Type 2 diabetes and cognitive impairment: contributions from neuroimaging.
Type 2 diabetes mellitus (T2D) and Alzheimer disease (AD) are major public health burdens associated with aging. As the age of the population rapidly increases, a sheer increase in the incidence of these diseases is expected. Research has identified T2D as a risk factor for cognitive impairment and potentially AD, but the neurobiological pathways that are affected are only beginning to be understood. The rapid advances in neuroimaging in the past decade have added significant understanding to how T2D affects brain structure and function and possibly lead to AD. This article provides a review of studies that have utilized structural and functional neuroimaging to identify neural pathways that link T2D to impaired cognitive performance and potentially AD. A primary focus of this article is the potential for neuroimaging to assist in understanding the mechanistic pathways that may provide translational opportunities for clinical intervention.


Pharmacogenetic Biomarkers Predictive of the Pharmacokinetics and Pharmacodynamics of Immunosuppressive Drugs.
In association with therapeutic drug monitoring of immunosuppressive drugs, pharmacogenetics has rapidly emerged as an additional tool to refine dose selection or, more interestingly to select, a priori, the first dose to administer. Pharmacogenetic biomarkers are now readily available in most transplantation centers, at a limited cost and within a limited analytical time frame, which make them compatible with the clinical decision process. However, despite some evidence of clear associations between polymorphisms in genes encoding metabolizing enzymes (CYP3A4/3A5, UGT1A9) or drug transporters (ABCB1, ABCC2, SLCO1B1) and pharmacokinetics of several immunosuppressive drugs, pre-emptive genotyping and selection of the optimal starting dose based on the genetic background of the patient is still rarely performed in clinical practice. The main reason is probably the lack of formal proof that clinical outcome really improves after genotype-based dosing. So far, the only clinical recommendation in relation to pharmacogenetic biomarkers should be a doubling of the starting tacrolimus dose in patients who are CYP3A5 expressers, and even in this case, some authors still do not recommend pre-emptive genotyping but only genotype-based adaptation if the CYP3A5 genotype is already known. However, with the rise of new technologies, as next generation sequencing, allowing to obtain pre-emptive genetic information, one must be aware that the question will no longer be whether to genotype or not but rather whether or not to use the information already there. There was therefore a need to update the information available in relation to pharmacogenetic biomarkers for calcineurin inhibitors, mycophenolic acid, and mammalian target of rapamycin inhibitors.


Expression of cyclooxygenase-2 in rat vascular smooth muscle cells is unrelated to nuclear factor-kappaB activation.
The promoter region of cyclooxygenase-2 (COX-2) gene contains binding sites for a number of important transcription factors including cyclic AMP response element, nuclear factor-IL6, nuclear factor-kappaB (NF-kappaB) and TGF-beta response element. Several reports have documented that the activation of NF-kappaB triggers the expression of COX-2 gene. In the present study, NF-kappaB was activated by TNF-alpha in rat aortic smooth muscle cells as demonstrated by electrophoretic mobility shift assay. The activity of NF-kappaB induced by TNF-alpha was blocked by calpain inhibitor I, a potent NF-kappaB inhibitor. However, the activation of NF-kappaB was not related to the expression of COX-2 induced by TNF-alpha since calpain inhibitor I blocked the activation of NF-kappaB but not the expression of COX-2 mRNA or protein. Mutation of rat COX-2 NF-kappaB-like sites in the promoter region did not significantly reduce the promoter activity. These results suggest that the transcriptional regulation of COX-2 expression by NF-kappaB depends upon the types of cells studied and that activation of this transcription factor alone does not play an important role in the expression of COX-2 in rat smooth muscle cells.


Chorioretinal ischemia and angiogenic milieu following photodynamic therapy.
To investigate the development of chorioretinal ischemia and expression of angiogenic factors following photodynamic therapy (PDT) in normal rat chorioretina. Pimonidazole (hypoxia marker) was intraperitoneally administrated 15 min before PDT (to identify the intra-PDT ischemia) and at 10 days and 20 days after PDT (to identify post-PDT ischemia) in 14 Brown-Norway rats (4 rats at each point and 2 rats serving as controls). After enucleation and cryosection at each point, immunohistofluorescent (IHF) staining for pimonidazole was evaluated with confocal scanning microscopy. In another 14 rats, the expression of angiogenic factors following PDT was demonstrated in PDT-irradiated normal chorioretina. Four rats were randomly selected at 3, 7, and 14 days following PDT with 2 rats serving as controls (verteporfin-/laser-). The expressions of vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), and hypoxia-inducible factor (HIF)-1a were evaluated at each point. Diode laser (689 nm, 25 J/cm(2)) was irradiated before verteporfin infusion in the left eye (verteporfin-/laser+) and after infusion in the right eye (verteporfin+/laser+) in each experiment. Intensity of pimonidazole uptake increased during PDT and at 10 and 20 days following PDT. The intensity of pimonidazole was the most pronounced immediately after PDT irradiation, but VEGF expression was rarely detected immediately after PDT. VEGF, IGF, and HIF-1a expression increased at 3 days and 7 days. At 14 days after PDT, the expression of VEGF was sustained, but that of IGF and HIF-1a was irregular. These results show that significant chorioretinal ischemia develops in the irradiated area following PDT and that the ischemia is most pronounced during PDT irradiation. Along with post-PDT overexpression of angiogenic factors, this may be a mechanism contributing to PDT resistance or recurrence of chorioretinal neovascular lesions.


Initial Reduction of CO2 on Pd-, Ru-, and Cu-Doped CeO2(111) Surfaces: Effects of Surface Modification on Catalytic Activity and Selectivity.
Surface modification by metal doping is an effective treatment technique for improving surface properties for CO2 reduction. Herein, the effects of doped Pd, Ru, and Cu on the adsorption, activation, and reduction selectivity of CO2 on CeO2(111) were investigated by periodic density functional theory. The doped metals distorted the configuration of a perfect CeO2(111) by weakening the adjacent Ce-O bond strength, and Pd doping was beneficial for generating a highly active O vacancy. The analyses of adsorption energy, charge density difference, and density of states confirmed that the doped metals were conducive for enhancing CO2 adsorption, especially for Cu/CeO2(111). The initial reductive dissociation CO2 → CO* + O* on metal-doped CeO2(111) followed the sequence of Cu- > perfect > Pd- > Ru-doped CeO2(111); the reductive hydrogenation CO2 + H → COOH* followed the sequence of Cu- > perfect > Ru- > Pd-doped CeO2(111), in which the most competitive route on Cu/CeO2(111) was exothermic by 0.52 eV with an energy barrier of 0.16 eV; the reductive hydrogenation CO2 + H → HCOO* followed the sequence of Ru- > perfect > Pd-doped CeO2(111). Energy barrier decomposition analyses were performed to identify the governing factors of bond activation and scission along the initial CO2 reduction routes. Results of this study provided deep insights into the effect of surface modification on the initial reduction mechanisms of CO2 on metal-doped CeO2(111) surfaces.


New records of Niceforo's big-eared bat, Trinycterisnicefori (Sanborn, 1949) (Chiroptera, Phyllostomidae), from the state of Maranhão, Brazil.
Niceforo's big-eared bat, Trinycterisnicefori (Sanborn, 1949), is a monotypic species which has been recorded in a number of Brazilian states, but has a disjunct distribution in this country. This study presents the first record of T.nicefori in the Brazilian state of Maranhão. The specimens were collected in the municipalities of Godofredo Viana and Cândido Mendes, in fragments of the Amazon forest. One male (forearm: 38.00 mm, weight: 6 g) and one female (39.68 mm, 8 g) specimens were collected. The specimens presented chestnut-colored fur, and a chin with a pair of dermal pads arranged in a V-shape, without a central papilla. The COI gene sequences were plotted in the BOLD Systems platform, which confirmed the morphological identification of the species, with a 99.1% similarity in the male, and 99.4% in the female to existing sequences. This record extends the known distribution of T.nicefori in Brazil by approximately 310 km to the most eastern part of the Amazon Biome.


Gestational length affects neurocognition in early-onset schizophrenia.
Obstetric complications (OC) have been linked to an increased risk for schizophrenia in offspring, especially in early-onset schizophrenia (EOS). Extensive cognitive deficits occur in EOS, although no study has yet to investigate the relationship between OC and cognition in EOS. This study aims to examine the frequency of OC in EOS compared to controls, and also investigates the relationship between OC and neurocognitive dysfunction in the two groups. Nineteen EOS patients and 53 healthy controls were tested with the MATRICS Consensus Cognitive Battery (MCCB), and the cognitive measures were combined with OC data from the Norwegian Birth Registry. The results indicated no group differences in OC in EOS and healthy controls, but a shorter gestational length in the EOS group led to significant decreases in the overall neurocognitive composite score, and in processing speed. This suggests that the poorer neuropsychological performances commonly found in EOS may be partly attributable to the length of gestation. The worsened neurocognitive functioning did not appear among controls, so gestational length had a different impact on the two groups. Our findings indicated that a shorter gestational length did not increase the risk for developing EOS, but did significantly affect the cognitive difficulties in this group.


The epidermal growth factor receptor pathway: a model for targeted therapy.
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase receptor that is frequently expressed in epithelial tumors. The EGFR was the first receptor to be proposed as a target for cancer therapy, and after 2 decades of intensive research, there are several anti-EGFR agents available in the clinic. Recent advances in our understanding in the mechanisms of receptor activation and function, discovery of primary and secondary EGFR somatic mutations, as well as a new generation of anti-EGFR agents provide new leads on the clinical targeting of this receptor and may serve as a model for strategies aimed at targeting other receptors.


Lessons Learned From the COVID-19 Pandemic as Experienced by Older Adults Treated for COVID-19.
In order to provide the best care, the perspective of older COVID-19 patients must be involved in the development of treatment protocols. This study describes the experiences of older adults affected by COVID-19 who recovered in the hospital or at home. Qualitative semi-structured interviews were conducted with 23 older adults affected by COVID-19. A content-based thematic analysis was conducted. Nine categories were identified as recurring topics, which were grouped into three major themes. The first theme describes experiences in the first phase of the disease when older adults fell ill. The second theme includes experiences during the illness, ranging from illness severity to participation in decision-making, communication barriers and isolation effects. The final theme covers the recovery course, residual symptoms and social aspects. Older adults treated for COVID-19 experienced a feeling of being in a fast-paced whirlwind and lost total control over the situation. Extra attention should be paid to shared decision making, coordinated information provision and the instalment of a primary contract to the patient. The uncertainty of their situation, isolation measures and fears could result in psychological consequences and hinder rehabilitation in older adults.


