The neural basis of the imitation drive.
Spontaneous imitation is assumed to underlie the acquisition of important skills by infants, including language and social interaction. In this study, functional magnetic resonance imaging (fMRI) was used to examine the neural basis of 'spontaneously' driven imitation, which has not yet been fully investigated. Healthy participants were presented with movie clips of meaningless bimanual actions and instructed to observe and imitate them during an fMRI scan. The participants were subsequently shown the movie clips again and asked to evaluate the strength of their 'urge to imitate' (Urge) for each action. We searched for cortical areas where the degree of activation positively correlated with Urge scores; significant positive correlations were observed in the right supplementary motor area (SMA) and bilateral midcingulate cortex (MCC) under the imitation condition. These areas were not explained by explicit reasons for imitation or the kinematic characteristics of the actions. Previous studies performed in monkeys and humans have implicated the SMA and MCC/caudal cingulate zone in voluntary actions. This study also confirmed the functional connectivity between Urge and imitation performance using a psychophysiological interaction analysis. Thus, our findings reveal the critical neural components that underlie spontaneous imitation and provide possible reasons why infants imitate spontaneously.


[The value of exploratory anterior tympanotomy in differentiating causes of conductive hearing loss and assessment of their treatment results].
The aim of examination was value of exploratory anterior tympanotomy in differentiation causes of conductives hearing loss and assessment of results treatment. Materials of examinations determined 34 patients aged 15-66 years, treated in 1995-2000 years, who qualified to exploratory anterior tympanotomy in aim decision of cause of conductives hearing loss. Among of examined were 14 patients with suspicion of otosclerosis (41.2%), 12 patients with unclear etiology of hypoacusis (35.3) and 8 patients with deterioration of hearing after stapedectomy (23.5%). Preoperative diagnostic embraced: a history, otolaryngologic examination, full audiologic examination and chosen cases of radiologic assessment of temporal bone by computer tomography. After perioperative decision cause of conductive hypoacousis were performed of operations of improved hearing and comprised of average hearing loss by CPT and PTA pre- and postoperative treatment. After performed of exploratory tympanotomy there vere stated following causes of conductive hypoacusis: otosclerosis (61.8%), separated of prosthesis after stapedectomy (14.7%) synechia of prosthesis with tympanic membrane (8.8%) and in singles causes of ossicular synechia in tympanic cavum (5.9%), tympanosclerosis (5.9%) and vitium of middle ear (2.9%). The best of hearing improvement after repairment operations of conductive system were obtained in cases of stapedectomy, exchange of prosthesis after stapedectomy, reconstruction of system by TORP prosthesis, however smaller improvement after operations of synechias of stapes prosthesis with surroundings and postoperation of tympanosclerosis.


Method for image-based measurement of the reversible and irreversible contribution to the transverse-relaxation rate.
A multislice NMR imaging pulse sequence capable of measuring both the reversible and irreversible contribution to the transverse-relaxation rate (R'2 and R2) in a single scan is described. The method, termed GESFIDE (gradient-echo sampling of FID and echo) is based on sampling the descending and ascending portions of a Hahn echo with a train of gradient echoes. R2 and R'2 are computed by exploiting the differential evolution of the transverse magnetization before and after the phase-reversal pulse. Salient features of the method are its insensitivity to RF pulse imperfections and its high precision and efficiency. Applications examined involve the characterization of magnetically inhomogeneous tissues and biomaterials such as trabecular bone marrow in the skeleton and brain iron.


Participation of proteinase-activated receptor-2 in passive cutaneous anaphylaxis-induced scratching behavior and the inhibitory effect of tacrolimus.
Proteinase-activated receptor-2 (PAR2) may be an important regulator of skin mast cell function during cutaneous inflammation and hypersensitivity. However, little is known of the role of PAR2 in allergic pruritus, because mast cells, which are thought to be responsible for this symptom, can release a number of different pruritogens. In the present study, we investigated the effects of several agents on passive cutaneous anaphylaxis-induced scratching behavior in ICR mice. As a result, cetirizine and ketanserin produced dose-dependent inhibition of scratching behavior induced by passive cutaneous anaphylaxis. Combined cetirizine with ketanserin exhibited significant inhibitory effects for the number of passive cutaneous anaphylaxis-induced scratching behavior. Pretreatment of the experimental animals with PAR2-neutralizing antibody and protease inhibitor leupeptin significantly inhibited passive cutaneous anaphylaxis-induced scratching behavior. Furthermore, we found that topical application of tacrolimus significantly reduced the number of scratching behavior induced by passive cutaneous anaphylaxis in a dose-dependent manner. Combined cetirizine with tacrolimus also exhibited significant inhibitory effects for the number of passive cutaneous anaphylaxis-induced scratching behavior. Tacrolimus in doses of 3% and 10% significantly inhibited tryptase-induced scratching behavior. These results suggest that PAR2 may be involved in passive cutaneous anaphylaxis-induced scratching behavior and tacrolimus produces an anti-allergic pruritus effect in ICR mice.


Fabrication of new restorations with a consideration of oral hygiene.
Maintenance of adequate and effective oral hygiene is crucial for the long-term success of any dental therapy. This article discusses a case that failed due to the poor oral hygiene of the patient. Fabrication of uncomplicated restorations, patient education, motivation, maintenance and recall are important factors to be considered when treatment planning patients with poor oral hygiene.


The Effectiveness of Acupuncture for Dysphagia after Stroke: A Systematic Review and Meta-Analysis.
This study reviewed and evaluated existing evidence of the efficacy of acupuncture as a clinical treatment for dysphagia after stroke. Five English and four Chinese databases were searched from inception to March 2020. All randomized controlled trials (RCTs) incorporating acupuncture or acupuncture combined with other interventions for the treatment of dysphagia after stroke were enrolled. All data were independently assessed and extracted by two authors. The bias risk assessment recommended by the Cochrane Collaboration's tool was used to assess the quality of the selected studies. This meta-analysis was conducted by using RevMan 5.3. Pooled analyses were calculated by the mean difference (MD) and 95% confidence interval (CI). Heterogeneity was assessed by the I 2 test. Thirty-five studies involving 3024 patients were analyzed. The meta-analysis showed that the therapeutic efficacy of acupuncture combined with other interventions was better than that of the control group for the standardized swallowing assessment (SSA) score (MD = -3.78, 95% CI: -4.64 to -2.91, P < 0.00001), Ichiro Fujishima rating scale (IFRS) score (MD = 1.68, 95% CI: 1.16 to 2.20, P < 0.00001), videofluoroscopic swallowing study (VFSS) score (MD = 2.26, 95% CI: 1.77 to 2.74, P < 0.00001), and water swallowing test (WST) score (MD = -1.21, 95% CI: -1.85 to -0.57, P= 0.0002). In studies reporting adverse effects, no serious outcome from an adverse event was confirmed. This systematic review indicated that acupuncture could be an effective therapy for treating dysphagia after stroke although stricter evaluation standards and rigorously designed RCTs are needed.


Arginine Vasotocin and Neuropeptide Y Vary with Seasonal Life-History Transitions in Garter Snakes.
Transitions between life-history stages are often accompanied by dramatic behavioral switches that result from a shift in motivation to pursue one resource over another. While the neuroendocrine mechanisms that regulate such behavioral transitions are poorly understood, arginine vasotocin (AVT) and neuropeptide Y (NPY) are excellent candidates because they modulate reproductive and feeding behavior, respectively. We asked if seasonal changes in AVT and NPY are concomitant with the seasonal migration to and from the feeding grounds in red-sided garter snakes (Thamnophis sirtalis parietalis). Male and female snakes were collected in different migratory states during both the spring and fall. The total number of AVT- and NPY-immunoreactive (ir) cells was then quantified in each brain region of interest. To correct for potential variation in region volume related to sexually dimorphic body size in this species, we first determined that snout-vent length is an accurate proxy for regional brain volume. We then corrected each individual's ir cell number by its SVL to directly compare seasonal changes in AVT and NPY between males and females. Within the supraoptic nucleus, both males and females had more AVT-ir cells during the fall compared with spring. As predicted, males had significantly more AVT-ir cells during the spring mating season in the hypothalamus (HYP) and bed nucleus of the stria terminalis, brain regions important in regulating reproductive behavior. Females also had significantly more AVT-ir cells in the HYP during the spring, as well as a significantly higher number of hypothalamic AVT cells than males. During the fall, males had significantly more NPY-ir cells in the cortex and posterior HYP compared with spring, possibly reflecting increased feeding behavior during summer foraging. Females did not exhibit significant main effects of season on NPY-ir cell number in any region. Neither AVT- nor NPY-ir cell number varied significantly with migratory status, but we did observe significant changes related to seasonal transitions in reproductive state. Our results indicate that changes in brain AVT and NPY are associated with seasonal transitions in reproductive and foraging behaviors, and may be involved in mediating sex differences in the timing of life-history events.


Serum 25-hydroxyvitamin D status in chinese children with vitiligo: a case-control study.
Vitamin D can play a vital role in autoimmune diseases. Epidemiologic evidence demonstrates vitamin D deficiency excited in adult patients with vitiligo. To investigate 25-hydroxyvitamin D (25(OH)D) levels in children with vitiligo and explore possible relevant factors. A total of 114 patients and 100 controls were included in our case-control study. We analyzed the required data collected by the questionnaire and examination to reveal the correlation with 25(OH)D levels. The mean serum 25(OH)D levels in patients and controls were 43.62 ± 19.23 and 67.87 ± 19.45 nmol/L, respectively. The rate of deficient in patients and controls are 14.9% and 2%, respectively. There was significant difference between the 2 groups. Significant differences also existed on different ages comparing serum vitamin D levels of patients with controls ( P < .001). Age was an independent factor affecting 25(OH)D level ( P = .032). Two (1.8%) and 4 (3.5%) of children with vitiligo have comorbid autoimmune diseases and family history, respectively. There was no correlation between sex, duration of disease, type of vitiligo, skin lesion location, stage, family history, and comorbid autoimmune diseases with 25(OH)D levels. Serum vitamin D level was associated with onset vitiligo children. More sunshine and vitamin D fortified foods are necessary among children with age. The rates of children vitiligo with family history has decreased in China.


