Animal-Assisted Interventions Improve Mental, But Not Cognitive or Physiological Health Outcomes of Higher Education Students: a Systematic Review and Meta-analysis.
Due to the high burden of mental health issues among students at higher education institutions world-wide, animal-assisted interventions (AAIs) are being used to relieve student stress. The objective of this study was to systematically review of the effects of AAIs on the mental, physiological, and cognitive outcomes of higher education students. Randomized controlled trials using any unfamiliar animal as the sole intervention tool were included in this review. Study quality was assessed using the Cochrane Risk-of-Bias tool. Where possible, effect sizes (Hedges' g) were pooled for individual outcomes using random-effects meta-analyses. Albatross plots were used to supplement the data synthesis. Of 2.494 identified studies, 35 were included. Almost all studies used dogs as the intervention animal. The quality of most included studies was rated as moderate. Studies showed an overall reduction of acute anxiety and stress. For other mental outcomes, studies showed smaller, but nonetheless beneficial effects. Studies showed no clear effect on physiological or cognitive outcomes. Strong methodological heterogeneity between studies limited the ability to draw clear conclusions. The online version contains supplementary material available at 10.1007/s11469-022-00945-4.


Insights into the pharmacological and therapeutic effects of apigenin in liver injuries and diseases.
Liver diseases are a spectrum of diseases that include hepatic steatosis, nonalcoholic fatty liver disease, hepatitis, liver fibrosis, cirrhosis, and hepatic cancer. These diseases not only severely decrease the quality of life for patients, but also cause financial burden. Although apigenin (APG) has recently become the primary treatment for liver injuries and diseases (LIADs), there has been no systematic review of its use. To review the existing literature and put forward novel strategies for future APG research on LIADs. A search was conducted in PubMed, Science Direct, Research Gate, Web of Science, VIP, Wanfang, and CNKI, and 809 articles were obtained. After applying inclusion and exclusion criteria, 135 articles were included. APG is promising in treating LIADs via various mechanisms arising from its anti-inflammation, anti-proliferation, anti-infection, anti-oxidation, and anti-cancer properties. This review summarizes the evidence supporting the use of APG as a treatment for LIADs and provides an insight into the intestinal microbiota, which may have important implications in its future clinical use.


Matching between regional coronary vasodilator capacity and corresponding circumferential strain in individuals with normal and increasing body weight.
To define the relationship between regional coronary vasodilator capacity and myocardial circumferential strain at rest in normal weight, overweight, and obese individuals with normal global left-ventricular function. Myocardial blood flow at rest and during pharmacologic vasodilation was measured with (13)N-ammonia PET/CT in mL/g/minute in normal weight control (CON, n = 12), overweight (OW, n = 10), and obese individuals (OB, n = 10). In addition, resting myocardial function was evaluated as circumferential strain (Єc, %) by MRI. Global myocardial flow reserve (MFR) did not differ significantly between CON and OW (2.98 ± 0.96 vs 2.70 ± 0.66, P = .290), whereas it declined significantly in OB (1.98 ± 1.04, P = .030). Further, global Єc (%) was comparable between CON, OW, and OB (-0.24 ± 0.03, -0.23 ± 0.02, and -0.23 ± 0.04) but it was lowest in OB when normalized to the rate-pressure product (NЄc: -0.31 ± 0.06, -0.32 ± 0.05, and -0.26 ± 0.08). When MFR of the three major coronary territories was correlated with corresponding Єc, a positive association was observed in CON (r = 0.36, P = .030), in OW (r = 0.54, P = .002), and also in OB when relating NЄc to coronary vascular resistance during pharmacologic vasodilation (r = -0.46, P = .010). Higher coronary vasodilator capacity is related to corresponding regional circumferential strain at rest in non-obese individuals, while this is also observed for reduced MFR in obesity.


[Expression of aquaporin-4 in isolated and purified rat alveolar type II cells].
To explore the expression of aquaporin-4 (AQP4) in isolated and purified rat alveolar type II cells. Rat alveolar type II cells were isolated, purified and identified by special staining and electron microscopy. The distribution of AQP4 in alveolar type II cells was observed by immunocytochemistry and immunoelectron microscope with affinity-purified antibodies to human AQP4. Immunocytochemistry showed staining for AQP4 in rat alveolar type II cells, and immunoelectron microscope demonstrated the presence of AQP4 on the membrane of the cells. AQP4 is expressed in alveolar type II cells in rats, and may play a role in water transportation in the respiratory system.


Sex-specific trends in suicide method, Canada, 1971-1985.
Between 1971 and 1985, sex-specific suicide rates in Canada have diverged, with male rates increasing and female rates decreasing. Using linear regression techniques, we examined changes in sex- and method-specific rates and their association with changes in overall sex-specific rates. 92% of the variability in the overall female rates was explained by the declining rate for poisoning by solid or liquid substances. The most important change for males was the increasing rate for hanging, strangulation and suffocation which explained 65% of the change in the overall rate.