Personal digital assistants: a review of their application in graduate medical education.
Personal digital assistants (PDAs) have become widely used in medicine and may be especially useful in achieving the goals of graduate medical education. The complex challenges that residents and their program directors in graduate medical education programs confront may be met more readily with the use of these devices. The PDA's ability to serve as an informational database, an organizer of patient-specific information, a tracking tool that can be used by program directors to enhance curriculum design, and a tool for conducting education research are some of the ways that these devices might favorably affect residency training in graduate medical education programs.


Short bowel syndrome in infancy and childhood. Analysis of survival in 60 patients.
This report concerns 60 infants and children with short bowel syndrome, most commonly caused by necrotizing enterocolitis in this study. Resection of atretic or gangrenous bowel was performed in 53 patients, tapering enteroplasty and primary anastomosis was performed in 13 patients, and temporary enterostomies were performed in 40 patients. Second-look laparotomy was useful in two of four cases of questionable bowel viability. The ileocecal valve was resected in 33 patients and remained intact in 27. The mean length of remaining bowel was 58.4 cm (range 13 to 150 cm). Seven patients with total aganglionosis and mid to proximal small bowel extension were managed with an initial enterostomy, whereas three had a pull-through procedure with an aganglionic patch enteroplasty. All patients received total parenteral nutrition and early enteral feedings. Home hyperalimentation was attempted when 50 percent of the calorie intake was enteral. Intestinal adaptation required from 3 to 14 months. Frequent setbacks were related to catheter sepsis, rotavirus infection, carbohydrate intolerance, and liver dysfunction. The overall survival rate was 85 percent, with mortality due to liver failure and sepsis associated with total parenteral nutrition.


Nutritional status of primary school children from low income households in kuala lumpur.
Growth status was examined in relation to gender and age factors in urban primary school children (6-10 years old) from low income households in Kuala Lumpur, Wilayah Persekutuan. The sample consisted of 4212 boys (53%) and 3793 girls (47%). Data on weight and height data were obtained from two sources - investigator's and teachers' measurements of the school children. This study defined mildly and significantly underweight, stunted or wasted as z-score below minus one and below minus two of the NCHS/CDC reference median, respectively. Approximately 52% (n = 4149), 50% (n = 3893) and 30% (n = 2568) of the school children were underweight, stunted and wasted, respectively. However, the majority of these undernourished children were in the mild category. Prevalence of overweight (> 2 SD of NCHS/WHO reference median) was found in 5.8% of the sample. For both, prevalence of undernutrition and overnutrition, more boys than girls were found to be underweight stunted wasted and overweight. Compared to girls, boys had lower mean z-scores for the variables height-for-age (p<0.05) and weight-for-height (p<0.01). Older children had significantly lower mean z-scores for height-for-age (p<0.001) but higher mean z-scores for weight-for-height (P<0.001) than younger children. This finding indicates that with increasing age, stunting is associated with improved weight-for-height or that the children's weights have been adapted to their short statures. In conclusion, results demonstrate a high prevalence of underweight, stunting and wasting and an increasing prevalence of overweight among these low-income school children. Efforts recommended to address health and nutrition problems among school children should include health and nutrition monitoring (e.g. growth monitoring using the existing growth data collected by schools) and interventions.


Aberrant nuclear morphology in the mouse myeloma SP2/0 cell line.
The mouse myeloma SP2/0 cell line when grown in supplemented Dulbecco's modified Eagle's media spontaneously produced aberrant nucleated cells which increased in frequency with cell culture age. These cells underwent cytological changes associated with apoptosis, that is, the condensation of chromatin followed by karyorrhexis and the production of small apoptotic bodies. Aberrant cells were induced by media changes, centrifugation, and temperature shocking. The rapid induction of aberrant cells by a media change suggests that the mechanism of fragmentation was not associated with cell division.


Aortic calcifications and arterial stiffness as predictors of cardiovascular events in incident renal transplant recipients.
Renal transplant recipients have an increased risk of cardiovascular (CV) disease. Arterial stiffness (AS) and aortic calcifications (ACs) are well-known CV risk factors in patients with chronic kidney disease. We aimed to determine the prognostic value of AS and AC in incident renal transplant recipients (RTRs). We conducted a prospective study in 253 single RTR. AC were scored by means of lumbar X-ray. Carotid-femoral pulse wave velocity (PWV) was assessed in a subgroup of 115 patients. AC were present in 61% of patients. After a mean follow-up of 36 months, 32 CV events occurred in the overall group and 13 events in the PWV subgroup. When we accounted for age, gender, and CV history, AC score (HR, hazard ratio 1.09 per 1 unit increase; 95% CI 1.02-1.17) and PWV (HR 1.45 per 1 m/s; 95% CI 1.16-1.8) remained an independent predictor of CV events in Cox-regression analyses. Using receiver operating characteristics, the area under the curve for predicting CV events amounted to 0.80 and 0.72 for sum AC and PWV, respectively. Both AS and AC are strong predictors of future CV events in an incident RTR population. These vascular assessments are readily available and easy to perform, making them ideal tools for further risk stratification. (ClinicalTrials.gov number: NCT00547040).


Ion channels in opossum kidney cells.
This review discusses the activation of ion transport pathways during regulatory volume decrease in opossum kidney (OK) cells. OK cells regulate their volume when exposed to a hypotonic medium. The changes in cell volume are caused by activation of ion transport pathways and the accompanying osmotically driven water movement so that the increased cell volume returns toward physiological levels. The reshrinking of hypotonically swollen cells is termed regulatory volume decrease. In OK cells separate K+ and Cl- conductances are activated. The Na+/H+ cotransport system seems not to be involved. The potassium pathway is mediated by a K+ channel with a slope conductance of about 12 pS. The occasionally observed widely distributed Ca2(+)- and voltage-dependent K+ channel of large unit conductance (120 pS) seems not to be involved. The volume regulatory decrease is accompanied by a cell depolarization from a resting potential of about -60 mV to about -20 mV followed by a repolarization. It will be discussed whether the depolarization is caused by the observed activation of stretch-sensitive ion channels of about 30 and 40 pS, respectively. The transient behavior of the cell volume parallels the time-dependent change of the total membrane current. For both recording techniques the volume regulatory decrease can be blocked by quinine. In addition an inward rectifying K+ channel of about 80 pS has been observed in high KCl solution.


One dose versus three weekly doses of benzathine penicillin G for patients co-infected with HIV and early syphilis: a multicenter, prospective observational study.
One dose of benzathine penicillin G (BPG) has been recommended for HIV-infected patients with early syphilis (primary, secondary, and early latent syphilis) in the sexually transmitted diseases treatment guidelines, but clinical data to support such a recommendation are limited. We prospectively observed the serological response to 1 or 3 weekly doses of BPG in HIV-infected adults who sought treatment of early syphilis at 8 hospitals around Taiwan. Rapid plasma reagin (RPR) titers were followed every 3-6 months after treatment. The serological response was defined as a 4-fold or greater decline in RPR titers at 12 months of treatment. The missing values were treated by following the last-observed-carried-forward principle. We hypothesized that 1 dose was non-inferior to 3 weekly doses of BPG with the non-inferiority margin for the difference of serological response set to 10%. Between 2007 and 2012, 573 patients completed at least 12 months of follow-up: 295 (51.5%) receiving 1 dose of BPG (1-dose group) and 278 (48.5%) 3 doses (3-dose group). Overall, 198 patients (67.1%; 95% confidence interval [CI], 61.4-72.5%) in the 1-dose group achieved serological response at 12 months, as did 208 patients (74.8%; 95% CI, 69.3-79.8%) in the 3-dose group (one-sided 95% CI of the difference, 15.1%). In the multivariate analysis, secondary syphilis (adjusted odds ratio [AOR], 1.90; 95% CI 1.17-3.09), RPR titer ≥32 (AOR, 1.93; 95% CI, 1.38-2.69), and 3 doses of BPG (AOR, 1.68; 95% CI, 1.20-2.36) were independently associated with a serological response. The time to the first episode of treatment failure was 1184 (standard deviation [SD], 70.5) and 1436 (SD, 80.0) days for 1- and 3-dose group, respectively. Single-dose BPG resulted in a higher serological failure rate and shorter time to treatment failure than 3 weekly doses of BPG in the treatment of early syphilis in HIV-infected patients.


The expression of Claudin-4 in gastric cancer tissue: A single center experience.
Gastric cancer (GC) is still one of the most common malignancies with the majority of the tumors diagnosed at advanced stage. The need for identification of prognostic and early detection biomarkers is thus compulsory. Claudins are biomarkers that are currently evaluated in the literature in the frame of epithelial-mesenchymal transition. The purpose of this investigation was to study the expression of claudin-4 in the various histological subtypes of GC and to evaluate its prognostic value. This investigation was performed on gastric tumors obtained from 66 (46 men and 20 women) patients with documented gastric adenocarcinoma who underwent total or partial gastrectomy and regional lymphadenectomy from 2003 till 2011. Features such as tumor size, depth of invasion, grade and histological subtype, lymphovascular space invasion and regional lymph nodes involvement were also evaluated. Immunohistochemistry (IHC) was used for assessing the expression of claudin-4 with a semi-quantitative model. 66.7% of our cases showed abnormal claudin-4 expression in IHC. Claudin-4 was significantly correlated with tumor T stage and with intestinal type classification. The correlation of claudin-4 tissue expression with patient overall survival survival (OS) or disease-free survival (DFS) was not statistically significant, as well as with age, gender, tumor N stage, grade, TNM stage, positive lymph node ratio or lymphovascular invasion. Literature stands equivocal about the exact role and prognostic value of claudin-4 and histopathology and tumor invasiveness in patients with GC. Our results further strengthen the need of larger studies to fully elucidate the predictive role of claudin-4 in the natural history of GC.