A high-throughput assay for screening the abilities of per- and polyfluoroalkyl substances in inducing plasma kallikrein-like activity.
The plasma consists of multiple functional serine zymogens, such as plasma kallikrein-kinin system (KKS), which are vulnerable to exogenous chemical exposure, and may closely relate to the deleterious effects. Testing whether the anthropogenic chemicals could increase the kallikrein-like activity in plasma or not would be of great help to understand their potentials in triggering the cascade activation of the plasma zymogens and explain the corresponding hematotoxicity. In this study, a novel high-throughput ex vivo assay was established to screen the abilities of emerging chemicals like per- and polyfluoroalkyl substances (PFASs) in inducing kallikrein-like activities on basis of using rat plasma as the protease zymogen source. Upon the optimization of the conditions in the test system, the assay gave sensitive fluorescent response to the stimulation of the positive control, dextran sulfate, and the dose-response showed a typical S-shaped curve with EC50 of 0.24 mg/L. The intra-plate and inter-plate relative standard deviations (RSDs) were less than 10% in the quantitative range of dextran sulfate, indicating a good reliability and repeatability of this newly-established assay. Using this method, several alternatives or congeners of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), including 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFESA), Ag-PFOA, K-PFOA, Na-PFOA and ammonium pentadecafluorooctanoate (APFO), were further screened, and their capabilities in inducing kallikrein-like activities were identified. The ex vivo assay newly-developed in the present study would be promising in high-throughput screening of the hematological effects of emerging chemicals of concern.


[Laparoscopic treatment of perforated duodenal ulcer: 84 cases in Tunisia].
The purpose of this study was to evaluate the feasibility, efficacy and safety of the laporascopic treatment of perforated duodenal ulcer. This retrospective study included patients who underwent laparoscopic treatment of perforated duodenal ulcer during the seven-year period from 2001 to 2007. The procedure included direct suture of the perforated ulcer followed by peritoneal lavage. All patients received medical treatment including Helicobacter pylori eradication and proton pump inhibitor therapy. A total of 84 patients underwent laparoscopic surgery for perforated duodenal ulcer during the study period. There were 81 men and 3 women with a mean age of 28 years. Laparoscopic examination confirmed diagnosis of perforated duodenal ulcer in all cases. Direct suture of the ulcer was successful in 72 cases. In the remaining 12 cases conversion to open surgery was necessary due to difficulty in achieving peritoneal lavage in 6 cases, ulcer size and edge friability in 5, and septic shock in one. The mean duration of the procedure was 95 minutes (range, 60 to 180 minutes). The mean postoperative complication rate was 15.4%. Complications included peritonintis in one case and digestive fistula in one. There were no postoperative deaths. All patients were re-examined after 25 months. Two patients presented recurrences after the laparoscopic treatment and required tri-therapy. Laparoscopic suture of perforated duodenal ulcer is safe and effective. It avoids the need for laparotomy that is associated with a risk for septic and parietal complications. Since medical treatment is effective for ulcerous disease, there are currently no indications for radical treatment.


Towards the Application of Fuzzy Logic for Developing a Novel Indoor Air Quality Index (FIAQI).
In the past few decades, Indoor Air Pollution (IAP) has become a primary concern to the point. It is increasingly believed to be of equal or greater importance to human health compared to ambient air. However, due to the lack of comprehensive indices for the integrated assessment of indoor air quality (IAQ), we aimed to develop a novel, Fuzzy-Based Indoor Air Quality Index (FIAQI) to bridge the existing gap in this area. We based our index on fuzzy logic, which enables us to overcome the limitations of traditional methods applied to develop environmental quality indices. Fifteen parameters, including the criteria air pollutants, volatile organic compounds, and bioaerosols were included in the FIAQI due mainly to their significant health effects. Weighting factors were assigned to the parameters based on the medical evidence available in the literature on their health effects. The final FIAQI consisted of 108 rules. In order to demonstrate the performance of the index, data were intentionally generated to cover a variety of quality levels. In addition, a sensitivity analysis was conducted to assess the validity of the index. The FIAQI tends to be a comprehensive tool to classify IAQ and produce accurate results. It seems useful and reliable to be considered by authorities to assess IAQ environments.


A systematic examination of smoke-free policies in multiunit dwellings in Virginia as reported by property managers: implications for prevention.
In most states, smoking has been curtailed to some extent in public buildings, workplaces, and restaurants. The next frontier for smoke-free policies is the multiunit dwelling industry. However, the extent to which smoke-free housing currently is available is unknown. The purpose of this study was to measure the market for smoke-free housing in Virginia and to identify barriers to adopting smoke-free policies. Telephone interviews were conducted with property managers of rental apartments, townhouses, senior housing, and public housing in four Virginia cities. Four cities in Virginia. Two hundred sixty-three property managers in four cities in Virginia (approximately 75 property managers per city). Property managers were administered a brief telephone survey. Only 33.8% of property managers reported some type of smoke-free policy, with only 15% of those policies prohibiting smoking in residential units. Most property managers without a smoke-free policy were not considering adopting such a policy for a variety of reasons. The availability of smoke-free multiunit dwellings is severely lacking. This study identified a number of science-based and legal misperceptions that may prevent the adoption of smoke-free policies. Correction of these misperceptions is warranted to increase the availability of smoke-free housing. Such policies will be useful in creating environments that support good health practices while simultaneously protecting tenants from exposure to secondhand smoke.


Apatinib Plus Temozolomide: An Effective Salvage Treatment for Recurrent Glioblastoma.
Treatment for recurrent glioblastoma is poor, and there is a need for better therapies. Here we retrospectively assessed the efficacy and toxicity of temozolomide plus apatinib, an oral small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 in recurrent glioblastoma. A retrospective analysis of patients with recurrent glioblastoma who underwent apatinib plus temozolomide treatment was performed. Apatinib was given at 500 mg once daily. Temozolomide was administered at 200 mg/m2/d on days 1-5 or 50 mg/m2/d continuous daily according to whether they had experienced temozolomide maintenance treatment before. The main clinical data collected included tumor characteristics, status of MGMT promoter, and IDH mutation, number of relapse, response, survival, adverse reactions, and salvage therapies. From April 2016 to August 2019, thirty-one patients were identified. The objective response rate was 26.3%, and the disease control rate was 84.2%. The progression-free survival (PFS) at 6 months and overall survival (OS) at 12 months were 44.6 and 30.2%. The median PFS and OS were 4.9 and 8.2 months, respectively. Two patients achieved long PFS of 30.9 and 38.7+ months. The median survival time after progression of the patients with or without salvage bevacizumab was 5.1 versus 1.2 months. The most common grade 3 or 4 toxicities were hypertension (5.8%), decreased appetite (5.8%), and thrombocytopenia (4.3%), most of which were resolved after symptomatic treatment or dose reduction. Apatinib plus temozolomide is an effective salvage regimen with manageable toxicities for recurrent glioblastoma and could not reduce the sensitivity to bevacizumab.


Functional macrophages and gastrointestinal disorders.
Macrophages (MΦ) differentiate from blood monocytes and participate in innate and adaptive immunity. Because of their abilities to recognize pathogens and activate bactericidal activities, MΦ are always discovered at the site of immune defense. MΦ in the intestine are unique, such that in the healthy intestine, they possess complex mechanisms to protect the gut from inflammation. In these complex mechanisms, they produce anti-inflammatory cytokines, such as interleukin-10 and transforming growth factor-β, and inhibit the inflammatory pathways mediated by Toll-like receptors. It has been demonstrated that resident MΦ play a crucial role in maintaining intestinal homeostasis, and they can be recognized by their unique markers. Nonetheless, in the inflamed intestine, the function of MΦ will change because of environmental variation, which may be one of the mechanisms of inflammatory bowel disease (IBD). We provide further explanation about these mechanisms in our review. In addition, we review recent discoveries that MΦ may be involved in the development of gastrointestinal tumors. We will highlight the possible therapeutic targets for the management of IBD and gastrointestinal tumors, and we also discuss why more details are needed to fully understand all other effects of intestinal MΦ.


Caspase 9 promoter polymorphisms and risk of primary lung cancer.
Caspase-9 (CASP-9) is an initiator CASP in the apoptosome-driven apoptosis pathway and plays an important role in the development and progression of cancer. Polymorphisms in the promoter region of the CASP-9 gene may influence the promoter activity of this gene, thereby modulating susceptibility to lung cancer. To test this hypothesis, we examined the association of four polymorphisms [-1263A>G, -905T>G, -712C>T and -293_-275delCGTGAGGTCAGTGCGGGGA (-293del)] in the CASP-9 promoter with the risk of lung cancer in a Korean population. The CASP-9 genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency-matched for age and gender. The -1263 GG genotype was associated with a significantly decreased risk of lung cancer compared with the -1263 AA genotype or combined -1263 AA+AG genotype [adjusted odds ratio (OR)=0.64, 95% confidence interval (95% CI)=0.42-0.98, P=0.04 and adjusted OR=0.67, 95% CI=0.46-0.97, P=0.01, respectively]. For the -712C>T polymorphism, individuals with at least one -712T allele were at a significantly increased risk of lung cancer compared with those harboring the -712 CC genotype (adjusted OR=1.42, 95% CI=1.06-1.89, P=0.02). Consistent with the results of genotype analyses, the -1263G/-712C (G-C) haplotype was associated with a significantly decreased risk of lung cancer [adjusted OR=0.59, 95% CI=0.47-0.75, P and Bonferroni corrected P (Pc)<0.001]. Moreover, the risk of lung cancer decreased in a dose-dependent manner as the number of the G-C haplotypes increased (adjusted OR=0.60, 95% CI=0.45-0.81, P=0.0007 and Pc=0.0014 for the G-C heterozygotes and adjusted OR=0.34, 95% CI=0.17-0.68, P=0.0023 and Pc=0.0046 for the G-C homozygotes; P(trend)<0.001). The promoter assay revealed the G-C haplotype to have a significantly higher promoter activity than the -1263G/-712T and -1263A/-712C haplotypes. These results suggest that CASP-9 promoter polymorphisms affect CASP-9 expression and contribute to genetic susceptibility to lung cancer.


Photochemistry of riboflavin derivatives in methanolic solutions.
Light-induced degradation of the riboflavin derivatives is reported, including 5-deaza-riboflavin, iso-6,7-riboflavin, 3-methyl-tetra-acetyl-riboflavin (3MeTARF), and 3-benzyl-lumiflavin. The studied compounds undergo photolytic processes with considerable quantum yields in methanolic solutions (φ ≈ 10(-3)-10(-4) mol einst(-1)). Photolysis in anaerobic conditions is more efficient than that in the presence of oxygen. Experiments show that triplet excited state of flavin molecules is involved in the reactions. The main photoproducts are the respective alloxazinic and isoalloxazinic derivatives of the substrates. 3MeTARF reveals higher photostability than riboflavin. The values of photodegradation quantum yields were estimated for the four studied derivatives.


