Estimated Glomerular Filtration Rate in Short-Risk Stratification in Acute Myocardial Infarction.
Renal dysfunction is associated with a higher risk of cardiovascular disease in patients with acute myocardial infarction (AMI). The aim of this study was to investigate the independent prognostic value of renal dysfunction and its incremental predictability risk after adjusting for well-known clinical factors in patients with AMI. 751 consecutive patients with AMI admitted to the Coronary Care Unit (CCU) were included. Patients were grouped into 2 categories according to the baseline estimated glomerular filtration rate (eGFR) on admission (eGFR <60 vs. eGFR ≧60 ml/min/1.73 m2). C-reactive protein and white blood cell count (WBC) as well as clinical prognostic variables were assessed. The endpoint was mortality during CCU stay. The discriminatory power was estimated by the C-index. The patient group with an eGFR <60 ml/min/1.73 m2 was older, had more cardiovascular risk factors, a lower left ventricular ejection fraction and higher cardiovascular mortality during CCU stay (13 vs. 3%). Logistic regression analysis revealed the following predictors of mortality: degree of renal impairment (eGFR <60 ml/min/1.73 m2), hazard ratio (HR) = 2.2 (95% CI 1.1-4.3; p = 0.028); WBC >11,000 × 106/l, HR = 2.3 (95% CI 1.2-4.5; p = 0.017); Killip class on admission, HR = 3.8 (95% CI 1.7-8.5; p = 0.001), and New York Heart Association Functional Classification, HR = 3.6 (95% CI 1.7-7.4; p = 0.001). The adjusted C-index was 0.78 for baseline clinical variables and 0.84 for eGFR. In patients with AMI, decreased eGFR is an important prognostic factor for impaired cardiac function and mortality in the short-term follow-up. The eGFR may be reliably used in the risk stratification of patients with AMI.


Antibacterial new clerodane diterpenes from the surface of Haplopappus foliosus.
A biologically monitored fractionation of the resinous exudate extract of Haplopappus foliosus DC. is reported. Purification of the two active fractions yielded 2-alpha-hydroxy- cis-cleroda-3,13(Z),8(17)-trien-15-oic acid (1) and 2-alpha-acetoxy- cis-cleroda-3,13(Z),8(17)-trien-15-oic acid (2), two new clerodane diterpenes.


Methods for assessing the adequacy of practice and improving room disinfection.
The value of objectively monitoring and improving environmental cleaning in health care settings is becoming increasingly recognized as an important component of interventions to mitigate the transmission of health care-associated pathogens. Whereas the 2010 Centers for Disease Control and Prevention tool kit "Options for Evaluating Environmental Cleaning" provides detailed guidance related to implementing such programs, there is a need to clearly understand the value and limitations of various environmental cleaning monitoring approaches to ensure the favorable impact of such activities.


Intragraft coagulation events and delayed graft function in clinical renal transplantation.
Cold preservation, reperfusion damage, immunosuppressive drugs, and uremia-induced acquired thrombophilias increase the risk of thrombotic complications in renal transplantation. Intragraft fibrin deposition may be associated with delayed graft function. We studied coagulation and fibrinolysis in 45 patients of a larger trial in renal transplantation: perioperative antithymocyte globulin (group A, n=15), perioperative basiliximab (group B, n=16), and conventional triple therapy (group C, n=14). Blood samples for prothrombin fragment F1+2, plasminogen activator inhibitor (PAI)-1, d-dimer, tPA antigen, tPA activity, and platelet counts were obtained simultaneously at 1 and 5 min after reperfusion from iliac artery and graft vein for calculation of transrenal changes. Because antithymocyte globulin activates coagulation and fibrinolysis, group A was analyzed separately. Groups B and C were pooled (group BC). In group BC, transrenal D-dimer release occurred at 1 min, tPA-antigen release at 1 and 5 min, and transrenal PAI-1 uptake at 5 min postreperfusion. tPA activity increased marginally only at 1 min. High graft tPA-antigen release at 5 min and D-dimer release at 1 min were associated with delayed graft function. In group A, transrenal tPA-antigen release occurred at 1 and 5 min and D-dimer release at 1 min. There were no transrenal F1+2 changes in either group. Although graft PAI-1 uptake inhibits tPA activity, graft releases D-dimer at early reperfusion without concomitant F1+2 release. Data suggest thrombin and fibrin formation already before cold preservation during donor care and organ retrieval. This fibrin deposition increases risk of delayed graft function.


Deep wound infections after spinal fusion in children with cerebral palsy: a prospective cohort study.
Prospective cohort. To (1) calculate the rate of deep wound infection in children with cerebral palsy (CP) after spinal fusion surgery; (2) identify factors (patient, laboratory, and surgical) associated with deep wound infection development; and (3) report causative organisms. Wound infection after spine fusion for CP is more common than after spine fusion for most other diagnoses. We prospectively gathered data on 204 consecutive pediatric patients with CP who underwent surgery at 7 institutions. Univariate and multivariate regression analysis was performed to analyze patient, laboratory, and surgical characteristics to identify factors that were significantly associated with infection development. Statistical significance was set at a value of P less than 0.05. Deep wound infection developed in 13 (6.4%) children. The mean time to infection development was 34.2 ± 60.2 days. On univariate analysis, older age, larger curve size, presence of gastrostomy/gastrojejunostomy tube, higher preoperative serum white blood cell count, and longer operative time were significantly associated with deep wound infection. On multivariate analysis, only the presence of a gastrostomy/gastrojejunostomy tube remained significant (1.9-fold risk of deep wound infection compared with patients without tubes). Escherichia coli was the most common organism cultured from the wound sites (5 patients). Other infective agents were: Pseudomonas aeruginosa (2), methicillin-susceptible Staphylococcus aureus (1), Proteus mirabilis (1), and polymicrobial organisms (4). Deep wound infection occurred in 6.4% of children with CP after spinal fusion. The presence of a gastrostomy/gastrojejunostomy tube was a significant predictor of infection. Gram-negative organisms were the most common causative agents. Surgeons should be cognizant of these factors when treating children with CP and may consider Gram-negative antibiotic prophylaxis.


[The return home of a child or adolescent after a diabetes diagnosis].
The diagnosis of diabetes in a child or adolescent upsets the family dynamics. After the initial shock of the diagnosis, the child and their parents are given guidance to help them acquire a level of autonomy adapted to their needs. The aim of this early therapeutic education is to enable them to envisage resuming existing activities or organising new projects, as soon as they leave hospital.


Characterization of otoconin-95, the major protein of murine otoconia, provides insights into the formation of these inner ear biominerals.
During the course of a study aimed at identifying inner ear-specific transcripts, a 1,906-bp murine cDNA predicted to encode a secreted 469-aa protein with two domains of homology with the secreted phospholipases A2 was isolated. This transcript is specifically expressed in the inner ear from embryonic day 9.5. The encoded 95-kDa glycoprotein is the major protein of the utricular and saccular otoconia and thus was named otoconin-95. By immunohistofluorescence, otoconin-95 also was detected in the cupulae of the semicircular canals and in previously undescribed transient granular structures of the cochlea. Otoconin-95 was found to be synthesized by various nonsensory cell types, but not by the supporting cells of the sensory epithelia, which produce the otoconial precursor vesicles. In addition, multiple isoforms generated by differential splicing were observed in different combinations during development. Based on the present results, we propose a model for the formation of the otoconia.


Correction: High-risk additional chromosomal abnormalities at low blast counts herald death by CML.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Dysplastic erythroid precursors in the myelodysplastic syndromes and the acute myeloid leukemias: Is there biologic significance? (How should blasts be counted?).
The role of bone marrow dysplastic erythroid precursors (EP) in both MDS and AML has been the subject of considerable debate over the past several decades. We have analyzed a large series of adults with MDS and focused on whether any% of EP identified in the bone marrow aspirates of over 1400 patients selected from the Dusseldorf, Germany adult MDS Registry has prognostic relevance. The data was examined for varying% of blasts, the WHO prognostic MDS subtypes and the IPSS-R. We did not identify any adjustment of bone marrow blast percentage by%EP, incuding the 50% rule" developed by the FAB leukemia working group, to have a meaningful impact on outcome, either leukemic risk of progression or overall survival. There was a trend for a%EP<15% to actually have a worse survival than any other EP subset. We can no longer recommend the application of the "50% rule" in the calculation of the% of myeloblasts in bone marrow aspirates.


Defection-selective solubilization and chemically-responsive solubility switching of single-walled carbon nanotubes with cucurbit[7]uril.
Single-walled carbon nanotubes (SWCNTs) were suspended in aqueous media with cucurbit[7]uril (CB7), while SWCNTs were insoluble with cucurbit[5]uril (CB5). Moreover, defection-selective solubilization of SWCNTs with CB7 was demonstrated.


A large-scale view of the evolution of amniote development: insights from somitogenesis in reptiles.
Uncovering the genetic and developmental changes that generate morphological diversity is one of the longstanding challenges in biology. The developmental process generating the spine, one of the defining features of vertebrates, constitutes one of these core questions. The vertebral column is patterned in early development through the formation of segments, called somites, regulated by gene networks collectively called the segmentation clock. While previous studies of somite development in amniotes have focused almost exclusively on the mouse and chick model systems, the growing availability of genomic sequences in other taxa has opened up the possibility of comparative developmental studies in nontraditional reptilian models, such as the anole lizard, alligator, and snake. These studies have identified conserved features of the segmentation clock, but they have also challenged previous assumptions and identified divergence in the genetic networks. Ongoing work will help to elucidate which of these morphological changes may be explained by divergences in development in amniote evolution.


Significant increase of 8-hydroxydeoxyguanosine in liver DNA of rats following short-term exposure to the peroxisome proliferators di(2-ethylhexyl)phthalate and di(2-ethylhexyl)adipate.
8-Hydroxydeoxyguanosine (8-OH-dG) levels were examined in liver and kidney DNA after di(2-ethylhexyl)phthalate (DEHP), di(2-ethylhexyl)adipate (DEHA) and phthalic anhydride administration to male 6-week-old F-344 rats in the diet at concentrations of 1.2, 2.5 and 1.5%, respectively. Significant increases in 8-OH-dG levels were observed only in the liver (target organ of DEHP and DEHA carcinogenesis) DNA after 1 and 2 weeks of treatment with DEHP and DEHA, respectively. The results suggest the involvement of oxidative DNA damage in hepatocarcinogenesis by peroxisome proliferators.


