamic parameters change under the natural volume overload of pregnancy. 46 healthy pregnant women were echocardiographically examined during the course of pregnancy. To evaluate left ventricular diastolic function, mitral inflow and pulmonary venous flow profiles were used. Fractional shortening and left ventricular muscle mass were calculated. In the course of pregnancy the left ventricular muscle mass index increased (from 66 +/- 6 to 96 +/- 9 g/m(2)), fractional shortening decreased (from 38 +/- 4 to 32 +/- 6%) and a disturbed diastolic relaxation pattern was documented. Eight weeks after delivery, all left ventricular systolic and diastolic functional parameters returned to normal values. The natural volume overload in pregnancy leads to a reversible 'physiological' left ventricular hypertrophy, a short-term decrease in systolic function and a significant change in left ventricular diastolic function.


Pancreatic lipase inhibitory constituents from Morus alba leaves and optimization for extraction conditions.
The leaves of Morus alba (Moraceae) have been traditionally used for the treatment of metabolic diseases including diabetes and hyperlipidemia. Thus, inhibitory effect of M. alba leaves on pancreatic lipase and their active constituents were investigated in this study. Twenty phenolic compounds including ten flavonoids, eight benzofurans, one stilbene and one chalcones were isolated from the leaves of M. alba. Among the isolated compounds, morachalcone A (20) exerted strong pancreatic lipase inhibition with IC50 value of 6.2 μM. Other phenolic compounds containing a prenyl group showed moderate pancreatic lipase inhibition with IC50 value of <50 μM. Next, extraction conditions with maximum pancreatic lipase inhibition and phenolic content were optimized using response surface methodology with three-level-three-factor Box-Behnken design. Our results suggested the optimized extraction condition for maximum pancreatic lipase inhibition and phenolic content as ethanol concentration of 74.9%; temperature 57.4 °C and sample/solvent ratio, 1/10. The pancreatic lipase inhibition and total phenolic content under optimized condition were found to be 58.5% and 26.2 μg GAE (gallic acid equivalent)/mg extract, respectively, which were well matched with the predicted value.


Dyshaemopoiesis in adults: a practical classification for diagnosis and management.
Dyshaemopoiesis is a heterogeneous disease that may be classified into non-clonal and clonal dyshaemopoiesis. Non-clonal dyshaemopoiesis comprises reversible disorders with DNA synthesis impairment in dividing cells of the bone marrow by avitaminosis through various mechanisms or direct DNA damage from multiple causes. Complete haematologic recovery is obtained after vitamin supplementation or suppression of a myelotoxic agent. On the contrary, clonal dyshaemopoiesis is a group of chronic and usually irreversible diseases that may culminate in acute leukaemia (AL). These so called myelodysplastic syndromes (MDS) and their variants may be classified as primary, secondary and other diseases with doubtful clonality. A detailed classification of dyshaemopoiesis in adults may offer partial help in the diagnosis and management of dyshaemopoiesis. Pathobiological studies in progress allow better understanding of MDS and consequently the establishment of new modalities of treatment.


The "Economic Battle" Now and Then: (E)valuation Patterns of Distributive Justice in Cuban State-Socialism.
This article disentangles and explores some commonly made assumptions about egalitarian state-socialist ideologies. Based on the conceptual framework of the multiprinciple approach of justice, it presents the results of an in-depth analysis of (e)valuation patterns of distributive justice in Cuban state-socialism. The analysis mainly focuses on ideational conceptions of distributive justice (just rewards), but it also accounts for distribution outcomes and resulting (in)equalities (actual rewards). The results of the comparative case study of the Cuban framework of institutions and political leaders' views in two periods of time, the early 1960s and the 2010s, point to (e)valuation patterns that are generally labelled as egalitarian, such as the allocation rules of outcome equality and (non-functional) needs. However, contrary to common assumptions about egalitarian state-socialist ideologies, the results also point to several other patterns, including equity rules as well as functional and productivist allocation rules. I argue that many of these (e)valuation patterns, in their connection to the discursive storyline of the Cuban economic battle, are indeed compatible with egalitarian state-socialist ideology.


High-throughput phenotyping with electronic medical record data using a common semi-supervised approach (PheCAP).
Phenotypes are the foundation for clinical and genetic studies of disease risk and outcomes. The growth of biobanks linked to electronic medical record (EMR) data has both facilitated and increased the demand for efficient, accurate, and robust approaches for phenotyping millions of patients. Challenges to phenotyping with EMR data include variation in the accuracy of codes, as well as the high level of manual input required to identify features for the algorithm and to obtain gold standard labels. To address these challenges, we developed PheCAP, a high-throughput semi-supervised phenotyping pipeline. PheCAP begins with data from the EMR, including structured data and information extracted from the narrative notes using natural language processing (NLP). The standardized steps integrate automated procedures, which reduce the level of manual input, and machine learning approaches for algorithm training. PheCAP itself can be executed in 1-2 d if all data are available; however, the timing is largely dependent on the chart review stage, which typically requires at least 2 weeks. The final products of PheCAP include a phenotype algorithm, the probability of the phenotype for all patients, and a phenotype classification (yes or no).


[Tibial intramedullary nailing without open drilling].
By means on the basis of a prospective study of 33 osteosynthesis with the unreamed tibia nail (UTN) the following conclusions were found: 1. A technical simple, intramedullary solid strength bearing device in only two diameters is available, therefore costs for stock keeping are low. Systematic interlocking of the nail is necessary. Regarding the multiplicity of indication as well as the mechanical character the UTN is close to the principle of the internal fixator. 2. As a result of its solid constitution remarkable hollow cavities do not exist, so that retention of hematoma or secretions is limited (prophylaxis of infection). 3. In case of a closed nailing procedure the less rigid fracture fixation is favourable for the biology of the bone healing (fracture hematoma, less traumatic procedure without reaming of the medullary cavity, etc.). 4. The frequently observed breakage of interlocking bolts leads spontaneously to a dynamisation favourable as to time and therefore to a better bone healing process (callus formation). 5. Time intervals of bony fractures consolidation are significantly shorter compared to the exclusive osteosynthesis with the external fixator [3]. 6. The unreamed tibia nail is an implant for both primary stabilisation of closed diaphyseal fractures of the tibia with soft tissue injury and for secondary procedure/treatment for example after external fixator osteosynthesis or initial non-operative treatment. Early change of procedure seems to be of importance.


Biodegradation of agricultural herbicides in sequencing batch reactors under aerobic or anaerobic conditions.
This study investigated the biodegradability of the herbicides isoproturon and 2,4-dichlorophenoxyacetic acid (2,4-D) in sequencing batch reactors (SBRs). Two laboratory-scale (2L liquid volume) SBRs were employed: one reactor performing under aerobic and the other under anaerobic conditions. The aerobic SBR was operated at an ambient temperature (22+/-2 degrees C), while the anaerobic SBR was run in the lower mesophilic range (30+/-2 degrees C). Each bioreactor was seeded with a 3:1 mixture (by weight) of fresh sludge and biomass that had been previously exposed to both herbicides. The effect of herbicide concentration on either treatment process was explored at a hydraulic retention time (HRT) of 48 h, using glucose as a supplemental carbon substrate. Although no isoproturon degradation was observed in either system during the study, complete 2,4-D removal occurred after an acclimation period of approximately 30 d (aerobic SBR) and 70 d (anaerobic SBR). The aerobic reactor achieved complete 2,4-D utilization at feed concentrations up to 500 mg/L. A further increase to 700 mg/L, however, proved to be inhibitory since 2,4-D biodegradation was negligible. On the other hand, the anaerobic SBR was able to degrade 120 mg/L of 2,4-D, which corresponds to 40% of the maximum feed concentration applied. Moreover, glucose was consumed first throughout the experiment in a sequential utilization pattern relating to 2,4-D, with biodegradation of both substrates following closely first-order kinetics.