Application of Network Analysis to Flow Systems with Alternating Wave Channels: Part B. (Superimposed Drag-Pressure Flows in Extrusion).
Due to progress in the development of screw designs over recent decades, numerous high-performance screws have become commercially available in single-screw extrusion. While some of these advanced designs have been studied intensively, others have received comparatively less attention. We developed and validated a semi-numerical network-theory-based modeling approach to predicting flows of shear-thinning polymer melts in wave-dispersion screws. In the first part (Part A), we systematically reduced the complexity of the flow analysis by omitting the influence of the screw rotation on the conveying behavior of the wave zone. In this part (Part B), we extended the original theory by considering the drag flow imposed by the screw. Two- and three-dimensional melt-conveying models were combined to predict locally the conveying characteristics of the wave channels in a discretized flow network. Extensive experiments were performed on a laboratory single-screw extruder, using various barrel designs and wave-dispersion screws. The predictions of our semi-numerical modeling approach for the axial pressure profile along the wave-dispersion zone accurately reproduce the experimental data. Removing the need for time-consuming numerical simulations, this modeling approach enables fast analyses of the conveying behavior of wave-dispersion zones, thereby offering a useful tool for design and optimization studies and process troubleshooting.


Couples' perceptions of effective and ineffective ingredients of marital therapy.
Reports from 15 couples of the helpful and hindering aspects of their marital therapy were sorted into 12 effective ingredient categories and 5 ineffective categories. The couples were interviewed after receiving eight sessions of marital therapy. Results indicate that couples expect marital therapists to be active, directive, and focused while providing a safe and empathic therapeutic environment. Also, couples identified therapist mistakes such as wasting time and being unclear in therapy as detrimental to therapy. The implications of these empirically derived processes for the theory, research, and practice of marital therapy are discussed.


The impact of antiretroviral therapy in resource-limited settings and current HIV therapeutics.
Four million people of the global total of 35 million with HIV infection are from South-East Asia. ART is currently utilized by 15 million people and has led to a dramatic decline in the mortality rate, including those in low- and middle-income countries. A reduction in sexually transmitted HIV and in comorbidities including tuberculosis has also followed. Current recommendations for the initiation of antiretroviral therapy in people who are HIV+ are essentially to initiate ART irrespective of CD4 cell count and clinical stage. The frequency of HIV testing should be culturally specific and based on the HIV incidence in different key populations but phasing in viral load technology in LMIC is an urgent priority and this needs resources and capacity. With the availability of simplified potent ART regimens, persons with HIV now live longer. The recent WHO treatment guidelines recommending routine HIV testing and earlier initiation of treatment should be the stepping stone for ending the AIDS epidemic and to meet the UNAIDS mission of 90*90*90.


Recruitment and retention of healthy and high-risk older adults for a multiyear influenza vaccination study.
Evaluate five different recruitment strategies for their capacity to enroll and retain both healthy and vulnerable older adults as part of a multiyear influenza vaccination study. We analyzed recruitment methods and other characteristics ofindividuals who participated in or were considered for five sequential one-year studies. Of 940 screened individuals, 820 met eligibility criteria with 795 enrolled over the five-year study (307 primary participants). Among these enrollees, 63.4% were female and 95.5% were white, with mean ages of 75.3 (older group) and 30.6 (younger group). More than a half (56.7%) of the participants enrolled more than once, participating an average of 2.56 (SD = 1.6) times. The majority (81.9%) of individuals recruited each year were return participants identified during earlier recruitments. Physician referrals resulted in only 5.3% recruitments. Recruitment and retention of study subjects, especially older adults, was facilitated by the existence ofa database listing past participants.


Self-reported occupational physical activity and cardiorespiratory fitness: Importance for cardiovascular disease and all-cause mortality.
This study aimed to investigate whether workers with the combination of high occupational physical activity (OPA) and low cardiorespiratory fitness have an increased risk of cardiovascular disease (CVD) and all-cause mortality. Using multivariable Cox proportional hazards regression, we analyzed 2190 males and 2534 females from the Copenhagen City Heart Study, aged 20-67 years and with no known CVD at study entry in 1991-1994, for the risk of CVD and all-cause mortality from independent, stratified and combinations of self-reported OPA (ie, low, moderate and high) and cardiorespiratory fitness (low, same and higher as peers) at baseline. During a median follow-up of 18.5 years, 257 and 852 individuals died from CVD and any cause, respectively. In the fully-adjusted model, an increased risk for CVD mortality was found for those with low compared to high self-reported cardiorespiratory fitness [hazard ratio (HR) 2.17, 95% confidence interval (95% CI) 1.40-3.38), for those with high compared to low OPA (HR 1.45, 95% CI 1.05-2.00), and for those with high compared to low OPA within the strata of low self-reported cardiorespiratory fitness (HR 2.83, 95% CI 1.24-6.46). Moreover, those with the combination of high OPA and low self-reported cardiorespiratory fitness had an increased risk for CVD mortality compared to those with the combination of low OPA and high self-reported cardiorespiratory fitness (HR 6.22, 95% CI 2.67-14.49). Rather similar, but lower risk estimates were found for all-cause mortality. These findings may have important implications for CVD prevention among workers with excessive cardiovascular strain at work.


[Hemodynamic, endocrinological and psychological investigations on subjects during helicopter flights].
The emergency transport in an ambulance can be a considerable physical and psychological stress for the patient. In this article we report on a stress test with 23 volunteers transported in an emergency helicopter. We determined the hemodynamic and endocrinological values of 23 volunteers after a standardised 15-minute transportation in a helicopter type EC 135. During the take-off we registered an increase of the heart rate of 18% and endocrinological parameters were elevated up to 51%. All the registered values were within the physiological tolerance level. Psychological tests showed a feeling of fear and agitation before take-off, but after the flight the volunteers reported less stress than expected. The stress situation is caused by fear of the flight, that cannot be objectively justified. The relatively low stress induction by helicopter transportation might be an indication that there should be more patient transport with modern helicopters, especially for non-trauma patients. This subject deserves further investigation.


Experiences of persons with multiple chemical sensitivity with mental health providers.
In this paper, we summarize the results of an online survey of persons in the United States with chemical intolerance/multiple chemical sensitivity who sought help from mental health providers, including counselors, psychologists, psychiatrists, and others. Respondents reported on their most recent contact with a provider, describing reasons for the contact, accommodations requested and received, and suggestions for how the experience could be more helpful. Overall, though clients were accommodated in small ways, some received no accommodation, and many felt that the providers needed to be more knowledgeable regarding chemical intolerance. Results are discussed in terms of the importance of providers becoming more aware of multiple chemical sensitivity and more willing to make their services accessible to these clients.


Biological advances and clinical applications of Fc receptors for IgG.
There are three classes of Fc gamma receptor proteins, Fc gamma RI (CD64), Fc gamma RII (CDw32), and Fc gamma RIII (CD16), which are encoded by at least eight genes. In this review we summarize some of the biological advances in the Fc gamma receptors during the past year, specifically: 1) identification of genes and their products; 2) regulation of gene expression and modulation of receptor number; 3) cellular functions and mechanisms of signal transduction; 4) ligand binding and the role of polymorphisms; and 5) soluble Fc gamma receptors. We also highlight the direct clinical applications of this Fc gamma receptor research.


Description of Paracoccus endophyticus sp. nov., isolated from Gastrodia elata Blume.
A Gram-stain-negative, strictly aerobic, non-motile strain, SYSUP0003T, was isolated from tubers of Gastrodia elata Blume. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SYSUP0003T belonged to the genus Paracoccus, with the highest sequence similarity to the type strain of Paracoccus sediminis (97.5 %). Strain SYSUP0003T grew at pH 6.0-8.0 and 4-30 °C with optimum growth at pH 7.0 and 28 °C. Strain SYSUP0003T could tolerate up to 1 % (w/v) NaCl and grew optimally in the absence of NaCl. The isoprenoid quinone of strain SYSUP0003T was Q-10. The major fatty acids were C18 : 0, C16 : 0, C10 : 0 3-OH and summed feature 7. The polar lipids were diphosphatidylglycerol (DPG), aminophospholipids (AL), phosphatidylglycerol (PG), phosphatidylcholine (PC) and four unidentified polar lipids (L). The genome size was 3 204 685 bp, with a DNA G+C content of 69.7 mol%. The average nucleotide identity values between strain SYSUP0003T and P. sediminis DSM 26170T (ANIm 84.2 %, ANIb 75.6 %), Paracoccus solventivorans DSM 6637T (ANIm 84.5 %, ANIb 76.9 %) and Paracoccus alkenifer DSM 11593T (ANIm 84.3 %, ANIb 77.3 %) were below the cut-off level (95-96 %) for species delineation. Based on phenotypic, chemotaxonomic and molecular characterizations, strain SYSUP0003T represents a novel species of the genus Paracoccus, for which the name Paracoccus endophyticus sp. nov. is proposed. The type strain is SYSUP0003T (=KCTC 62180T=CGMCC 1.16545T).


NPHS2 mutations in late-onset focal segmental glomerulosclerosis: R229Q is a common disease-associated allele.
Mutations in NPHS2, encoding podocin, have been identified in childhood onset focal and segmental glomerulosclerosis (FSGS). The role of NPHS2 in adult disease is less well defined. We studied 30 families with FSGS and apparent autosomal recessive inheritance and 91 individuals with primary FSGS. We screened family members for NPHS2 mutations. NPHS2 mutations appeared to be responsible for disease in nine of these families. In six families, the affected individuals were compound heterozygotes for a nonconservative R229Q amino acid substitution. This R229Q variant has an allele frequency of 3.6% in a control population. In these families, R229Q was the only mutation identified on one of the two disease-associated NPHS2 alleles. We used in vitro-translated podocin and purified nephrin to investigate the effect of R229Q on their interaction and found decreased nephrin binding to the R229Q podocin. These data suggest that this common polymorphism contributes to the development of FSGS. Chromosomes bearing the R229Q mutation share a common haplotype defining an approximately 0.2-Mb region. R229Q appears to enhance susceptibility to FSGS in association with a second mutant NPHS2 allele. Identification of R229Q mutations may be of clinical importance, as NPHS2-associated disease appears to define a subgroup of FSGS patients unresponsive to corticosteroids.


