Lack of association between ipratropium bromide and mortality in elderly patients with chronic obstructive airway disease.
Ipratropium is commonly used for the management of elderly patients with obstructive airway disease. However, a recent report suggested that its use might be associated with a significant increase in mortality. A study was therefore conducted to compare all-cause mortality rates between users and non-users of ipratropium in elderly patients with either asthma or chronic obstructive pulmonary disease (COPD). A retrospective cohort study was performed using linked data from the Canadian Institute for Health Information, the Ontario Drug Benefit Program, the Ontario Health Insurance Plan, and the Ontario Registered Persons database. A total of 32 393 patients were identified who were aged 65 years or older and who had been discharged from hospital with asthma or COPD between 1 April 1992 and 31 March 1997. All-cause mortality rates were compared between those treated and those not treated with ipratropium following discharge from hospital. In total, 49% of patients received ipratropium within 90 days of discharge. After adjusting for age, sex, comorbidity, use of health services, and other airway medications there was no significant association in patients with COPD between the use of ipratropium and mortality (relative risk (RR) 1.03; 95% confidence interval (CI) 0.98 to 1.08). In patients with asthma, however, there was a slight increase in the relative risk of mortality associated with the use of ipratropium (RR 1.24; 95% CI 1.11 to 1.39). A dose-response increase in the mortality rate was not observed with increasing use of ipratropium in either COPD or asthma. The use of ipratropium in patients with COPD was not associated with an increase in mortality. However, in asthma there was a small increase in the mortality rate. Since asthmatic patients who received ipratropium had greater use of other airway medications and health services, the difference in mortality rate between users and non-users may be a reflection of unmeasured differences in asthma severity.


Role of CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 genes in the susceptibility to acute leukemias.
Acute leukemias (ALs) are heterogeneous diseases. Functional polymorphisms in the genes encoding detoxification enzymes cause inter-individual differences, which contribute to leukemia susceptibility. The CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 polymorphisms in ALL (n = 156) and AML (n = 94) patients and 140 healthy controls were genotyped by PCR and/or PCR-RFLP using blood or bone marrow samples. No association was observed between the GSTT1 gene deletion and patients (OR = 0.8, 95% CI = 0.4-1.7 for AMLs and OR = 0.9, 95% CI = 0.5-1.6 for ALLs). Patients with ALL and AML had a higher prevalence of the GSTM1 deletions compared to controls but only the difference among adult AML patients (OR = 2.1, 95% CI = 1.0-4.2) was statistically significant. The CYP2D6*3 variant allele frequency was lower in the overall acute leukemia patients (0.6%) compared to controls (P = 0.03). CYP2D6*1/*3 genotype frequency also showed a protective association in AML patients (OR = 0.09, 95% CI = 0.01-1.7; P = 0.04). We also found a risk association for CYP2E1*5 in ALL and AML (OR = 3.6, 95% CI = 1.4-9.4 and OR = 3.9, 95% CI = 1.4-10.5, respectively). No association was found for the studied CYP2D6*4, CYP1A1*2A, and GSTT1"null" variants and the risk of acute leuke-mia (ALL or AML). This case-control study suggests a contribution of CYP2E1, CYP2D6, and GSTM1 "null" variants to the development of acute leukemias.


Development of reproductive engineering techniques at the RIKEN BioResource Center.
Reproductive engineering techniques are essential for assisted reproduction of animals and generation of genetically modified animals. They may also provide invaluable research models for understanding the mechanisms involved in the developmental and reproductive processes. At the RIKEN BioResource Center (BRC), I have sought to develop new reproductive engineering techniques, especially those related to cryopreservation, microinsemination (sperm injection), nuclear transfer, and generation of new stem cell lines and animals, hoping that they will support the present and future projects at BRC. I also want to combine our techniques with genetic and biochemical analyses to solve important biological questions. We expect that this strategy makes our research more unique and refined by providing deeper insights into the mechanisms that govern the reproductive and developmental systems in mammals. To make this strategy more effective, it is critical to work with experts in different scientific fields. I have enjoyed collaborations with about 100 world-recognized laboratories, and all our collaborations have been successful and fruitful. This review summarizes development of reproductive engineering techniques at BRC during these 15 years.


Species divergence and repeated ancient hybridization in a Sulawesian lake system.
An increasing volume of empirical studies demonstrated that hybridization between distant lineages may have promoted speciation in various taxa. However, the timing, extent and direction of introgressive hybridization remain unknown in many cases. Here, we report a possible case in which repeated hybridization promoted divergence of Oryzias ricefishes (Adrianichthyidae) on Sulawesi, an island of Wallacea. Four Oryzias species are endemic to the Malili Lake system in central Sulawesi, which is composed of five tectonic lakes; of these, one lake is inhabited by two species. Morphological and population genomic analyses of genome-wide single-nucleotide polymorphisms revealed that these two sympatric species are phylogenetically sister to but substantially reproductively isolated from each other. Analyses of admixture and comparison of demographic models revealed that the two sympatric species experienced several substantial introgressions from outgroup populations that probably occurred soon after they had secondary contact with each other in the lake. However, the ratio of migrants from the outgroups was estimated to be different between the two species, which is consistent with the hypothesis that these introgressions aided their divergence or prevented them from forming a hybrid swarm. Repeated lake fragmentations and fusions may have promoted diversification of this freshwater fish species complex that is endemic to this ancient lake system.


Relevant evidence, reasonable policy and the right to emigrate.
In this article I respond to commentaries by Javier Hidalgo and Phillip Cole. Javier Hidalgo believes that we would be justified in restricting the liberties of health personnel if we had compelling evidence that this would bring about beneficial consequences. He is sceptical that this evidence exists or would ever be forthcoming. Hidalgo therefore supports my position, at least in theory, that where there is good evidence concerning relevant beneficial consequences for remedying important losses associated with high skill migration, we may permissibly restrict health personnel's freedom to migrate through introduction of carefully crafted compulsory service and taxation programmes. So one important issue is whether such evidence is or could ever become available in a form useful to members of government. By contrast, Phillip Cole expresses significant reservations about the policies I argue are permissible under certain conditions. He believes that health workers should never be required to comply with the sorts of taxation and compulsory services programmes I recommend. I show that the programmes for which I argue are not as onerous as Cole imagines and therefore that they can be justified. I also show that relevant evidence exists to address Hidalgo's concerns.


Resolving Toxic DNA repair intermediates in every E. coli replication cycle: critical roles for RecG, Uup and RadD.
DNA lesions or other barriers frequently compromise replisome progress. The SF2 helicase RecG is a key enzyme in the processing of postreplication gaps or regressed forks in Escherichia coli. A deletion of the recG gene renders cells highly sensitive to a range of DNA damaging agents. Here, we demonstrate that RecG function is at least partially complemented by another SF2 helicase, RadD. A ΔrecGΔradD double mutant exhibits an almost complete growth defect, even in the absence of stress. Suppressors appear quickly, primarily mutations that compromise priA helicase function or recA promoter mutations that reduce recA expression. Deletions of uup (encoding the UvrA-like ABC system Uup), recO, or recF also suppress the ΔrecGΔradD growth phenotype. RadD and RecG appear to avoid toxic situations in DNA metabolism, either resolving or preventing the appearance of DNA repair intermediates produced by RecA or RecA-independent template switching at stalled forks or postreplication gaps. Barriers to replisome progress that require intervention by RadD or RecG occur in virtually every replication cycle. The results highlight the importance of the RadD protein for general chromosome maintenance and repair. They also implicate Uup as a new modulator of RecG function.


Intergenerational transmission of violence: The mediating role of adolescent psychopathology symptoms.
Evidence on the intergenerational continuity of intimate partner violence (IPV) suggests small to moderate associations between childhood exposure and young adult IPV involvement, suggesting an indirect effects model. Yet, few prospective studies have formally tested meditational mechanisms. The current study tested a prospective (over 9 years) moderated-mediational model in which adolescent psychopathology symptoms (i.e., internalizing, externalizing, and combined) mediated the association between exposure to IPV in middle childhood and young adult IPV perpetration. In a more novel contribution, we controlled for proximal young adult partner and relationship characteristics. The sample consisted of n = 205 participants, who were, on average, assessed for exposure to parent IPV at age 12.30 years, adolescent psychopathology symptoms at age 15.77 years, and young adult IPV at 21.30 years of age. Data suggest a small, significant direct path from IPV exposure to young adult perpetration, mediated only through adolescent externalizing. Gender moderation analyses reveal differences in sensitivity to exposure across developmental periods; for males, effects of exposure were intensified during the transition to adolescence, whereas for females, effects were amplified during the transition to adulthood. In both cases, the mediational role of psychopathology symptoms was no longer significant once partner antisocial behavior was modeled. Findings have important implications for both theory and timing of risk conveyance.


A Pilot, Web-Based HIV/STI Prevention Intervention Targeting At-Risk Mexican American Adolescents: Feasibility, Acceptability, and Lessons Learned.
Information technology provides new avenues to increase opportunities to deliver HIV/STI prevention interventions in a confidential, sensitive, and engaging manner for youth. While technology-based HIV/STI interventions show promise in preventing HIV/STI among different populations, few have targeted young Latinas. This pilot study examined the feasibility and acceptability of a bilingual, web-based HIV/STI prevention intervention among Latino females aged 15-19. We used a mix-method approach, including a prospective 2-group design with 3 repeated measures, and a post-intervention focus group discussion. We recruited 14 participants from an alternative high school and randomized into each study condition. Participants took 5 structurally equivalent modules focusing on either HIV/STI prevention (intervention) or nutrition/exercise (comparison) and completed assessments before the intervention, immediately post-intervention, and 2 months post-intervention. The findings suggested that the intervention had high levels of feasibility and acceptability. We discuss the keys to success, challenges encountered, and future directions.


