Challenges and opportunities in occupational medicine.
Recent position papers of the American College of Physicians and the Institute of Medicine have emphasized the role of primary care physicians in occupational medicine. Although opportunities for physicians to become certified in occupational medicine have expanded, shortages in the specialty are likely to persist throughout the 1990s. To help acquaint osteopathic physicians with some of the challenges facing the specialty of occupational medicine, this article addresses the extent of occupational illnesses, health-related policies in the workplace, the delivery of occupational medical services, and graduate medical education.


Gene Prioritization for Imaging Genetics Studies Using Gene Ontology and a Stratified False Discovery Rate Approach.
Imaging genetics is an emerging field in which the association between genes and neuroimaging-based quantitative phenotypes are used to explore the functional role of genes in neuroanatomy and neurophysiology in the context of healthy function and neuropsychiatric disorders. The main obstacle for researchers in the field is the high dimensionality of the data in both the imaging phenotypes and the genetic variants commonly typed. In this article, we develop a novel method that utilizes Gene Ontology, an online database, to select and prioritize certain genes, employing a stratified false discovery rate (sFDR) approach to investigate their associations with imaging phenotypes. sFDR has the potential to increase power in genome wide association studies (GWAS), and is quickly gaining traction as a method for multiple testing correction. Our novel approach addresses both the pressing need in genetic research to move beyond candidate gene studies, while not being overburdened with a loss of power due to multiple testing. As an example of our methodology, we perform a GWAS of hippocampal volume using both the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA2) and the Alzheimer's Disease Neuroimaging Initiative datasets. The analysis of ENIGMA2 data yielded a set of SNPs with sFDR values between 10 and 20%. Our approach demonstrates a potential method to prioritize genes based on biological systems impaired in a disease.


Local exchange of metabolites shapes immunity.
Immune cell differentiation and function depend on metabolic changes for the provision of energy and metabolites. Consequently, cellular metabolism relies on the availability of micronutrients such as vitamins and energy-rich sources including amino acids and fatty acids. The bone marrow controls the continuous production of blood cells and is thereby reliant on the sophisticated interplay of progenitor and mature immune cells with its stromal microenvironment. The significance of stromal subsets in immunopoiesis is undisputed; however, our current knowledge is limited to their role in the production and secretion of a variety of soluble proteins such as cytokines. In contrast, the role of the haematopoietic niche in controlling and providing nutrients such as fatty acids, amino acids and vitamins, which are required for immune cell differentiation and function, remains largely elusive. In this review, we summarize the current understanding of local nutritional exchange and control between immune and stromal cells in peripheral tissue and, when it is known, in the bone marrow. The parallels found between peripheral tissues and bone marrow stroma raises the question of how local metabolism is capable of influencing haematopoiesis and immunopoiesis. A better understanding of the local exchange of nutrients in the bone marrow can be used to improve immune cell formation during ageing, after haematopoietic stem cell transplantation and during immune challenge.


Increased false negative sentinel node biopsy rates after preoperative chemotherapy for invasive breast carcinoma.
Sentinel lymph node dissection (SLND) has been a promising new technique in breast carcinoma staging, but could be unreliable in certain patient subsets. The current study assessed whether age, preoperative chemotherapy, tumor size, and/or previous excisional biopsy influenced the identification of sentinel nodes (SLNs) or the reliability of a node-negative SLND in predicting a node negative axilla. Eighty-two patients who had clinically negative axillae underwent SLND followed by Level I/II axillary lymph node dissection (ALND). SLNDs were performed using both technetium-99m (Tc-99m) labeled colloid and isosulfan blue dye. SLNs were analyzed by hematoxlyin and eosin and immunocytochemical techniques. SLNs were successfully identified in 80% of patients. Mapping success was decreased among postmenopausal women but was not influenced by preoperative chemotherapy, large tumor size, or previous excisional biopsy. Of the 31 successfully mapped, node positive patients, 5 had false negative (FN) SLNDs (overall FN rate = 16%). Of the 9 successfully mapped patients who had received preoperative chemotherapy and had positive axillary nodes, 3 had FN SLND (FN rate = 33%). The presence of clinically positive lymph nodes before chemotherapy did not predict which patients would have a subsequent FN SLND. T3 tumor size, but not previous excision, was associated significantly with increased FN rate, although the FN rate for previous excision was 11%. No FN SLND occurred with T1/T2 tumors that were not excised previously and had not received preoperative chemotherapy. Preoperative chemotherapy was associated with an unacceptably high FN rate for SLND. While larger tumor size also was associated with FN SLND, this effect might have been due to preoperative chemotherapy use in these patients. Small sample size precluded determining whether excisional biopsy before mapping increased FN SLND rates independently.


Comparison of seasonal soil microbial process in snow-covered temperate ecosystems of northern China.
More than half of the earth's terrestrial surface currently experiences seasonal snow cover and soil frost. Winter compositional and functional investigations in soil microbial community are frequently conducted in alpine tundra and boreal forest ecosystems. However, little information on winter microbial biogeochemistry is known from seasonally snow-covered temperate ecosystems. As decomposer microbes may differ in their ability/strategy to efficiently use soil organic carbon (SOC) within different phases of the year, understanding seasonal microbial process will increase our knowledge of biogeochemical cycling from the aspect of decomposition rates and corresponding nutrient dynamics. In this study, we measured soil microbial biomass, community composition and potential SOC mineralization rates in winter and summer, from six temperate ecosystems in northern China. Our results showed a clear pattern of increased microbial biomass C to nitrogen (N) ratio in most winter soils. Concurrently, a shift in soil microbial community composition occurred with higher fungal to bacterial biomass ratio and gram negative (G-) to gram positive (G+) bacterial biomass ratio in winter than in summer. Furthermore, potential SOC mineralization rate was higher in winter than in summer. Our study demonstrated a distinct transition of microbial community structure and function from winter to summer in temperate snow-covered ecosystems. Microbial N immobilization in winter may not be the major contributor for plant growth in the following spring.


Restless legs syndrome and cardiovascular disease: a research roadmap.
In this paper, we first critically appraise the epidemiologic literature examining the association of restless legs syndrome (RLS) with cardiovascular disease (CVD) and then consider whether lessons learned from the study of cardiovascular consequences of other sleep disorders might inform a research agenda to examine the potential mechanisms of cardiovascular morbidity of RLS. Cross-sectional and longitudinal studies are both mixed as to whether there is a meaningful association of RLS and CVD. On the other hand, numerous cross-sectional and longitudinal observational studies have shown a strong association of obstructive sleep apnea (OSA) with CVD risk. Each of the potential mediating mechanisms in OSA may also be assessed in RLS, including 1) neural mechanisms such as increased central sympathetic outflow, impaired baroreflex function, diminished heart rate and blood pressure variability, and increased chemoreflex sensitivity, 2) metabolic mechanisms such as glucose intolerance and reduced insulin sensitivity/diabetes as a result of sleep disturbance in RLS, 3) oxidative stress, 4) systemic or vascular inflammatory mechanisms, and 5) vascular mechanisms including impaired endothelial functioning, increased aortic stiffness, hypothalamic-pituitary axis activation or renin-angiotensin-aldosterone activation. Three known characteristics of RLS may contribute to these specific mechanisms of increased cardiovascular risk: 1) periodic limb movements of sleep, which are associated with large increases in heart rate and blood pressure, 2) sleep fragmentation and sleep deprivation, which are known to produce adverse consequences for neural, metabolic, oxidative, inflammatory, and vascular systems, and 3) iron deficiency, which is an emerging risk for cardiovascular disease. Future research priorities include additional epidemiologic studies which characterize multiple CVD risk factors, case-control studies which examine known markers of cardiovascular risk, and small clinical trials which assess the effects of RLS treatment on intermediate physiological markers such as sympathetic activity or baroreflex control, measures of vascular stiffness and reactivity, or measures of insulin sensitivity and glucose tolerance.


Teaching smoking cessation skills to senior medical students: a block-randomized controlled trial of four different approaches.
Medical practitioners have considerable untapped potential to assist patients in stopping smoking. However, marked deficits have been found in the amount and type of training medical practitioners receive in smoking cessation counseling with little attention paid to determination of effective training methods. A randomized controlled trial was conducted to examine the relative effectiveness of four different educational programs in teaching smoking cessation skills to 5th-year medical students in an Australian medical school. The four programs comprised: (a) a traditional didactic lecture mode (control group), (b) audio feedback through the use of audiotaped role plays, (c) role plays with peer feedback, and (d) video feedback. Students' smoking cessation intervention skills were assessed prior to training and at the end of term via videotaped interviews with simulated patients. Senior medical students demonstrated significantly improved skills in smoking intervention when exposed to any of the educational approaches other than traditional didactic teaching. No overall differences in smoking intervention skills were found between the three experimental training methods. Specific training in smoking cessation techniques is necessary to increase the intervention skills of medical students. Traditional teaching methods are ineffective in developing smoking cessation intervention skills. Enhanced teaching, of an appropriate nature, at undergraduate and postgraduate levels is needed.


Implementation of corticosteroids in treatment of COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK: prospective, cohort study.
Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70-0·89], p=0·0001, for 70-79 years; 0·52 [0·46-0·58], p<0·0001, for >80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75-80% in January, 2021. Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. UK National Institute for Health Research and UK Medical Research Council.


Helicobacter pylori and esophageal cancer risk: a meta-analysis.
We conducted this meta-analysis to examine the association between Helicobacter pylori and esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma. We searched the PubMed database, the ISI database, and the references of the selected articles. Case-control or nested case-control studies were selected if they used serology or endoscopic methods to detect H. pylori in the stomach and if control subjects were not restricted to upper gastrointestinal tract cancer or peptic ulcer disease patients. A total of 19 studies were used for this analysis. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using the DerSimonian-Laird method. Q statistics and I(2) statistics were calculated to examine heterogeneity. Subgroup analyses were conducted by CagA status. For EAC, the summary OR (95% CI) was 0.56 (0.46-0.68). There was little heterogeneity among studies (I(2) = 15%). Further analysis showed that colonization with CagA-positive strains was inversely associated with EAC risk (OR, 0.41; 95% CI, 0.28-0.62) but colonization with CagA-negative strains was not (OR, 1.08; 95% CI, 0.76-1.53). For esophageal squamous cell carcinoma, the summary OR (95% CI) was 1.10 (0.78-1.55). However, there was substantial heterogeneity among studies (I(2) = 73%), with statistically significant associations in both directions. Our results suggest an inverse association between CagA-positive H. pylori colonization and risk of EAC. The prominent decline of H. pylori colonization in the past few decades may be partly responsible for the recent increase in EAC incidence in Western countries.


