Showing papers by "Health Science University published in 2009"
TL;DR: In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 × 10−7 and included previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.
Abstract: Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish individuals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.
1,340 citations
TL;DR: Four new genome-wide significant loci near the SOST gene at 17q21, the MARK3 gene at 14q32, the SP7 gene at 12q13 and the TNFRSF11A (RANK) gene at 18q21 are identified and nonsynonymous SNPs in the C17orf53, LRP4, ADAM19 and IBSP genes were suggestively associated with bone density.
Abstract: In an extended genome-wide association study of bone mineral density among 6,865 Icelanders and a follow-up in 8,510 subjects of European descent, we identified four new genome-wide significant loci. These are near the SOST gene at 17q21, the MARK3 gene at 14q32, the SP7 gene at 12q13 and the TNFRSF11A (RANK) gene at 18q21. Furthermore, nonsynonymous SNPs in the C17orf53, LRP4, ADAM19 and IBSP genes were suggestively associated with bone density.
345 citations
TL;DR: It is demonstrated that aging alters the neuromuscular response to short-term disuse and recovery in humans, and Notably, immobilization had a greater impact on neuronal motor function in old individuals, while young individuals were more affected at the muscle level.
Abstract: Inactivity is a recognized compounding factor in sarcopenia and muscle weakness in old age. However, while the negative effects of unloading on skeletal muscle in young individuals are well elucidated, only little is known about the consequence of immobilization and the regenerative capacity in elderly individuals. Thus the aim of this study was to examine the effect of aging on changes in muscle contractile properties, specific force, and muscle mass characteristics in 9 old (61-74 yr) and 11 young men (21-27 yr) after 2 wk of immobilization and 4 wk of retraining. Both young and old experienced decreases in maximal muscle strength, resting twitch peak torque and twitch rate of force development, quadriceps muscle volume, pennation angle, and specific force after 2 wk of immobilization (P < 0.05). The decline in quadriceps volume and pennation angle was smaller in old compared with young (P < 0.05). In contrast, only old men experienced a decrease in quadriceps activation. After retraining, both young and old regained their initial muscle strength, but old had smaller gains in quadriceps volume compared with young, and pennation angle increased in young only (P < 0.05). The present study is the first to demonstrate that aging alters the neuromuscular response to short-term disuse and recovery in humans. Notably, immobilization had a greater impact on neuronal motor function in old individuals, while young individuals were more affected at the muscle level. In addition, old individuals showed an attenuated response to retraining after immobilization compared with young individuals.
328 citations
TL;DR: Interleukin (IL)-23–mediated gelatinase A (matrixmetalloproteinase [MMP]-2) up-regulation in the ileum of infected mice protected mice from the development of T. gondii–induced immunopathology and suggested that these enzymes may be useful targets for treatment of intestinal inflammation.
Abstract: Peroral infection with Toxoplasma gondii leads to the development of small intestinal inflammation dependent on Th1 cytokines. The role of Th17 cells in ileitis is unknown. We report interleukin (IL)-23–mediated gelatinase A (matrixmetalloproteinase [MMP]-2) up-regulation in the ileum of infected mice. MMP-2 deficiency as well as therapeutic or prophylactic selective gelatinase blockage protected mice from the development of T. gondii–induced immunopathology. Moreover, IL-23–dependent up-regulation of IL-22 was essential for the development of ileitis, whereas IL-17 was down-regulated and dispensable. CD4+ T cells were the main source of IL-22 in the small intestinal lamina propria. Thus, IL-23 regulates small intestinal inflammation via IL-22 but independent of IL-17. Gelatinases may be useful targets for treatment of intestinal inflammation.
262 citations
TL;DR: A comprehensive list of principles relevant for properly describing Health Informatics evaluations has been developed and it is believed that better publication of both quantitative and qualitative evaluation studies is an important step toward the vision of evidence-based Health In formatics.
217 citations
TL;DR: The increase of survival in elderly men is encouraging but the lesser improvement in women and, in particular, the widening gap for breast cancer suggest that many barriers still delay access to care and that enhanced prevention and clinical management remain major issues.
179 citations
TL;DR: This work investigates the possibility that H4 receptors may be expressed in both the human and mouse CNS, and binds several neuroactive drugs, including amitriptyline and clozapine.
Abstract: Background and purpose: The histamine H4 receptor is the most recently identified of the G protein-coupled histamine receptor family and binds several neuroactive drugs, including amitriptyline and clozapine. So far, H4 receptors have been found only on haematopoietic cells, highlighting its importance in inflammatory conditions. Here we investigated the possibility that H4 receptors may be expressed in both the human and mouse CNS.