Historical Perspective and Future Direction of Blood Vessel Developments.
Over the past 40 years, remarkable advances have been made in our understanding of successful blood vessel regeneration, starting with the failures of early tissue-engineered vascular grafts designed using isolated components or molecules, such as collagen gels. The vascular tissue engineers are today better educated and have steered ongoing research developments toward clinical developments of more complete vascular grafts that replicate the multitude of specialized arterial aspects required for function.


Effects of cyano, ethynyl and ethylenedioxy groups on the photophysical properties of carbazole-based porphyrins.
The synthesis and photophysical properties of cyano and ethynyl substituted carbazole-based porphyrins were investigated. The introduction of ethynyl groups induced red shifts, while that of cyano groups induced blue shifts of their absorption bands, which was supported by MO calculations. Ethylenedioxy-appended porphyrins were also prepared via a coupling reaction. The conjugated and electronic substituent effects on the photophysical properties of the carbazole-based porphyrins have been elucidated by using both experimental results and calculations. Among these porphyrins, the ethylenedioxy-appended selenaporphyrin displayed intensified and red-shifted absorption in the NIR region up to 1178 nm.


Predicting protein functions from redundancies in large-scale protein interaction networks.
Interpreting data from large-scale protein interaction experiments has been a challenging task because of the widespread presence of random false positives. Here, we present a network-based statistical algorithm that overcomes this difficulty and allows us to derive functions of unannotated proteins from large-scale interaction data. Our algorithm uses the insight that if two proteins share significantly larger number of common interaction partners than random, they have close functional associations. Analysis of publicly available data from Saccharomyces cerevisiae reveals >2,800 reliable functional associations, 29% of which involve at least one unannotated protein. By further analyzing these associations, we derive tentative functions for 81 unannotated proteins with high certainty. Our method is not overly sensitive to the false positives present in the data. Even after adding 50% randomly generated interactions to the measured data set, we are able to recover almost all (approximately 89%) of the original associations.


Risk Factors for Thrombosis, Overshunting and Death in Infants after Modified Blalock-Taussig Shunt.
The Modified Blalock-Taussig shunt procedure can provide increased flow of blood to the lungs for babies born with certain congenital heart defects. We evaluated 44 subjects under 2 years of age who had a Modified Blalock-Taussig shunt (MBTS) procedure performed from 2009-2013, to investigate risk factors for thrombosis, overshunting and death. The study subjects included in our investigation were severely cyanotic newborns with pulmonary stenosis or atresia and duct dependent circulation, and infants having Tetralogy of Fallot with small pulmonary arteries who underwent a MBTS procedure in our facility from 2009-2013. We duly noted patient preoperative characteristics such as hemoglobin, hematocrit, mean platelet volume, prothrombin time and partial thromboplastin time. Our study investigated the risk factors for post-operative overcirculation, thrombosis and death. The age and weight of patients in our study at the time of procedure ranged from 1 day to 20 months old (median 12 days), and 2.4 kg to 12 kg (mean 4.6 kg), respectively. A total of 8 patients died following surgery, and. 4 (9.1%) had shunt thrombosis, of which one died during shunt revision. Partial thromboplastin time was 28.7 seconds in patients with thrombosis, and 35 in all other patients (p = 0.04). Overcirculation was detected in 5 patients; shunt size/body weight was 1.25 in patients who had overcirculation, and 1.06 in all other patients. It is important to assess risk factors associated with the MBTS operation. The results of our study suggest that a preoperative low aPTT value may be an indicator for thrombosis in infants who have undergone MBTS surgery.


Fiber optic sensor for acoustic detection of partial discharges in oil-paper insulated electrical systems.
A fiber optic interferometric sensor with an intrinsic transducer along a length of the fiber is presented for ultrasound measurements of the acoustic emission from partial discharges inside oil-filled power apparatus. The sensor is designed for high sensitivity measurements in a harsh electromagnetic field environment, with wide temperature changes and immersion in oil. It allows enough sensitivity for the application, for which the acoustic pressure is in the range of units of Pa at a frequency of 150 kHz. In addition, the accessibility to the sensing region is guaranteed by immune fiber-optic cables and the optical phase sensor output. The sensor design is a compact and rugged coil of fiber. In addition to a complete calibration, the in-situ results show that two types of partial discharges are measured through their acoustic emissions with the sensor immersed in oil.


Expenditure patterns by age and income among mature adults: does age matter?
Using data from the 1984-85 Consumer Expenditure Survey (CES), we examined how expenditure patterns of elderly persons (aged 65-74 and 75 and over) at different income-to-needs levels differ from those of younger mature adults (aged 45-54 and 55-64) at similar income-to-needs levels. Patterns of spending are examined in a variety of areas within three domains--giving, recreation, and essentials. Several important differences exist in the ways that households headed by persons of different ages allocate their expenditures in the domains of essentials and recreation, but few differences exist in the domain of giving. Consistent income group differences exist in expenditure patterns across virtually every area within the three domains. Both age and income differences remain significant when multivariate analyses are performed; thus, the story told is one in which both age and income play important roles.


Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings.
A wide range of derivatives with new pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline skeleton was synthesized by free-radical intramolecular cyclization of o-bromophenyl-substituted pyrrolylpyridinium salts using the (TMS)3SiH/AIBN system. The cyclization provides generally good yields of pyrido[2,1-a]pyrrolo[3,4-c]isoquinoline hydrobromides having no additional radical-sensitive substituents. The free bases can be obtained from the synthesized hydrobromides in quantitative yield by basification at room temperature. The selectivity control of intramolecular arylation was achieved by replacing the halogen: the use of 1-(2-(ortho-bromophenyl)-4-(ortho-iodophenyl)pyrrol-3-yl)pyridinium bromide makes it possible to obtain a monocyclization product, and the bicyclization product from the dibromo derivative. The procedure is also applicable to obtain 3-arylpyrido[2,1-a]pyrrolo[3,2-c]isoquinoline derivatives including 2-unsubstituted skeletons that are inaccessible via Pd-catalyzed cyclization.


Physical Activity in De Novo Parkinson Disease: Daily Step Recommendation and Effects of Treadmill Exercise on Physical Activity.
People with Parkinson disease (PD) have low physical activity (PA) levels and are at risk for cardiovascular events. The 3 purposes of this study were to determine a step threshold that corresponds to meeting aerobic PA guidelines, determine effects of treadmill exercise on PA, and quantify the relationship between changes in daily steps and fitness. This was a secondary analysis of the Study in Parkinson's Disease of Exercise trial, which randomized participants to high-intensity treadmill exercise, moderate-intensity treadmill exercise, or usual care for 6 months. Daily steps and moderate- to vigorous-intensity PA (MVPA) were assessed at baseline and once each month using an activity monitor. Fitness was assessed via graded exercise test at baseline and at 6 months. A step threshold that corresponds to meeting PA guidelines was determined by receiver operating characteristic curves. The effect of treadmill exercise on PA was examined in those below the step threshold (ie, the least active participants). Pearson r correlations determined the relationship between daily steps and fitness. Individuals with de novo PD (n = 110) were included. Those with ≥4200 steps were 23 times more likely (95% CI = 7.72 to 68) to meet PA guidelines than those with <4200 steps. For those with <4200 steps at baseline (n = 33), only those in the high-intensity exercise group increased daily steps (median of differences = 1250 steps, z = -2.35) and MVPA (median of differences = 12.5 minutes, z = -2.67) at 6 months. For those with <4200 steps, changes in daily steps were not associated with changes in fitness (r = .183). In people with PD and <4200 daily steps at baseline, high-intensity treadmill exercise increased daily steps and MVPA, but these changes were not associated with changes in fitness. People with PD should be encouraged to take ≥4200 daily steps to meet PA guidelines through walking.


Collagenous Gastritis and Helicobacter pylori Infection: A Mere Coincidence?
A 21-year-old woman presented to our clinic after 7 years of abdominal pain, diarrhea, and iron-deficiency anemia. Initial upper endoscopy revealed severe inflammation and nodularity of the gastric body and active Helicobacter pylori infection. After eradication therapy, esophagogastroduodenoscopy showed gastric atrophy with nodularity resolution. Histopathology revealed scattered plasma cells, eosinophils, and collagen deposition suggestive of collagenous gastritis. H. pylori can induce proinflammatory cytokines, resulting in fibroblast upregulation. Collagenous gastritis may be caused by an inflammatory response associated with type I, II, and III collagen. Although further research is warranted, we hypothesize that chronic inflammation from H. pylori may lead to collagenous gastritis.


Predictors of remission in patients with non-radiographic axial spondyloarthritis receiving open-label adalimumab in the ABILITY-3 study.
This analysis assessed baseline predictors of remission in patients with non-radiographic axial spondyloarthritis (nr-axSpA) who received open-label adalimumab therapy. ABILITY-3 enrolled 673 adult patients with nr-axSpA who had objective evidence of inflammation by MRI or elevated high-sensitivity C reactive protein at screening, active disease and an inadequate response to two or more non-steroidal anti-inflammatory drugs. Patients received adalimumab 40 mg every other week during a 28-week open-label lead-in period. Clinical remission was defined as Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS ID; score <1.3) and Assessment of SpondyloArthritis international Society partial remission (ASAS PR; score <2/10 in each of the four ASAS domains). Stepwise logistic regression was used to identify baseline predictors of remission at week 12 and at final visit (last postbaseline visit up to week 28). Only patients without missing data were included. Overall, 593 patients were included in the ASDAS ID and 596 in the ASAS PR analysis at week 12. Younger age (≤45 years), male sex, positive human leucocyte antigen (HLA)-B27 and higher Spondyloarthritis Research Consortium of Canada (SPARCC) MRI sacroiliac joint score were consistent predictors of remission by both ASAS ID and ASDAS PR at week 12. Results were generally similar in the final visit analysis. Other variables did not consistently predict remission. In ABILITY-3, consistent and strong baseline predictors of remission included younger age, male sex, HLA-B27 positivity and higher SPARCC MRI sacroiliac joint score among patients with active nr-axSpA receiving adalimumab therapy, similar to previous findings in ankylosing spondylitis.