Preliminary X-ray diffraction analysis of human chorionic gonadotropin.
Hexagonal bipyramidal crystals of deglycosylated human chorionic gonadotropin have been grown using the method of vapor diffusion against ammonium sulfate. These crystals grow to nearly 0.4 mm along each axis, diffract to better than 3.5-A resolution and are relatively stable to irradiation. The crystals belong to the hexagonal space group P6(1)22 or enantiomer, and have unit cell parameters a = b = 88.7 A and c = 177.3 A.


Machine-learning-derived rules set excludes risk of Parkinson's disease in patients with olfactory or gustatory symptoms with high accuracy.
Chemosensory loss is a symptom of Parkinson's disease starting already at preclinical stages. Their appearance without an identifiable etiology therefore indicates a possible early symptom of Parkinson's disease. Supervised machine-learning was used to identify parameters that predict Parkinson's disease among patients having sought medical advice for chemosensory symptoms. Olfactory, gustatory and demographic parameters were analyzed in 247 patients who had reported for chemosensory symptoms. Unsupervised machine-learning, implanted as so-called fast and frugal decision trees, was applied to map these parameters to a diagnosis of Parkinson's disease queried for in median 9 years after the first interview. A symbolic hierarchical decision rule-based classifier was created that comprised d = 5 parameters, including scores in tests of odor discrimination, odor identification and olfactory thresholds, the age at which the chemosensory loss has been noticed, and a familial history of Parkinson's disease. The rule set provided a cross-validated negative predictive performance of Parkinson's disease of 94.1%; however, its balanced accuracy to predict the disease was only 58.9% while robustly above guessing. Applying machine-learning techniques, a classifier was developed that took the shape of a set of six hierarchical rules with binary decisions about olfaction-related features or a familial burden of Parkinson's disease. Its main clinical strength lies in the exclusion of the possibility of developing Parkinson's disease in a patient with olfactory or gustatory loss.


Association of serum lipid levels with psychotic symptoms in first-episode and drug naïve outpatients with major depressive disorder: a large-scale cross-sectional study.
Background Major depressive disorder (MDD) is a prevalent psychiatric disorder, with increasing evidence that patients with MDD display psychotic symptoms. Studies have shown the association between lipid levels and MDD, but few have explored the relationship between lipids and psychotic symptoms in MDD. The objective of this study was to compare the differences of lipid levels between patients with psychotic major depressive disorder (PMD) and those with non-psychotic major depressive disorder (NPMD) in first-episode and drug-naive (FEDN) MDD patients. Methods A total of 1718 outpatients with FEDN MDD were recruited. In addition to collecting basic information, their blood specimens were also collected to detect serum TC, HDL-C, TG, and LDL-C. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) were used to assess their depression, anxiety, and psychotic symptoms respectively. Results Compared to those with NPMD, those with PMD had higher scores on HAMD, HAMA, and more elevated serum TC, TG, and LDL-C levels, but lower HDL-C levels (all p < 0.05). Further logistic regression analysis showed that TG, the severity of depressive and anxiety symptoms were significantly associated with psychotic symptoms (p < 0.05). Limitations No causal relationship could be drawn due to the cross-sectional design. Conclusions Psychotic symptoms in patients with MDD may be predicted by lipid levels in the future. Our findings suggest that TG seems to predict the presence of current psychotic features among patients with FEDN MDD.


Aqueous RAFT Synthesis of Low Molecular Weight Anionic Polymers for Determination of Structure/Binding Interactions with Gliadin.
Gliadin, a component of gluten and a known epitope, is implicated in celiac disease (CeD) and results in an inflammatory response in CeD patients when consumed. Acrylamide-based polyelectrolytes are employed as models to determine the effect of molecular weight and pendent group on non-covalent interaction modes with gliadin in vitro. Poly(sodium 2-acrylamido-2-methylpropane sulfonate) and poly(sodium 3-methylpropyl-3-butanoate) are synthesized via aqueous reversible addition fragmentation chain transfer (aRAFT) polymerization and characterized by gel permeation chromatography-multiangle laser light scattering. The polymer/gliadin blends are examined via circular dichroism, zeta potential measurements, 8-anilinonaphthalene-1-sulfonic acid fluorescence spectroscopy, and dynamic light scattering. Acrylamide polymers containing strong anionic pendent groups have a profound effect on gliadin secondary structure and solution behavior below the isoelectric point, while polymers containing hydrophobic character only have a minor impact. The polymers have little effect on gliadin secondary structure and solution behavior at the isoelectric point.


A new strain of Arthrinium phaeospermum isolated from Carex kobomugi Ohwi is capable of gibberellin production.
Plant growth-promoting endophytic fungi with gibberellin-producing ability were isolated from the roots of Carex kobomugi Ohwi, a common sand-dune plant, and bioassayed for plant growth-promotion. A new strain, Arthrinium phaeospermum KACC43901, promoted growth of waito-c rice and Atriplex gemelinii. Analysis of its culture filtrate showed the presence of bioactive GA(1) (0.5 ng/ml), GA(3) (8.8 ng/ml), GA(4) (4.7 ng/ml) and GA(7) (2.2 ng/ml) along with physiologically inactive GA(5) (0.4 ng/ml), GA(9) (0.6 ng/ml), GA(12) (0.4 ng/ml), GA(15) (0.4 ng/ml), GA(19) (0.9 ng/ml) and GA(24) (1.8 ng/ml). The fungal isolate was identified through sequence homology and phylogenetic analysis of 18S rDNA (internal transcribed region).


Risk factors for radiographic progression of osteoarthritis after partial meniscectomy of discoid lateral meniscus tear.
Partial meniscectomy has been preferred in the treatment of discoid lateral meniscus (DLM) with tear, rather than total or subtotal meniscectomy, which could lead to late radiographic degenerative changes. One or more risk factors contribute to radiographic progression of osteoarthritis after partial meniscectomy of DLM tear. Inclusion criteria were consecutive patients who underwent arthroscopic surgeries for DLM tear from January 2005 to December 2010 by one surgeon. Exclusion criteria were preoperative osteoarthritis with KL grade 3 or more, osteochondritis dissecans, minimal width of meniscal remnant less than 6mm after meniscectomy, meniscal repair of an unstable discoid meniscus, age over 60years, loss to follow-up for a minimum of 5years and simultaneous surgery on articular cartilage or anterior cruciate ligament. According to the KL grade at the last follow-up, all enrolled knees were sorted into no progression to knee osteoarthritis (KL grade 1 or 2 - NOA) and progression to osteoarthritis (KL grade 3 or 4 - POA) groups. Multivariate logistic regression was used to analyze the risk factors of high-grade osteoarthritis. In comparison with NOA group (n=135) and POA group (n=67), prolonged symptom duration, increased relative percentage of DLM thickness (RPDT) and the presence of horizontal tear were significant risk factors. The presence of horizontal tear (P=0.048, adjusted OR=19.364) was the strongest predictor, compared with prolonged symptom duration (P=0.030, adjusted OR=1.150) and increased RPDT (P=0.003, adjusted OR=1.377). Horizontal tear, prolonged symptom duration, and increased RPDT are significant risk factors for radiographic progression to high-grade osteoarthritis after partial meniscectomy of DLM tear with a minimum follow-up of 5years. III, case-control study.


Evaluation of neonatal and maternal morbidity in mothers with gestational diabetes: a population-based study.
Gestational diabetes mellitus (GDM) is the most frequent complication during pregnancy. Untreated GDM is a severe threat to maternal and neonatal health. Based on recent evidence, up to 15% of all pregnancies may be affected by GDM. We hypothesized that in a rural birth cohort, higher maternal BMI and adverse socioeconomic conditions would promote GDM, which in turn would lead to adverse effects on pregnancy outcomes. The current study is a part of a population-based cohort study examining the health and socioeconomic information from 5801 mothers and their children. The study, titled the Survey of Neonates in Pomerania (SNiP), was based in northeastern Pomerania, Germany (2002-2008). The cumulative incidence of GDM was 5.1%. Multiple logistic regression revealed prepregnancy overweight (OR 1.84 (95% CI 1.27-2.68)), prepregnancy obesity (OR 3.67 (2.48-5.44)) and maternal age (OR 1.06 (1.03-1.08)) as risk factors for GDM (p = 0.001). Alcohol use during pregnancy (OR 0.61 (0.41-0.90), a higher monthly income (OR 0.62 (0.46-0.83)), and the highest level of education (OR 0.44 (0.46-0.83)) decreased the risk of GDM. Newborns of GDM mothers had an increased risk of hypoglycaemia (OR 11.71 (7.49-18.30)) or macrosomia (OR 2.43 (1.41-4.18)) and were more often delivered by primary (OR 1.76 (1.21-2.60)) or secondary C-section (OR 2.00 (1.35-2.97)). Moreover, they were born 0.78 weeks (95% CI -1.09 - -0.48 weeks) earlier than infants of mothers without diabetes, resulting in higher percentage of late preterm infants with a gestational age of 32-36 weeks (11.1% vs. 6.96%). Age and BMI before pregnancy were the predominant mediators of the increased risk of GDM, whereas a higher income and educational level were protective. GDM affected relevant perinatal and neonatal outcomes based on its association with an increased risk of delivery by C-section, preterm birth, macrosomia at birth and neonatal hypoglycaemia.


Pre-pregnancy and pregnancy-related factors and the risk of excessive or inadequate gestational weight gain.
Gestational weight gain consistent with the Institute of Medicine's recommendations is associated with better maternal and infant outcomes. The objective was to quantify the effect of pre-pregnancy factors, pregnancy-related health conditions, and modifiable pregnancy factors on the risks of inadequate and excessive gestational weight gain. A longitudinal cohort of pregnant women (N=1100) who completed questions about diet and weight gain during pregnancy and delivered a singleton, full-term infant. Gestational weight gain was inadequate for 14% and excessive for 53%. Pre-pregnancy factors contributed 74% to excessive gain, substantially more than pregnancy-related health conditions (15%) and modifiable pregnancy factors (11%). Pre-pregnancy factors, pregnancy-related health conditions, and modifiable pregnancy factors contributed fairly equally to the risk of inadequate gain. Interventions to prevent excessive gestational gain may need to start before pregnancy. Women at risk for inadequate gain would also benefit from interventions directed toward modifiable factors during pregnancy.