Methods: Immunological and pharmacological studies were performed using a novel anti-H4 receptor antibody in both human and mouse brains, and electrophysiological techniques in the mouse brain respectively. Pharmacological tools, selective for the H4 receptor and patch clamp electrophysiology, were utilized to confirm functional properties of the H4 receptor in layer IV of the mouse somatosensory cortex.
Results: Histamine H4 receptors were prominently expressed in distinct deep laminae, particularly layer VI, in the human cortex, and mouse thalamus, hippocampal CA4 stratum lucidum and layer IV of the cerebral cortex. In layer IV of the mouse somatosensory cortex, the H4 receptor agonist 4-methyl histamine (20 µmol·L−1) directly hyperpolarized neurons, an effect that was blocked by the selective H4 receptor antagonist JNJ 10191584, and promoted outwardly rectifying currents in these cells. Monosynaptic thalamocortical CNQX-sensitive excitatory postsynaptic potentials were not altered by 4-methyl histamine (20 µmol·L−1) suggesting that H4 receptors did not act as hetero-receptors on thalamocortical glutamatergic terminals.
Conclusions and implications: This is the first demonstration that histamine H4 receptors are functionally expressed on neurons, which has major implications for the therapeutic potential of these receptors in neurology and psychiatry.
172 citations
TL;DR: A small-angle x-ray scattering-based imaging technique that reveals the distribution and orientation of nano-scale structures over extended areas by combining two measurement and analysis schemes, rendering the technique suitable for a broad range of applications, e.g. in materials science and bio-imaging.
Abstract: We describe a small-angle x-ray scattering-based imaging technique that reveals the distribution and orientation of nano-scale structures over extended areas. By combining two measurement and analysis schemes, complementary structural information is available which renders the technique suitable for a broad range of applications, e.g. in materials science and bio-imaging. Through a combination of current techniques and on-line analysis schemes, measurements with a so far unprecedented combination of speed, dynamic range and point density became feasible. This is illustrated by data recorded for a section of a mouse soleus muscle visualizing fine muscle and Achilles tendon structures down to the 10?nm range over a 10?mm2 sample area.
151 citations
TL;DR: Whether postoperative intra-articular injections of autologous marrow aspirate and hyaluronic acid after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring in a goat model is investigated.
Abstract: Purpose: The purpose of the study was to determine whether postoperative intra-articular injections of autologous marrow aspirate (MA) and hyaluronic acid (HA) after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring. Methods: In a goat model we created a 4-mm full-thickness articular cartilage defect in the stifle joint (equivalent to 1.6 cm in the human knee) and conducted subchondral drilling. The animals were divided into 3 groups: group A (control), no injections; group B (HA), weekly injection of 1 mL of sodium hyaluronate for 3 weeks; and group C (HA MA), similar to group B but with 2 mL of autologous MA in addition to HA. MA was obtained by bone marrow aspiration, centrifuged, and divided into aliquots for cryopreservation. Fifteen animals were equally divided between the groups and sacrificed 24 weeks after surgery, when the joint was harvested, examined macroscopically and histologically. Results: Of the 15 animals, 2 from group A had died of non‐surgery-related complications and 1 from group C was excluded because of a joint infection. In group A the repair constituted mainly scar tissue, whereas in group B there was less scar tissue, with small amounts of proteoglycan and type II collagen at the osteochondral junction. In contrast, repair cartilage from group C animals showed almost complete coverage of the defect with evidence of hyaline cartilage regeneration. Histology assessed by Gill scoring was significantly better in group C with 1-way analysis of variance yielding an F statistic of 10.611 with a P value of .004, which was highly significant. Conclusions: Postoperative intraarticular injections of autologous MA in combination with HA after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring in a goat model. Clinical Relevance: After arthroscopic subchondral drilling, this novel technique may result in better articular cartilage regeneration. Key Words: Articular cartilage—Arthroscopic subchondral drilling—Hyaline cartilage—Hyaluronic acid—Mesenchymal stem cells—Microfracture.
141 citations
TL;DR: This exploration of inter professional collaboration in IHC identified a broad array of key factors associated with interprofessional collaboration that are critical to better understand the functioning of IHC clinics, and provide guidance for creation or maintenance of successful clinics.
136 citations
TL;DR: This data indicates that using probiotics as a treatment for eczema may be a viable option, but the results of intervention trials have been mixed.