Cannabinoids in the management of difficult to treat pain.
This article reviews recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms, as well as randomized clinical trials employing cannabinoids in pain treatment. Tetrahydrocannabinol (THC, Marinol((R))) and nabilone (Cesamet((R))) are currently approved in the United States and other countries, but not for pain indications. Other synthetic cannabinoids, such as ajulemic acid, are in development. Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation. Sativex((R)), a cannabis derived oromucosal spray containing equal proportions of THC (partial CB(1) receptor agonist ) and cannabidiol (CBD, a non-euphoriant, anti-inflammatory analgesic with CB(1) receptor antagonist and endocannabinoid modulating effects) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis, and in 2007 for intractable cancer pain. Numerous randomized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain, rheumatoid arthritis and cancer pain. An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006. Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles. Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise.


Cannabinoid CB2R receptors are upregulated with corneal injury and regulate the course of corneal wound healing.
CB2R receptors have demonstrated beneficial effects in wound healing in several models. We therefore investigated a potential role of CB2R receptors in corneal wound healing. We examined the functional contribution of CB2R receptors to the course of wound closure in an in vivo murine model. We additionally examined corneal expression of CB2R receptors in mouse and the consequences of their activation on cellular signaling, migration and proliferation in cultured bovine corneal epithelial cells (CECs). Using a novel mouse model, we provide evidence that corneal injury increases CB2R receptor expression in cornea. The CB2R agonist JWH133 induces chemorepulsion in cultured bovine CECs but does not alter CEC proliferation. The signaling profile of CB2R activation is activating MAPK and increasing cAMP accumulation, the latter perhaps due to Gs-coupling. Lipidomic analysis in bovine cornea shows a rise in acylethanolamines including the endocannabinoid anandamide 1 h after injury. In vivo, CB2R deletion and pharmacological block result in a delayed course of wound closure. In summary, we find evidence that CB2R receptor promoter activity is increased by corneal injury and that these receptors are required for the normal course of wound closure, possibly via chemorepulsion.


Kallmann's syndrome: mirror movements associated with bilateral corticospinal tract hypertrophy.
To investigate the etiology of mirror movements in patients with X-linked Kallmann's syndrome (xKS) through statistical analysis of pooled white matter data from structural MR images. Mirror movements occur in 85% of xKS patients. Previous electrophysiologic studies have suggested an abnormal ipsilateral corticospinal tract projection in xKS patients exhibiting mirror movements. However, an alternative hypothesis has proposed a functional lack of transcallosal inhibitory fibers. T1-weighted brain scans were normalized into stereotaxic space with segregation of gray and white matter to allow comparison of pooled white matter data on a voxel-by-voxel basis using SPM-96 software. Nine xKS patients were compared with two age-matched groups of nonmirroring individuals: nine patients with autosomal Kallmann's syndrome (aKS) and nine age-matched normal (healthy) men. Hypertrophy of the corpus callosum was found in both Kallmann's syndrome groups: the anterior and midsection in xKS, and the genu and posterior section in aKS. Bilateral hypertrophy of the corticospinal tract was found only in the group of xKS patients exhibiting mirror movements. SPM analysis was validated by an independent region of interest analysis of corpus callosum size. Although morphometry on its own cannot determine the cause of mirror movements, the specific finding of a hypertrophied corticospinal tract in xKS is consistent with electrophysiologic evidence suggesting that mirror movements in xKS result from abnormal development of the ipsilateral corticospinal tract fibers.


Identification of novel plant peroxisomal targeting signals by a combination of machine learning methods and in vivo subcellular targeting analyses.
In the postgenomic era, accurate prediction tools are essential for identification of the proteomes of cell organelles. Prediction methods have been developed for peroxisome-targeted proteins in animals and fungi but are missing specifically for plants. For development of a predictor for plant proteins carrying peroxisome targeting signals type 1 (PTS1), we assembled more than 2500 homologous plant sequences, mainly from EST databases. We applied a discriminative machine learning approach to derive two different prediction methods, both of which showed high prediction accuracy and recognized specific targeting-enhancing patterns in the regions upstream of the PTS1 tripeptides. Upon application of these methods to the Arabidopsis thaliana genome, 392 gene models were predicted to be peroxisome targeted. These predictions were extensively tested in vivo, resulting in a high experimental verification rate of Arabidopsis proteins previously not known to be peroxisomal. The prediction methods were able to correctly infer novel PTS1 tripeptides, which even included novel residues. Twenty-three newly predicted PTS1 tripeptides were experimentally confirmed, and a high variability of the plant PTS1 motif was discovered. These prediction methods will be instrumental in identifying low-abundance and stress-inducible peroxisomal proteins and defining the entire peroxisomal proteome of Arabidopsis and agronomically important crop plants.


Risk of irritable bowel syndrome in first-degree, second-degree and third-degree relatives of affected individuals: a nationwide family study in Sweden.
IBS aggregates in families, but the familial risk of IBS has only been determined in first-degree relatives and spouses. This nationwide study aimed to determine the familial risk of IBS in first-degree, second-degree, and third-degree relatives and spouses of affected individuals in order to estimate the relative influences of genes and shared family environment. We performed a case-cohort study. The Swedish Multigeneration Register was linked to the Hospital Discharge Register for the period 1987-2010 and the Swedish Outpatient Care Register for 2001-2010. ORs for IBS were calculated for relatives of individuals who had been diagnosed with IBS compared with relatives of individuals unaffected by IBS as the reference group. ORs were also determined for IBS cases diagnosed in primary healthcare in four Swedish counties (2001-2007). The ORs for IBS were 1.75 in siblings (95% CI 1.63 to 1.89), 1.82 in offspring (1.67 to 1.97), 1.90 in parents (1.76 to 2.05), 1.10 in maternal half-siblings (0.88 to 1.39), 1.78 in paternal half-siblings (1.48 to 2.15), 1.27 in nieces/nephews (1.18 to 1.38), 1.11 in cousins (1.04 to 1.18), and 1.51 in spouses (1.24 to 1.84) of probands diagnosed with IBS. The OR for probands diagnosed in primary healthcare was 1.82 in siblings (1.52 to 2.18), and 1.82 in offspring (1.49 to 2.21). The increased IBS risk among first-degree relatives and also second-degree and third-degree relatives indicates a genetic component of the familial clustering of IBS. However, a non-genetic contribution is also suggested by the increased risk among spouses.


Bmx tyrosine kinase regulates TLR4-induced IL-6 production in human macrophages independently of p38 MAPK and NFkapp}B activity.
Chronic inflammation, as seen in conditions such as rheumatoid arthritis and Crohn disease, is in part driven by discordant production of inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-6 (IL-6). Tyrosine kinase activity is essential to lipopolysaccharide-induced cytokine production in monocytes, and previous studies by us and others have implicated a role for the Tec kinase Bruton's tyrosine kinase (Btk) in inflammatory cytokine production. Here we show that knockdown of Btk using RNA interference results in decreased tumor necrosis factor-alpha, but not IL-6 production. Further investigations into the signaling mechanisms regulating IL-6 production led to the discovery that the Tec kinase bone marrow tyrosine kinase gene in chromosome X (Bmx) regulates Toll-like receptor-induced IL-6 production. Our data further showed that Bmx-dependent super-induction of IL-6 does not involve nuclear factor-kappaB activity. More detailed investigations of pathways downstream of Bmx signaling revealed that Bmx targets the IL-6 3' untranslated region to increase mRNA stabilization via a novel, thus far undefined, p38 mitogen activated protein kinase-independent pathway. These data have important implications for the design of therapeutics targeted against specific cytokines and their regulators in inflammatory disease.


Nutrition effects on ocular diseases in the aging eye.
We reviewed the data from the clinical trials of nutritional supplements for the treatment of age-related cataract and age-related macular degeneration (AMD) to determine future directions of research and treatment. Data from the controlled clinical trials are presented and reviewed for potential opportunities for further research into the treatment of cataracts and AMD. Two trials using daily multivitamins/minerals demonstrated a reduction in the progression of nuclear cataract, but increased the risk of posterior subcapsular cataract. For AMD, the Age-Related Eye Disease Study (AREDS) formulation (vitamins C, E, beta-carotene, zinc, and copper) reduced the risk of progression to advanced AMD by 25% at 5 years. Because beta-carotene is associated with increased lung cancer in former smokers, lutein/zeaxanthin could replace beta-carotene and provide an incremental increase in the beneficial effects beyond the effects of the AREDS formulation. In addition, a randomized clinical trial of B vitamins demonstrated a beneficial effect for AMD with the vitamin B complex. Future evaluation may include additional assessments of nutrients for the treatment of progression of cataract and AMD. A modest reduction would have significant impact as the numbers of persons affected with these two leading causes of blindness are projected to double in the next decade. An important step would be to develop surrogate outcomes to increase efficiency in clinical trials. More detailed phenotyping, especially of AMD, is required as it appears to be not one disease, but a group of diseases. Genotype-phenotype analyses may help to target pathways that are important in AMD.


Cationic hemicellulose-based hydrogels for arsenic and chromium removal from aqueous solutions.
In this work the synthesis of hemicellulose-based hydrogels and their application for the removal of arsenic and chromium ions is described. In a first step O-acetyl galactoglucomannan (GGM) was subjected to a transesterification applying glycidyl methacrylate (GMA) for the synthesis of novel GGM macromonomers. Two distinguished and purified GGM fractions with molar mass of 7.1 and 28 kDa were used as starting materials. The resulting GGM macromonomers (GGM-MA) contained well-defined amounts of methacrylate groups as determined by (1)H NMR spectroscopy. Selected GGM-MA derivatives were consecutively applied as a crosslinker in the synthesis of tailored hydrogels using [2-(methacryloyloxy)ethyl]trimethylammonium chloride (MeDMA) as monomer. The swelling rate of the hydrogels was determined and the coherence between the swelling rate and the hydrogel composition was examined. The morphology of the GGM-based hydrogels was analysed by SEM and the hydrogels revealed a high surface area and were assessed in respect to their ability to remove arsenate and chromate ions from aqueous solutions. The presented bio-based hydrogels are of high interest especially for the mining industries as a sustainable material for the treatment of their highly contaminated wastewaters.