Characterization of Junin arenavirus cell entry.
Junín virus (JUNV) entry is conducted by receptor-mediated endocytosis. To explore the cellular entry mechanism of JUNV, inhibitory effects of drugs affecting the main endocytic pathways on JUNV entry into Vero cells were analysed. Compounds that impair clathrin-mediated endocytosis were shown to reduce virus internalization without affecting virion binding. In contrast, drugs that alter lipid-raft microdomains, impairing caveola-mediated endocytosis, were not able to block virus entry. To show direct evidence of JUNV entry, transmission electron microscopy was performed; it showed JUNV particles of about 60-100 nm in membrane depressions that had an electron-dense coating. In addition, JUNV particles were found within invaginations of the plasma membrane and vesicles that resembled those of pits and clathrin-coated vesicles. Taken together, these results demonstrate that clathrin-mediated endocytosis is the main JUNV entry pathway into Vero cells and represent an important contribution to the characterization of the arenavirus multiplication cycle.


Steps toward Maturation of Embryonic Stem Cell-Derived Cardiomyocytes by Defined Physical Signals.
Cardiovascular disease remains a leading cause of mortality and morbidity worldwide. Embryonic stem cell-derived cardiomyocytes (ESC-CMs) may offer significant advances in creating in vitro cardiac tissues for disease modeling, drug testing, and elucidating developmental processes; however, the induction of ESCs to a more adult-like CM phenotype remains challenging. In this study, we developed a bioreactor system to employ pulsatile flow (1.48 mL/min), cyclic strain (5%), and extended culture time to improve the maturation of murine and human ESC-CMs. Dynamically-cultured ESC-CMs showed an increased expression of cardiac-associated proteins and genes, cardiac ion channel genes, as well as increased SERCA activity and a Raman fingerprint with the presence of maturation-associated peaks similar to primary CMs. We present a bioreactor platform that can serve as a foundation for the development of human-based cardiac in vitro models to verify drug candidates, and facilitates the study of cardiovascular development and disease.


Distinct germination response of endangered and common arable weeds to reduced water potential.
Arable weeds are one of the most endangered species groups in Europe. Modern agriculture and intensive land-use management are the main causes of their dramatic decline. However, besides the changes in land use, climate change may further challenge the adaptability of arable weeds. Therefore, we investigated the response pattern of arable weeds to different water potential and temperature regimes during the phase of germination. We expected that endangered arable weeds would be more sensitive to differences in water availability and temperature than common arable weeds. To this end, we set up a climate chamber experiment where we exposed seeds of five familial pairs of common and endangered arable weed species to different temperatures (5/15, 10/20 °C) and water potentials (0.0 to -1.2 MPa). The results revealed a significant relationship between the reaction of arable weed species to water availability and their Red List status. The effects of reduced water availability on total germination, mean germination time and synchrony were significantly stronger in endangered than in common arable weeds. Therefore, global climate change may present a further threat to the survival of endangered arable weed species.


Intracellular calcium oscillations signal apoptosis rather than activation in in vitro aged mouse eggs.
We have previously demonstrated that initiation of intracellular calcium ([Ca2+]i) oscillations in mouse eggs signals activation or apoptotic death depending on the age of the eggs in which the oscillations are induced. To extend these studies, mouse eggs were aged in vitro to 24, 32, and 40 h post-hCG and injected with sperm cytosolic factor (SF), adenophostin A, or sperm (intracytoplasmic sperm injection), and the times at which signs of apoptosis first appeared were examined. These treatments, which induced [Ca2+]i oscillations, caused fragmentation and other signs of programmed cell death in eggs as early as 32 h post-hCG. The susceptibility of aged eggs to apoptosis appeared to be due to cytoplasmic deficiencies, because fusion of recently ovulated eggs with aged, SF-injected eggs prevented fragmentation. Evaluation of mRNA and protein levels of the apoptotic regulatory proteins Bcl-2 and Bax showed a prominent decrease in the amounts of Bcl-2 mRNA and protein in aged eggs, whereas Bax mRNA levels did not appear to be changed. Lastly, the Ca2+ responses induced by the aforementioned Ca2+ agonists ceased in advance in aged eggs. Together, these results suggest that one or several critical cytosolic molecules involved in the regulation of Ca2+ homeostasis, and in maintaining the equilibrium between anti- and proapoptotic proteins, is either lost or inactivated during postovulatory egg aging, rendering the fertilizing Ca2+ signal into an apoptosis-inducing signal.


Quercetin increased bioavailability and decreased methylation of green tea polyphenols in vitro and in vivo.
The extensive methylation of green tea polyphenols (GTPs) in vivo may limit their chemopreventive potential. We investigated whether quercetin, a natural inhibitor of catechol-O-methyltransferase (COMT) and multidrug resistance proteins (MRPs), will differentially increase the intracellular concentration and decrease the methylation of GTPs in different cancer cell lines. Intrinsic COMT activity was lowest in lung cancer A549 cells, intermediate in kidney 786-O cells and highest in liver HepG2 cells. Quercetin increased the cellular absorption of epigallocatechin gallate (EGCG) four-fold in A549 cells with a decreased methylation rate from 63 to 19%, 2-fold in 786-O cells with a decreased methylation from 97% to 56%, while no significant effect was observed in HepG2 cells. The combination significantly decreased the activity and protein expression of COMT and decreased the protein expression of MRP1 compared to individual treatments. The combination exhibited the strongest increase in antiproliferation in A549 cells, an intermediate effect in 786-O cells and lowest effect in HepG2 cells. The effect of quercetin on bioavailability and metabolism of GTPs was confirmed in vivo. Severe combined immunodeficiency (SCID) mice were administered brewed green tea (GT) and a diet supplemented with 0.4% quercetin alone or in combination for 2 weeks. We observed a 2- to 3-fold increase of total and non-methylated EGCG in lung and kidney and an increasing trend in liver. In summary, combining quercetin with GT provides a promising approach to enhance the chemoprevention of GT. Responses of different cancers to the combination may vary by tissue depending on the intrinsic COMT and MRP activity.


Viral load and HIV treatment attitudes as correlates of sexual risk behavior among HIV-positive gay men.
People living with HIV who achieve an "undetectable" viral load may assume that they are less infectious, leading to increased sexual risk. We examined the relation between perceiving that one has an undetectable viral load and sexual risk taking among gay men. HIV-positive participants (N=60) completed measures assessing HIV serostatus, perceived HIV viral load (detectable vs. undetectable), sexual risk and treatment attitudes. Contrary to hypotheses, HIV-positive men with detectable viral loads were more likely to report unprotected anal sex with a nonprimary partner than were men reporting undetectable viral loads. Although a significant minority endorsed the belief that an HIV-positive partner with an undetectable viral load is less infectious, this belief was unrelated to sexual risk. Multivariate analyses showed that the strongest predictor of sexual risk was a measure assessing participants' reduced concern over HIV stemming from the availability of improved HIV treatments. After controlling for reduced HIV concern, viral load status was no longer a significant predictor of risk. Results suggest that reduced concern about the consequences of HIV infection may be more important than perceived health status as a determinant of risky sex and highlight the need for continued prevention efforts among people who are HIV-positive.


Exceptional Risk: Healthy Volunteers' Perceptions of HIV/AIDS Clinical Trials.
As with all early-stage testing of investigational drugs, clinical trials targeting HIV/AIDS can pose unknown risks to research subjects. Unlike sick participants seeking a therapeutic benefit, the motivations and barriers for healthy volunteers are more complex and understudied. Drawing on interviews and clinical trial data from 178 healthy volunteers, we examine how they perceive HIV/AIDS studies in the early stages of testing. A subset of healthy volunteers see phase I HIV/AIDS studies as particularly risky for reasons ranging from fear of catching the disease or having long-lasting and uncomfortable side effects to inexplicable fears that they cannot even articulate. Some participants have had past negative experiences in such trials that inform these views, but others cite information from staff and other participants as influential. Healthy volunteers' general fears concerning AIDS also shape their views of participating in phase I HIV/AIDS clinical trials.


Assessment of Noninvasive Low-Frequency Ultrasound as a Means of Treating Injuries to Suspensory Ligaments in Horses: A Research Paper.
Therapeutic ultrasound is a noninvasive technique, which is well tolerated by horses, does not need sedation, and can easily be performed in a routine clinical setting. Twenty-three client-owned sport horses were recruited at Clinica Equina San Biagio and included in this case study. Treatment of the injured suspensory ligament apparatus was administered using an EQ Pro, low-frequency therapeutic unit (38 kHz). The noninvasive treatment consisted of massaging the injured area in combination with a traditional ultrasound gel while maintaining the head of the device in direct contact with the injured area. The results indicate that 20 of the 23 horses in this study benefitted from EQ Pro treatment and, following a routine rehabilitation program, returned to competition status: a success rate of 87%. Furthermore, treatment duration was 3.3 ± 0.4 weeks on average, with a healthy outcome as assessed by ultrasound at 6.8 ± 1.9 weeks. Among the 23 horses in this study, 65% of them benefitted from EQ Pro treatment of a duration of just ≤3.3 weeks. It is concluded that EQ Pro therapy is a promising and effective form of treatment for horses with suspensory ligament injury. It is furthermore rapid and easy to use in the Equine Veterinary Clinic setting and does not require sedation. Future studies should now focus on the mechanisms by which this new treatment activates the healing process of the suspensory ligaments of injured horses.


