Transforming systems of consumption and production for achieving the sustainable development goals: moving beyond efficiency.
The United Nations formulated the sustainable development goals (SDGs) in 2015 as a comprehensive global policy framework for addressing the most pressing social and environmental challenges currently facing humanity. In this paper, we analyse SDG 12, which aims to "ensure sustainable consumption and production patterns." Despite long-standing political recognition of this objective, and ample scientific evidence both on its importance and on the efficacy of various ways of promoting it, the SDGs do not provide clear goals or effective guidance on how to accomplish this urgently needed transformation. Drawing from the growing body of research on sustainable consumption and production (SCP), the paper identifies two dominant vantage points-one focused on promoting more efficient production methods and products (mainly through technological improvement and informed consumer choice) and the other stressing the need to consider also overall volumes of consumption, distributional issues, and related social and institutional changes. We label these two approaches efficiency and systemic. Research shows that while the efficiency approach contains essential elements of a transition to sustainability, it is by itself highly unlikely to bring about sustainable outcomes. Concomitantly, research also finds that volumes of consumption and production are closely associated with environmental impacts, indicating a need to curtail these volumes in ways that safeguard social sustainability, which is unlikely to be possible without a restructuring of existing socioeconomic arrangements. Analysing how these two perspectives are reflected in the SDGs framework, we find that in its current conception, it mainly relies on the efficiency approach. On the basis of this assessment, we conclude that the SDGs represent a partial and inadequate conceptualisation of SCP which will hamper implementation. Based on this determination, this paper provides some suggestions on how governments and other actors involved in SDGs operationalisation could more effectively pursue SCP from a systemic standpoint and use the transformation of systems of consumption and production as a lever for achieving multiple sustainability objectives.


[Plasmoblastic lymphoma initially recognized as ovarian tumor].
Plasmablastic lymphoma is an uncommon B-cell lymphoma representing <3% of all non-Hodgkin lymphoma associated with human immunodeficiency virus infection. It displays a distinctive affinity for extranodal presentation in the oral cavity. The case of a plasmablastic lymphoma present in the ovary, cervix and soft thigh tissues of a 27-year-old woman with human immunodeficiency infection is reported.


Investigations of anticholinestrase and antioxidant potentials of methanolic extract, subsequent fractions, crude saponins and flavonoids isolated from Isodon rugosus.
Based on the ethnomedicinal uses and the effective outcomes of natural products in various diseases, this study was designed to evaluate Isodon rugosus as possible remedy in oxidative stress, alzheimer's and other neurodegenerative diseases. Acetylecholinestrase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of crude methanolic extract (Ir.Cr), resultant fractions (n-hexane (Ir.Hex), chloroform (Ir.Cf), ethyl acetate (Ir.EtAc), aqueous (Ir.Aq)), flavonoids (Ir.Flv) and crude saponins (Ir.Sp) of I. rugosus were investigated using Ellman's spectrophotometric method. Antioxidant potential of I. rugosus was determined using DPPH, H2O2 and ABTS free radicals scavenging assays. Total phenolic and flavonoids contents of plant extracts were determined and expressed in mg GAE/g dry weight and mg RTE/g of dry sample respectively. Among different fractions Ir.Flv and Ir.Cf exhibited highest inhibitory activity against AChE (87.44 ± 0.51, 83.73 ± 0.64%) and BChE (82.53 ± 0.71, 88.55 ± 0.77%) enzymes at 1 mg/ml with IC50 values of 45, 50 for AChE and 40, 70 μg/ml for BChE respectively. Activity of these fractions were comparable to galanthamine causing 96.00 ± 0.30 and 88.61 ± 0.43% inhibition of AChE and BChE at 1 mg/ml concentration with IC50 values of 20 and 47 μg/ml respectively. In antioxidant assays, Ir.Flv, Ir.Cf, and Ir.EtAc demonstrated highest radicals scavenging activities in DPPH and H2O2 assays which were comparable to ascorbic acid. Ir.Flv was found most potent with IC50 of 19 and 24 μg/ml against DPPH and H2O2 radicals respectively. Whereas antioxidant activates of plant samples against ABTS free radicals was moderate. Ir.Cf, Ir.EtAc and Ir.Cr showed high phenolic and flavonoid contents and concentrations of these compounds in different fractions correlated well to their antioxidant and anticholinestrase activities. It may be inferred from the current investigations that the Ir.Sp, Ir.Flv and various fractions of I. rugosus are good sources of anticholinesterase and antioxidant compounds. Different fractions can be subjected to activity guided isolation of bioactive compounds effective in neurological disorders.


Sensors, controls, and man-machine interface for advanced teleoperation.
Some advances have been made in teleoperator technology through the introduction of various sensors, computers, automation, and new man-machine interface devices and techniques for remote manipulator control. The development of dexterous articulated mechanisms, smart sensors, flexible computer controls, intelligent man-machine interfaces, and innovative system designs for advanced teleoperation is, however, far from complete, and poses many interdisciplinary challenges. This article summarizes the state of the art, gives a brief outline of the basic problems, and presents the results of teleoperator research and development at the Jet Propulsion Laboratory.


Tissue accumulation and species-specific metabolism of technical pentabrominated diphenyl ether (DE-71) in two predator fish.
The tissue-specific accumulation and species-specific metabolism of polybrominated diphenyl ethers (PBDEs) in two predator fish species (redtail catfish and oscar fish) feeding on the same prey (tiger barb) that was exposed to technical pentabrominated diphenyl ether (DE-71) in the laboratory were investigated. The trends in the wet-weight tissue concentration of PBDEs in two predatory fish species suggested that the tissue distribution of PBDEs occurs through a series of events involving passive diffusion to the lipid compartment. A comparison of the fugacities of PBDEs in various tissues and in the serum revealed that the liver, gill, and perivisceral adipose tissue readily achieved equilibrium with the serum, but the muscle, kidney, and intestine exhibited the potential to accumulate PBDEs. The lower fugacities of PBDEs in the intestine may have significance in the transportation of PBDEs from prey to predatory fish. No tissue-specific differences in PBDE congener profiles were found, while interspecies differences in PBDE profiles were evident. The difference in profiles between two species could be attributed to species-specific debromination of PBDE. No metabolic debromination of PBDE was observed in redtail catfish, but extensive debromination of PBDEs occurred in oscar fish. Several hydroxylated PBDEs (OH-PBDEs) were detected in serum samples from the two fish species, but no methoxylated PBDEs were found. The similarities in the OH-PBDE congener profile and the ratio of OH-PBDEs to total PBDEs between the two fish species indicated that the hydroxylation of PBDEs might not be species-specific.


Is thin in everywhere?: A cross-cultural comparison of a subsection of Tripartite Influence Model in Australia and Malaysia.
Despite growing research investigating prevalence rates of BD among Malaysian women, there has been limited research conducted in Malaysia with respect to factors contributing to its development and consequences. This study tested a subsection of the Tripartite Influence Model, investigating whether sociocultural influences (family, peers, media) lead to thin ideal internalization, which in turn lead to body dissatisfaction (BD) and subsequently restrained eating and bulimic behaviours in both Australian and Malaysian women. Participants were 421 Australian and 399 Malaysian female emerging adults aged between 18 and 25 years, (M = 20.76; SD = 2.86) who completed questionnaires assessing sociocultural influences, thin ideal internalization, body dissatisfaction, restrained eating and bulimic behaviours. The model, largely supported in both cultures, had two points of difference. For Malaysian but not Australian women, family influence was significantly linked with internalization of the thin ideal. Although BD was significantly linked with restrained eating as predicted for Australian women (albeit rather weakly), it was not significantly linked with restrained eating for Malaysian women. The striking similarity of results across both cultures, suggests that Western body ideals, with their corresponding negative sequelae, have infiltrated the collectivist and developing nation of Malaysia.


Human In Situ Study of the effect of Bis(2-Methacryloyloxyethyl) Dimethylammonium Bromide Immobilized in Dental Composite on Controlling Mature Cariogenic Biofilm.
Cariogenic oral biofilms cause recurrent dental caries around composite restorations, resulting in unprosperous oral health and expensive restorative treatment. Quaternary ammonium monomers that can be copolymerized with dental resin systems have been explored for the modulation of dental plaque biofilm growth over dental composite surfaces. Here, for the first time, we investigated the effect of bis(2-methacryloyloxyethyl) dimethylammonium bromide (QADM) on human overlying mature oral biofilms grown intra-orally in human participants for 7⁻14 days. Seventeen volunteers wore palatal devices containing composite specimens containing 10% by mass of QADM or a control composite without QADM. After 7 and 14 days, the adherent biofilms were collected to determine bacterial counts via colony-forming unit (CFU) counts. Biofilm viability, chronological changes, and percentage coverage were also determined through live/dead staining. QADM composites caused a significant inhibition of Streptococcus mutans biofilm formation for up to seven days. No difference in the CFU values were found for the 14-day period. Our findings suggest that: (1) QADM composites were successful in inhibiting 1⁻3-day biofilms in the oral environment in vivo; (2) QADM significantly reduced the portion of the S. mutans group; and (3) stronger antibiofilm activity is required for the control of mature long-term cariogenic biofilms. Contact-killing strategies using dental materials aimed at preventing or at least reducing high numbers of cariogenic bacteria seem to be a promising approach in patients at high risk of the recurrence of dental caries around composites.


Silk fibroin peptide suppresses proliferation and induces apoptosis and cell cycle arrest in human lung cancer cells.
Silkworm cocoon was recorded to cure carbuncle in the Compendium of Materia Medica. Previous studies have demonstrated that the supplemental silk protein sericin exhibits anticancer activity. In the present study, we investigated the effects of silk fibroin peptide (SFP) extracted from silkworm cocoons against human lung cancer cells in vitro and in vivo and its possible anticancer mechanisms. SFP that we prepared had high content of glycine (~ 30%) and showed a molecular weight of ~ 10 kDa. Intragastric administration of SFP (30 g/kg/d) for 14 days did not affect the weights, vital signs, routine blood indices, and blood biochemical parameters in mice. MTT assay showed that SFP dose-dependently inhibited the growth of human lung cancer A549 and H460 cells in vitro with IC50 values of 9.921 and 9.083 mg/mL, respectively. SFP also dose-dependently suppressed the clonogenic activity of the two cell lines. In lung cancer H460 xenograft mice, intraperitoneal injection of SFP (200 or 500 mg/kg/d) for 40 days significantly suppressed the tumor growth, but did not induce significant changes in the body weight. We further examined the effects of SFP on cell cycle and apoptosis in H460 cells using flow cytometry, which revealed that SFP-induced cell cycle arrest at the S phase, and then promoted cell apoptosis. We demonstrated that SFP (20-50 mg/mL) dose-dependently downregulates Bcl-2 protein expression and upregulates Bax protein in H460 cells during cell apoptosis. The results suggest that SFP should be studied further as a novel therapeutic agent for the treatment of lung cancer.