Parathyroid hormone gene analysis in autosomal hypoparathyroidism using an intragenic tetranucleotide (AAAT)n polymorphism.
We have identified a polymorphic tetranucleotide consisting of (AAAT)n within the first intron of the parathyroid hormone (PTH) gene, and have used this to investigate the segregation of the PTH gene and idiopathic hypoparathyroidism in 7 affected and 21 unaffected members from three families. An association between the PTH locus and autosomal dominant idiopathic hypoparathyroidism in one family was excluded by observing recombination between the two loci. In the remaining two families with autosomal recessive idiopathic hypoparathyroidism, the PTH locus was not similarly excluded. We had previously demonstrated a donor splice site mutation of the PTH gene in one of these families, and PTH gene abnormalities were therefore sought in the second of these families. DNA sequence analysis of the three exons, together with 4 exon-intron boundaries and the promoter region of the PTH gene revealed no abnormalities, thereby indicating molecular pathology at another locus. Thus, our analysis of idiopathic hypoparathyroidism reveals genetic heterogeneity for this disorder. In addition, our identification of a microsatellite polymorphism of the PTH gene should help further segregation studies of this locus in families with parathyroid disorders.


Perirhinal and parahippocampal cortices of the macaque monkey: Intrinsic projections and interconnections.
We investigated the topographic and laminar organization of the intrinsic projections and interconnections of the macaque monkey perirhinal and parahippocampal cortices. Discrete anterograde tracer injections placed at various rostrocaudal and mediolateral levels in these cortices revealed extensive associational connections both within and between the perirhinal and parahippocampal cortices. Areas 35, 36rm, 36rl, 36cm, and 36cl are highly interconnected, whereas area 36d (encompassing the dorsal portion of the medial temporal pole) shares only modest connections with the rest of the perirhinal cortex. Areas TH, TFm, and TFl of the parahippocampal cortex also share an extensive network of associational connections that tend to be heaviest within a given subdivision. Area 36c of the perirhinal cortex is the main interface between the perirhinal and parahippocampal cortices. Its heaviest connections are with area 36r and the anterior aspect of area TF. The laminar organization of all these connections is typical of associational projections. Anterograde tracer experiments revealed that these projections are distributed through both deep and superficial layers, although heavier projections are directed toward the superficial layers. Results of retrograde tracer experiments suggested that the projections from caudal areas (36c or TF) to area 36r are of the feedforward type, whereas the projections from areas 36r and 36c to area TF are of the feedback type. These findings suggest that the perirhinal cortex is at a higher level than the parahippocampal cortex in the hierarchy of associational cortices. We discuss the functional implications of the organization of these extensive networks of intrinsic, associational projections.


Expression of neurotensin messenger RNA in a human carcinoid tumor.
Neurotensin (NT), a distal gut peptide, has important regulatory and trophic effects throughout the gut; however the intracellular mechanisms that regulate the gene expression and release of human NT are not known. The purpose of this endeavor was to study a functioning human pancreatic carcinoid cell line (called BON) in vitro that expresses the NT gene, and to study the effect of the cyclic adenosine monophosphate (cAMP) signal-transduction pathway on the expression and release of human NT. RNA was prepared from BON cell line (which has been established in this laboratory); the RNA was analyzed for NT mRNA expression by Northern hybridization with a complementary DNA probe. RNA blot analysis demonstrated that the NT gene is expressed in BON and is transcribed to two mRNAs of 1.0- and 1.5-kb sizes. In the second part of this study, BON cells were treated with either forskolin (FSK), which increases intracellular levels of cAMP, or with serotonin (5-HT), which reduces cAMP in BON cells. Forskolin produced a dose-dependent increase in NT peptide release and, furthermore, FSK (10(-6) mol/L) rapidly increased NT mRNA abundance 1 hour after addition; conversely, 5-HT (10(-5) mol/L) decreased NT mRNA at 1 hour. Neurotensin mRNA levels returned to control values by 3 hours after either FSK or 5-HT, which suggests that the transcript half-life for NT is relatively short. These findings show that the expression and peptide release of human NT is mediated, in part, by the cAMP signal-transduction pathway. Our human carcinoid cell line will provide a useful model to study the in vitro regulation of NT gene expression and peptide release.


A cluster randomized controlled trial to assess the impact on intimate partner violence of a 10-session participatory gender training curriculum delivered to women taking part in a group-based microfinance loan scheme in Tanzania (MAISHA CRT01): study protocol.
Worldwide, almost one third (30%) of women who have been in a relationship have experienced physical and/or sexual violence from an intimate partner. Given the considerable negative impacts of intimate partner violence (IPV) on women's physical health and well-being, there is an urgent need for rigorous evidence on violence prevention interventions. The study, comprising a cluster randomized controlled trial (RCT) and in-depth qualitative study, will assess the impact on women's past year experience of physical and/or sexual IPV of a participatory gender training curriculum (MAISHA curriculum) delivered to women participating in group-based microfinance in Tanzania. More broadly, the study aims to learn more about the factors that contribute to women's vulnerability to violence and understand how the intervention impacts on the lives of women and their families. Sixty-six eligible microfinance loan groups are enrolled and randomly allocated to: the 10-session MAISHA curriculum, delivered over 20 weeks (n = 33); or, to no intervention (n = 33). Study participants are interviewed at baseline and at 24 months post-intervention about their: household; partner; income; health; attitudes and social norms; relationship (including experiences of different forms of violence); childhood; and community. For the qualitative study and process evaluation, focus group discussions are being conducted with study participants and MAISHA curriculum facilitators. In-depth interviews are being conducted with a purposive sample of 18 participants. The primary outcome, assessed at 24 months post-intervention, is a composite of women's reported experience of physical and/or sexual IPV during the past 12 months. Secondary outcomes include: reported experience of physical, sexual and emotional/psychological IPV during the past 12 months, attitudes towards IPV and reported disclosure of IPV to others. The study forms part of a wider programme of research (MAISHA) that includes: a complementary cluster RCT evaluating the impact of delivering the MAISHA curriculum to women not receiving formal group-based microfinance; an economic evaluation; and a cross-sectional survey of men to explore male risk factors associated with IPV. MAISHA will generate rigorous evidence on violence prevention interventions, as well as further insights into the different forms and consequences of violence and drivers of violence perpetration. ClinicalTrials.gov ID: NCT02592252 , registered retrospectively on 13 August 2015.


The adverse effects of radiotherapy on the structure of dental hard tissues and longevity of dental restoration.
Purpose: The main goal of this study was to evaluate the impact of different ionizing radiation doses on the mineral (carbonate/phosphate ratio, crystallinity index [CI]) and organic (amide III/phosphate, amide I sub-band ratios) structures, as well as the microhardness, of enamel and dentin, along with their influence on the bonding strength stability of the etch-and-rinse (ER) and self-etch (SE) dental adhesive strategies.Materials and methods: Enamel and dentin human tissue specimens were irradiated (with 0, 20, 40, and 70 Gy radiation doses, respectively) and sectioned to perform an attenuated total reflection-Fourier transform IR spectroscopy assay (ATR-FTIR) and the Vickers microhardness (VHN) test to conduct a biochemical and biomechanical evaluation of the tissues. Regarding the adhesive properties, restored enamel and dentin specimens exposed to the same radiation doses were submitted to microshear bond strength (μSBS) tests for enamel in immediate time (IM) and to microtensile bond strength (μTBS) tests after for IM and 12-month (12 M) period of time, Mann-Whitney U tests were implemented, using the ATR-FTIR data for significant differences (α < 0.05), and three- and two-way analyses of variance, along with post-testing, were performed on the μTBS and μSBS data (MPa), respectively (Tukey post hoc test at α = 0.05).Results: The ATR-FTIR results showed a significant decrease (p < .05) in the amide III/phosphate ratio after 20 Gy for the enamel and after 40 Gy for the dentin. The CI was significantly reduced for both tissues after a dose of 70 Gy (p < .05). All radiation doses significantly decreased microhardness values, relative to the respective enamel and dentin controls (p < .05). In both tissues and adhesive strategies, the decrease in bond strength was influenced by ionizing radiation starting from 40 Gy. The ER strategy showed high percentages of enamel cohesive failure. In general, ER in both tissues showed greater and more stable bond strength than SE against increased radiation doses and long term.Conclusions: It is possible to conclude that structural alterations of enamel and dentin are generated by all radiation doses, decreasing the microhardness of dental hard tissues and influencing bond strength over time, starting at 40 Gy radiation dose. The etch-and-rinse strategy demonstrates better adhesive performance but generates cohesive fractures in the enamel.


Life isn't flat: taking cancer biology to the next dimension.
Classically, most cell culture experiments have been performed under adherent 2D conditions. Cells in the human body grow within an organized 3D matrix, surrounded by other cells. The behavior of individual cells is controlled through their interactions with their immediate neighbors and the extracellular matrix. The complex summation of these multiple signals determines whether a given cell undergoes differentiation, apoptosis, proliferation, or invasion. In 2D culture many of these complex interactions are lost. As a result, there are a growing number of studies which report differences in phenotype, cellular signaling, cell migration, and drug responses when the same cells are grown under 2D or 3D culture conditions. One potential application of these techniques is to anticancer drug discovery, which has long been hampered by the lack of good preclinical models. Compounds with good antitumor activity in 2D cell culture models often fail to translate into the clinic. Here we suggest that the response of cancer cells to drugs is determined in part by the 3D tumor microenvironment and discuss models to re-create the 3D tumor microenvironment in vitro. It is likely that the adoption of these and other 3D models will allow us to more closely re-create the behavior of the tumor in vivo which may lead to identifying better anticancer drug candidates at an earlier stage of development.