Yoga for Health-Related Quality of Life in Adult Cancer: A Randomized Controlled Feasibility Study.
An increase in patient-led uptake of complementary therapies in adult cancer has led to a need for more rigorous study of such interventions and their outcomes. This study therefore aimed to evaluate the feasibility and acceptability of a yoga intervention in men and women receiving conventional treatment for a cancer diagnosis. Prospective, mixed methods feasibility trial allocated participants to receive one of three yoga interventions over a four-week study period. Data collection was completed through online survey of QOL-CA/CS and customized surveys. Fifteen participants were included (11 female) undergoing treatment for breast, prostate, colorectal, brain, and blood and lung cancer. Two participants dropped out and complete qualitative and quantitative data sets were collected from 12 participants and four yoga instructors. Other outcome measures included implementation costs patient-reported preferences for yoga intervention and changes in QOL-CA/CS. Three types of yoga intervention were safely administered in adult cancer. Mixed methods, cost-efficiency, QOL-CA/CS, and evidence-based design of yoga intervention have been used to establish feasibility and patient-preferences for yoga delivery in adult caner. Results suggest that, with some methodological improvements, a large-scale randomized controlled trial is warranted to test the efficacy of yoga for male and female cancer patients. This trial is registered with Clinicaltrials.gov NCT02309112.


Bcl-2 expression and apoptosis in nephrotoxic nephritis.
The product of the Bcl-2 proto-oncogene has been shown to prolong cell survival by preventing apoptosis in several cell lineages. To investigate the regulatory mechanisms of apoptosis in glomerulonephritis, we examined the expression pattern of the Bcl-2 protein together with cellular events in rat nephrotoxic nephritis. Bcl-2 protein and proliferating cell nuclear antigen were detected in glomeruli by immunohistochemistry. Morphologic changes of apoptosis were identified by electron and light microscopy and an in situ DNA nick end labeling method. The first (heterologous) phase began with significant neutrophil infiltration shortly after the injection of nephrotoxic serum. Both Bcl-2 expression and the number of proliferating cells in the glomeruli were at maximum at 24 h in the heterologous phase. Glomerular hypercellularity with an influx of macrophages and the number of apoptotic glomerular cells peaked on day 14 in the second (autologous) phase. Glomerulonephritis resolved after that. These results suggest that overexpression of the Bcl-2 protein may play a role in glomerular cell survival and exacerbation of glomerulonephritis. Apoptosis may occur as an active mechanism in the resolution of the autologous phase in nephrotoxic nephritis.


A systematically coarse-grained solvent-free model for quantitative phospholipid bilayer simulations.
We present an implicit solvent coarse-grained (CG) model for quantitative simulations of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers. The absence of explicit solvent enables membrane simulations on large length and time scales at moderate computational expense. Despite improved computational efficiency, the model preserves chemical specificity and quantitative accuracy. The bonded and nonbonded interactions together with the effective cohesion mimicking the hydrophobic effect were systematically tuned by matching structural and mechanical properties from experiments and all-atom bilayer simulations, such as saturated area per lipid, radial distribution functions, density and pressure profiles across the bilayer, P(2) order, etc. The CG lipid model is shown to self-assemble into a bilayer starting from a random dispersion. Its line tension and elastic properties, such as bending and stretching modulus, are semiquantitatively consistent with experiments. The effects of (i) reduced molecular friction and (ii) more efficient integration combine to an overall speed-up of 3-4 orders of magnitude compared to all-atom bilayer simulations. Our CG lipid model is especially useful for studies of large-scale phenomena in membranes that nevertheless require a fair description of chemical specificity, e.g., membrane patches interacting with movable and transformable membrane proteins and peptides.


Matrix metalloproteinase-9 expression in carotid atherosclerotic plaque and contrast-enhanced MRI in a swine model.
A swine model of carotid atherosclerosis may greatly facilitate the identification of imaging characteristics of vulnerable plaques and the preclinical evaluation of endovascular intervention. In this study we assess the association of matrix metalloproteinase (MMP)-9 expression and neovascularity in carotid atherosclerotic plaques with MRI patterns in a swine model. Carotid atherosclerosis models were created in miniswine using a combination of partial ligation and a high cholesterol diet. The animals were imaged in a 1.5 T MR scanner at 3 months and carotid arteries were obtained for histopathological and immunohistochemical examination. Contrast-enhanced T1-weighted imaging (T1WI) was used to match the histology findings. The contrast-to-noise ratio (CNR) of the plaques on T1WI and contrast-enhanced T1WI were measured and the association of MMP-9 expression and neovascularity in the carotid plaque with CNR on MRI was analyzed. Forty carotid artery segments were matched between MRI and histology. All segments were advanced carotid atherosclerotic plaques. The matched contrast-enhanced T1WI and histology slices showed good correlation for ratio of plaque size to lumen diameter (r=0.94, p<0.001). Plaque CNR on contrast-enhanced T1WI was higher in plaques with strong MMP-9 expression than in those with weak MMP-9 expression (p=0.05). Plaque CNR on contrast-enhanced T1WI was also higher in plaques with marked neovascularization than in those without (p=0.02). Increased plaque CNR on contrast-enhanced T1WI is associated with MMP-9 expression and neovascularization in carotid atherosclerotic plaques and may be used to identify vulnerable plaques.


Population- and genome-specific patterns of linkage disequilibrium and SNP variation in spring and winter wheat (Triticum aestivum L.).
Single nucleotide polymorphisms (SNPs) are ideally suited for the construction of high-resolution genetic maps, studying population evolutionary history and performing genome-wide association mapping experiments. Here, we used a genome-wide set of 1536 SNPs to study linkage disequilibrium (LD) and population structure in a panel of 478 spring and winter wheat cultivars (Triticum aestivum) from 17 populations across the United States and Mexico. Most of the wheat oligo pool assay (OPA) SNPs that were polymorphic within the complete set of 478 cultivars were also polymorphic in all subpopulations. Higher levels of genetic differentiation were observed among wheat lines within populations than among populations. A total of nine genetically distinct clusters were identified, suggesting that some of the pre-defined populations shared significant proportion of genetic ancestry. Estimates of population structure (F(ST)) at individual loci showed a high level of heterogeneity across the genome. In addition, seven genomic regions with elevated F(ST) were detected between the spring and winter wheat populations. Some of these regions overlapped with previously mapped flowering time QTL. Across all populations, the highest extent of significant LD was observed in the wheat D-genome, followed by lower LD in the A- and B-genomes. The differences in the extent of LD among populations and genomes were mostly driven by differences in long-range LD ( > 10 cM). Genome- and population-specific patterns of genetic differentiation and LD were discovered in the populations of wheat cultivars from different geographic regions. Our study demonstrated that the estimates of population structure between spring and winter wheat lines can identify genomic regions harboring candidate genes involved in the regulation of growth habit. Variation in LD suggests that breeding and selection had a different impact on each wheat genome both within and among populations. The higher extent of LD in the wheat D-genome versus the A- and B-genomes likely reflects the episodes of recent introgression and population bottleneck accompanying the origin of hexaploid wheat. The assessment of LD and population structure in this assembled panel of diverse lines provides critical information for the development of genetic resources for genome-wide association mapping of agronomically important traits in wheat.


Effect of potassium citrate therapy on stone recurrence and residual fragments after shockwave lithotripsy in lower caliceal calcium oxalate urolithiasis: a randomized controlled trial.
To evaluate the efficacy of potassium citrate treatment in preventing stone recurrences and residual fragments after shockwave lithotripsy (SWL) for lower pole calcium oxalate urolithiasis. One hundred ten patients who underwent SWL because of lower caliceal stones and who were stone free or who had residual stone 4 weeks later were enrolled in the study. The average patient age was 41.7 years. All patients had documented simple calcium oxalate lithiasis without urinary tract infection and with normal renal morphology and function. Four weeks after SWL, patients who were stone free (N = 56) and patients who had residual stones (N = 34) were independently randomized into two subgroups that were matched for sex, age, and urinary values of citrate, calcium, and uric acid. One group was given oral potassium citrate 60 mEq per day, and the other group served as controls. In patients who were stone free after SWL and receiving medical treatment, the stone recurrence rate at 12 months was 0 whereas untreated patients showed a 28.5% stone recurrence rate (P < 0.05). Similarly, in the residual fragment group, the medically treated patients had a significantly greater remission rate than the untreated patients (44.5 v 12.5%; P < 0.05). Potassium citrate therapy significantly alleviated calcium oxalate stone activity after SWL for lower pole stones in patients who were stone free. An important observation was the beneficial effect of medical treatment on stone activity after SWL among patients with residual calculi.


Live high-train low associated with increased haemoglobin mass as preparation for the 2003 World Championships in two native European world class runners.
It is unclear whether world class endurance athletes, in contrast with less well trained subjects, increase their haemoglobin mass on a regimen of living high and training low (LHTL). To assess whether haemoglobin mass increases in world class athletes on LHTL and whether this increase is associated with peak performance at a subsequent important competition. Two Swiss world class runners (one 5000 m and one marathon) lived for 26 days (18 hours a day) at an altitude of 2456 m and trained at 1800 m. This LHTL camp was the preparation for the World Athletic Championships taking place 27-29 days after the end of the camp. Haemoglobin mass and other haematological variables were measured before and after the LHTL camp. The performance parameter was the race times during that period. Haemoglobin mass increased by 3.9% and 7.6%, and erythrocyte volume by 5.8% and 6.3%. The race times, as well as the ranking at the World Championships, indicated clearly improved performance after the LHTL camp. The results suggest that LHTL with an adequate dose of hypoxia can increase haemoglobin mass even in world class athletes, which may translate into improved performance at important competitions at sea level.