Computational and experimental analysis of pinch-off and scaling.
Pinch-off and scaling during drop formation are studied using high-accuracy computation and ultrafast, high-resolution imaging. The interface of a water drop (viscosity mu is approximately 1 cP) is shown to overturn prior to breakup for the first time in experiments, well before the dynamics transitions from the potential flow (PF) to the inertial-viscous (IV) regime. A drop of 83% glycerol-water solution (mu is approximately 85 cP) is shown to exhibit a transition from the PF to the IV regime both computationally and experimentally. The computed value of the minimum neck radius in the latter case follows Eggers's universal solution until it becomes unstable.


The Usefulness of the Short Form-8 for Chronic Pain in the Orofacial Region: A Prospective Cohort Study.
Background and purpose Given that chronic pain has become a major problem in recent years, affecting approximately 30% of the general population, this study used the Japanese version of the Short Form-8 (SF-8) to investigate (1) the quality of life (QOL) of patients with burning mouth syndrome (BMS) or persistent idiopathic facial pain (PIFP) (compared with a Japanese control group) and (2) whether therapeutic intervention improves the QOL and reduces pain (comparison between 0 and 12 weeks) of patients with BMS or PIFP. Materials and methods A total of 63 patients diagnosed with either BMS (n=45) or PIFP (n=18) were included in this study. The diagnostic criteria for BMS and PIFP were established based on the third edition of the International Classification of Headache Disorders. Results Our study results showed that while Physical Component Summary (PCS) in patients with BMS or PIFP improved with treatment, it did not improve to the national standard value (NSV) after 12 weeks of intervention. In contrast, the Mental Component Summary (MCS) improved to the same level as the NSV after 12 weeks of intervention. Conclusions We found that therapeutic intervention improves MCS and reduces pain; however, improving PCS requires time.


[Pathophysiology of focal cerebral ischemia: fundamental aspects and its projection on clinical practice].
The aim of this study is to review the basic aspects of focal cerebral ischemia as a fundamental element in clinical practice and of neuroprotective strategies. Ischemia triggers several different responses in nerve tissue which, according to the degree of energetic limitation, can be adaptive or lead to cell death due to necrosis or apoptosis. Establishing these processes is a complex task and the mechanisms involved have still not been fully explained; this is made more difficult by the fact that many of them are simultaneous and also because of the implications they may have, not only in cell death but also in the adaptation of the neurons that suffered ischemic stress and survived. We outline the foundations for understanding the physiopathological phenomena at work in ischemia: neuronal stress and death, and the reaction of the macroglial and microglial cells. This is also illustrated by original images from research into cell response to ischemia at a pre-clinical level in an experimental model of focal cerebral ischemia in rats, evaluated using, for example, hematoxylin-eosin and immunohistochemical techniques for several cell markers. Cell death in ischemia is a complex phenomenon that can have two different outcomes: necrotic death or apoptotic death. Basic knowledge of the pathophysiology of ischemia and of the response of microglial and macroglial cells is the foundation for elaborating neuroprotective-type strategies, which must not only be oriented towards preventing acute cell death, but also later modes of cell death or strengthening the surviving tissue.


Severe meconium aspiration syndrome is not caused by aspiration of meconium.
Meconium aspiration syndrome can present clinically with different degrees of severity, ranging from a mild form of respiratory compromise to severe forms that may result in perinatal death despite mechanical ventilation or extracorporeal membrane oxygenation. However, advances in our knowledge concerning meconium aspiration syndrome have revealed that most cases of severe meconium aspiration syndrome are not in fact causally related to the aspiration of meconium but rather are caused by other pathologic processes occurring in utero, primarily chronic asphyxia and infection. Proper understanding of the causative processes underlying fetal or neonatal compromise in these cases is essential to direct future research into preventive or therapeutic treatments and for counseling of the parents of an affected child.


Immunological recovery after bone marrow transplantation for severe aplastic anaemia: a Brazilian experience.
Twenty-nine patients with severe aplastic anaemia (SAA) were submitted to bone marrow transplantation (BMT) and their immunological recovery analysed. Total lymphocyte counts, estimation of B lymphocytes, T lymphocytes and their subsets, natural-killer (NK) activity were performed. Cells with the CD8+ phenotype and NK activity were the first signs of immunological recovery, whereas the CD4+ subset recovered later in patients who suffered from acute graft versus host disease (GvHD) and infections. Acute and chronic GvHD, cirrhosis, rejection and HIV viral infection contributed to the persistence of the profound immunodeficiency status observed after BMT. Our results did not differ greatly from the others and confirmed that BMT may be performed in underdeveloped countries despite the difficulties it might pose.


Intrafat Sequestration of Artemisinin Disguised as a Purulent Collection during a Posterolateral Hip Approach.
The posterolateral hip approach is the oldest and most used way to implant total hip arthroplasty. The anterior part of the oblique portion of this posterolateral approach corresponds more or less to the superolateral quadrant of the buttock in which the intramuscular injection of various drugs, including the compounds derived from artemisinin, is carried out. Thus, in a malarial endemic area where gluteal injections of the compounds derived from artemisinin are not rare, poor performance of an injection by the deposition of the product in the fat and not deeply in the muscle can be at the origin of the sequestration of the drug in adipose tissue and give the macroscopic appearance of a pus. The authors present a case of intrafat sequestration of artemisinin taken for purulent collection during a posterolateral hip approach for total hip arthroplasty.


Learner conceptions of health advocacy: 'Going above & beyond' or 'kind of an expectation'.
Health advocacy is a core component of physician competency frameworks. However, advocacy has lacked a clear definition and is understood and enacted variably across contexts. Due to their mobility across contexts, learners are uniquely positioned to provide insight into the tensions that have made this role so difficult to define, but that may be central to this role. The purpose of this study was to map the tensions and contours in conceptions of health advocacy among learners across a variety of learning contexts. We used constructivist grounded theory and interviewed nine medical students and twenty residents in family, paediatric and internal medicine from across our university's distributed programmes. Data were analysed concurrently using open, focussed and theoretical coding to establish themes and relationships between themes. Learners understood health advocacy in two overlapping but distinct ways: as a set of behaviours and as a sense of 'going above and beyond', through additional effort, time or risk. These two conceptions overlapped and were often in tension. 'Going above and beyond' sometimes aligned with identifiable advocacy behaviours; at other times, 'going above and beyond' did not align with definitions of health advocacy in competency frameworks and aligned more closely with 'patient-centred care'. Our findings suggest that learners perceive that there are important elements of health advocacy that cannot be captured in universal behaviours that apply across contexts. 'Going above and beyond' describes a sense of grappling with sociocultural barriers to patient-centred care and striving towards better systems and better care for individuals. This more abstract and contextually bound notion of health advocacy may not lend itself easily to definition in competency frameworks and thus adds challenges to both teaching and assessment.


Regulation of prostaglandin EP1 and EP4 receptor signaling by carrier-mediated ligand reuptake.
After synthesis and release from cells, prostaglandin E2 (PGE2) undergoes reuptake by the prostaglandin transporter (PGT), followed by cytoplasmic oxidation. Although genetic inactivation of PGT in mice and humans results in distinctive phenotypes, and although experiments in localized environments show that manipulating PGT alters downstream cellular events, a direct mechanistic link between PGT activity and PGE2 (EP) receptor activation has not been made. Toward this end, we created two reconstituted systems to examine the effect of PGT expression on PGE2 signaling via two of its receptors (EP1 and EP4). In human embryonic kidney cells engineered to express the EP1 receptor, exogenous PGE2 induced a dose-dependent increase in cytoplasmic Ca(2+). When PGT was expressed at the plasma membrane, the PGE2 dose-response curve was right-shifted, consistent with reduction in cell surface PGE2 availability; a potent PGT inhibitor acutely reversed this shift. When bradykinin was used to induce endogenous PGE2 release, PGT expression similarly induced a reduction in Ca(2+) responses. In separate experiments using Madin-Darby Canine Kidney cells engineered to express the PGE2 receptor EP4, bradykinin again induced autocrine PGE2 signaling, as judged by an abrupt increase in intracellular cAMP. As in the EP1 experiments, expression of PGT at the plasma membrane caused a reduction in bradykinin-induced cAMP accumulation. Pharmacological concentrations of exogenous PGE2 induced EP4 receptor desensitization, an effect that was mitigated by PGT. Thus, at an autocrine/paracrine level, plasma membrane PGT regulates PGE2 signaling by decreasing ligand availability at cell surface receptors.


Regulation of cartilage remodeling by IL-1: evidence for autocrine synthesis of IL-1 by chondrocytes.
Evidence is presented for the synthesis of Interleukin-1 (IL-1) by joint synovial tissue and chondrocytes. Purified preparations of mouse and human recombinant forms of this factor stimulate the synthesis of a secretory protease by cartilage. The IL-1 stimulated chondrocyte protease is capable of converting latent collagenase to its active form. Other proteases such as trypsin and the mercurial aminophenyl mercuric acetate will not activate collagenase in the absence of this protease. Evidence is presented showing that chondrocytes synthesize IL-1 suggesting autocrine control of cartilage matrix turnover.


Effect of domestic processing on the cooking time, nutrients, antinutrients and in vitro protein digestibility of the African yambean (Sphenostylis stenocarpa).
The effects of processing (soaking, dehulling, fermentation and heat treatment) on the cooking time, protein, mineral, tannin, phytate and in vitro protein digestibility (IVPD) of the African yambean (AYB) were examined. The cooking time ranged from 90-155 minutes. Soaking reduced cooking time by about 50 percent. Soaking for 12 hours was the most appropriate to reduce cooking time, tannin and phytate levels. It improved in vitro protein digestibility (IVPD). Prolonged soaking (24 hours) decreased calcium (Ca) and iron (Fe) values by 19 percent and 35 percent, respectively. Dehulling showed that Ca, Fe, magnesium (Mg) and zinc (Zn) were concentrated in the seed coat of the AYB. The seeds soaked and dehulled retained Mg and Zn. Dehulling reduced tannin but had no significant effect on phytate and the IVPD of the AYB except for seeds soaked for 12 hours before dehulling. Soaking for 24 hours before dehulling significantly increased crude protein content by 16 percent (p < 0.05). Blanching and roasting increased the IVPD by 8-11 percent. Fermentation had no effect on the crude protein, Ca, Fe, Mg and Zn but significantly reduced phytate content of the AYB. Fermentation had no advantage over heat treatment with respect to improving the in vitro protein digestibility of the AYB.


