Fitness versus Fatness: Which Influences Health and Mortality Risk the Most?
Cardiorespiratory fitness (CRF) is a more powerful predictor of mortality than body mass index or adiposity, and improving CRF is more important than losing body fat for reducing risk of cardiovascular disease and all-cause mortality. Data on reduced morbidity and mortality associated with increased CRF are strong and consistent. By contrast, data on intentional weight loss and mortality are uncertain, and weight loss-induced risk factor modification may be largely transient. Because weight loss maintenance is poor and considering the health risks associated with chronic weight instability ( "yo-yo" dieting), we propose an alternative paradigm that focuses on improving CRF rather than reducing body weight. We contend that this is a safer alternative for management of obesity and the associated comorbidities. Exercise adherence may improve if clinicians emphasized to their patients the importance of CRF compared with weight loss in improving health and reducing the risk of chronic diseases.


A step toward autonomy in education: probing into the effects of practicing self-assessment, resilience, and creativity in task supported language learning.
Self-assessment (SA) can provide students with opportunities to self-evaluate, or make judgments about their learning process and products of learning. Regarding the importance of SA, this survey pursued to examine the effects of practicing SA on Saudi Arabian EFL learners' resilience, creativity, and autonomy in task supported language learning. To fulfill these objectives, 60 intermediate EFL learners were chosen and separated accidentally into two groups of control and experimental. They were then pre-tested using three related questionnaires of resilience, creativity, and autonomy. Next, the treatment was practiced on the two groups. Eight lessons of Touchstone Book 3 were taught to the experimental group using SAvia applying different tasks. On the other hand, the lessons were trained to the control group without using SA and tasks. The aforementioned questionnaires were re-administered as the post-tests following the completion of all lessons. Independent and paired samples t-test findings displayed that the control and experimental groups performed differently on the three post-tests. In essence, the results showed that the experimental group's resilience, creativity, and autonomy were all improved by the treatment. The research's implications and conclusions were then outlined. The implications of the research can allow students to evaluate their own progress and skill development critically.


Prognostic Usefulness of Myocardial Work in Patients With Heart Failure and Reduced Ejection Fraction Treated by Sacubitril/Valsartan.
The noninvasive assessment of myocardial work (MW) by pressure-strain loops analysis (PSL) is a relative new tool for the evaluation of myocardial performance. Sacubitril/Valsartan is a treatment for heart failure with reduced ejection fraction (HFrEF) which has a spectacular effect on the reduction of cardiovascular events (major adverse cardiovascular events [MACEs]). This study aimed to evaluate the short- and medium-term effect of Sacubitril/Valsartan treatment on MW parameters and the prognostic value of MW in this specific group of patients. Seventy-nine patients with HFrEF (mean age: 66 ± 12 years; LV ejection fraction: 28% ± 9%) were prospectively included in the study and treated with Sacubitril/Valsartan. Echocardiographic examination was performed at baseline, and after 6- and 12-month of therapy with Sacubitril/Valsartan. Sacubitril/Valsartan significantly increased myocardial constructive work (CW) (1023 ± 449 vs 1424 ± 484 mm Hg%, p <0.0001) and myocardial work efficiency (WE) [87 (78to 90) vs 90 (86 to 95), p <0.0001]. During FU (2.6 ± 0.9 years), MACEs occurred in 13 (16%) patients. After correction for LV size, LV ejection fraction and WE, global myocardial constructive work (CW) was the only predictor of MACEs [hazard ratio [HR] 0.99 (0.99 to 1.00), p = 0.04]. A CW <910 mm Hg identified patients at particularly increase risk of MACEs [HR 11.09 (1.45 to 98.94), p = 0.002, log-rank test p <0.0001]. In conclusion, in patients with HFrEF who receive a comprehensive background beta-blocker and mineral-corticoid receptor antagonist therapy, Sacubitril/Valsartan induces a significant improvement of myocardial CW and WE. In this population, the estimation of CW before the initiation of Sacubitril/Valsartan allows the prediction of MACEs.


Rivers influence the population genetic structure of bonobos (Pan paniscus).
Bonobos are large, highly mobile primates living in the relatively undisturbed, contiguous forest south of the Congo River. Accordingly, gene flow among populations is assumed to be extensive, but may be impeded by large, impassable rivers. We examined mitochondrial DNA control region sequence variation in individuals from five distinct localities separated by rivers in order to estimate relative levels of genetic diversity and assess the extent and pattern of population genetic structure in the bonobo. Diversity estimates for the bonobo exceed those for humans, but are less than those found for the chimpanzee. All regions sampled are significantly differentiated from one another, according to genetic distances estimated as pairwise FSTs, with the greatest differentiation existing between region East and each of the two Northern populations (N and NE) and the least differentiation between regions Central and South. The distribution of nucleotide diversity shows a clear signal of population structure, with some 30% of the variance occurring among geographical regions. However, a geographical patterning of the population structure is not obvious. Namely, mitochondrial haplotypes were shared among all regions excepting the most eastern locality and the phylogenetic analysis revealed a tree in which haplotypes were intermixed with little regard to geographical origin, with the notable exception of the close relationships among the haplotypes found in the east. Nonetheless, genetic distances correlated with geographical distances when the intervening distances were measured around rivers presenting effective current-day barriers, but not when straight-line distances were used, suggesting that rivers are indeed a hindrance to gene flow in this species.


Patient-Centered Care Transitions After Injury Hospitalization: A Comparative Effectiveness Trial.
The investigation aimed to compare two approaches to the delivery of care for hospitalized injury survivors, a patient-centered care transition intervention versus enhanced usual care. This pragmatic comparative effectiveness trial randomized 171 acutely injured trauma survivors with three or more early postinjury concerns and high levels of emotional distress to intervention (I; n = 85) and enhanced usual care control (C; n = 86) conditions. The care transition intervention components included care management that elicited and targeted improvement in patients' postinjury concerns, 24/7 study team cell phone accessibility, and stepped-up care. Posttraumatic concerns, symptomatic distress, functional status, and statewide emergency department (ED) service utilization were assessed at baseline and over the course of the 12 months after injury. Regression analyses assessed intervention and control group outcome differences over time. Over 80% patient follow-up was attained at each time point. Intervention patients demonstrated clinically and statistically significant reductions in the percentage of any severe postinjury concerns expressed when compared to controls longitudinally (Wald chi-square = 11.29, p = 0.01) and at the six-month study time point (C = 74%, I = 53%; Fisher's exact test, p = 0.02). Comparisons of ED utilization data yielded clinically significant cross-sectional differences (one or more three- to six-month ED visits; C = 30.2%, I = 16.5%, [relative risk (95% confidence interval] C versus I = 2.00 (1.09, 3.70), p = 0.03) that did not achieve longitudinal statistical significance (F (3, 507) = 2.24, p = 0.08). The intervention did not significantly impact symptomatic or functional outcomes. Orchestrated investigative and policy efforts should continue to evaluate patient-centered care transition interventions to inform American College of Surgeons' clinical guidelines for U.S. trauma care systems.


Glutamine and glucose metabolism during thymocyte proliferation. Pathways of glutamine and glutamate metabolism.
Energy metabolism in proliferating cultured rat thymocytes was compared with that of freshly prepared non-proliferating resting cells. Cultured rat thymocytes enter a proliferative cycle after stimulation by concanavalin A and Lymphocult T (interleukin-2), with maximal rates of DNA synthesis at 60 h. Compared with incubated resting thymocytes, glucose metabolism by incubated proliferating thymocytes was 53-fold increased; 90% of the amount of glucose utilized was converted into lactate, whereas resting cells metabolized only 56% to lactate. However, the latter oxidized 27% of glucose to CO2, as opposed to 1.1% by the proliferating cells. Activities of hexokinase, 6-phosphofructokinase, pyruvate kinase and aldolase in proliferating thymocytes were increased 12-, 17-, 30- and 24-fold respectively, whereas the rate of pyruvate oxidation was enhanced only 3-fold. The relatively low capacity of pyruvate degradation in proliferating thymocytes might be the reason for almost complete conversion of glucose into lactate by these cells. Glutamine utilization by rat thymocytes was 8-fold increased during proliferation. The major end products of glutamine metabolism are glutamate, aspartate, CO2 and ammonia. A complete recovery of glutamine carbon and nitrogen in the products was obtained. The amount of glutamate formed by phosphate-dependent glutaminase which entered the citric acid cycle was enhanced 5-fold in the proliferating cells: 76% was converted into 2-oxoglutarate by aspartate aminotransferase, present in high activity, and the remaining 24% by glutamate dehydrogenase. With resting cells the same percentages were obtained (75 and 25). Maximal activities of glutaminase, glutamate dehydrogenase and aspartate aminotransferase were increased 3-, 12- and 6-fold respectively in proliferating cells; 32% of the glutamate metabolized in the citric acid cycle was recovered in CO2 and 61% in aspartate. In resting cells this proportion was 41% and 59% and in mitogen-stimulated cells 39% and 65% respectively. Addition of glucose (4 mM) or malate (2 mM) strongly decreased the rates of glutamine utilization and glutamate conversion into 2-oxoglutarate by proliferating thymocytes and also affected the pathways of further glutamate metabolism. Addition of 2 mM-pyruvate did not alter the rate of glutamine utilization by proliferating thymocytes, but decreased the rate of metabolism beyond the stage of glutamate significantly. Formation of acetyl-CoA in the presence of pyruvate might explain the relatively enhanced oxidation of glutamate to CO2 (56%) by proliferating thymocytes.


Metagenomic insights of the infant microbiome community structure and function across multiple sites in the United States.
The gut microbiome plays an important role in early life, protecting newborns from enteric pathogens, promoting immune system development and providing key functions to the infant host. Currently, there are limited data to broadly assess the status of the US healthy infant gut microbiome. To address this gap, we performed a multi-state metagenomic survey and found high levels of bacteria associated with enteric inflammation (e.g. Escherichia, Klebsiella), antibiotic resistance genes, and signatures of dysbiosis, independent of location, age, and diet. Bifidobacterium were less abundant than generally expected and the species identified, including B. breve, B. longum and B. bifidum, had limited genetic capacity to metabolize human milk oligosaccharides (HMOs), while B. infantis strains with a complete capacity for HMOs utilization were found to be exceptionally rare. Considering microbiome composition and functional capacity, this survey revealed a previously unappreciated dysbiosis that is widespread in the contemporary US infant gut microbiome.