Cloning of cDNA for a novel mouse membrane glycoprotein (gp42): shared identity to histocompatibility antigens, immunoglobulins and neural-cell adhesion molecules.
A full-length clone encoding a murine membrane glycoprotein, gp42, was selected from a mouse fibroblast cDNA expression library by screening with a polyclonal antiserum. The deduced amino acid (aa) sequence indicates that gp42 is a transmembrane protein of 273 aa with a large N-terminal portion exposed outside the cell and a short cytoplasmic domain. Computer assisted analysis shows that gp42 is distinct from previously characterized proteins, but shares a number of structural features with the class II histocompatibility antigens. The sizes of the extracellular domains of gp42 and of class II histocompatibility antigens are similar, the position of four cysteines and the location of several aa residues are conserved. Some of these conserved residues are also present in immunoglobulins (Ig) and in the neural-cell adhesion molecule, thus indicating that gp42 is a new member of the Ig superfamily.


Trunk muscle coordination in reaction to load-release in a position without vertical postural demand.
The aim of this study was to investigate the coordination between the innermost muscle layer of the ventro-lateral abdominal wall, the transversus abdominis (TrA), and other trunk muscles, in reaction to a load-release without the postural demand of keeping the trunk upright. Eleven healthy male volunteers participated. Intramuscular fine-wire electromyography (EMG) was obtained bilaterally from the TrA, rectus abdominis (RA), obliquus externus (OE) and erector spinae (ES) muscles. The subjects lay on their right side on a horizontal swivel-table with immobilized pelvis and lower limbs and with the trunk strapped to a movable platform allowing for trunk flexion and extension. Subjects maintained trunk flexion or extension at different force levels against a static resistance, which was suddenly released. They were instructed to resume the start position as fast as possible. EMG signals were analysed with respect to amplitude and timing of muscle activation. Following released static flexion, TrA increased its activity in synergy with ES. Also in released static extension, TrA increased its activity, but now in synergy with RA and OE. The direction-independent activation of TrA indicates a role of this muscle in controlling inter-segmental movements of the lumbar spine. This function was not accompanied by an early activation of TrA as has been shown previously for trunk perturbations in standing, i.e. a situation with an additional demand of maintaining the trunk posture upright against gravity.


Molnupiravir combined with different repurposed drugs further inhibits SARS-CoV-2 infection in human nasal epithelium in vitro.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic with unprecedented economic and societal impact. Currently, several vaccines are available and multitudes of antiviral treatments have been proposed and tested. Although many of the vaccines show clinical efficacy, they are not equally accessible worldwide. Additionally, due to the continuous emergence of new variants and generally short duration of immunity, the development of effective antiviral treatments remains of the utmost importance. Since the emergence of SARS-CoV-2, substantial efforts have been undertaken to repurpose existing drugs for accelerated clinical testing and emergency use authorizations. However, drug-repurposing studies using cellular assays often identify hits that later prove ineffective clinically, highlighting the need for more complex screening models. To this end, we evaluated the activity of single compounds that have either been tested clinically or already undergone extensive preclinical profiling, using a standardized in vitro model of human nasal epithelium. Furthermore, we also evaluated drug combinations based on a sub-maximal concentration of molnupiravir. We report the antiviral activity of 95 single compounds and 30 combinations. We show that only a few single agents are highly effective in inhibiting SARS-CoV-2 replication while selected drug combinations containing 10 µM molnupiravir boosted antiviral activity compared to single compound treatment. These data indicate that molnupiravir-based combinations are worthy of further consideration as potential treatment strategies against coronavirus disease 2019 (COVID-19).


Social health insurance without corporate actors: changes in self-regulation in Germany, Poland and Turkey.
Social health insurance in Western Europe has for many years been characterized by self-regulation in which specific conditions of healthcare financing and provision have been regulated by social-insurance institutions through mutual self-governance. However, the principle of self-regulation has recently been weakened by increased state regulation and market competition, which were introduced in response to economic and social changes. Even in Germany, which has been regarded as an "ideal-type" health insurance system and in which self-regulation remains at the core of healthcare governance, more direct state intervention has gained in importance. On the other hand, in countries such as Poland and Turkey, where this tradition of self-regulation is missing, social health insurance is deemed a financing instrument but not an instrument of governance and corporate actors are not accorded a significant role in regulation. This article investigates how social health insurance systems are regulated in contexts in which corporate actors' role is either diminishing or absent by focusing on three crucial areas of regulation: financing, the remuneration of medical doctors, and the definition of the healthcare benefit package. In Germany, state regulation has increased in healthcare financing and remuneration while the role of corporate actors has grown in the definition of the benefits package. In Poland and Turkey, on the other hand, reforms have maintained the status quo in terms of the strong regulatory, budgetary, and managerial powers of the state and very limited involvement of corporate actors.


World Health Organization Guidelines for Feeding Low Birth Weight Infants: Effects of Implementation in First Referral Level Health Facilities in India.
To evaluate the effect of implementing World Health Organization (WHO) low birth weight (LBW) feeding guidelines in First Referral Level health facilities in India. This was a before-and-after study conducted at two First Referral Level health facilities in India. In the pre and post implementation periods of 4 mo each, the authors compared knowledge and skills of health care providers (HCPs) with regard to feeding of LBW infants using multiple choice and short answer questions and objective structured clinical examinations. The authors also enrolled in the two periods, separate cohorts of LBW infants along with their mothers at birth, and followed them till 2 wk of age or death/discharge. Quality of care received by the infants was assessed at 24-48 h and at discharge/2 wk using pre-determined parameters based on which quality scores were assigned by experienced neonatologists. Knowledge and skills of the mothers were also assessed at these time points through semi structured questionnaires and observation checklists. Guidelines were implemented using specially prepared training material through seminars, workshops, refresher courses and on-job support. Overall knowledge (62 ± 16 vs. 75 ± 15, n = 55; p < 0.01) and skill scores (298 ± 37 vs. 348 ± 52, p < 0.05) of HCPs improved. Correct knowledge increased among the mothers at the time of discharge (7.1 % vs. 63.4 %; p < 0.01). However, there was no improvement in maternal feeding skills at either 24-48 h or at discharge and key feeding practices remained unchanged. Though there was increased uptake of kangaroo mother care (0 vs. 21.9 %; p < 0.01) and alternate methods of feeding (15.9 % vs. 31.7 %; p = 0.03) by discharge/14 d, there was no significant improvement in overall quality of care of LBW infants (4.8 % vs. 6.7 %; p = 0.55). For the Guidelines to be fully effective, additional efforts on part of HCPs/additional staff and efforts to promote generic early feeding practices in addition to LBW focused guidelines would be required.