A posteriori quasi-sectioning of the three-dimensional reconstructions of scanning holographic microscopy.
A method to obtain the axial locations of objects reconstructed by scanning holographic microscopy with submicrometer accuracy is presented and demonstrated. The method combines the holographic advantage of capturing three-dimensional (3D) information in a single two-dimensional scan, with the possibility of optically sectioning the 3D holographic reconstruction a posteriori. The method is demonstrated experimentally for pointlike features (fluorescent beads), and the limitation of the method for features of arbitrary size and shape is discussed.


Quinazoline derivative compound (11d) as a novel angiogenesis inhibitor inhibiting VEGFR2 and blocking VEGFR2-mediated Akt/mTOR /p70s6k signaling pathway.
We previously reported a series of quinazoline derivatives as vascular-targeting anticancer agents. In this study, we investigated the mechanism underlying the anti-angiogenic activity of the quinazoline derivative compound 11d. We examined the effects of quinazoline derivative 11d: on vascular endothelial growth factor receptor-2 (VEGFR2) activation via VEGFR2-specific activation assay. Reverse transcription and immunohistochemistry were used to detect vascular endothelial growth factor (VEGF), VEGFR2, and the VEGFR2-mediated Akt/mTOR/p70s6k signaling pathway in human umbilical vascular endothelial cells and hepatocellular carcinoma cells (HepG-2) after treatment with various concentrations of 11d: (0, 6.25, 12.5, and 25 μM) for 24 hr. The compound 11d: exhibited potent inhibitory activity against VEGFR2 with an IC50 of 5.49 μM. This compound significantly downregulated VEGF, VEGFR2, and the VEGFR2-mediated Akt/mTOR/p70s6k signaling pathway in vitro. The mechanism underlying the anti-angiogenic activity of the quinazoline derivative 11d: possibly involves the inhibition of VEGFR2 and the downregulation of VEGF, VEGFR2, and the VEGFR2-mediated Akt/mTOR/p70s6k signaling pathway. Overall, the findings indicate that the studied class of compounds is a source of potential antiproliferative and anti-angiogenic agents, which must be further investigated.


Further studies on the relationship between drug-induced mast-cell secretion and local cell proliferation.
A single intraperitoneal injection of Compound 48/80 in rats causes mast cell activation which is followed by a proliferation in fibroblasts and mesothelial cells in the mesentery. The same is true of organ-cultured rat mesentery, but in cultured guinea-pig mesentery Compound 48/80 has no morphological effects on mast cells and does not induce proliferation. The relationship between mast-cell secretion and cell proliferation in surrounding cells was studied further in the investigation now presented. Proliferation was estimated (a) by cytophotometric Feulgen DNA measurements in individual fibroblast and mesothelial cell nuclei; (b) by measurements of incorporation of 3H-TdR into DNA; (c) and by estimation of mitotic frequency. Mast-cell secretion was studied morphologically and by biochemical quantitation of histamine release. Compound 48/80 is a potent mast cell activator in the rat, stimulating mast cells to secretion. The results of this study suggest that Polymyxin B, another powerful mast-cell activator, apparently chemically unrelated to Compound 48/80, also stimulates the mesenterial cells to proliferation in the rat. In the guinea-pig Compound 48/80 does not induce mast-cell secretion or proliferation in fibroblasts and mesothelial cells in the mesentery. The results give further evidence that the cell proliferation induced by Compound 48/80 and Polymyxin B in rat mesentery is causally related to mast-cell secretion.


Effect of the incorporation of a low-band-gap small molecule in a conjugated vinylene copolymer: PCBM blend for organic photovoltaic devices.
The effect of the incorporation of a low-band-gap small-molecule BTD-TNP on the photovoltaic properties of vinylene copolymer P:PCBM bulk heterojunction solar cells has been investigated. The introduction of this small molecule increases both the short-circuit photocurrent and the overall power conversion efficiency of the photovoltaic device. The incident photon-to-current efficiency (IPCE) of the device based on P:PCBM:BTD-TNP shows two distinct bands, which correspond to the absorption bands of P:PCBM and BTD-TNP. Furthermore, it was found that the IPCE of the device has also been enhanced even at the wavelengths corresponding to the absorption band of P:PCBM, when the thermally annealed blend was used in the device. This indicates that the excitons that are generated in copolymer P are dissociated into charge carriers more effectively in the presence of the BTD-TNP small molecule at the copolymer P:PCBM interface by energy transfer from P to the small molecule. Therefore, we conclude that the BTD-TNP small molecule acts as light-harvesting photosensitizer and also provides a path for the generated exciton in copolymer P toward the P:PCBM interface for efficient charge separation. The overall power conversion efficiency for the P:PCBM:BTD-TNP photovoltaic device is about 1.27%, which has been further enhanced up to 2.6%, when a thermally annealed blend layer is used.


Multiple eruptive squamoproliferative lesions during anti-PD1 immunotherapy for metastatic melanoma: Pathogenesis, immunohistochemical analysis and treatment.
Treatment with anti-PD1 inhibitors may enhance the risk for developing low grade squamoproliferative skin tumors. Immunohistochemical (IHC) analysis of the immune tumor microenvironment (TME) allows exploration of the pathogenesis and relationship with the PD1/PDL1 axis. Patients with eruptive keratoacanthoma (KA)-like lesions were recruited from the Melanoma Institute Australia, a tertiary referral specialist melanoma treatment center from January 2015 to August 2017. Clinicopathologic evaluation and IHC features of tumor cells (PDL1 expression) and peritumoral microenvironment (PD1, FOXP3, PDL1, CD4:CD8 expressing cells) in 12 eruptive KA-like lesions, were compared with solitary KAs in age and sex matched non-anti-PD1 treated controls. Four patients with repeated episodes of eruptive KA-like and lichenoid lesions developing 2-7 months after commencing pembrolizumab for AJCC stage IV melanoma, were recruited. Eruptive KA-like squamoproliferative lesions occurred in sun exposed sites and in areas of resolving, concomitant or delayed lichenoid reactions. Histologically, the lesions were well-differentiated squamoproliferative lesions resembling infundibulocystic squamous cell carcinoma or KA. IHC of cases and controls revealed low PDL1 expression of both squamous tumor cells and the TME immune cells. The numbers of immunosuppressive FOXP3 positive Tregs and PD1-expressing T-cells were higher in the cases than the controls but the CD4:CD8 ratio (2:1) was similar. The patients best responded to acitretin and were managed surgically if they demonstrated neoplastic features. Accelerated squamoproliferative growth in actinically damaged keratinocytes associated with lichenoid eruptions may be unmasked in patients treated with anti-PD1 immunotherapy potentially contributed to by a local cutaneous immunosuppressed TME.


QSAR studies on chalcones and flavonoids as anti-tuberculosis agents using genetic function approximation (GFA) method.
Design of compounds having good anti-tubercular activity is gaining much importance in the field of tuberculosis research due to reemergence of antibiotic resistance strains. In this paper quantitative structure activity relationships (QSAR) were developed on chalcones, chalcone-like compounds, flavones and flavanones to understand the relationship between biological activity and structural features. Genetic function approximation (GFA) method was used to identify the descriptors that would lead to good regression equations. The best molecular descriptors identified were Jurs descriptors (Jurs charged partial surface area), hydrogen bond donor, principal moment of inertia, molecular energy, dipole magnetic, molecular area, absorption, distribution, metabolism and excretion (ADME) properties and Chi indices (Kier & Hall chi connectivity indices). Excellent statistically significant models were developed by this approach (r(2)=0.8-0.97) for the four groups of compounds. The cross validated r(2) (XV r(2)) which is an indication of the predictive capability of the model for all the cases was also very good (=0.79-0.94).


An approach to deep brain stimulation for severe treatment-refractory Tourette syndrome: the UK perspective.
Deep brain stimulation (DBS) is an emerging therapeutic option for severe, treatment-resistant Tourette Syndrome (TS), with about 40 cases reported in the scientific literature over the last decade. Despite the production of clinical guidelines for this procedure from both European and USA centres, a number of unresolved issues still persist, mainly in relation to eligibility criteria and brain targets. The present article illustrates the UK perspective on DBS in TS and proposes consensus-based recommendations for double-blind controlled trials.


The use of occluding tinted contact lenses.
We explored the clinical issues surrounding the use of tinted contact lenses for vision occlusion in cases of debilitating vision disturbance, such as intractable diplopia. We report the results with four patients fit with occluding tinted contact lenses. Vision occlusion by contact lenses provided a suitable comfortable occlusion method with improved cosmesis compared to occlusion by spectacles. Lens parameters and tint specifications were ordered for each patient. Correct lens care and handling were necessary to avoid contact lens related ocular inflammation. Provided that lens care is satisfactory and the patient does not have unreasonable expectations, a tinted contact lens can be a useful alternative to a covered spectacle lens or eye patch when occluding one eye, such as in cases of intractable diplopia, severe vision distortion, or intolerable photophobia.


Developing an assessment of fire-setting to guide treatment in secure settings: the St Andrew's Fire and Arson Risk Instrument (SAFARI).
Arson and fire-setting are highly prevalent among patients in secure psychiatric settings but there is an absence of valid and reliable assessment instruments and no evidence of a significant approach to intervention. To develop a semi-structured interview assessment specifically for fire-setting to augment structured assessments of risk and need. The extant literature was used to frame interview questions relating to the antecedents, behaviour and consequences necessary to formulate a functional analysis. Questions also covered readiness to change, fire-setting self-efficacy, the probability of future fire-setting, barriers to change, and understanding of fire-setting behaviour. The assessment concludes with indications for assessment and a treatment action plan. The inventory was piloted with a sample of women in secure care and was assessed for comprehensibility, reliability and validity. Staff rated the St Andrews Fire and Risk Instrument (SAFARI) as acceptable to patients and easy to administer. SAFARI was found to be comprehensible by over 95% of the general population, to have good acceptance, high internal reliability, substantial test-retest reliability and validity. SAFARI helps to provide a clear explanation of fire-setting in terms of the complex interplay of antecedents and consequences and facilitates the design of an individually tailored treatment programme in sympathy with a cognitive-behavioural approach. Further studies are needed to verify the reliability and validity of SAFARI with male populations and across settings.