Cytoprotective effects of ginsenoside Rd on apoptosis-associated cell death in the isolated human pancreatic islets.
Ginsenoside Rd (GS-Rd), one of the main pharmacologically active components of ginseng, has shown the potential to stabilize mitochondrial membrane integrity and decrease apoptotic death in neuronal and non-neuronal cells. The present study aimed to evaluate the effect of this bioactive molecule on the apoptosis-associated cell death in human pancreatic islets. In this regard human pancreatic islets were isolated and grouped for the treatment with GS-Rd. The isolated islets were treated with different concentrations of GS-Rd. After 24 and 72 h of incubation, the islets were evaluated in terms of viability, BAX, BCL2, and insulin gene expression, BAX, BCL2, and caspase-3 protein expression, apoptosis, and glucose-induced insulin/C-peptide secretion. Our results revealed the islet survival was significantly decreased in the control group after 72 h of incubation. However, GS-Rd inhibited the progress of the islet death in the treated groups. TUNEL staining revealed that the preventive effect of this molecule was caused by the inhibition of apoptosis-associated death. In this regard, the activation of caspase-3 was down-regulated in the presence of GS-Rd. GS-Rd did not exhibit undesirable effects on glucose-induced insulin and C-peptide stimulation secretion. In conclusion, GS-Rd inhibited the progress of death of cultured human pancreatic islets by diminishing the apoptosis of the islet cells.


Does Obtaining a Diagnosis of Interstitial Cystitis/Bladder Pain Syndrome Improve Symptoms or Quality of Life? A Cross-sectional Questionnaire-Based Study.
The aim of this study was to investigate whether receiving a clinical diagnosis of interstitial cystitis (IC) or bladder pain syndrome (BPS) improves patients' symptoms, health-related quality of life (HRQOL), or ability to cope with their symptoms. In this cross-sectional study, participants with self-reported IC/BPS completed an online questionnaire recalling their perceived change in symptoms after diagnosis and treatment. The questionnaire included demographic information, overall HRQOL measured on a visual analog scale (VAS), O'Leary-Sant Interstitial Cystitis Problem Index, the Urinary Impact Questionnaire, and questions regarding patient beliefs about diagnosis. HRQOL and symptom impact scales were compared before and after diagnosis and treatment. Demographic data, symptom data, and beliefs were examined for correlation with improvement in quality of life after diagnosis. A total of 1052 participants initiated the survey and were included in the analysis; most of them identified as female, non-Hispanic, and white (90%). Before symptom onset, median VAS HRQOL score was 87 (interquartile range [IQR], 77-95). Median scores nadired at 34 (IQR, 20-59) after symptom onset before diagnosis, but improved to 61 after diagnosis and treatment (IQR, 38-74; all P < 0.001). Scores remained stable after diagnosis and initiation of treatment with a median score of 65 at the time of survey (IQR, 37-80; P > 0.05). Age, insurance type, and improvement in scores on the symptom impact scale predicted improvement in HRQOL after diagnosis and treatment in the multivariable model. Participants reported improvements on global and symptom-specific quality of life measures after diagnosis and treatment for IC/BPS.


Mercury and trace element distribution in organic tissues and regional brain of fetal rat after in utero and weaning exposure to low dose of inorganic mercury.
Since it is still absent data about the toxic risk of low dose, especially an environmentally relevant dose of mercury to fetus after their prenatal exposure, this present work was designed to investigate the metabolism of Hg and its effect on the levels of essential trace elements in the organic tissues and the brain regions of infant rats after their exposure to environmentally relevant low dose of Hg(II) during the whole pregnant and weaning period. The pregnant female rats were exposed to a very low dose of 0.2 microg Hg2+/ml (as HgCl2, 12 rats/group) in drinking water from prenatal day 0 continued to postnatal day 20. The contents of Hg and other elements (Cu, K, Mg, Mn, Na, Ca, Co, Fe, Se and Zn) in the liver, kidney, heart, spleen, pancreas and the brain regions (cerebrum, cerebellum, brain stem, hippocampus, thalamus and the remains) of the maternal and their infant rats were determined. The highest Hg contents were found in kidney of both maternal and infant rats. Considering the percentage of Hg accumulation, approximately 52.7%, 38.7%, and 1.66% were found in kidney, liver and brain for maternal rats, respectively, while 23.7%, 48.9% and 15.6% for infant rats. The important findings in this work were that the low dose of inorganic mercury appeared to accumulate in the brain of offspring and more Hg was present in infant brain than in their mother. As in the brain regions, the highest Hg content was present in infant hippocampus and cerebellum, whereas the Hg contents in maternal brains varied not so much. The imbalances of Fe/Cu, Cu/Zn, Zn/Se mass ratios and the molar ratios of Hg over other elements in the Hg-exposed rats were observed.


Multi-photon excited luminescence of magnetic FePt core-shell nanoparticles.
We present magnetic FePt nanoparticles with a hydrophilic, inert, and biocompatible silico-tungsten oxide shell. The particles can be functionalized, optically detected, and optically manipulated. To show the functionalization the fluorescent dye NOPS was bound to the FePt core-shell nanoparticles with propyl-triethoxy-silane linkers and fluorescence of the labeled particles were observed in ethanol (EtOH). In aqueous dispersion the NOPS fluorescence is quenched making them invisible using 1-photon excitation. However, we observe bright luminescence of labeled and even unlabeled magnetic core-shell nanoparticles with multi-photon excitation. Luminescence can be detected in the near ultraviolet and the full visible spectral range by near infrared multi-photon excitation. For optical manipulation, we were able to drag clusters of particles, and maybe also single particles, by a focused laser beam that acts as optical tweezers by inducing an electric dipole in the insulated metal nanoparticles. In a first application, we show that the luminescence of the core-shell nanoparticles is bright enough for in vivo multi-photon imaging in the mouse neocortex down to cortical layer 5.


Role of cholera toxin in enteric colonization by Vibrio cholerae O1 in rabbits.
The role of cholera toxin (CT) in mucosal colonization by Vibrio cholerae O1 was studied in rabbits by using toxinogenic V. cholerae and nontoxinogenic (A-B+ or A-B-) recombinant mutants derived from them. After oral inoculation, toxinogenic strains colonized intestinal mucosa significantly more efficiently than did either A-B- or A-B+ mutants; average colonization was increased 1.5- to 30-fold with toxinogenic strains, depending on the inoculum used and the portion of intestine studied. Additionally, colonization by an A-B- mutant was increased to the levels of its toxinogenic parent by coadministration of CT with the inoculum. We conclude that CT contributes significantly to mucosal colonization by V. cholerae and that this effect is not due to an interaction of the CT B subunit with its mucosal receptor. The possibility that this effect contributes to the in vivo selection of hypertoxinogenic variants of V. cholerae is considered.


R-Type Fonticins Produced by Pragia fontium Form Large Pores with High Conductance.
Fonticins are phage tail-like bacteriocins produced by the Gram-negative bacterium Pragia fontium from the family Budviciaceae. This bacterium produces contractile-type particles that adsorb on the surface of sensitive bacteria and penetrate the cell wall, probably during contraction, in a way similar to the type VI secretion system. We characterized the pore-forming activity of fonticins using both living cells and in vitro model membranes. Using a potassium leakage assay, we show that fonticins are able to permeabilize sensitive cells. On black lipid membranes, single-pore conductance is about 0.78 nS in 1 M NaCl and appears to be linearly dependent on the increasing molar strength of NaCl solution, which is a property of considerably large pores. In agreement with these findings, fonticins are not ion selective for Na+, K+, and Cl-. Polyethylene glycol 3350 (PEG 3350) molecules of about 3.5 nm in diameter can enter the fonticin pore lumen, whereas the larger molecules cannot pass the pore. The size of fonticin pores was confirmed by transmission electron microscopy. The terminal membrane-piercing complex of the fonticin tube probably creates a selective barrier restricting passage of macromolecules. IMPORTANCE Phage tail-like bacteriocins are now the subject of research as potent antibacterial agents due to their narrow host specificity and single-hit mode of action. In this work, we focused on the structure and mode of action of fonticins. According to some theories, related particles were initially adapted for passage of double-stranded DNA (dsDNA) molecules, but fonticins changed their function during the evolution; they are able to form large pores through the bacterial envelope of Gram-negative bacteria. As various pore-forming proteins are extensively used for nanopore sequencing and stochastic sensing, we decided to investigate the pore-forming properties of fonticin protein complexes on artificial lipid membranes. Our research revealed remarkable structural properties of these particles that may have a potential application as a nanodevice.


Utility of a simplified ultrasound assessment to assess interstitial pulmonary fibrosis in connective tissue disorders--preliminary results.
Interstitial pulmonary fibrosis (IPF) is a frequent manifestation in patients with connective tissue disorders (CTD). Recently the ultrasound (US) criterion validity for its assessment has been proposed; however, the US scoring systems adopted include the study of several lung intercostal spaces (LIS), which could be time-consuming in daily clinical practice. The aim of this study was to investigate the utility of a simplified US B-lines scoring system compared with both the US comprehensive assessment and the high-resolution computed tomography (HRCT) findings of IPF in CTD patients. Thirty-six patients with a diagnosis of CTD were enrolled. Each patient underwent chest HRCT and lung US by an experienced radiologist and rheumatologist, respectively. Both comprehensive and simplified US B-lines assessments were scanned. The comprehensive US assessment was performed at 50 LIS level, whereas the simplified US assessment included bilaterally 14 LIS; for the anterior chest: the second LIS along the para-sternal lines, the fourth LIS along the mid-clavear, anterior axillary and mid-axillary lines; for the posterior chest: the eighth LIS along the paravertebral, sub-scapular and posterior axillary lines. For criterion validity, HRCT was considered the gold standard. Feasibility, inter and intra-observer reliability was also investigated. A highly significant correlation between comprehensive and simplified US assessment was found (P = 0.0001). A significant correlation was also found between the simplified US assessment and HRCT findings (P = 0.0006). Kappa values for the inter-observer simplified US assessment were in a range from 0.769 to 0.885, whereas the concordance correlation coefficient values for the intra-observer were from 0.856 to 0.955. There was a relevant difference in time spent on comprehensive (mean 23.3 ± SD 4.5 minutes) with respect to the simplified US assessment (mean 8.6 ± SD 1.4) (P < 0.00001). Our results provide a new working hypothesis in favor of the utility of a simplified US B-lines assessment as an adjunct method to assess IPF in patients with CTD.