Abstract: Summary
Background Probiotics have been proposed as a treatment for eczema, but the results of intervention trials have been mixed.
Objective To evaluate the efficacy of probiotics for treating eczema by performing a systematic review of randomized-controlled trials (RCTs).
Design We searched the Cochrane Skin Group Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, AMED, LILACS, ISI Web of Science, the reference lists of articles, ongoing clinical trial registers and conference proceedings. RCTs of live orally ingested microorganisms for the treatment of eczema were eligible for inclusion.
Results Twelve trials (781 participants) were identified. Meta-analysis of data from five of these trials showed that there was no significant reduction in eczema symptoms with probiotic treatment compared with placebo (mean difference −0.90 points on a 20-point visual analogue scale; 95% confidence interval −2.84, 1.04). Meta-analysis of data from seven trials showed no significant difference in investigator rated eczema severity between probiotic and placebo treatments. Subgroup analysis by eczema severity or presence of atopy did not identify a specific population in which probiotic treatment was effective. There was significant heterogeneity between studies; however, the results of three studies that used the same probiotic strain were concordant. The adverse events search identified case reports of sepsis and bowel ischaemia caused by probiotics.
Conclusions Currently, probiotics cannot be recommended for treating eczema. The heterogeneity between studies may be attributable to probiotic strain-specific effects, which means that novel probiotic strains may still have a role in eczema management.
TL;DR: The incidence of hip fracture was higher in western areas of Japan than in eastern areas in both men and women and the exact reasons for this are unknown, but drug therapy for osteoporosis and fall prevention programs might have influenced the results.
Abstract: Summary
We estimated the number of hip fracture patients in 2007 in Japan and investigated the trends in incidence during a 20-year period from 1987 to 2007. Despite the increasing number of new patients, the incidence of hip fracture in some age groups showed the possibility of decline.
TL;DR: In this paper, the subbasal nerve density and tortuosity at 5 corneal locations were determined and investigated to determine whether these microstructural observations correlate with cornealing sensitivity.
Abstract: Purpose: To determine the subbasal nerve density and tortuosity at 5 corneal locations and to investigate whether these microstructural observations correlate with corneal sensitivity. Method: Sixty eyes of 60 normal human subjects were recruited into 1 of 3 age groups, group 1: aged ,35 years, group 2: aged 35–50 years, and group 3: aged .50 years. All eyes were examined using slit-lamp biomicroscopy, noncontact corneal esthesiometry, and slit scanning in vivo confocal microscopy. Results: The mean subbasal nerve density and the mean corneal sensitivity were greatest centrally (14,731 6 6056 mm/mm2 and 0.38 6 0.21 millibars, respectively) and lowest in the nasal mid periphery (7850 6 4947 mm/mm2 and 0.49 6 0.25 millibars, respectively). The mean subbasal nerve tortuosity coefficient was greatest in the temporal mid periphery (27.3 6 6.4) and lowest in the superior mid periphery (19.3 6 14.1). There was no significant difference in mean total subbasal nerve density between age groups. However, corneal sensation (P = 0.001) and subbasal nerve tortuosity (P = 0.004) demonstrated significant differences between age groups. Subbasal nerve density only showed significant correlations with corneal sensitivity threshold in the temporal cornea and with subbasal nerve tortuosity in the inferior and nasal cornea. However, these correlations were weak. Conclusions: This study quantitatively analyzes living human corneal nerve structure and an aspect of nerve function. There is no strong correlation between subbasal nerve density and corneal sensation. This study provides useful baseline data for the normal living human cornea at central and mid-peripheral locations
TL;DR: Genotyped 27 single-nucleotide polymorphisms in 14 genes from obese subjects and suggest that some SNPs identified by genome-wide association studies in the Caucasians also confer susceptibility to obesity in Japanese subjects.