Quantitation of fragment X formation during thrombolytic therapy with streptokinase and tissue plasminogen activator.
We have determined the extent of fragment X formation during thrombolytic therapy by integration over time of the plasma fibrinopeptide B beta 1-42 concentration. This peptide is quantitatively released when fragment X is formed by plasmin action on fibrinogen or fibrin I. In response to streptokinase (SK) and rt-PA, 264 +/- 54 and 95 +/- 12 mg/dl respectively of fibrinogen was converted to fragment X. By immunoblotting, fragment X was demonstrated as early as 5 min after SK and 30 min after rt-PA, and was still evident 24 h after treatment. Patients treated with SK showed extensive further plasmin degradation of fragment X to fragments Y and D. Thus fragment X concentrations tend to be more similar in the two groups than would be expected from the extent of fibrinogen breakdown. Fragment X forms clots, but these have lower tensile strength and are more susceptible to further plasmin lysis than clots of fibrin. Thus the similar bleeding observed in the two treatment groups might be a reflection of their similar plasma fragment X concentrations.


4-Meth-oxy-3-(meth-oxy-meth-yl)benzalde-hyde.
In the title compound, C10H12O3, the dihedral angle between the benzene ring and the meth-oxy-methyl side chain is 9.7 (2)°. The O atom of the aldehyde group and the C atom of the meth-oxy group deviate from the plane of the ring by 0.039 (3) and 0.338 (4) Å, respectively. The only inter-molecular inter-actions are very weak C-H⋯π inter-actions.


Accumulation of Mg to Diffusive Gradients in Thin Films (DGT) Devices: Kinetic and Thermodynamic Effects of the Ionic Strength.
Availability of magnesium is a matter of concern due to its role in many environmental and biological processes. Diffusive Gradients in Thin Films (DGT) devices can measure Mg availability in situ. This work shows that Mg accumulation in water largely increases when ionic strength (I) decreases. This phenomenon can be explained from (i) the increase of both the association equilibrium (K) and rate (ka,R) constants for the reaction between Mg cations and resin sites, and (ii) the growing contribution of the partitioning of Mg cations at the resin-gel interface, as I decreases. Two theoretical models that take into account electrical interactions among Mg cations, background electrolyte, and resin sites can successfully be used to determine ka,R and K at each I. Both models yield similar ka,R values, which fulfill an expression for the kinetic salt effect. For freshwater (with a typical salinity of 10 mM and circumneutral pH), the binding of Mg is so fast and strong that the simplest perfect-sink DGT expression can be helpful to predict (overestimation lower than 5%) the accumulation in solutions with Mg concentrations up to 1 mM whenever the deployment time is below 9 h. Perfect sink conditions can still be applied for longer times, in systems with either a lower I or a lower Mg concentration.


Alcohol intake and the risk of intracerebral hemorrhage in the elderly: The MUCH-Italy.
To investigate the role of alcohol as a causal factor for intracerebral hemorrhage (ICH) and whether its effects might vary according to the pathogenic mechanisms underlying cerebral bleeding. We performed a case-control analysis, comparing a cohort of consecutive white patients with ICH aged 55 years and older with a group of age- and sex-matched stroke-free controls, enrolled in the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) between 2002 and 2014. Participants were dichotomized into excessive drinkers (>45 g of alcohol) and light to moderate drinkers or nondrinkers. To isolate the unconfounded effect of alcohol on ICH, we used causal directed acyclic graphs and the back-door criterion to select a minimal sufficient adjustment set(s) of variables for multivariable analyses. Analyses were performed on the whole group as well as separately for lobar and deep ICH. We analyzed 3,173 patients (1,471 lobar ICH and 1,702 deep ICH) and 3,155 controls. After adjusting for the preselected variables in the minimal sufficient adjustments, heavy alcohol intake was associated with deep ICH risk (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.36-2.09) as well as with the overall risk of ICH (OR, 1.38; 95% CI, 1.17-1.63), whereas no effect was found for lobar ICH (OR, 1.01; 95% CI, 0.77-1.32). In white people aged 55 years and older, high alcohol intake might exert a causal effect on ICH, with a prominent role in the vascular pathologies underlying deep ICH.


Cellular immunolocalization of gastric and pancreatic lipase in various tissues obtained from dogs.
To determine cellular immunolocalization of canine gastric lipase (cGL) and canine pancreatic lipase (cPL) in various tissues obtained from clinically healthy dogs. Samples of 38 tissues collected from 2 climically healthy dogs. The cGL and cPL were purified from gastric and pancreatic tissue, respectively, obtained from dogs. Antisera against both proteins were developed, using rabbits, and polyclonal antibodies were purified by use of affinity chromatography. Various tissues were collected from 2 healthy dogs. Primary antibodies were used to evaluate histologic specificity. Replicate sections from the collected tissues were immunolabeled for cGL and cPL and examined by use of light microscopy. Mucous neck cells and mucous pit cells of gastric glands had positive labeling for cGL, whereas other tissues did not immunoreact with cGL. Pancreatic acinar cells had positive labeling for cPL, whereas other tissues did not immunoreact with cPL. We concluded that cGL and cPL are exclusively expressed in gastric glands and pancreatic acinar cells, respectively. Also, evidence for cross-immunoreactivity with other lipases or related proteins expressed by other tissues was not found for either protein. Analysis of these data suggests that gastric lipase is a specific marker for gastric glands and that pancreatic lipase is a specific marker for pancreatic acinar cells. These markers may have clinical use in the diagnosis of gastric and exocrine pancreatic disorders, respectively.


Blue fluorescent dye-protein complexes based on fluorogenic cyanine dyes and single chain antibody fragments.
Fluoromodules are complexes formed upon the noncovalent binding of a fluorogenic dye to its cognate biomolecular partner, which significantly enhances the fluorescence quantum yield of the dye. Previously, several single-chain, variable fragment (scFv) antibodies were selected from a yeast cell surface-displayed library that activated fluorescence from a family of unsymmetrical cyanine dyes covering much of the visible and near-IR spectrum. The current work expands our repertoire of genetically encodable scFv-dye pairs by selecting and characterizing a group of scFvs that activate fluorogenic violet-absorbing, blue-fluorescing cyanine dyes, based on oxazole and thiazole heterocycles. The dye binds to both yeast cell surface-displayed and soluble scFvs with low nanomolar K(d) values. These dye-protein fluoromodules exhibit high quantum yields, approaching unity for the brightest system. The promiscuity of these scFvs with other fluorogenic cyanine dyes was also examined. Fluorescence microscopy demonstrates that the yeast cell surface-displayed scFvs can be used for multicolor imaging. The prevalence of 405 nm lasers on confocal imaging and flow cytometry systems make these new reagents potentially valuable for cell biological studies.


Salt in freshwaters: causes, effects and prospects - introduction to the theme issue.
Humans are globally increasing the salt concentration of freshwaters (i.e. freshwater salinization), leading to significant effects at the population, community and ecosystem level. The present theme issue focuses on priority research questions and delivers results that contribute to shaping the future research agenda on freshwater salinization as well as fostering our capacity to manage salinization. The issue is structured along five topics: (i) the estimation of future salinity and evaluation of the relative contribution of the different drivers; (ii) the physiological responses of organisms to alterations in ion concentrations with a specific focus on the osmophysiology of freshwater insects and the responses of different organisims to seawater intrusion; (iii) the impact of salinization on ecosystem functioning, also considering the connections between riparian and stream ecosystems; (iv) the role of context in moderating the response to salinization. The contributions scrutinise the role of additional stressors, biotic interactions, the identify of the ions and their ratios, as well as of the biogeographic and evolutionary context; and (v) the public discourse on salinization and recommendations for management and regulation. In this paper we introduce the general background of salinization, outline research gaps and report key findings from the contributions to this theme issue.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.


Patients' experiences with hospital care in five countries.
Analysis of patient surveys carried out in Germany, Sweden, Switzerland, the United Kingdom, and the United States in 1998-2000 revealed high rates of problems during inpatient hospital stays. Problems with information and education, coordination of care, respect for patients' preferences, emotional support, physical comfort, involvement of family and friends, and continuity and transition were prevalent in all five countries. These dimensions of patients' experience appear to be salient and relevant in each of the five countries, but attempts to develop international rankings based on this type of evidence will have to overcome a number of methodological problems.


Micro-treatment options for components of organic fraction of MSW in residential areas.
There is a growing interest in management of MSW through micro-treatment of organic fraction of municipal solid wastes (OFMSW) in many cities of India. The OFMSW fraction is high (>80%) in many pockets within South Indian cities like Bangalore, Chikkamagalur, etc. and is largely represented by vegetable, fruit, packing and garden wastes. Among these, the last three have shown problems for easy decomposition. Fruit wastes are characterized by a large pectin supported fraction that decomposes quickly to organic acids (becomes pulpy) that eventually slow down anaerobic and aerobic decomposition processes. Paper fraction (newsprint and photocopying paper) as well as paddy straw (packing), bagasse (from cane juice stalls) and tree leaf litter (typical garden waste and street sweepings) are found in reasonably large proportions in MSW. These decompose slowly due to poor nutrients or physical state. We have examined the suitability of these substrates for micro-composting in plastic bins by tracking decomposition pattern and physical changes. It was found that fruit wastes decompose rapidly to produce organic acids and large leachate fraction such that it may need to be mixed with leachate absorbing materials (dry wastes) for good composting. Leaf litter, paddy straw and bagasse decompose to the tune of 90, 68 and 60% VS and are suitable for composting micro-treatment. Paper fractions even when augmented with 10% leaf compost failed to show appreciable decomposition in 50 days. All these feedstocks were found to have good biological methane potential (BMP) and showed promise for conversion to biogas under a mixed feed operation. Suitability of this approach was verified by operating a plug-flow type anaerobic digester where only leaf litter gathered nearby (as street sweepings) was used as feedstock. Here only a third of the BMP was realized at this scale (0.18 m(3 )biogas/kg VS 0.55 m(3)/kg in BMP). We conclude that anaerobic digestion in plug-flow like digesters appear a more suitable micro-treatment option (2-10 kg VS/day) because in addition to compost it also produces biogas for domestic use nearby.