Primary Candida meningitis and chronic granulomatous disease.
The occurrence of two rare entities in a single patient can be fortuitous or may signify some deeper relationship. A young boy was recently treated for primary Candida meningitis. Autopsy findings suggested to an experienced pathologist the presence of chronic granulomatous disease (CGD), unrecognized during his life. The patient's identical twin brother was tested and found to have the typical laboratory features of CGD. The literature on Candida meningitis was reviewed and 15 cases were discovered that apparently arose in the absence of recognized predisposing causes. All but one of these cases occurred in males, and most occurred during the first three decades of life. The case reports and literature review presented herein suggest that CGD should be suspected when a case of "primary" Candida meningitis is encountered.


Protecting clinical trials in cystic fibrosis during the SARS-CoV-2 pandemic: risks and mitigation measures.
The SARS-CoV-2 pandemic has disrupted clinical trials worldwide. The European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN) has tracked clinical trial disruption by surveying its 58 trial sites across 17 European countries and collated information on measures to mitigate the impact of the pandemic and ensure trial continuity. Here, we present recommendations on how to reduce the risk of SARS-CoV-2 exposure to patients and trial staff by implementing remote trial visits where possible, using home assessments, video and phone calls, electronic consent, and home delivery of study drugs. We discuss the practicalities of remote source data verification, protocol amendments, changing trial site location, and staff absences and home working. We outline recommendations on how to protect trial outcomes, including home assessments, safety reporting, protocol deviations, and recruitment challenges. Finally, we discuss the importance of continued access to study drugs via extension trials for some patients. This guidance was co-created from the shared knowledge and experience of sites in our network and was re-distributed directly to all ECFS-CTN sites to help mitigate the impact of further waves of the SARS-CoV-2 pandemic. We will also use this guidance to assist companies, academia, and consortia with future protocol design and risk mitigation plans. This guidance can be applied to clinical trials in other diseases and could help sites that are not supported by clinical trial networks.


Chlorhexidine spray versus chlorhexidine mouthwash in the control of dental plaque after periodontal surgery.
This clinical trial aimed at comparing 2 different means of delivering chlorhexidine digluconate (CHX) in the oral hygiene phase during the 2 weeks following periodontal surgery. 40 patients were randomly divided into 2 groups: A (using CHX mouthwash) and B (using CHX spray). Professional oral hygiene was carried out immediately before surgical operation. For 7 days after surgery, group A used CHX mouthwash and group B CHX spray on the teeth involved in the surgical procedure, while mechanical oral hygiene was maintained only on the teeth not involved surgically. After suture removal, on the 7th day, patients were allowed to perform mechanical oral hygiene also on surgical sites. Plaque index (PI) and stain index (SI) were evaluated on the 7th and 14th days after the operation. In both groups, PI increased similarly with respect to the baseline in surgically involved teeth, being 0.25+/-0.41 (SD) and 0.15+/-0.26, respectively, in A and B, on day 7, and 0.14+/-0.23 (A) and 0.10+/-0.22 (B), on day 14. There was no significant difference between A and B on either day 7 or 14. On the contrary, SI increased significantly in respect to the baseline over the 14 days in group A at both involved and not involved sites, while it did not differ from the baseline in group B. The present results indicate that the efficacy of CHX spray in the post-surgical control of dental plaque is not different from that of CHX mouthwash. Tooth staining, on the contrary, was significantly lower in the group using CHX spray. The observed effects might be related to the way of delivering CHX and to the total dose administered, about 80% lower in group B in respect to A. Further studies are needed to validate the preliminary findings of the present study.


Neighborhood built environment and physical activity of Japanese older adults: results from the Aichi Gerontological Evaluation Study (AGES).
Although many studies have reported the association between neighborhood built environment (BE) and physical activity (PA), less is known about the associations for older populations or in countries besides the US and Australia. The aim of this paper is to examine the associations for older adult populations in Japan. Our analyses were based on cross-sectional data from the Aichi Gerontological Evaluation Study (AGES), conducted in 2003. The respondents were older adults, aged 65 years or over (n = 9,414), from 8 municipalities across urban, suburban, and rural areas. The frequency of leisure time sports activity and total walking time were used as the outcome variables. Using geographic information systems (GIS), we measured residential density, street connectivity, number of local destinations, access to recreational spaces, and land slope of the respondents' neighborhoods, based on network distances with multiple radii (250 m, 500 m, 1,000 m). An ordinal logistic regression model was used to analyze the association between PA and BE measures. Population density and presence of parks or green spaces had positive associations with the frequency of sports activity, regardless of the selected buffer zone. The analysis of total walking time, however, showed only a few associations. Our findings provide mixed support for the association between PA and the characteristics of BE measures, previously used in Western settings. Some characteristics of the neighborhood built environment may facilitate leisure time sports activity, but not increase the total walking time for Japanese older adults.


[Research on the actual conditions of alcohol dependence, the harmful use of alcohol and the optimal treatment in gastroenterological inpatients].
The goal of the study was to examine the status, Stages of Change and motivation, alcohol dependence, and harmful use of alcohol in gastroenterological inpatients. We interviewed 141 gastroenterological inpatients and analyzed their medical charts. The interviews used the Alcohol Use Disorders Identification Test (AUDIT), CAGE questionnaire and questions pertaining to drinking behavior, diagnosis, self-awareness of drinking/alcohol dependency, physician instructions regarding abstinence, and Stages of Change. The proportion of patients who screened positive was calculated based on the AUDIT, CAGE and International Classification of Diseases (ICD)-10 alcohol dependence/harmful use criteria. Alcohol dependence was defined as a score >or= 15 on the AUDIT, and harmful use as 8-14 on the AUDIT or meeting ICD-10 criteria for harmful use. Patients with alcohol dependence or harmful use comprised the hazardous drinking group. Common disorders in this group and in patients in a non-drinking group were compared by Fisher exact test. Stages of Change were also determined in the hazardous drinking group and factors regarding motivation and Stages of Change were analyzed using logistic regression analysis. Of the 141 patients, 18 (12.8%) scored >or= 15 on the AUDIT, 19 (13.5%) scored L 2 on the CAGE, and 48 (34%) scored >or= 8 on the AUDIT. Among those who met the ICD-10 criteria, 16.3% had alcohol dependence and 17.7% exhibited harmful use of alcohol. Significantly, common disorders in the hazardous drinking group included liver disease, colonic diverticulitis, gout/hyperuricemia, and pancreatitis. Of the alcohol-dependent patients, 52% were in the Preparation stage. After the Contemplation stage, instructions to abstain from alcohol were the most significant motivational factor. Many gastroenterological inpatients exhibited alcohol dependence and about half of these patients were able to prepare for behavioral changes related to drinking. Therefore, the gastroenterological ward may help in secondary prevention of alcohol dependence and harmful use.


Molecular mechanisms of CD200 inhibition of mast cell activation.
CD200 and its receptor CD200R are both type I membrane glycoproteins that contain two Ig-like domains. Engagement of CD200R by CD200 inhibits activation of myeloid cells. Unlike the majority of immune inhibitory receptors, CD200R lacks an ITIM in the cytoplasmic domain. The molecular mechanism of CD200R inhibition of myeloid cell activation is unknown. In this study, we examined the CD200R signaling pathways that control degranulation of mouse bone marrow-derived mast cells. We found that upon ligand binding, CD200R is phosphorylated on tyrosine and subsequently binds to adapter proteins Dok1 and Dok2. Upon phosphorylation, Dok1 binds to SHIP and both Dok1 and Dok2 recruit RasGAP, which mediates the inhibition of the Ras/MAPK pathways. Activation of ERK, JNK, and p38 MAPK are all inhibited by CD200R engagement. The reduced activation of these MAPKs is responsible for the observed inhibition of mast cell degranulation and cytokine production. Similar signaling events were also observed upon CD200R engagement in mouse peritoneal cells. These data define a novel inhibitory pathway used by CD200R in modulating mast cell function and help to explain how engagement of this receptor in vivo regulates myeloid cell function.


Zinc Isotope Ratios as Indicators of Diet and Trophic Level in Arctic Marine Mammals.
Carbon and nitrogen stable isotope ratios of bone collagen are an established method for dietary reconstruction, but this method is limited by the protein preservation. Zinc (Zn) is found in bioapatite and the isotopic compositions of this element constitute a very promising dietary indicator. The extent of fractionation of Zn isotopes in marine environments, however, remains unknown. We report here on the measurement of zinc, carbon and nitrogen isotopes in 47 marine mammals from the archaeological site of Arvik in the Canadian Arctic. We undertook this study to test and demonstrate the utility of Zn isotopes in recent mammal bone minerals as a dietary indicator by comparing them to other isotopic dietary tracers. We found a correlation between δ66Zn values and trophic level for most species, with the exception of walruses, which may be caused by their large seasonal movements. δ6Zn values can therefore be used as a dietary indicator in marine ecosystems for both modern and recent mammals.


Different Occlusal Schemes in a Persistent Protruding Complete Denture Wearer.
Different types of artificial teeth and occlusal designs can be used in complete dentures. Bilateral balanced occlusion, lingualized occlusion, canine guidance, and monoplane are the main occlusal designs; however there is no agreement on which tooth arrangement is ideal for achieving success in complete dentures. This report presents an alternative for persistent involuntary protruding complete denture wearers through the use of artificial teeth with higher cusps. Due to an old and worn pair of complete dentures, the patient had the habit of protruding. New dentures were made with Biotone artificial teeth and in the trial session, the patient would still protrude. A new set was made with Premium artificial teeth, which present higher cusps. With these dentures, the involuntary protrusion did not occur. From the delivery to the follow-up sessions, the patient stopped protruding.