The co-colonization prevalence of Pseudomonas aeruginosa and Aspergillus fumigatus in cystic fibrosis: A systematic review and meta-analysis.
The co-colonization prevalence of P. aeruginosa and A. fumigatus in cystic fibrosis (CF) has been inconsistently reported. The purpose of this systematic review and meta-analysis was to estimate the overall co-colonization prevalence of P. aeruginosa and A. fumigatus in CF. The Embase, PubMed and Web of Science databases were systematically searched for studies reporting the co-colonization prevalence of P. aeruginosa and A. fumigatus in CF. The co-colonization prevalence of two pathogenic microorganisms in the individual studies was assessed by calculating the proportion and 95% confidence interval (CI). The random effects model was used to calculate the pooled prevalence. The I2 test was used to assess statistical heterogeneity. The funnel plot and two statistical methods were used to assess publication bias. Twenty-three eligible studies were included in this analysis. The pooled co-colonization prevalence of P. aeruginosa and A. fumigatus in CF patients was 15.8% (95% CI: 9.9-21.8). The co-colonization prevalence of P. aeruginosa and A. fumigatus chronic colonization was lower than that of intermittent colonization, higher in sputum cultures than in bronchoalveolar lavage (BAL) cultures, and lower in children than in adults. There was a statistically significant difference in co-colonization prevalence among studies from different decades, but the prevalence was similar in different geographical regions and with different study types. The co-colonization prevalence of P. aeruginosa and A. fumigatus in the lower respiratory tract of CF patients was high. The anti-infective treatment in exacerbation of CF should be considered to cover the two pathogenic microorganisms simultaneously. Large-scale research is still needed to obtain more accurate co-colonization data.


Computer-based recognition of dysmorphic faces.
Genetic syndromes often involve craniofacial malformations. We have investigated whether a computer can recognize disease-specific facial patterns in unrelated individuals. For this, 55 photographs (256 x 256 pixel) of patients with mucopolysaccharidosis type III (n=6), Cornelia de Lange (n=12), fragile X (n=12), Prader-Willi (n=12), and Williams-Beuren (n=13) syndromes were preprocessed by a Gabor wavelet transformation. By comparing the feature vectors at 32 facial nodes, 42/55 (76%) of the patients were correctly classified. In another four patients (7%), the correct and an incorrect diagnosis scored equally well. Clinical geneticists who were shown the same photographs achieved a recognition rate of 62%. Our results prove that certain syndromes are associated with a specific facial pattern and that this pattern can be described in mathematical terms.


Gene Expression Profiling of the Sciatic Nerve in Streptozotocin-Induced Diabetic Rats with Peripheral Neuropathy.
To investigate the candidate biomarkers and molecular mechanisms involved in the early phase of experimental diabetic peripheral neuropathy (DPN). Diabetes in Sprague-Dawley rats was induced with streptozotocin (STZ) treatment, followed with neurological tests and histological examinations to assess the neuropathic symptoms of DPN. Microarray was performed on the sciatic nerve tissues from control rats and DPN rats at then6th week after diabetes induction, and differentially expressed genes (DEGs) between them were identified and applied for further bioinformatic analyses. Experimental DPN rats were successfully constructed, presenting significantly decreased withdrawal threshold and motor nerve conduction velocity, and typical histological changes in the sciatic nerve. 597 DEGs (186 up- and 411 downregulated) were identified in DPN rats. DEGs from the 3 most highly connected clusters in the protein-protein interaction network were enriched for biological processes or pathways such as "cell division," "cell cycle," "protein phosphorylation," "chemokine signaling pathway," "neuropeptide signaling pathway," "response to drug," "cellular response to insulin stimulus," "PPAR signaling pathway," and "glycerophospholipid metabolism." Thirteen genes were identified as the hub DEGs in the PPI network. Eleven transcriptional factors (TFs) targeting 9 of the 13 hub DEGs were predicted. The present study identified a pool of candidate biomarkers such as Cdk1, C3, Mapk12, Agt, Adipoq, Cxcl2, and Mmp9 and molecular mechanisms which may be involved in the early phase of experimental DPN. The findings provide clues for exploring new strategies for the early diagnosis and treatment of DPN.