Hydrolysis of alphas1- and beta-casein-derived peptides with a broad specificity aminopeptidase and proline specific aminopeptidases from Lactococcus lactis subsp. cremoris AM2.
Aminopeptidase hydrolysis of alpha(s)1 - and beta-casein-derived synthetic peptides containing non-consecutive and consecutive proline residues was characterised. Aminopeptidase P (Pep P) (EC 220.127.116.11) or post-proline dipeptidyl aminopeptidase (PPDA) (EC 184.108.40.206) along with lysine-paranitroanilide hydrolase (KpNA-H) (EC 184.108.40.206) activities are required in the degradation of peptides containing non-consecutive proline residues. However, both Pep P and PPDA along with KpNA-H are required for hydrolysis of peptides containing consecutive proline residues. The results demonstrate the mechanism by which combinations of purified general and proline specific aminopeptidases from Lactococcus lactis subsp. cremoris AM2 hydrolyse peptides containing proline residues.


Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice.
Missense mutations in the beta-amyloid precursor protein gene (APP) co-segregate with a small subset of autosomal dominant familial Alzheimer's disease (FAD) cases wherein deposition of the 39-43 amino acid beta-amyloid (A beta) peptide and neurodegeneration are principal neuropathological hallmarks. To accurately examine the effect of missense mutations on APP metabolism and A beta production in vivo, we have introduced yeast artificial chromosomes (YACs) containing the entire approximately 400 kbp human APP gene encoding APP harboring either the asparagine for lysine and leucine for methionine FAD substitution at codons 670 and 671 (APP(K670N/M671L)), the isoleucine for valine FAD substitution at codon 717 (APP(V7171)) or a combination of both substitutions into transgenic mice. We demonstrate that, relative to YAC transgenic mice expressing wild-type APP, high levels of A beta peptides are detected in the brains of YAC transgenic mice expressing human APP(K670N/M671L) that is associated with a concomitant diminution in the levels of apha-secretase-generated soluble APP derivatives. Moreover, the levels of longer A beta peptides (species terminating at amino acids 42/43) are elevated in YAC transgenic mice expressing human APP(V7171). These mice should prove valuable for detailed analysis of the in vivo effects of the APP FAD mutations in a variety of tissues and throughout aging and for testing therapeutic agents that specifically alter APP metabolism and A beta production.


Collaborative Regulation of LRG1 by TGF-β1 and PPAR-β/δ Modulates Chronic Pressure Overload-Induced Cardiac Fibrosis.
Despite its established significance in fibrotic cardiac remodeling, clinical benefits of global inhibition of TGF (transforming growth factor)-β1 signaling remain controversial. LRG1 (leucine-rich-α2 glycoprotein 1) is known to regulate endothelial TGFβ signaling. This study evaluated the role of LRG1 in cardiac fibrosis and its transcriptional regulatory network in cardiac fibroblasts. Pressure overload-induced heart failure was established by transverse aortic constriction. Western blot, quantitative reverse transcription polymerase chain reaction, immunofluorescence, and immunohistochemistry were used to evaluate the expression level and pattern of interested targets or pathology during fibrotic cardiac remodeling. Cardiac function was assessed by pressure-volume loop analysis. LRG1 expression was significantly suppressed in left ventricle of mice with transverse aortic constriction-induced fibrotic cardiac remodeling (mean difference, -0.00085 [95% CI, -0.0013 to -0.00043]; P=0.005) and of patients with end-stage ischemic-dilated cardiomyopathy (mean difference, 0.13 [95% CI, 0.012-0.25]; P=0.032). More profound cardiac fibrosis (mean difference, -0.014% [95% CI, -0.029% to -0.00012%]; P=0.048 for interstitial fibrosis; mean difference, -1.3 [95% CI, -2.5 to -0.2]; P=0.016 for perivascular fibrosis), worse cardiac dysfunction (mean difference, -2.5 ms [95% CI, -4.5 to -0.4 ms]; P=0.016 for Tau-g; mean difference, 13% [95% CI, 2%-24%]; P=0.016 for ejection fraction), and hyperactive TGFβ signaling in transverse aortic constriction-operated Lrg1-deficient mice (mean difference, -0.27 [95% CI, -0.47 to -0.07]; P<0.001), which could be reversed by cardiac-specific Lrg1 delivery mediated by adeno-associated virus 9. Mechanistically, LRG1 inhibits cardiac fibroblast activation by competing with TGFβ1 for receptor binding, while PPAR (peroxisome proliferator-activated receptor)-β/δ and TGFβ1 collaboratively regulate LRG1 expression via SMRT (silencing mediator for retinoid and thyroid hormone receptor). We further demonstrated functional interactions between LRG1 and PPARβ/δ in cardiac fibroblast activation. Our results established a highly complex molecular network involving LRG1, TGFβ1, PPARβ/δ, and SMRT in regulating cardiac fibroblast activation and cardiac fibrosis. Targeting LRG1 or PPARβ/δ represents a promising strategy to control pathological cardiac remodeling in response to chronic pressure overload.


Magnetic resonance imaging features of leukoaraiosis in elderly dogs.
Leukoaraiosis is a descriptive term used to designate bilateral, symmetrical, white matter lesions identified in brains of elderly human patients. These lesions are isointense to normal in magnetic resonance imaging (MRI) T1-weighted pulse sequences, non-contrast enhancing, and hyperintense in T2-weighted and FLAIR pulse sequences. Pathophysiologic mechanisms for leukoaraiosis remain incompletely understood; however, an ischemic origin is currently being favored. Age-related changes, such as brain atrophy, ventricular enlargement, and well-demarcated sulci, have also been previously described in dogs over 9 years of age. Objectives of this retrospective case series study were to describe MRI features of leukoaraiosis and brain atrophy in a group of elderly dogs. The Dick White Referrals MRI database between October 2009 and April 2016 was reviewed. Dogs with bilaterally symmetrical periventricular areas of T2 and FLAIR hyperintensity compatible with leukoaraiosis, and older than 9 years, were included. Fourteen dogs met the inclusion criteria, with a total of 18 MRI studies available for review. Median age for sampled dogs was 13 years. Ten dogs had MRI signs of concurrent brain atrophy; one of them had signs of brain atrophy before leukoaraiotic changes could be identified. In those cases where serial MRIs were available, progressive reduction of interthalamic adhesion thickness was observed. The current study introduces leukoaraiosis as a descriptive term for the MRI sign of bilaterally symmetrical, periventricular T2, and FLAIR hyperintensities in brains of elderly dogs. Future studies are needed to determine pathophysiologic mechanisms for this MRI sign.


Novel column generation-based optimization approach for poly-pathway kinetic model applied to CHO cell culture.
Mathematical modelling can provide precious tools for bioprocess simulation, prediction, control and optimization of mammalian cell-based cultures. In this paper we present a novel method to generate kinetic models of such cultures, rendering complex metabolic networks in a poly-pathway kinetic model. The model is based on subsets of elementary flux modes (EFMs) to generate macro-reactions. Thanks to our column generation-based optimization algorithm, the experimental data are used to identify the EFMs, which are relevant to the data. Here the systematic enumeration of all the EFMs is eliminated and a network including a large number of reactions can be considered. In particular, the poly-pathway model can simulate multiple metabolic behaviors in response to changes in the culture conditions. We apply the method to a network of 126 metabolic reactions describing cultures of antibody-producing Chinese hamster ovary cells, and generate a poly-pathway model that simulates multiple experimental conditions obtained in response to variations in amino acid availability. A good fit between simulated and experimental data is obtained, rendering the variations in the growth, product, and metabolite uptake/secretion rates. The intracellular reaction fluxes simulated by the model are explored, linking variations in metabolic behavior to adaptations of the intracellular metabolism.


A guide to the natural history of freshwater lake bacteria.
Freshwater bacteria are at the hub of biogeochemical cycles and control water quality in lakes. Despite this, little is known about the identity and ecology of functionally significant lake bacteria. Molecular studies have identified many abundant lake bacteria, but there is a large variation in the taxonomic or phylogenetic breadths among the methods used for this exploration. Because of this, an inconsistent and overlapping naming structure has developed for freshwater bacteria, creating a significant obstacle to identifying coherent ecological traits among these groups. A discourse that unites the field is sorely needed. Here we present a new freshwater lake phylogeny constructed from all published 16S rRNA gene sequences from lake epilimnia and propose a unifying vocabulary to discuss freshwater taxa. With this new vocabulary in place, we review the current information on the ecology, ecophysiology, and distribution of lake bacteria and highlight newly identified phylotypes. In the second part of our review, we conduct meta-analyses on the compiled data, identifying distribution patterns for bacterial phylotypes among biomes and across environmental gradients in lakes. We conclude by emphasizing the role that this review can play in providing a coherent framework for future studies.


See, feel, act: Hierarchical learning for complex manipulation skills with multisensory fusion.
Humans are able to seamlessly integrate tactile and visual stimuli with their intuitions to explore and execute complex manipulation skills. They not only see but also feel their actions. Most current robotic learning methodologies exploit recent progress in computer vision and deep learning to acquire data-hungry pixel-to-action policies. These methodologies do not exploit intuitive latent structure in physics or tactile signatures. Tactile reasoning is omnipresent in the animal kingdom, yet it is underdeveloped in robotic manipulation. Tactile stimuli are only acquired through invasive interaction, and interpretation of the data stream together with visual stimuli is challenging. Here, we propose a methodology to emulate hierarchical reasoning and multisensory fusion in a robot that learns to play Jenga, a complex game that requires physical interaction to be played effectively. The game mechanics were formulated as a generative process using a temporal hierarchical Bayesian model, with representations for both behavioral archetypes and noisy block states. This model captured descriptive latent structures, and the robot learned probabilistic models of these relationships in force and visual domains through a short exploration phase. Once learned, the robot used this representation to infer block behavior patterns and states as it played the game. Using its inferred beliefs, the robot adjusted its behavior with respect to both its current actions and its game strategy, similar to the way humans play the game. We evaluated the performance of the approach against three standard baselines and show its fidelity on a real-world implementation of the game.