Assessment of mortality from COVID-19 in a multicultural multi-ethnic patient population.
Studies indicate that ethnicity and socioeconomic disparity are significant facilitators for COVID-19 mortality. The United Arab Emirates, distinctly has a population of almost 12% citizens and the rest, immigrants, are mainly unskilled labourers. The disparate socio-economic structure, crowded housing conditions, and multi-ethnic population offer a unique set of challenges in COVID-19 management. Patient characteristics, comorbidities, and clinical outcomes data from the electronic patient medical records were retrospectively extracted from the hospital information system of the two designated public COVID-19 referral hospitals. Chi-square test, logistic regression, and odds ratio were used to analyse the variables. From, the total of 3072 patients, less than one-fifth were females; the Asian population (71.2%);followed by Middle Eastern Arabs (23.3%) were the most infected by the virus. Diabetes Mellitus (26.8%), hypertension (25.7%) and heart disease (9.6%) were the most prevalent comorbidities observed among COVID-19 patients. Kidney disease as comorbidity significantly diminished the survival rates (Crude OR 9.6, 95% CI (5.6-16.6), p < 0.001) and (Adjusted OR 5.7 95% CI (3.0 - 10.8), p < 0.001), as compared to those patients without kidney disease. Similarly, the higher age of patients between 51 and 65 years, significantly decreased the odds for survival (Crude OR 14.1 95% CI (3.4-58.4), p < 0.001) and (Adjusted OR 12.3 95% CI (2.9 - 52.4), p < 0.001). Patient age beyond 66 years, further significantly decreased the odds for survival (Crude OR 36.1 95% CI (8.5-154.1), p < 0.001), and (Adjusted OR 26.6 95% CI (5.7 - 123.8), p < 0.001). Our study indicates that older ages above 51 years and kidney disease increased mortality significantly in COVID-19 patients. Ethnicity was not significantly associated with mortality in the UAE population. Our findings are important in the management of the COVID-19 disease in the region with similar economic, social, cultural, and ethnic backgrounds.


Oxidative cellular damage associated with transformation of Helicobacter pylori from a bacillary to a coccoid form.
Exposure to unfavorable conditions results in the transformation of Helicobacter pylori, a gastric pathogen, from a bacillary form to a coccoid form. The mechanism and pathophysiological significance of this transformation remain unclear. The generation of the superoxide radical by H. pylori has previously been shown to inhibit the bactericidal action of nitric oxide, the concentration of which is relatively high in gastric juice. With the use of chemiluminescence probes, both the quality and quantity of reactive oxygen species generated by H. pylori have now been shown to change markedly during the transformation from the bacillary form to the coccoid form. The transformation of H. pylori was associated with oxidative modification of cellular proteins, including urease, an enzyme required for the survival of this bacterium in acidic gastric juice. Although the cellular abundance of urease protein increased during the transformation, the specific activity of the enzyme decreased and it underwent aggregation. Specific activities of both superoxide dismutase and catalase in H. pylori also decreased markedly during the transformation. The transformation of H. pylori was also associated with oxidative modification of DNA, as revealed by the generation of 8-hydroxyguanine, and subsequent DNA fragment. These observations indicate that oxidative stress elicited by endogenously generated reactive oxygen species might play an important role in the transformation of H. pylori from the bacillary form to the coccoid form.


Identification of genes expressed in response to acid stress in Synechocystis sp. PCC 6803 using DNA microarrays.
Plant cells are always exposed to various environmental stresses such as high light, low temperature and acid rain, and thus have to respond in order to survive these stresses. Although some mechanisms of responses to high light and low temperature etc., have been clarified, there is little information about the acclimation process to acid stress. In this study, the gene expression changes of Synechocystis sp. PCC 6803 in response to acid stress were examined using DNA microarrays (CyanoCHIP). We compared gene expression profiles of the cells treated at pH 8 (control) and pH 3 for 0.5, 1, 2 or 4 h. As a result, we found that 32 genes were upregulated by more than 3-fold, and 29 genes were downregulated by at least 3-fold after the acid treatment. Among these upregulated genes, expressions of slr0967 and sll0939 kept-increasing until 4 h under the acid stress and increased by 7 to 16-fold after the 4 h treatment. This suggests that the products of these two genes play important roles in the acid acclimation process.


Prospective randomized study of endovenous radiofrequency obliteration (closure procedure) versus ligation and stripping in a selected patient population (EVOLVeS Study).
This study was designed as a prospective multicenter randomized comparison of procedure-related complications, patient recuperation, and quality-of-life outcomes between patients undergoing vein stripping with high ligation and patients undergoing great saphenous vein (GSV) obliteration with temperature-controlled radiofrequency ablation without adjunctive high ligation (Closure procedure). Eighty-five patients (86 limbs) from five sites (France, 2; Austria, 1; United States, 2) were randomly allocated to undergo radiofrequency obliteration (RFO) or stripping and high ligation (S&L). Final analysis included data for 44 limbs in the RFO group and 36 limbs in the S&L group. Follow-up examinations were performed at 72 hours, 1 week, 3 weeks, and 4 months. All patients completed the CIVIQ2 quality-of-life (QOL) questionnaire and underwent clinical and ultrasound examinations at each follow-up visit. Immediate success on the day of treatment was reported for 95% (42 of 44) of limbs in the RFO group and 100% (36 of 36) of limbs in the S&L group. In seven RFO limbs (16.3%) a scan obtained 72 hours after the procedure showed flow in the proximal GSV. Five of these segments had reflux in the open segment. At 1 week two of these closed, and an additional segment closed at 3 weeks. In no cases did flow reappear after complete occlusion of the GSV. Time to return to normal activities was significantly less in the RFO group (mean, 1.15 days; 95% confidence interval [CI], 0.05-2.34) compared with the S&L group (mean, 3.89 days; CI, 2.67-5.12; P =.02). In the RFO group, 80.5% of patients returned to routine activities of daily living within 1 day, compared with 46.9% of patients in the S&L group (P <.01). Patients in the RFO group were able to return to work in 4.7 days (CI, 1.16-8.17), compared with 12.4 days (CI, 8.66-16.23) for the S&L group (P <.05). Analysis of the QOL surveys showed statistically significant differences in favor of the RFO group for global score and pain score during follow-up. The magnitude of the difference, however, progressively decreased between 1 week and 4 months. In the absence of significant complications, such as deep vein thrombosis and pulmonary embolism, severe neuritic sequelae, and skin burns, there are significant early advantages to endovascular obliteration of the GSV compared with conventional vein stripping.


Chronic enteropathy associated with SLCO2A1 gene and hereditary fructose intolerance: A coincidence of two rare diseases.
Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a rare disorder characterized by multiple small intestine ulcers. Patients with CEAS typically present with chronic anemia and gastrointestinal bleeding. Besides CEAS, SLCO2A1 mutations cause primary hypertrophic osteoarthropathy (PHO) which is considered as an extraintestinal manifestation in CEAS patients. Since CEAS and Crohn's disease are clinically indistinguishable, patients are often misdiagnosed with Crohn's disease. Herein, we describe a 4-year-old Turkish girl with CEAS due to homozygous pathogenic variant (c.656C > T) in SLCO2A1 with concomitant hereditary fructose intolerance (HFI) caused by homozygous pathogenic variant (c.1005C > G) in ALDOB. Prompt restriction of fructose, sucrose and sorbitol resulted in hepatomegaly regression and mild amelioration of patient's symptoms. Despite budesonide and azathioprine treatments, patient's protein losing enteropathy and chronic anemia did not improve. Although previous CEAS cases were reported from East Asian countries, it is likely to occur in people from other geographic areas. CEAS seems to be underdiagnosed and high index of suspicion is required for the diagnosis of this rare entity. Patients with prior diagnosis of Crohn's disease with no response to immunosuppressive treatment or anti-TNF therapy should be re-evaluated for possible CEAS diagnosis.


Whole exome sequencing identified three ABCC6 variants in two Pakistani families with pseudoxanthoma elasticum phenotype.
Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder of ectopic mineralization and fragmentation of elastic fibers in skin, eyes, cardiovascular and digestive system. PXE is caused by sequence variants in ABCC6, which encodes multidrug resistance-associated protein 6 (MRP6, also known as the ABCC6 protein). MRP6 is an important regulator of inorganic plasma pyrophosphate that acts as an inhibitor of ectopic mineralization observed in PXE patients with low inorganic plasma pyrophosphate levels. The current study was designed to investigate underlying genetic defect in two unrelated Pakistani families affected with PXE. Whole exome sequencing followed by Sanger sequencing was performed to identify causative variants. A novel homozygous frameshift variant (c.1799_1805dupGTCTGGT) was identified in one family and two previously reported missense variants (c.2294G > A and c.2974G > A) in compound heterozygous form in the other family. We identified ABCC6 variants that are likely cause of the PXE disease in the tested families. Genetic analysis of these families could be useful for pre-symptomatic diagnosis and genetic counselling of the affected families.


An effective coaching intervention for people with low recovery expectations and low back pain: a content analysis.
A health coaching intervention in addition to usual physiotherapy care increased recovery expectation and activity in people with non-chronic NSLBP and low recovery expectation. We aimed to fully describe the coaching intervention to allow replication and enable a deeper understanding of the mechanisms behind health coaching in this setting. A qualitative analysis was conducted using notes taken by the coach during the health coaching intervention. Two researchers independently applied open coding and content analysis, using the factors of low recovery expectation identified in a previous qualitative investigation as a framework. For the majority of participants coaching rapidly progressed to goal setting and action planning, with less time spent on increasing the importance and confidence to return to activity. The factors of the person, progression, pain, performance and treatment were addressed across all phases of the coaching intervention. This effective health coaching intervention for people with non-chronic NSLBP and low recovery expectation concentrated on goal setting and action planning and addressed the essential factors of recovery expectations. This study suggests that coaching interventions are likely to be different in this population compared to similar interventions in chronic conditions due to pre-existing levels of readiness to change.


Refusal as Radical Care? Moving Beyond Modern Industrial Agriculture.
In this contribution we approach the refusal of modern industrial agriculture, as an act of radical care. We begin by recognizing the unprecedented crises of biodiversity losses and climate disruptions, amidst widespread inequality in a global pandemic, which are linked with modern agricultural development. This development is underpinned by the objectification of 'nature' that is designed into strategies and technologies of extraction and control like chemical pesticides, synthetic fertilizers, hybrid seeds, genetic engineering and digitalization. Refusal of strategies and technologies of modern objectification, we argue, is an act of radical care that is geared towards nurturing alternatives grounded in the Earth's pluriverse.