[Effects of Recombinant Human Erythropoietin on MPC-11 Myeloma Cells Cultured In Vitro].
To explore the effect of recombinant human erythropoietin (rhEPO) on myeloma cell line MPC-11 in vitro and its anti-tumor mechamism so as to provide the theoretic evidence for treatment of multiple myeloma by using rhEPO. MPC-11 cells were cultured in RPMI 1640 medium, then the MPC-11 cells in logarithmic growth phase were seed in 96 well culture plates at a density of 1×104/ml cells with 100 µl per well. For all the experiments, the control and rhEPO groups were set up, and the rhEPO group was divided into different concentration groups: 20, 40, 60, 80, 100, 200 and 400 rhEPO U/ml. The cultured MPC-11 cells in each groups were collected at day 1, 2, 3, 4, 5 and 6, and the viability of MPC-11 cells was assayed by using CCK-8 method, the MPC-11 cell apoptosis was detected by flow cytometry with Annexin V/PI double staining, the levels of IL-6, IgG and kappa light chain in cell supernatant were detected by ILISA. The apoptosis rate in MPC-11 cells treated with 200 U/ml of rhEPO at day 21 was significantly higher than that in control group(P<0.05); the apoptosis rate in MPC-11 cells treated with 400 U/ml of rhEPO at day 10, 15, 21 was higher than that in control group at same time points, respectively (P<0.05), suggesting that the MPC-11 cell apoptosis rate was enhanced with increase of rhEPO concentration and prolonging of culture time(P<0.05), the IL-6 level in supernatant of cell treated with 400 U/ml of rhEOP for 15 days was lower than that in control group(P<0.05), while the IL-6 level in supernatant of cells treated with 100, 200, 400 U/ml of rhEPO for 21 days decreased (P<0.05); The levels of IgG and kappa light chain in supernatant of cells treated with 400 U/ml of rhEPO for 21 days all were significantly lower than those in control group(P<0.05). The rhEPO can induce apoptosis of MPC-11 cells with concentration- and time-dependent manner, and can reduce levels of IgG, kappa light chain secreted by MPC-11 cells with time-dependent manner.


[Coarctation of the aorta as a cause of difficult-to-control hypertension].
Coarctation of the aorta (CoA) is a congenital narrowing of the proximal descending aorta, which may express itself as resistant hypertension in children and young adults. A 25-year old female is known with hypertension for 9 years. Due to persistent hypertension despite telmisartan and amlodipine, she is referred to the outpatient clinic internal medicine, where a systolic murmur is heard. Consequently, she is referred to the cardiologist, who identifies a well-functioning bicuspid aortic valve and a severe CoA with extensive collateral circulation. The CoA is treated by stent implantation. After 7 months, the patient is normotensive without any antihypertensive medication. Hypertension in children and young adults is a rare finding and often has a secondary cause. CoA is characterized by a combination of hypertension and a systolic blood pressure gradient between upper and lower extremities. Early diagnosis and treatment are crucial to avoid late cardiovascular complications.


Post-mortem assessment in vascular dementia: advances and aspirations.
Cerebrovascular lesions are a frequent finding in the elderly population. However, the impact of these lesions on cognitive performance, the prevalence of vascular dementia, and the pathophysiology behind characteristic in vivo imaging findings are subject to controversy. Moreover, there are no standardised criteria for the neuropathological assessment of cerebrovascular disease or its related lesions in human post-mortem brains, and conventional histological techniques may indeed be insufficient to fully reflect the consequences of cerebrovascular disease. Here, we review and discuss both the neuropathological and in vivo imaging characteristics of cerebrovascular disease, prevalence rates of vascular dementia, and clinico-pathological correlations. We also discuss the frequent comorbidity of cerebrovascular pathology and Alzheimer's disease pathology, as well as the difficult and controversial issue of clinically differentiating between Alzheimer's disease, vascular dementia and mixed Alzheimer's disease/vascular dementia. Finally, we consider additional novel approaches to complement and enhance current post-mortem assessment of cerebral human tissue. Elucidation of the pathophysiology of cerebrovascular disease, clarification of characteristic findings of in vivo imaging and knowledge about the impact of combined pathologies are needed to improve the diagnostic accuracy of clinical diagnoses.


Evolution of human receptor binding affinity of H1N1 hemagglutinins from 1918 to 2009 pandemic influenza A virus.
The recent outbreak of the novel 2009 H1N1 influenza in humans has focused global attention on this virus, which could potentially have introduced a more dangerous pandemic of influenza flu. In the initial step of the viral attachment, hemagglutinin (HA), a viral glycoprotein surface, is responsible for the binding to the human SIA alpha2,6-linked sialopentasaccharide host cell receptor (hHAR). Dynamical and structural properties, based on molecular dynamics simulations of the four different HAs of Spanish 1918 (H1-1918), swine 1930 (H1-1930), seasonal 2005 (H1-2005), and a novel 2009 (H1-2009) H1N1 bound to the hHAR were compared. In all four HA-hHAR complexes, major interactions with the receptor binding were gained from HA residue Y95 and the conserved HA residues of the 130-loop, 190-helix, and 220-loop. However, introduction of the charged HA residues K145 and E227 in the 2009 HA binding pocket was found to increase the HA-hHAR binding efficiency in comparison to the three previously recognized H1N1 strains. Changing of the noncharged HA G225 residue to a negatively charged D225 provides a larger number of hydrogen-bonding interactions. The increase in hydrophilicity of the receptor binding region is apparently an evolution of the current pandemic flu from the 1918 Spanish, 1930 swine, and 2005 seasonal strains. Detailed analysis could help the understanding of how different HAs effectively attach and bind with the hHAR.


RNA processing and its regulation: global insights into biological networks.
In recent years views of eukaryotic gene expression have been transformed by the finding that enormous diversity can be generated at the RNA level. Advances in technologies for characterizing RNA populations are revealing increasingly complete descriptions of RNA regulation and complexity; for example, through alternative splicing, alternative polyadenylation and RNA editing. New biochemical strategies to map protein-RNA interactions in vivo are yielding transcriptome-wide insights into mechanisms of RNA processing. These advances, combined with bioinformatics and genetic validation, are leading to the generation of functional RNA maps that reveal the rules underlying RNA regulation and networks of biologically coherent transcripts. Together these are providing new insights into molecular cell biology and disease.


Psychiatric and psychosomatic symptoms are increasing problems among Swedish schoolchildren.
Paediatricians and other professionals in Sweden note that the amount of children with psychiatric and psychosomatic symptoms is growing in number. Suicide attempts among the young (15-24 y) increased by more than 30% from 1998-2003. The Swedish National Board for Health and Welfare's 2004 guidelines for school healthcare shed light on this increasing problem among schoolchildren. An article in this issue of Acta Paediatrica, "Living conditions and psychosomatic complaints in Swedish schoolchildren", analyses economic stress as a causative factor leading to psychosomatic symptoms such as headache, abdominal pain and difficulty in falling asleep. Living conditions, however, most likely include other factors related to our modern and ever-changing society that also have an impact on the growing child. Psychiatric health is changing for the worse among Swedish schoolchildren. The cause is multifactorial. Economic stress is one factor, but there are also other possible causes related to modern society that correlate to the increase of psychosomatic problems among schoolchildren. Three major problems are among those suspected: impaired education and deficient working environment in Swedish schools, a general lack of adult contact and guidance, and excessive computer and TV use.


Anticonvulsant activity of Hypericum scabrum L.; possible mechanism involved.
Hypericum (H.) spp. has been used in traditional medicine for their anticonvulsant effect for many years. In spite of many works on this genus, little is known about H. scabrum. In this work, anticonvulsant activity of H. scabrum was investigated. Anticonvulsant activity of aqueous extract was evaluated by pentylenetetrazole (PTZ) induced convulsion and picrotoxin induced convulsion. Also, nitric oxide radical scavenging was investigated as a possible mechanism involved. Extract (125-500 mg kg-1, i.p.) significantly delayed the onset of PTZ induced convulsion. At 500 mg kg-1, 100% protection against mortality was observed. At this dose, it significantly prolonged the onset of picrotoxin induced convulsion in mice, too. It showed significant nitric oxide radical scavenging activity. Mechanism of anticonvulsant activity may be through GABA and/or nitric oxide pathway.


The mechanisms of harmonic sound generation during phonation: A multi-modal measurement-based approach.
Sound generation during voiced speech remains an open research topic because the underlying process within the human larynx is hardly accessible for direct measurements. In the present study, harmonic sound generation during phonation was investigated with a model that replicates the fully coupled fluid-structure-acoustic interaction (FSAI). The FSAI was captured using a multi-modal approach by measuring the flow and acoustic source fields based on particle image velocimetry, as well as the surface velocity of the vocal folds based on laser vibrometry and high-speed imaging. Strong harmonic sources were localized near the glottis, as well as further downstream, during the presence of the supraglottal jet. The strongest harmonic content of the vocal fold surface motion was verified for the area near the glottis, which directly interacts with the glottal jet flow. Also, the acoustic back-coupling of the formant frequencies onto the harmonic oscillation of the vocal folds was verified. These findings verify that harmonic sound generation is the result of a strong interrelation between the vocal fold motion, modulated flow field, and vocal tract geometry.


A Pan-Cancer Analysis of the Oncogenic Role of Cell Division Cycle-Associated Protein 4 (CDCA4) in Human Tumors.
To unravel the oncogenic role of CDCA4 in different cancers from the perspective of tumor immunity. Raw data on CDCA4 expression in tumor samples and paracancerous samples were obtained from TCGA and GTEX databases. In addition, we investigated pathological stages and the survival analysis of CDCA4 in pan-cancer across Gene Expression Profiling Interactive Analysis (GEPIA) database. Cox Proportional Hazards Model shows that high CDCA4 levels are associated with several vital indicators in oncology. On the one hand, we explored the correlation between CADA4 expression and tumor immune infiltration by the TIMER tool; On the other hand, we utilized the methods of CIBERSORT and ESTIMATE computational to evaluate the proportion of tumor infiltrating immune cells (TIIC) and the amounts of stromal and immune components based on TCGA database. The use of antineoplastic drugs and the expression of CDCA4 also showed a high correlation via linear regression. Protein-Protein Interaction analysis was performed in the GeneMANIA database, and enrichment analysis was performed and predicted signaling pathways were identified by using Gene Ontology and Kyoto Encyclopedia of Genes. The correlation between CDCA4 expression with Copy number variations (CNV) and methylation is detailed, respectively. Molecular biology experiments including Western blotting, flow cytometry, EDU staining, Transwell and Wound Healing assay to validate the cancer promoting role of CDCA4 in hepatocellular carcinoma (HCC). Most tumors highly expressed CDCA4. Elevated CDCA4 expression was associated with poor OS and DFS. There was a significant correlation between CDCA4 expression and TITCs. Moreover, markers of TIICs exhibited distinct patterns of CDCA4 associated immune infiltration. In addition, we pay attention to the association between the expression of CDCA4 and the use of the anti-tumor drugs. CDCA4 is related to biological progress (BP), cellular component (CC) and molecular function (MF). Dopaminergic Synapse, AMPK, Sphingolipid, Chagas Disease, mRNA Surveillance were significantly enriched pathways in positive and negative correlation genes with CDCA4. CNV is thought to be a positive correlation with CDCA4 expression. Conversely, methylation is negative correlation with CDCA4 expression. Molecular biology experiments confirm a cancer promoting role for CDCA4 in HCC. CDCA4 may serve as a biomarker for cancer immunologic infiltration and poor prognosis, providing a new way of thinking for cancer treatment.