Genomic selection for spot blotch in bread wheat breeding panels, full-sibs and half-sibs and index-based selection for spot blotch, heading and plant height.
Genomic selection is a promising tool to select for spot blotch resistance and index-based selection can simultaneously select for spot blotch resistance, heading and plant height. A major biotic stress challenging bread wheat production in regions characterized by humid and warm weather is spot blotch caused by the fungus Bipolaris sorokiniana. Since genomic selection (GS) is a promising selection tool, we evaluated its potential for spot blotch in seven breeding panels comprising 6736 advanced lines from the International Maize and Wheat Improvement Center. Our results indicated moderately high mean genomic prediction accuracies of 0.53 and 0.40 within and across breeding panels, respectively which were on average 177.6% and 60.4% higher than the mean accuracies from fixed effects models using selected spot blotch loci. Genomic prediction was also evaluated in full-sibs and half-sibs panels and sibs were predicted with the highest mean accuracy (0.63) from a composite training population with random full-sibs and half-sibs. The mean accuracies when full-sibs were predicted from other full-sibs within families and when full-sibs panels were predicted from other half-sibs panels were 0.47 and 0.44, respectively. Comparison of GS with phenotypic selection (PS) of the top 10% of resistant lines suggested that GS could be an ideal tool to discard susceptible lines, as greater than 90% of the susceptible lines discarded by PS were also discarded by GS. We have also reported the evaluation of selection indices to simultaneously select non-late and non-tall genotypes with low spot blotch phenotypic values and genomic-estimated breeding values. Overall, this study demonstrates the potential of integrating GS and index-based selection for improving spot blotch resistance in bread wheat.


(Nitrato-κ(2) O,O')bis-[(E)-N-(pyridin-4-yl-methyl-idene-κN)hy-droxy-amine]-silver(I).
In the mononuclear title compound, [Ag(NO3)(C6H6N2O)2], the Ag(I) atom is located on a twofold rotation axis and the nitrate-chelated Ag(I) atom is further coordinated by two aromatic N atoms of hydroxyl-amine ligands in a distorted tetra-hedral geometry. In the crystal, the nitrate ion has 2 symmetry with the N atom and one O atom located on the twofold rotation axis, and is linked to hy-droxy groups of the hydroxyl-amine ligands by O-H⋯O hydrogen bonds, generating a chain running along the b axis.


[The analytical reliability of clinical laboratory information and role of the standards in its support].
The article deals with the factors impacting the reliability of clinical laboratory information. The differences of qualities of laboratory analysis tools produced by various manufacturers are discussed. These characteristics are the causes of discrepancy of the results of laboratory analyses of the same analite. The role of the reference system in supporting the comparability of laboratory analysis results is demonstrated. The project of national standard is presented to regulate the requirements to standards and calibrators for analysis of qualitative and non-metrical characteristics of components of biomaterials.


Psychological assessment of patients with temporomandibular disorders: confirmatory analysis of the dimensional structure of the Brief Symptoms Inventory 18.
This article analyzes the psychometric and structural properties of the Brief Symptoms Inventory 18 in a sample of patients with temporomandibular disorders (TMDs), given the convenience of a brief evaluation of distress in these patients. Confirmatory factor analysis was carried out in a sample of 114 patients with TMDs. Two models were tested: the theoretical model with the original structure proposed--which considers three dimensions--and the empirical model obtained through the exploratory factor analysis initially carried out by Leonard R. Derogatis--which consists of the four-factor structure. Both models reached satisfactory indexes in confirmatory factor analysis. Empirical and theoretical reasons led us to prefer the original proposal of three dimensions: somatization, depression and anxiety, and general distress. The Brief Symptoms Inventory 18 has been demonstrated to be a reliable and valid tool for the assessment of distress in patients with TMDs, with the advantage of its simplicity and ease of application.


Use of massively multiple merged data for low-resolution S-SAD phasing and refinement of flavivirus NS1.
An emergent challenge in macromolecular crystallography is the identification of the substructure from native anomalous scatterers in crystals that diffract to low to moderate resolution. Increasing the multiplicity of data sets has been shown to make previously intractable phasing problems solvable and to increase the useful resolution in model refinement. For the West Nile virus nonstructural protein 1 (NS1), a protein of novel fold, the utility of exceptionally high multiplicity data is demonstrated both in solving the crystal structure from the anomalous scattering of the native S atoms and in extending the useful limits of resolution during refinement. A high-multiplicity data set from 18 crystals had sufficient anomalous signal to identify sulfur sites using data to 5.2 Å resolution. Phases calculated to 4.5 Å resolution and extended to 3.0 Å resolution were of sufficient quality for automated building of three-quarters of the final structure. Crystallographic refinement to 2.9 Å resolution proceeded smoothly, justifying the increase in resolution that was made possible by combining multiple data sets. The identification and exclusion of data from outlier crystals is shown to result in more robust substructure determination.


Changing the law, changing the culture: rethinking the "sleepy resident" problem.
Ms. Whetsell examines the Bell Regulations, which limit New York's hospital residents' work hours and require increased supervision from senior doctors, in light of the currently pending federal bill that seeks to do the same. The article argues that the federal government should draw lessons from the New York experience before proceeding with similar guidelines. The article notes that many roadblocks have prevented successful implementation of the New York policy, including a long-standing tradition of "hazing" first-year residents with long, unsupervised hours; medical community resistance to the notion of residents' sleep deprivation and dislike of government interference; and a general fear within the medical community of increased medical malpractice liability and other indicia of "blame culture." The Article concludes that the most effective approach to patient safety related to residency sleep deprivation should work within hospital culture, not against it. The proposed alternative approach would encourage patient safety strategies that value teamwork and cross-discipline collaboration, and consequently result in greater satisfaction for residents, hospitals, and patients.


Boron-based inhibitors of acyl protein thioesterases 1 and 2.
Ras proteins are of importance in cell proliferation, and hence their mutated forms play causative roles in many kinds of cancer in different tissues. Inhibition of the Ras-depalmitoylating enzyme acyl protein thioesterases APT1 and -2 is a new approach to modulating the Ras cycle. Here we present boronic and borinic acid derivatives as a new class of potent and nontoxic APT inhibitors. These compounds were detected by extensive library screening using chemical arrays and turned out to inhibit human APT1 and -2 in a competitive mode. Furthermore, one of the molecules was demonstrated to inhibit Erk1/2 phosphorylation significantly.


A phosphatidylinositol 3-kinase inhibitor induces a senescent-like growth arrest in human diploid fibroblasts.
The signal transduction cascade initiated by the activation of phosphoinositide 3-kinase (PI-3 kinase) is implicated in mitogenic and antiapoptotic signaling generated by growth factors in a variety of cell types. We have examined the consequences of an inhibition of this pathway in human diploid fibroblasts. We find that a specific PI-3 kinase inhibitor (LY294002) causes growth arrest in these cells accompanied by changes in gene expression that are similar to those seen during cellular senescence. A second inhibitor, PD58029, which is specific for the mitogen-activated protein kinase kinase 1 (MEK-1), also induces a growth arrest but does not induce the same spectrum of gene expression. The pattern of gene expression in the presence the MEK-1 inhibitor is similar to that seen during growth arrest induced by serum starvation. The specific phenotypic changes seen following inhibition of PI-3 kinase are: an increase in beta-galactosidase activity; a decrease in EPC-1 gene expression; and a dramatic increase in collagenase gene expression. Thus, growth arrest with a PI-3 kinase inhibitor induces a senescent-like phenotype that is not seen when cells are growth arrested by either serum starvation or a MEK-1 inhibitor.


Causes of death among people with myelomeningocele: A multi-institutional 47-year retrospective study.
This study aimed to analyze organ system-based causes and non-organ system-based mechanisms of death (COD, MOD) in people with myelomeningocele (MMC), comparing urological to other COD. A retrospective review was performed of 16 institutions in Canada/United States of non-random convenience sample of people with MMC (born > = 1972) using non-parametric statistics. Of 293 deaths (89% shunted hydrocephalus), 12% occurred in infancy, 35% in childhood, and 53% in adulthood (documented COD: 74%). For 261 shunted individuals, leading COD were neurological (21%) and pulmonary (17%), and leading MOD were infections (34%, including shunt infections: 4%) and non-infectious shunt malfunctions (14%). For 32 unshunted individuals, leading COD were pulmonary (34%) and cardiovascular (13%), and leading MOD were infections (38%) and non-infectious pulmonary (16%). COD and MOD varied by shunt status and age (p < = 0.04), not ambulation or birthyear (p > = 0.16). Urology-related deaths (urosepsis, renal failure, hematuria, bladder perforation/cancer: 10%) were more likely in females (p = 0.01), independent of age, shunt, or ambulatory status (p > = 0.40). COD/MOD were independent of bladder augmentation (p= >0.11). Unexplained deaths while asleep (4%) were independent of age, shunt status, and epilepsy (p >= 0.47). COD varied by shunt status. Leading MOD were infectious. Urology-related deaths (10%) were independent of shunt status; 26% of COD were unknown. Life-long multidisciplinary care and accurate mortality documentation are needed.