Effect of postharvest nicotinamide treatment on NAD+ metabolism and redox status in strawberry fruit during storage.
The increased activity of PARP enzymes is associated with a deficiency of NAD+, as well as with a loss of NADPH and ATP, and consequent deterioration of the redox state in fruits. In this study, we checked whether treatment with nicotinamide (NAM) would affect PARP-1 expression and NAD+ metabolism in strawberry fruit during storage. For this purpose, strawberry fruits were treated with 10 mM NAM and co-treated with NAM and UV-C, and then stored for 5 days at 4 °C. Research showed that nicotinamide contributes to reducing oxidative stress level by reducing PARP-1 mRNA gene expression and the protein level resulting in higher NAD+ availability, as well as improving energy metabolism and NADPH levels in fruits, regardless of whether they are exposed to UV-C. The above effects cause fruits treated with nicotinamide to be characterised by higher anti-radical activity, and a lower level of reactive oxygen species in the tissue.


Orchestration of the S-phase and DNA damage checkpoint pathways by replication forks from early origins.
The S-phase checkpoint activated at replication forks coordinates DNA replication when forks stall because of DNA damage or low deoxyribonucleotide triphosphate pools. We explore the involvement of replication forks in coordinating the S-phase checkpoint using dun1Delta cells that have a defect in the number of stalled forks formed from early origins and are dependent on the DNA damage Chk1p pathway for survival when replication is stalled. We show that providing additional origins activated in early S phase and establishing a paused fork at a replication fork pause site restores S-phase checkpoint signaling to chk1Delta dun1Delta cells and relieves the reliance on the DNA damage checkpoint pathway. Origin licensing and activation are controlled by the cyclin-Cdk complexes. Thus, oncogene-mediated deregulation of cyclins in the early stages of cancer development could contribute to genomic instability through a deficiency in the forks required to establish the S-phase checkpoint.


Evaluation under real-life conditions of a stand-alone fall detector for the elderly subjects.
Elderly patients unable to get up after a fall or to activate an alarm mechanism are particularly at risk of complications and need to be monitored with extreme care. The different risk factors have fostered the development of stand-alone devices facilitating early detection of falls. We aimed at assessing performance of the Vigi'Fall(®) system, a cutting edge fall detector associating a "passive release" mechanism attached to the patient and including external sensors; in the event of a fall, the system automatically triggers an alarm, and it also incorporates embedded confirmation software. We have put it to the test under real-life conditions so as to evaluate not only its efficacy, but also and more particularly its acceptability and tolerability in elderly subjects. The study ran from March 2007 through December 2008 in a geriatric ward with 10 subjects over 75 years of age, all of whom presented with a risk of falling. For eight patients wearing an accelerometric sensor, eight "falling" events and 30 "alarm release" events were recorded. Sensitivity and specificity of the device came to 62.5 and 99.5% respectively. For the two patients wearing the complete device, no events were detected. Not a single adverse occurrence was noted. Local tolerance was excellent in all but one of the subjects. Our results clearly show that the device may be worn by patients without discomfort over prolonged periods of time, and also demonstrate that the verification component will help to increase sensitivity in real-life conditions to a level comparable to the level attained in our laboratory studies.


An interpretable RL framework for pre-deployment modeling in ICU hypotension management.
Computational methods from reinforcement learning have shown promise in inferring treatment strategies for hypotension management and other clinical decision-making challenges. Unfortunately, the resulting models are often difficult for clinicians to interpret, making clinical inspection and validation of these computationally derived strategies challenging in advance of deployment. In this work, we develop a general framework for identifying succinct sets of clinical contexts in which clinicians make very different treatment choices, tracing the effects of those choices, and inferring a set of recommendations for those specific contexts. By focusing on these few key decision points, our framework produces succinct, interpretable treatment strategies that can each be easily visualized and verified by clinical experts. This interrogation process allows clinicians to leverage the model's use of historical data in tandem with their own expertise to determine which recommendations are worth investigating further e.g. at the bedside. We demonstrate the value of this approach via application to hypotension management in the ICU, an area with critical implications for patient outcomes that lacks data-driven individualized treatment strategies; that said, our framework has broad implications on how to use computational methods to assist with decision-making challenges on a wide range of clinical domains.


The use of IVIG in neurological disease.
The studies cited herein highlight the potential benefits of IVIG therapy in a group of neurological disorders that are associated with aberrant immune responses. Indeed, all of the disorders discussed, except epilepsy, are associated with autoreactivity. The trials are preliminary and short-term and, except for idiopathic CIDP, uncontrolled. Interpretation of the findings of these uncontrolled studies is complicated by the fact that the natural history of all of these disorders is to show fluctuations. IVIG appears to be a potentially useful and safe agent in the treatment of patients with MG, intractable epilepsy, MS, and CIDP. Its place in the therapeutic approach to these neurological diseases must await the completion of controlled trials. Since other therapeutic modalities have already proven to be useful in several of these disorders, it will be important to determine if IVIG is more efficacious, safer, and more cost-effective. It is also worth considering whether the combination of IVIG and any of these more traditional approaches would provide added therapeutic benefit.


Poor induction of interferon-induced 2',5'-oligoadenylate synthetase (2-5 AS) in cells persistently infected with mumps virus is caused by decrease of STAT-1 alpha.
Poor induction of interferon-induced 2',5'-oligoadenylate synthetase (2-5AS) has been demonstrated in cells persistently infected with mumps virus as compared with uninfected cells. As for the number of interferon (IFN) receptors and the level of IFN regulatory factors (IRF-1 and IRF-2) mRNAs, there was little difference between them. Therefore, it is suggested that the IFN-alpha signaling system is ineffective in the persistently infected cells. Components of IFN-stimulating gene factor 3 alpha (ISGF-3 alpha), STAT-1 alpha (p91) and STAT-2 (p113), were investigated in human amnion (FL), human nasopharyngeal cancer (KB), human T-lymphoid (HUT 78), and human B-lymphoid (Akata) cells persistently infected with mumps virus. STAT-1 alpha, but not STAT-2, disappeared in these persistently infected cells, and this factor was not restored by treatment of these cells with IFN. However, no difference was observed between the levels of STAT-1 alpha mRNA transcript in persistently infected and uninfected control cells. It is reasonable to infer that the poor induction of 2-5AS activity is due to the decrease of STAT-1 alpha in correlation with the IFN-signal transduction pathway. Furthermore, induction of other IFN-stimulated genes (ds-RNA activated protein kinase, PKR, and MxA protein) was also reduced in the cells persistently infected with mumps virus.


A comparison of early diagnostic utility of Alzheimer disease biomarkers in brain magnetic resonance and cerebrospinal fluid.
The goals of this study were to compare the early diagnostic utility of Alzheimer disease biomarkers in the CSF with those in brain MRI in conditions found in our clinical practice, and to ascertain the diagnostic accuracy of both techniques used together. Between 2008 and 2009, we included 30 patients with mild cognitive impairment (MCI) who were examined using 1.5 Tesla brain MRI and AD biomarker analysis in CSF. MRI studies were evaluated by 2 radiologists according to the Korf́s visual scale. CSF biomarkers were analysed using INNOTEST reagents for Aβ1-42, total-tau and phospho-tau181p. We evaluated clinical changes 2 years after inclusion. By 2 years after inclusion, 15 of the original 30 patients (50%) had developed AD (NINCDS-ADRA criteria). The predictive utility of AD biomarkers in CSF (RR 2.7; 95% CI, 1.1-6.7; P<.01) was greater than that of MRI (RR 1.5; 95% CI 95%, 0.7-3.4; P<.2); using both techniques together yielded a sensitivity and a negative predictive value of 100%. Normal results on both complementary tests ruled out progression to AD (100%) within 2 years of inclusion. Our results show that the diagnostic accuracy of biomarkers in CSF is higher than that of biomarkers in MRI. Combined use of both techniques is highly accurate for either early diagnosis or exclusion of AD in patients with MCI.


Pharmacokinetics, pharmacodynamics and safety of LPM3480392 in two phase I clinical trials in healthy Chinese male subjects.
Drugs for acute postoperative pain and breakthrough cancer pain are still urgent in clinical. LPM3480392 is a G-protein-biased ligand at the μ-opioid receptor and showed potent analgesia in nonclinical studies. Two phase I studies of LPM3480392 were conducted in healthy Chinese male volunteers to explore its tolerability, pharmacokinetics and pharmacodynamics under single ascending doses (Study I 0.1-3.0 mg, 30 min) and different infusion times (Study II, 0.6-1.0 mg, 2-15 min). There was one serious adverse event (AE) observed in Study II, and the rest AEs were mild or moderate in severity and resolved by the end of the study. Plasma LPM3480392 maximum concentration (Cmax ) (under lower infusion rate) and area under the plasma concentration-time curve (AUCs) were generally increased with dose. Moreover, LPM3480392 at a dose of 0.6 mg under a 2 min infusion rate elicited effective analgesia as the peak effect within 10-30 min, which was measured by cold pain test and pupillometry. These findings suggest that LPM3480392 could be a potential treatment for acute pain management.


Patterns of failure in high-metastatic node number human papillomavirus-positive oropharyngeal carcinoma.
The 8th edition American Joint Committee on Cancer staging system for resected HPV-positive oropharynx carcinoma (HPV+ OPC) highlights high node number as a critical determinant of survival. We sought to characterize outcomes and patterns of failure in patients with high pathologically involved node number oropharynx cancer. We retrospectively identified 116 HPV+ OPC patients sequentially treated with neck dissection and either resection or intraoperative brachytherapy of the primary tumor between 2010 and 2016. External beam radiation was given based on the pathologic findings. Cox proportional hazards regression was used for multivariate analysis. With a median follow-up of 27 months, the 3-year overall survival and progression free survival (PFS) were 89% and 81%, respectively. On multivariate analysis, ≥5 involved lymph nodes was significantly associated with worse PFS (hazard ratio 4.3, 95% confidence interval (CI) 1.5-12.0, P = 0.001). Rates of 3-year locoregional recurrence (LRR) in patients with ≤4 vs ≥5 were 6% and 22% (log-rank P = 0.12). Rates of 3-year distant metastases (DM) were 12% and 53% between ≤4 and ≥5 (log-rank P < 0.001). Our findings confirm that patients with 5 or more involved lymph nodes appear to have substantially worsened rates of disease recurrence. While these patients appear to be at high risk of both LRR and DM, the predominant mechanism of failure is distant, and the rate of DM in this group was over 50%. Dedicated clinical trials in this patient population are warranted with a focus on mitigating the high DM rate.