Bacteremia following postoperative choledochofiberscopy--a prospective study.
The following investigation was undertaken in order to determine the frequency and clinical consequences of bacteremia after postoperative choledochofiberscopy. A total of 100 patients were prospectively studied for the frequencies of bacteremia after postoperative choledochoscopy. Positive blood cultures were obtained in 15%; at 5-minutes period in seven patients, at 15-minutes in eight patients and at 30-minutes in two patients. There were two patients with positive cultures at 5 minutes and 10 minutes periods. All the bacteria species cultured were aerobes. Enterococcus, E-coli and Klebsilla were the most commonly cultured bacteria. The frequencies of occurrence of bacteremia seemed not be influenced by the existence of residual stones, session of the endoscopy and duration of the procedure. Six of the 15 bacteremic patients developed cholangitis within 24 hours of the procedure. They all recovered with antibiotic treatment. Patients with negative blood cultures were not found with cholangitic symptoms after the postoperative choledochoscopy. The results of our study indicated that fifteen percent of patients undergoing postoperative choledochofiberscopy are associated with bacteremia. We believe that with adequate aseptic preparation and meticulous, gentle manipulation, routine prophylactic antibiotics may not be necessary for postoperative choledochoscopy in selected conditions.


No aggregate change in homosexual HIV risk behaviour among gay men attending the Gay Pride festivals, United Kingdom, 1993-1995.
To examine aggregate changes in homosexual HIV risk-taking among gay men attending the Gay Pride festival in the United Kingdom over a 3-year period during which HIV prevention activity targeted at this population increased considerably. Three cross-sectional self-completion questionnaires at yearly intervals asking identical questions on sexual behaviour in the preceding year. Lesbian and Gay Pride festival held in London, June 1993, 1994 and 1995. Men attending the festival who were UK resident, had ever had sex with another man and who were willing to fill out a questionnaire (n = 1620, 1753 and 1168 in 1993, 1994 and 1995, respectively). Self-reported numbers of sexual partners, sexual partners with whom anopenile intercourse occurred and sexual partners with whom anopenile intercourse occurred without a condom. Over the 3-year period there were no changes in the proportion of men engaging in any of the sexual behaviour measures. At each cross-section, one in three men (514 out of 1566, 511 out of 1612, 351 out of 1059 in 1993, 1994 and 1995, respectively) had engaged in anopenile intercourse without a condom with at least one male partner in the preceding year and one in 10 (162 out of 1566, 156 out of 1612, 103 out of 1059 in 1993, 1994 and 1995, respectively) had done so with more than one male partner. Despite an increase in prevention work targeted at this population, aggregate levels of sexual risk-taking have remained very stable. A reassessment of the efficacy of current HIV prevention messages and methods with this population is urgently required.


Effects of retinoic acid on the differentiation of THP-1 cell lines containing aneuploid or diploid chromosomes.
The effects of retinoic acid on the differentiation of human monocytic leukemia cell lines containing aneuploid (THP-1-Cs5) or diploid chromosomes (THP-1-R) were studied and compared. The induction of cell adhesion to a substratum, phagocytosis of sheep red blood cells (SRBC) or IgG-coated SRBC, pinocytosis of dextran sulfate, and NBT dye reduction by the cells were examined. The occurrence of these processes was much greater in RA-treated THP-1-Cs5 cells than in RA-treated THP-1-R cells. Of all these functional activities, the most remarkable differences between the two cell types were seen for cell adhesion and phagocytosis of SRBC. Morphological changes in RA-treated THP-1-Cs5 cells were observed by light and electron microscopy. RA-treated THP-1-Cs5 cells had a moderately-developed Golgi apparatus, and abundant lysosomes, mitochondria and lipid droplets in the cytoplasm. Among various retinoids examined, RA was the strongest inducer of the differentiation of the THP-1-Cs5 cells into mature cells. These findings suggest that THP-1-Cs5 cells which contain aneuploid chromosomes are more efficiently functionally differentiated by RA than are THP-1-R cells.


Some chemistry of tris(pyrazolyl)methylthiolate derivatives.
An efficient synthetic method for the preparation of TAS tris(pyrazolyl)methylthiolate (3) is reported. Nucleophilic exchange reactions with 3 gave (pyr)C(=S)SC(pyr)3 (4) and MeSC(pyr)3 (5). 5 acts as scorpionate ligand in [MeSC(pyr)3Cr(CO)3] (6), from the decomposition of TDAE2+ [SC(pyr)3Mo(CO)3-]2 by SO2FCl TDAE2+[O=MoF4-F-Mo(=O)Cl4]2- (8) was isolated. The X-ray structures of 3-6 and 8 are discussed.


Tracking Progress Towards the Sustainable Development Goals in Four Rural Villages in Limpopo, South Africa.
Measuring national progress towards the Sustainable Development Goals (SDGs) enables the identification of gaps which need to be filled to end poverty, protect the planet and improve lives. Progress is typically calculated using indicators stemming from published methodologies. South Africa tracks progress towards the SDGs at a national scale, but aggregated data may mask progress, or lack thereof, at local levels. To assess the progress towards achievement of the SDGs in four low-income, rural villages (Giyani) in South Africa and to relate the findings to national SDG indicators. Using data from a cross-sectional environmental health study, the global indicator framework for the SDGs was applied to calculate indicators for Giyani. Local progress towards SDG achievement was compared with national progress, to contextualize and supplement national scale tracking. Village scores were mostly in line with country scores for those indices which were computable, given the available data. Low data availability prevented a complete local progress assessment. Higher levels of poverty prevail in the study villages compared to South Africa as a whole (17.7% compared to 7.4%), high unemployment (49.0% compared to 27.3%) and lack of access to information via the Internet (only 4.2% compared to 61.8%) were indicators in the villages identified as falling far short of the South African averages. Understanding progress towards the SDGs at a local scale is important when trying to unpack national progress. It shines a light upon issues that are not picked up by national composite assessments yet require most urgent attention. Gaps in data required to measure progress towards targets represents a serious stumbling block, preventing the creation of a true reflection of local and national scale progress.


What contributes to predicting change in the treatment of dissociation: initial levels of dissociation, PTSD, or overall distress?
Individuals with dissociative disorders (DDs) suffer from high levels of dissociation as well as posttraumatic stress disorder (PTSD) and general distress. No research has investigated how changes in dissociation relate to changes in other symptoms over the course of treatment in patients with DD. Using a prospective, naturalistic design, we collected reports of symptoms from a sample of therapists and their patients diagnosed with dissociative identity disorder or dissociative disorder not otherwise specified who participated in the Treatment Outcome of Patients with Dissociative Disorders study. The patients completed surveys at intake (Time 1) into the study and at 30-month follow-up (Time 4). We found that dissociative symptoms, including amnesia, depersonalization/derealization, and absorption, at the initial assessment of the study ("initial") were related to initial levels of PTSD and general distress and that changes in dissociative symptoms were related to changes in PTSD and general distress. Initial dissociation was a significant predictor of change in dissociation at 30 months when we controlled for length of time for follow-up, length of time practicing therapy, and length of time treating dissociative patients. Our results suggest that a reduction in dissociative symptoms in DD patients is associated with reductions in the overall severity of dissociative, posttraumatic stress, and distress symptoms.


Costs of detection and treatment of cervical cancer, cervical dysplasia and genital warts in the UK.
Infection with human Papillomavirus (HPV) is a necessary cause of cervical cancer (CC) and genital warts (GW). HPV vaccination studies have shown excellent efficacy against HPV-induced lesions. To assess the cost-effectiveness of a HPV quadrivalent (6, 11, 16 and 18) vaccine it is necessary to estimate the costs of managing current levels of HPV-related diseases. This study estimates the annual 2003 expenditures in the UK for CC screening, follow-up of abnormal findings, CC treatment and GW treatment. CC screening programmes provided the annual number of screening tests, their results and use of colposcopy procedures in women with abnormal findings. Incident CC cases and hospital admissions for CC in 2003 were used to estimate CC costs. Health Protection Agency data provided the annual number of new, recurrent or persistent cases of GW treated in Genitourinary Medicine (GUM) clinics. Treatment patterns for managing GW were estimated by GUM clinicians. The annual physician visits, tests, procedures, hospital admissions and topical genital wart medications were costed to estimate the total annual expenditures for CC and GW. There were 4.8 million screening tests and 230 303 colposcopy procedures. Estimated costs for screening, management of abnormal and inadequate findings were 138.5 million pounds sterlings. Annual management costs for incident and prevalent CC cases were 46.8 million pounds sterlings. There were an estimated 76 457 incident and 55 657 recurrent/persistent GW cases in 2003. The costs for managing these cases were approximately 22.4 million pounds sterlings. Total annual estimated costs for CC screening, management and treatment of GW were 208 million pounds sterlings and ranged from 186.9 pounds sterlings to 214 million pounds sterlings based upon sensitivity analyses. The direct medical costs for the NHS associated with detection and management of CC, cervical dysplasia and treatment of GW in the UK are substantial. These medical costs are invaluable for future cost-effectiveness analyses of a quadrivalent HPV vaccine programme.


Generative Local Metric Learning for Nearest Neighbor Classification.
We consider the problem of learning a local metric in order to enhance the performance of nearest neighbor classification. Conventional metric learning methods attempt to separate data distributions in a purely discriminative manner; here we show how to take advantage of information from parametric generative models. We focus on the bias in the information-theoretic error arising from finite sampling effects, and find an appropriate local metric that maximally reduces the bias based upon knowledge from generative models. As a byproduct, the asymptotic theoretical analysis in this work relates metric learning to dimensionality reduction from a novel perspective, which was not understood from previous discriminative approaches. Empirical experiments show that this learned local metric enhances the discriminative nearest neighbor performance on various datasets using simple class conditional generative models such as a Gaussian.