What do we really know about consumer-driven health plans?
ABOUT CDHPs: Employers began offering consumer-driven health plans (CDHPs) in 2001 when a handful started offering health reimbursement arrangements (HRAs). They then started offering health savings account (HSA)-eligible plans after the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 included a provision to allow individuals with certain high-deductible health plans to contribute to an HSA. This report summarizes what is known about CDHPs, which include both HRAs and HSAs. OFFER RATES: Surveys show that employers offering a CDHP increased from less than 5 percent in 2005 to between 12-15 percent by 2009. Growth in offer rates can be seen across all firm sizes. Recently, the percentage of small firms that offered a CDHP declined while larger firms continued to add a CDHP as an option. Overall, 19.1 million, or 11 percent of individuals with private insurance, were enrolled in a CDHP in 2009. More recent data suggest that by 2010, 10 million people were in an HSA-eligible plan. PREMIUMS: Generally, premiums for CDHPs were lower than premiums for non-CDHPs. A number of studies have tried to explain the differences in premiums. One found savings ranged from 15.5 percent to a low of -4.7 percent, with average savings of 4.8 percent. However, the study found that most of the savings was due to younger, healthier workers choosing CDHPs and concluded that once typical risk- and benefit-adjustment factors were taken into account, CDHPs saved only 1.5 percent. There is strong evidence that initially CDHP enrollees will be healthier than non-CDHP enrollees, but that over time the CDHP population has a significantly higher illness burden. IMPACT OF CDHPS ON PREVENTIVE SERVICES: The studies agree that use of preventive services did not change (upward or downward) as a result of the CDHP. IMPACT OF CDHPS ON MEDICATION ADHERENCE: The studies found that overall use of brand-name prescription drugs fell and, while there was some offset from increased use of generic drugs, some enrollees stopped their use of prescription drugs. CDHP enrollees increased their use of the mail-order pharmacy option. Overall use of prescription drugs among CDHP enrollees with certain chronic conditions fell, or did not increase when enrollees met their deductible. One study found that the financial incentives of the plan are not sufficient in driving behavior, and that educational outreach also matters. NEED FOR FURTHER RESEARCH: Despite the growing body of evidence on the effect of CDHPs on cost and quality, there are many unanswered questions about these plans. Most of the research to date has focused on HRA-based plans. Little systematic research has been conducted on HSA-eligible enrollees. The differences between these plans are significant enough to warrant separate analyses. Also, most of the research to date has ignored the impact of the account on the use of services and on spending. Individuals may use health care services differently depending on how much money is being contributed to the account, especially relative to the deductible, amounts rolled over, and portability of the account.


Risk of chronic kidney disease after cancer nephrectomy.
The incidence of early stage renal cell carcinoma (RCC) is increasing and observational studies have shown equivalent oncological outcomes of partial versus radical nephrectomy for stage I tumours. Population studies suggest that compared with radical nephrectomy, partial nephrectomy is associated with decreased mortality and a lower rate of postoperative decline in kidney function. However, rates of chronic kidney disease (CKD) in patients who have undergone nephrectomy might be higher than in the general population. The risks of new-onset or accelerated CKD and worsened survival after nephrectomy might be linked, as kidney insufficiency is a risk factor for cardiovascular disease and mortality. Nephron-sparing approaches have, therefore, been proposed as the standard of care for patients with type 1a tumours and as a viable option for those with type 1b tumours. However, prospective data on the incidence of de novo and accelerated CKD after cancer nephrectomy is lacking, and the only randomized trial to date was closed prematurely. Intrinsic abnormalities in non-neoplastic kidney parenchyma and comorbid conditions (including diabetes mellitus and hypertension) might increase the risks of CKD and RCC. More research is needed to better understand the risk of CKD post-nephrectomy, to develop and validate predictive scores for risk-stratification, and to optimize patient management.


Impact of a Novel Smartphone App (CureApp Smoking Cessation) on Nicotine Dependence: Prospective Single-Arm Interventional Pilot Study.
Mobile apps have been considered to provide active and continuous support for smoking cessation. However, it is yet to be known whether a smoking cessation smartphone app improves long-term abstinence rates in nicotine-dependent patients. This study aimed to evaluate the long-term abstinence effect of a novel smartphone app, CureApp Smoking Cessation (CASC), in patients with nicotine dependence. In this prospective, interventional, multicenter, single-arm study, we provided the CASC app to all the participants, who used it daily for 24 weeks. The CASC app includes features to maximize the therapeutic effect of pharmacological therapies and counseling at outpatient clinics for smoking cessation. The primary endpoint was a continuous abstinence rate (CAR) from weeks 9 to 24, whereas secondary endpoints were CARs from weeks 9 to 12 and 9 to 52. Of the 56 adult smokers recruited, 1 did not download the app; therefore, 55 participants constituted the full analysis sample. The CAR from weeks 9 to 24 was 64% (35/55, 95% CI 51%-76%), whereas the CARs from weeks 9 to 12 and 9 to 52 were 76% (42/55, 95% CI 65%-88%) and 58% (32/55, 95% CI 46%-71%), respectively. These CARs were better than the results of the national survey on outpatient clinics with regard to smoking cessation under the National Health Insurance Program and that of the varenicline phase 3 trial in Japan and the United States. There was only 1 participant who dropped out during the 12 weeks of the treatment period. This treatment decreased the scores related to withdrawal and craving symptoms. The addition of CASC to usual smoking cessation therapies resulted in high CARs, high patient retention rates, and improvement of cessation-related symptoms. The smartphone app CASC is a feasible and useful tool to help long-term continuous abstinence that can be combined with a standard smoking cessation treatment program.


Absence of processing enzymes for inactive renin in mouse blood but polymorphonuclear neutrophils contain active renin.
The possible role of enzymes in plasma and blood cells for the conversion of inactive renin was investigated in mice of the Balb C strain. The concentrations of both inactive and active renin were unchanged in unfractionated plasma and whole blood during incubation at 37 degrees C for 5 h, indicating, that inactive renin had not been activated. Purified platelets, mononuclear cells (monocytes and lymphocytes), and polymorphonuclear leukocytes were incubated separately with partially purified inactive renin at 37 degrees C for 1 h. Inactive renin was neither activated nor degraded by whole blood cells. Polymorphonuclear neutrophils were also obtained in mice after i.p. injection of fluid thioglycollate medium. Extracts of the polymorphonuclear neutrophils were incubated with partially purified, inactive renin. During incubation at pH 7.5 for 1 h at 37 degrees C, inactive renin was stable and no activation was registered, whereas degradation, without a concomitant increase in active renin, occurred at pH 4.5. Extracts of polymorphonuclear neutrophils were found to contain active, but no inactive renin. The mean amount of renin per cell was 0.5 X 10(-11) Goldblatt units (GU) (range 0.3 X 10(-11) GU - 0.9 X 10(-11) GU; n = 6). These findings argue against a role for the blood cells and plasma in a physiological activation of inactive renin, and do not support the concept that activation of inactive renin in the circulation may participate in homeostasis.


Influence of fog on the signal to interference plus noise ratio of the imaging laser radar using a 16-element APD array.
This paper investigates the signal to interference plus noise ratio (SINR) performance of the imaging laser radar (ILR) system operating at a wavelength of 905 nm using an avalanche photodiode array under the fog condition. We analysis the glow image of the light source, which is formed by the laser spot irradiated on a standard Lambertian target. Based on the proposed theoretical model, we determine the interference due to the glow inter-channel crosstalk under different fog conditions for a targeted channel. We show that, for transmission spans less than several tens of meters the interference due to glow crosstalk is higher than the fog (light to medium) induced losses. However, for a link range longer than 21 m the glow crosstalk induced interference is lower than the heavy fog induced attenuation. The proposed system performance is evaluated by developing an experimental test bed and using a dedicated indoor atmospheric chamber under homogeneously controlled fog conditions. We show that, under different fog conditions experimental results for changing SINR levels match well with the predicted data. The results shown can be used for design optimization of the ILR system when operated under fog conditions.


Cross-Resistance of Acquired Radioresistant Colorectal Cancer Cell Line to gefitinib and regorafenib.
Usually, chemoradiotherapy can be used for the treatment of locally advanced colorectal cancer (CRC) before surgery. On the other hand, some studies have shown that fractional radiation of tumor cells leads to chemoresistance. The aim of this study was to evaluate the chemoresistance of radioresistant sub-line (RR sub-line). This study was done in Hamadan University of Medical Sciences in 2017-2018. MTT assay and sub-G1 fraction analysis by flow cytometry were used to evaluate cross-resistance of RR sub-line to gefitinib and regorafenib. Real-time PCR was used to investigate the role of four miRNAs and their target genes in the cross-resistance of RR sub-line. The t test and repeated measures test were used for the assessment of statistical significance between groups. The IC50 of gefitinib and regorafenib for RR sub-line were significantly higher than those of the parental cell line. On the other hand, the resistance index of RR sub-line for gefitinib and regorafenib were 1.92 and 1.44, respectively. The sub-G1 fraction of RR sub-line following treatment with gefitinib and regorafenib was significantly lower than that of the parental cell line (P=0.012 and P=0.038, respectively). The expression of miR-9, Let-7e, and Let-7b in RRsub-line was significantly lower than that of the parental cell line. However, NRAS, IGF1R, NFKB1, and CCND1 found to be upregulated in RR sub-line in comparison with the parental cell line. We can conclude that the acquired RR sub-line was cross-resistance to gefitinib and regorafenib. Furthermore, miR-9/NFKB1, let-7b/CCND1, let-7e/NRAS, and IGF1R played essential roles in the chemoradioresistance of CRC.


Assessing clonality of Vibrio cholerae strains isolated during four consecutive years (2004 - 2007) in Iran.
Genotypic and phenotypic characterizations of 50 clinical Vibrio cholerae isolates obtained during 4 consecutive y from 2004 to 2007 in Iran were studied. Antimicrobial susceptibility test, biochemical fingerprinting with Phene Plate system (PhP-RV) and pulsed-field gel electrophoresis (PFGE) were performed. Antibiotic susceptibility test of all isolates showed 12 different profiles. The predominant antimicrobial resistance profile (62%) was simultaneous resistance to SXT, streptomycin, chloramphenicol and erythromycin. PFGE revealed a total of 9 pulsotypes with a single dominant type in each y under study. PhP-RV revealed 6 common and 10 single types constituting 80% and 20% of the isolates, respectively. Diversity index of PhP-RV was 0.853, indicative of homogeneity among the isolates. Data obtained from PhP-RV was in close agreement with the results of PFGE genotyping. A comparison of the published PFGE patterns performed using the PulseNet protocol revealed the presence of similar patterns between some of our isolates and the isolates from Pakistan, Nepal and India, suggestive of dissemination of common V. cholerae clones in this region of the world. This could, in part, be due to human travel or occurrence of analogous DNA rearrangements, resulting in the emergence of similar V. cholerae genotypes in regional countries.


HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo.
Microtubules are cylindrical cytoskeletal structures found in almost all eukaryotic cell types which are involved in a great variety of cellular processes. Reversible acetylation on the epsilon-amino group of alpha-tubulin Lys40 marks stabilized microtubule structures and may contribute to regulating microtubule dynamics. Yet, the enzymes catalysing this acetylation/deacetylation have remained unidentified until recently. Here we report that beta-tubulin interacts with histone deacetylase-6 (HDAC-6) in a yeast two-hybrid assay and in vitro. We find that HDAC-6 is a micro tubule-associated protein capable of deacetylating alpha-tubulin in vivo and in vitro. HDAC-6's microtubule binding and deacetylation functions both depend on the hdac domains. Overexpression of HDAC-6 in mammalian cells leads to tubulin hypoacetylation. In contrast, inhibition of HDAC-6 function by two independent mechanisms--pharmacological (HDAC inhibitors) or genetic (targeted inactivation of HDAC-6 in embryonic stem cells)--leads to hyperacetylation of tubulin and microtubules. Taken together, our data provide evidence that HDAC-6 might act as a dual deacetylase for tubulin and histones, and suggest the possibility that acetylated non-histone proteins might represent novel targets for pharmacological therapy by HDAC inhibitors.


Computerized back postural assessment in physiotherapy practice: Intra-rater and inter-rater reliability of the MIDAS system.
Assessment of spinal posture during physiotherapy practice is routine, yet few objective measures exist to this end. The Middlesbrough Integrated Digital Assessment System (MIDAS) is a low cost portable system able to record 3D information on posture. The purpose of this study was to assess both the intra-rater and inter-rater reliability of the MIDAS system. Twenty-five healthy subjects were recruited. A repeated measures design was used to record fifteen pre-palpated landmarks on the back of each subject. To limit the sources of variability, the principal researcher palpated the landmarks for each subject. Each of three raters took two measurements on each subject in a standardized upright posture. X (medio-lateral), Y (antero-posterior) and Z (height) landmark positions were recorded via a computer interface. Both intra-rater agreement (mean ICCs - rater 1 r=0.970, rater 2 r=0.965 and rater 3 r=0.965, p< 0.001) and inter-rater agreement (mean ICCs r=0.967, p< 0.001) was very high between repeated measures and between markers. Error values for the z-axis (height) were the lowest. The MIDAS demonstrated both high inter-rater and intra-rater reliability and provides an objective method for the assessment of posture in physiotherapy practice.


Cohort profile: The Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) - A prospective HIV cohort in rural Tanzania.
The Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) is a single-site, open and ongoing prospective cohort of people living with human immunodeficiency virus (PLWHIV) established in 2005 at the Chronic Diseases Clinic of Ifakara (CDCI), within the Saint Francis Referral Hospital (SFRH) in Ifakara, Tanzania. The objectives of KIULARCO are to (i) provide patient and cohort-level information on the outcomes of HIV treatment; (ii) provide cohort-level information on opportunistic infections and comorbidities; (iii) evaluate aspects of human immunodeficiency virus (HIV) care and treatment that have national or international policy relevance; (iv) provide a platform for studies on improving HIV care and treatment in sub-Saharan Africa; and (v) contribute to generating local capacity to deal with the challenges posed by the HIV/AIDS pandemic in this region. Moreover, KIULARCO may serve as a model for other healthcare settings in rural sub-Saharan Africa. Since 2005, all patients diagnosed with HIV at the Saint Francis Referral Hospital are invited to participate in the cohort, including non-pregnant adults, pregnant women, adolescents, children and infants. The information collected includes demographics, baseline and follow-up clinical data, laboratory data, medication history, drug toxicities, diagnoses and outcomes. Real-time data are captured during the patient encounter through an electronic medical record system that allowed transition to a paperless clinic in 2013. In addition, KIULARCO is associated with a biobank of cryopreserved plasma samples and cell pellets collected from all participants before and at different time-points during antiretroviral treatment. Up to the end of 2016, 12 185 PLWHIV have been seen at the CDCI; 9218 (76%) of whom have been enrolled into KIULARCO and 6965 (76%) of these have received ART from the clinic. Patients on ART attend at least every 3 months, with laboratory monitoring every 6 months. KIULARCO data have been used to generate relevant information regarding ART outcomes, opportunistic infections, non-AIDS comorbidities, prevention of mother-to-child transmission of HIV, paediatric HIV, and mortality and retention in care. Requests for collaborations on analyses can be submitted to the KIULARCO scientific committee. KIULARCO provides a framework for improving the quality of care of people living with HIV in sub-Saharan Africa, to generate relevant information to evaluate ART programmes and to build local capacity to deal with HIV/AIDS. The comprehensiveness of the data collected, together with the biobank spanning over ten years has created a unique research platform in rural sub-Saharan Africa.


Effect of ethanol extract of Trigonella foenum graecum (Fenugreek) seeds on Freund's adjuvant-induced arthritis in albino rats.
Trigonella foenum graecum is an Iranian medicinal plant used for the treatment of rheumatoid arthritis and inflammation. The present study was designed to investigate the beneficial outcome of the plant T. foenum graecum on adjuvant-induced arthritis in albino rats. Ethanol extract of T. foenum graecum was tested against Freund's complete adjuvant-induced arthritis in rats. In the present study, paw volume was measured on the 4th, 8th, 14th and 21st day. On day 22, animals were anaesthetized, and blood samples were collected for the estimation of haemoglobin, white blood cells (WBC), differential white blood cells, erythrocyte sedimentation rate (ESR), red blood cells (RBC), interleukins (IL-1α, IL-1β, IL-2, IL-6) and tumour necrosis factor-α (TNF-α). The animals were sacrificed, and the cartilage tissue was isolated for estimation of lipid peroxidation (LPO), superoxide dismutase (SOD) and glutathione (GSH). Administration with both doses of T. foenum graecum (200 and 400 mg/kg) significantly (P < 0.05) decreased the paw oedema and restored body weight. T. foenum graecum significantly (P < 0.05) reduced the differential WBC count, ESR and WBC (5.833 ± 0.703, 6.989 ± 58.5) content and also showed significant (P < 0.05) increase in RBC and Hb (4.783 ± 0.46, 15.46 ± 0.158) content. T. foenum graecum significantly (P < 0.05) decreased the IL-1α, IL-1β, IL-2, IL-6 and TNF-α levels. It also significantly decreased the levels of LPO and increased the SOD and GSH levels in cartilage tissue. In this study, T. foenum graecum 400-mg/kg dose showed more prominent results compared to the 200-mg/kg dose of T. foenum graecum. The results obtained in this study suggest that anti-inflammatory and antioxidant activities of T. foenum graecum may be the possible reason behind the observed anti-arthritic activity.


Impact of urbanisation and altitude on the incidence of, and risk factors for, hypertension.
Most of the data regarding the burden of hypertension in low-income and middle-income countries comes from cross-sectional surveys instead of longitudinal studies. We estimated the incidence of, and risk factors for, hypertension in four study sites with different degree of urbanisation and altitude. Data from the CRONICAS Cohort Study, conducted in urban, semiurban and rural areas in Peru, was used. An age-stratified and sex-stratified random sample of participants was taken from the most updated census available in each site. Hypertension was defined as systolic blood pressure ≥140 mm Hg, or diastolic blood pressure ≥90 mm Hg, or self-report physician diagnosis and current treatment. The exposures were study site and altitude as well as modifiable risk factors. Incidence, incidence rate ratios (IRRs), 95% CIs and population-attributable fractions (PAFs) were estimated using generalised linear models. Information from 3237 participants, mean age 55.8 (SD±12.7) years, 48.4% males, was analysed. Overall baseline prevalence of hypertension was 19.7% (95% CI 18.4% to 21.1%). A total of 375 new cases of hypertension were recorded, including 5266 person-years of follow-up, with an incidence of 7.12 (95% CI 6.44 to 7.88) per 100 person-years. Individuals from semiurban site were at higher risk of hypertension compared with highly urbanised areas (IRR=1.76; 95% CI 1.39 to 2.23); however, those from high-altitude sites had a reduced risk (IRR=0.74; 95% CI 0.58 to 0.95). Obesity was the leading risk factor for hypertension with a great variation according to study site with PAF ranging from 12.5% to 42.4%. Our results suggest heterogeneity in the progression towards hypertension depending on urbanisation and site altitude.


Lower sedentary metabolic rate in women compared with men.
Since females have a greater prevalence of obesity compared with males, the question arises whether females have lower metabolic rate than males after adjusting for differences in body weight and composition. 24-h energy expenditure (24EE), basal metabolic rate (BMR), and sleeping metabolic rate (SMR) were measured in a respiratory chamber in 235 healthy, nondiabetic Caucasian subjects (114 males, 121 females). Body composition was determined by hydrodensitometry. 24EE was 124 +/- 38 kcal/d (P less than 0.002) higher in males than females after adjusting for differences in fat-free mass, fat mass, and age. Spontaneous physical activity was not significantly different between males and females. Since adjusted 24EE was 106 +/- 39 kcal/d (P less than 0.01) higher in females during the luteal phase of the menstrual cycle compared with females during the follicular phase, energy expenditure was analyzed in a subset (greater than 50 yr) to minimize the confounding effect of menstrual status. 24EE (160 +/- 66 kcal/d; P less than 0.03), BMR (116 +/- 45; P less than 0.02), and SMR (208 +/- 68 kcal/d; P less than 0.005) were higher in males compared with females of the older subset after adjusting for differences in body composition, age, and activity. In summary, sedentary 24EE is approximately 5-10% lower in females compared with males after adjusting for differences in body composition, age, and activity.