Contact Sensitization to Emulsifying Agents: An Underrated Issue?
The evidence on the safety of topical preparations containing emulsifiers is limited. The aims of the study were to assess (1) the prevalence of sensitization to some emulsifiers commonly found in topical products, (2) the sensitization to emulsifiers in relation to sex, age, and predisposing factors, and (3) the frequency of concomitant sensitization to other common allergens. All consecutive patients presenting to the Allergy Unit of our Dermatological Department for allergological investigation were enrolled. All patients were patch tested with the Italian Società Italiana di Dermatologia Allergologica Professionale ed Ambientale baseline series and an additional emulsifiers series. Doubtful patch test reactions were not considered. Of 310 patients, 50 (16%) were sensitized to emulsifiers with 72 positive reactions. Lauryl polyethylene glycol/polypropylene glycol-18/18 methicone gave 26 positive reactions, glyceryl oleate 19, myristyl alcohol, and Amerchol L101 11. Concomitant sensitization to emulsifiers was found in 16 patients. Patients allergic to emulsifiers showed concomitant allergic reactions to allergens commonly found in cosmetics. No significant differences by sex, age, atopic diathesis, and clinical pattern at presentation were noticed. Contact allergy to emulsifiers is more frequent than reported. Patients allergic to emulsifiers show frequent positive patch tests to other constituents of cosmetics and topical products.


Cigarette smoke combined with staining beverages decreases luminosity and increases pigmentation in composite resin restorations.
This study evaluated the effect of cigarette smoke combined or not with colored beverages on the color change of a composite resin before and after repolishing procedures. Composite specimens were allocated into six groups (N = 10): 1) control (no colorant); 2) cigarette smoke; 3) coffee; 4) coffee and cigarette smoke; 5) red wine; and 6) red wine and cigarette smoke. During 21 days, groups 2, 4, and 6 were exposed daily to the smoke from 20 cigarettes, and groups 3, 4, 5, and 6 were immersed in coffee or red wine for 4 minutes each day. Color measurements were performed with a spectrophotometer at baseline, after 21 days, and after repolishing procedures. Statistical analysis indicated the exposure to cigarette smoke and staining beverages resulted in decreased luminosity (P = .0001) and increased red pigmentation in most experimental groups (P < .05). In groups 3, 4, and 6, an increased yellowish coloration (P = .001) was observed. Irrespective of the experimental group, total color changes were clinically significant (AE > 7.5). Repolishing resulted in greater luminosity, as well as decreased yellow pigmentation (P < .05). It could be concluded that combined staining agents such as cigarette smoke and red wine irreversibly change resin color regardless of the use of repolishing procedures.


Nonalcoholic fatty liver disease is associated with an increased risk of heart block in hospitalized patients with type 2 diabetes mellitus.
Recent studies suggested that nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiac tachyarrhythmias (mainly atrial fibrillation) in patients with and without type 2 diabetes mellitus. The aim of this study was to examine whether an association also exists between NAFLD and heart block. We have retrospectively evaluated a hospital-based cohort of 751 patients with type 2 diabetes discharged from our Division of Diabetes and Endocrinology during years 2007-2014. Standard electrocardiograms were performed on all patients. Diagnosis of NAFLD was based on ultrasonography, whereas the severity of advanced hepatic fibrosis was based on the fibrosis (FIB)-4 score and other non-invasive fibrosis markers. Overall, 524 (69.8%) patients had NAFLD and 202 (26.9%) had heart block (defined as at least one block among first-degree atrio-ventricular block, second-degree block, third-degree block, left bundle branch block, right bundle branch block, left anterior hemi-block or left posterior hemi-block) on electrocardiograms. Patients with NAFLD had a remarkably higher prevalence of any persistent heart block than those without NAFLD (31.3% vs. 16.7%, p<0.001); this prevalence was particularly increased among those with higher FIB-4 score. NAFLD was associated with a threefold increased risk of prevalent heart block (adjusted-odds ratio 3.04, 95% CI 1.81-5.10), independently of age, sex, hypertension, prior ischemic heart disease, hemoglobin A1c, microvascular complication status, use of medications and other potentially confounding factors. In conclusion, this is the largest cross-sectional study to show that NAFLD and its severity are independently associated with an increased risk of prevalent heart block in hospitalized patients with type 2 diabetes.


Familial occurrence of the g syndrome.
We report the familial occurrence of the G syndrome of multiple congenital anomalies affecting a mother and her three sons. All showed the characteristic syndromal facies, a low total ridge count, pronounced hypertelorism, and mild mental retardation, and severe dysphagia in infancy which improved with age but persisted in the boys (it has disappeared in the mother). One of the boys had a left cleft lip and cleft palate, another had a unilateral cleft lip. All boys had hypospadias: penile in two (with descended testes) and perineal in another (with cryptorchidism). Familial occurrence in this family is compatible with autosomal dominant inheritance.


Inflammation and Healthy Lifestyle Choices Influence Cardiometabolic Risks in African American Women.
Individuals of African origin in Europe and the Caribbean have a lower prevalence of coronary heart disease (CHD) than do Europeans and European Americans; however, African Americans, especially women, do not possess the same low CHD prevalence as Africans. As such, this study was designed to determine whether highly sensitive C-reactive protein (hsCRP) and fitness (V˙O2max) cluster with other cardiometabolic risks (CMRs) or whether their influence is independent of other CMRs in African American women. Fifty African American women were compared on fasting glucose, triglyceride, high-density lipoprotein cholesterol, blood pressure, and adiposity-based hsCRP classifications (low <1, group 1; moderate >1, group 2). Participants were obese but metabolically healthy. Oxygen uptake (V˙O2max) was correlated with systolic blood pressure, and percentage of fat in group 1. V˙O2max was related to systolic blood pressure, diastolic blood pressure, low-density lipoprotein-cholesterol, and percentage of fat, and hsCRP was related to triglycerides, and percentage of fat was related to diastolic blood pressure in group 2. These data indicate that CMRs are inversely related to V˙O2max at moderate hsCRP values in African American women. Inflammation and obesity are relatively independent of other CMRs. Inflammation along with sedentary lifestyles may contribute to the disparity observed for CHD morbidity and mortality in African American women. Adding the CMR profile may improve the prediction of CHD in African American women.


Magnetic properties of hydrothermally recrystallized magnetite crystals.
The discrepancy between the magnetic hysteresis properties of magnetite crystals that are precipitated from solution (<0.3 micrometer) and of crushed sifted grains (>0.3 micrometer) is not an inherent property of magnetite but is caused by the highly stressed state of crushed material and by adhering finer fragments. The size trends of magnetic properties exhibited by submicrometer-size precipitated grains continue in the size range from 1 micrometer to 1 millimeter in a set of hydrothermally recrystallized magnetite crystals. Coercive forces of these narrowly sized crystals follow a power law over a wide size range (0.1 micrometer to 1 millimeter) as predicted by theory. Dislocation etch pits show similar dislocation densities for hydrothermally grown (3 x 10(10) meter (-2)) and natural (1 x 10(10) meter(-2)) magnetite crystals. Hysteresis parameters of hydrothermally grown crystals are similar to those of natural crystals but are about one-fifth of those for crushed grains.


General Steps to Standardize the Laboratory Measurement of Serum Total 25-Hydroxyvitamin D.
The Vitamin D Standardization Program (VDSP) has collaborated with numerous groups and agencies to assemble a set of tools, i.e., a reference measurement system, that can be used to establish the traceability of 25-hydroxyvitamin D [25(OH)D] assays to relevant reference measurement procedures and reference materials. This is done with the goal of verifying end-user laboratory performance using precise statistical criteria to determine whether a specific assay is standardized. The purpose of this paper was to outline a set of steps that routine clinical and research laboratories can use to standardize their 25(OH)D assays using these tools. These steps apply to laboratories using commercially developed immunoassay measurement systems as well as in-house assays, usually based on high HPLC or LC tandem MS measurement systems. The steps are (1) initial calibration, (2) initial assessment of accuracy and bias, (3) assessment of total percent CV and mean bias, (4) use of trueness controls, and (5) participation in accuracy-based performance testing and/or external quality assessment schemes. The goal of each laboratory assay is to have a total CV of ≤10% and mean bias of ≤5%. Rigorous and less rigorous but low-cost options for meeting these statistical criteria are provided. Research laboratories who infrequently measure 25(OH)D are advised to repeat steps 1-4 for every measurement cycle. For users of commercial immunoassays who have relatively little control over standardization, we present an option for using trueness controls to develop a master equation that can be used to standardize results to the reference methods.


Investigation of the land subsidence and its consequences of large groundwater withdrawal in Rafsanjan, Iran.
Land subsidence is a phenomenon that involves the lowering or settling of the earth's surface due to various factors. The land subsidence due to groundwater withdrawal over the world has been seen in many areas. A decrease in ground water level would cause an increase in effective stresses at clay layers which results consolidation of lower layers. Since about 1980, it has been proven that Kerman Province subsidence in Iran is due to extensive ground water withdrawal. Overdraft of groundwater, an increasing of about 6 times since 1969 to 1999, has caused a decline of about 28 m in groundwater level. The rate of subsidence recently is about 5-15 cm. for decline of about one meter in groundwater level. In Rafsanjan area, many problems such as increase in the salinity of groundwater, land subsidence and consequently earth fissures and cracks in buildings are caused by groundwater withdrawal.


Play or not to play-An analysis of the mechanism of the zero-commission Chinese outbound tours through a game theory approach.
The purpose of this study is to demystify the mechanism of the so-called zero-commission tours that have become synonymous with the booming Chinese outbound tourism market in the past decade. Two models of game theory are applied to identify nine proposed key factors that constitute the "zero-tour" phenomenon. These involve interactions in both the temporal and spatial dimensions of all of the stakeholders concerned with such tours, from outbound tourists and outbound and inbound operators to local guides and governments both within and beyond the Chinese border. It is concluded that zero-commission tours, underpinned by the proposed factors and notwithstanding their current legal and practical viability, have a tremendous negative impact on all of the stakeholders. This study may serve as a reference for the drafting and implementation of both policy and business countermeasures to curb zero-commission tours, thus facilitating more positive contributions from Chinese outbound tourism to the development of world tourism.