Abstract: There is evidence that the obesity phenotype in the Caucasian populations is associated with variations in several genes, including neuronal growth regulator 1 (NEGR1), SEC16 homolog B (SCE16B), transmembrane protein 18 (TMEM18), ets variant 5 (ETV5), glucosamine-6-phosphate deaminase 2 (GNPDA2), prolactin (PRL), brain-derived neurotrophic factor (BDNF), mitochondrial carrier homolog 2 (MTCH2), Fas apoptotic inhibitory molecule 2 (FAIM2), SH2B adaptor protein 1 (SH2B1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog (MAF), Niemann-Pick disease, type C1 (NPC1), melanocortin 4 receptor (MC4R) and potassium channel tetramerisation domain containing 15 (KCTD15). To investigate the relationship between obesity and these genes in the Japanese population, we genotyped 27 single-nucleotide polymorphisms (SNPs) in 14 genes from obese subjects (n=1129, body mass index (BMI) > or =30 kg m(-2)) and normal-weight control subjects (n=1736, BMI <25 kg m(-2)). The SNP rs10913469 in SEC16B (P=0.000012) and four SNPs (rs2867125, rs6548238, rs4854344 and rs7561317) in the TMEM18 gene (P=0.00015), all of which were in almost absolute linkage disequilibrium, were significantly associated with obesity in the Japanese population. SNPs in GNPDA2, BDNF, FAIM2 and MC4R genes were marginally associated with obesity (P<0.05). Our data suggest that some SNPs identified by genome-wide association studies in the Caucasians also confer susceptibility to obesity in Japanese subjects.
TL;DR: Findings confirmed that cancer cachexia has far reaching implications for patients and their families, extending beyond physical problems into psychological, social and emotional issues.
TL;DR: To study the prognostic value of depressive symptoms on heart failure readmission and mortality, a large and clinically relevant population of hospitalized HF patients adjusted for disease severity by B‐type natriuretic peptide level is studied.
Abstract: Aims
To study the prognostic value of depressive symptoms on heart failure (HF) readmission and mortality, in a large and clinically relevant population of hospitalized HF patients adjusted for disease severity by B-type natriuretic peptide (BNP) level.
Methods and results
We studied 958 patients enrolled after hospitalization for HF; 37% female; mean age 71 ± 11 years; New York Heart Association class II (51%) or III/IV (49%). Left ventricular ejection fraction: 33% ± 14%, and median BNP level: 454 pg/mL (75% CI, 195–876 pg/mL). In total, 377 patients (39%) had depressive symptoms [Centre for Epidemiological Studies Depression Scale (CES-D) score ≥16] and 200 (21%) had severe depressive symptoms (score ≥24). During 18 months of follow-up, 386 (40%) patients reached the primary endpoint of death or readmission for HF. In multivariate analyses, CES-D was significantly associated with the primary endpoint [hazard ratio (HR) 1.13, P = 0.02], and also with both individual components of the primary endpoint [HF readmission (HR 1.165, P = 0.02) and mortality (HR 1.169, P = 0.02)]. Patients with severe depressive symptoms had a >40% higher risk for HF readmission or death.
Conclusion
In patients with HF, depression is independently associated with poor outcomes. These findings highlight the need for continued exploration of whether improvements in depression lead to better cardiovascular outcomes.
The study was registered at clinical trial (www.trialregister.nl): NCT 98675639.
TL;DR: It is demonstrated that Pim-1 is a pivotal regulator involved in hypoxia-induced chemoresistance, and targeting PIM-1 may improve the chemotherapeutic strategy for solid tumors.
Abstract: Hypoxia changes the responses of cancer cells to many chemotherapy agents, resulting in chemoresistance. The underlying molecular mechanism of hypoxia-induced drug resistance remains unclear. Pim-1 is a survival kinase, which phosphorylates Bad at serine 112 to antagonize drug-induced apoptosis. Here we show that hypoxia increases Pim-1 in a hypoxia-inducible factor-1α-independent manner. Inhibition of Pim-1 function by dominant-negative Pim-1 dramatically restores the drug sensitivity to apoptosis induced by chemotherapy under hypoxic conditions in both in vitro and in vivo tumor models. Introduction of siRNAs for Pim-1 also resensitizes cancer cells to chemotherapy drugs under hypoxic conditions, whereas forced overexpression of Pim-1 endows solid tumor cells with resistance to cisplatin, even under normoxia. Dominant-negative Pim-1 prevents a decrease in mitochondrial transmembrane potential in solid tumor cells, which is normally induced by cisplatin (CDDP), followed by the reduced activity of Caspase-3 and Caspase-9, indicating that Pim-1 participates in hypoxia-induced drug resistance through the stabilization of mitochondrial transmembrane potential. Our results demonstrate that Pim-1 is a pivotal regulator involved in hypoxia-induced chemoresistance. Targeting Pim-1 may improve the chemotherapeutic strategy for solid tumors.
TL;DR: A positive but not significant correlation was observed between the professional and patient-based evaluations of aesthetic outcomes and patients with tooth agenesis had a high risk of severe root resorption after orthodontic treatment.