Whole-body kinematic and dynamic response of restrained PMHS in frontal sled tests.
The literature contains a wide range of response data describing the biomechanics of isolated body regions. Current data for the validation of frontal anthropomorphic test devices and human body computational models lack, however, a detailed description of the whole-body response to loading with contemporary restraints in automobile crashes. This study presents data from 14 frontal sled tests describing the physical response of postmortem human surrogates (PMHS) in the following frontal crash environments: A) (5 tests) driver position, force-limited 3-point belt plus airbag restraint (FLB+AB), 48 km/h deltaV. B) (3 tests) passenger position, FLB+AB restraint, 48 km/h deltaV. C) (3 tests) passenger position, standard (not force-limited) 3-point belt plus air bag restraint (SB+AB), 48 km/h deltaV. D) (3 tests) passenger position, standard 3-point belt restraint (SB), 29 km/h deltaV. Reported data include x-axis and z-axis (SAE occupant reference frame) accelerations of the head, spine (upper, middle, and lower), and pelvis; rate of angular rotation of the head about y-axis; displacements of the head, upper spine, pelvis and knee relative to the vehicle buck; and deformation contours of the upper and lower chest. A variety of kinematic trends are identified across the different test conditions, including a decrease in head and thorax excursion and a change in the nature of the excursion in the driver position compared to the passenger position. Despite this increase in forward excursion when compared to the driver's side FLB+AB tests, the passenger's side FLB+AB tests resulted in greater peak thoracic (T8) x-axis accelerations (passenger's side -29 g; driver's side -22 g;) and comparable maximum chest deflection (passenger's side - 23+/-3.1% of the undeformed chest depth; driver's side - 23+/-5.6%; ). In the 48 km/h passenger's side tests, the head excursion associated with the force-limiting belt system was approximately 15% greater than that for a standard belt system in tests that were otherwise identical. This was accompanied by a decrease in chest deflection of approximately 20% with the force-limiting system. Despite the decrease in test speed, the 29 km/h passenger's side tests with standard (not force-limiting) 3-point belt restraints resulted in maximum chest deflection (16+/-5.6% average) comparable to that observed in the 48 km/h, FLB+AB, driver's side tests (21+/-3.1% average). Finally, forward head excursion was slightly higher in the 29 km/h passenger's side tests (33+/-1.1 cm average) than in the 48 km/h driver's side tests (27+/-3.7 cm average), and was lower than that in the 48 km/h FLB+AB (58+/-4.4 cm average) and SB+AB (46+/-2.1 cm average) passenger's side tests.


A prospective, double-blind, randomized, controlled clinical trial comparing standard wound care with adjunctive hyperbaric oxygen therapy (HBOT) to standard wound care only for the treatment of chronic, non-healing ulcers of the lower limb in patients with diabetes mellitus: a study protocol.
It has been suggested that the use of adjunctive hyperbaric oxygen therapy improves the healing of diabetic foot ulcers, and decreases the risk of lower extremity amputations. A limited number of studies have used a double blind approach to evaluate the efficacy of hyperbaric oxygen therapy in the treatment of diabetic ulcers. The primary aim of this study is to assess the efficacy of hyperbaric oxygen therapy plus standard wound care compared with standard wound care alone in preventing the need for major amputation in patients with diabetes mellitus and chronic ulcers of the lower limb. One hundred and eighteen (59 patients per arm) patients with non-healing diabetic ulcers of the lower limb, referred to the Judy Dan Research and Treatment Centre are being recruited if they are at least 18 years of age, have either Type 1 or 2 diabetes with a Wagner grading of foot lesions 2, 3 or 4 on lower limb not healing for at least 4 weeks. Patients receive hyperbaric oxygen therapy every day for 6 weeks during the treatment phase and are provided ongoing wound care and weekly assessments. Patients are required to return to the study centre every week for an additional 6 weeks of follow-up for wound evaluation and management. The primary outcome is freedom from having, or meeting the criteria for, a major amputation (below knee amputation, or metatarsal level) up to 12 weeks after randomization. The decision to amputate is made by a vascular surgeon. Other outcomes include wound healing, effectiveness, safety, healthcare resource utilization, quality of life, and cost-effectiveness. The study will run for a total of about 3 years. The results of this study will provide detailed information on the efficacy of hyperbaric oxygen therapy for the treatment of non-healing ulcers of the lower limb. This will be the first double-blind randomized controlled trial for this health technology which evaluates the efficacy of hyperbaric oxygen therapy in prevention of amputations in diabetic patients. ClinicalTrials.gov Identifier: NCT00621608.


crossveinless-c is a RhoGAP required for actin reorganisation during morphogenesis.
Members of the Rho family of small GTPases are required for many of the morphogenetic processes required to shape the animal body. The activity of this family is regulated in part by a class of proteins known as RhoGTPase Activating Proteins (RhoGAPs) that catalyse the conversion of RhoGTPases to their inactive state. In our search for genes that regulate Drosophila morphogenesis, we have isolated several lethal alleles of crossveinless-c (cv-c). Molecular characterisation reveals that cv-c encodes the RhoGAP protein RhoGAP88C. During embryonic development, cv-c is expressed in tissues undergoing morphogenetic movements; phenotypic analysis of the mutants reveals defects in the morphogenesis of these tissues. Genetic interactions between cv-c and RhoGTPase mutants indicate that Rho1, Rac1 and Rac2 are substrates for Cv-c, and suggest that the substrate specificity might be regulated in a tissue-dependent manner. In the absence of cv-c activity, tubulogenesis in the renal or Malpighian tubules fails and they collapse into a cyst-like sack. Further analysis of the role of cv-c in the Malpighian tubules demonstrates that its activity is required to regulate the reorganisation of the actin cytoskeleton during the process of convergent extension. In addition, overexpression of cv-c in the developing tubules gives rise to actin-associated membrane extensions. Thus, Cv-c function is required in tissues actively undergoing morphogenesis, and we propose that its role is to regulate RhoGTPase activity to promote the coordinated organisation of the actin cytoskeleton, possibly by stabilising plasma membrane/actin cytoskeleton interactions.


Anticoagulation therapy among patients presenting to the emergency department with symptomatic atrial fibrillation - the FinFib2 study.
Atrial fibrillation (AF) causes numerous visits to emergency departments (EDs). We evaluated the thromboembolic and bleeding risk profile and use of oral anticoagulation (OAC) therapy among patients presenting with symptomatic AF to ED. Within a 2-week period, all patients whose primary reason for the ED visit was AF were enrolled into this prospective study in 35 EDs around Finland. The risk of thromboembolic and bleeding events was assessed by the CHA2DS2VASc and the HAS-BLED score, respectively. Thereafter, we evaluated whether OAC was used according to the contemporary management guidelines. The study population included 1013 patients (mean age 70±13 years, 52.4% men) with newly or previously diagnosed symptomatic AF. The mean CHA2DS2VASc and HAS-BLED score was 3.1±2.1 and 1.9±1.2, respectively. At admission, 76.3% of the patients with previously diagnosed AF and CHA2DS2VASc score of at least 2 were using OAC (warfarin 92.3%). However, the international normalized ratio was not at the therapeutic level in 41.9% of them. At discharge, 84.1% of the high-risk patients (85.5% of previously diagnosed and 79.6% of newly diagnosed) and 57.0 and 37.0% of the moderate-risk and low-risk patients were on OAC, respectively. Of the high-risk patients, 5.4% were treated with aspirin. These data showed that OAC was prescribed frequently to patients with symptomatic AF and risk factors for stroke. However, in patients using warfarin, international normalized ratio was not at the therapeutic level in a large proportion of the patients with previously diagnosed AF.


Ultrastructure, organization and cytochemistry of cytoplasmic crystalline inclusions in Origanum dictamnus L. leaf chlorenchyma cells.
In the cytoplasm of chlorenchyma cells in primary Origanum dictamnus leaves, rectangular prism-like crystals occur, which, as shown by pepsin digestion, are proteinaceous. In sections they usually show either a square lattice or striations running parallel to the short or long axis. In both cases the interspacings are estimated to be about 100 A, suggesting that the arrangement of the crystallographic planes possesses tetragonal symmetry. High magnifications of the crystalline inclusions together with analysis of their diffraction patterns showed that the striations are composed of double helices of protein macromolecules. In leaves 3-4 mm long, eroded crystals are often observed. When leaves are larger than 5 mm, no crystalline bodies can be identified in chlorenchyma cells. It is possible that they represent a storage form of protein, which is used later by the developing cells.


Confocal scanning optical microscope using single-mode fiber for signal detection.
A single-mode fiber is employed as a detector in a confocal scanning optical microscope (CSOM) instead of a pinhole and its optical property is studied. The optical system is always coherent, which is fundamentally different from the CSOM with a finite-sized pinhole. The coherent transfer function and the axial response are calculated. Experimentally, the coherent image is taken and the axial response is also measured.


Self-Management Interventions for Facilitating Life Participation for Persons with Kidney Failure: A Systematic Review.
For persons with kidney failure life participation is a critically important outcome, strongly linked to quality of life and mortality. To support patients' self-management abilities, three domains are typically emphasized: medical-management, emotional-management and management of everyday life (i.e. role-management). While role-management is strongly linked to life participation, there is currently limited research on interventions designed to support it. We explored existing self-management interventions that aim to support everyday life functioning, rather than only medical-management. In this systematic review and qualitative meta-synthesis, we searched MEDLINE, Embase, CINAHL, PsycINFO, Web of Science and CENTRAL up to April 2022 for interventional studies involving self-management interventions designed, at least partly, to support management of everyday life. Sandelowski and Barosso's guidelines were used to analyze and synthesize the results. A taxonomy of everyday self-management strategies was used to further explore intervention content. Study quality was assessed using the Cochrane Collaboration's risk-of-bias tools. Evidence of effectiveness was summarized and a meta-analysis of eligible outcomes was conducted. Of 22,667 records, 53 studies were included in the meta-synthesis. The majority of self-management interventions focused on medical-management. Included interventions involved strategies to support eight domains: Activities of daily living, Work and school life, Meaningful occupations, Leisure activities, Mobility and travel, Interpersonal relationships, Role-functioning, and Social participation. Major interventions focused on providing education, skill training, counseling, and cognitive behavioral therapy. Evidence of effectiveness was reported across a wide range of patient-reported outcomes, including (health-related) quality of life, depression, and self-efficacy. Studies were geographically concentrated and of moderate to low quality. Despite its well-recognized importance, research on interventions to improve life participation mostly consists of pilot and feasibility studies, and studies of low quality. Interventions are reported heterogeneously, limiting comparability, and are restricted to specific regions and cultures, limiting generalizability.