The reliability of portable fixed dynamometry during hip and knee strength assessments.
Insufficient lower extremity strength may be a risk factor for lower extremity injuries such as noncontact anterior cruciate ligament tears. Therefore, clinicians need reliable instruments to assess strength deficiencies. To assess the intrarater, interrater, intrasession, and intersession reliability of a portable fixed dynamometer in measuring the strength of the hip and knee musculature. Crossover study. Sports medicine research laboratory. Three raters (A, B, C) participated in this 2-phase study. Raters A and B tested 11 healthy college graduate students (2 men, 9 women) in phase 1. Raters A and C tested 26 healthy college undergraduate students (7 men, 19 women) in phase 2. The dependent variables for the study were hip adductor, hip abductor, hip flexor, hip extensor, hip internal rotator, hip external rotator, knee flexor, and knee extensor peak force. The phase 1 intrasession intraclass correlation coefficients for sessions 1, 2, and 3 ranged from 0.88 to 0.99 (SEM = 0.08-3.02 N), 0.85 to 0.99 (SEM = 0.26-3.88 N), and 0.92 to 0.96 (SEM = 0.52-2.76 N), respectively. Intraclass correlation coefficients ranged from 0.57 to 0.95 (SEM = 1.72-13.15 N) for phase 1 intersession values, 0.70 to 0.94 (SEM = 1.42-9.20 N) for phase 2 intrarater reliability values, and 0.69 to 0.88 (SEM = 1.20-8.50 N) for phase 2 interrater values. The portable fixed dynamometer showed good to high intrasession and intersession reliability values for hip and knee strength. Intrarater and interrater reliability were fair to high, except for hip internal rotation, which showed poor reliability.


A stochastic model for annual reproductive success.
Demographic stochasticity can have large effects on the dynamics of small populations as well as on the persistence of rare genotypes and lineages. Survival is sensibly modeled as a binomial process, but annual reproductive success (ARS) is more complex and general models for demographic stochasticity do not exist. Here we introduce a stochastic model framework for ARS and illustrate some of its properties. We model a sequence of stochastic events: nest completion, the number of eggs or neonates produced, nest predation, and the survival of individual offspring to independence. We also allow multiple nesting attempts within a breeding season. Most of these components can be described by Bernoulli or binomial processes; the exception is the distribution of offspring number. Using clutch and litter size distributions from 53 vertebrate species, we demonstrate that among-individual variability in offspring number can usually be described by the generalized Poisson distribution. Our model framework allows the demographic variance to be calculated from underlying biological processes and can easily be linked to models of environmental stochasticity or selection because of its parametric structure. In addition, it reveals that the distributions of ARS are often multimodal and skewed, with implications for extinction risk and evolution in small populations.


Direct demonstration of iron in a term placenta in two cases of beta-thalassemia.
The aim of this study was to quantify iron in the placentas at the end of pregnancy in two patients suffering from beta-thalassemia and compare the data to that recorded from the placentas of healthy women. Iron was quantified in placental specimens taken after the delivery. The specimens were subjected to chemical treatments in order to remove extracellular iron and leave the intracellular iron intact. After coloration, each specimen was subjected to quantitative analysis of images in order to identify and quantify iron. Our results demonstrated that in beta-thalassemia there is an accumulation of iron in the outer basal cytoplasm of the epithelial cells of placental cotyledons.


Verbal communication skills in typical language development: a case series.
The aim of the current study was to investigate verbal communication skills in children with typical language development and ages between 6 and 8 years. Participants were 10 children of both genders in this age range without language alterations. A 30-minute video of each child's interaction with an adult (father and/or mother) was recorded, fully transcribed, and analyzed by two trained researchers in order to determine reliability. The recordings were analyzed according to a protocol that categorizes verbal communicative abilities, including dialogic, regulatory, narrative-discursive, and non-interactive skills. The frequency of use of each category of verbal communicative ability was analyzed (in percentage) for each subject. All subjects used more dialogical and regulatory skills, followed by narrative-discursive and non-interactive skills. This suggests that children in this age range are committed to continue dialog, which shows that children with typical language development have more dialogic interactions during spontaneous interactions with a familiar adult.


Novosphingobium malaysiense sp. nov. isolated from mangrove sediment.
A novel bacterium, strain MUSC 273(T), was isolated from mangrove sediments of the Tanjung Lumpur river in the state of Pahang in peninsular Malaysia. The bacterium was yellow-pigmented, Gram-negative, rod-shaped and non-spore-forming. The taxonomy of strain MUSC 273(T) was studied by a polyphasic approach and the organism showed a range of phenotypic and chemotaxonomic properties consistent with those of the genus Novosphingobium. The 16S rRNA gene sequence of strain MUSC 273(T) showed the highest sequence similarity to those of Novosphingobium indicum H25(T) (96.8 %), N. naphthalenivorans TUT562(T) (96.4 %) and N. soli CC-TPE-1(T) (95.9 %) and lower sequence similarity to members of all other species of the genus Novosphingobium. Furthermore, in phylogenetic analyses based on the 16S rRNA gene sequence, strain MUSC 273(T) formed a distinct cluster with members of the genus Novosphingobium. DNA-DNA relatedness of strain MUSC 273(T) to the type strains of the most closely related species, N. indicum MCCC 1A01080(T) and N. naphthalenivorans DSM 18518(T), was 29.2 % (reciprocal 31.0 %) and 17 % (reciprocal 18 %), respectively. The major respiratory quinone was ubiquinone Q-10, the major polyamine was spermidine and the DNA G+C content was 63.3±0.1 mol%. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidyldimethylethanolamine, phosphatidylcholine and sphingoglycolipid. The major fatty acids were C18 : 1ω7c, C17 : 1ω6c, C16 : 0, C15 : 0 2-OH and C16 : 1ω7c. Comparison of BOX-PCR fingerprints indicated that strain MUSC 273(T) represented a unique DNA profile. The combined genotypic and phenotypic data showed that strain MUSC 273(T) represents a novel species of the genus Novosphingobium, for which the name Novosphingobium malaysiense sp. nov. is proposed. The type strain is MUSC 273(T) ( = DSM 27798(T) = MCCC 1A00645(T) = NBRC 109947(T)).


Pneumocystis carinii pneumonia in patients with AIDS: evaluation of lavage and staining techniques in diagnosis.
The diagnostic yield of unilateral vs. bilateral bronchoalveolar lavage (BAL) was prospectively evaluated in 65 consecutive patients suspected of having Pneumocystis carinii pneumonia (PCP) complicating acquired immune deficiency syndrome (AIDS). Gram-Weigert (GW), Papanicolaou (PAP), and Gomori's methenamine silver (GMS) stains were used for identification of P. carinii in all cases. Forty-eight patients had PCP that was identified by GW staining of BAL in 47/48 patients followed by PAP/GMS staining of BAL in 44/48 patients and PAP/GMS staining of bronchial washings in 40/48 patients. In patients with bilateral interstitial infiltrates, unilateral lavage was sufficient for diagnosis of PCP when GW stain was utilized. In patients with PCP complicating AIDS, the diagnostic yield of BAL may be increased by use of both GW and GMS stains.


Treatment of galactorrhea-amenorrhea.
A patient complaining of abnormal lactation and amenorrhea should be evaluated for a pituitary tumor. The work-up includes a thorough history and physical examination, serum prolactin and thyroid-stimulating hormone (TSH) determinations, and radiographic assessment of the pituitary gland. The treatment of choice for hyperprolactinemia leading to abnormal lactation is bromocriptine mesylate, even when small pituitary tumors are present. Surgery is reserved for patients who fail to respond to medical treatment and have tumors larger than 1 cm.


DNA Methylation of the Leptin Gene Promoter is Altered by Chronic Alcohol Exposure in an Animal Model for Alcohol Dependence.
Appetite-regulating peptides, such as leptin, are linked to craving and have been in the focus of alcohol dependence research for years. The objective of our study was to investigate the dynamics of leptin gene promoter methylation during alcohol withdrawal and specific treatment in a rodent (rat) model for alcohol dependence. DNA methylation was measured using direct bisulfite sequencing at 0 h, 24 h, and 6 days of alcohol withdrawal as well as after treatment with alpha-melanocyte-stimulating hormone (alpha-MSH), Beta-Endorphin, or saline. We found significantly lower methylation levels in alcohol-consuming animals compared to alcohol-naïve animals. During 6 days of alcohol deprivation, this difference in methylation vanished. Leptin methylation of the alpha-MSH-treated group and 6 days alcohol-deprived animals was significantly higher than that in saline-treated animals, possibly indicating compensatory effects of the treatment. Our results further expand on previous findings from human studies that explain leptin's role in bridging the gap between alcohol consumption and appetite regulation.


Child Head Circumference and Placental MFSD2a Expression Are Associated to the Level of MFSD2a in Maternal Blood During Pregnancy.
Gestational diabetes mellitus (GDM) is a world-wide health challenge, which prevalence is expected to increase in parallel to the epidemic of obesity. Children born from GDM mothers have lower levels of docosahexaenoic acid (DHA) in cord blood, which might influence their neurodevelopment. Recently, the membrane transporter Major Family Super Domain 2a (MFSD2a) was associated with the selective transportation of DHA as lysophospholipids. The expression of the DHA membrane transporter MFSD2a is lower in GDM placentas, which could affect materno-fetal DHA transport. Humans with homozygous inactivating mutations in the MFSD2a gene present severe microcephaly and intellectual impairments. Herein, we intended to identify early blood biomarkers that may be of use during pregnancy to monitor the offspring development and the adequate nutritional interventions, such as nutritional supplementation, that may be selected to improve it. We evaluated MFSD2a expression in maternal blood at the third trimester of pregnancy, and its potential relationship with the expression of placental MFSD2a at delivery and child outcomes. Three groups of pregnant women were recruited: 25 controls, 23 GDM with dietary treatment, and 20 GDM with insulin treatment. Maternal and neonatal anthropometric and biochemical parameters were evaluated. MFSD2a was analyzed in placenta, blood and serum. MFSD2a protein expression in maternal blood was significantly lower in GDM groups and correlated with placental MFSD2a and Z-score neonatal head circumference during the first 6 months of life. The cord/maternal serum ratio of DHA, a solid indicator of materno-fetal DHA transport, was reduced in GDM groups and correlated with MFSD2a in maternal blood at the third trimester and in placenta at delivery. This indicates that altered MFSD2a levels in maternal blood during pregnancy might influence placental nutrient transport and fetal neurodevelopment. Furthermore, MFSD2a levels in maternal blood on the third trimester were inversely correlated to DHA in maternal serum lyso-PL. Thus, the level of MFSD2a in maternal blood could be used as a potential biomarker for the early detection of disturbances of MFSD2a expression during pregnancy and the subsequent consequences for the neurodevelopment of the child, as well as it may help to choose the optimal treatment approach for the affected subjects.