Within-day variation of bioelectrical resistance measurements in patients with chronic obstructive pulmonary disease.
The relative contribution of a meal, exercise and diuretic therapy to within day variation of resistance values from bioelectrical impedance measurements was studied in several groups of patients with severe Chronic Obstructive Pulmonary Disease (COPD). All patients were in a stable clinical condition. Fasting resistance (RES) in the early morning was significantly higher than RES values during the day ((mean +/- SD): 26 +/- 21 Ohms, p < 0.001). Relative to a non-fasting pre-meal value no significant decrease in RES was measured within 4h after ingestion of the meal. RES did not change significantly after a submaximal exercise challenge on the bicycle ergometer. No consistent effect of oral diuretics (40 mg furosemide), was established within 5h after administration. Measurements on two consecutive days at the same time in the nourished state, were highly reproducible: mean change 4 +/- 20 Ohms, NS). We conclude that in patients with stable COPD, within day variation has only a slight impact on the estimation of fat free mass for between-patient comparison, but it is important to take this into account during follow up studies.


Clinical and biological parameters associated with fracture recurrence according to fracture liaison service dataset.
This study describes the characteristics of 337 patients seen by the fracture liaison service of the Amiens University Hospital for at least two osteoporotic fractures between 2009 and 2019. Results showed that recurrent fracture occurs rapidly after the index fracture. Rheumatological and therapeutic managements are not sufficient, mainly because of cognitive disorders or patients' refusal. The aim of this study was to describe the characteristics of patients taken in charge by a fracture liaison service and sustaining a recurrent osteoporotic fracture. This was a retrospective and monocentric study based on the dataset of patients included in the FLS of the Department of Rheumatology of the Amiens University Hospital. To be included in the study cohort, patients must have had at least two consecutive osteoporotic fractures between January 2009 and December 2019. Three hundred thirty-seven patients were included. The mean age at index fracture was 77.3 ± 12.5 years. Eighty-four percent of the patients were women. 89.3% of the patients had a Charlson comorbidity index between 1 and 4. Nearly half of the patients had cognitive disorders. Femoral neck was the most frequent site for both index and recurrent fractures. Thirty-seven percent of patients benefited from a consultation in Rheumatology after their index fracture. The main reasons for the lack of follow-up were cognitive disorders and patient rejection. Our study showed that recurrent fracture occurs rapidly after the index fracture and that rheumatological and therapeutic managements are not sufficient, mainly because of cognitive disorders or patients' refusal impairing the patients to benefit from specialized management.


New achievements on biological aspects of copper complexes Casiopeínas®: interaction with DNA and proteins and anti-Trypanosoma cruzi activity.
The mixed-chelate copper(II) complexes Casiopeínas® have been tested in several models in vitro and in vivo, showing promising antitumoral results. However, their mechanism of action remains to be defined. Trying to get a deeper insight into their molecular mode of action, further analyses, including gel electrophoresis, atomic force microscopy and circular dichroism were carried out to study their interaction with DNA and some cytoskeleton proteins. Our results revealed that the interaction of Casiopeínas triggers DNA cleavage by a free radical mechanism. The tested complexes showed a differential response to reducing and scavenger agents. Differences on target preference were also evident using double stranded oligonucleotides as sequence competitors. Surprisingly, distamycin A, a minor groove binder, enhanced the Casiopeínas' action on DNA. On the other hand, the tested Casiopeínas produce strong changes in protein structure of tubulin, integrin and fibronectin. All together these results suggest a multiple mode of action for these metal-based drugs. In addition, since it has been proposed that antitumor drugs efficiently interacting with DNA could also show activity against Trypanosoma cruzi, etiologic agent of Chagas disease, we evaluated the activity of these compounds on this protozoan parasite. The tested complexes showed in vitro anti-T. cruzi activity similar to the anti-trypanosomal reference drug Nifurtimox.


Ethylenediamine assisted functionalization of self-organized poly (d, l-lactide-co-glycolide) patterned surface to enhance cancer cell isolation.
Protein functionalized micro-scale patterned structures are developed using a biocompatible polymer PLGA (poly (d, l-lactide-co-glycolide)) via thin film dewetting and by step-wise chemical conjugations with EDA (ethylenediamine) and anti-EpCAM (Epithelial Cell Adhesion Molecule) antibodies to target the epithelial cell adhesion molecules of cancer cells. The effectiveness of such protein functionalized patterned surface is checked through cell isolation process using blood samples spiked with different cancer cells such as MCF-7, A549, MDA-MB-231. An efficient capture yield of 92% is obtained with MCF-7 cells over a two hour incubation time. The study demonstrates the effects of cell concentration and incubation time on the binding of cancer cells to the modified patterned surfaces. For the first time, a simple and inexpensive method is reported to fabricate functionalized PLGA patterned surface for an efficient isolation of cancer cells from diluted blood samples. The method shows the potential to be used as an effective platform for the development of an improved circulating tumor cell (CTC) isolation device from the clinical blood sample.


Cognitive change in obese adolescents losing weight.
To investigate how obese adolescents think about themselves in terms of exercise, eating, and appearance and whether these cognitions change over the course of a residential weight loss camp. Obese adolescents [N = 61; age, 14.1 (+/-0.2) years; BMI, 33.9 (+/-0.7) kg/m(2)] completed assessments of body weight and height and self-esteem and a sentence-completion test eliciting thoughts and beliefs about exercise, eating, and appearance at the start and end of the camp (mean stay, 26 days). They were compared with a single assessment of 20 normal-weight adolescents [age, 15.4 (+/-0.2) years; BMI, 21.8 (+/-0.5) kg/m(2)]. The obese adolescents lost 5.7 kg and reduced their BMI SD score by 0.25. Camp residence was associated with a significant reduction in the number of negative automatic thoughts and an increase in positive thoughts, especially related to exercise and appearance. There was no change in conditional beliefs, either functional or dysfunctional. Including BMI SD score change as a covariate took away all the main and interaction effects of time, showing that cognitive change was largely accounted for by the reduction in weight. Despite this improvement, campers remained cognitively more negative and dysfunctional than the normal-weight comparison adolescents. Obese adolescents not only lost weight, but they improved their self-representation, specifically in terms of automatic thoughts about exercise and appearance. Although these are short-term cognitive changes, they reflect positively on the camp experience and show the value of psychological improvement in assessing obesity-treatment outcomes.


It's all a matter of necessity and concern: A structural equation model of adherence to antihypertensive medication.
Hypertension is often treated pharmacologically, yet adherence is poor. Beliefs about antihypertensive medicine, i.e., the necessity-concern framework (NCF), are valuable for explaining adherence. Therefore, a model structure is transferred from hypercholesterolemia to hypertension, assuming a mediating role of the NCF. Patients with hypertension (n=273) were surveyed online about demographics, health- and treatment-related factors, control beliefs, necessity and concern beliefs about their medication, and adherence. The data were analyzed using structural equation modeling (SEM). Necessity was positively (β=0.26, p=0.009) and concern was negatively (β=-0.51, p=0.020) associated with adherence. The NCF mediated the influence of background variables on adherence. Necessity was associated with comorbidity (β=-0.36, p<0.001), treatment time (β=0.19, p=0.004), emotionally supportive doctor-patient communication (β=0.12, p=0.045), side effects (β=0.16, p=0.013), personal control (β=-0.13, p=0.022), and treatment control (β=0.29, p<0.001). Concern was associated with side effects (β=0.38, p<0.001) and beliefs about medicine in general being harmful (β=0.61, p<0.001). The model fit was acceptable (RMSEA=0.61). The transferred adherence model with the necessity-concern framework as a mediating factor was confirmed in hypertension, explaining more variance than previous approaches (23%). A personalized, emotionally supportive doctor-patient communication could be key to addressing beliefs about medicine and therefore to increasing adherence.


Relation of the -514C/T polymorphism in the hepatic lipase gene to serum HDL and LDL cholesterol levels in postmenopausal women under hormone replacement therapy.
Hepatic lipase (HL) is a lipolytic enzyme that catalyzes hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins. Recently, a -514C/T polymorphism in the promoter region of the HL gene was found to be associated with variations in hepatic lipase activity and serum high density lipoprotein cholesterol (HDL-C) levels. Postmenopausal hormone replacement therapy (HRT) has known favorable effects on serum lipid and lipoprotein levels. In this study, we examined the relation between the -514C/T polymorphism and serum lipid and lipoprotein levels in postmenopausal women prior to and after 3 months of HRT. Significant associations between the -514 C/T polymorphism and HDL-C, low density lipoprotein cholesterol (LDL-C) and apolipoprotein A-I (apo A-I) levels were observed before and/or after 3 months of HRT. With HRT, serum total cholesterol (TC), LDL-C and apolipoprotein B (apo B) levels were reduced significantly (P=0.0001), and HDL-C and apo A-I levels were increased significantly (P=0.0001). However, the degrees of change in lipid and lipoprotein levels due to HRT did not differ significantly between the HL genotypes.


Wearable technology in stroke rehabilitation: towards improved diagnosis and treatment of upper-limb motor impairment.
Stroke is one of the main causes of long-term disability worldwide, placing a large burden on individuals and society. Rehabilitation after stroke consists of an iterative process involving assessments and specialized training, aspects often constrained by limited resources of healthcare centers. Wearable technology has the potential to objectively assess and monitor patients inside and outside clinical environments, enabling a more detailed evaluation of the impairment and allowing the individualization of rehabilitation therapies. The present review aims to provide an overview of wearable sensors used in stroke rehabilitation research, with a particular focus on the upper extremity. We summarize results obtained by current research using a variety of wearable sensors and use them to critically discuss challenges and opportunities in the ongoing effort towards reliable and accessible tools for stroke rehabilitation. Finally, suggestions concerning data acquisition and processing to guide future studies performed by clinicians and engineers alike are provided.


After-hours emergency department care: Does time or day of arrival affect survival?
To determine whether after-hours presentation to EDs is associated with differences in 7-day and 30-day mortality. The influence of patient case-mix and workforce staffing differences are also explored. We conducted a retrospective observational study of 3.7 million ED episodes across 30 public hospitals in Queensland, Australia during May 2013-September 2015 using routinely collected hospital data linked to hospital staffing data and the death registry. Episodes were categorised as within/after-hours using time of presentation. Staffing was derived from payroll records and explored by defining 11 staffing ratios. Weekend presentation was slightly more associated (7-day mortality odds ratio 1.05, 95% confidence interval [CI] 1.01-1.10) or no more associated (30-day mortality odds ratio 1.01, 95% CI 0.98-1.03) with death than weekday presentation. When weeknights are included in the 'after-hours' period, odds ratios are smaller, so that after-hours presentation is no more associated (7-day mortality odds ratio 1.03, 95% CI 0.99-1.08) or less associated (30-day mortality odds ratio 0.95, 95% CI 0.93-0.97) with death. No significant after-hours patient case-mix differences were observed between weekday and weekend presentations for 7-day mortality. In other combinations of outcome and after-hours definition, some differences (especially measures relating to severity of presenting condition) were found. Staffing ratios were not strongly associated with any within/after-hours differences in ED mortality. After-hours presentation on the weekend to an ED is associated with higher 7-day mortality even after controlling for case-mix.