Muscle-protein catabolism after injury in man, as measured by urinary excretion of 3-methylhistidine.
1. Urinary excretion of 3-methylhistidine, an index of the rate of muscle breakdown, has been measured during the first 7 days in patients after elective surgery or accidental injury. 2. There was no major difference between the mean daily excretion after skin grafting or total hip replacement, or in injured patients who were hyperketonaemic for the first 24 h after admission. 3. The group of injured patients who did not develop hyperketonaemia had a mean urinary 3-methylhistidine excretion which was twice that of the other groups. 4. It is concluded that increased breakdown of muscle protein makes a major contribution to the greater urinary nitrogen excretion in the normoketonaemic group of injured patients.


Oleogel-structured composite for the stabilization of ω3 fatty acids in fish oil.
This study examined the encapsulation and stabilization of É·3 in fish oil into a multi-compartment system consisting of β-cyclodextrins (β-CD) complexation within an oleogel structure, which was further coated with a layer of whey protein isolate (WPI). The formation of β-CD-fish oil complex was confirmed by thermogravimetric analysis and Fourier-transform infrared spectroscopy. Particle size and ζ-potential of the oleogel-based oil-in-water emulsion did not change significantly over a 28-day storage period under different pH conditions (pH 3.5-7) and NaCl concentrations (50-500 mg L-1). The WPI-coated oleogel and β-CD-fish oil complex were subjected to UVC light exposure and quantified by their eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) contents. Results indicated that more than 50 wt% of both EPA and DHA were retained after a 4 h UV exposure period in the WPI-coated system. In addition, sensory evaluation results showed a decreased fish oil odor in the WPI-coated oleogel samples. Overall, the results from this study demonstrated that this oleogel-structured composite incorporating β-CD-fish oil complexes can be formed successfully to retain lipophilic components with decreased undesirable fish oil odor.


[Kidney, Fluid, and Acid-Base Balance].
Kidneys play an important role to maintain human homeostasis. They contribute to maintain body fluid, electrolytes, and acid-base balance. Especially in fluid control, we, physicians can intervene body fluid balance using fluid resuscitation and diuretics. In recent years, one type of fluid resuscitation, hydroxyl ethyl starch has been extensively studied in the field of intensive care. Although their effects on fluid resuscitation are reasonable, serious complications such as kidney injury requiring renal replacement therapy occur frequently. Now we have to pay more attention to this important complication. Another topic of fluid management is tolvaptan, a selective vasopressin-2 receptor antagonist Recent randomized trial suggested that tolvaptan has a similar supportive effect for fluid control and more cost effective compared to carperitide. In recent years, Stewart approach is recognized as one important tool to assess acid-base balance in critically ill patients. This approach has great value, especially to understand metabolic components in acid-base balance. Even for assessing the effects of kidneys on acid-base balance, this approach gives us interesting insight. We should appropriately use this new approach to treat acid-base abnormality in critically ill patients.


Assessing Therapeutic Efficacy of MEK Inhibition in a KRASG12C-Driven Mouse Model of Lung Cancer.
Purpose: Despite the challenge to directly target mutant KRAS due to its high GTP affinity, some agents are under development against downstream signaling pathways, such as MEK inhibitors. However, it remains controversial whether MEK inhibitors can boost current chemotherapy in KRAS-mutant lung tumors in clinic. Considering the genomic heterogeneity among patients with lung cancer, it is valuable to test potential therapeutics in KRAS mutation-driven mouse models.Experimental Design: We first compared the pERK1/2 level in lung cancer samples with different KRAS substitutions and generated a new genetically engineered mouse model whose tumor was driven by KRAS G12C, the most common KRAS mutation in lung cancer. Next, we evaluated the efficacy of selumetinib or its combination with chemotherapy, in KRASG12C tumors compared with KRASG12D tumors. Moreover, we generated KRASG12C/p53R270H model to explore the role of a dominant negative p53 mutation detected in patients in responsiveness to MEK inhibition.Results: We determined higher pERK1/2 in KRASG12C lung tumors compared with KRASG12D Using mouse models, we further identified that KRASG12C tumors are significantly more sensitive to selumetinib compared with KrasG12D tumors. MEK inhibition significantly increased chemotherapeutic efficacy and progression-free survival of KRASG12C mice. Interestingly, p53 co-mutation rendered KRASG12C lung tumors less sensitive to combination treatment with selumetinib and chemotherapy.Conclusions: Our data demonstrate that unique KRAS mutations and concurrent mutations in tumor-suppressor genes are important factors for lung tumor responses to MEK inhibitor. Our preclinical study supports further clinical evaluation of combined MEK inhibition and chemotherapy for lung cancer patients harboring KRAS G12C and wild-type p53 status. Clin Cancer Res; 24(19); 4854-64. ©2018 AACR.


The Influence of Relaxing and Self-Selected Stimulating Music on Vertical Jump Performance in Male Volleyball Players.
Most research concerning the effects of music on physical performance was conducted using endurance parameters. This study investigated the effects of relaxing (RLX) vs. self-selected stimulating music (SM) vs. no music (NM) on jump height (JH), jump power (PWR), and average rest period between jumps (RP) in 13 athletes (age: 25.5 ± 2.6 years). After a warm-up and listening to music (1 min) or NM, participants completed five squat jumps on a force plate. Psychological ratings of mood were assessed using a questionnaire before warm-up and after jumping. A one-way ANOVA was conducted to compare effects of music on JH, PWR, and RP. A Friedman test with Wilcoxon signed-rank test was used to detect changes in mood. There were no significant effects of music on JH (p = 0.162) and PWR (p = 0.162). A trend towards longer RP in RLX when compared to SM was detected (+2.72 s, +22%, p = 0.059, d = 0.35). Participants felt more "relaxed" (+3 ranks) and more "powerful" after listening to SM (+2 ranks). Following NM and RLX, athletes felt more "energetic" (each +3 ranks) but less energetic (-3 ranks) after SM. In conclusion, this study did not find any performance-enhancing effects of self-selected SM on jump performance. The influences of music on psychological ratings were inconclusive. For this reason, no evidence-based guidelines for the practical application of music in elite jumping athletes can be made, and more studies are warranted.


A case of mislabeled textbooks: misnomer of the traditional "bicaval" view.
Since the early beginning of the transesophageal echocardiography (TEE) era, standardized tomographic views describing cardiac key structures have been provided. They have become the basis of TEE and have not been modified for decades. During our recent structural interventional cases, it has come to our attention that the structure frequently labeled "inferior vena cava" in textbooks and journal articles illustrating the bicaval TEE view is, in fact, the coronary sinus. Our manuscript illustrates our observation.


Factors Associated With Occipital Pressure Ulcers in Hospitalized Infants and Children.
The occiput is a common location for development of pressure ulcers in hospitalized infants and young children. However, risk factors associated with occurrence of the ulcers have not been fully described. To identify factors associated with development of occipital pressure ulcers in acutely ill infants and children. Charts of all patients with occipital pressure ulcers reported in a computerized safety event reporting system since its implementation in 2005 and of any patients with such ulcers recalled by members of the skin care special interest group were reviewed retrospectively. During a 4-year period, 60 cases of occipital pressure ulcers were identified: 40% stage I, 12% stage II, 30% unstageable, and 18% deep tissue Injury. The median age of the sample was 12 months. Among the patients, 86% were in the intensive care unit with cardiovascular or pulmonary problems. A total of 68% had comorbid conditions. Most of the patients were less than 1 year old; were critically ill, requiring high-risk therapies; and had multiple medical devices in place. Patients with the ulcers were commonly treated with mechanical ventilation (83%) and sedation (74%) and were described as agitated (42%). Many of these patients were receiving vasoactive medications (50%) and had vascular access devices in the neck that restricted head movement (45%). When documented, the median Braden Q score was 16. Infants and children at risk for occipital pressure ulcers can be prospectively identified, allowing implementation of nursing interventions to prevent these ulcers.


Cell replacement therapy and the evasion of destructive immunity.
The potential of human embryonic stem (ES) cells to meet the growing demand for cell types and tissues for the treatment of chronic and degenerative diseases has been widely acclaimed. Nevertheless, their use in cell replacement therapy poses a number of significant challenges, not least of which is their subsequent rejection by the recipient's immune system. Here we explore the extent of the immunological barriers encountered and evaluate the potential of different approaches to overcoming these issues of which somatic nuclear transfer (SNT) and the induction of transplanation tolerance are currently the most promising.


Gender-Specificity in Sexual Interest in Bisexual Men and Women.
The present study assessed the gender-specificity of sexual interest of bisexually-identified men and women, compared to gay men and lesbian women. Utilizing viewing time as a measure of sexual interest, self-identified bisexual men (N = 50) and women (N = 54) rated the sexual appeal of sexually provocative pictures while the amount of time spent viewing each picture was inconspicuously measured. As hypothesized, bisexual men and women demonstrated a pattern of sexual interest that was significantly less gender-specific than that of a gay/lesbian sample. That is, bisexual men and women (1) viewed other-sex pictures significantly longer than gay men/lesbian women viewed other-sex pictures and (2) rated other sex pictures significantly more sexually appealing than gay men/lesbians rated other-sex pictures. Additionally, the difference in viewing times and appeal ratings between male and female sexual stimuli for bisexuals was significantly less than the difference evidenced by gay men and lesbians. These findings suggest that self-identified bisexual men and women demonstrate a truly bisexual pattern of sexual interest, characterized by greater other-sex attraction and less gender-specificity than is true for gay men and lesbians.


Kinetic isotope effect in malonaldehyde determined from path integral Monte Carlo simulations.
The primary H/D kinetic isotope effect on the intramolecular proton transfer in malonaldehyde is determined from quantum instanton path integral Monte Carlo simulations on a fully dimensional and validated potential energy surface for temperatures between 250 and 1500 K. Our calculations, based on thermodynamic integration with respect to the mass of the transferring particle, are significantly accelerated by the direct evaluation of the kinetic isotope effect instead of computing it as a ratio of two rate constants. At room temperature, the KIE from the present simulations is 5.2 ± 0.4. The KIE is found to vary considerably as a function of temperature and the low-T behaviour is dominated by the fact that the free energy derivative in the reactant state increases more rapidly than in the transition state. Detailed analysis of the various contributions to the quantum rate constant together with estimates for rates from conventional transition state theory and from periodic orbit theory suggest that the KIE in malonaldehyde is dominated by zero point energy effects and that tunneling plays a minor role at room temperature.