Preface to the 9th Biennial COAST Conference: Harnessing Technology and Biomedicine for Personalized Orthodontics.
The Consortium on Orthodontic Advances in Science and Technology (COAST) convened for its 9th biennial conference titled 'Harnessing Technology and Biomedicine for Personalized Orthodontics' to explore cutting-edge craniofacial research towards building the foundations for precision care in orthodontics. Seventy-five faculty, scholars, private practitioners, industry, residents and students met at the UCLA Arrowhead Lodge on 6-9 November 2022 for networking, scientific presentations and facilitated discussions. Thirty-three speakers provided state-of-the-art, evidence-based scientific and perspective updates in craniofacial and orthodontic-related fields. The overall format included an Education Innovation Award Faculty Development Career Enrichment (FaCE) workshop focused on faculty career development, three lunch and learns, keynote or short talks and poster presentations. The 2022 COAST Conference was organized thematically to include (a) genes, cells and environment in craniofacial development and abnormalities; (b) precision modulation of tooth movement, retention and facial growth; (c) applications of artificial intelligence in craniofacial health; (d) precision approaches to Sleep Medicine, OSA and TMJ therapies; and (e) precision technologies and appliances. The collective advances in orthodontics and science represented in the manuscripts of this issue fulfil our goal of laying solid foundations for personalized orthodontics. Participants elevated the need for stronger industry-academic research partnerships to leverage knowledge gained from large datasets with treatment approaches and outcomes; systematizing the potential of big data including through multi-omics and artificial intelligence approaches; refining the genotype: phenotype correlation to create biotechnology that will rescue inherited dental and craniofacial defects; evolving studies of tooth movement, sleep apnoea and TMD treatment to accurately measure dysfunction and treatment successes; and maximizing the integration of newer orthodontic devices and digital workflows. Technological advances combined with those in biomedicine and machine learning are rapidly changing the delivery of health care including that in orthodontics. These advances promise to lead to enhanced customization, efficiencies and outcomes of patient care in routine orthodontic problems and in severe craniofacial problems, OSA and TMD.


Integrating distribution kinetics and toxicodynamics to assess repeat dose neurotoxicity in vitro using human BrainSpheres: a case study on amiodarone.
For ethical, economical, and scientific reasons, animal experimentation, used to evaluate the potential neurotoxicity of chemicals before their release in the market, needs to be replaced by new approach methodologies. To illustrate the use of new approach methodologies, the human induced pluripotent stem cell-derived 3D model BrainSpheres was acutely (48 h) or repeatedly (7 days) exposed to amiodarone (0.625-15 µM), a lipophilic antiarrhythmic drug reported to have deleterious effects on the nervous system. Neurotoxicity was assessed using transcriptomics, the immunohistochemistry of cell type-specific markers, and real-time reverse transcription-polymerase chain reaction for various genes involved in the lipid metabolism. By integrating distribution kinetics modeling with neurotoxicity readouts, we show that the observed time- and concentration-dependent increase in the neurotoxic effects of amiodarone is driven by the cellular accumulation of amiodarone after repeated dosing. The development of a compartmental in vitro distribution kinetics model allowed us to predict the change in cell-associated concentrations in BrainSpheres with time and for different exposure scenarios. The results suggest that human cells are intrinsically more sensitive to amiodarone than rodent cells. Amiodarone-induced regulation of lipid metabolism genes was observed in brain cells for the first time. Astrocytes appeared to be the most sensitive human brain cell type in vitro. In conclusion, assessing readouts at different molecular levels after the repeat dosing of human induced pluripotent stem cell-derived BrainSpheres in combination with the compartmental modeling of in vitro kinetics provides a mechanistic means to assess neurotoxicity pathways and refine chemical safety assessment for humans.


Tobacco use and associated factors among school students in Dubai, 2010: intervention study.
Tobacco smoking is an emerging problem among adolescents in the United Arab Emirates (UAE). This study aimed to measure the prevalence of current tobacco use and its associated factors among school students in Dubai Emirate and to determine the impact of an intervention programme on knowledge and attitudes towards tobacco use. A school-based intervention programme was carried out among 2457 students aged 10-20 years and data were collected with a self-administered questionnaire. Of the students, 14.6% were tobacco users, mostly cigarettes (11.2%) and waterpipes (2.2%). The most common self-reported reasons for smoking were for the experience (29.4%), for stress relief (22.5%) and because their peers smoked (21.9%). Stepwise logistic regression analysis showed that the predictors of tobacco use were: male, higher age, UAE national, higher school level, government school, low knowledge about tobacco and family history of smoking. There were significant improvements in knowledge and attitudes scores after the health education intervention programme.


Tumor Incidence in Patients with Non-Alcoholic Fatty Liver Disease.
The incidence of cancer is increasing worldwide. The role of comorbidities in this development is debated. The aim of this study was to investigate the significance of non-alcoholic fatty liver disease (NAFLD) for the incidence of cancer of various kinds in Germany. Between 2000 and 2015, data on 31 587 patients with established NAFLD were collected for analysis. A control group (n = 31 587) assembled for comparison was matched for sex, age, treating physician, and Charlson Comorbidity Index (CCI). By 10 years after the index date, 15.3% of patients with NAFLD and 13.4% of patients in the control group had been diagnosed with cancer (p <0.001). Patients with NAFLD exhibited significantly higher rates of male genital cancers (HR 1.26; 95% confidence interval [1.06; 1.5]; p = 0.008), skin cancer (HR 1.22 [1.07; 1.38]; p = 0.002) and breast cancer (HR 1.2 [1.01; 1.43]; p = 0.036). In this analysis, the rate of hepatocellular carcinoma did not differ between patients with NAFLD and patients without NAFLD (0.19% vs. 0.12%; p = 0.204). NAFLD slightly increases the risk of breast cancer in women, genital cancer in men, and skin cancer irrespective of sex. Thus, NAFLD can be considered a marker of increased cancer risk.


[Melatonin treatment of a blind child with serious sleep disorders].
Children with developmental and neurological disabilities are prone to develop serious sleep-wake cycle disorders that may be difficult to treat. Case history. A 5-year old blind boy with multiple disabilities developed a chronic sleep-wake cycle disorder as his main clinical problem. Treatment included introduction of strict sleep habits and strengthening of environmental "zeitgebers". After five months melatonin 3 mg was administered at night for 4 weeks. The observation period also included 3 weeks without melatonin. Sleep was registered prospectively by a sleep diary. Strict sleep habits combined with strengthening of "zeitgebers" partially improved the sleep problems, but did not establish a normal sleep pattern. When melatonin was added, he normalized his sleep pattern in a few days. His sleep problems returned during the weeks in which he did not receive melatonin. No side effects were observed. Melatonin is a promising treatment alternative for serious sleep problems in blind children.


Strength Assessment of Trunk Rotator Muscles: A Multicenter Reliability Study.
Trunk rotator strength plays an important role in sports performance and health. A reliable method to assess these muscles with functional electromechanical dynamometer has not been described. Therefore, the objectives of this paper were (I) to explore the reliability of different strength variables collected in isokinetic and isometric conditions during two trunk rotator exercises, and (II) to determine the relationship of isometric and dynamic strength variables collected in the same exercise. A repeated measures design was performed to evaluate the reliability of the horizontal cable woodchop (HCW) and low cable woodchop (LCW) exercises. Reliability was assessed using t-tests of paired samples for the effect size, the standard error of measurement, the coefficient of variation (CV) and the intraclass correlation coefficient (ICC). The Pearson's (r) correlation coefficient was used to explore the association between isometric and isokinetic tests. HCW exercise is more reliable than LCW exercise in assessing trunk rotator muscles. The strength manifestation that should be used is the average strength, and the most reliable evaluation was the HCW at 0.40 m·s-1 concentric (ICC = 0.89; CV = 10.21%) and eccentric (ICC = 0.85; CV = 9.33%) contraction and the dynamic condition that most correlated with the isometric was LWC at 0.50 m·s-1 (r = 0.83; p < 0.01). HCW is a reliable exercise to measure trunk rotator muscles.


Soil penetration by maize roots is negatively related to ethylene-induced thickening.
Radial expansion is a classic response of roots to a mechanical impedance that has generally been assumed to aid penetration. We analysed the response of maize nodal roots to impedance to test the hypothesis that radial expansion is not related to the ability of roots to cross a compacted soil layer. Genotypes varied in their ability to cross the compacted layer, and those with a steeper approach to the compacted layer or less radial expansion in the compacted layer were more likely to cross the layer and achieve greater depth. Root radial expansion was due to cortical cell size expansion, while cortical cell file number remained constant. Genotypes and nodal root classes that exhibited radial expansion in the compacted soil layer generally also thickened in response to exogenous ethylene in hydroponic culture, that is, radial expansion in response to ethylene was correlated with the thickening response to impedance in soil. We propose that ethylene insensitive roots, that is, those that do not thicken and can overcome impedance, have a competitive advantage under mechanically impeded conditions as they can maintain their elongation rates. We suggest that prolonged exposure to ethylene could function as a stop signal for axial root growth.


Metal-on-metal hip resurfacing with an uncemented femoral component. A seven-year follow-up study.
Metal-on-metal hip resurfacing with hybrid fixation has been introduced as an alternative to standard total hip arthroplasty, especially for young and active patients. There are few studies in the literature on the midterm results of cementless femoral side resurfacing. The purpose of this study was to present our seven-year clinical results of a series of twenty cementless metal-on-metal hip resurfacing procedures. Between 1999 and 2000, eighteen patients (twenty hips) underwent primary metal-on-metal hip resurfacing with uncemented femoral and acetabular components. One patient was lost to follow-up. This left eleven men and six women, who had a mean age of forty-five years at the time of surgery. Clinical and radiographic examinations were performed prospectively, and the results were analyzed. The mean duration of follow-up was 7.4 years. There were four revisions, none of which was due to aseptic failure of the femoral component. Two were due to loosening of the acetabular component, one was due to a late hematogenous infection, and one was due to persistent pain despite normal radiographic findings. The mean preoperative Harris hip score was 54 points, and it increased to 94 points at the time of the last follow-up. Radiographic examination of the hips for which the procedure was successful revealed no femoral or acetabular radiolucencies, no migration of any implant, and no osteolysis. The radiographs of one patient (two hips) showed substantial narrowing of the femoral necks (a mean of 12%), which stabilized at three years postoperatively. This patient had a Harris hip score of 100 points for both hips at six years. This study suggests that cementless femoral fixation may be a viable alternative to fixation with cement in metal-on-metal hip resurfacing. Further study of this concept in larger numbers of patients is warranted.


[The hearing function in the patients presenting with the intralabyrinthine distribution of giant cholesteatoma].
The objective of the present study was to evaluate the state of the hearing function in the patients presenting with the intralabyrinthine distribution of giant cholesteatoma before and after the surgical treatment based on the results of examination by the subjective and objective methods. The possibility of preservation of the hearing function after the surgical intervention has been demonstrated.