Gene polymorphisms of oxidative stress enzymes: prediction of elderly renutrition.
The free radical theory of aging suggests that damage caused by oxidative stress leads to impaired physiologic functions. This damage is stemmed by an adequate antioxidant status, which minimizes the occurrence of infection, thus potentially playing a role in improving nutritional status. The role played by genetic factors remains unknown. The aim of this study was to investigate whether a single nucleotide polymorphism (SNP) of a gene coding for endogenous antioxidant enzymes could influence either nutritional status or renutrition process in an elderly population. Nutritional and inflammatory status were studied in 77 elderly outpatients and in 99 malnourished elderly inpatients over 6 wk of health care treatment. Renutrition efficiency was evaluated with use of the ratio between initial transthyretinemia and 6-wk variation. A genetic study was performed on superoxide dismutase (Ala-9Val), glutathione peroxidase (Pro197Leu), and catalase (from promoter to the first intron). Among the SNPs studied, the G-844A, A-89T, and C-20T catalase SNPs could each be markers predicting renutrition efficiency. These catalase mutant alleles were associated with a lower efficiency of renutrition in malnourished elderly subjects, regardless of initial nutritional and inflammatory status. Genotyping one of these catalase SNPs could make it possible to identify a high-risk subpopulation of mutant allele carriers within the elderly polypathological population. In a malnutrition setting, this subpopulation should be given personalized health care, including a strengthened refeeding program. Thus, catalase genotyping could enable earlier recovery of satisfactory nutritional status and thus avoid the consequences of malnutrition, which are especially deleterious in the elderly.


Drawing data for a 3D historical reconstruction of Shakespeare's first Globe Theatre.
The first Globe Theatre was one of the main outdoor playhouses in London in the early 17th century. Although it was built in 1599 and was destroyed in a fire in 1613, its history has survived to the present day as the theatre that was able to accommodate most of William Shakespeare's plays. Extensively studied during the last century, it has been attempted to be reconstructed several times in different parts of the world, although the information present does not allow for an exact reconstruction. The data presented here have been collected from the various interpretations offered in literature by the main scholars of the first Globe Theatre and re-elaborated according to criteria of coherence with vernacular building techniques and ease and feasibility of construction. What is presented is the methodology probably used by the Globe's carpenter Peter Street to draw the plan and then build the theatre. The data presented were used to provide a virtual reconstruction of the first Globe Theatre, featured in the article " Towards reconstructing the Shakespeare's first Globe Theatre: A virtual model for research and development", published in the Frontiers of Architectural Research by the same authors [1]. The data can be used to confirm, improve, or reconstruct the first Globe, as well as most Elizabethan theatres, similar in type and form.


Implications of surgical intervention in the treatment of neuroblastomas: 20-year experience of a single institution.
The implications of surgical intervention for neuroblastomas were assessed in one institution. We analyzed the clinical characteristics and extension of resection in 123 pediatric patients with neuroblastoma diagnosed between 1985 and 2004. The 5-year survival rate of the 82 patients under 12 months of age, 59 of whom were treated with complete resection of the primary tumor, was 97%. The 5-year survival rate of the 41 patients over 12 months of age did not differ significantly according to whether complete (n = 19) or incomplete resection (n = 22) was performed (46 vs. 38%, respectively). No local recurrence was observed in ten patients over 12 months of age with stage 4 disease who underwent complete resection of the primary tumor; however, four of these ten patients died of metastatic recurrence. Considering that the majority of infantile neuroblastomas in this study had favorable biology, complete resection might be unnecessary for patients under 12 years of age. For advanced neuroblastomas in patients over 12 months of age, the main treatment for metastasis is systemic chemotherapy, although extirpation of the primary tumor without extensive surgery might prevent local recurrence when combined with radiation therapy.


Isolation and characterization of novel lytic bacteriophages that infect multi drug resistant clinical strains of Escherichia coli.
The pathogenic strains of Escherichia coli (E. coli) are frequent cause of urinary tract infections including catheter-associated, soft tissue infections and sepsis. The growing antibiotic resistance in E. coli is a major health concern. Bacteriophages are specific for their bacterial host, thus providing a novel and effective alternatives. This study focuses on isolation of bacteriophages from urban sewage treatment plants. Initially 50 different bacteriophages have been isolated against non-resistant reference E. coli strain and fifty multidrug resistant clinical isolates of extraintestinal infections. Out of which only thirty-one lytic phages which gave clear plaques were further analysed for different physico-chemical aspects such as thermal inactivation, pH, effect of organic solvents and detergents. Two bacteriophages, ASEC2201 and ASEC2202, were selected for their ability to withstand temperature fluctuation from -20 to 62 °C and a pH range from 4 to 10. They also showed good survival (40-94%) in the presence of organic solvents like ethanol, acetone, DMSO and chloroform or ability to form plaques even after the treatment with detergents like SDS, CTAB and sarkosyl. Both efficiently killed reference strain and 40-44% of multidrug resistant clinical isolates of E. coli. Later ASEC2201 and ASEC2202 were subjected to morphological characterisation through transmission electron microscopy, which revealed them to be tailed phages. The genomic analysis confirmed them to be Escherichia phages which belonged to family Drexlerviridae of Caudovirales.


MEK inhibitor and anti-EGFR antibody overcome sotorasib resistance signals and enhance its antitumor effect in colorectal cancer cells.
The Kirsten rat sarcoma (KRAS) oncogene was "undruggable" until sotorasib, a KRASG12C selective inhibitor, was developed with promising efficacy. However, inhibition of mutant KRAS in colorectal cancer cells (CRC) is ineffective due to feedback activation of MEK/ERK downstream of KRAS. In this study, we screened for combination therapies of simultaneous inhibition to overcome sotorasib resistance using our previously developed Mix Culture Assay. We evaluated whether there was an additive effect of sotorasib administered alone and in combination with two or three drugs: trametinib, a MEK inhibitor, and cetuximab, an anti-epidermal growth factor receptor (EGFR) antibody. The MAPK pathway was reactivated in KRASG12C-mutated cell lines treated with sotorasib alone. Treatment with KRAS and MEK inhibitors suppressed the reactivation of the MAPK pathway, but upregulated EGFR expression. However, the addition of cetuximab to this combination suppressed EGFR reactivation. This three-drug combination therapy resulted in significant growth inhibition in vitro and in vivo. Our data suggest that reactive feedback may play a key role in the resistance signal in CRC. Simultaneously inhibiting KRAS, MEK, and EGFR is a potentially promising strategy for patients with KRASG12C-mutated CRC.


Effective palliation by low dose local radiotherapy for recurrent and/or chemotherapy refractory non-follicular lymphoma patients.
In this work, we have studied the response rates and duration of response after low-dose (4 Gy) involved field radiotherapy (LD-IF-RT) in relapsed or chemotherapy refractory indolent and aggressive lymphoma patients. 71 patients (177 symptomatic sites) received LD-IF-RT consisting of 39 males and 32 females with a median age of 69 years (range 43-93). Patients included were those with small lymphocytic lymphoma/chronic lymphocytic leukaemia (n=23), marginal zone lymphoma, nodal type (n=18), mantle cell lymphoma (n=17), and diffuse large B-cell lymphoma (n=13). Bulky disease (5 cm) was present in 73% of all patients. A median of two prior chemotherapy regimens (range 0-10) preceded LD-IF-RT. Median time since diagnosis was 31 months (range 1-216 months). Time to (local) progression was calculated according to the Kaplan-Meier method. Differences in response rates were compared using the chi2-test. The results showed that overall response rate was 87%; complete remission (CR) was reached in 34 patients (48%) and a partial remission (PR) in 28 patients (39%). Stable disease (SD) was maintained in nine patients (13%). The median time to progression (TP) was 12 months and the median time to local progression (TLP) was 22 months. The 34 CR patients showed a median TP of 16 months and a median TLP of 23 months. None of the factors studied (age, sex, lymphoma subtype, radiotherapy regimen, number of prior regimens or time since diagnosis, number of positive sites or largest lymphoma diameter) were found to relate to response. At time of death 70% of patients were without in-field progression after LD-IF-RT. It appears that LD-IF-RT is a valuable asset in the management of relapsed disease in both indolent and aggressive lymphoma and should be considered to palliate symptoms in patients with recurrent and/or chemotherapy refractory disease.