Beyond the cholinergic hypothesis: do current drugs work in Alzheimer's disease?
Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory and cognitive loss, and represents the leading cause of dementia in elderly people. Besides the complex biochemical processes involved in the neuronal degeneration (formation of senile plaques containing Abeta peptides, and development of neurofibrillary tangles), other molecular and neurochemical alterations, like cholinergic deficit due to basal forebrain degeneration, also occur. Because acetylcholine has been demonstrated to be involved in cognitive processes, the idea to increase acetylcholine levels to restore cognitive deficits has gained interest (the so-called cholinergic hypothesis). This has led to the development of drugs able to prevent acetylcholine hydrolysis (acetylcholinesterase inhibitors). However, the analysis of clinical efficacy of these drugs in alleviating symptoms of dementia showed unsatisfactory results. Despite such critical opinions on the efficacy of these drugs, it should be said that acetylcholinesterase inhibitors, and for some aspects memantine also, improve memory and other cognitive functions throughout most of the duration of the disease. The pharmacological activity of these drugs suggests an effect beyond the mere increase of acetylcholine levels. These considerations are in agreement with the idea that cognitive decline is the result of a complex and not fully elucidated interplay among different neurotransmitters. The role of each of the neurotransmitters implicated has to be related to a cognitive process and as a consequence to its decline. The current review aims to highlight the positive role of cholinergic drugs in alleviating cognitive deficits during wake as well as sleep. Moreover, we suggest that future therapeutic approaches have to be developed to restore the complex interplay between acetylcholine and other neurotransmitters systems, such as dopamine, serotonin, noradrenaline, or glutamate, that are likely involved in the progressive deterioration of several cognitive functions such as attention, memory, and learning.


[Long-term results of open stent-grafting applied with a Matsui-Kitamura( MK) stent in treatment of arch aneurysm].
We report the initial and long-term results of open stent-grafting (OSG) applied with a Matsui-Kitamura (MK) stent in the treatment of thoracic aortic aneurysm (TAA). From August 2005 to March 2013, OSG for TAA was applied in 46 cases( male/female, 36/10, 54-86 years old, mean age 71). During deep hypothermic circulatory arrest with antegrade selective cerebral perfusion, stent graft was delivered through the transected proximal aortic arch, followed by arch replacement with a 4-branched prosthesis. Operative mortality within 30 days was 6.5%(respiratory failure in 1, multiple organ failure in 1and ischemic enteritis in 1) and there was 1 in hospital death due to brain stem infarction. Perioperative morbidity included 2( 4.3%) stroke, 5( 10.9%) spinal cord injuries( paraplegia in 1, paraparesis in 1 and transient paraparesis in 3). In long-term follow-up, survival was 86.8%, 77.2%, and 72.0% for 1, 3 and 5 years. Freedom from aortic event was 97.3%, 93.8% and 89.1% for 1, 3 and 5 years. Theseresults suggested the OSG method applied with a MK stent is a useful surgical procedure for the treatment of TAA.


Distinction between high-affinity [3H]phencyclidine binding sites and muscarinic receptors in guinea-pig ileum muscle.
[3H]Phencyclidine ([3H]PCP) binding was studied in guinea-pig ileum muscle membranes. Specific binding of [3H]PCP was time dependent, reversible and saturable, with an equilibrium dissociation constant of 154 nM and maximum binding of 12.9 pmol/mg of protein at pH 9. Its pH dependency suggests that the unionized PCP is the pharmacologically active form. The binding site was on a protein which was sensitive to heat, proteolytic enzymes and the carboxylic group reagent dicyclohexylcarbodiimide, but insensitive to phospholipase A and C, concanavalin A, dithiothreitol and N-ethylmaleimide. Specific [3H]PCP binding was displaced effectively by several PCP analogs and Ca++ channel antagonists including verapamil, to which these sites had a high affinity. These high-affinity PCP-binding sites were found at a much higher concentration in the same membrane preparation than muscarinic receptor sites identified by their specific binding of [3H]quinuclidinyl benzilate. PCP bound to both sites, but with a lower affinity to the muscarinic receptor sites. The PCP and muscarinic receptor sites differed in their sensitivities to pH and drug specifities .


Methods for the differential integrative omic analysis of plasma from a transgenic disease animal model.
Multitiered quantitative analysis of biological systems is rapidly becoming the desired approach to study hierarchical functional interactions between proteins and metabolites. We describe here a novel systematic approach to analyze organisms with complex metabolic regulatory networks. By using precise analytical methods to measure biochemical constituents and their relative abundance in whole plasma of transgenic ApoE*3-Leiden mice and an isogenic wild-type control group, simultaneous snapshots of metabolic and protein states were obtained. Novel data processing and multivariate analysis tools such as Impurity Resolution Software (IMPRESS) and Windows-based linear fit program (WINLIN) were used to compare protein and metabolic profiles in parallel. Canonical correlations of the resulting data show quantitative relationships between heterogeneous components in the TG animals. These results, obtained solely from whole plasma analysis allowed us, in a rapid manner, to corroborate previous findings as well as find new events pertaining to dominant and peripheral events in lipoprotein metabolism of a genetically modified mammalian organism in relation to ApoE3, a key mediator of lipoprotein metabolism.


Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells.
The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34(+)) leukemic versus normal specimens. Our data indicate that CD34(+) AML cells have elevated expression of multiple glutathione pathway regulatory proteins, presumably as a mechanism to compensate for increased oxidative stress in leukemic cells. Consistent with this observation, CD34(+) AML cells have lower levels of reduced glutathione and increased levels of oxidized glutathione compared with normal CD34(+) cells. These findings led us to hypothesize that AML cells will be hypersensitive to inhibition of glutathione metabolism. To test this premise, we identified compounds such as parthenolide (PTL) or piperlongumine that induce almost complete glutathione depletion and severe cell death in CD34(+) AML cells. Importantly, these compounds only induce limited and transient glutathione depletion as well as significantly less toxicity in normal CD34(+) cells. We further determined that PTL perturbs glutathione homeostasis by a multifactorial mechanism, which includes inhibiting key glutathione metabolic enzymes (GCLC and GPX1), as well as direct depletion of glutathione. These findings demonstrate that primitive leukemia cells are uniquely sensitive to agents that target aberrant glutathione metabolism, an intrinsic property of primary human AML cells.


A Scoping Review: Mapping the Evidence for Undergraduate Concussion Education and Proposing the Content for Medical Student Concussion Teaching.
Concussion is a common yet complex condition, with each new case requiring assessment by a medical doctor. Recent research has shown that doctors working in the UK have significant knowledge deficits regarding concussion diagnosis and management. The aim of this scoping review was to map out the evidence about how undergraduate medical students are being educated about concussion. This scoping review involved seven research papers identified by searching five online databases in October 2020. Search terms relevant to concussion included: brain injuries, post-concussion syndrome, brain concussion and concussion, combined with search criteria for undergraduate education: medical students, undergraduate medical education, or curriculum. All seven papers were published in North America, with five papers recruiting medical students from single institutions (n = 590) and two papers surveying universities. Canadian medical schools have shown an upward trend in the quantity of teaching about concussion-specific teaching: from 0.57 to 2.65 h between 2012 and 2018. Lectures were the commonest mode of delivery of teaching, followed by problem-based learning and clinical rotations. The studies reach a common conclusion that medical students are not being adequately prepared for diagnosing and managing concussion, with insufficient undergraduate teaching, particularly exposure during clinical rotations, cited as the cause. Concussion: education of medical students is inadequate in North America. Medical schools should help address this by providing lectures and clinical presentations on concussion to learn from, particularly via problem-based learning. There is a paucity of evidence about concussion education in other geographical areas.


A cross-sectional survey on principal investigators' clinical research knowledge in Japan.
Principal investigators (PIs) play a key role in clinical research, and must thus understand the role of clinical research support staff to conduct successful and appropriate clinical research. This study evaluates clinical research capabilities by examining the clinical research knowledge of PIs and clinical research support staff. The participants of this cross-sectional study were academic researchers and clinical research support staff from Japanese universities and research institutions. The participants comprised of 54 respondents, among whom 36 were PIs (physicians) and 18 were clinical research support staff. A self-administered electronic survey was created and evaluated by experts, with 50 knowledge items. Mann-Whitney U tests were used to determine the significance of the differences in knowledge between clinical research support staff and PIs. We compared the correct answer rate of clinical research support staff and PIs for each knowledge category and observed that the clinical research support staff scored significantly higher than the PIs in all aspects of clinical research knowledge sections, including total score. Our findings showed that PIs did not have the same amount of clinical research knowledge as the clinical research support staff. Clinical research knowledge is essential for investigators, especially PIs, to protect patients and promote medical breakthroughs. Thus, more accessible clinical research education and mandatory knowledge testing will allow PIs to lead successful clinical research and further the level of medical research in Japan.


Evidence of Signaling and Adhesion Roles for β-Catenin in the Sponge Ephydatia muelleri.
β-Catenin acts as a transcriptional coactivator in the Wnt/β-catenin signaling pathway and a cytoplasmic effector in cadherin-based cell adhesion. These functions are ancient within animals, but the earliest steps in β-catenin evolution remain unresolved due to limited data from key lineages-sponges, ctenophores, and placozoans. Previous studies in sponges have characterized β-catenin expression dynamics and used GSK3B antagonists to ectopically activate the Wnt/β-catenin pathway; both approaches rely upon untested assumptions about the conservation of β-catenin function and regulation in sponges. Here, we test these assumptions using an antibody raised against β-catenin from the sponge Ephydatia muelleri. We find that cadherin-complex genes coprecipitate with endogenous Em β-catenin from cell lysates, but that Wnt pathway components do not. However, through immunostaining we detect both cell boundary and nuclear populations, and we find evidence that Em β-catenin is a conserved substrate of GSK3B. Collectively, these data support conserved roles for Em β-catenin in both cell adhesion and Wnt signaling. Additionally, we find evidence for an Em β-catenin population associated with the distal ends of F-actin stress fibers in apparent cell-substrate adhesion structures that resemble focal adhesions. This finding suggests a fundamental difference in the adhesion properties of sponge tissues relative to other animals, in which the adhesion functions of β-catenin are typically restricted to cell-cell adhesions.