Back pain and its risk factors in Brazilian adolescents: a longitudinal study.
Owing to the lack of longitudinal studies in Latin American countries, we aimed to evaluate back pain and its risk factors in a 3-year longitudinal study of Brazilian adolescents. We analysed data of 525 adolescents (aged 11-16 years) attending primary school (fifth to eighth grade) in Brazil. The students were administered the self-reported Back Pain and Body Posture Evaluation Instrument (BackPEI) questionnaire in 2011 and at a follow-up evaluation that was conducted 3 years later (2014). Back pain was the outcome variable; the exposure variables included exercise, behavioural, hereditary and postural factors. Generalized estimating equations were used to perform a Poisson regression model with robust variance to evaluate the risk factors for back pain. The prevalence of back pain at baseline was 56% (n = 294); this increased significantly at the 3-year follow-up evaluation to 65.9% (n = 346). The frequency of experiencing back pain also significantly increased after 3 years in both boys (p = 0.002) and girls (p = 0.001). The prevalence of back pain increased significantly in adolescents up to the age of 13 years, stabilized in those aged 14 years and older and was higher among girls. A family history of back pain (in the parents), watching television for lengthy periods and carrying a backpack asymmetrically were predictors for back pain.


Synergic Effect of Allopurinol in Combination with Nitroheterocyclic Compounds against Trypanosoma cruzi.
Combination therapy has gained attention as a possible strategy for overcoming the limitations of the present therapeutic arsenal for Chagas disease. The aim of this study was to evaluate the effect of allopurinol in association with nitroheterocyclic compounds on infection with the Y strain of Trypanosoma cruzi The in vitro effect of allopurinol plus benznidazole or nifurtimox on intracellular amastigotes in infected H9c2 cells was assessed in a 72-h assay. The interactions were classified as synergic for both allopurinol-nifurtimox (sums of fractional inhibitory concentrations [∑FICs] = 0.49 ± 0.08) and allopurinol-benznidazole (∑FICs = 0.48 ± 0.09). In the next step, infected Swiss mice were treated with allopurinol at 30, 60, and 90 mg/kg of body weight and with benznidazole at 25, 50, and 75 mg/kg in monotherapy and in combination at the same doses; as a reference treatment, another group of animals received benznidazole at 100 mg/kg. Allopurinol in monotherapy led to a smaller or nil effect in the reduction of parasite load and mortality rate. Treatment with benznidazole at suboptimal doses induced a transient suppression of parasitaemia with subsequent relapse in all animals treated with 25 and 50 mg/kg and in 80% of those that received 75 mg/kg. Administration of the drugs in combination significantly increased the cure rate to 60 to 100% among mice treated with benznidazole at 75 mg/kg plus 30, 60, or 90 mg/kg of allopurinol. These results show a positive interaction between allopurinol and benznidazole, and since both drugs are commercially available, their use in combination may be considered for the assessment in the treatment of Chagas disease patients.


Relationship between kidney function and liver histology in subjects with nonalcoholic steatohepatitis.
We assessed whether nonalcoholic steatohepatitis (NASH) diagnosed by liver biopsy is associated with decreased kidney function and whether such association is independent of insulin resistance and features of the metabolic syndrome. We enrolled 80 consecutive overweight patients with biopsy-proven NASH and 80 nonsteatotic control subjects who were matched for age, gender, and body mass index. Chronic kidney disease (CKD) was defined as the presence of estimated GFR (eGFR) of ≤60 ml/min per 1.73 m(2) and/or abnormal albuminuria (i.e., urinary albumin/creatinine ratio ≥30 mg/g). NASH patients had significantly (P < 0.001) lower eGFR (75.3 ± 12 versus 87.5 ± 6 ml/min per 1.73 m(2)) and a greater frequency of abnormal albuminuria (14 versus 2.5%) and CKD (25 versus 3.7%) than control subjects. The significant differences in eGFR, albuminuria, and CKD that were observed between the two groups were only slightly weakened after adjustment for age, gender, body mass index, smoking status, insulin resistance (by homeostasis model assessment), and components of the metabolic syndrome. Notably, histologic severity of NASH (i.e., fibrosis stage) was strongly associated with either decreasing eGFR or increasing albuminuria (P < 0.01 or less), independently of potential confounding factors. Our findings suggest that patients with biopsy-proven NASH have moderately decreased eGFR and a higher frequency of abnormal albuminuria and CKD than matched control subjects and that the severity of NASH histology is associated with decreased kidney function, independently of traditional risk factors, insulin resistance, and components of the metabolic syndrome.


Computational Modeling and Reverse Engineering to Reveal Dominant Regulatory Interactions Controlling Osteochondral Differentiation: Potential for Regenerative Medicine.
The specialization of cartilage cells, or chondrogenic differentiation, is an intricate and meticulously regulated process that plays a vital role in both bone formation and cartilage regeneration. Understanding the molecular regulation of this process might help to identify key regulatory factors that can serve as potential therapeutic targets, or that might improve the development of qualitative and robust skeletal tissue engineering approaches. However, each gene involved in this process is influenced by a myriad of feedback mechanisms that keep its expression in a desirable range, making the prediction of what will happen if one of these genes defaults or is targeted with drugs, challenging. Computer modeling provides a tool to simulate this intricate interplay from a network perspective. This paper aims to give an overview of the current methodologies employed to analyze cell differentiation in the context of skeletal tissue engineering in general and osteochondral differentiation in particular. In network modeling, a network can either be derived from mechanisms and pathways that have been reported in the literature (knowledge-based approach) or it can be inferred directly from the data (data-driven approach). Combinatory approaches allow further optimization of the network. Once a network is established, several modeling technologies are available to interpret dynamically the relationships that have been put forward in the network graph (implication of the activation or inhibition of certain pathways on the evolution of the system over time) and to simulate the possible outcomes of the established network such as a given cell state. This review provides for each of the aforementioned steps (building, optimizing, and modeling the network) a brief theoretical perspective, followed by a concise overview of published works, focusing solely on applications related to cell fate decisions, cartilage differentiation and growth plate biology. Particular attention is paid to an in-house developed example of gene regulatory network modeling of growth plate chondrocyte differentiation as all the aforementioned steps can be illustrated. In summary, this paper discusses and explores a series of tools that form a first step toward a rigorous and systems-level modeling of osteochondral differentiation in the context of regenerative medicine.


Assessing teen smoking patterns: the weekend phenomenon.
Adolescent cigarette smokers may have more daily variability in their smoking patterns than adults. A better understanding of teen smoking patterns can inform the development of more effective adolescent smoking cessation interventions. Teen smokers seeking cessation treatment (N=366) reported the number of cigarettes smoked on each day of a typical week. A paired t-test was used to examine differences between weekday (Sunday-Thursday) and weekend (Friday-Saturday) smoking. Main effects and interactions for race/ethnicity and gender were assessed using a 2-way ANOVA for the following variables: typical weekly smoking, average weekday smoking, average weekend smoking, and difference between weekday and weekend smoking. Scheffé post hoc tests were used to analyze any statistically significant differences. There was significantly more weekend smoking compared to weekday smoking, p<0.001. The difference in weekday versus weekend smoking levels was larger for females than for males, p<0.05. Hispanics reported less typical weekly smoking, p<0.001, less weekday smoking, p<0.001, and less weekend day smoking, p<0.01, compared to Caucasians and multi-racial teens. There was no difference in weekend day versus weekday smoking by race/ethnic background. Using a more detailed assessment of smoking quantity captures patterns of adolescent smoking that may lead to more effective smoking cessation interventions.


Comprehensive analysis of lipid dynamics variation with lipid composition and hydration of bicelles using nuclear magnetic resonance (NMR) spectroscopy.
Bicelles of various lipid/detergent ratios are commonly used in nuclear magnetic resonance (NMR) studies of membrane-associated molecules without the need to freeze the sample. While a decrease in the size (defined at a low temperature or by the q value) of a bicelle decreases its overall order parameter, the variation of lipid dynamics with a change in the lipid/detergent ratio is unknown. In this study, we report a thorough atomistic level analysis on the variation of lipid dynamics with the size and hydration level of bicelles composed of a phospholipid, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and a detergent, 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC). Two-dimensional (2D) separated-local-field NMR experiments were performed on magnetically aligned bicelles to measure (1)H-(13)C dipolar couplings, which were used to determine order parameters at various (head-group, glycerol, and acyl chain) regions of lipids in the bilayer. From our analysis, we uncover the extreme sensitivity of the glycerol region to the motion of the bicelle, which can be attributed to the effect of viscosity because of an extensive network of hydrogen bonds. As such, the water-membrane interface region exhibits the highest order parameter values among all three regions of a lipid molecule. Our experimental results demonstrate that the laboratory-frame 2D proton-detected-local-field pulse sequence is well-suited for the accurate measurement of motionally averaged (or long-range) weak and multiple (1)H-(13)C dipolar couplings associated with a single carbon site at the natural abundance of (13)C nuclei.


Dissecting of the Deterioration in Eating Quality for Erect Panicle (Ep) Type High Yield Japonica Super Rice in Northest China.
Ep type is an important morphological improvement (following dwarf breeding and ideal plant type) that has contributed to breeding super-high yielding, and shows a pleiotropic effect in increasing grain yield and also nitrogen-use efficiency (NUE) in rice. Nevertheless, it remains unclear whether Ep has adverse effects on eating quality and how it affects nitrogen uptake and assimilation. In this study, we developed a pair of near-isogenic lines (NILs) for panicle type (NIL-Ep, NIL-non Ep) in the Liaogeng 5 (LG5) and Akihikari (AKI) backgrounds. Rice plants of the NIL-Ep had higher grain numbers per panicle in the middle to bottom spike positions than plants of the NIL-non Ep. The increased grain number is not only is the key factor leading to increased yield but also is the reason for reduced the eating quality. The content of prolamin and glutelin was significantly higher in NIL-Ep, which resulted in higher hardness and worse viscosity of rice after cooking. In addition, the activity of several essential enzymes catalyzing nitrogen metabolism was higher in the NIL-Ep line grains than in the NIL-non Ep, especially from the mid to late grain filling stage. Based on these results, we conclude that Ep positively regulates grain protein accumulation, primarily through enhancing the activity of enzymes involved in nitrogen assimilation and redistribution during the mid to late grain-filling stage, resulting in excessive accumulation of grain protein and decreased eating quality.