On the sensitivity of the tourniquet pain test.
Twenty-four chronic pain patients were given, on each of 4 successive days, oral doses of 60 mg morphine, 60 mg codeine, 600 mg aspirin and placebo, using a double-blind counterbalanced design. Two hours after ingestion, subjective pain estimates and tourniquet pain scores were obtained. Variability of the tourniquet pain scores was too great for differences in response to the analgesics to be significant. However, differences in pain estimates were also too small to discriminate among the drugs, and the lack of sensitivity may be a function of pain chronicity. The tourniquet techniques will continue to be useful until there is a purely objective measure of the severity of clinical pain.


A molecularly imprinted ratiometric fluorescence sensor based on blue/red carbon quantum dots for the visual determination of thiamethoxam.
Neonicotinoids such as thiamethoxam (TMX) were widely used in agricultural production and tended to accumulate in the environment, potentially harming human and ecosystem health. To enable widespread monitoring of TMX residues, it was essential to design a reliable and sensitive detection method. Here, we developed a novel smartphone-enablled molecularly imprinted ratiometric fluorescence sensing system for selective on-site detection of TMX. It was based on blue-emission carbon dots (CDs) wrapped with a molecularly imprinted layer (B-CDs@MIPs), which provided the response signal, while red-emission CDs (R-CDs) served as an internal reference. The fluorescence signal ratio of the sensor increased with the TMX concentration, resulting in an obvious fluorescence color change from red to blue. The sensor exhibited a satisfactory limit of detection (LOD) of 13.5 nM in fluorescence analysis while LOD of 70.1 nM in visual determination. In addition, the sensing system was validated using food and environment samples, exhibiting recoveries from 91.40% to 105.7%, indicating excellent reliability for TMX detection in actual samples. Thus, the sensing system developed in this study offered promising prospects for visual detection of pesticide residues in complex environmental samples.


Normalization of the electromyography amplitude during a multiple-set resistance training protocol: Reliability and differences between approaches.
The first aim was to investigate the impact of different electromyography (EMG) parameters as a reference to normalize the EMG amplitude of the superficial quadriceps femoris muscles across different sets of a knee extension exercise. The second aim is to examine the reliability between days of the EMG parameters used as a reference. Eleven young males attended the laboratory on 4 different days and performed one repetition maximum test, maximumvoluntary isometric contractions, and a resistance training protocol until failure. Surface EMG was placed over the rectus femoris, vastus lateralis, and vastus medialis muscles. Seven EMG parameters were calculated from the tasks and used to normalize EMG amplitude measured during the resistance training protocol. A repeated-measures two-way ANOVA was used (normalized EMG amplitude × set) to compare normalized EMG across sets, while an intraclass correlation coefficient, coefficient of variation, and Bland-Altman plots were used to calculate the intra-day reliability of the EMG parameters. The present investigation showed that normalized EMG amplitude of the superficial muscles of the quadriceps measured during a knee extension exercise is influenced by the EMG parameter and depends on the muscle. While rectus femoris and vastus lateralis normalized EMG amplitude presented one parameter among seven showing similar value to the other parameters, VM showed two. Lastly, all EMG parameters for all muscles presented an overall excellent reliability and agreement between days.


Genetic factors of susceptibility and of severity in primary biliary cirrhosis.
In primary biliary cirrhosis (PBC), pathogenesis is influenced by genetic factors that remain poorly elucidated up to now. We investigated the impact of sequence diversity in candidate genes involved in immunity (CTLA-4 and TNFalpha), in bile formation (10 hepatobiliary transporter genes) and in the adaptative response to cholestasis (three nuclear receptor genes) on the susceptibility and severity of PBC. A total of 42 Ht SNPs were identified and compared in 258 PBC patients and two independent groups of 286 and 269 healthy controls. All participants were white continental individuals with French ancestry. Ht SNPs of CTLA-4 and TNFalpha genes were significantly associated with susceptibility to PBC. The progression rate of liver disease under ursodeoxycholic acid (UDCA) therapy was significantly linked to SNPs of TNFalpha and SLC4A2/anion exchanger 2 (AE2) genes. A multivariate Cox regression analysis including clinical and biochemical parameters showed that SLC4A2/AE2 variant was an independent prognostic factor. These data point to a primary role of genes encoding regulators of the immune system in the susceptibility to PBC. They also demonstrate that allelic variations in TNFalpha and SLC4A2/AE2 have a significant impact on the evolutive profile of PBC under UDCA therapy.


Economic and ecological transformation processes in East German water management regimes: the role of property rights and governance structures.
As in many fen land regions in East Germany, long-standing intensive arable farming--enabled by reclamation--has caused soil deterioration and high water runoff in the Schraden region. The more than ten years of economic and political transformation that followed the breakdown of the socialist regime has worsened the situation and even added new problems. The visible consequences are droughts in the summer, waterlogged plots in the spring, and worn-down water management facilities that operate in an uncoordinated or even unauthorized way. Given the local public-good character of some features of the fen land, the common-pool character of the ecosystem's intermittently scarce resource water, and the conflicting interests of regional stakeholders, it is argued that the reallocation of property rights over reclamation systems, together with ineffective coordination mechanisms, have caused the physical and institutional failure of the water management system and so impeded appropriate land use.


FDG-PET is an effective imaging modality to detect and quantify age-related atherosclerosis in large arteries.
The main aim of this research was to determine the changes of FDG uptake in large arteries with aging as visualized by FDG-PET imaging. We examined the presence of arterial FDG uptake in 149 subjects (61 males, 88 females; age range 5-83 years) who underwent whole-body PET scans for the assessment of non-cardiovascular disorders. The subjects were divided into eight age decade groups, with at least 12 subjects in each group. The presence of FDG uptake was recorded in the ascending, arch, descending thoracic and abdominal segments of the aorta, as well as in iliac and femoral arteries. We then calculated the percentage of segments with visible FDG uptake for each age group. Mean SUVs were calculated for each of the arterial segments and compared among the age groups. Among 149 subjects, 145 were noted to have visible uptake in at least one segment of the large vessels. Percentage of segments with visible FDG uptake increased with age (p < 0.01). Mean SUVs of the ascending aorta, aortic arch, descending thoracic aorta, iliac arteries and femoral arteries increased with age (p < 0.01). Prevalence and intensity of FDG uptake in large arteries generally increases with aging. Increased FDG uptake likely represents the presence of active inflammatory process of atherosclerotic plaque. The magnitude of inflammation within the wall of the large arteries increases with aging.


Dielectric characterization of neutralized and nonneutralized chitosan upon drying.
Isothermal dielectric loss spectra of neutralized and nonneutralized chitosan were acquired in successive runs from -130 degrees C up to increasing final temperatures, in a frequency range between 20 Hz and 1 MHz. Essentially, three relaxation processes were detected in the temperature range covered: (i) a beta-wet process, detected when the sample has a higher water content that vanishes after heating to 150 degrees C; (ii) a beta process, which is located at temperatures below 0 degrees C, becoming better defined and maintaining its location after annealing at 150 degrees C independently of the protonation state of the amino side group; and (iii) a sigma process that deviates to higher temperatures with drying, being more mobile in the nonneutralized form. Moreover, in dried neutralized chitosan, a fourth process was detected in the low frequency side of the secondary beta process that diminishes after annealing. Whether this process is a distinct relaxation of the dried polymer or a deviated beta-wet process due to the loss of water residues achieved by annealing is not straightforward. Only beta and sigma processes persist after annealing at 150 degrees C. The changes in molecular mobility upon drying of these two relaxation processes were evaluated.