Engineering the Charge Transport of Ag Nanocrystals for Highly Accurate, Wearable Temperature Sensors through All-Solution Processes.
All-nanocrystal (NC)-based and all-solution-processed wearable resistance temperature detectors (RTDs) are introduced. The charge transport mechanisms of Ag NC thin films are engineered through various ligand treatments to design high performance RTDs. Highly conductive Ag NC thin films exhibiting metallic transport behavior with high positive temperature coefficients of resistance (TCRs) are achieved through tetrabutylammonium bromide treatment. Ag NC thin films showing hopping transport with high negative TCRs are created through organic ligand treatment. All-solution-based, one-step photolithography techniques that integrate two distinct opposite-sign TCR Ag NC thin films into an ultrathin single device are developed to decouple the mechanical effects such as human motion. The unconventional materials design and strategy enables highly accurate, sensitive, wearable and motion-free RTDs, demonstrated by experiments on moving or curved objects such as human skin, and simulation results based on charge transport analysis. This strategy provides a low cost and simple method to design wearable multifunctional sensors with high sensitivity which could be utilized in various fields such as biointegrated sensors or electronic skin.


Enhancing Retinal Endothelial Glycolysis by Inhibiting UCP2 Promotes Physiologic Retinal Vascular Development in a Model of Retinopathy of Prematurity.
We address the hypothesis that uncoupling protein 2 (UCP2), a cellular glucose regulator, delays physiologic retinal vascular development (PRVD) by interfering with glucose uptake through glucose transporter 1 (Glut1). In the rat 50/10 oxygen-induced retinopathy (OIR) model, retinal Glut1 and UCP2 were measured and compared to room air (RA)-raised pups at postnatal day 14 (p14). Pups in OIR and RA received intraperitoneal genipin, an UCP2 inhibitor, or control every other day from p3 until p13. Analyses at p14 included avascular/total retinal area (AVA), Western blots of retinal UCP2 and Glut1, and immunostaining of Glut1 in retinal cryosections. Intravitreal neovascular/total retinal area (IVNV) was analyzed at p18, and electroretinograms were performed at p26. Glut1 and phosphorylated VEGFR2 (p-VEGFR2), glucose uptake, adenosine triphosphate (ATP) production, and cell proliferation were measured in human retinal microvascular endothelial cells (hRMVECs) pretreated with genipin or transfected with UCP2siRNA, Glut1siRNA, or control siRNA when incubated with VEGF or PBS. At p14, OIR pups had increased AVA with decreased Glut1 and increased UCP2 in the retina compared to RA retinas. Intraperitoneal genipin increased retinal Glut1 and reduced AVA. Compared to control, treatment with genipin or knockdown of UCP2 significantly increased Glut1, glucose uptake, ATP production, VEGF-induced p-VEGFR2 and cell proliferation in hRMVECs. Knockdown of Glut1 inhibited VEGF-induced p-VEGFR2. Genipin-treated OIR pups with decreased AVA at p14 had reduced IVNV at p18 and increased amplitudes in a- and b-waves at p26. Extending PRVD by increasing retinal endothelial glucose uptake may represent a strategy to prevent severe retinopathy of prematurity and vision loss.


Exploring the value of qualitative research films in clinical education.
Many healthcare professionals use both quantitative and qualitative research to inform their practice. The usual way to access research findings is through peer-reviewed publications. This study aimed to understand the impact on healthcare professionals of watching and discussing a short research based film. The film, 'Struggling to be me' portrays findings from a qualitative synthesis exploring people's experiences of chronic pain, and was delivered as part of an inter-professional postgraduate e-learning module. The innovation of our study is to be the first to explore the impact of qualitative research portrayed through the medium of film in clinical education. All nineteen healthcare professionals enrolled on the course in December 2013 took part in on-line interviews or focus groups. We recorded and transcribed the interviews verbatim and used the methods of Grounded Theory to analyse the interview transcripts. Watching and discussing the film became a stimulus for learning : (a) A glimpse beneath the surface explored a pro-active way of seeing the person behind the pain (b) Pitfalls of the Medical Model recognised the challenge, for both patient and clinician, of 'sitting with' rather than 'fixing' an ill person; (c) Feeling bombarded by despair acknowledged the intense emotions that the clinicians brings to the clinical encounter; (d) Reconstructing the clinical encounter as a shared journey reconstructed the time-constrained clinical encounter as a single step on a shared journey towards healing, rather than fixing. Films portraying qualitative research findings can stimulate a pro-active and dialectic form of knowing. Research-based qualitative films can make qualitative findings accessible and can be a useful resource in clinical training. Our research presents, for the first time, specific learning themes for clinical education.


Knowledge, attitude and practice towards medicines among school teachers in Lalitpur district, Nepal before and after an educational intervention.
Few studies regarding Knowledge, Attitude and Practice (KAP) towards medicines among school teachers have been carried out in Nepal. Obtaining baseline KAP is important to note deficiencies and plan appropriate interventions. School teachers have to know about medicines as they can be an important source of information about rational and safe use of medicines. The department of Clinical Pharmacology, KIST Medical College, Lalitpur, conducted a study regarding KAP of school teachers about medicines before and after an educational intervention from April 2011 to December 2011. The study was done in selected schools of Lalitpur district. Teachers were selected on a voluntary basis after obtaining written informed consent. Gender, ethnic or caste group, native place, age, educational qualifications, subject taught were noted. An educational intervention using a combination of methods like presentations, brainstorming sessions, interactive discussions using posters and distribution of information leaflets about the use of medicines was conducted. The KAP and overall scores among subgroups according to gender, age, level of education, subject, ethnicity, type of school (primary vs. secondary and government vs. private school) were studied. KAP and overall scores before and after the intervention was compared using Wilcoxon signed ranks test as the scores were not normally distributed. A total of 393 teachers participated before and after the intervention. The median (interquartile range) knowledge, attitude and practice scores before the intervention were 63 (10), 23 (5) and 270 (48) respectively while the overall score was 356. The median knowledge, attitude and practice scores after the intervention were 71 (10), 28 (5) and 270 (48) respectively while the overall score increased to 369. Maximum possible score of knowledge, attitude and practice were 100, 40 and 320 respectively. Scores improved significantly for knowledge (p<0.001), attitude (p<0.001) and total scores (p<0.001) but not for practice (p=0.528). The intervention was effective in improving knowledge and attitude of the teachers. More studies among school teachers about their knowledge, attitude and practice about medicines are required in Nepal.


Conformation and interaction of short nucleic acid double-stranded helices. II. Proton magnetic resonance studies on the hydrogen-bonded NH-N protons of ribosyl ApApGpCpUpU helix.
A self-complementary ribohexanucleotide, ApApGpCpUpU, was synthesized and its NH-N hydrogen-bonded protons were studied by proton magnetic resonance. At 1 degree C, 0.17 M Na+, pH 7.6 with 10 mM phosphate-0.1 mM EDTA in H2O, three proton resonances are found in the low-field region with the following chemical shifts and line widths at half-height: 13.2 ppm (80 Hz), 13.5 ppm (30 Hz), and 14.2 ppm (44 Hz). The existence of these resonances indicates the formation of a self-complementary, hydrogen-bonded duplex under these conditions. Upon elevation of temperature, these three resonances sequentially broaden and finally all disappear near 35 degrees C. Unambiguous assignments of these three resonances can be made to the terminal A(1)-U(6) pairs, interior A(2)-U(5) pairs, and to the middle G(3)-C(4) pairs. The assignments were based on (i) the differential sensitivities of the line widths of these resonances to thermal variation, as well as on (ii) a comparison of the computed chemical shifts with the observed chemical shifts. The quantitative aspects of the NH proton transfer between helix, coil, and water are discussed in relationship to the line widths of these resonances and the lifetime of the helix state. The computed chemical shifts of the NH-N resonances based on the A-RNA (or A'-RNA) model agree more closely with the observed chemical shifts than the computed values based on the B-DNA model. These results suggest that the helical duplex of A2GCU2 assumes a conformation similar to A-RNA (or A'-RNA) in aqueous solution. The results on both the NH-N resonances and the C-H resonances are summarized and discussed in terms of the helical conformation of (A2GCU2)2.


Long-term mortality after gastric bypass surgery.
Although gastric bypass surgery accounts for 80% of bariatric surgery in the United States, only limited long-term data are available on mortality among patients who have undergone this procedure as compared with severely obese persons from a general population. In this retrospective cohort study, we determined the long-term mortality (from 1984 to 2002) among 9949 patients who had undergone gastric bypass surgery and 9628 severely obese persons who applied for driver's licenses. From these subjects, 7925 surgical patients and 7925 severely obese control subjects were matched for age, sex, and body-mass index. We determined the rates of death from any cause and from specific causes with the use of the National Death Index. During a mean follow-up of 7.1 years, adjusted long-term mortality from any cause in the surgery group decreased by 40%, as compared with that in the control group (37.6 vs. 57.1 deaths per 10,000 person-years, P<0.001); cause-specific mortality in the surgery group decreased by 56% for coronary artery disease (2.6 vs. 5.9 per 10,000 person-years, P=0.006), by 92% for diabetes (0.4 vs. 3.4 per 10,000 person-years, P=0.005), and by 60% for cancer (5.5 vs. 13.3 per 10,000 person-years, P<0.001). However, rates of death not caused by disease, such as accidents and suicide, were 58% higher in the surgery group than in the control group (11.1 vs. 6.4 per 10,000 person-years, P=0.04). Long-term total mortality after gastric bypass surgery was significantly reduced, particularly deaths from diabetes, heart disease, and cancer. However, the rate of death from causes other than disease was higher in the surgery group than in the control group.