Infrared spectra, structure, and bonding of the GeH3-CrH, HGe[triple bond]MoH3, and HGe[triple bond]WH3 molecules in solid neon and argon.
Laser ablated chromium, molybdenum, and tungsten atoms react with germane during condensation in excess noble gases. The chromium reaction stopped at the germyl metal hydride, molybdenum gave some hydride but mostly germylidyne, and tungsten reacted spontaneously to give only the germylidyne species. These molecules were identified by isotopic shifts, density-functional theory product energy and frequency calculations, and comparison to the analogous methane and silane reaction products. Effective bond orders for the HGe[triple bond]MoH3 and HGe[triple bond]WH3 molecules are 2.82 and 2.87 using the B3LYP density functional, and are slightly lower than their silicon and carbon analogues. Our calculated Ge[triple bond]M triple bond lengths for these simple trihydride complexes are 0.05 to 0.10 A shorter than those measured for larger group 6 organometallic complexes.


Stressful, isolated, yet diverse: Green roofs have rich microbiomes that are not dominated by oligotrophic taxa.
Green roofs are unique ecosystems combining two major community assembly filters, namely stress and spatial isolation. As such, they represent an interesting model ecosystem in community ecology. In this study, we characterized the microbiome structure on 19 green roofs and 5 urban parks as a benchmark comparison (i.e. non-isolated, non-stressful habitats). Green roofs were not species depauperate, showing similar α-diversity compared to surrounding parks. We also did not find an overrepresentation of bacterial phyla typically recognized as oligotrophs, which calls into question the notion of green roofs as highly stressful habitats for bacteria, and/or the conservatism of nutritional ecophysiology at the phylum level. The geographical position of a roof, or its degree of spatial isolation (assessed through its height and area) were not important predictors of microbiome diversity and structure, suggesting that dispersal limitations impose little constraints on green roof microbiome assembly. Finally, key microbial groups (e.g. archaeal nitrifiers, Actinobacteria) were much less frequent and/or abundant on green roofs, which may have important implications for nutrient cycling and urban biogeochemistry. More work will be required to phenotype the microorganisms overrepresented on green roofs and specifically measure key soil processes in these unique urban ecosystems.


Relation of cranial ultrasound abnormalities in low-birthweight infants to motor or cognitive performance at ages 2, 6, and 9 years.
This study sought to determine whether neonatal cranial ultrasound abnormalities are related to motor and cognitive outcomes in low-birthweight (LBW, <2000 g) children without major motor or cognitive disability. The relation of neonatal cranial ultrasound abnormalities to motor performance and general cognitive ability at ages 2, 6, and 9 years was examined in a prospectively followed regional cohort of LBW children, excluding those with major disability, and controlling for other risk factors. Compared with children without ultrasound abnormalities, children with abnormalities indicative of ischemic white-matter injury had poorer motor performance at all three ages and, at age 2, lower general cognitive ability. The latter finding was not seen when motor performance was also controlled for. It was concluded that in LBW children without major motor or cognitive disability, ischemic white-matter injury indicated by neonatal cranial ultrasound abnormalities adversely affected motor performance at ages 2, 6, and 9 years, but not general cognitive ability.


Relationship of spasticity to knee angular velocity and motion during gait in cerebral palsy.
This study investigated the effects of spasticity in the hamstrings and quadriceps muscles on gait parameters including temporal spatial measures, knee position, excursion and angular velocity in 25 children with spastic diplegic cerebral palsy (CP) as compared to 17 age-matched peers. While subjects were instructed to relax, an isokinetic device alternately flexed and extended the left knee at one of the three constant velocities 30 degrees/s, 60 degrees/s and 120 degrees/s, while surface electromyography (EMG) electrodes over the biceps femoris and the rectus femoris recorded muscle activity. Patients then participated in 3D gait analysis at a self-selected speed. Results showed that, those with CP who exhibited heightened stretch responses (spasticity) in both muscles, had significantly slower knee angular velocities during the swing phase of gait as compared to those with and without CP who did not exhibit stretch responses at the joint and the tested speeds. The measured amount (torque) of the resistance to passive flexion or extension was not related to gait parameters in subjects with CP; however, the rate of change in resistance torque per unit angle change (stiffness) at the fastest test speed of 120 degrees/s showed weak to moderate relationships with knee angular velocity and motion during gait. For the subset of seven patients with CP who subsequently underwent a selective dorsal rhizotomy, knee angular extension and flexion velocity increased post-operatively, suggesting some degree of causality between spasticity and movement speed.


Axis IV--psychosocial and environmental problems--in the DSM-IV.
The aim of this study was to further explore the properties of axis IV in the Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV). In a naturalistic cross-sectional design, a group (n = 163) of young (18-25 years old) Swedish psychiatric outpatients was assessed according to DSM-IV. Psychosocial and environmental problems/axis IV were evaluated through structured interviewing by a social worker and by self-assessment on a questionnaire. Reliability between professional assessment and self-assessment of axis IV was examined. Concurrent validity of axis IV was also examined. Reliability between professional and self-assessed axis IV was fair to almost perfect, 0.31-0.83, according to prevalence and bias-adjusted kappa. Categories of psychosocial stress and environmental problems were related to the presence of axis I disorders, co-morbidity, personality disorders and decreasing Global Assessment of Functioning (GAF) values. The revised axis IV according to DSM-IV seems to have concurrent validity, but is still hampered by limited reliability.


Enzyme kinetic modelling as a tool to analyse the behaviour of cytochrome P450 catalysed reactions: application to amitriptyline N-demethylation.
1. To determine kinetic parameters (Vmax, K(m)) for cytochrome P450 (CYP) mediated metabolic pathways, nonlinear least squares regression is commonly used to fit a model equation (e.g., Michaelis Menten [MM]) to sets of data points (reaction velocity vs substrate concentration). This method can also be utilized to determine the parameters for more complex mechanisms involving allosteric or multi-enzyme systems. Akaike's Information Criterion (AIC), or an estimation of improvement of fit as successive parameters are introduced in the model (F-test), can be used to determine whether application of more complex models is helpful. To evaluate these approaches, we have examined the complex enzyme kinetics of amitriptyline (AMI) N-demethylation in vitro by human liver microsomes. 2. For a 15-point nortriptyline (NT) formation rate vs substrate (AMI) concentration curve, a two enzyme model, consisting of one enzyme with MM kinetics (Vmax = 1.2 nmol min-1 mg-1, K(m) = 24 microM) together with a sigmoidal component (described by an equation equivalent to the Hill equation for cooperative substrate binding; Vmax = 2.1 nmol min-1 mg-1, K' = 70 microM; Hill exponent n = 2.34), was favoured according to AIC and the F-test. 3. Data generated by incubating AMI under the same conditions but in the presence of 10 microM ketoconazole (KET), a CYP3A3/4 inhibitor, were consistent with a single enzyme model with substrate inhibition (Vmax = 0.74 nmol min-1 mg-1, K(m) = 186 microM, K1 = 0.0028 microM-1). 4. Sulphaphenazole (SPA), a CYP2C9 inhibitor, decreased the rate of NT formation in a concentration dependent manner, whereas a polyclonal rat liver CYP2C11 antibody, inhibitory for S-mephenytoin 4'-hydroxylation in humans, had no important effect on this reaction. 5. Incubation of AMI with 50 microM SPA resulted in a curve consistent with a two enzyme model, one with MM kinetics (Vmax = 0.72 nmol min-1 mg-1, K(m) = 54 microM) the other with 'Hill-kinetics' (Vmax = 2.1 nmol min-1 mg-1, K' = 195 microM; n = 2.38). 6. A fourth data-set was generated by incubating AMI with 10 microM KET and 50 microM SPA. The proposed model of best fit describes two activities, one obeying MM-kinetics (Vmax = 0.048 nmol min-1 mg-1, K(m) = 7 microM) and the other obeying MM kinetics but with substrate inhibition (Vmax = 0.8 nmol min-1 mg-1, K(m) = 443 microM, K1 = 0.0041 microM-1). 7. The combination of kinetic modelling tools and biological data has permitted the discrimination of at least three CYP enzymes involved in AMI N-demethylation. Two are identified as CYP3A3/4 and CYP2C9, although further work in several more livers is required to confirm the participation of the latter.


Alternative medicine in the workplace.
Workplace settings are ripe for the application of alternative medical interventions for a variety of reasons. Included among them are a shared interest in prevention by both the occupational and alternative medicine communities, economic incentives by corporations as major purchasers of healthcare to reduce healthcare costs and improve employee productivity, and the willingness of corporations to be differentially creative in their approach to delivering and purchasing healthcare. This paper describes the US workforce in transition, provides an overview of occupational medicine including current programs and emerging issues, describes the current applications of alternative medicine interventions in the workplace, and argues for future expanded application of alternative medicine in workplace settings.


Treatment of proliferative diabetic retinopathy using viscosurgery with vital dye.
Viscosurgery is a surgical procedure based on the injection of viscoelastic material between the retinal surface and the fibrovascular tissue in proliferative diabetic retinopathy (PDR), with the aim of separating these structures to facilitate their dissection. We describe a modified viscosurgical technique in which the viscoelastic material is combined with a vital dye (trypan blue), which allows us to determine the degree of adhesion between the structures. Viscosurgery with vital dye has advantages compared with conventional viscosurgery and constitutes a useful surgical approach in complicated cases of severe PDR, enhancing efficiency and safety in the dissection of fibrovascular proliferations and minimizing iatrogenic damage to the underlying retina. We used trypan blue viscosurgery in 8 eyes of 8 patients with severe PDR; in all cases, a satisfactory outcome was obtained without evidence of any complications.