Identifying metastasis-initiating miRNA-target regulations of colorectal cancer from expressional changes in primary tumors.
Colorectal cancer (CRC) is prevalent with high mortality, with liver metastasis contributing as a major factor that worsens the survival of patients. The roles of miRNAs in CRC have been elucidated, subsequent to recent studies that suggest the involvement of miRNAs in cancer biology. In this study, we compare the miRNA and gene expression profiles of primary tumors between two groups of patients (with and without liver metastasis) to identify the metastasis-initiating microRNA-target gene regulations. Analysis from 33 patients with metastasis and 14 patients without metastasis revealed that 17 miRNAs and their 198 predicted target genes are differentially expressed, where the target genes showed association with cancer progression and metastasis with statistical significance. In order to evaluate the clinical implications of the findings, we classified CRC patients of independent data into two groups based on the identified miRNA-target regulations, where one group was closer to primary tumors with metastasis than the other group. The comparison of survival showed statistically significant difference, thereby implying the roles of the identified miRNA-target regulations in cancer progression and metastasis. The identification of metastasis-initiating miRNA-target regulations in this study will lead to better understanding of the roles of miRNAs in CRC progression.


Verniciflavanol A, a profisetinidin-type-4-arylflavan-3-ol from toxicodendron vernicifluum protects SH-SY5Y cells against H2O2-Induced oxidative stress.
Eleven undescribed derivatives of flavan, including flavan-3,4-diols vernicinosides A-H and profisetinidin-type-4-arylflavan-3-ols verniciflavanols A-C, together with eight known compounds were purified from the heartwood of Toxicodendron vernicifluum. The chemical structures of the undescribed compounds were characterized by spectroscopic data interpretation, including NMR (1H and 13C NMR HSQC and HMBC) and HRESIMS analysis. CD data analysis was conducted to assign the absolute configurations of the undescribed compounds and the active compound verniciflavanol A was also confirmed by ECD experiment. The absolute configuration of the sugar moiety was identified by GC analysis of chiral derivatives in the hydrolysate. MTT assay was applied to test these compounds against H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells. Results found that verniciflavanol A demonstrated the best potential in protecting SH-SY5Y cells against H2O2-induced oxidative stress by inhibiting cell apoptosis and attenuate reactive oxygen species (ROS) level and mitochondrial dysfunction. And the underlying mechanism was confirmed to be associated with Nrf2-antioxidant response element signaling and IL-6 cell survival pathways.


Neutrophil Gelatinase-Associated Lipocalin: A Biomarker for Early Diagnosis of Urinary Tract Infections in Infants.
Early diagnosis of urinary tract infection (UTI) is challenging in infants due to unspecific symptoms, difficulty in urine collection and possible contamination. The aim of this study was to assesses the usefulness of serum and urine neutrophil gelatinase-associated lipocalin (sNGAL and uNGAL, respectively) in the diagnosis of febrile and non-febrile UTI in infants. This prospective observational study enrolled 66 infants with the first episode of UTI and 18 healthy controls. At the time of enrollment, sNGAL, uNGAL, urinalysis, urine culture, white blood cell count (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and serum creatinine (sCr) were assessed. We found that, on average, both sNGAL and uNGAL levels were significantly higher in febrile UTI, compared to non-febrile UTI and controls. In turn, the mean sNGAL level, but not uNGAL, was significantly higher in the non-febrile UTI group compared to controls. sNGAL positively correlated with WBC, CRP, ESR and PCT, and uNGAL with CRP and leukocyturia. The receiver operating curves (ROC) demonstrate that the optimum cut-off of 76.2 ng/ml for sNGAL (sensitivity 92.9%, specificity 94.4%, and the area under the curve (AUC) of 0.98) and of 42.2 ng/ml for uNGAL (sensitivity 73.8%, specificity 72.2%, and AUC of 0.76) for diagnosing febrile UTI and 39.0 ng/ml for sNGAL (sensitivity 83.3%, specificity 55.6%, and AUC of 0.70) for diagnosing non-febrile UTI. In conclusion, serum NGAL is an excellent marker for the early diagnosis of febrile UTI, with sensitivity and specificity higher than those of urine NGAL. Diagnostic sensitivity of serum NGAL is smaller in non-febrile infants suffering from UTI, and urine NGAL is not useful for this purpose at all.


Association between high-sensitivity cardiac troponin I measured at emergency department and complications of emergency coronary artery bypass grafting.
High-sensitivity cardiac troponin I (hs-cTnI) is a widely used biomarker to identify ischemic chest pain in the Emergency Department (ED), but the clinical impact on emergency coronary artery bypass grafting (eCABG) remains undetermined. We aimed to evaluate the clinical impact of hs-cTnI measured at the ED by comparing outcomes of eCABG in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) which comprises unstable angina (UA) and non-ST-segment-elevation myocardial infarction (NSTEMI). From January 2012 to March 2016, 242 patients undergoing eCABG were grouped according to serum hs-cTnI level in the ED. The primary endpoint was major cardiovascular cerebral event (MACCE) defined as a composite of all-cause death, myocardial infarction, repeat revascularization, and stroke. The incidence of each MACCE composite, in addition to postoperative complications such as acute kidney injury, reoperation, atrial fibrillation, and hospital stay duration were also compared. Patients were divided into two groups: UA [<0.04 ng/mL, n = 102] and NSTEMI [≥0.04 ng/mL, n = 140]. The incidence of MACCE did not differ between the two groups. Postoperative acute kidney injury was more frequent in the NSTEMI group after adjusting for confounding factors (6.9% vs. 23.6%; odds ratio, 2.76; 95% confidence interval, 1.09-6.99; p-value = 0.032). In-hospital stay was also longer in the NSTEMI group (9.0 days vs. 15.4 days, p-value = 0.008). ECABG for UA and NSTEMI patients showed comparable outcomes, but hs-cTnI elevation at the ED may be associated with immediate postoperative complications.


Tris-(4,4'-di-tert-butyl-2,2'-bi-pyridine)(trans-4-tert-butyl-cyclo-hexa-nolato)-deca-μ-oxido-hepta-oxido-hepta-vanadium aceto-nitrile monosolvate including another unknown solvent mol-ecule.
The title hepta-nuclear alkoxido(oxido)vanadium(V) oxide cluster complex, [V7(C10H19O)O17(C18H24N2)3]·CH3CN, was obtained by the reaction of [V8O20(C18H24N2)4] with 4-tert-butyl-cyclo-hexa-nol (mixture of cis and trans) in a mixed CHCl3/CH3CN solvent. The complex has a V7O18N6 core with approximately C s symmetry, which is composed of two VO4 tetra-hedra, two VO6 octa-hedra and three VO4N2 octa-hedra. In the crystal, these complexes are linked together by weak inter-molecular C-H⋯O hydrogen bonds between the 4,4'-di-tert-butyl-2,2'-bi-pyridine ligand and the V7O18N6 core, forming a one-dimensional network along the c-axis direction. Besides the complex, the asymmetric unit contains one CH3CN solvent mol-ecule. The contribution of other disordered solvent mol-ecules to the scattering was removed using the SQUEEZE option in PLATON [Spek (2015 ▸). Acta Cryst. C71, 9-18]. The unknown solvent mol-ecules are not considered in the chemical formula and other crystal data.


Association between frailty and life satisfaction among older people in Shandong, China: the differences in age and general self-efficacy.
Frailty and other functional declines may be related to life satisfaction (LS) in the general elderly population. This study aims to investigate the association between frailty and LS among older individuals (age ≥60) and the impacts of age and general self-efficacy on the relationships. Using data from the 2017 Survey of the Shandong elderly Family Health Service, a cross-sectional study was conducted and 7070 older people aged 60+ were analysed. LS was measured using the Satisfaction with Life Scale. A Frailty Index (ranged 0~1) was determined as a proportion of accumulated deficits over 51 categories. General self-efficacy was measured using the Chinese version of the General Self-Efficacy Scale. Multiple weighted linear regression was used to examine possible relationships between the research variables. There was a negative association between frailty and LS. A dose-response-type relationship between net income and LS was observed. The interaction between frailty and age was found to be significantly associated with LS. Frailty has a stronger negative impact on LS among the young-old (60-69 years) than among the middle-old (70-79 years) and old-old (80+ years), which suggests a protective effect of ageing on LS reduction due to frailty. However, this protective effect was observed among individuals with low and medium level self-efficacy. The relationship between frailty and LS generally weaken with age. The higher level of general self-efficacy may provide a partial buffer against the negative impact of frailty on LS. Interventions that target to prevent and manage frailty should consider being prioritised among the young-old population. Development of self-efficacy could serve as an important strategy to buffer the negative effect of frailty on LS among older people.


Treatment of subchondral cysts in patients with haemophilia.
The haemophilic arthropathy is a disabling disease that causes chronic pain and functional limitation, due to recurrent intra-articular bleeding, with impaired quality of life. The aim of this work is to present our 24-year experience in the treatment of subchondral cysts filled with hydroxyapatite coralline in patients with haemophilia. Thirty-seven male patients with forty-nine cystic lesions were treated and evaluated between 1990 and 2014. Thirty four patients were haemophilia type A, three were haemophilia type B, two patients had inhibitors to factor VIII. The average age was 23.6 years. The average follow-up was 10 years. The lesions were located: twenty-four in the tibia (49%), six in the talus (12.2%), seven in the ulna (14.4%), five in the humerus (10.2%), five in the femur (10.2%) and two in the distal radius (4%). In all patients' radiographs, Computed Tomography and Magnetic Resonance Imaging were performed before surgery. The lesions were treated when the injury was greater than 15% of the joint area, and when the joint area was greater than 1 cm of diameter. Surgical technique consisted of aspirating the cyst contents and refilling it with hydroxyapatite coralline. In forty-eight cysts, restitution of bone structure was achieved by impaction of hydroxyapatite coralline. The average time of bone restoration was 10 months. Only one patient required a second intervention. The treatment of subchondral cyst in PWH by aspiration and filling with hydroxyapatite coralline allows bone restoration and delays deterioration of the joint treated.