Abstract: Objectives: The outcome of oral rehabilitation is usually monitored with clinical tests rather than by patient's perception of change. The aim of this study was to describe the objective measure and subjective perception of oral rehabilitation in patients with tooth agenesis.
Material and methods: The study included 129 patients with tooth agenesis rehabilitated with implant- or tooth-supported reconstructions, and a control group of 58 patients. Professional assessments included biological, technical and aesthetic variables. An aesthetic index score included mucosal discoloration, crown morphology, crown color match, occlusal harmony, and papilla level. The Oral Health Impact Profile (OHIP) questionnaire was used to evaluate the patient-based outcomes. Six OHIP questions were subtracted to evaluate the patient-based aesthetic outcomes.
Results: Severe root resorption was observed in 36% of the patients in whom orthodontic treatment had been performed. Twelve percent of patients had implants with 5–7 mm peri-implant bone defects. Mucosal discoloration was recorded in 57% of the patients. Twelve percent of the patients had metal visible on the buccal side. The median scores for all five aesthetic variables were acceptable in 92% of the implant reconstructions and for 83% of the tooth-supported fixed dental prostheses (FDPs). The total OHIP score was inferior in rehabilitated patients with tooth agenesis to that of the control group without tooth agenesis. The total OHIP score after rehabilitation was <50 for 95% of the patients with tooth agenesis. The six OHIP questions concerning aesthetics demonstrated patient-based aesthetic problems in 41% of patients treated with implant-supported reconstructions and 47% of patients treated with tooth-supported FDPs. Ninety-eight percent of the group treated with implant-supported reconstructions and 84% of the patients in the tooth-supported FDP group were very satisfied or satisfied with the treatment outcome.
Conclusions: Patients with tooth agenesis had a high risk of severe root resorption after orthodontic treatment. A better aesthetic outcome was obtained with implant-supported reconstructions than with tooth-supported reconstructions. A positive but not significant correlation was observed between the professional and patient-based evaluations of aesthetic outcomes.
TL;DR: The effectiveness of water safety education programs could be strengthened by enhancing risk appraisal and coping skills and counter-acting the tendency of males and younger adults to overestimate their swimming ability and underestimate their risk with regard to drowning.
Abstract: Beach swimming is generally associated with a healthy lifestyle, yet the risk of drowning is universally significant. The purpose of the study was to investigate the factors associated with safe swimming behavior using protection motivation theory as a guiding theoretical framework. This cross-sectional study surveyed a sample of beachgoers (N = 3371) aged ≥16 years who completed an anonymous, self-report questionnaire to assess the associations between perceptions of the risk of drowning and safe swimming behavior. Compared with males, females perceived greater severity, vulnerability, response efficacy, and concern regarding their risk of drowning. Males, Maori, and 16 to 29 year olds reported higher self-efficacy scores compared to females, other ethnic groups, and older participants, respectively. After controlling for confounding variables, people perceiving a greater threat (severity) of experiencing difficulty while swimming as well as those reporting higher response efficacy (beliefs about the effectiveness of drowning prevention measures) were more likely to report safe swimming behavior. The effectiveness of water safety education programs could be strengthened by enhancing risk appraisal and coping skills and counter-acting the tendency of males and younger adults to overestimate their swimming ability and underestimate their risk with regard to drowning.
TL;DR: The influence of symptomatic anastomotic leakage after anterior resection for rectal cancer on short and long‐term mortality and local and distant recurrence was analysed.
Abstract: Objective The influence of symptomatic anastomotic leakage (AL) after anterior resection (AR) for rectal cancer on short and long-term mortality and local and distant recurrence was analysed.
Method All patients with a first diagnosis of rectal carcinoma were prospectively registered in a national database. This comprised 1494 Danish citizens who had had a curative AR between May 2001 and December 2004. Data on survival and recurrence were obtained from the National Patient Register. Multivariate analyses were performed.
Results Anastomotic leakage increased the 30-day mortality [odds ratio (OR) 4.01 (95% CI 2.24–7.17)]. Of other possible risk factors, only age had a significant interaction with leakage, as the risk of death within 30 days of AR decreased with increasing age. Long-term survival decreased significantly after AL [hazard ratio (HR) of 1.63, CI 1.21–2.19]. A total of 97 (6.7%) and 258 (18.0%) patients had local and distant recurrence respectively in the follow-up period. The risk of local and distant recurrence after AL was not different with HR of 1.50 (CI 0.84–2.69) and 1.13 (CI 0.76–1.69) respectively. No other factors influenced the risk of recurrence due to AL.