Facilitating the recovery of insect communities in restored streams by increasing oviposition habitat.
Recruitment limitation is known to influence species abundances and distributions. Recognition of how and why it occurs both in natural and in designed environments could improve restoration. Aquatic insects, for instance, rarely re-establish in restored streams to levels comparable to reference streams even years post restoration. We experimentally increased oviposition habitat in five out of ten restored streams in western North Carolina to test whether insect egg laying habitat was limiting insect populations in restored streams. A main goal was to test whether adding oviposition habitat in the form of rocks that partially protrude above the water surface could be used to increase the abundance and richness of stream insect eggs and larval insects in restored streams. Adding egg-laying habitat enhanced several response variables (e.g., protruding rocks, number of eggs, egg masses, egg morphotype richness, and oviposition habitat stability) to levels similar to those found in reference streams. Following the addition of protruding rocks, egg mass abundance increased by 186 % and richness increased by 77 % respectively in restored-treated streams. Densities of larval insects that attached their eggs to protruding rocks showed an overall pattern consistent with treatment effects due to the combination of non-significant and significant increases of several taxa and not just one taxon. Our results indicate that these stream insect populations are limited by oviposition habitat and that adding egg-laying habitat alleviated this component of recruitment limitation. However, the weaker larval response indicates that additional post-recruitment factors, such as egg or larval mortality, may still be limiting a full recovery of larval insect abundances in these restored streams. This study shows the importance of integrating information from animal life histories, ecology, and geomorphology into restoration practices to improve the recovery of aquatic insects, which are commonly used to assess water quality and the biological efficacy of stream restoration. This article is protected by copyright. All rights reserved.


Effects of therapeutic doses of Pregabalin on QTc interval in conscious rabbits.
Pregabalin (PRG) is a new antiepileptic drug that has been used as supportive therapy for partial seizures in patients. Although many neuro-psychiatric and non-cardiac drugs are known to prolong ventricular repolarization as manifested by QTc prolongation on ECG of which provokes torsades de pointes, there is limited data available regarding the characteristics of QT interval in conscious laboratory animals after PRG administration. For that purpose, effects of different therapeutic doses of oral PRG administration on Heart Rate (HR), QT and QTc values in rabbits were evaluated at a predefined time interval in this research. The study involved 28 New Zealand rabbits of both sexes, aged between 8 and 12 months. Animals were divided into four equal groups. Rabbits in control group (CG) received saline 0.5 ml/per animal orally. Group I, II and III were orally given single dose of PRG at 1.25 mg/kg, 2.5 mg/kg and 5 mg/kg, respectively. ECG records were taken before experiment (baseline) and at 1st, 2nd, 4th, and 6th hour (h) of experiment by direct writing electrocardiograph. HR, QT and QTc values were determined from ECG records. Heart rates increased in all groups when compared to baseline values. The increases were evident at 4th h in group II (p < 0.001), at 2nd h (p < 0.05) and 4th h (p < 0.001) in group III compared with CG. After application of PRG, QTc began to prolong at 1st h through the 4th of experiment and then turned to baseline values at 6th h of the experiment. The QTc values obtained at 2nd h in Group II and III (p < 0.05) and 4th h (p < 0.001) of application in group III were significantly different from CG. Changes obtained in HR, QT and QTc values in PRG treated rabbits were time and dose dependent (p < 0.001). Increase in HR and QTc prolongation determined in PRG given rabbits may implied that clinicians should take care of these changes when using this drug and further studies are required to fully understand the mechanism involved.


[Reproduction of European bank vole (Myodes glareolus, Rodentia) under conditions of natural geochemical anomalies].
Estimates of abundance, morpho-functional state of ovaries, potential and actual fecundity of European bank vole, Myodes glareolus, inhabiting the territories of natural geochemical anomalies that are situated over ultra-basic rock and have an excess content of chrome, nickel, and cobaltare obtained. The population adaptive response to extreme geochemical conditions that facilitates the species survival under unfavorable environmental conditions and is manifested through an increase in potential and actual fecundity, decline of pre-implantation mortality, and decrease in proportion of females with pre-implantation losses is revealed. It is shown that in anomalous areas the intensity of folliculogenesis in mature voles is independent of the population cycle phase. As for immature animals residing within geochemical anomalies, an increase in size and numbers of follicles in ovaries is observed which is indicative of maturation fastening. An increase in potential and actual fecundity, as well as changes in morpho-functional state of ovaries, can be interpreted as means of birth rate accelerating which is supposed to compensate high postnatal mortality and maintain population abundance.


Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704.
Double hit lymphoma (DHL) and double protein-expressing (MYC, BCL2) lymphomas (DPL) fare poorly with R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisolone); consolidative autologous stem cell transplant (ASCT) may improve outcomes. S9704, a phase III randomized study of CHOP +/-R with or without ASCT enabled evaluation of intensive consolidation. Immunohistochemistry (IHC) identified 27 of 198 patients (13·6%) with MYC overexpression; 20 (74%) harboured concurrent BCL2 overexpression. Four had DHL and 16 had DPL only. With median 127 months follow-up, there is a trend favouring outcomes after ASCT in DPL and MYC protein overexpressing patients, whereas all DHL patients have died irrespective of ASCT.


[Priority for live kidney donors in transplantation].
Patients in the Netherlands requiring a donor kidney spend 3 to 4 years on average on the transplant waiting list for a kidney from a deceased donor. Post-mortem donor kidneys are in short supply. Consequently, over the past 15 years, an increasingly number of living persons have donated a kidney. This development raises the question as to whether these donors ought to be given priority on the donor kidney waiting list in the event of subsequently suffering from severe renal insufficiency. The Health Council of the Netherlands concludes that there are sound medical-ethical and legal arguments for awarding live kidney donors with end-stage renal failure 500 points in the points system that Eurotransplant uses to determine the position on the waiting list. Adopting this approach would mean that donors would qualify for pre-emptive transplant of a post-mortem donor kidney. The Council is of the opinion that the proposal is reconcilable with national and international legal rules and the principles on which they are based.


Membranous obstruction of the inferior vena cava.
Membranous obstruction of the inferior vena cava (MOVC) is a rare clinical entity. The incidence is higher in Japan and Africa than that in USA and Europe. MOVC is considered to be different from the Budd-Chiari syndrome. There are differences in clinical manifestation and pathologic changes in the liver. Findings of the liver revealed cirrhosis in all patients but in one. Ascites and esophageal varices could be observed in 79% and in 58% of the patients, respectively. According to Sugiura's classification, they consisted of Type Ia in 63%, Type Ib in 11%, Type II in 11%, and Type III in 16%. Portopulmonary shunt by splenopneumopexy was successfully performed on 19 patients with MOVC in this clinic, of which diagnosis was established by cavography.


Interactions between contaminated aquatic environments and element uptake by Echinodorus amazinocus and Cryptocoryne undulata.
The objectives of this experimental study were to examine the interaction between metal contaminated aquatic environments and element uptake by Echinodorus amazinocus and Cryptocoryne undulata. Changes in element concentrations were investigated in three phases in aquatic environments: water, pore water and sediment. Additionally, the amounts of partial elements, relative uptakes, translocation factor and bio-concentration factor were evaluated for each plant. Growth analyses of both plants, as well as physical parameters of the water quality obtained from the reactors, were statistically evaluated by a two-sample t-test. Following the analyses, it was observed that the amount of all of the elements in each of the phases was different for each intermittent sample. Studies with C. undulata and E. amazinocus demonstrated that the concentration of all of the elements in the plants was changing relatively. It was also found that existing environmental conditions did not affect plant life negatively.


Bochdalek Hernia With Gastric Volvulus in an Adult: Common Symptoms for an Original Diagnosis.
Bochdalek hernias in adulthood are rare. Symptomatic Bochdalek hernias in adults are rarer, but may lead to fatal complications. Patients with acute gastric volvulus on diaphragmatic hernia are a diagnostic and therapeutic emergency.Here, we report a case of a 56-year-old woman diagnosed with epigastric pain, cough, vomiting since 2 weeks and shortness of breath. Complicated Bochdalek hernia was an incidental finding, diagnosed by chest radiograph, computed tomography (CT), and barium swallow study. Stomach was within the thorax in the left side due to left diaphragmatic hernia of a nontraumatic cause.The patient was prepared for the laparoscopic surgical repair, to close the defect. The patient recovered with accepted general condition and was discharged 9 days later.Diagnoses of Bochdalek hernias in adulthood are challenging. However, although rare, this possibility should be kept in mind to avoid fatal complications.


Intergenerational Relationships, Family Caregiving Policy, and COVID-19 in the United States.
Families and intergenerational relationships are important sources of risk for COVID-19 infection, especially for older adults who are at high risk of complications from the disease. If one family member is exposed to the virus they could serve as a source of transmission or, if they fall ill, the resources they provide to others could be severed. These risks may be especially heightened for family members who work outside the home and provide care, or for those family members who care for multiple generations. Policies have the potential to help families bear the burden of these decisions. This essay argues that policies that address health, employment, and other social issues have implications for families, and that policies aimed at families and caregivers can affect the health, employment, and the general well-being of the nation.


Scaling in the growth of geographically subdivided populations: invariant patterns from a continent-wide biological survey.
We consider statistical patterns of variation in growth rates for over 400 species of breeding birds across North America surveyed from 1966 to 1998. We report two results. First, the standard deviation of population growth rates decays as a power-law function of total population size with an exponent beta = 0.36 +/- 0.02. Second, the number of subpopulations, measured as the number of survey locations with non-zero counts, scales to the 3/4 power of total number of birds counted in a given species. We show how these patterns may be related, and discuss a simple stochastic growth model for a geographically subdivided population that formalizes the relationship. We also examine reasons that may explain why some species deviate from these scaling laws.


A gold(i)-catalysed three-component reaction via trapping oxonium ylides with allenamides.
A gold(i)-catalysed three-component reaction between alcohols (and water), α-aryl-α-diazoesters and allenamides has been developed, affording three-component products, tert-allylic ethers (and alcohols), in moderate to excellent yields with excellent geometric selectivity (E : Z > 20 : 1). In addition, this transformation proceeds smoothly with high functional group tolerance and a broad substrate scope under exceptionally mild reaction conditions. Remarkably, a gram-scale reaction is also successfully performed, and the corresponding three-component product can readily react with easily obtained reagents, furnishing diverse products in satisfactory yields.