Treating HIV-Positive/Non-AIDS Patients for Community-Acquired Pneumonia with ART.
This article reviews the most recent publications on community-acquired pneumonia (CAP) in the HIV-infected population on antiretroviral therapy (ART), focusing on epidemiology, prognostic factors, etiology, and antimicrobial therapy. The data discussed here were mainly obtained from a non-systematic review using Medline and references from relevant articles. CAP remains a major cause of morbidity and mortality among HIV-infected patients and incurs high health costs despite the introduction of ART. HIV-infected patients are generally known to be more susceptible to bacterial pneumonia. Streptococcus pneumoniae is the most frequently reported pathogen in HIV-infected patients on ART, who present a higher rate of bacteremia than non-HIV-infected patients. Several studies have also examined microbial etiology and prognostic factors of CAP in HIV-infected patients on ART. Despite the high rate of bacterial pneumonia in these patients, mortality rates are not higher than in patients without HIV infection.


Should medical students learn to develop a personal formulary? An international, multicentre, randomised controlled study.
This study was performed to determine whether students who are trained in developing a personal formulary become more competent in rational prescribing than students who have only learned to use existing formularies. This was a multicentre, randomised, controlled study conducted in eight universities in India, Indonesia, the Netherlands, the Russian Federation, Slovakia, South Africa, Spain and Yemen. Five hundred and eighty-three medical students were randomised into three groups: the personal formulary group (PF; 94), the existing formulary group (EF; 98) and the control group (C; 191). The PF group was taught how to develop and use a personal formulary, whereas e the EF group was taught how to review and use an existing formulary. The C group received no additional training and participated only in the tests. Student's prescribing skills were measured by scoring their treatment plans for written patient cases. The mean PF group score increased by 23% compared with 19% for the EF group (p < 0.05) and 6% for controls (p < 0.05). The positive effect of PF training was only significant in universities that had a mainly classic curriculum. Training in development and use of a personal formulary was particularly effective in universities with a classic curriculum and with traditional pharmacology teaching. In universities with a general problem-based curriculum, pharmacotherapy teaching can be based on either existing or personal formularies.


The subcellular distribution of carnosine, carnosine synthetase, and carnosinase in mouse olfactory tissues.
The dipeptide, carnosine, its synthetic enzyme, carnosine synthetase, and its degradative enzyme, carnosinase, appear to be localized in the cytosol of mouse olfactory bulb and epithelium. Mouse olfactory bulbs and epithelium were prelabeled in vivo with [3H]carnosine following intranasal irrigation with [3H]beta-alanine. [3H]carnosine co-distributed in olfactory bulb with lactate dehydrogenase with only 10% in the crude mitochondrial fraction. Similar results were also seen with endogenous carnosine distribution. Over 70% of the carnosine present in the crude mitochondrial fraction was localized in synaptosomes following sucrose gradient centrifugation. However, further fractionation of vesicle containing fractions from osmotically lysed crude mitochondrial fractions indicated that [3H]carnosine was not associated with vesicles. Nearly 70% of all the [3H]carnosine present in olfactory epithelium was soluble with most of the remainder in the crude nuclear fraction. The enzymes carnosine synthetase and carnosinase were clearly soluble in olfactory epithelium with 98% and 85% of the activity in the cytosol. Less than 2% was found in the crude mitochondrial fraction. In olfactory bulb both enzymes also appeared soluble.


Area under the curve as a dose metric for promotional responses following 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure.
An underlying basis of risk assessment is that an equivalent risk for a specified dose metric exists that allows for extrapolation of dose-response relationships between species. To better understand the use of area under the curve (AUC) as a dose metric for complex biological responses following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure, a study was designed using a physiologically based pharmacokinetic model in the female Sprague-Dawley rat that would result in equivalent AUCs of total liver TCDD with differing patterns of exposure. In the first group, rats received a high peak dose of 3500 ng TCDD/kg twice per week in the first week followed by a lower TCDD dose of 81 ng/kg twice per week for the remainder of the study. In the second group, rats received a gavage dose of 350 ng TCDD/kg in corn oil twice per week for the study duration of 15 weeks. Age-matched control rats received corn oil as a vehicle control. Placental glutathione S-transferase (PGST)-positive foci were measured in representative liver lobes by immunohistochemistry, as a representative complex biological response resulting from TCDD exposure. The median volume fraction was 0.045% in control rats and was significantly elevated in TCDD treatment groups. However, the volume fraction of PGST-positive foci was significantly higher in the TCDD group given the high peak dose during the first week of TCDD treatment compared with the group receiving the same average daily dose over the study duration: 0.74 versus 0.20%, respectively. These findings suggest that the peak magnitude of TCDD in liver rather than AUC may play a significant role in the induction of complex biological responses by TCDD.


Diagnostic and prognostic utility of molecular markers in synchronous bilateral breast carcinoma.
Histologic criteria have a limited role in determining whether the synchronous bilateral breast carcinomas represent two primaries or a metastasis to the contralateral breast. We studied the molecular analysis of synchronous bilateral breast carcinoma and whether they are originating from a single or different clone. We examined 17 patients with breast carcinoma, including 12 patients with synchronous bilateral carcinomas and control group of 5 infiltrating ductal carcinomas with regional lymph node metastases. Mutations were quantitatively determined to detect loss of heterozygosity (LOH) and microsatellite size alterations for a broad panel of 15 markers, involving 10 chromosomes using polymerase chain reaction. The carcinomas were classified as de novo or metastasis based on three levels of concordance: (1) marker-affected tumors were considered concordant if 50% or more of the same markers were mutated, (2) same gene copy affected, and (3) temporal sequence of mutation acquisition. In synchronous bilateral breast carcinoma patients, molecular analysis showed discordant mutations in all cases, supporting the diagnosis of de novo bilateral primary breast carcinomas. In patients with lymph node metastases, the primary breast carcinoma and metastases shared the same mutations, revealing a metastatic lesion. In conclusion, the application of molecular technology may play an important role for the differential diagnosis of dual primary carcinomas vs a metastatic breast cancer to contralateral breast. In this study, synchronous bilateral breast cancers represent two independent primaries rather than metastatic events.


Characterization of ammonium (methylammonium)/potassium antiport in Escherichia coli.
The energetics of ammonium ion transport by Escherichia coli have been studied using [14C]methylammonium as a substrate. Rapid assays for uptake allowed kinetic parameters (CH3NH3+ Km = 36 microM; Vmax = 4 nmol X s-1 X mg-1 to be determined in the absence of CH3NH3+ metabolism. Cells cultured in media containing 1 mM NH4+ failed to express CH3NH3+ transport activity. Methylammonium accumulated at levels which were 100-fold higher than those of the medium. This accumulation was dependent upon the addition of glucose or pyruvate. The entry of CH3NH3+ supported by glucose oxidation in an F1F0-ATPase-deficient mutant was blocked by uncoupler. Transport by wild-type cells under similar conditions was significantly inhibited by arsenate. Thus, CH3NH3+ uptake requires both ATP and an electrochemical H+ gradient. This transport activity was lost upon exposure of E. coli to osmotic shock, but could be recovered by incubation of shocked cells with boiled shock fluid or with glucose plus K+ in the presence of chloramphenicol. Similar reconstitution was observed in K+-depleted parental strains, but not in a mutant defective in K+ transport, demonstrating a requirement for internal K+. However, external K+ proved to be a noncompetitive inhibitor (Ki = 1 mM) of CH3NH3+ uptake by K+ -replete bacteria. External Na+ had no effect on transport. The addition of NH4+ or CH3NH3+ induced a rapid exodus of intracellular 86Rb+, an analog which was able to substitute for K+. The molar ratio of CH3NH3+ uptake to Rb+ exit was 1.12 +/- 0.11. These findings support a mechanism for CH3NH3+ (NH4+) accumulation which requires K+ antiport (exchange) and is driven by the electrochemical K+ gradient.


Protein loss of bovine dental enamel during in-vitro subsurface demineralization.
A chemical system based on the dialysis principle was used to study protein loss of dental enamel during demineralization with an acetic-acid buffer solution containing calcium and phosphate, in which the fluoride-ion activity was kept constant. This resulted in a subsurface lesion, with a depth of about 130 microns. After demineralization, protein material was isolated from the demineralization solution. u.v. Spectra of the protein showed strong absorbance between 240 and 300 nm. Amino-acid composition showed high glycine, glutamic acid, proline, serine and aspartic acid contents. After 10 days demineralization, the total protein loss was 3 micrograms cm-2; the mineral loss was 16 mg cm-2. Compared with the total enamel-protein content (0.06-0.09 wt per cent) protein loss (0.018 per cent of total lost material) was not proportional to the mineral loss, when a subsurface lesion was formed.


Family cognitive behaviour therapy for chronic fatigue syndrome: an uncontrolled study.
To examine the efficacy of family focused cognitive behaviour therapy for 11-18 year olds with chronic fatigue syndrome. Twenty three patients were offered family focused cognitive behaviour therapy. The main outcome was a fatigue score of less than 4 and attendance at school 75% of the time. Twenty patients completed treatment. Eighteen had completed all measures at six months follow up; 15 of these (83%) improved according to our predetermined criterion. Substantial improvements in social adjustment, depression, and fear were noted. Family focused cognitive behaviour therapy was effective in improving functioning and reducing fatigue in 11-18 year olds. Gains were maintained at six months follow up.


Studies on the formation, separation, and characterization of cyanogen bromide fragments of human AI apolipoprotein.
We have sought to obtain conditions for cyanogen bromide (CNBr) cleavage of apolipoprotein AI which would preserve, as far as possible, the biological activity of the resulting fragments. We found that the choice of solvent is an important consideration since modification of amino acids in different proteins varies with cleavage conditions. Initially, an analytical technique employing reversed-phase (RP)-HPLC which separates the four CNBr fragments in a single chromatographic step was established to monitor the products and extent of cleavage. In developing this technique, spectral data indicated damage to tyrosine and tryptophan residues during CNBr digestion. This problem was resolved by using 70% trifluoroacetic acid instead of 70% formic acid as the solvent, which had the added benefit of increasing the extent of cleavage of the Met86-Ser87 bond by 50%. We applied the information derived from the analytical RP-HPLC method to achieve the preparative isolation of CNBr fragments. This procedure included a gel permeation chromatography step using a citrate/urea buffer before RP-HPLC to isolate pure fragments in volatile buffers. Finally, we discuss aspects of structural integrity with an emphasis on modification of aromatic amino acids and deamidation of asparagine and glutamine residues.