Interplay between the gut microbiota and immune responses of ayu (Plecoglossus altivelis) during Vibrio anguillarum infection.
Gut microbiota plays fundamental roles in protection against pathogen invasion. However, the mechanism and extent of responses of gut microbiota to pathogenic infection are poorly understood. This study investigated the gut bacterial communities and immune responses of ayu (Plecoglossus altivelis) upon exposure to Vibrio anguillarum. The succession of V. anguillarum infection was evidenced by increased expression of immune genes and bacterial loads in ayu tissues, which in turn altered the composition and predicted functions of gut bacterial community. The dynamics of gut bacterial diversity and evenness were temporally stable in control ayu but were reduced in infected subjects, particularly at the late stages of infection. Variations in the gut microbiota were significantly associated with the expression levels of TNF-α (P = 0.019) and IL-1 β (P = 0.013). The profiles of certain gut bacterial taxa were indicative of V. anguillarum infection. Compared with healthy controls, the ayu infected with V. anguillarum possessed less complex, fewer connected, and lower cooperative gut bacterial interspecies interaction, coinciding with significant shifts in keystone species. These findings imply that V. anguillarum infection substantially disrupted the compositions and interspecies interaction of ayu gut bacterial community, thereby altering gut microbial-mediated functions and inducing host immune responses. This study provides an integrated overview on the interaction between the gut microbiota and host immune responses to pathogen infection from an ecological perspective.


Deuteriodifluoromethylation and gem-Difluoroalkenylation of Aldehydes Using ClCF2 H in Continuous Flow.
The deuteriodifluoromethyl group (CF2 D) represents a challenging functional group due to difficult deuterium incorporation and unavailability of precursor reagents. Herein, we report the use of chlorodifluoromethane (ClCF2 H) gas in the continuous flow deuteriodifluoromethylation and gem-difluoroalkenylation of aldehydes. Mechanistic studies revealed that the difluorinated oxaphosphetane (OPA) intermediate can proceed via alkaline hydrolysis in the presence of D2 O to provide α-deuteriodifluoromethylated benzyl alcohols or undergo a retro [2+2] cycloaddition under thermal conditions to provide the gem-difluoroalkenylated product.


Validation of biomarker-based risk prediction models.
The increasing availability and use of predictive models to facilitate informed decision making highlights the need for careful assessment of the validity of these models. In particular, models involving biomarkers require careful validation for two reasons: issues with overfitting when complex models involve a large number of biomarkers, and interlaboratory variation in assays used to measure biomarkers. In this article, we distinguish between internal and external statistical validation. Internal validation, involving training-testing splits of the available data or cross-validation, is a necessary component of the model building process and can provide valid assessments of model performance. External validation consists of assessing model performance on one or more data sets collected by different investigators from different institutions. External validation is a more rigorous procedure necessary for evaluating whether the predictive model will generalize to populations other than the one on which it was developed. We stress the need for an external data set to be truly external, that is, to play no role in model development and ideally be completely unavailable to the researchers building the model. In addition to reviewing different types of validation, we describe different types and features of predictive models and strategies for model building, as well as measures appropriate for assessing their performance in the context of validation. No single measure can characterize the different components of the prediction, and the use of multiple summary measures is recommended.


Animal models of allergen-specific immunotherapy in food allergy: Overview and opportunities.
Food allergy is an adverse reaction to otherwise harmless proteins in food. The disease is a major health problem of growing concern, affecting approximately 5%-8% of young children and 2%-4% of adults. No accepted strategy exists for prevention and treatment of food allergy, and strict avoidance of the offending food is presently the only viable management option. Living with food avoidance may have a huge impact on the quality of life of food allergic patients, with daily fear of serious or even fatal reactions. The urgent need for safe and efficient food allergy treatment options has led to massive research efforts to develop and improve strategies for food allergy immunotherapeutic approaches. A first step in developing new and improved strategies of immunotherapy often involves the use of animal models. In present review, we provide an overview of animal studies of allergen-specific immunotherapy highlighting opportunities and challenges for each approach. The presented models, almost exclusively performed in mice, assess therapeutic efficacy and immunological outcomes following oral, intraperitoneal, subcutaneous, epicutaneous, and sublingual administration of native allergens, or preparations of hydrolyzed allergen, T-cell-directed peptides, or allergen with immunomodulatory adjuvants. Recently, approaches using immune cell therapy have demonstrated efficacy. Current models mainly assess anaphylaxis as the primary clinical outcome. With the increased appreciation that food allergy is a heterogeneous disease presenting different phenotypes, there is a continued need to develop new disease-relevant therapeutic models of food allergy.


Relationship Between Skin Intrinsic Fluorescence--an Indicator of Advanced Glycation End Products-and Upper Extremity Impairments in Individuals With Diabetes Mellitus.
Accumulation of advanced glycation end products (AGEs) is thought to contribute to limited joint mobility in people with diabetes mellitus (DM), but the relationships among AGEs, shoulder structural changes, movement, and disability are not understood. The purpose of this study was to determine the differences and relationships among skin intrinsic fluorescence (SIF), a proxy measure of AGEs, biceps and supraspinatus tendon thickness, upper extremity movement, and disability in groups with and without DM. This was a cross-sectional, case-control study. Fifty-two individuals participated: 26 with type 2 DM and 26 controls matched for sex, age, and body mass index. The main outcome measures were: SIF; biceps and supraspinatus tendon thickness; 3-dimensional peak shoulder motion; and Disability of the Arm, Shoulder and Hand (DASH) questionnaire scores. Mean SIF measurements were 19% higher in the DM group compared with the control group (P<.05). Biceps tendons (mean and 95% confidence interval [CI]) (4.7 mm [4.4, 5.0] versus 3.2 mm [2.9, 3.5]) and supraspinatus tendons (6.4 mm [5.9, 6.8] versus 4.9 mm [4.4, 5.3]) were thicker and peak humerothoracic elevation (139° [135°, 146°] versus 150° [146°, 155°]) and glenohumeral external rotation (35° [26°, 46°] versus 51° [41°, 58°]) were reduced in the DM group compared with the control group (P<.05). In the DM group, SIF was correlated to biceps tendon thickness, DASH score, and shoulder motion (r=.44-.51, P<.05). The SIF score and shoulder strength explained 64% of the DASH scores (P<.01). Because this was a cross-sectional study design, a cause-effect relationship could not be established. Accumulation of AGEs in the connective tissues of individuals with DM appears to be associated with increased tendon thickness and decreased shoulder joint mobility and upper extremity function. Physical therapists should be aware of these possible metabolic effects on structure, movement, and disability when treating people with diabetes.


The Ethics of Big Data and Nursing Science.
Big data is a scientific, social, and technological trend referring to the process and size of datasets available for analysis. Ethical implications arise as healthcare disciplines, including nursing, struggle over questions of informed consent, privacy, ownership of data, and its possible use in epistemology. The author offers straight-thinking possibilities for the use of big data in nursing science.


Weight loss composition is one-fourth fat-free mass: a critical review and critique of this widely cited rule.
Maximizing fat loss while preserving lean tissue mass and function is a central goal of modern obesity treatments. A widely cited rule guiding expected loss of lean tissue as fat-free mass (FFM) states that approximately one-fourth of weight loss will be FFM (i.e. ΔFFM/ΔWeight = ∼0.25), with the remaining three-fourths being fat mass. This review examines the dynamic relationships between FFM, fat mass and weight changes that follow induction of negative energy balance with hypocaloric dieting and/or exercise. Historical developments in the field are traced with the 'Quarter FFM Rule' used as a framework to examine evolving concepts on obesity tissue, excess weight and what is often cited as 'Forbes' Rule'. Temporal effects in the fractional contribution of FFM to changes in body weight are examined as are lean tissue moderating effects such as ageing, inactivity and exercise that frequently accompany structured low-calorie diet weight loss protocols. Losses of lean tissue with dieting typically tend to be small, raising questions about study design, power and applied measurement method reliability. Our review elicits important questions related to the fractional loss of lean tissues with dieting and provides a foundation for future research on this topic.


Endoscopic ulcers as a surrogate marker of NSAID-induced mucosal damage.
The characteristic of a biomarker that makes it a useful surrogate is the ability to identify a high risk of clinically important benefits or harms occurring in the future. A number of definitions or descriptions of surrogate definition have been put forward. Most recently the Institute of Medicine of the National Academy of Sciences in the USA has put forward an evaluation scheme for biomarkers, looking at validation (assay performance), qualification (assessment of evidence), and utilisation (the context in which the surrogate is to be used). This paper examines the example of endoscopy as a surrogate marker of NSAID-induced mucosal damage using the Institute of Medicine criteria. The article finds extensive evidence that the detection of endoscopic ulcers is a valid marker. The process of qualification documents abundant evidence showing that endoscopic ulcers and serious upper gastrointestinal damage are influenced in the same direction and much the same magnitude by a variety of risk factors and interventions. Criticisms of validation and qualification for endoscopic ulcers have been examined, and dismissed. Context is the key, and in the context of serious NSAID-induced upper gastrointestinal harm, endoscopic ulcers represent a useful surrogate. Generalisability beyond this context is not considered.


The burden of surgical diseases on critical care services at a tertiary hospital in sub-Saharan Africa.
In many developing countries, including those of sub-Saharan Africa, care of the critically ill is poorly developed. We sought to elucidate the characteristics and outcomes of critically ill patients in order to better define the burden of disease and identify strategies for improving care. We conducted a cross sectional observation study of patients admitted to the intensive care unit at Kamuzu Central Hospital in 2010. Demographics, patient characteristics, clinical specialty and outcome data was collected for the 234 patients admitted during the study period. Older age and admission from trauma, general surgery or medical services were associated with increased mortality. The lowest mortality was among obstetrical and gynaecology patients. Use of the ventilator and transfusions were not associated with increased mortality. Patients with head injuries had the highest mortality rate. Rationing of critical care resources, using admitting diagnosis or scoring tools, can maximize access to critical care services in resource-limited settings. Furthermore, improvements of critical care services will be central to future efforts to reduce surgical morbidity and mortality and improving outcomes in all critically ill patients.