Color-Doppler sonography patterns in endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph-nodes.
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is commonly used for the pathological diagnosis in patients with mediastinal lymphadenopathy. Even though the accuracy of EBUS-TBNA is considered high, several authors have tried to outline characteristic ultrasound criteria for malignant mediastinal lymph-node identification to maximize this accuracy. Recently, a color-Doppler patterns classification has been proposed by Nakajima to target suspected mediastinal lymph-nodes. The aim of this study was to assess such classification. Clinical, sonographic and pathological data of patients with suspected malignant mediastinal lymph-nodes on computed tomography (CT) and/or on positron emission tomography (PET) were prospectively recorded. On the basis of color-Doppler patterns, mediastinal lymph-nodes were classified in four grades and the bronchial-artery inflow sign was noted according to the Nakajima classification. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predicted value (NPV) and accuracy were calculated using standard definitions. Seventy-five patients were enrolled in this prospective study, median age 66 years; 85% of patients had primary lung cancer and 15% had extra-thoracic malignancy. EBUS-TBNA was performed in 87 lymph-nodes (rate 1.16 per patient); 6 lymph-nodes had inadequate samples and were excluded from the analysis; 64 nodes were confirmed as malignant and 17 nodes as benign. Color-Doppler patterns classification was as follow: grade 0-I, 14 lymph-nodes; grade II-III, 67 lymph-nodes; bronchial-artery inflow sign, 8 lymph-nodes. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy of the classification were 0.93, 0.64, 0.84, 0.6 and 0.81 respectively. The color-Doppler sonography is a fast, reproducible and effective tool that could help in targeting suspected malignant lymph-nodes during EBUS-TBNA. The current study validates the efficacy of the color-Doppler patterns classification proposed by Nakajima.


Continuous curvilinear (circular) capsulorhexis and planned extracapsular cataract extraction--are they compatible?
The successful use of continuous curvilinear (circular) capsulorhexis (CCC) in planned extracapsular cataract extraction (ECCE) is dependent on the feasibility of safe nuclear delivery through the smaller anterior capsular opening. Experimental evidence supports the proposition that the anterior capsular rim can stretch without tearing to dimensions which allow for safe nucleus delivery. Clinical reports of accidental intracapsular expression during nucleus delivery in CCC seemingly contradict the experimental evidence. This paper examines this apparent contradiction and presents clinical evidence in the form of a series of 210 cases of planned ECCE with CCC. The technique used and a detailed analysis of the operative complications are presented. The results indicate that using a modified technique for nucleus delivery, CCC and planned ECCE are fully compatible techniques.


The Leeds food preference questionnaire after mild sleep restriction - A small feasibility study.
Besides the increased sedentary lifestyle and increased caloric intake, changes in dietary composition may play an important role in the increased prevalence of obesity. Because inadequate sleep could be a risk factor in the aetiology of obesity, reliable methods for assessing food intake and food choice after sleep restriction are needed. We translated the Leeds food preference questionnaire (LFPQ), addressing preferences for sweet/savoury tastes and low-fat/high-fat foods, into Dutch, and tested it in 15 mildly sleep-restricted psychology students. The participants completed the LFPQ in our laboratory on two separate occasions, with approximately one week in between. Sleep on the preceding night was not controlled, but mild sleep-restriction was confirmed by a short sleep latency test (sSLT) or a short maintenance of wakefulness test (sMWT). Each participant completed the sSLT and sMWT once, just before the LFPQ, in a cross-over design randomised for the first test. Differences were present in preferences for food items from different categories (sweet/savoury and low-fat/high-fat; p<0.001). The choice frequencies for various food categories were comparable on both occasions (p=0.27). The choice frequencies for individual items were also comparable on both occasions (p=0.27). The LFPQ is easily implemented under mild sleep-restricted conditions, and translation is straightforward. Future studies using the LFPQ after sleep restriction could elucidate if restricting sleep or longer periods affects food choice, which could underlie increases in obesity risk.


Regulation of hepatic lipogenesis by the transcription factor XBP1.
Dietary carbohydrates regulate hepatic lipogenesis by controlling the expression of critical enzymes in glycolytic and lipogenic pathways. We found that the transcription factor XBP1, a key regulator of the unfolded protein response, is required for the unrelated function of normal fatty acid synthesis in the liver. XBP1 protein expression in mice was elevated after feeding carbohydrates and corresponded with the induction of critical genes involved in fatty acid synthesis. Inducible, selective deletion of XBP1 in the liver resulted in marked hypocholesterolemia and hypotriglyceridemia, secondary to a decreased production of lipids from the liver. This phenotype was not accompanied by hepatic steatosis or compromise in protein secretory function. The identification of XBP1 as a regulator of lipogenesis has important implications for human dyslipidemias.


Divergent hemispheric reasoning strategies: reducing uncertainty versus resolving inconsistency.
Converging lines of evidence from diverse research domains suggest that the left and right hemispheres play distinct, yet complementary, roles in inferential reasoning. Here, we review research on split-brain patients, brain-damaged patients, delusional patients, and healthy individuals that suggests that the left hemisphere tends to create explanations, make inferences, and bridge gaps in information, while the right hemisphere tends to detect conflict, update beliefs, support mental set-shifts, and monitor and inhibit behavior. Based on this evidence, we propose that the left hemisphere specializes in creating hypotheses and representing causality, while the right hemisphere specializes in evaluating hypotheses, and rejecting those that are implausible or inconsistent with other evidence. In sum, we suggest that, in the domain of inferential reasoning, the left hemisphere strives to reduce uncertainty while the right hemisphere strives to resolve inconsistency. The hemispheres' divergent inferential reasoning strategies may contribute to flexible, complex reasoning in the healthy brain, and disruption in these systems may explain reasoning deficits in the unhealthy brain.


Nuclear and cytoplasmic genetic diversity in weed beet and sugar beet accessions compared to wild relatives: new insights into the genetic relationships within the Beta vulgaris complex species.
Hybridization between cultivated species and their wild relatives is now widely considered to be common. In the Beta vulgaris complex, the sugar beet seed multiplication areas have been the scene of inadvertent pollination of sugar beet seed bearers by wild ruderal pollen donors, generating a weedy form of beet which infests sugar beet fields in European countries. Up to now, investigations of evolutionary dynamics of genetic diversity within the B. vulgaris complex were addressed using few genetical markers and few accessions. In this study, we tackled this issue using a panel of complementary markers: five nuclear microsatellite loci, four mitochondrial minisatellite loci and one chloroplastic PCR-RFLP marker. We sampled 1,640 individuals that illustrate the actual distribution of inland ruderal beets of South Western France, weed beets and wild sea beets of northern France as well as the diversity of 35 contemporary European diploid cultivars. Nuclear genetic diversity in weed beets appeared to be as high as those of ruderal beets and sea beets, whereas the narrowness of cultivar accessions was confirmed. This genetic bottleneck in cultivars is even more important in the cytoplasmic genome as only one haplotype was found among all sugar beet cultivars. The large majority of weed beet populations also presented this unique cytoplasmic haplotype, as expected owing to their maternal cultivated origin. Nonetheless, various cytoplasmic haplotypes were found within three populations of weed beets, implying wild-to-weed seed flows. Finally, our findings gave new insights into the genetical relationships between the components of the B. vulgaris complex: (1) we found a very strong genetic divergence between wild sea beet and other relatives, which was unexpected given the recent evolutionary history and the full cross-compatibility of all taxa and (2) we definitely confirmed that the classification into cultivated, wild, ruderal and weed forms according to their geographical location, phenotype or their domesticated status is clearly in accordance with genetic clustering despite the very recent domestication process of sugar beet.


Recycled dentin root matrix for a carrier of recombinant human bone morphogenetic protein.
Dysfunctional teeth, donated by community dental clinics, were recycled for research on bone morphogenetic protein (BMP) in health and disease. The crown remnants were trimmed away, and the roots were washed in 70% alcohol, demineralized, lyophilized, and prepared in one of two forms: (1) human partially demineralized root dentin matrix (PDM) or (2) autolysed, antigen-extracted root matrix (AAAD), including attached cementum. Composites of either PDM or antigen-extracted, autolysed, delipidized allogenic dentin matrix (AAAM) and recombinant human bone morphogenetic protein (rhBMP-2) were implanted in either normal or athymic mice. The percentage of muscle replaced by heterotopic bone was estimated by computer-assisted random point analysis. Implants of PDM and AAAD made from dysfunctional teeth exhibited little or no endogenous BMP activity and failed to induce new bone formation. Composites of 1 microgram of rhBMP-2 per 70 mg of PDM carrier induced 61% replacement of muscle by bone formation; 1 microgram of rhBMP-2 in 70 mg of AAAM matrix induced 78% replacement of muscle mass by bone; 2 or 5 micrograms of rhBMP-2 and 70 mg of AAAM carrier induced 100% replacement of thigh muscle mass by bone. In athymic mice, the areas of new bone were only slightly greater than those in normal mice. These observations suggest that root dentin prepared from extracted teeth may be recycled for use as a carrier of rhBMP-2 because it induces new bone formation in the periodontium.