Improved spectral resolution of [13C,1H]-HSQC spectra of aromatic amino acid residues in proteins produced by cell-free synthesis from inexpensive 13C-labelled precursors.
Cell-free protein synthesis using eCells allows production of amino acids from inexpensive 13C-labelled precursors. We show that the metabolic pathway converting pyruvate, glucose and erythrose into aromatic amino acids is maintained in eCells. Judicious choice of 13C-labelled starting material leads to proteins, where the sidechains of aromatic amino acids display [13C,1H]-HSQC cross-peaks free of one-bond 13C-13C couplings. Selective 13C-labelling of tyrosine and phenylalanine residues is achieved simply by using different compositions of the reaction buffers.


Rational design of boropeptide thrombin inhibitors: beta, beta-dialkyl-phenethylglycine P2 analogs of DuP 714 with greater selectivity over complement factor I and an improved safety profile.
The potent boropeptide thrombin inhibitor DuP 714 caused side effects in laboratory animals that appear to be related to its ability to inhibit complement factor I, thereby activating the complement cascade. Using X-ray crystal structure information, we have designed compounds that have greater selectivity for thrombin over factor I and that have reduced tendency to produce these side effects.


Gating and blocking of calcium channels by dihydropyridines in the pancreatic B-cell.
The organic calcium-antagonist nifedipine inhibits glucose-stimulated 45Ca net uptake and insulin release by rat pancreatic islets. However, the chemically related dihydropyridine derivative BAY K 8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5- carboxylate) enhances 45Ca net uptake and insulin release and protects the B-cell against the inhibitory action of nifedipine. It is proposed that a regulatory site exists in or near the calcium channels, in the B-cell plasma membrane, and that occupation of this site by selected dihydropyridines may either facilitate or inhibit Ca2+ influx into the B-cell.


One step acid activation of bentonite derived adsorbent for the effective remediation of the new generation of industrial pesticides.
Herein, the facile one step acid activation of bentonite derived functionalized adsorbent (AB) for the effective remediation of both ionic and non-ionic secondary pesticides, ametryn and metolachlor has been attempted. The surface characteristics of AB were examined by the nitrogen adsorption-desorption analysis, scanning electron microscopy (SEM), and Fourier Transforms Infrared (FTIR) Spectroscopy. The adsorptive behavior was evaluated with respect to the effect of contact time, initial concentrations and solution pH. The equilibrium data were fitted to the Langmuir, Freundlich and Temkin isotherm models, while the adsorption kinetic was analyzed using the pseudo-first order and pseudo-second order kinetic equations. Thermodynamic parameters including the standard enthalpy change (ΔH°), standard entropy change (ΔS°), and Gibbs free energy change (ΔG°) were established. Thermodynamic analysis illustrated that the adsorption process was feasible and exothermic in nature, while the characterization findings verified the alteration of FTIR bands, and a high specific surface area of 464.92 m2/g, with a series of pores distributed over the surface. Equilibrium data was best confronted to the pseudo-second order kinetic model, while the adsorptive removal of ametryn and metolachlor onto AB was satisfactory described by the Langmuir isotherm model, with the monolayer adsorption capacities for ametryn and metolachlor of 2.032 and 0.208 mmole/g respectively. The findings outlined the potential of the newly develop AB for the on-site treatment of pesticide polluted water.


Rapid quantification of semen hepatitis B virus DNA by real-time polymerase chain reaction.
To examine the sensitivity and accuracy of real-time polymerase chain reaction (PCR) for the quantification of hepatitis B virus (HBV) DNA in semen. Hepatitis B viral DNA was isolated from HBV carriers' semen and sera using phenol extraction method and QIAamp DNA blood mini kit (Qiagen, Germany). HBV DNA was detected by conventional PCR and quantified by TaqMan technology-based real-time PCR (quantitative polymerase chain reaction (qPCR)). The detection threshold was 200 copies of HBV DNA for conventional PCR and 10 copies of HBV DNA for real time PCR per reaction. Both methods of phenol extraction and QIAamp DNA blood mini kit were suitable for isolating HBV DNA from semen. The value of the detection thresholds was 500 copies of HBV DNA per mL in the semen. The viral loads were 7.5X10(7) and 1.67X10(7) copies of HBV DNA per mL in two HBV infected patients' sera, while 2.14X10(5) and 3.02X10(5) copies of HBV DNA per mL in the semen. Real-time PCR is a more sensitive and accurate method to detect and quantify HBV DNA in the semen.


Glycosaminoglycans and chylomicron metabolism in control and nephrotic rats.
Nephrotic patients and rats with experimentally induced nephrotic syndrome have elevated plasma triglycerides and impaired triglyceride removal. This may be due to a defective interaction of chylomicrons and very low density lipoproteins with lipoprotein lipase. Since the glycosaminoglycan, heparan sulfate, was found to stimulate the lipoprotein lipase reaction in vitro, we investigated the plasma heparan sulfate content and measured the urinary excretion of heparan sulfate in control rats and rats with experimentally induced nephrotic syndrome. In addition, we studied the effect of heparan sulfate on the rate of removal of radiolabeled chylomicrons in nephrotic rats. Glycosaminoglycan concentrations in plasma were the same in control and nephrotic rats, although 35S incorporation in high charge glycosaminoglycans was markedly reduced. In addition, in nephrotic rats there is a marked reduction in the urinary excretion of heparan sulfate and chondroitin sulfate suggesting a markedly reduced turnover of these glycosaminoglycans. This was associated with increased plasma triglycerides in nephrotic rats. Nephrotic rats showed a reduced rate of clearance of injected chylomicrons. Intravenous administration of heparan sulfate completely and immediately corrected the chylomicron removal defect. We also noted a log-dose response effect of administered heparan sulfate on chylomicron removal. This effect was not due to a release of soluble lipoprotein lipase by heparan sulfate. These findings suggest that a rapidly turning over fraction of plasma heparan sulfate may play an important role in chylomicron clearance.


Urinary crystal surface binding substances on calcium oxalate crystals.
In order to study the effect of urinary crystal surface binding substances (CSBS), we extracted the naturally existing CSBS from urine from healthy individuals by conducting homogeneous crystallization of calcium oxalate. CSBS proved not to be promoters but rather strong inhibitors of calcium oxalate crystal growth and aggregation. It is suggested that CSBS exhibited their inhibitory effect by masking the growing sites and aggregating sites on the crystal surface. As for the characteristics of CSBS, we found around 10 peaks of molecular weight, and all of them contained both peptides and saccharides. The findings suggest that CSBS are composed of various kinds of glycoproteins and proteoglycans.


Caval extension of renal cell carcinoma. Results of surgical treatment.
Twenty-eight patients with renal cell carcinoma extending to the vena cava underwent surgical treatment consisting of radical nephrectomy and removal of tumor thrombus, which was at the level of the renal veins in 23 cases, the hepatic veins in 4, and extending above the diaphragm in 1 case. In 7 patients lymph nodes were invaded, and 8 had both positive nodes and extrarenal tumor diffusion discovered at surgery. The mean survival was 41.7 months for patients with only venous extension of the tumor, 16 months for patients with positive nodes, and 10.2 months for those with both nodal and extrarenal tumor diffusion.