The Indonesian National Nurses Association: aims and achievements.
Harif Fadhillah, Mustikasari Mustikasari (firstname.lastname@example.com), Apri Sunadi and Elsi Dwi Hapsari, Central Board of the Indonesian National Nurses Association.


Influence of chlortetracycline as an antibiotic residue on nitrous oxide emissions from wastewater treatment.
Strengthening the removal of antibiotics in wastewater treatment plants is a research focus, but whether antibiotics affect nitrous oxide (N2O) emissions from wastewater treatment remains to be determined. In this study, the effect of chlortetracycline (CTC) on N2O emissions in anaerobic/oxic/anoxic sequential batch reactors was investigated. Experimental results show that CTC promotes N2O emissions during biological nutrient removal. The addition of 0.1 mg/L CTC increased the N2O emission factor by 41.4% compared to the control. Mechanism exploration shows that CTC stimulates the release of extracellular polymeric substance (EPS) and binds to it, the generated EPS-CTC conjugates hinder or expand the mass transfer channel, which intensifies the electronic competition between oxidoreductases and the substrate competition between microorganisms, resulting in incomplete denitrification and nitrite accumulation, thereby increasing N2O emissions.


Pectin extraction from lime pomace by cold-active polygalacturonase-assisted method.
An Antarctic yeast was cultivated to produce and enzymatic extract with polygalacturonase activity, whose biochemical properties were studied. It assisted pectin extraction from lime pomace at 20 °C. The extract produced by Tausonia pullulans 8E had an optimum temperature of 40 °C and optimum pH of 5.0. At 20 °C, it displayed 54% of relative activity. A good pH-stability and thermostability were observed. Hg+2 and Co+2 inhibited its activity in 40 and 11%, respectively. Pectin was obtained from lime pomace at 20 °C, with 15% of yield after 120 min extraction. Uronic acid (46%) and neutral sugars (53%) were determined. Pectin's molecular weight was estimated in the order of 100,000 g mol-1. By anion-exchange chromatography, pectin-linked and free neutral sugars were observed. The high-methoxyl pectin was used to prepare low-calorie gels. It was demonstrated that this cold-active enzyme allows enzymatic-assisted pectin extraction at 20 °C.


[Clinical features and prognostic factors of elderly patients with mantle cell lymphoma].
Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage Ⅲ-Ⅳ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.


Continental scale inverse modeling of common organic water contaminants in European rivers.
The paper presents an analysis of measured riverine concentrations of 16 common organic water contaminants. From observed concentrations we back-calculate emissions and chemical half lives through a simple inverse model. The analysis does not allow identifying a single half life/emission factor combination, but a set of combinations which are Pareto-optimal (or "non-dominated"). The approach is shown to provide a rational basis for the screening of chemicals in rivers: with reference to the 16 chemicals considered here, estimated emission factors and half lives are consistent with the ones reported in other studies. For more precise estimates, prior knowledge about either emission factors or half lives is necessary. For the considered chemicals, loads to European seas can be subsequently estimated with an uncertainty usually within a factor of 2. The approach can be proposed for the inventorying of catchment-specific chemical pollutant emissions required for European environmental policies.


Competition between glassiness and order in a multispin glass.
A mean-field multispin interaction spin glass model is analyzed in the presence of a ferromagnetic coupling. The static and dynamical phase diagrams contain four phases (paramagnet, spin glass, ordinary ferromagnet, and glassy ferromagnet) and exhibit reentrant behavior. The glassy ferromagnet phase has anomalous dynamical properties. The results are consistent with a nonequilibrium thermodynamics that has been proposed for glasses.


Evaluation of left ventricular diastolic function using color kinesis.
Color kinesis (CK) is a real-time echocardiographic technique based on acoustic quantification that yields regional and global information by tracking and color-encoding endocardial motion. The aim of this study was to determine the feasibility and usefulness of diastolic CK images with ICK software to objectively assess global and regional left ventricular (LV) diastolic function. Accordingly, diastolic properties obtained from CK images were compared with conventional Doppler echocardiographic indices. We studied 56 subjects who underwent echocardiographic evaluation in our laboratory for assessment of cardiac structure and function. Criteria for inclusion included the presence of normal sinus rhythm and adequate two-dimensional echocardiographic imaging. Exclusion criteria were (1) all types of arrhythmias, (2) pericardial effusion, (3) heart rates <55 or >90 beats/min, (4) abnormal interventricular septal motion caused by right ventricular pressure or volume overload, (5) moderate to severe mitral or aortic regurgitation, and (6) mitral valve stenosis. Using pulsed Doppler echocardiography, peak velocities during rapid filling (E) and atrial contraction (A) were measured, and the E/A ratio and deceleration time of the E wave velocity (DT) were calculated. The time-velocity integral (TVI) of the E wave (TVI-R), A wave (TVI-A), and rapid-filling fraction (TVI-R/TVI-R+TVI-A) was measured. The early diastolic mitral annular velocity (Ea) was measured by tissue Doppler. The 56 subjects were divided into the following three groups: (1) an impaired relaxation group consisting of 30 patients with normal ejection fraction and a mitral inflow pattern with a reduced E/A ratio (E/A < 1.0); (2) a pseudonormal group consisting of 18 patients with a mitral inflow pattern with an increased E/A ratio (E/A > 1.0), an increased E/Ea ratio (E/Ea 10), and no shortened DT (≧140 ms) [patients with hypertrophic cardiomyopathy (HCM, n = 8), dilated cardiomyopathy (DCM, n = 8), and aortic valve stenosis (n = 2) were included in this group); and (3) a restrictive group consisting of eight patients with a mitral inflow pattern with an increased E/A ratio (E/A >1.5), an increased E/Ea ratio (E/Ea ≧10), and a shortened DT (<140 ms) [patients with DCM (n = 5) and HCM (n = 3) were included in this group]. As a control group, 20 normal subjects (30 ± 18 years) were selected on the basis of having high-quality echocardiographic images. Diastolic CK images were obtained from the LV midpapillary short-axis view. The analysis of CK diastolic images was performed by using ICK software. The CK-diastolic index (CK-DI) was defined as the degree of LV segmental expansion during the first 30% of diastole, expressed as a percentage. The mean CK-DI was calculated from the average CK-DI of six LV segments. No relationship was observed between mean CK-DI and rapid-filling fraction in any of the study subjects (r = -0.092, P > 0.2). Mean CK-DI was significantly lower in the restrictive group (34.2% ± 4.3%) compared with the normal group (70.6% ± 7.4%), the impaired relaxation group (50.5% ± 7.7%), and the pseudonormal group (42.3% ± 7.5%). The reduction of mean CK-DI was found to be associated with the progression of LV diastolic dysfunction. We conclude that the analysis of diastolic CK by using ICK software is a useful technique that can be applied to quantitative evaluation of LV global diastolic function.


Nectar intake and energy expenditure in a flower visiting bat.
In a coastal region of Venezuela the daily energy expenditure (DEE) and water turnover of the flower visiting bat Anoura caudifer was measured by using the doubly labeled water method. In flower visitors, this method allows independent measurement of energy intake and expenditure if the animals drink no additional water and if the nectar's energy content is known. An average DEE of 12.4 kcal/d and water exchange of 13.4 ml/d were found. Our data show a balanced energy budget when animals in the field imbibe nectar with a sugar concentration of 18-21%, which is roughly medial in the range of nectar concentrations of various bat flowers. The energy turnover of flower visiting bats is high compared with DEEs of other bat species, small mammals and birds; flower visiting bats seem to belong to those species having 'a fast spin of the life motor'.


Differentiating the pathological subtypes of primary lung cancer for patients with brain metastases based on radiomics features from brain CT images.
It is of high clinical importance to identify the primary lesion and its pathological types for patients with brain metastases (BM). The purpose of this study is to investigate the feasibility and accuracy of differentiating the primary adenocarcinoma (AD) and squamous cell carcinoma (SCC) of non-small-cell lung cancer (NSCLC) for patients with BM based on radiomics from brain contrast-enhanced computer tomography (CECT) images. A total of 144 BM patients (94 male, 50 female) were enrolled in this study with 102 with primary lung AD and 42 with SCC, respectively. Radiomics features from manually contoured tumors were extracted using python. Mann-Whitney U test and the least absolute shrinkage and selection operator (LASSO) logistic regression were applied to select relative radiomics features. Binary logistic regression and support vector machines (SVM) were applied to build models with radiomics features alone and with radiomics features plus age and sex. Fourteen features were selected from a total of 105 radiomics features for the final model building. The area under the curves (AUCs) and accuracy of SVM and binary logistic regression models were 0.765 vs. 0.769, 0.795 vs.0.828, and 0.716 vs. 0.726, 0.768 vs. 0.758, respectively, for models with radiomics features alone and models with radiomics features plus sex and age. Brain CECT radiomics are promising in differentiating primary AD and SCC to achieve optimal therapeutic management in patients with BM from NSCLC. • It is of high clinical importance to identify the primary lesion and its pathological types for patients with brain metastases (BM) to define the prognosis and treatment. • Few studies had investigated the feasibility and accuracy of differentiating the pathological subtypes of primary non-small-cell lung cancer between adenocarcinoma (AD) and squamous cell carcinoma (SCC) for patients with BM based on radiomics from brain contrast-enhanced CT (CECT) images, although CECT images are often the initial imaging modality to screen for metastases and are recommended on equal footing with MRI for the detection of cerebral metastases. • Brain CECT radiomics are promising in differentiating primary AD and SCC to achieve optimal therapeutic management in patients with BM from NSCLC with a highest area under the curve (AUC) of 0.828 and an accuracy of 0.758, respectively.


Mutation in continuous cultures of Schizosaccharomyces pombe II. Effect of amino acid starvation on mutational response and DNA concentration.
In agreement with the results obtained in Escherichia coli by other workers and our own previous data, the kinetics with which spontaneous mutations to resistance to the 12,13-epoxytrichothecene trichodermin accumulate in a lysine auxotroph of Schizosaccharomyces pombe are dependent upon the nutrilite used to limit the growth of the population. Under conditions of glucose-limitation mutation accumulation is proportional to generation time, while under lysine-limitation it becomes proportional to chronological time. In contrast to observations made in bacterial system, however, no significant change in the DNA content per cell is noted in slow growing cultures grown under amino acid starvation. These findings help to eliminate some of the theories put forward to explain the differential mutational responses observed under different growth limiting regimes.