Synthesis and characterization of a novel magnetic biochar from sewage sludge and its effectiveness in the removal of methyl orange from aqueous solution.
A novel magnetic biochar from sewage sludge (MSBC) using SrFe12O19 as magnetic substrate was successfully synthesized under high-temperature and oxygen-free conditions. Several techniques and methodologies (X-ray diffraction, Fourier transform infrared spectroscopy and vibrating sample magnetometer) were used to determine the surface functional groups and physicochemical properties of MSBC, which showed that the MSBC combined the features of both SrFe12O19 and sludge biochar (SBC). And then the adsorption behavior of methyl orange (MO) from aqueous solution onto the MSBC was investigated. And the influence of variables including pH, initial concentration of MO, adsorbent dosage and contact time was studied in detail. The optimal adsorption amount of MO (149.18 mg·g-1) was obtained with 600 MO mg·L-1, 2 MSBC g·L-1, at pH of 5 for 40 min. The equilibrium data were evaluated using Langmuir and Freundlich isotherms. The Langmuir model better described the absorption of MO. Besides, the kinetic data were analyzed using pseudo-first-order and pseudo-second-order equations, and the pseudo-second order exhibited the better fit for the kinetic studies (R2 = 0.9982). This study showed that MSBC could be utilized as an efficient, magnetically separable adsorbent for the environmental cleanup.


Anthropometric definitions for antiretroviral-associated lipodystrophy derived from a longitudinal South African cohort with serial dual-energy X-ray absorptiometry measurements.
The development of lipodystrophy is associated with the long-term use of antiretroviral therapy (ART). We assessed agreement between patient-reported lipodystrophy and body composition measures using dual-energy X-ray absorptiometry (DXA) and developed objective measures to define lipoatrophy and lipohypertrophy in black South Africans. One hundred and eighty-seven ART-naïve HIV-infected adults were enrolled in a 24-month longitudinal study. Self-reported information on regional fat loss and fat gain, anthropometry, and DXA measures were collected at baseline, three, six, 12, 18, and 24 months after starting ART. Receiver operating characteristic curves were used to describe the performance of anthropometric variables using change in limb and trunk fat measured by DXA, as the reference standard. The proportion of men and women who developed lipoatrophy and lipohypertrophy increased over the 24-month period, with lipoatrophy occurring more frequently in men (21% versus 10%). In women, lipoatrophy was best determined by thigh skinfold thickness (80.3% correctly classified) and mid-arm circumference (77.6% correctly classified). None of the anthropometric measures performed well for defining lipoatrophy in men. Anthropometric measures performed well for defining lipoatrophy in women, but not lipohypertrophy.


TRPM7 mediates kidney injury, endothelial hyperpermeability and mortality during endotoxemia.
Sepsis is the main cause of mortality in patients admitted to intensive care units. During sepsis, endothelial permeability is severely augmented, contributing to renal dysfunction and patient mortality. Ca2+ influx and the subsequent increase in intracellular [Ca2+]i in endothelial cells (ECs) are key steps in the establishment of endothelial hyperpermeability. Transient receptor potential melastatin 7 (TRPM7) ion channels are permeable to Ca2+ and are expressed in a broad range of cell types and tissues, including ECs and kidneys. However, the role of TRPM7 on endothelial hyperpermeability during sepsis has remained elusive. Therefore, we investigated the participation of TRPM7 in renal vascular hyperpermeability, renal dysfunction, and enhanced mortality induced by endotoxemia. Our results showed that endotoxin increases endothelial hyperpermeability and Ca2+ overload through the TLR4/NOX-2/ROS/NF-κB pathway. Moreover, endotoxin exposure was shown to downregulate the expression of VE-cadherin, compromising monolayer integrity and enhancing vascular hyperpermeability. Notably, endotoxin-induced endothelial hyperpermeability was substantially inhibited by pharmacological inhibition and specific suppression of TRPM7 expression. The endotoxin was shown to upregulate the expression of TRPM7 via the TLR4/NOX-2/ROS/NF-κB pathway and induce a TRPM7-dependent EC Ca2+ overload. Remarkably, in vivo experiments performed in endotoxemic animals showed that pharmacological inhibition and specific suppression of TRPM7 expression inhibits renal vascular hyperpermeability, prevents kidney dysfunction, and improves survival in endotoxemic animals. Therefore, our results showed that TRPM7 mediates endotoxemia-induced endothelial hyperpermeability, renal dysfunction, and enhanced mortality, revealing a novel molecular target for treating renal vascular hyperpermeability and kidney dysfunction during endotoxemia, sepsis, and other inflammatory diseases.


Plant quality and local adaptation undermine relocation in a bog specialist butterfly.
The butterfly Boloria aquilonaris is a specialist of oligotrophic ecosystems. Population viability analysis predicted the species to be stable in Belgium and to collapse in the Netherlands with reduced host plant quality expected to drive species decline in the latter. We tested this hypothesis by rearing B. aquilonaris caterpillars from Belgian and Dutch sites on host plants (the cranberry, Vaccinium oxycoccos). Dutch plant quality was lower than Belgian one conferring lower caterpillar growth rate and survival. Reintroduction and/or supplementation may be necessary to ensure the viability of the species in the Netherlands, but some traits may have been selected solely in Dutch caterpillars to cope with gradual changes in host plant quality. To test this hypothesis, the performance of Belgian and Dutch caterpillars fed with plants from both countries were compared. Dutch caterpillars performed well on both plant qualities, whereas Belgian caterpillars could not switch to lower quality plants. This can be considered as an environmentally induced plastic response of caterpillars and/or a local adaptation to plant quality, which precludes the use of Belgian individuals as a unique solution for strengthening Dutch populations. More generally, these results stress that the relevance of local adaptation in selecting source populations for relocation may be as important as restoring habitat quality.


Diagnosis in bile acid-CoA: amino acid N-acyltransferase deficiency.
Cholate-CoA ligase (CCL) and bile acid-CoA: amino acid N-acyltransferase (BAAT) sequentially mediate bile-acid amidation. Defects can cause intrahepatic cholestasis. Distinction has required gene sequencing. We assessed potential clinical utility of immunostaining of liver for CCL and BAAT. Using commercially available antibodies against BAAT and CCL, we immunostained liver from an infant with jaundice, deficiency of amidated bile acids, and transcription-terminating mutation in BAAT. CCL was normally expressed. BAAT expression was not detected. Immunostaining may facilitate diagnosis in bile-acid amidation defects.


The role of excited-state character, structural relaxation, and symmetry breaking in enabling delayed fluorescence activity in push-pull chromophores.
Thermally activated delayed fluorescence (TADF) is a current promising route for generating highly efficient light-emitting devices. However, the design process of new chromophores is hampered by the complicated underlying photophysics. In this work, four closely related donor-π-acceptor-π-donor systems are investigated, two of which were synthesised previously, with the aim of elucidating their varying effectiveness for TADF. We outline that the frontier orbitals are insufficient for discriminating between the molecules. Subsequently, a detailed analysis of the excited states at a correlated ab initio level highlights the presence of a number of closely spaced singlet and triplet states of varying character. Results from five density functionals are compared against this reference revealing dramatic changes in, both, excited state energies and wavefunctions following variations in the amount of Hartree-Fock exchange included. Excited-state minima are optimised in solution showing the crucial role of structural variations and symmetry breaking for producing a strongly emissive S1 state. The adiabatic singlet-triplet gaps thus obtained depend strongly on the range separation parameter used in the hybrid density functional calculations. More generally, this work highlights intricate differences present between singlet and triplet excited state wavefunctions and the challenges in describing them accurately.


Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin.
Neutrophil granulocytes form the body's first line of antibacterial defense, but they also contribute to tissue injury and noninfectious, chronic inflammation. Proteinase 3 (PR3) and neutrophil elastase (NE) are 2 abundant neutrophil serine proteases implicated in antimicrobial defense with overlapping and potentially redundant substrate specificity. Here, we unraveled a cooperative role for PR3 and NE in neutrophil activation and noninfectious inflammation in vivo, which we believe to be novel. Mice lacking both PR3 and NE demonstrated strongly diminished immune complex-mediated (IC-mediated) neutrophil infiltration in vivo as well as reduced activation of isolated neutrophils by ICs in vitro. In contrast, in mice lacking just NE, neutrophil recruitment to ICs was only marginally impaired. The defects in mice lacking both PR3 and NE were directly linked to the accumulation of antiinflammatory progranulin (PGRN). Both PR3 and NE cleaved PGRN in vitro and during neutrophil activation and inflammation in vivo. Local administration of recombinant PGRN potently inhibited neutrophilic inflammation in vivo, demonstrating that PGRN represents a crucial inflammation-suppressing mediator. We conclude that PR3 and NE enhance neutrophil-dependent inflammation by eliminating the local antiinflammatory activity of PGRN. Our results support the use of serine protease inhibitors as antiinflammatory agents.


Catheter-based aortography fails to identify aortic atherosclerotic lesions detected on transesophageal echocardiography.
Transesophageal echocardiography is used to detect the aortic arch pathology during diagnostic workup of ischemic stroke events. Conventional angiography is increasingly used in diagnosing and treating atherosclerotic vascular lesions in patients with ischemic stroke. Although catheter-based aortography can be performed with cerebral angiography, there is limited information about the utility of aortography in identifying atherosclerotic abnormalities of the aortic arch. A retrospective chart review was performed to identify patients who underwent aortography as part of their angio-graphic study and transesophageal echocardiography. Both studies were reviewed independently in the absence of knowledge of the results of the other study. The findings of these aortograms were correlated with the findings of transesophageal echocardiography. A total of 34 patients underwent both aortography and echocardiography. Of a total of 34 trans esophageal echocardiograms, 29 showed abnormal findings in the aorta (85%) and 5 appeared normal (15%). These aortic abnormalities included mild to moderate atherosclerosis in 18 cases (52%), moderate to severe atherosclerosis in 4 cases (12%), and severe atherosclerosis in 7 cases (21%). None of these abnormalities were detected by aortography. No disease was visualized in the origin of the supraaortic arteries. Aortic arch atherosclerosis is common in patients with ischemic stroke; however, aortograms acquired during conventional angiography fail to identify abnormalities detected on transesophageal echocardiogram.