Adenosine deaminase activity in patients with carcinoma of the bladder.
Adenosine deaminase is an important enzyme in purine metabolism, and patients with abnormal lymphocyte and erythrocyte adenosine deaminase levels have been shown to have impaired immune competence. Since immune factors have been shown to be important in patients with transitional cell carcinoma of the bladder we studied adenosine deaminase activity in the hemic cells of 48 patients with this tumor. Lymphocyte adenosine deaminase levels were elevated in patients with transitional cell carcinoma and correlated with stage, activity, clinical course and tumor resection but not with tumor grade. Erythrocyte adenosine deaminase levels also were elevated in patients with transitional cell carcinoma but did not correlate with other disease parameters. Lymphocyte adenosine deaminase activity in patients with transitional cell carcinoma may be a sensitive indicator of disease activity and further studies may provide insight into the host-tumor relationship at the enzyme level.


Stress-induced crystal-to-crystal transformations in high-density polyethylene-layered silicate nano-composites: a spectroscopic study.
High-density polyethylene (HDPE)-clay nano-composites have been prepared using the melt intercalation technique. Organically modified montmorillonite at various loadings (0.5--7%) was used as a nano-additive. Fourier transform infrared spectroscopy (FT-IR) was utilized for the first time to monitor the stress-induced crystal-to-crystal transformations of the polyethylene matrix with respect to the clay loading as well as to the degree of mechanical strain. In addition, polarized infrared measurements revealed information on both the orientation and the stress-induced distortion of the crystals. It was concluded that the crystal-to-crystal transformations are hindered by the presence of the clay, which also prevented the crystals from orienting even at low clay loadings (1%). Finally, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) measurements confirmed the presence of the stress-induced crystalline structures in agreement with the infrared measurements.


Inhibition of lymphocyte activation in splenic and gut-associated lymphoid tissues following oral exposure of mice to 7,12-dimethylbenz[a]anthracene.
The hypothesis that 7,12-dimethyl-benz[a]anthracene (DMBA) suppresses immune function in mice via an inhibition of lymphocyte activation was examined in these studies. Daily exposure of B6C3F1 mice to DMBA (cumulative doses of 1.4 to 140 mg/kg) via the oral route for 14 days was found to inhibit phytohemagglutinin (PHA) and lipopolysaccharide mitogen responses in lymphoid cells obtained from the spleen. Peyer's Patches, and mesenteric lymph nodes. The 14 mg/kg cumulative dose of DMBA produced no significant decrease in the number of recovered viable cells, yet mitogen responses were suppressed by approximately 50% in the spleen and mesenteric lymph nodes, and by greater than 70% in the Peyer's Patches. DMBA inhibited PHA-induced Ca+2 mobilization measured by flow cytometry in each of these three lymphoid tissues. There was no change in the percentage of T cells recovered from the spleen, mesenteric lymph nodes, or Peyer's Patches. Peyer's Patch lymphocytes obtained from the GI tract appeared to be slightly more sensitive to inhibition of mitogen responsiveness and perhaps Ca+2 mobilization, potentially due to the oral route of exposure to DMBA. These studies provide evidence that DMBA inhibits early events associated with lymphocyte activation in mice.


Retracted: Effective Strategies to Promote the Cultivation of Public Legal Consciousness from the Perspective of Social Psychology.
[This retracts the article DOI: 10.1155/2022/8275938.].


Cellular characteristics of chronic myelocytic leukemia basophilic crisis cells: phenotype, responsiveness to and receptor gene expression for various kinds of growth factors and cytokines.
Leukemic cells from a patient with chronic myelocytic leukemia (CML) basophilic crisis were examined in an in vitro clonogenic assay using recombinant human hematopoietic growth factors to elucidate the proliferative and differentiative behaviors. More than 90% of the leukemic cells showed the morphologic characteristics of basophils and were positive for CD11b and CD13. The phenotype of the leukemic cells was different from that of mast cells. In the clonogenic assay using various recombinant growth factors, the leukemic cells were responsive to interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), but not to granulocyte-CSF (G-CSF), erythropoietin (Epo), or IL-4. IL-5 showed synergistic effects on colony formations induced by both IL-3 and GM-CSF. Transcripts of the GM-CSF receptor alpha chain gene were detected in the leukemic cells, but transcripts of the IL-4 receptor gene were not. Furthermore, c-kit and IL-7 receptor genes were expressed in the leukemic cells. Our results suggest that the differentiation pathway of basophils is different from that of mast cells, even though the receptor gene for stem cell factor (c-kit) was expressed on the basophilic leukemic cells, as it was on mast cells.


Toxicity and efficacy of ifosfamide, carboplatin and etoposide (modified ICE) as a salvage chemotherapy in Japanese patients with relapsed or refractory aggressive non-Hodgkin's lymphoma.
The combination of ifosfamide, carboplatin and etoposide (modified ICE), was evaluated for its toxicity and activity in relapsed or refractory aggressive non-Hodgkin's lymphoma. Twenty patients, 14-69 years of age, with relapsed (19 cases) or refractory (one case) aggressive non-Hodgkin's lymphoma were treated with modified ICE therapy, consisting of ifosfamide 6 g/m2 (1.2 g/m2 day 1-5), carboplatin 400 mg/m2 (day 1) and etoposide 500 mg/m2 (100 mg/m2 day 1-5). The regimen was repeated at approximately 28-day intervals. All patients had undergone a doxorubicin-containing regimen before modified ICE therapy. Median total dose of previously received doxorubicin was 406 mg/m2 (range: 200-825 mg/m2). The median interval from diagnosis to modified ICE therapy was 9.4 months (range: 3.6-121 months). Two patients achieved CR and five achieved PR out of 16 patients with measurable lesions (response rate 43.8%; 95% confidence interval 19.0-68.6%). Median overall survival was 227 days (range: 41-552 days) from the start of modified ICE therapy. Myelosuppression was the most serious toxicity, namely 16 patients (80%) and 11 patients (55%) showed grade 4 neutropenia and grade 4 thrombocytopenia after the first course, respectively. Modified ICE therapy might be an active regimen with acceptable toxicity as a salvage chemotherapy in aggressive non-Hodgkin's lymphoma.


What if 0 is not equal to 0? Inter-personal health utilities anchoring using the largest health gains.
Prioritizing health technologies requires comparisons of improvements in longevity or quality of life (QoL), or both. For this purpose, value sets are constructed that contain weights assigned to health states based on societal preferences. I show that how this is typically done may distort the results by giving unjustifiably larger impact to individuals who prioritize improvements in QoL over longevity. The problem results from equating the utility differences between being dead and full health across people, ignoring the fact that interpersonal utility comparisons are forbidden (or at least problematic) in economics. I propose another approach: the numerical value of maximal health gain (either in longevity or QoL) is assumed to be equal across individuals, to remove the impact of the range of utilities differing between people. I test this approach using EQ-5D-5L and EQ-5D-3L utilities elicited in Poland for two modeling techniques: a simple econometric model and a Bayesian one that accounts for censoring. The proposed approach increases the utilities of the worst health state: from [Formula: see text] to [Formula: see text] in EQ-5D-5L and from about [Formula: see text] to [Formula: see text] in EQ-5D-3L. In the Bayesian approach, the impact is greater: from [Formula: see text] to [Formula: see text] for EQ-5D-5L and from [Formula: see text] to [Formula: see text] for EQ-5D-3L. I discuss some normative arguments why the proposed approach may be more justifiable for aggregating individual preferences for health outcomes.