Conclusion Anastomotic leakage after AR for rectal cancer increases the 30-day and long-term mortality, but AL did not increase the risk of local and distant recurrence.
TL;DR: It is suggested that general strategy training improves performance in both trained and untrained activities compared to traditional therapy; and that a specific motor imagery protocol can improve mobility and recovery in the affected upper extremity in people living with the chronic effects of stroke.
Abstract: Objective: The objective of this critical review was to examine the literature regarding the use of cognitive strategies to acquire motor skills in people who have had a stroke, to determine which ...
TL;DR: The data show that vitamin C deficiency in early postnatal life results in impaired neuronal development and a functional decrease in spatial memory in guinea pigs, and it is speculated that this unrecognized effect of Vitamin C deficiency may have clinical implications for high-risk individuals, such as in children born from vitamin C-deficient mothers.
TL;DR: The findings lend further support to the involvement of serotonin, noradrenaline and dopamine pathways on obesity and glucose homeostasis, in particular when combined genotype associations are explored.
Abstract: Background: Candidate genes of psychological importance include 5HT2A, 5HT2C, and COMT, implicated in the serotonin, noradrenaline and dopamine pathways, which also may be involved in regulation of energy balance. We investigated the associations of single nucleotide polymorphisms (SNPs) of these genes with obesity and metabolic traits. Methodology/Principal Findings: In a population of 166 200 young men examined at the draft boards, obese men (n=726, BMI$31.0 kg/m 2 ) and a randomly selected group (n=831) were re-examined at two surveys at mean ages 46 and 49 years (S-46, S-49). Anthropometric, physiological and biochemical measures were available. Logistic regression analyses were used to assess age-adjusted odds ratios. No significant associations were observed of 5HT2A rs6311, 5HT2C rs3813929 and COMT rs4680 with obesity, except that COMT rs4680 GG-genotype was associated with fat-BMI (OR=1.08, CI=1.01–1.16). The SNPs were associated with a number of physiological variables; most importantly 5HT2C rs3813929 T-allele was associated with glucose (OR=4.56, CI=1.13–18.4) and acute insulin response (OR=0.65, CI=0.44–0.94) in S-49. COMT rs4680 GG-genotype was associated with glucose (OR=1.04, CI=1.00–1.09). Except for an association between 5HT2A rs6311 and totalcholesterol at both surveys, significant in S-46 (OR=2.66, CI=1.11–6.40), no significant associations were observed for the other phenotypes. Significant associations were obtained when combined genotype of 5HT2C rs3813929 and COMT rs4680 were examined in relation to BMI (OR=1.12, CI=1.03–1.21), fat-BMI (OR=1.22, CI=1.08–1.38), waist (OR=1.13, CI=1.04– 1.22), and cholesterol (OR=5.60, CI=0.99–31.4). Analyses of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) revealed, a 12.3% increased frequency of 5HT2C rs3813929 T-allele and an 11.6% increased frequency of COMT rs4680 GGgenotype in individuals with IGT or T2D (x 2 , p=0.05 and p=0.06, respectively). Examination of the combined genotypes of 5HT2C and COMT showed a 34.0% increased frequency of IGT or T2D (x 2 , p=0.01). Conclusions: The findings lend further support to the involvement of serotonin, noradrenaline and dopamine pathways on obesity and glucose homeostasis, in particular when combined genotype associations are explored.
TL;DR: If clinicians intend to address the needs of family members as well as patients, current approaches to goal-planning (and rehabilitation funding) may need to be reconsidered.
Abstract: Primary objective: Although family involvement is frequently identified as a key element of successful rehabilitation, questions remain about ‘how’ clinicians can best involve them. This study explored how clinicians talk about the involvement of families in goal-planning during rehabilitation of adults with acquired brain injury.Research design: Qualitative study drawing on grounded theory to elicit practitioner perspectives.Methods and procedures: Nine clinicians from a range of professional backgrounds were interviewed. Interview data were transcribed and analysed using the constant comparative method of grounded theory. NVivo software was used to assist with data management.Main outcomes and results: While family were often considered valuable contributors to the goal-planning process, they were also seen as potential barriers to the negotiation of goals between clinicians and patients and to patient–clinician relationships. Clinicians described restricting involvement of family members in situations ...
TL;DR: The intervention is feasible and outcomes based on parental reports provide preliminary support for the efficacy of the program.