Active site models for the Cu(A) site of peptidylglycine α-hydroxylating monooxygenase and dopamine β-monooxygenase.
A mononuclear copper(II) superoxo species has been invoked as the key reactive intermediate in aliphatic substrate hydroxylation by copper monooxygenases such as peptidylglycine α-hydroxylating monooxygenase (PHM), dopamine β-monooxygenase (DβM), and tyramine β-monooxygenase (TβM). We have recently developed a mononuclear copper(II) end-on superoxo complex using a N-[2-(2-pyridyl)ethyl]-1,5-diazacyclooctane tridentate ligand, the structure of which is similar to the four-coordinate distorted tetrahedral geometry of the copper-dioxygen adduct found in the oxy-form of PHM (Prigge, S. T.; Eipper, B. A.; Mains, R. E.; Amzel, L. M. Science2004, 304, 864-867). In this study, structures and physicochemical properties as well as reactivity of the copper(I) and copper(II) complexes supported by a series of tridentate ligands having the same N-[2-(2-pyridyl)ethyl]-1,5-diazacyclooctane framework have been examined in detail to shed light on the chemistry dictated in the active sites of mononuclear copper monooxygenases. The ligand exhibits unique feature to stabilize the copper(I) complexes in a T-shape geometry and the copper(II) complexes in a distorted tetrahedral geometry. Low temperature oxygenation of the copper(I) complexes generated the mononuclear copper(II) end-on superoxo complexes, the structure and spin state of which have been further characterized by density functional theory (DFT) calculations. Detailed kinetic analysis on the O(2)-adduct formation reaction gave the kinetic and thermodynamic parameters providing mechanistic insights into the association and dissociation processes of O(2) to the copper complexes. The copper(II) end-on superoxo complex thus generated gradually decomposed to induce aliphatic ligand hydroxylation. Kinetic and DFT studies on the decomposition reaction have suggested that C-H bond abstraction occurs unimolecularly from the superoxo complex with subsequent rebound of the copper hydroperoxo species to generate the oxygenated product. The present results have indicated that a superoxo species having a four-coordinate distorted tetrahedral geometry could be reactive enough to induce the direct C-H bond activation of aliphatic substrates in the enzymatic systems.


Supratentorial regions of acute ischemia associated with clinically important swallowing disorders: a pilot study.
Dysphagia is a common problem after stroke associated with significant morbidity and mortality. Except for patients with brain stem strokes, particularly lateral medullary strokes, it is difficult to predict which cases are likely to develop swallowing dysfunction based on their neuroimaging. Clear models of swallowing control and integration of cortico-bulbar input have not been defined and the role of subcortical structures is unclear. The purpose of this study was to identify supratentorial regions of interest (ROIs) that might be related to clinically important dysphagia in acute stroke patients, focusing on subcortical structures. We studied 29 acute supratentorial ischemic stroke cases admitted to our institution between 2001 and 2005 diagnoses with first ischemic stroke and without history of swallowing dysfunction. Subjects had MRI within 24 hours. Cases were defined as those subjects who were diagnosed as dysphagic after clinical evaluation by a speech language pathologist (SLP) and whose dysphagia was considered clinically significant, ie, requiring treatment by diet modification. Controls were defined as those patients who: (1) passed the stroke unit's dysphagia screening, (2) had a clinical evaluation by SLP that did not result in a diagnosis of dysphagia or diet modifications, or (3) had no documented evidence of dysphagia evaluation or treatment during hospitalization and were discharged on a regular diet. A trained technician, blinded to case-control status, examined 12 ROIs for dysfunctional tissue in diffusion and perfusion-weighted images. The odds ratio (OR) of dysphagia was calculated for each ROI. Logistic regression models were used to adjust for stroke severity (NIHSS) and volume. Analysis of data on 14 cases and 15 controls demonstrated significant differences in the unadjusted odds of dysphagia for the following ROIs: (1) primary somatosensory, motor, and motor supplementary areas (PSSM; OR=10, P=0.009); (2) orbitofrontal cortex (OFC; OR=6.5, P=0.04); (3) putamen, caudate, basal ganglia (PCBG; OR=5.33, P=0.047); and (4) internal capsule (IC; OR=26; P=0.005). Nonsignificant differences were found in the insula and temporopolar cortex. Adjusted OR of dysphagia for subjects with strokes affecting the IC was 17.8 (P=0.03). Adjusted odds ratios for the PSSM, OFC, and PCBG were not statistically significant. Significantly increased odds of dysphagia were found in subjects with IC involvement. Other supratentorial areas that may be associated with dysphagia include the PSSM, OFC, and PCBG. Analysis of additional areas was limited by the number of subjects in our sample. Future studies with larger sample size are feasible and will contribute to the development of a full swallowing control model.


Functional Divergence of the Nuclear Receptor NR2C1 as a Modulator of Pluripotentiality During Hominid Evolution.
Genes encoding nuclear receptors (NRs) are attractive as candidates for investigating the evolution of gene regulation because they (1) have a direct effect on gene expression and (2) modulate many cellular processes that underlie development. We employed a three-phase investigation linking NR molecular evolution among primates with direct experimental assessment of NR function. Phase 1 was an analysis of NR domain evolution and the results were used to guide the design of phase 2, a codon-model-based survey for alterations of natural selection within the hominids. By using a series of reliability and robustness analyses we selected a single gene, NR2C1, as the best candidate for experimental assessment. We carried out assays to determine whether changes between the ancestral and extant NR2C1s could have impacted stem cell pluripotency (phase 3). We evaluated human, chimpanzee, and ancestral NR2C1 for transcriptional modulation of Oct4 and Nanog (key regulators of pluripotency and cell lineage commitment), promoter activity for Pepck (a proxy for differentiation in numerous cell types), and average size of embryological stem cell colonies (a proxy for the self-renewal capacity of pluripotent cells). Results supported the signal for alteration of natural selection identified in phase 2. We suggest that adaptive evolution of gene regulation has impacted several aspects of pluripotentiality within primates. Our study illustrates that the combination of targeted evolutionary surveys and experimental analysis is an effective strategy for investigating the evolution of gene regulation with respect to developmental phenotypes.


Character strengths and well-being across the life span: data from a representative sample of German-speaking adults living in Switzerland.
Character strengths are positive, morally valued traits of personality. This study aims at assessing the relationship between character strengths and subjective well-being (i.e., life satisfaction, positive and negative affect) in a representative sample of German-speaking adults living in Switzerland (N = 945). We further test whether this relationship is consistent at different stages in life. Results showed that hope, zest, love, social intelligence and perseverance yielded the highest positive correlations with life satisfaction. Hope, zest, humor, gratitude and love presented the highest positive correlations with positive affect. Hope, humor, zest, honesty, and open-mindedness had the highest negative correlations with negative affect. When examining the relationship between strengths and well-being across age groups, in general, hope, zest and humor consistently yielded the highest correlations with well-being. Additionally, in the 27-36 years group, strengths that promote commitment and affiliation (i.e., kindness and honesty) were among the first five positions in the ranking of the relationship between strengths and well-being. In the 37-46 years group, in addition to hope, zest and humor, strengths that promote the maintenance of areas such as family and work (i.e., love, leadership) were among the first five positions in the ranking. Finally, in the 47-57 years group, in addition to hope, zest and humor, strengths that facilitate integration and a vital involvement with the environment (i.e., gratitude, love of learning) were among the first five positions in the ranking. This study partially supports previous findings with less representative samples on the association between character strengths and well-being, and sheds light on the relative importance of some strengths over others for well-being across the life span.


Amide Proton Transfer Contrast Distribution in Different Brain Regions in Young Healthy Subjects.
To define normal signal intensity values of amide proton transfer-weighted (APTw) magnetic resonance (MR) imaging in different brain regions. Twenty healthy subjects (9 females, mean age 29 years, range 19 - 37 years) underwent MR imaging at 3 Tesla. 3D APTw (RF saturation B1,rms = 2 μT, duration 2 s, 100% duty cycle) and 2D T2-weighted turbo spin echo (TSE) images were acquired. Postprocessing (image fusion, ROI measurements of APTw intensity values in 22 different brain regions) was performed and controlled by two independent neuroradiologists. Values were measured separately for each brain hemisphere. A subject was scanned both in prone and supine position to investigate differences between hemispheres. A mixed model on a 5% significance level was used to assess the effect of gender, brain region and side on APTw intensity values. Mean APTw intensity values in the hippocampus and amygdala varied between 1.13 and 1.57%, in the deep subcortical nuclei (putamen, globus pallidus, head of caudate nucleus, thalamus, red nucleus, substantia nigra) between 0.73 and 1.84%, in the frontal, occipital and parietal cortex between 0.56 and 1.03%; in the insular cortex between 1.11 and 1.15%, in the temporal cortex between 1.22 and 1.37%, in the frontal, occipital and parietal white matter between 0.32 and 0.54% and in the temporal white matter between 0.83 and 0.89%. APTw intensity values were significantly impacted both by brain region (p < 0.001) and by side (p < 0.001), whereby overall values on the left side were higher than on the right side (1.13 vs. 0.9%). Gender did not significantly impact APTw intensity values (p = 0.24). APTw intensity values between the left and the right side were partially reversed after changing the position of one subject from supine to prone. We determined normal baseline APTw intensity values in different anatomical localizations in healthy subjects. APTw intensity values differed both between anatomical regions and between left and right brain hemisphere.


Social media use for nutrition outcomes in young adults: a mixed-methods systematic review.
Social media has been widely adopted by young adults, consequently health researchers are looking for ways to leverage this engagement with social media for the delivery of interventions and health promotion campaigns. Weight gain and sub-optimal dietary choices are common in young adults, and social media may be a potential tool to facilitate and support healthier choices. We conducted a mixed-methods systematic review of studies examining social media use for nutrition-related outcomes in young adults. Seven databases [EBscohost, ERIC, ProQuest Central, PubMed, Ovid, Scopus, and Emerald] were systematically searched; 1225 abstracts were screened, and 47 full-text articles were assessed for eligibility. Study designs included both quantitative, such as experimental and observational studies, and qualitative, such as focus groups and interviews, approaches. Quality was assessed using the Mixed Methods Appraisal Tool. Quantitative and qualitative results were examined separately, and then synthesized. Twenty-one studies were included although their use of social media was highly variable. The main purpose of social media was to provide information and social support to participants. In the nine randomized controlled trials, social media was used as one aspect of a multi-faceted intervention. Interventions had a positive statistically significant impact on nutritional outcomes in 1/9 trials. Engagement with the social media component of interventions varied, from 3 to 69%. Young adults appear to be open to receiving healthy eating and recipe tips through social media, however, they are reluctant to share personal weight-related information on their online social networks. Information-dissemination is now an acceptable use of social media by young adults. Using social media effectively for social support, either via private groups or public pages, requires careful evaluation as its effectiveness is yet to be demonstrated in experimental designs. Concerns about public social media use may be a contributing factor to poor engagement with social media in research intervention studies aimed at influencing weight. Future research should consider how to best engage with young adults using social media, how to more effectively use social media to support young adults and to facilitate social and peer-to-peer support in making healthier choices.