Chemical angioplasty for medically refractory reversible cerebral vasoconstriction syndrome.
Medically refractory reversible cerebral vasoconstriction syndrome (RCVS), a rare variant of RCVS, poses a significant therapeutic challenge. Herein we describe a case of medically refractory RCVS that required treatment with intra-arterial (IA) verapamil and subsequent nimodipine, resulting in both angiographic and clinical improvement after failing to respond to hemodynamic augmentation. We also supplement a description of our case with a review of other case studies and case series in which IA calcium channel blockers were used to treat RCVS. We propose that the case we outline below demonstrates that neurointerventional management with IA verapamil is appropriate and effective as an early intervention of medically refractory RCVS. Using PubMed and Google Scholar, we performed a search of the English language literature with several combinations of the keywords "intra-arterial", "calcium channel blockers", "reversible cerebral vasoconstriction syndrome", "RCVS", "nimodipine", "verapamil", "milrinone", and "nicardipine" to identify studies in which RCVS was treated with IA calcium channel blockers. We identified eight case studies and case series that met our inclusion criteria. Eighteen patients are encompassed in these eight studies. IA administration of calcium channel blockers has been shown to return cerebral vessels to their normal caliber in patients with medically refractory RCVS. However, there are no randomized controlled trials of the treatment of RCVS, and further studies are needed to elucidate the optimal treatment protocol for medically refractory RCVS.


Biotreatment of high strength nitrate waste using immobilized preadapted sludge.
One of the major wastes generated by fertilizer, explosive, and nuclear industries are nitrate (as high as 1,000 ppm NO(3)N) whose removal before disposal has become a growing concern. In this study, an active denitrifying sludge was immobilized onto support materials like cloth and polyurethane foam and their denitrification efficiency on high nitrate wastes [1,000 ppm NO(3) (225 ppm NO(3)N), 5,000 ppm NO(3) (1,129 ppm NO(3)N), 7,500 ppm NO(3) (1,693 ppm NO(3) N)] was studied. Results showed complete degradation of the nitrate wastes (225 ppm NO(3)N, 1,129 ppm NO(3)N, and 1,693 ppm NO(3)N) without any accumulation of nitrite in a period of only 1, 4, and 10 h, respectively. Based on adhering and entrapment principle, an immobilization unit was developed using a combination of cloth and foam as well as both individually. This system used for treating such high nitrate wastes was found to be quite effective in waste water treatment, particularly in problems associated with solid-liquid separation. The batch column reactor was run in about 45 batches without any loss in activity or reactor stability.


Prognostic role of time to positivity of blood culture in children with Pseudomonas aeruginosa bacteremia.
Pseudomonas aeruginosa (P. aeruginosa) is a major Gram-negative pathogen, which has been reported to result in high mortality. We aim to investigate the prognostic value and optimum cut-off point of time-to-positivity (TTP) of blood culture in children with P. aeruginosa bacteremia. From August 2014 to November 2018, we enrolled the inpatients with P. aeruginosa bacteremia in a 1500-bed tertiary teaching hospital in Chongqing, China retrospectively. Receiver operating characteristic (ROC) analysis was used to determine the optimum cut-off point of TTP, and logistic regression were employed to explore the risk factors for in-hospital mortality and septic shock. Totally, 52 children with P. aeruginosa bacteremia were enrolled. The standard cut-off point of TTP was18 h. Early TTP (≤18 h) group patients had remarkably higher in-hospital mortality (42.9% vs 9.7%, P = 0.014), higher incidence of septic shock (52.4% vs12.9%, P = 0.06), higher Pitt bacteremia scores [3.00 (1.00-5.00) vs 1.00 (1.00-4.00), P = 0.046] and more intensive care unit admission (61.9% vs 22.6%, P = 0.008) when compared with late TTP (> 18 h) groups. Multivariate analysis indicated TTP ≤18 h, Pitt bacteremia scores ≥4 were the independent risk factors for in-hospital mortality (OR 5.88, 95%CI 1.21-21.96, P = 0.035; OR 4.95, 95%CI 1.26-27.50, P = 0.024; respectively). The independent risk factors for septic shock were as follows: TTP ≤18 h, Pitt bacteremia scores ≥4 and hypoalbuminemia (OR 6.30, 95%CI 1.18-33.77, P = 0.032; OR 8.15, 95%CI 1.15-42.43, P = 0.014; OR 6.46, 95% CI 1.19-33.19 P = 0.031; respectively). Early TTP (≤18 hours) appeared to be associated with worse outcomes for P. aeruginosa bacteremia children.


5-Hydroxyeicosatetraenoic acid biosynthesis by gestational tissues: effects of inflammatory cytokines.
Our purpose was to determine whether inflammatory cytokines can modulate the production of arachidonate lipoxygenase metabolites by gestational tissues. Primary cultures of amnion, chorion, and decidual cells were incubated in the presence and absence of interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6. Supernatants were assayed for leukotriene B4, leukotriene C4, 5-, 12- and 15-hydroxyeicosatetraenoic acid by means of specific radioimmunoassays. Cellular proteins were determined. 5-Hydroxyeicosatetraenoic acid production was significantly increased by interleukin-1 beta and interleukin-6 treatment in amnion, chorion, and decidual cells. Tumor necrosis factor-alpha elicited a modest increase, which was not statistically significant, in mean 5-hydroxyeicosatetraenoic acid production by these cells. Production rates of leukotrienes B4 and C4 and 12 and 15-hydroxyeicosatetraenoic acid were not affected by treatment with interleukin-1 beta. Inflammatory cytokines generated in response to intrauterine infection may modulate uterine activity by stimulation of 5-hydroxyeicosatetraenoic acid biosynthesis.


Special Populations-Surgical Infants.
Congenital gastrointestinal disorders and other surgical diagnoses share many common problems: increased nutritional requirements to prevent catabolism, enhance wound healing, and provide optimal growth; impaired motility and altered intestinal flora leading to feeding intolerance requiring long-term parenteral nutrition; gastroesophageal reflux and poor feeding mechanics requiring tube feedings and support; growth failure; poor barrier function and risk of infection; and other long-term sequelae. Consequently, the surgical "at-risk" infant requires specialized nutritional support to meet their increased requirements to ensure adequate growth and meet the increased demands from critical illness.


Blood pressure and body mass index: a comparison of the associations in the Caucasian and Asian populations.
A strong association between blood pressure (BP) and body mass index (BMI) has been observed in developed and developing countries. Whether there are differences in these associations between Caucasians and Asians remains unknown. Our objective was to compare the associations of BP with fatness measures in the Caucasian and Asian samples. The study used data from two population-based cross-sectional studies conducted using similar methodology: a survey in Australia in 1998-1999 (n = 832 adults aged 25-64 years; 47% male) and a survey in Vietnam in 2005 (n = 1978 adults aged 25-64 years; 46% male). Participants completed questionnaires and attended clinics for physical measurements including BP and anthropometry. Linear regression was used for analysis. Independent of age, there were strong associations between BP indices and BMI in each sample, but the patterns of associations were different. Among Caucasians, pulse pressure (PP) increased with increasing BMI because the slope of systolic pressure with BMI exceeded the slope of diastolic pressure with BMI (P<0.001 for both sexes). In contrast, among Asians, PP decreased with increasing BMI. Associations between BMI and BP are different between Caucasian and Asian populations. Among Asians, the stronger association of increasing BMI and diastolic BP, but not PP, suggests a different pathophysiology related to hypertension.