Nurses' views on sexuality. Why, what, and how to change.
What practicing professional nurses believe about the sexual functioning of their patients has a direct influence on the patients' psychological well being. A preliminary investigation identifying some of nurses' beliefs demonstrated their attitudes and knowledge about the effects of chronic disease on sexuality. Staff development educators can assist nursing staff to change attitudes and improve knowledge through an educational program outlined in this article.


Differential response of digesta- and mucosa-associated intestinal microbiota to dietary insect meal during the seawater phase of Atlantic salmon.
Intestinal digesta is commonly used for studying responses of microbiota to dietary shifts, yet evidence is accumulating that it represents an incomplete view of the intestinal microbiota. The present work aims to investigate the differences between digesta- and mucosa-associated intestinal microbiota in Atlantic salmon (Salmo salar) and how they may respond differently to dietary perturbations. In a 16-week seawater feeding trial, Atlantic salmon were fed either a commercially-relevant reference diet or an insect meal diet containing ~ 15% black soldier fly (Hermetia illucens) larvae meal. The digesta- and mucosa-associated distal intestinal microbiota were profiled by 16S rRNA gene sequencing. Regardless of diet, we observed substantial differences between digesta- and mucosa-associated intestinal microbiota. Microbial richness and diversity were much higher in the digesta than the mucosa. The insect meal diet altered the distal intestinal microbiota resulting in higher microbial richness and diversity. The diet effect, however, depended on the sample origin. Digesta-associated intestinal microbiota showed more pronounced changes than the mucosa-associated microbiota. Multivariate association analyses identified two mucosa-enriched taxa, Brevinema andersonii and Spirochaetaceae, associated with the expression of genes related to immune responses and barrier function in the distal intestine, respectively. Our data show that salmon intestinal digesta and mucosa harbor microbial communities with clear differences. While feeding insects increased microbial richness and diversity in both digesta- and mucosa-associated intestinal microbiota, mucosa-associated intestinal microbiota seems more resilient to variations in the diet composition. To fully unveil the response of intestinal microbiota to dietary changes, concurrent profiling of digesta- and mucosa-associated intestinal microbiota is recommended whenever feasible. Specific taxa enriched in the intestinal mucosa are associated to gene expression related to immune responses and barrier function. Detailed studies are needed on the ecological and functional significance of taxa associated to intestinal microbiota dwelling on the mucosa.


[Investigation of periodic distributions of amino acids in the sequences of fiber proteins of bacteriophage T4].
Sequences of amino acids of some fiber proteins may have a periodic structure. To analyze this periodicity Fourier transform of a mathematical image of symbolic sequence of amino acids in a protein is sometimes used. In this work we employed one (out of few possible) particular way of doing Fourier transform as the most straightforward and optimal. Employing this optimal Fourier transform method we analyzed periodicity of fiber proteins in bacteriophage T4. As a result we managed to confirm that a certain periodicity exists in the investigated proteins. It was found that for a number of proteins the alternation of elements of the same group in the amino acid sequence with a rather small period T = 15 exists, whereas for some other proteins alternations have small periods 10 and 8. The new result is a discovery of relatively large periods of amino acids alternations, which divide the amino acids sequence of the protein into 4 or 6 equal parts. These data on the amino acids periodicity allowed us to align amino acids sequences in accordance with the established periods of both types, in agreement with certain results obtained in X-ray crystallography and electron microscopy experiments.


Colloidal Plastic Crystals in a Shear Field.
We study the structure and viscoelastic behavior of 3D plastic crystals of colloidal dumbbells in an oscillatory shear field based on a combination of small-angle neutron scattering experiments under shear (rheo-SANS) and Brownian dynamics computer simulations. Sterically stabilized dumbbell-shaped microgels are used as hard dumbbell model systems which consist of dumbbell-shaped polystyrene (PS) cores and thermosensitive poly(N-isopropylacrylamide) (PNIPAM) shells. Under increasing shear strain, a discontinuous transition is found from a twinned-fcc-like crystal to a partially oriented sliding-layer phase with a shear-molten state in between. In the novel partially oriented sliding-layer phase, the hard dumbbells exhibit a small but finite orientational order in the shear direction. We find that this weak correlation is sufficient to perturb the nature of the nonequilibrium phase transition as known for hard sphere systems. The discontinuous transition for hard dumbbells is observed to be accompanied by a novel yielding process with two yielding events in its viscoelastic shear response, while only a single yielding event is observed for sheared hard spheres. Our findings will be useful in interpreting the shear response of anisotropic colloidal systems and in generating novel colloidal crystals from anisotropic systems with applications in colloidal photonics.


Biological variation in tPA-induced plasma clot lysis time.
Hypofibrinolysis is a risk factor for venous and arterial thrombosis, and can be assessed by using a turbidimetric tPA-induced clot lysis time (CLT) assay. Biological variation in clot lysis time may affect the interpretation and usefulness of CLT as a risk factor for thrombosis. Sufficient information about assay variation and biological variation in CLT is not yet available. Thus, this study aimed to determine the analytical, within-subject and between-subject variation in CLT. We collected blood samples from 40 healthy individuals throughout a period of one year (average 11.8 visits) and determined the CLT of each plasma sample in duplicate. The mean (± SD) CLT was 83.8 (± 11.1) minutes. The coefficients of variation for total variation, analytical variation, within-subject variation and between-subject variation were 13.4%, 2.6%, 8.2% and 10.2%, respectively. One measurement can estimate the CLT that does not deviate more than 20% from its true value. The contribution of analytical variation to the within-subject variation was 5.0%, the index of individuality was 0.84 and the reference change value was 23.8%. The CLT was longer in the morning compared to the afternoon and was slightly longer in older individuals (> 40 years) compared to younger (≤40 years) individuals. There was no seasonal variation in CLT and no association with air pollution. CLT correlated weakly with fibrinogen, C-reactive protein, prothrombin time and thrombin generation. This study provides insight into the biological variation of CLT, which can be used in future studies testing CLT as a potential risk factor for thrombosis.


Genome-wide biological response fingerprinting (BioReF) of the Chinese botanical formulation ISF-1 enables the selection of multiple marker genes as a potential metric for quality control.
Quality control plays a critical role in the process of translating the traditional/alternative medicines into modern evidence-based therapies. High performance liquid chromatography (HPLC) is widely applied to assess the chemical composition of botanical drug products. The chromatographic fingerprints or chemical profiles are currently used as the de facto quality control metric. As a complement to chemical profiles, a biological quality control assessment offers distinct advantages. This study describes a genome-wide biological response fingerprinting (BioReF) approach to define a set of marker genes that define a signature pattern for a specific botanical formulation. These marker genes are chosen on the basis of the levels of the regulated expression and the involvement in the cellular signaling pathways. Subsequently, qRT-PCR technique is used to simultaneously monitor the gene expression of multiple marker genes in an efficient and quantitative manner. This set of marker genes represents the biological responses of human cells to the chemical composition of the botanical drug that could serve as potential quality control of botanical drugs in terms of the consistency of biological activities. We demonstrate the BioReF approach with a well-documented Chinese Medicine formula, designated as ISF-1, traditionally used for the management of post-stroke disorders. A set of nine marker genes were selected to assess the batch-to-batch consistency of the biological effects of ISF-1. This approach provides a potential comprehensive and cost-effective quality control metric of the biological activities of botanical drugs.


Repeat Annual Colorectal Cancer Screening in Rural Community Clinics: A Randomized Clinical Trial to Evaluate Outreach Strategies to Sustain Screening.
The majority of colorectal cancer (CRC) research using the fecal immunochemical test (FIT) has studied short-term screening results in predominantly urban areas. The purpose of this study was to evaluate the effectiveness of 2 outreach strategies embedded in a health literacy intervention on repeat CRC screening in rural community clinics. A 2-arm randomized controlled trial was conducted in 4 rural clinics in Louisiana. During a regularly scheduled clinic visit, participants ages 50-75 received a FIT kit and brief educational intervention. Participants were randomized to receive an automated call or a personal call by a prevention counselor after 4 weeks and 8 weeks if FIT kits were not returned. In year 2, materials were mailed, and follow-up calls were conducted as in year 1. The primary outcome was repeat FIT-the return of the FIT kit in both years. Of 568 eligible participants, 55% were female, 67% were African American, and 39% had low health literacy. Repeat FIT rates were 36.5% for those receiving the automated call and 33.6% for those receiving a personal call (P = .30). No annual FITs were returned in 30% of participants, while only 1 FIT was returned by 35% of participants (31% only year 1 and 4% only year 2). Sustaining CRC screening with FIT is challenging in rural clinics. A lower cost automated call was just as effective as the personal call in promoting repeat annual screening. However, more intensive strategies are needed to improve long-term FIT screening among rural participants.


Implantable subcutaneous venous access devices: is port fixation necessary? A review of 534 cases.
Conventional surgical technique of subcutaneous venous port placement describes dissection of the port pocket to the pectoralis fascia and suture fixation of the port to the fascia to prevent inversion of the device within the pocket. This investigation addresses the necessity of that step. Between October 8, 2004 and October 19, 2007, 558 subcutaneous chest ports were placed at our institution; 24 cases were excluded from this study. We performed a retrospective review of the remaining 534 ports, which were placed using standard surgical technique with the exception that none were sutured into the pocket. Mean duration of port use, total number of port days, indications for removal, and complications were recorded and compared with the literature. Mean duration of port use was 341 days (182,235 total port days, range 1-1279). One port inversion/flip occurred, which resulted in malfunction and necessitated port revision (0.2%). Other complications necessitating port removal included infection 26 (5%), thrombosis n = 2 (<1%), catheter fracture/pinch n = 1 (<1%), pain n = 2 (<1%), and skin erosion n = 3 (1%). There were two arrhythmias at the time of placement; neither required port removal. The overall complication rate was 7%. The 0.2% incidence of port inversion we report is concordant with that previously published, although many previous reports do not specify if suture fixation of the port was performed. Suture fixation of the port, in our experience, is not routinely necessary and may negatively impact port removal.