Abstract: Objective The purpose of this study was to evaluate the feasibility and preliminary outcomes of a social skills group intervention program for child brain tumor survivors. Methods Participants were 32 survivors (14 females) aged 8–18 years. Medulloblastoma (28%) was the main diagnosis. The intervention consisted of eight 2-hr weekly sessions focused on social skills including friendship making and assertion. Survivors and parents completed measures of social skills, quality of life, behavior and depression, at baseline, pre- and postintervention, and 6 months later. Results Feasibility analyses revealed promising acceptability, retention, recruitment, and treatment fidelity. Significant improvement was found after intervention based on parents’ reports of self-control [F(1,27) ¼5.97, p<.05], social skills [F(1,28) ¼5.70, p<.05], and quality of life [F(1,15) ¼17.98, p<.01]. Conclusions The intervention is feasible and outcomes based on parental reports provide preliminary support for the efficacy of the program.
TL;DR: It is shown that when R253 and R254 (which are the homologues of R14 and R15 in PTEN) are mutated to alanines in Ci-VSP, phosphatase activity is disrupted, as revealed by a lack of effect on the ionic currents of KCNQ2/3, where current decrease is a measure of phosphate activity.
Abstract: The Ciona intestinalis voltage sensor–containing phosphatase (Ci-VSP) shares high homology with the phosphatidylinositol phosphatase enzyme known as PTEN (phosphatase and tensin homologue deleted on chromosome 10). We have taken advantage of the similarity between these proteins to inquire about the coupling between the voltage sensing and the phosphatase domains in Ci-VSP. Recently, it was shown that four basic residues (R11, K13, R14, and R15) in PTEN are critical for its binding onto the membrane, required for its catalytic activity. Ci-VSP has three of the basic residues of PTEN. Here, we show that when R253 and R254 (which are the homologues of R14 and R15 in PTEN) are mutated to alanines in Ci-VSP, phosphatase activity is disrupted, as revealed by a lack of effect on the ionic currents of KCNQ2/3, where current decrease is a measure of phosphatase activity. The enzymatic activity was not rescued by the introduction of lysines, indicating that the binding is an arginine-specific interaction between the phosphatase binding domain and the membrane, presumably through the phosphate groups of the phospholipids. We also found that the kinetics and steady-state voltage dependence of the S4 segment movement are affected when the arginines are not present, indicating that the interaction of R253 and R254 with the membrane, required for the catalytic action of the phosphatase, restricts the movement of the voltage sensor.
TL;DR: An adaptive, model-based predictive controller designed to incorporate the unique metabolic state of the neonate was developed that made optimum use of the very limited available BG measurements in the neonatal intensive care unit and provided robustness against BG sensor error and longer BG measurement intervals.
Abstract: Background:Premature neonates often experience hyperglycemia, which has been linked to worsened outcomes. Insulin therapy can assist in controlling blood glucose (BG) levels. However, a reliable, robust control protocol is required to avoid hypoglycemia and to ensure that clinically important nutrition goals are met.Methods:This study presents an adaptive, model-based predictive controller designed to incorporate the unique metabolic state of the neonate. Controller performance was tested and refined in virtual trials on a 25-patient retrospective cohort. The effects of measurement frequency and BG sensor error were evaluated. A stochastic model of insulin sensitivity was used in control to provide a guaranteed maximum 4% risk of BG < 72 mg/dl to protect against hypoglycemia as well as account for patient variability over 1–3 h intervals when determining the intervention. The resulting controller is demonstrated in two 24 h clinical neonatal pilot trials at Christchurch Women's Hospital.Results:Time in th...
TL;DR: The present studies suggest that the diabetogenic impact of the C-allele of rs4607103 near ADAMTS9 may in part be mediated through decreased insulin sensitivity of peripheral tissues.