Brefeldin A arrests the intracellular transport of a precursor of complement C3 before its conversion site in rat hepatocytes.
The effects of brefeldin A on intracellular transport and posttranslational modification of complement C3 (C3) were studied in primary culture of rat hepatocytes. In the control culture C3 was synthesized as a precursor (pro-C3), which was processed to the mature form with alpha- and beta-subunits before its discharge into the medium. In the presence of brefeldin A the secretion of C3 was strongly blocked, resulting in accumulation of pro-C3. However, after a prolonged interval the mature form of C3 was finally secreted. The results indicate that brefeldin A impedes translocation of pro-C3 to the Golgi complex where pro-C3 is converted to the mature form, but not its proteolytic processing, in contrast to the effects of monensin and weakly basic amines.


Morphological profiling by means of the Cell Painting assay enables identification of tubulin-targeting compounds.
In phenotypic compound discovery, conclusive identification of cellular targets and mode of action are often impaired by off-target binding. In particular, microtubules are frequently targeted in cellular assays. However, in vitro tubulin binding assays do not correctly reflect the cellular context, and conclusive high-throughput phenotypic assays monitoring tubulin binding are scarce, such that tubulin binding is rarely identified. We report that morphological profiling using the Cell Painting assay (CPA) can efficiently detect tubulin modulators in compound collections with a high throughput, including annotated reference compounds and unannotated compound classes with unrelated chemotypes and scaffolds. Small-molecule tubulin binders share similar CPA fingerprints, which enables prediction and experimental validation of microtubule-binding activity. Our findings suggest that CPA or a related morphological profiling approach will be an invaluable addition to small-molecule discovery programs in chemical biology and medicinal chemistry, enabling early identification of one of the most frequently observed off-target activities.


Enantioseparation and stereoselective dissipation of the novel chiral fungicide pydiflumetofen by ultra-high-performance liquid chromatography tandem mass spectrometry.
Pydiflumetofen is a novel and efficient broad-spectrum chiral fungicide consisting of a pair of enantiomers. A simple and sensitive chiral analytical method was established to determine the enantiomers of this chiral fungicide in food and environmental samples by ultra-high-performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-MS/MS) using QuEChERS method coupled with octadecylsilane-dispersive solid-phase extraction (C18-dSPE) as extraction procedure. The specific optical rotation and the absolute configuration of the enantiomers were identified by polarimetry and electronic circular dichroism (ECD). The elution order of the pydiflumetofen enantiomers on Lux Cellulose-2 was S-(-)-pydiflumetofen and R-(+)-pydiflumetofen. The average recoveries of eleven matrices ranged from 71.3% to 107.4%. The intraday relative standard deviations (RSDs) were less than 11.8%, and the interday RSDs were less than 12.6% for the two enantiomers. Stereoselective dissipation in pakchoi and soil were observed: S-(-)-pydiflumetofen was degraded faster than R-(+)-pydiflumetofen in pakchoi, causing the enantiomer fraction (EF) of the enantiomers to change from 0.50 to 0.42 in 7 days. However, R-(+)-pydiflumetofen was degraded faster than S-(-)-pydiflumetofen in soil, causing the EF of the enantiomers to change from 0.49 to 0.52 in 21 days. This study provides a method for monitoring pydiflumetofen enantiomer residues, which is crucial for improving risk assessments and the development of chiral pesticides.


The endothelial cell protein C receptor: cell surface conductor of cytoprotective coagulation factor signaling.
Increasing evidence links blood coagulation proteins with the regulation of acute and chronic inflammatory disease. Of particular interest are vitamin K-dependent proteases, which are generated as a hemostatic response to vascular injury, but can also initiate signal transduction via interactions with vascular receptors. The endothelial cell protein C receptor (EPCR) is a multi-ligand vitamin K-dependent protein receptor for zymogen and activated forms of plasma protein C and factor VII. Although the physiological role of the EPCR-FVII(a) interaction is not well-understood, protein C binding to EPCR facilitates rapid generation of APC in response to excessive thrombin generation, and is a central requirement for the multiple signal-transduction cascades initiated by APC on both vascular endothelial and innate immune cells. Exciting recent studies have highlighted the emerging role of EPCR in modulating the cytoprotective properties of APC in a number of diverse inflammatory disorders. In this review, we describe the structure-function relationships, signal transduction pathways, and cellular interactions that enable EPCR to modulate the anticoagulant and anti-inflammatory properties of its vitamin K-dependent protein ligands, and examine the relevance of EPCR to both thrombotic and inflammation-associated disease.


Utility of platelet function analyzer as a screening tool for the diagnosis of von Willebrand disease in adolescents with menorrhagia.
Von Willebrand disease (VWD), and in particular, VWD type 1 and low VW factor (defined as Von Willebrand Ristocetin cofactor activity (RCoF) <30 and <50 IU/dl, respectively with normal multimers) are frequently detected in adolescents with menorrhagia and both groups benefit from similar management. Platelet function analyzer (PFA-100®) is often used as a screening test to detect VWD. We analyzed the utility of PFA-100® as a screening tool in the detection of VWD type 1 and low VW factor (VWF) in an exclusive adolescent population with menorrhagia. The study population consisted of adolescents with menorrhagia who had simultaneously drawn blood samples for VWD and PFA-100®. Abnormal PFA-100® was defined as values >183 seconds for collagen/epinephrine and/or >126 seconds for collagen/ADP. Of a total of 235 patients tested, 23 patients had RCoF <50 IU/dl and normal multimer patterns. Statistical analysis of the utility of PFA-100® in detecting RCoF <50 IU/dl with normal multimers yielded sensitivity, specificity, positive predictive, and negative predictive values of 52%, 89%, 34%, and 95%, respectively. Based on our results, PFA-100® was not sufficiently sensitive to detect RCoF values <50 IU/dl with normal multimer patterns in teen-aged women with menorrhagia. We conclude that in the setting of adolescent menorrhagia, PFA-100® does not have utility as an initial screening test for the diagnosis of VWD and in particular, low VWF and that clinicians need to be aware of this limitation of PFA-100® while evaluating adolescents with menorrhagia.


Proximate factors influencing egg cannibalism in the land snail Arianta arbustorum (Pulmonata, Helicidae).
Factors affecting oophagy among siblings in the land snail Arianta arbustorum were studied in 3 populations from different altitudes in Switzerland. The degree of egg cannibalism in A. arbustorum is a function of hatching asynchrony since the earliest hatched snails will devour the unhatched eggs in the same clutch. Clutch size, egg density and amount of vegetable food available to newly hatched snails did not affect the degree of cannibalism. Snails from 3 populations were similar in terms of incubation time and intrinsic hatching asynchrony of the clutches. However, they differed in degree of cannibalism when the hatching asynchrony had been experimentally increased. Snails from a lowland forest showed a higher degree of cannibalism than did those from an alpine mountain slope. The parent snails differed in terms of incubation time and hatching synchrony in their clutches. Under natural conditions, the length of the hatching spread and, as a result, the degree of cannibalism will depend additionally on the mode of oviposition (batches or single; clumped or dispersed), on the spatial heterogeneity of egg-laying places and on climatic conditions (e.g. drought).


[Modern biology, imagery and forensic medicine: contributions and limitations in examination of skeletal remains].
Forensic examination is often requested when skeletal remains are discovered. Detailed visual observation can provide much information, such as the human or animal origin, sex, age, stature, and ancestry, and approximate time since death. New three-dimensional imaging techniques can provide further information (osteometry, facial reconstruction). Bone chemistry, and particularly measurement of stable or unstable carbon and nitrogen isotopes, yields information on diet and time since death, respectively. Genetic analyses of ancient DNA are also developing rapidly. Although seldom used in a judicial context, these modern anthropologic techniques are nevertheless available for the most complex cases.