MACRO- AND MICROGEOGRAPHIC STRUCTURE OF A SPATIALLY SUBDIVIDED BEETLE SPECIES IN NATURE.
Spatial subdivision of species can affect their population structure by allowing processes such as limited dispersal, spatial heterogeneity in selective pressures, small population sizes, and random events to operate. By studying species restricted to islands or "island" habitats, one can attempt to determine which of these factors have affected the current structure of the population. Collops georgianus (Coleoptera: Melyridae), a beetle species endemic to the "island" habitat of granitic rock outcrops, was chosen to see how its spatially subdivided distribution has affected its genetic structure. Its genetic structure was examined on both a macrogeographic and a microgeographic level using protein electrophoresis. Macrogeographically, 12 populations throughout its range were sampled. The discontinuous distribution of outcrops, and thus populations, throughout its range, has determined the connectivity of the populations. Significant variation in allele frequencies and substructuring (FST = 0.192) was found throughout the range, but there was no spatial autocorrelation. Microgeographically, in the central part of the range, where outcrops are denser and more continuously distributed in space, there was evidence of isolation by distance. Very little variation in allele frequencies was found, but a low but significant level of substructuring occurred among the populations. Comparison of disjunct and continuous populations microgeographically revealed no effect of disjunct distributions, although a significant effect of distance was detected. Effective population size variation among populations and between years, compounded with the effects of local extinctions, suggest that random processes such as drift and founder effects are important determinants of the population's genetic structure.


Risk for cardiovascular disease in Japanese patients with rheumatoid arthritis: a large-scale epidemiological study using a healthcare database.
To study risk for cardiovascular disease (CVD) in Japanese patients with rheumatoid arthritis (RA). We used a Medical Data Vision database mainly composed of health insurance claim data and diagnosis-procedure combination data from Japan. Patients with RA diagnosed from April 2011 to March 2014 at 71 hospitals were identified with the International Classification of Diseases 10th revision (ICD-10) and history of anti-RA drug prescription. Hospitalizations for CVD including ischemic heart disease, heart failure, and stroke were identified by a combination of diagnosis (ICD-10) and diagnostic procedures. CVD incidence rate ratio (IRR) for RA versus osteoarthritis was calculated. Risk factors were analyzed using univariate and multivariate Cox proportional hazard models with baseline C-reactive protein (CRP) and traditional risk factors as covariates. We identified 8658 patients with RA. The age-sex adjusted IRR for RA versus osteoarthritis was high for total CVD [2.12; 95 % confidence interval (CI) 1.93-2.32], ischemic heart disease (2.16; 95 % CI 1.86-2.50), heart failure (2.34; 95 % CI 2.07-2.65), and stroke (1.68; 95 % CI 1.41-2.00). Risk factor analysis showed a tendency for cardiovascular risk to increase with higher baseline CRP, although the difference was not statistically significant (hazard ratio 1.43; 95 % CI 0.99-2.07). Our study indicates an increased risk for CVD and an association between systemic inflammation and CVD in Japanese RA patients.


The quality management system as a tool for improving stakeholder confidence.
The Corps of Engineers works with local restoration advisory boards (RAB) to exchange information and develop plans for restoration of closed military bases for civilian reuse. Meetings of the RAB to discuss progress in environmental assessment and restoration of former defense sites can be contentious due to the complex technical nature of the information to be shared and the personal stake that the members of the community have in ensuring that contentious areas are restored for safe use. A prime concern of community representatives is often the quality of the data used to make environmental decisions. Laboratory case narratives and data flags may suggest laboratory errors and low data quality to those without an understanding of the information's full meaning. RAB members include representatives from local, state, and tribal governments, the Department of Defense, the Environmental Protection Agency, and the local community. The Corps of Engineers representatives usually include project technical and management personnel, but these individuals may not have sufficient expertise in the project quality assurance components and laboratory data quality procedures to completely satisfy community concerns about data quality. Communication of this information to the RAB by a quality assurance professional could serve to resolve some of the questions members have about the quality of acquired data and proper use of analytical results, and increase community trust that appropriate decisions are made regarding restoration. Details of the effectiveness of including a quality assurance professional in RAB discussions of laboratory data quality and project quality management are provided in this paper.


Low-level X Chromosome Mosaicism: A Common Finding in Women Undergoing IVF.
To determine the incidence of X chromosome mosaicism in women undergoing in vitro fertilization (IVF) treatment and present preimplantation genetic testing for aneuploidy (PGT-A) outcome of this group. A total of 1,058 women undergoing IVF and 154 women with no fertility problems were enrolled in the study. Karyotyping from peripheral blood lymphocytes was performed by conventional cytogenetics. Twenty-nine women with X mosaicism underwent PGT-A by array-comparative genomic hybridization from embryos at the blastocyst stage. Out of 1,058 women undergoing IVF, 166 (15.7%) had an abnormal karyotype. The most common finding (14.6%) was X chromosome mosaicism. Its frequency was higher in women >35 years old and reached 46.1% in those >45 years of age. PGT-A results of 130 blastocysts tested showed that 29/117 (24.8%) were euploid; 17/29 (60%) were transferred and 10/17 (70%) were successfully implanted, indicating that PGT-A may be an option for women with low-level X chromosome mosaicism undergoing IVF in order to improve the likelihood of a successful pregnancy outcome.


Intravenous aspirin challenge as a diagnosis of nonsteroidal anti-inflammatory drugs hypersensitivity.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a major cause of drug-induced hypersensitivity, called "NSAID hypersensitivity". A confirmative diagnosis is necessary for ensuring drug safety and finding alternative drugs. No reliable test other than direct challenge is diagnostic. An intravenous (IV) aspirin challenge has rarely been tried. To assess the safety and efficacy of the aspirin IV provocation test. A retrospective and descriptive study in a hospital. Clinical data were reviewed in patients who had aspirin IV provocation test with lysine aspirin. In 71 patients suspected of having NSAID hypersensitivity, aspirin IV provocation test was performed. Most provocations were performed on the same day. Forty-three (60.6%) showed a positive response to the challenge. The positive reactions were rescued mostly by antihistamines or glucocorticoids and rarely with bronchodilators and epinephrine. Three patients who showed a negative response to the aspirin challenge were shown to have single-NSAID hypersensitivity. For confirmation of NSAID hypersensitivity in these patients, the sensitivity of the IV aspirin provocation test was 93.5%. Aspirin IV provocation test with lysine aspirin on the same day is safe and efficacious for diagnosing NSAID hypersensitivity.


A delta-rule model of numerical and non-numerical order processing.
Numerical and non-numerical order processing share empirical characteristics (distance effect and semantic congruity), but there are also important differences (in size effect and end effect). At the same time, models and theories of numerical and non-numerical order processing developed largely separately. Currently, we combine insights from 2 earlier models to integrate them in a common framework. We argue that the same learning principle underlies numerical and non-numerical orders, but that environmental features determine the empirical differences. Implications for current theories on order processing are pointed out.


Two-wave-band color-mixing binoculars for the detection of wholesome and unwholesome chicken carcasses: a simulation.
Visual inspection of wholesome and unwholesome chicken carcasses with a novel two-narrowband color-mixing technique for optically enhanced binoculars is simulated. From mean spectra of wholesome, airsacculitis (air-sac), cadaver, inflammatory process (IP), septicemia-toxemia (septox), and tumor chicken samples, 10 nm wave-band pairs are selected using color difference and chromaticness difference indices for simulation of multitarget and single-target detection. The color appearance simulation uses the CIECAM97s color appearance model. Results show that for multitarget detection, the wave-band pair of (454 nm, 578 nm) is able to differentiate all six chicken conditions. For single-target detection of wholesome, air-sac, cadaver, and tumor, the wave-band pairs of (449 nm, 571 nm), (441 nm, 576 nm), (458 nm, 576 nm), and (431 nm, 501 nm), respectively, easily distinguish the target condition from the other five conditions. For single-target detection of IP and septox, the wave-band pairs of (454 nm, 591 nm) and (454 nm, 590 nm), respectively, are able to differentiate the target conditions from wholesome and tumor conditions but have difficulty with the other chicken conditions. The two-color-mixing technique shows promise for use in small-scale processing plant environments to improve the visual inspection process.


ECG-gated MDCT after aortic and mitral valve surgery.
The purpose of this article is to review the utility of ECG-gated MDCT in evaluating postsurgical findings in aortic and mitral valves. Normal and pathologic findings after aortic and mitral valve corrective surgery are shown in correlation with the findings of the traditionally used imaging modalities echocardiography and fluoroscopy to assist in accurate noninvasive anatomic and dynamic evaluation of postsurgical valvular abnormalities. Because of its superior spatial and adequate temporal resolution, ECG-gated MDCT has emerged as a robust diagnostic tool in the evaluation and treatment of patients with postsurgical valvular abnormalities.


[A survey of correlation between serum 25-hydroxyvitamin D levels and dyslipidemia rlsk among middle-aged individuals in Beijing].
To evaluate vitamin D status in middle-aged subjects in Beijing and explore the correlation between serum 25-hydroxyvitamin D[25(OH)D] levels and dyslipidemia. A total of 448 individuals over 40 years old were enrolled in the cross-sectional survey. The general information, blood biochemical and lipid profiles and serum 25(OH)D levels were collected. The subjects were either divided into two groups (the dyslipidemia group and the non-dyslipidemia group) based on the lipid levels, or four groups according to quartiles of 25(OH)D levels. The association between 25(OH)D levels and dyslipidemia risk was analyzed by a logistic regression analysis. A total of 234 cases were in dyslipidemia group, which accounted for 52.23% of the subjects. The serum 25(OH)D levels were significantly lower in the dyslipidemia group than in the non-dyslipidemia group both in men and in women (all P<0.05). The median serum 25(OH)D level in the total subjects was 15.7 (12.2, 20.1)μg/L with 91.1% subjects of serum 25(OH)D level<30 μg/L. The proportion of subjects with dyslipidemia (high TC, high TG, high LDL-C, or low HDL-C) increased with the decrease of 25(OH)D level quartiles (P<0.05). After adjustment of confounding factors, the logistic regression analysis showed that subjects in the lowest 25(OH) D quartile group had 143% higher risks for dyslipidemia than those in the highest quartile group. These findings indicate that 25(OH)D insufficiency is highly prevalent among middle-aged individuals and it may be associated with the risk of dyslipidemia.