Abstract: Backround A meta-analysis combining results from three genome-wide association studies and followed by large-scale replication identified six novel type 2 diabetes loci. Subsequent studies of the effect of these variants on estimates of the beta-cell function and insulin sensitivity have been inconclusive. We examined these variants located in or near the JAZF1 (rs864745), THADA (rs7578597), TSPAN8 (rs7961581), ADAMTS9 (rs4607103), NOTCH2 (rs10923931) and the CDC123/CAMK1D (rs12779790) genes for associations with measures of pancreatic beta-cell function and insulin sensitivity. Methodology/Results Oral and intravenous glucose stimulated insulin release (n = 849) and insulin sensitivity (n = 596) estimated from a hyperinsulinemic euglycemic clamp were measured in non-diabetic offspring of type 2 diabetic patients from five European populations. Assuming an additive genetic model the diabetes-associated major C-allele of rs4607103 near ADAMTS9 associated with reduced insulin-stimulated glucose uptake (p = 0.002) during a hyperinsulinemic euglycemic clamp. However, following intravenous and oral administration of glucose serum insulin release was increased in individuals with the C-allele (p = 0.003 and p = 0.01, respectively). A meta-analyse combining clamp and IVGTT data from a total of 905 non-diabetic individuals showed that the C-risk allele associated with decreased insulin sensitivity (p = 0.003) and increased insulin release (p = 0.002). The major T-allele of the intronic JAZF1 rs864745 conferring increased diabetes risk was associated with increased 2nd phase serum insulin release during an IVGTT (p = 0.03), and an increased fasting serum insulin level (p = 0.001). The remaining variants did not show any associations with insulin response, insulin sensitivity or any other measured quantitative traits. Conclusion The present studies suggest that the diabetogenic impact of the C-allele of rs4607103 near ADAMTS9 may in part be mediated through decreased insulin sensitivity of peripheral tissues.
TL;DR: Eight mononuclear iron(II) complexes of N(4)-3,5-di(2-pyridyl)-1,2,4-triazole (Rdpt) ligands have been prepared and characterized, allowing probing of the relationship between ligand substituent and the nature of the coordinating nitrogen atoms.
Abstract: Eight mononuclear iron(II) complexes of N(4)-3,5-di(2-pyridyl)-1,2,4-triazole (Rdpt) ligands have been prepared and characterized. In all cases the iron(II)/ligand ratio used is 1:3, giving red complexes of the general formula [Fe(II)(Rdpt)(3)](BF(4))(2) x solvents, in 55-89% yield. The ligands differ only in the nature of the N(4)-substituent (amino, pyrrolyl, iso-butyl, methyl, phenyl, para-tolyl, 3,5-dichlorophenyl, and 4-pyridyl; for ligands adpt, pldpt, ibdpt, medpt, phdpt, ptdpt, Cldpt, and pydpt, respectively) allowing substituent effects on the properties of the resulting iron(II) complexes to be probed. The low temperature crystal structures of seven of the complexes reveal low spin iron(II) environments. Packing analyses reveal anion-pi and acetonitrile-pi interactions involving the tetrafluoroborate counteranions and interstitial acetonitrile molecules, respectively. Both "pi-pockets" and "pi-sandwiches" are observed. Solid state magnetic susceptibility measurements (4-300 K) indicate the iron(II) is low spin (LS) in all complexes at all temperatures studied, except for [Fe(II)(pldpt)(3)](BF(4))(2) x 1 1/2 H(2)O which has the beginnings of spin crossover (SCO) at elevated temperatures. Downfield shifts and peak broadening observed in the variable temperature (1)H NMR studies indicate that in d(3)-nitromethane solution the LS [Fe(II)(Rdpt)(3)](2+) complexes are in equilibrium with a trace of a high spin (HS) species. (15)N NMR spectra (measured and calculated) of the ligands reveal that altering the N(4)-substituent changes the chemical shift of the N(1) triazole and pyridine nitrogen atoms, allowing probing of the relationship between ligand substituent and the nature of the coordinating nitrogen atoms.
TL;DR: Nurses' experiences of delivering spiritual support in a palliative care setting in the Republic of Ireland are described, resulting in the creation of a spiritual tapestry that 'weaves' together care and compassion with skills and knowledge in their nursing practice.
Abstract: This study aims to describe nurses' experiences of delivering spiritual support in a palliative care setting in the Republic of Ireland. The authors conducted semi-structured interviews with 22 nurses working in the area of specialist palliative care. A content analysis of the transcriptions revealed five sub-themes: understanding spirituality; the art of nursing in spiritual care; education and learning; the challenge of spiritual caring; and the dimensions of time. The resulting creation of a spiritual tapestry provided an overall theme. Nurses in this study were spiritually self-aware and placed a high value on the spiritual element of their caring role. Nurses described their individual understanding of spirituality and discussed how they recognized and addressed a patient's spiritual needs. Time was described as essential to the provision of spiritual support and appeared to be a significant resource challenge to the provision of spiritual care. The challenges of assessing spiritual needs and measuring outcomes of care were also reported. Participants in this study described the creation of a spiritual tapestry that 'weaves' together care and compassion with skills and knowledge in their nursing practice.