Neural mechanisms of visual attention: object-based selection of a region in space.
Objects play an important role in guiding spatial attention through a cluttered visual environment. We used event-related functional magnetic resonance imaging (ER-fMRI) to measure brain activity during cued discrimination tasks requiring subjects to orient attention either to a region bounded by an object (object-based spatial attention) or to an unbounded region of space (location-based spatial attention) in anticipation of an upcoming target. Comparison between the two tasks revealed greater activation when attention selected a region bounded by an object. This activation was strongly lateralized to the left hemisphere and formed a widely distributed network including (a) attentional structures in parietal and temporal cortex and thalamus, (b) ventral-stream object processing structures in occipital, inferior-temporal, and parahippocampal cortex, and (c) control structures in medial- and dorsolateral-prefrontal cortex. These results suggest that object-based spatial selection is achieved by imposing additional constraints over and above those processes already operating to achieve selection of an unbounded region. In addition, ER-fMRI methodology allowed a comparison of validly versus invalidly cued trials, thereby delineating brain structures involved in the reorientation of attention after its initial deployment proved incorrect. All areas of activation that differentiated between these two trial types resulted from greater activity during the invalid trials. This outcome suggests that all brain areas involved in attentional orienting and task performance in response to valid cues are also involved on invalid trials. During invalid trials, additional brain regions are recruited when a perceiver recovers from invalid cueing and reorients attention to a target appearing at an uncued location. Activated brain areas specific to attentional reorientation were strongly right-lateralized and included posterior temporal and inferior parietal regions previously implicated in visual attention processes, as well as prefrontal regions that likely subserve control processes, particularly related to inhibition of inappropriate responding.


Structural characteristics of Tla products.
Biochemical study of thymus leukemia antigen (TL) from thymocytes of various Tla genotypes and from leukemia cells revealed features that, given present evidence, are peculiar to TL among class I products of the H-2:Qa:Tla region of chromosome 17. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of TL from thymocytes of all TL+ mouse strains, precipitated by anti-TL antiserum or monoclonal antibodies, showed two closely migrating bands of equal intensity in the heavy (H) chain position (45-50,000 mol wt). Comparison of these two bands by two-dimensional isoelectric focusing (2D IEF)-SDS-PAGE and 2D chymotryptic peptide mapping showed no differences indicative of protein dissimilarity. Thus, the two components of the H chain doublet may differ only in a feature of glycosylation that does not affect charge. The two leukemias studied gave only a single band in the H chain position. On 2D peptide mapping and 2D IEF-SDS-PAGE, the patterns for TL of Tlaa and Tlae thymocytes, which are closely related serologically, were broadly similar, but clearly different from the pattern typical of Tlac and Tlad thymocytes. 2D peptide maps of TL from Tlaa thymocytes and Tlaa leukemia cells did not differ. Leukemia cells of Tlab origin (thymocytes TL-) gave 2D peptide and 2D IEF-SDS-PAGE patterns of a third type. With the exception of Tlaa, thymocytes of TL+ mice yielded additional TL products of higher molecular weight than the TL H chain.


The effect of white tea on serum TNF-α/NF-κB and immunohistochemical parameters in cisplatin-related renal dysfunction in female rats.
Nephrotoxicity is the most important side effect of the antineoplastic drug cisplatin, thereby restricting its use. The aim of this study was to investigate the protective effects of white tea infusions (WT) against renal damage induced by cisplatin (CP) in rats by biochemical and histopathological means. This study used 24 female Sprague Dawley rats at 12-14 weeks of age and weighing 250-300 g. Rats were divided into three groups: Control, CP and CP + WT groups. CP was injected 7 mg/kg i.p as a single dose/rat in the CP group. White tea was given at a dose of 0.5% (w/v) for 4 weeks. At the end of the experiment, blood urea nitrogen (BUN), creatinine, uric acid, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nuclear factor kappa B (NF-κB) along with caspase-3 in the kidney were evaluated in study. BUN, creatinine, TNF-α, NF-κB and IL-6 levels of the CP group showed a statisically significant increase in comparison to the control group. TNF-α, NF-κB and IL-6 levels showed a statistically significant decrease in the CP + WT group with respect to the CP group. Caspase-3 levels in tubular epithelial cells decreased in CP + WT group compared with CP group (p = 0.02). White tea infusions reduced significantly the nephrotoxicity of CP. The anti-nephrotoxic feature of the infusion may be attributed primarily to its anti-inflammatory and anti-apoptotic characteristics.


Acoustic devices for particle and cell manipulation and sensing.
An emerging demand for the precise manipulation of cells and particles for applications in cell biology and analytical chemistry has driven rapid development of ultrasonic manipulation technology. Compared to the other manipulation technologies, such as magnetic tweezing, dielectrophoresis and optical tweezing, ultrasonic manipulation has shown potential in a variety of applications, with its advantages of versatile, inexpensive and easy integration into microfluidic systems, maintenance of cell viability, and generation of sufficient forces to handle particles, cells and their agglomerates. This article briefly reviews current practice and reports our development of various ultrasonic standing wave manipulation devices, including simple devices integrated with high frequency (>20 MHz) ultrasonic transducers for the investigation of biological cells and complex ultrasonic transducer array systems to explore the feasibility of electronically controlled 2-D and 3-D manipulation. Piezoelectric and passive materials, fabrication techniques, characterization methods and possible applications are discussed. The behavior and performance of the devices have been investigated and predicted with computer simulations, and verified experimentally. Issues met during development are highlighted and discussed. To assist long term practical adoption, approaches to low-cost, wafer level batch-production and commercialization potential are also addressed.


Surgery and neurodevelopmental outcome of very low-birth-weight infants.
Reduced death and neurodevelopmental impairment among infants is a goal of perinatal medicine. To assess the association between surgery during the initial hospitalization and death or neurodevelopmental impairment of very low-birth-weight infants. A retrospective cohort analysis was conducted of patients enrolled in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database from 1998 through 2009 and evaluated at 18 to 22 months' corrected age. Twenty-two academic neonatal intensive care units participated. Inclusion criteria were birth weight 401 to 1500 g, survival to 12 hours, and availability for follow-up. A total of 12 111 infants were included in analyses. Surgical procedures; surgery also was classified by expected anesthesia type as major (general anesthesia) or minor (nongeneral anesthesia). Multivariable logistic regression analyses planned a priori were performed for the primary outcome of death or neurodevelopmental impairment and for the secondary outcome of neurodevelopmental impairment among survivors. Multivariable linear regression analyses were performed as planned for the adjusted mean scores of the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development, Second Edition, for patients born before 2006. A total of 2186 infants underwent major surgery, 784 had minor surgery, and 9141 infants did not undergo surgery. The risk-adjusted odds ratio of death or neurodevelopmental impairment for all surgery patients compared with those who had no surgery was 1.29 (95% CI, 1.08-1.55). For patients who had major surgery compared with those who had no surgery, the risk-adjusted odds ratio of death or neurodevelopmental impairment was 1.52 (95% CI, 1.24-1.87). Patients classified as having minor surgery had no increased adjusted risk. Among survivors who had major surgery compared with those who had no surgery, the adjusted risk of neurodevelopmental impairment was greater and the adjusted mean Bayley scores were lower. Major surgery in very low-birth-weight infants is independently associated with a greater than 50% increased risk of death or neurodevelopmental impairment and of neurodevelopmental impairment at 18 to 22 months' corrected age. The role of general anesthesia is implicated but remains unproven.


Rotational quenching of H2O by He: mixed quantum/classical theory and comparison with quantum results.
The mixed quantum/classical theory (MQCT) formulated in the space-fixed reference frame is used to compute quenching cross sections of several rotationally excited states of water molecule by impact of He atom in a broad range of collision energies, and is tested against the full-quantum calculations on the same potential energy surface. In current implementation of MQCT method, there are two major sources of errors: one affects results at energies below 10 cm(-1), while the other shows up at energies above 500 cm(-1). Namely, when the collision energy E is below the state-to-state transition energy ΔE the MQCT method becomes less accurate due to its intrinsic classical approximation, although employment of the average-velocity principle (scaling of collision energy in order to satisfy microscopic reversibility) helps dramatically. At higher energies, MQCT is expected to be accurate but in current implementation, in order to make calculations computationally affordable, we had to cut off the basis set size. This can be avoided by using a more efficient body-fixed formulation of MQCT. Overall, the errors of MQCT method are within 20% of the full-quantum results almost everywhere through four-orders-of-magnitude range of collision energies, except near resonances, where the errors are somewhat larger.


Gender differences in postural stability among children.
This study aimed to examine the gender differences in postural stability among 8-12 year-old children. Twenty-six children participated in this repeated measures study to measure the centre of pressure (COP) under one normal condition ( hard surface, eyes open, and looking straight ahead) and two challenging sensory conditions (ECHB: eyes closed and head back; and EOCS: eyes open and compliant surface) in randomized order. Girls had significantly lower COP path velocity (COP-PV, p < 0.05, medium effect), smaller radial displacement (COP-RD, p < 0.05, medium effect), and lower area velocity (COP-AV, p < 0.05, medium effect) as compared to boys when the three conditions were pooled. Gender differences were found in the percentage changes in COP-RD during ECHB (p < 0.05, large effect) and EOCS (p < 0.05, medium effect), and in COP-AV during both ECHB and EOCS conditions (p < 0.05, medium effect). Postural stability performance of girls had higher correlations with age (-0.62 vs. -0.40), body mass (-0.60 vs. -0.42), foot length (-0.68 vs. -0.45), and physical activity level (-0.45 vs. 0.02), as compared to boys. Girls had better postural stability than boys but were more affected by altered sensory input information. Girls are more capable of integrating their sensory inputs, whereas boys treat each sensory input somewhat separately and rely more on somatosensory feedback. Exercises such as standing on unstable surfaces with eyes open instead of eye closed and head back are more beneficial to children's postural stability control system.