Characterization of minimal lesions related to the presence of visna/maedi virus in the mammary gland and milk of dairy sheep.
In order to characterize the complete range of lesions, especially minimal, affecting mammary gland and viral antigen distribution and target cells using immunohistochemistry in naturally Visna/maedi (VM) 84 infected sheep were studied, forty-four from flocks with clinical cases (A) and 35 randomly sampled from two abattoirs (B) together with five negative controls (C). An immunocytochemistry technique was developed and further milk samples (n = 39) were used to study viral excretion, carrier cells and the role of milk and colostrum in the transmission of the disease. All sheep from group C and three sheep from group B were negative to VM in tissue sections by histopathology, immunohistochemistry and PCR, and also in serum using ELISA. Several degrees of CD3 + lymphocytic interstitial mastitis were observed in groups A and B: minimal (+) n = 26 sheep; moderate (++), n = 32 and severe (+++), n = 12. No differences in lesion distribution were observed between groups A and B. Viral presence was confirmed by immunohistochemistry using two different antibodies and/or PCR in every tissue with lesions while serology was negative in six sheep with lesions. Two milk samples taken from milk tanks from two flocks from group A and fourteen milk samples from 29 infected sheep from group B were positive to VM (most of them from animals with moderate and severe lesions). Positivity was only found in macrophages, even in focal and minimal lesions, while no positivity was observed in epithelial or any other cells in either tissue and milk samples. This new observation of the minimal lesions described in this work increased the prevalence of VM lesions in mammary gland up to 90.9% and VM should be considered as a differential diagnosis when minimal interstitial lesions are detected. A high prevalence of VM was observed in intensive milk-producing sheep, ELISA serology did not detect as positivity all infected animals, while histology, IHC or PCR showed higher sensitivity. The cytological technique developed was very useful in milk-cell studies using hematoxylin and eosin and immunocytochemistry. Viral detection in milk samples (16/39) confirms a potential but limited role of milk/colostrum in viral transmission.


Using Observational Assessment to Help Identify Factors Associated with Parent Participation Engagement in Community-Based Child Mental Health Services.
Parent engagement in child mental health (MH) services has received growing attention due to its significance in intervention outcomes and evidence-based care. In particular, parent participation engagement (PPE) reflects active and responsive contributions in and between sessions. Yet, limited research has examined factors associated with PPE, particularly within community-based MH services where PPE is low and highly diverse families are often served. This study examined child, parent, and therapist factors associated with PPE in a sample of racially/ethnically diverse parent-child dyads receiving publicly-funded, community-based MH services. This prospective study included 18 parent-child dyads receiving community-based MH services from 17 therapists in five outpatient clinics for child disruptive behaviors. PPE was measured using in-session observational assessment of therapy recordings. Child factors that were examined included age, first time child MH service use, and intensity of child behavior problems. Parent factors included ethnicity, education, depression symptoms, and parent motivation to participate in therapy. Therapist factors included therapist training in parent-mediation interventions, attitudes towards organizational functioning, and attitudes towards parent participation strategies. Results from linear regression analyses indicated that first time child MH service use, intensity of child behavior problems, parent ethnicity and motivation to participate in therapy, as well as therapists' training and attitudes about their practice were each significantly associated with PPE. Results highlight specific child, parent, and therapist characteristics that may impact observed PPE in child MH therapy. These findings underscore the importance of considering the influence of family and provider factors on PPE in community-based child MH services.


The Hitchhiker's guide to the rhinencephalon.
Pathology of the rhinencephalon has been a subject of interest in the fields of neurodegenerative diseases, trauma, epilepsy and other neurological conditions. Most of what is known about the human rhinencephalon comes from comparative anatomy studies in other mammals and histological studies in primates. Functional imaging studies can provide new and important insight into the function of the rhinencephalon in humans but have limited spatial resolution, limiting its contribution to the study of the anatomy of the human rhinencephalon. In this study we aim to provide a brief and objective review of the anatomy of this important and often overlooked area of the nervous system.


Concept analysis of moral courage in nursing: A hybrid model.
Moral courage is one of the most fundamental virtues in the nursing profession, however, little attention has been paid to it. As a result, no exact and clear definition of moral courage has ever been accessible. This study is carried out for the purposes of defining and clarifying its concept in the nursing profession. This study used a hybrid model of concept analysis comprising three phases, namely, a theoretical phase, field work phase, and a final analysis phase. To find relevant literature, electronic search of valid databases was utilized using keywords related to the concept of courage. Field work data were collected over an 11 months' time period from 2013 to 2014. In the field work phase, in-depth interviews were performed with 10 nurses. The conventional content analysis was used in two theoretical and field work phases using Graneheim and Lundman stages, and the results were combined in the final analysis phase. Ethical consideration: Permission for this study was obtained from the ethics committee of Tehran University of Medical Sciences. Oral and written informed consent was received from the participants. From the sum of 750 gained titles in theoretical phase, 26 texts were analyzed. The analysis resulted in 494 codes in text analysis and 226 codes in interview analysis. The literature review in the theoretical phase revealed two features of inherent-transcendental characteristics, two of which possessed a difficult nature. Working in the field phase added moral self-actualization characteristic, rationalism, spiritual beliefs, and scientific-professional qualifications to the feature of the concept. Moral courage is a pure and prominent characteristic of human beings. The antecedents of moral courage include model orientation, model acceptance, rationalism, individual excellence, acquiring academic and professional qualification, spiritual beliefs, organizational support, organizational repression, and internal and external personal barriers. Professional excellence resulting from moral courage can be crystallized in the form of provision of professional care, creating peace of mind, and the nurse's decision making and proper functioning.


Bridging the urological divide.
The advanced disease clinical presentations, higher morbidity and mortality rates and lack of available treatment options in prostate cancer care, attest to disparities in the delivery and outcomes of urological services in Black men of African lineage in both the Developed and Developing countries. This gap in health care and services in the global management of prostate cancer denotes the urological divide.Through the experience of a Developing country urologist with a comparative literature review, this presentation defines the determinants of the disparity through deficiencies in human, material and financial resources, as is most prevalent in Developing countries.Solutions to ending health care disparities must take into account the existing development phase of Third World countries and thus determine whether the Developed countries should export a total service delivery system or seek primarily to advance the competence and skills of the existing Developing country resources.Collaboration in prostate cancer research has the greatest promise and sustainability of bridging this urological divide and is of mutual benefit to both entities.


A vault nanoparticle vaccine induces protective mucosal immunity.
Generation of robust cell-mediated immune responses at mucosal surfaces while reducing overall inflammation is a primary goal for vaccination. Here we report the use of a recombinant nanoparticle as a vaccine delivery platform against mucosal infections requiring T cell-mediated immunity for eradication. We encapsulated an immunogenic protein, the major outer membrane protein (MOMP) of Chlamydia muridarum, within hollow, vault nanocapsules (MOMP-vaults) that were engineered to bind IgG for enhanced immunity. Intranasal immunization (i.n) with MOMP-vaults induced anti-chlamydial immunity plus significantly attenuated bacterial burden following challenge infection. Vault immunization induced anti-chlamydial immune responses and inflammasome formation but did not activate toll-like receptors. Moreover, MOMP-vault immunization enhanced microbial eradication without the inflammation usually associated with adjuvants. Vault nanoparticles containing immunogenic proteins delivered to the respiratory tract by the i.n. route can act as "smart adjuvants" for inducing protective immunity at distant mucosal surfaces while avoiding destructive inflammation.


Comparison of Two 3D-Printed Indirect Bonding (IDB) Tray Design Versions and Their Influence on the Transfer Accuracy.
Objective: This study aims to investigate the transfer accuracy of two different design versions for 3D-printed indirect bonding (IDB) trays. Materials and Methods: Digital plaster models of 27 patients virtually received vestibular attachments on every tooth using OnyxCeph³™ (Image Instruments, Chemnitz, Germany). Based on these simulated bracket and tube positions, two versions of transfer trays were designed for each dental arch and patient, which differed in the mechanism of bracket retention: Variant one (V1) had arm-like structures protruding from the tray base and reaching into the horizontal and vertical bracket slots, and variant two (V2) had a pocket-shaped design enclosing the brackets from three sides. Both tray designs were 3D-printed with the same digital light processing (DLP) printer using a flexible resin-based material (IMPRIMO® LC IBT/Asiga MAX™, SCHEU-DENTAL, Iserlohn, Germany). Brackets and tubes (discovery® smart/pearl, Ortho-Cast M-Series, Dentaurum, Ispringen, Germany) were inserted into the respective retention mechanism of the trays and IDB was performed on corresponding plaster models. An intraoral scan (TRIOS® 3W, 3Shape, Copenhagen, Denmark) was performed to capture the actual attachment positions and compared to the virtually planned positions with Geomagic© Control (3D Systems Inc., Rock Hill, SC, USA) using a scripted calculation tool, which superimposed the respective tooth surfaces. The resulting attachment deviations were determined in three linear (mesiodistal, vertical and orovestibular) and three angular (torque, rotation and tip) directions and analyzed with a descriptive statistical analysis. A comparison between the two IDB tray designs was conducted using a mixed model analysis (IBM, SPSS® Statistics 27, Armonk, NY, USA). Results: Both design versions of the 3D-printed IDB trays did not differ significantly in their transfer accuracy (p > 0.05). In total, 98% (V1) and 98.5% (V2) of the linear deviations were within the clinically acceptable range of ±0.2 mm. For the angular deviations, 84.9% (V1) and 86.8% (V2) were within the range of ±1°. With V1, most deviations occurred in the mesiodistal direction (3.3%) and in rotation (18%). With V2, most deviations occurred in the vertical direction (3.8%) and in palatinal and lingual crown torque (16.3%). Conclusions: The transfer accuracies of the investigated design versions for 3D-printed IDB trays show good and comparable results albeit their different retention mechanisms for the attachments and are, therefore, both suitable for clinical practice.


Long-term followup with evaluation of the surgical and functional results of the ileal pouch reservoir in restorative proctocolectomy for ulcerative colitis.
Aims. Evaluate the early and long term surgical and functional results of the ileal pouch-reservoir (IPAA) in patients with intractable ulcerative colitis. Material and Methods. Followup of 134 consecutive patients with W-or J-ileal pouch by diseases-specific and general health (SF-36) questionnaire. In the first 44 patients, early and late followup was performed. Results. Followup was performed 7.4 years (0.5-17 years) after construction of W (n = 9) and J (n = 125) ileal pouch, which had similar results. There were 14.9% early and 43.6% late complications with 12.7% early and 19.5% late reoperations. Protecting loop-ileostomy used in 54 patients (43.9%), did not protect against complications. Thirteen reservoirs (9.8%) were resected (n = 8) or deactivated (n = 5) due to functional failure. Operation time, postoperative complications and pouchitis were determinators for reservoir failure and reduced quality of life. The functional results at followup of 44 patients at 2.5 years (0.8-6.7 years) and 11.5 years (8.2-19.2 years) were remarkably similar. Conclusions. IPAA is a good option for most patients when medication fails. 10% experience failure with inferior quality of life. Protective stoma will not reduce failure rates. After an initial time period, reservoir function will not change over time.