Bitter pill to swallow: a case of accidental poisoning with digitalis purpurea.
While digitoxicity secondary to therapeutic use is frequent, due to its distinctive appearance and unpleasant taste accidental ingestion of digitalis purpurea (foxglove) is uncommon. This report relates the case of two previously healthy individuals who inadvertently consumed significant quantities of digitalis in its plant form. Both men presented in first-degree atrioventricular block and had digoxin levels of 4.9 μg/litre, but were otherwise stable and made unremarkable recoveries with repeated dose activated charcoal.


Representing Exact Electron Densities by a Single Slater Determinant in Finite Basis Sets.
The premise for Kohn-Sham density functional theory is that the exact electron density can be generated by a set of orbitals in a single Slater determinant. While this is ensured in a complete basis set, it has been shown that it cannot hold in small basis sets. The present work probes how accurately a reference electron density of the full-CI type can be reproduced by a set of orbitals in a single Slater determinant, as a function of the basis set used for the fitting electron density. The key finding is that the fitting error may be significant for basis sets of double- or triple-ζ quality. It is also shown that it is important that the fitting basis set includes the same basis functions as used for generating the reference electron density. The main limitation in a given basis set is the lack of higher order polarization functions. The error for practical purposes becomes insignificant for basis sets of quadruple-ζ or better quality, and this should be the choice when assessing the accuracy of exchange-correlation functionals by comparing electron densities to accurate reference results generated by wave function methods. The methodology in the present work can be used to transform an electron density from a multideterminant wave function into a set of orbitals in a single Slater determinant, and this may be useful for developing and testing new exchange-correlation functionals.


Protective Effect of Vaccinium myrtillus Extract on X-ray Irradiation-Induced Retinal Toxicity via eNOS and 8-OHdGexpression.
Every year, hundreds of thousands of cancer patients receive radiotherapy treatment. Oxidative stress is observed in healthy tissues due to irradiation exposure. The present study is the first to address the effects of Vaccinium myrtillus (whortleberry, WB) against the effects of x-ray irradiation on retinal tissue. Twenty-four Sprague-Dawley rats were randomly allocated into 4 groups: (1) control group: rats without any treatment, (2) x-ray irradiation group: 8 Gray (Gy) RT for 2 days, (3) 100 mg WB extract + x-ray irradiation group: 8 Gy irradiation for 2 days and followed by intraperitoneal (IP) WB extract (100 mg/kg) supplementation for 10 days, (4) 200 mg WB extract + x-ray irradiation group: 8 Gy irradiation for 2 days and followed by intraperitoneal (IP) WB extract (200 mg/kg) supplementation for 10 days. Eyes were enucleated on the 10th day after RT for histopathological, immunohistochemical (8-hydroxy deoxyguanosine (8-OHdG), endothelial nitric oxide synthase (eNOS), and biochemical analyses (glutathione peroxidase (GSH), and malondialdehyde (MDA). The GSH levels significantly decreased and MDA levels and 8-OHdG staining increased after x-ray irradiation compared to the control group. Combined x-ray irradiation +WB treatment significantly increased GSH levels and significantly decreased MDA production and 8-OHdG staining. However, eNOS staining was not affected in any of the groups. Besides, x-ray irradiation significantly increased cell losses and edematous areas. The WB significantly reversed the cellular damage in ganglion cells, inner nuclear, and outer nuclear layers in quantitative analyses. The x-ray irradiation caused significant retinal impairment, and additional WB therapy provided protective effects against radiation-induced retinopathy. These results may suggest WB extract as an adjuvant therapy to reverse retinal impairments after x-ray irradiation.


Action-Outcome Knowledge Dissociates From Behavior in Obsessive-Compulsive Disorder Following Contingency Degradation.
In obsessive-compulsive disorder (OCD), actions persist despite being inappropriate to the situation and without relationship to the overall goal. Dysfunctional beliefs have traditionally been postulated to underlie this condition. More recently, OCD has been characterized in terms of an imbalance between the goal-directed and the habit systems. To test these competing hypotheses, we used a novel experimental task designed to test subjective action-outcome knowledge of the effectiveness of actions (i.e., instrumental contingency), together with the balance between goal-directed and habitual responding. Twenty-seven patients with OCD and 27 healthy control subjects were tested on a novel task involving the degradation of an action-outcome contingency. Sensitivity to instrumental contingency and the extent to which explicitly reported action-outcome knowledge guided behavior were probed by measuring response rate and subjectively reported judgments. Patients with OCD responded more than healthy control subjects in situations in which an action was less causally related to obtaining an outcome. However, patients showed intact explicit action-outcome knowledge, as assessed by self-report. In patients, the relationship between causality judgment and responding was altered; therefore, their actions were dissociated from explicit action-outcome knowledge. These findings indicate reduced sensitivity to instrumental contingency in OCD, reinforcing the notion of a deficient goal-directed system in this disorder. By showing a dissociation between subjectively reported action-outcome knowledge and behavior, the data provide experimental evidence for the ego-dystonic nature of OCD.


Natural killer cells, gamma delta T cells and classical monocytes are associated with systolic blood pressure in the multi-ethnic study of atherosclerosis (MESA).
Hypertension is a major source of cardiovascular morbidity and mortality. Recent evidence from mouse models, genetic, and cross-sectional human studies suggest increased proportions of selected immune cell subsets may be associated with levels of systolic blood pressure (SBP). We assayed immune cells from cryopreserved samples collected at the baseline examination (2000-2002) from 1195 participants from the multi-ethnic study of atherosclerosis (MESA). We used linear mixed models, with adjustment for age, sex, race/ethnicity, smoking, exercise, body mass index, education, diabetes, and cytomegalovirus titers, to estimate the associations between 30 immune cell subsets (4 of which were a priori hypotheses) and repeated measures of SBP (baseline and up to four follow-up measures) over 10 years. The analysis provides estimates of the association with blood pressure level. The mean age of the MESA participants at baseline was 64 ± 10 years and 53% were male. A one standard deviation (1-SD) increment in the proportion of γδ T cells was associated with 2.40 mmHg [95% confidence interval (CI) 1.34-3.42] higher average systolic blood pressure; and for natural killer cells, a 1-SD increment was associated with 1.88 mmHg (95% CI 0.82-2.94) higher average level of systolic blood pressure. A 1-SD increment in classical monocytes (CD14++CD16-) was associated with 2.01 mmHG (95% CI 0.79-3.24) lower average systolic blood pressure. There were no associations of CD4+ T helper cell subsets with average systolic blood pressure. These findings suggest that the innate immune system plays a role in levels of SBP whereas there were no associations with adaptive immune cells.


Reflection of mentors and mentees at initiation of Faculty Mentorship Program at Aga Khan University: A perspective.
To explore perception of mentors and mentees about 'Mentorship Program at Aga Khan University Medical College (AKU-MC) from a structured feedback form. A retrospective study was conducted for evaluation of mentorship program at AKU-MC during the period from Jan 2019 to March, 2021. Responses on validated "Pre-intervention Probe Forms", from forty-seven mentors and fourteen mentees inducted in the program were reviewed. Confidentiality and anonymity of data were deliberated. All replies to each question were entered in a separate worksheet to determine the frequency and percentage of answers. Responses conveying same message, but worded differently were then grouped. All the mentees (n=14) responded positively to the question on the "understanding of the mentoring program. The mentees (n=12, 86%) recognized the potential of the program to transfer knowledge and skills, (n=11, 79%) supported its role for achievement of goals, (n=7, 50%), acknowledged its role in faculty relationships. The mentors expressed their enthusiasm to help the mentee's in their professional development. They (n=20, 43%) offered support to set career goals, (n=29, 62%) proposed transfer of knowledge, skills, and experiences to achieve goals, (n=15, 32%) decided to be "role models". Some (n=10, 21%) forecasted improved communication skills, (n=14, 30%) boosted leadership capabilities, (n=13, 28%) expected improved work performance, (n=15, 32%) opinioned that networking and leadership qualities will impact the growth of the mentee to meet the university's expectations. Both mentors and mentees recognized the importance of the faculty mentorship program at AKU-MC for professional guidance, development and improvement in work performance.


Escherichia coli genes affecting recipient ability in plasmid conjugation: are there any?
How does the recipient cell contribute to bacterial conjugation? To answer this question we systematically analyzed the individual contribution of each Escherichia coli gene in matings using plasmid R388 as a conjugative plasmid. We used an automated conjugation assay and two sets of E. coli mutant collections: the Keio collection (3,908 E. coli single-gene deletion mutants) and a collection of 20,000 random mini-Tn10::Km insertion mutants in E. coli strain DH5alpha. The combined use of both collections assured that we screened > 99% of the E. coli non-essential genes in our survey. Results indicate that no non-essential recipient E. coli genes exist that play an essential role in conjugation. Mutations in the lipopolysaccharide (LPS) synthesis pathway had a modest effect on R388 plasmid transfer (6 - 32% of wild type). The same mutations showed a drastic inhibition effect on F-plasmid transfer, but only in liquid matings, suggesting that previously isolated conjugation-defective mutants do in fact impair mating pair formation in liquid mating, but not conjugative DNA processing or transport per se. We conclude from our genome-wide screen that recipient bacterial cells cannot avoid being used as recipients in bacterial conjugation. This is relevant as an indication of the problems in curbing the dissemination of antibiotic resistance and suggests that conjugation acts as a pure drilling machine, with little regard to the constitution of the recipient cell.


Characterization of a Gemella-like organism from the oral cavity of a dog: description of Gemella palaticanis sp. nov.
A hitherto unknown Gram-positive, catalase-negative, facultatively anaerobic coccus isolated from a vesicle on the gum of a dog was characterized by phenotypic and molecular taxonomic methods. Comparative 16S rRNA gene sequencing studies demonstrated that the isolate represents a new subline within the genus Gemella. The unknown bacterium was readily distinguished from all currently described members of this genus, Gemella haemolysans, Gemella bergeri, Gemella morbillorum and Gemella sanguinis, by biochemical tests and electrophoretic analysis of whole-cell proteins. On the basis of phylogenetic and phenotypic evidence, it is proposed that the unknown bacterium be classified as Gemella palaticanis sp. nov. The type strain of Gemella palaticanis is CCUG 39489T.