Anxiety and depression symptoms and response to methylphenidate in children with attention-deficit hyperactivity disorder and tic disorder.
This study examined response to methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD) and chronic multiple tic disorder. The primary goal was to determine if children with anxiety or depression symptoms showed a less favorable response to treatment. Subjects were 38 prepubertal children who participated in an 8-week, double-blind, placebo-controlled, methylphenidate crossover evaluation. Treatment effects were assessed with direct observations of child behavior in public school and clinic settings; rating scales completed by parents, teachers, and clinicians; and laboratory analogue tasks. There was little evidence (group data) that children with anxiety or depression symptoms responded in a clinically different manner to methylphenidate than youngsters who did not exhibit these symptoms, particularly in school observations of the core features of ADHD. Seeming differences between children with and without comorbid anxiety or depression symptoms and drug response are likely explained by differences in pretreatment levels of negativistic behaviors (i.e., symptoms of oppositional defiant disorder or conduct disorder). Methylphenidate appears to be effective for the management of ADHD behaviors in children with mild to moderate anxiety or depression symptoms; nevertheless, much research remains to be performed in this area.


Tensions within the academic health center.
A variety of forces are converging to unbalance the internal environment of the academic health center, and the dean of the medical school sits uneasily in the resulting vortex of conflicting needs and demands. For example, the introduction of Medicare in 1965 profoundly changed the size and complexity of medical school departments and greatly stimulated the growth of hospitals. More stresses have come from rising health care expectations of the public; the replacement of free-for-service indemnity health care by managed care and vertically integrated health care systems; the proliferation of academic specialties and subspecialties; and the recent growth in the academic medical center, which is seen as a threat to the academic integrity of the university. Within the medical school there are tensions between basic and clinical research, between education and research, between education and clinical practice, and between the dean and department chairs over allocation of resources. Perhaps the most complex tensions exist between the medical school dean and the academic hospital director. The overarching tension in the academic health center results from striving to balance the need to fulfill academic goals with the need to fill hospital beds to maintain financial solvency. This tension will not lessen so long as there is no common vision for the academic health center as a whole, and will probably increase with the forthcoming changes in health care reform. The dean and the hospital director must forge a strong alliance, and the hospital must realize that for its continuing success, it must support the academic program.(ABSTRACT TRUNCATED AT 250 WORDS)


Protein A immunoadsorption therapy in HIV-related immune thrombocytopenia: a preliminary report.
Nine homosexual patients with immune thrombocytopenia were treated with autologous plasma that had been perfused over silica-immobilized Staphylococcus aureus protein A (SpA). Pretreatment platelet counts ranged from 10,000 to 98,000 cells/mm3 (mean: 54,000 cells/mm3). Six patients responded to therapy. Platelets increased by a mean of 95,000 cells/mm3 (p less than 0.007) and reached normal levels (greater than 150,000 cells/mm3) in four patients. Increased platelet counts are presently sustained in these four individuals after 5 months of follow-up. Increases in platelet counts significantly correlated with decreases in platelet-associated IgG (PAIgG), platelet-directed IgG (PDIgG), and immune complexes (CIC). PAIgG and PDIgG declined by a mean of 67% (p less than 0.003) and 58% (p less than 0.007), respectively. CIC decreased by a mean of 37% (p = 0.02). Complement was concomitantly activated in all four examined patients. C3a and C5a increased 23-fold and 2.6-fold, respectively, while total hemolytic complement decreased by 50%. Activated complement components and removal of CIC and IgG thus may contribute to the platelet-enhancing activity of SpA immunoadsorption therapy.


Okamoto syndrome in a girl of Caucasian origin.
We report the clinical and genetic evaluation of a 2-year-old Greek female with striking phenotypic similarities to the three previously published cases of Okamoto syndrome. The main features were characteristic facies, cleft palate, generalized hypotonia, severe developmental delay, congenital hydronephrosis, and congenital heart defects. Routine chromosome testing and whole-genome high-resolution comparative genetic hybridization analysis were negative for any gross numerical or structural chromosome aberrations and for microdeletions/duplications of more than 3 million base pairs respectively. Fluorescence in situ hybridization analysis for 22q11.2 deletion and DNA analysis of the protein tyrosine phosphatase, non-receptor type II gene were normal, thus excluding DiGeorge and Noonan syndromes. Our patient did not show most of the cardinal features of Schinzel-Giedion, otopalatodigital, and C-trigonocephaly syndromes. Moreover, in our patient some new malformations were identified: unilateral kidney hypoplasia and severe anal stenosis. The latter was considered as pertinent and is described here to establish a wider clinical spectrum of Okamoto syndrome. At the age of 3 years 6 months the child continues to show severe growth failure and significant global developmental delay. For the practising paediatrician it is prudent to bear Okamoto syndrome in mind, especially in children with learning disability and a pattern of dysmorphic features.


Synovial cutaneous fistula complicating a reverse total shoulder arthroplasty.
Reverse total shoulder arthroplasty is becoming a common form of shoulder arthroplasty that is often performed in the setting of rotator cuff pathology. Infection is a rare complication but is more common in reverse total shoulder arthroplasty than in hemiarthroplasty or anatomic total shoulder arthroplasty. We present the case of a 69-year-old patient with a reverse total shoulder arthroplasty who presented with purulent drainage from the skin of his anterior shoulder. Computed tomography arthrogram confirmed the presence of a synovial cutaneous fistula. Synovial cutaneous fistula is a rare variant of periprosthetic infection that, to our knowledge, has not been described previously in the setting of a reverse total shoulder arthroplasty. Computed tomography arthrogram proved to be a reliable method for confirming the diagnosis and was used for operative planning to remove the hardware.


Role of committed minorities in times of crisis.
The surprising social phenomena of the Arab Spring and the Occupy Wall Street movement posit the question of whether the active role of committed groups may produce political changes of significant importance. Under what conditions are the convictions of a minority going to dominate the future direction of a society? We address this question with the help of a Cooperative Decision Making model (CDMM) which has been shown to generate consensus through a phase-transition process. We observe that in a system of a finite size the global consensus state is not permanent and times of crisis occur when there is an ambiguity concerning a given social issue. The correlation function within the cooperative system becomes similarly extended as it is observed at criticality. This combination of independence (free will) and long-range correlation makes it possible for very small but committed minorities to produce substantial changes in social consensus.


Medication administration through enteral feeding tubes.
An overview of enteral feeding tubes, drug administration techniques, considerations for dosage form selection, common drug interactions with enteral formulas, and methods to minimize tube occlusion is given. Enteral nutrition through a feeding tube is the preferred method of nutrition support in patients who have a functioning gastrointestinal tract but who are unable to be fed orally. This method of delivering nutrition is also commonly used for administering medications when patients cannot swallow safely. However, several issues must be considered with concurrent administration of oral medications and enteral formulas. Incorrect administration methods may result in clogged feeding tubes, decreased drug efficacy, increased adverse effects, or drug-formula incompatibilities. Various enteral feeding tubes are available and are typically classified by site of insertion and location of the distal tip of the feeding tube. Liquid medications, particularly elixirs and suspensions, are preferred for enteral administration; however, these formulations may be hypertonic or contain large amounts of sorbitol, and these properties increase the potential for adverse effects. Before solid dosage forms are administered through the feeding tube, it should be determined if the medications are suitable for manipulation, such as crushing a tablet or opening a capsule. Medications should not be added directly to the enteral formula, and feeding tubes should be properly flushed with water before and after each medication is administered. To minimize drug-nutrient interactions, special considerations should be taken when administering phenytoin, carbamazepine, warfarin, fluoroquinolones, and proton pump inhibitors via feeding tubes. Precautions should be implemented to prevent tube occlusions, and immediate intervention is required when blockages occur. Successful drug delivery through enteral feeding tubes requires consideration of the tube size and placement as well as careful selection and appropriate administration of drug dosage forms.


Carbon Dots Detect Water-to-Ice Phase Transition and Act as Alcohol Sensors via Fluorescence Turn-Off/On Mechanism.
Highly fluorescent carbon nanoparticles called carbon dots (CDs) have been the focus of intense research due to their simple chemical synthesis, nontoxic nature, and broad application potential including optoelectronics, photocatalysis, biomedicine, and energy-related technologies. Although a detailed elucidation of the mechanism of their photoluminescence (PL) remains an unmet challenge, the CDs exhibit robust, reproducible, and environment-sensitive PL signals, enabling us to monitor selected chemical phenomena including phase transitions or detection of ultralow concentrations of molecular species in solution. Herein, we report the PL turn-off/on behavior of aqueous CDs allowing the reversible monitoring of the water-ice phase transition. The bright PL attributable to molecular fluorophores present on the CD surface was quenched by changing the liquid aqueous environment to solid phase (ice). Based on light-induced electron paramagnetic resonance (LEPR) measurements and density functional theory (DFT) calculations, the proposed kinetic model assuming the presence of charge-separated trap states rationalized the observed sensitivity of PL lifetimes to the environment. Importantly, the PL quenching induced by freezing could be suppressed by adding a small amount of alcohols. This was attributed to a high tendency of alcohol to increase its concentration at the CD/solvent interface, as revealed by all-atom molecular dynamics simulations. Based on this behavior, a fluorescence "turn-on" alcohol sensor for exhaled breath condensate (EBC) analysis has been developed. This provided an easy method to detect alcohols among other common interferents in EBC with a low detection limit (100 ppm), which has a potential to become an inexpensive and noninvasive clinically useful diagnostic tool for early stage lung cancer screening.