Functional characterization of a SUMO deconjugating protease of Plasmodium falciparum using newly identified small molecule inhibitors.
Small ubiquitin-related modifier (SUMO) is implicated in the regulation of numerous biological processes including transcription, protein localization, and cell cycle control. Protein modification by SUMO is found in Plasmodium falciparum; however, its role in the regulation of the parasite life cycle is poorly understood. Here we describe functional studies of a SUMO-specific protease (SENP) of P. falciparum, PfSENP1 (PFL1635w). Expression of the catalytic domain of PfSENP1 and biochemical profiling using a positional scanning substrate library demonstrated that this protease has unique cleavage sequence preference relative to the human SENPs. In addition, we describe a class of small molecule inhibitors of this protease. The most potent lead compound inhibited both recombinant PfSENP1 activity and P. falciparum replication in infected human blood. These studies provide valuable new tools for the study of SUMOylation in P. falciparum.


Tetranychus urticae mites do not mount an induced immune response against bacteria.
The genome of the spider mite Tetranychus urticae, a herbivore, is missing important elements of the canonical Drosophila immune pathways necessary to fight bacterial infections. However, it is not known whether spider mites can mount an immune response and survive bacterial infection. In other chelicerates, bacterial infection elicits a response mediated by immune effectors leading to the survival of infected organisms. In T. urticae, infection by either Escherichia coli or Bacillus megaterium did not elicit a response as assessed through genome-wide transcriptomic analysis. In line with this, spider mites died within days even upon injection with low doses of bacteria that are non-pathogenic to Drosophila Moreover, bacterial populations grew exponentially inside the infected spider mites. By contrast, Sancassania berlesei, a litter-dwelling mite, controlled bacterial proliferation and resisted infections with both Gram-negative and Gram-positive bacteria lethal to T. urticae This differential mortality between mite species was absent when mites were infected with heat-killed bacteria. Also, we found that spider mites harbour in their gut 1000-fold less bacteria than S. berlesei We show that T. urticae has lost the capacity to mount an induced immune response against bacteria, in contrast to other mites and chelicerates but similarly to the phloem feeding aphid Acyrthosiphon pisum Hence, our results reinforce the putative evolutionary link between ecological conditions regarding exposure to bacteria and the architecture of the immune response.


[A case report of chronic encapsulated intracerebral hematoma].
Chronic encapsulated intracerebral hematoma is a rare clinicopathological entity. The authors reported a case of a 52-year-old male who presented with progressive sensory disturbance of the left extremities three weeks prior to admission. Plain CT and MRI scans revealed a subcortical mass in the right temporal lobe associated with extensive peritumoral edema and intratumoral hemorrhage (mixed intensity on T1WI, low intensity on T2WI). There was a ring-like enhancement with GdDTPA. These findings strongly suggested metastatic melanoma associated with intratumoral hemorrhage. During the operation, the mass appeared partly at the surface of the brain and was easily extirpated totally. Histologically, the specimen showed chronic encapsulated hematoma with a thick, fibrous capsule and there was no evidence of neoplasm. The postoperative course was uneventful and follow up CT scan showed disappearance of the mass and the surrounding edema. The relevant literature was reviewed, and the pathogenesis of this entity was discussed.


Fast and accurate detection of spread source in large complex networks.
Spread over complex networks is a ubiquitous process with increasingly wide applications. Locating spread sources is often important, e.g. finding the patient one in epidemics, or source of rumor spreading in social network. Pinto, Thiran and Vetterli introduced an algorithm (PTVA) to solve the important case of this problem in which a limited set of nodes act as observers and report times at which the spread reached them. PTVA uses all observers to find a solution. Here we propose a new approach in which observers with low quality information (i.e. with large spread encounter times) are ignored and potential sources are selected based on the likelihood gradient from high quality observers. The original complexity of PTVA is O(N α ), where α ∈ (3,4) depends on the network topology and number of observers (N denotes the number of nodes in the network). Our Gradient Maximum Likelihood Algorithm (GMLA) reduces this complexity to O (N2log (N)). Extensive numerical tests performed on synthetic networks and real Gnutella network with limitation that id's of spreaders are unknown to observers demonstrate that for scale-free networks with such limitation GMLA yields higher quality localization results than PTVA does.


Vocabulary development in Greek children: a cross-linguistic comparison using the Language Development Survey.
This study investigated vocabulary size and vocabulary composition in Greek children aged 1;6 to 2;11 using a Greek adaptation of Rescorla's Language Development Survey (LDS; Rescorla, 1989). Participants were 273 toddlers coming from monolingual Greek-speaking families. Greek LDS data were compared with US LDS data obtained from the instrument's normative sample (Achenbach & Rescorla, 2000). Vocabulary size increased markedly with age, but Greek toddlers appeared to get off to a slower start in early word learning than US children. The correlation between percentage word use scores in Greek and US samples was moderate in size, indicating considerable overlap but some differences. Common nouns were the largest category among the fifty most frequent words in both samples. Numbers of adjectives and verbs were comparable across languages, but people and closed-class words were more numerous in the Greek sample. Finally, Greek late talkers showed similar patterns of vocabulary composition to those observed in typically developing Greek children.


Coping with patients suffering from overactive bladder: experiences of family caregivers in Hong Kong.
This article examines the experiences of family caregivers working with patients affected by overactive bladder (OAB) in Hong Kong. Chronic diseases create physical and emotional burdens not only for patients but also for family caregivers, who often experience physical and emotional burnout and social impairment. Extensive literature has pertained to caregiver experiences in western and non-western settings; however, few studies have addressed the livelihoods and experiences of family caregivers of patients with OAB in ethnic Chinese communities. Because of the increasing prevalence of OAB worldwide, this study investigated the experiences of such caregivers in Hong Kong, examining their emotional and social needs. A qualitative research design with individual semistructured interviews was adopted, and snowball sampling was used to recruit 35 family caregivers who were referred by patients with OAB. The participants were interviewed individually from May to August 2013. A phenomenological approach was adopted in the data analysis. The data revealed that all participants had unpleasant experiences in caring for family members with OAB. A sense of powerlessness, helplessness, confusion and guilt, as well as grievances and social withdrawal, was prevalent, causing great physical and emotional suffering and subsequent physical and emotional burnout. These negative experiences were often caused by confusion regarding caretaking duties. The negative emotions of the participants and their family members also caused a lack of communication and mutual understanding about the disease, causing care-giving to be even more confusing and difficult. Furthermore, because of traditional Chinese cultural values and gender expectations, male participants experienced the triple burden of employment, domestic duties and care-giving. More holistic social and healthcare support services should be provided for care-giving family members of patients with OAB patients, empowering such caregivers to attend to family members and care for their own emotional well-being.


[Attachment, mentalization and autonomy in anorexia nervosa and bulimia nervosa].
Attachment insecurity and difficulty with mentalization are common in patients with eating disorders and might be related to their symptoms and lack of autonomy.
 AIM: To investigate the role of attachment and mentalization in the course of anorexia nervosa (AN) and bulimia nervosa (BN).
 METHOD: Patients with AN and BN were assessed at the start of treatment, and after 1 year and 1.5 years concerning attachment security and mentalization in relation to eating disorder and co-morbid symptoms and autonomy. The results at the start of treatment were compared to those of controls without an eating disorder.
 RESULTS: Attachment insecurity and low level of mentalization were more prevalent in patients than in controls, and associated with borderline personality disorder and/or self-injurious behaviour. Attachment security increased after 1 year of treatment. Recovery from eating disorder after 1 year was related to higher level of mentalization and improvement of autonomy. Low pre-treatment level of mentalization predicted persistence of eating disorder until 1.5 years of follow-up.
 CONCLUSION: Good mentalization is associated with recovery from eating disorder. More research on the effect of mentalization based treatment for patients with eating disorders, with or without borderline personality disorder, is recommended.


Time Required to Achieve Minimal Clinically Important Difference and Substantial Clinical Benefit After Arthroscopic Treatment of Femoroacetabular Impingement.
Minimal clinically important difference (MCID) defines the minimum degree of quantifiable outcome improvement that a patient perceives as the result of an intervention or in the process of healing. Substantial clinical benefit (SCB) defines the amount of quantifiable outcome improvement that is needed for a patient to feel substantially better. Little is known about when clinically significant outcome improvement is achieved. To investigate the time-dependent nature of MCID and SCB after hip arthroscopy for femoroacetabular impingement (FAI). Cohort study; Level of evidence, 2. An institutional hip preservation registry was queried. The modified Harris Hip Score, Hip Outcome Score, and 33-item International Hip Outcome Tool (iHOT-33) were administered to patients undergoing hip arthroscopy for FAI. Follow-up times for outcome measures were classified into 3 periods: 5 to 11 months (6 months), 12 to 23 months (1 year), and 24 to 35 months (2 years). Cumulative probabilities for achieving MCID and SCB were calculated with Kaplan-Meier survival curve analysis and interval censoring. A Weibull parametric regression analysis evaluated the odds of achieving earlier MCID. A total of 719 patients undergoing primary hip arthroscopy were included. The mean ± SD age was 32.5 ± 10.5 years, and the majority were female (n = 380, 52.9%). Across all 4 outcome instruments, patients had the highest probability for achieving MCID and SCB by the 6-month postoperative period. The iHOT-33 demonstrated the highest probability for capturing MCID and SCB improvement at each of the 3 periods, with 76.0%, 84.8%, and 93.6% achieving MCID by 6 months, 1 year, and 2 years, respectively. Similarly, the probabilities of achieving SCB on the iHOT-33 were as follows: 57.1%, 68.0%, and 71.7%. A similar trend was demonstrated across other outcome tools. Older male patients and those with Outerbridge classification 1 to 4 (vs grade 0) had a significantly increased risk for taking a longer time to achieve MCID and SCB. Additionally, patients with higher preoperative outcome scores took a longer time to achieve MCID and SCB. At least half of patients treated with hip arthroscopy for FAI achieve MCID and SCB within the first 6 months after the procedure. However, clinically significant outcome improvement continues to be attained until 2 years postoperatively. Female patients, younger individuals, and those without chondral defects achieve faster clinical outcome improvement. These findings can be helpful for establishing shared decision-making aids and follow-up guidelines for arthroscopic treatment of FAI.