The soft tissue and skeletal anatomy of two Late Jurassic ichthyosaur specimens from the Solnhofen archipelago.
Ichthyosaurs from the Solnhofen Lagerstätte are among the only examples of soft tissue preservation in the major Middle Jurassic-middle Cretaceous family Ophthalmosauridae. However, few such specimens are currently described, and the taphonomical pathways for the preservation of soft tissue are not well understood. In order to answer this, two new ichthyosaur specimens, one nearly complete and one isolated tail, are described here. The nearly complete specimen is assigned to Aegirosaurus sp. It is accompanied by large amounts of incrustation pseudomorphs (epimorphs) of soft tissue preserved as apatite. It also preserves a nearly complete gastral basket, for the first time in ophthalmosaurids. Soft tissue samples were analyzed using X-ray diffraction (XRD) and scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS) analysis. The analyses confirm the presence of apatite, with phosphate most likely derived from the body itself.


Feather pattern development.
Experiments on skin development in amniotes have shown conclusively that the pattern of cutaneous appendages is determined by the dermis. The following concept of feather pattern formation is proposed. The diameter of feather rudiments and the dermal cell density inside the dermal feather condensations are genetically fixed, region-specific parameters. The first feather rudiment is established along the middorsal line (in the lumbar region) as soon as a sufficient width of dense dermis is available. This occurs at about 6 1/2 days in the chick embryo. The next rudiments are formed in front of and behind the first one, within the longitudinal band of dense dermis. They are laid down as close as possible to the first one, given rudiment diameter and dermal condensation cell density. In other words, as they form, the middorsal rudiments are tangent circles.. Later they become separated from one another due to longitudinal growth. As progressively more dense dermis becomes available to the sides of the middorsal row of rudiments, new rudiments are being laid down lateral to the middorsal row, in successive longitudinal rows, until, by 9 or 10 days, all the available dense dermis has been used up. Again, the rudiments in the lateral rows, given their diameter and dermal condensation cell density, develop as close as possible to those of the preceding row, i.e. tangentially to two neighbouring rudiments of the preceding row, thus generating a hexagonal pattern.


Multiprotein Adsorption from Human Serum at Gold and Oxidized Iron Surfaces Studied by Atomic Force Microscopy and Polarization-Modulation Infrared Reflection Absorption Spectroscopy.
Multiprotein adsorption from complex body fluids represents a highly important and complicated phenomenon in medicine. In this work, multiprotein adsorption from diluted human serum at gold and oxidized iron surfaces is investigated at different serum concentrations and pH values. Adsorption-induced changes in surface topography and the total amount of adsorbed proteins are quantified by atomic force microscopy (AFM) and polarization-modulation infrared reflection absorption spectroscopy (PM-IRRAS), respectively. For both surfaces, stronger protein adsorption is observed at pH 6 compared to pH 7 and pH 8. PM-IRRAS furthermore provides some qualitative insights into the pH-dependent alterations in the composition of the adsorbed multiprotein films. Changes in the amide II/amide I band area ratio and in particular side-chain IR absorption suggest that the increased adsorption at pH 6 is accompanied by a change in protein film composition. Presumably, this is mostly driven by the adsorption of human serum albumin, which at pH 6 adsorbs more readily and thereby replaces other proteins with lower surface affinities in the resulting multiprotein film.


[Distribution Characteristics and Risk Assessment of Phthalic Acid Esters in Agricultural Products Around the Pearl River Delta. South China].
In order to investigate and assess the distribution of pathalic acid easters (PAEs) in agricultural products from typical areas of the Pearl River Delta, South China, 131 agricultural products were sampled for determination of 6 PAEs priority pollutants classified by the U. S. EPA by GC-FID. The results showed that the total contents of the PAEs (sigma PAEs) in agricultural products samples ranged from nd to 79.86 mg x kg(-1) and the mean value was 2.84 mg x kg(-1), with the detected ratio of 98.5%. The average concentrations of sigma PAEs in different types of agricultural products were ordered by vegetables (3.03 mg x kg(-1)) > rice (2.52 mg x kg(-1)) > fruits (1.26 mg x kg(-1)). The mean concentration of PAEs distributed in the four typical cities of the Pearl River Delta, and decreased in the sequence of Zhuhai (6.53 mg x kg(-1)) > Dongguan (2.59 mg x kg(-1)) > Huizhou (1.53 mg x kg(-1)) > Zhongshan (1.12 mg x kg(-1)). Di-n-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DnOP) contributed more than 90. 8% of the total PAEs in samples, and were the main components of PAEs in agricultural products from the Pearl River Delta, with higher percentage contents and detected ratio. Meanwhile, the average concentrations of sigma PAEs in cabbage mustard, lettuce occurred in Zhuhai and Dongguan cities, followed by lettuce and leaf lettuce in the corresponding DEHP from Zhuhai city, both exceeded the suggested standards in U.S.A. and Europe and were of high health risk. There were significant differences among 14 various vegetables in the contents of the 6 PAEs compounds, and the sigma PAEs contents in cabbage mustard and lettuce as part of leafy vegetables were higher than those in other vegetables, while the lowest were detected in flowering cabbage and edible amaranth. Therefore, the type of vegetables and its growing environment exposed to the atmosphere and soil were the main factors that significantly affected their accumulation of PAEs concentrations.


Influenza viruses, 1957-60.
During the period 1957-60 large numbers of influenza A viruses were received at the World Influenza Centre from countries throughout the world. With one exception all the strains were antigenically closely related to the A2 viruses isolated early in the Asian influenza epidemic, and strikingly different from the A1 strains of the previous decade. The A2 viruses were very uniform antigenically and in other in vitro characteristics such as insensitivity to the beta-inhibitor of agglutination. However, many of the strains, particularly during the early stages of the epidemic, showed a low avidity for antibody.At the same time as the influenza A viruses showed a large antigenic change the influenza B viruses showed a lesser antigenic change from earlier influenza B viruses. As with influenza A, the new influenza B viruses have replaced earlier B strains.In 1960 one strain of influenza virus A1 was recovered from a soldier in England. Evidence is presented that this could not be explained as a laboratory pick-up and the suggestion is put forward that this patient may have harboured virus in latent form for many years.


Functional specialization of Chlamydomonas reinhardtii cytosolic thioredoxin h1 in the response to alkylation-induced DNA damage.
DNA damage occurs as a by-product of intrinsic cellular processes, like DNA replication, or as a consequence of exposure to genotoxic agents. Organisms have evolved multiple mechanisms to avoid, tolerate, or repair DNA lesions. To gain insight into these processes, we have isolated mutants hypersensitive to DNA-damaging agents in the green alga Chlamydomonas reinhardtii. One mutant, Ble-1, showed decreased survival when it was treated with methyl methanesulfonate (MMS), bleomycin, or hydrogen peroxide (H2O2) but behaved like the wild type when it was exposed to UVC irradiation. Ble-1 carries an extensive chromosomal deletion that includes the gene encoding cytosolic thioredoxin h1 (Trxh1). Transformation of Ble-1 with a wild-type copy of Trxh1 fully corrected the MMS hypersensitivity and partly restored the tolerance to bleomycin. Trxh1 also complemented a defect in the repair of MMS-induced DNA strand breaks and alkali-labile sites. In addition, a Trxh1-beta-glucuronidase fusion protein translocated to the nucleus in response to treatment with MMS. However, somewhat surprisingly, Trxh1 failed to correct the Ble-1 hypersensitivity to H2O2. Moreover, Trxh1 suppression by RNA interference in a wild-type strain resulted in enhanced sensitivity to MMS and DNA repair defects but no increased cytotoxicity to H2O2. Thioredoxins have been implicated in oxidative-stress responses in many organisms. Yet our results indicate a specific role of Chlamydomonas Trxh1 in the repair of MMS-induced DNA damage, whereas it is dispensable for the response to H2O2. These observations also suggest functional specialization among cytosolic thioredoxins since another Chlamydomonas isoform (Trxh2) does not compensate for the lack of Trxh1.


Neurotransmitter sampling and storage for capillary electrophoresis analysis.
Quantitative analysis of signaling molecules from single cells and cellular materials requires careful validation of the analytical methods. Strategies have been investigated that enable single neurons and neuronal tissues to be stored before being assayed for many low-weight, biologically active molecules, such as serotonin, dopamine, and citrulline. Both metacerebral cell and pedal ganglia homogenates isolated from Pleiuohbrain-Chae californica have been studied by capillary electrophoresis with two complimentary laser-induced fluorescence detection methods. For homogenized ganglia samples, several cellular analytes (such as arginine and citrulline) are unaffected by standing at room temperature for days. Many other analytes in the biological matrix, including the catecholamines and indolamines, degrade by 20% within 10 h at room temperature. Rapidly freezing samples or preserving them with ascorbic acid preserves more than 80% of the dopamine and about 70% of the serotonin even after five days. In addition, serotonin and dopamine remain completely stable for at least five days by combining the ascorbic acid preservation and freezing at -20 degrees C. The timing of preservation is critical in maintaining the original composition of the biological samples. Using our optimum storage protocol of freezing the sample within 2 h after isolation, we can store frozen homogenate ganglia samples for more than four weeks before assay while still obtaining losses less than 10% of the original serotonin and dopamine. The nanoliter-volume single cell samples, however, must be analyzed within 4 h to obtain losses of less than 10% for serotonin related metabolites.


A one-degree-of-freedom assistive exoskeleton with inertia compensation: the effects on the agility of leg swing motion.
Many of the current implementations of exoskeletons for the lower extremities are conceived to either augment the user's load-carrying capabilities or reduce muscle activation during walking. Comparatively little research has been conducted on enabling an exoskeleton to increase the agility of lower-limb movements. One obstacle in this regard is the inertia of the exoskeleton's mechanism, which tends to reduce the natural frequency of the human limbs. A control method is presented that produces an approximate compensation of the inertia of an exoskeleton's mechanism. The controller was tested on a statically mounted, single-degree-of-freedom (DOF) exoskeleton that assists knee flexion and extension. Test subjects performed multiple series of leg-swing movements in the context of a computer-based, sprint-like task. A large initial acceleration of the leg was needed for the subjects to track a virtual target on a computer screen. The uncompensated inertia of the exoskeleton mechanism slowed down the transient response of the subjects' limb, in comparison with trials performed without the exoskeleton. The subsequent use of emulated inertia compensation on the exoskeleton allowed the subjects to improve their transient response for the same task.