[Expressions and clinical significance of TGF-βRII and NF-κB in oral squamous cell carcinoma].
To investigate the expression of nuclear factor κappa-B (NF-κB) and transforming growth factor β receptor II (TGF-βRII) and their clinical pathological significance in oral squamous cell carcinoma(OSCC). The expression of NF-κB and TGF-βRII in 60 OSCC samples, 20 adjacent tissues, 29 metastatic lymph nodes and 10 non-metastatic lymph nodes were detected by immunohistological method. Statistical analysis was performed with SPSS 20.0 software package. The expression of NF-κB in OSCC and metastatic lymph nodes was significantly higher than that in the adjacent tissues and non-metastatic lymph nodes, respectively (P<0.05). However, the expression of TGF-βRII in OSCC and metastatic lymph nodes was significantly lower than that in the adjacent tissues and non-metastatic lymph nodes, respectively (P<0.05). NF-κB was negatively correlated with TGF-βRII. The expression of NF-κB in patients with lower differentiation, lymphatic metastasis and higher grade were significantly higher than in patients with higher differentiation, lower grade and without lymphatic metastasis (P<0.05), respectively. NF-κB was a predicator of OSCC. NF-κB is negatively correlated with TGF-βRII.NF-κB and TGF-βRII are associated with the progression of OSCC. NF-κB may promote angiogenesis through down-regulating the expression of TGF-βRII, which promotes progression of OSCC.


The effects of slip velocity on a micropolar fluid through a porous channel with expanding or contracting walls.
In this paper, a simple mathematical model depicting blood flow in the deforming porous channel is developed with an emphasis on the permeability property of the blood vessel and slip boundary based on Beavers and Joseph slip condition. In this study, the blood is represented by a micropolar fluid. With such an ideal model, the governing equations are reduced to ordinary ones by introducing suitable similar transformations. Homotopy analysis method is employed to obtain the expressions for velocity and microrotation fields. Graphs are sketched for some values of parameters such as slip coefficient and expansion ratio, and the associated dynamic characteristics are analysed in detail.


Madelung Deformity of the Wrist Managed Conservatively.
A 19-year-old female presented with pain, deformity, and slightly restricted left wrist motion for five years with gradual progression. Physical examination revealed volar subluxation of the left hand, dorsally prominent ulnar styloid, radial and dorsal bowing of the distal forearm, and mild restriction in wrist dorsiflexion. Radiographs showed a failure of ossification of the ulnar side of the distal radial epiphysis, increased radial inclination angle, dorsal subluxation of the distal ulna, V-shaped proximal carpal row due to proximal migration of the lunate, and increased interosseous space. A diagnosis of Madelung deformity of the left wrist was made. Conservative management with oral analgesics, activity restriction, and a volar splint was done as the patient was skeletally mature, had only mild pain with no functional limitation or gross deformity. At the six-month follow-up, she was doing well with decreased pain and no new complaints.


A reliable control system for measurement on film thickness in copper chemical mechanical planarization system.
In recent years, a variety of film thickness measurement techniques for copper chemical mechanical planarization (CMP) are subsequently proposed. In this paper, the eddy-current technique is used. In the control system of the CMP tool developed in the State Key Laboratory of Tribology, there are in situ module and off-line module for measurement subsystem. The in situ module can get the thickness of copper film on wafer surface in real time, and accurately judge when the CMP process should stop. This is called end-point detection. The off-line module is used for multi-points measurement after CMP process, in order to know the thickness of remained copper film. The whole control system is structured with two levels, and the physical connection between the upper and the lower is achieved by the industrial Ethernet. The process flow includes calibration and measurement, and there are different algorithms for two modules. In the process of software development, C++ is chosen as the programming language, in combination with Qt OpenSource to design two modules' GUI and OPC technology to implement the communication between the two levels. In addition, the drawing function is developed relying on Matlab, enriching the software functions of the off-line module. The result shows that the control system is running stably after repeated tests and practical operations for a long time.


Stress and Disease Onset in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
To explore the potential contribution of stress as a trigger for disease onset in patients with antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). 53 AAV and 85 rheumatoid arthritis (RA) patients as well as 53 healthy controls (HC) were thoroughly asked for the number and impact of stressful life events, coping strategies, and available social support 12 months prior to disease onset. Anxiety, depression, personality dimensions, insomnia, and fatigue were also determined. AAV patients reported higher scoring of the impact of stressful life events compared to the RA and HC group prior to disease onset (2.8 ± 3.1 vs 1.8 ± 2.1 vs 1.7 ± 2.3, p-values: 0.047 and 0.053, respectively). While the number of reported stressful events was found to be significantly higher in AAV vs RA patients but not HC, certain coping strategies and social support features were more commonly implemented by AAV patients compared to HC, but not RA patients. As far as personality and other psychosocial characteristics, AAV patients displayed significantly higher psychoticism traits compared to RA, with no other differences being detected between AAV patients and both RA and HC. After adjusting for potential cofounders, scoring of the impact of stressful life events >3 was independently associated with AAV development compared to both RA and HC [ORs (95% CI): 4.6 (1.6-13.4) and 4.4 (1.0-19.0), respectively]. The perceived impact of stressful life events prior to disease onset emerged as a contributing factor for AAV development.


Fast and accurate detection of action potentials from somatic calcium fluctuations.
Large-scale recording from a population of neurons is a promising strategy for approaching the study of complex brain functions. Taking advantage of the fact that action potentials reliably evoke transient calcium fluctuations in the cell body, functional multineuron calcium imaging (fMCI) monitors the suprathreshold activity of hundreds of neurons. However, a limitation of fMCI is its semi-manual procedure of spike extraction from somatic calcium fluctuations, which is not only time consuming but is also associated with human errors. Here we describe a novel automatic method that combines principal-component analysis and support vector machine. This simple algorithm determines the timings of the spikes in calcium fluorescence traces more rapidly and reliably than human operators.


PuHox52-mediated hierarchical multilayered gene regulatory network promotes adventitious root formation in Populus ussuriensis.
Adventitious root (AR) formation is critically important in vegetative propagation through cuttings in some plants, especially woody species. However, the underlying molecular mechanisms remain elusive. Here, we report the identification of a poplar homeobox gene, PuHox52, which was induced rapidly (within 15 min) at the basal ends of stems upon cutting and played a key regulatory role in adventitious rooting. We demonstrated that overexpression of PuHox52 significantly increased the number of ARs while suppression of PuHox52 had the opposite effect. A multilayered hierarchical gene regulatory network (ML-hGRN) mediated by PuHox52 was reverse-engineered and demonstrated to govern AR formation. PuHox52 regulated AR formation through upregulation of nine hub regulators, including a jasmonate signaling pathway gene, PuMYC2, and an auxin signaling pathway gene, PuAGL12. We also identified coherent type 4 feed-forward loops within this ML-hGRN; PuHox52 repressed PuHDA9, which encodes a histone deacetylase, and led to an increase in acetylation and presumably expression of three hub regulators, PuWRKY51, PuLBD21 and PuIAA7. Our results indicate that the ML-hGRN mediated by PuHox52 governs AR formation at the basal ends of stem cuttings from poplar trees.


Diagnostic and Statistical Manual of Mental Disorders-5: implications for older adults and their families.
The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) is targeted for publication in May 2013. Older adults and their families should be aware of the potential impact that changes in this important document may have on diagnosis and treatment of mental health concerns. Two specific changes related to a new category of Neurocognitive Disorders and a new interpretation of criteria for depression after bereavement are discussed in this article. Nurses can help older adults and their families understand the new DSM-5 terminology and encourage them to discuss risks, benefits, and likely outcomes of diagnoses, procedures, and treatments that may seem unfamiliar.


Preschoolers' generosity increases with understanding of the affective benefits of sharing.
Research has demonstrated that sharing with others is rewarding, suggesting a proximal mechanism of humans' extraordinary tendency to engage in prosocial behavior. The current study explored the cognitive basis of the relation between generosity and happiness early in ontogeny. We demonstrate that preschool children understand the relation between generosity and happiness. Moreover, our results show that children's emotion ratings are predictive for their subsequent sharing behavior. This finding provides evidence for the theoretical claim that prosocial behavior may be related to the anticipation of positive feelings, and that this mechanism may explain early instances of generosity in preschool children.


A universal transgene silencing method based on RNA interference.
Inducible gene expression systems have contributed significantly to the understanding of molecular regulatory networks. Here we describe a simple and powerful RNA interference-based method that can silence the expression of any transgene. We first used an IRES bicistronic lentiviral vector and showed that targeting the second cistron with a specific siRNA resulted in silencing of both transgenes. We then inserted a siRNA minimal target sequence in the 3'-untranslated region (3'-UTR) of a transgene and showed that the cognate siRNA delivered by a lentiviral vector led to the partial silencing of the transgene. The multimerization of this siRNA target sequence led to the highly efficient silencing of four different transgenes. This new method to silence transgene expression is more versatile than existing methods of conditional inactivation of gene expression, such as transcriptional switches or site-specific recombination. It is applicable to a wide variety of models including primary cells, terminally differentiated cells and transgenic animals.


A portable telerehabilitation system for remote evaluations of impaired elbows in neurological disorders.
A portable teleassessment system was designed for remote evaluation of elbow impairments in patients with neurological disorders. A master device and a slave device were used to drive a mannequin arm and the patient's arm, respectively. The elbow flexion angle and torque were measured at both the master and slave devices, and sent to each other for teleoperation. To evaluate spasticity/contracture of the patient's elbow remotely, the clinician asked the patient to relax the elbow, moved the mannequin arm at a selected velocity, and haptically felt the resistance from the patient's elbow. In other tasks, the patient moved his/her elbow voluntarily and the clinician observed the corresponding mannequin arm movement and determined the active range of motion (ROM). The clinician could also remotely resist the patient's movement and evaluate the muscle strength. To minimize the effect of network latency, two different teleoperation schemes were used depending on the speed of the tasks. For slow movement tasks, real-time teleoperations were performed using control architectures that considered causality of the tasks, with performance similar to that during an in-person examination. For tasks involving fast movements, a teach-and-replay teleoperation scheme was used which provided the examiner with transparent and stable haptic feeling. Overall, the teleassessment system allowed the clinician to remotely evaluate the impaired elbow of stroke survivors, including assessment of the passive ROM, active ROM, muscle strength, velocity-dependent spasticity, and catch angle.