Holistic Sustainability Assessment of Riparian Buffer Designs: Evaluation of Alternative Buffer Policy Scenarios Integrating Stream Water Quality and Costs.
Riparian buffer zones (RBZs) have been shown to be effective best management practices (BMPs) in controlling non-point source pollutants in waterbodies. However, the holistic sustainability assessment of individual RBZ designs is lacking. We present a methodology for evaluating the holistic sustainability of RBZ policy scenarios by integrating environmental and economic indicators simulated in three watersheds in the southeastern USA. We developed three unique sets of 40, 32, and 48 RBZ policy scenarios as decision management objectives (DMOs), respectively, in Back Creek, Sycamore Creek, and Greens Mill Run watersheds (Virginia and North Carolina) by combining the RBZ-widths with vegetation types (grass, urban, naturalized, wildlife, three-zone forest, and two-zone forest). We adapted the RBZ-hydrologic and water quality system assessment data of instream water quality parameters (dissolved oxygen, total phosphorus, total nitrogen, total suspended solids-sediment and biochemical oxygen demand) as environmental indicators, recently published by U.S. EPA. We calculated 20-year net present value costs as economic indicators using the RBZ's establishment, maintenance, and opportunity costs data published by the Natural Resources Conservation Service. The mean normalized net present value costs varied by DMOs ranging from 4% (grass RBZ-1.9 m) to 500% (wildlife RBZ-91.4 m) across all watersheds, due primarily to the width and the opportunity costs. The mean normalized environmental indicators varied by watersheds, with the largest change in total nitrogen due to urban RBZs in Back Creek (60-95%), Sycamore Creek (37-91%), and Greens Mill (52-93%). The holistic sustainability assessments revealed the least to most sustainable DMOs for each watershed, from least sustainable wildlife RBZ (score of 0.54), three-zone forest RBZ (0.32), and three-zone forest RBZ (0.62), respectively, for Back Creek, Sycamore Creek, and Greens Mill, to most sustainable urban RBZ (1.00) for all watersheds.


Changes of protein stiffness during folding detect protein folding intermediates.
Single-molecule force-quench atomic force microscopy (FQ-AFM) is used to detect folding intermediates of a simple protein by detecting changes of molecular stiffness of the protein during its folding process. Those stiffness changes are obtained from shape and peaks of an autocorrelation of fluctuations in end-to-end length of the folding molecule. The results are supported by predictions of the equipartition theorem and agree with existing Langevin dynamics simulations of a simplified model of a protein folding. In the light of the Langevin simulations the experimental data probe an ensemble of random-coiled collapsed states of the protein, which are present both in the force-quench and thermal-quench folding pathways.


The creation of phenomena in interactive biorobotics.
In so-called interactive biorobotics, robotic models of living systems interact with animals in controlled experimental settings. By observing how the focal animal reacts to the stimuli delivered by the robot, one tests hypotheses concerning the determinants of animal behaviour in social contexts. Building on previous methodological reconstructions of interactive biorobotics, this article reflects on the claim, made by several authors in the field, that this strategy may enable one to explain social phenomena in animals. The answer offered here will be negative: interactive biorobotics does not contribute to the explanation of social phenomena. However, it may greatly contribute to the study of animal behaviour by creating social phenomena in the sense discussed by Ian Hacking, i.e. by precisely defining new phenomena to be explained. It will be also suggested that interactive biorobotics can be combined with more classical robot-based approaches to the study of living systems, leading to a so-called simulation-interactive strategy for the mechanistic explanation of social behaviour in animals.


Aging effects on the ERP correlates of involuntary attentional capture in speech sound analysis.
In an auditory oddball paradigm, 16 old and 16 young adults were asked to ignore binaurally presented disyllabic speech sounds and to watch a silent movie while event-related potentials (ERPs) were recorded. Four types of phonetic deviants occurred on, respectively: (1) the Stressed-First syllable, (2) the Unstressed-First syllable, (3) the Stressed-Second syllable and (4) the Unstressed-Second syllable. The nature of the phonetic change was the same across the four deviants. A P3a was seen only for deviant 3 in the elderly while observed for deviants 1 and 3 in the young. The mismatch negativities (MMNs) to deviants 1 and 2 were reduced compared with those to the other two deviants in both age groups. It is concluded that the ability to use salient prosody to involuntarily capture attention for speech sounds is preserved in normal aging. The lack of P3a response to deviant 1 in the elderly may result from the combined effects of backward masking and age-related temporal encoding inefficiency as indicated by reduced MMNs for the elderly.


Labyrinthine projection to the hypoglossal nucleus.
Evoked potentials and responses of single hypoglossal neurons were recorded in response to electrical stimulation of the labyrinth. In addition, the spontaneous electrical activity of hypoglossal neurons was significantly modified in response to ipsi- and contralateral static tilt of the whole animal and thermic stimulation of the labyrinth. The experiment showed that the labyrinth modulates the electrical activity of hypoglossal neurons with phasic inputs in response to ampullar stimulation and with tonic inputs in response to macular stimulation. The vestibular phasic influence of hypoglossal neurons represents the most adequate functional pattern to obtain a quick, short lasting response of the tongue muscles instantly modifiable with every abrupt head displacement. On the contrary, the vestibular tonic influence of hypoglossal neurons represents the most adequate functional pattern to obtain not only adjustment but also maintenance of the muscular lingual response to static displacement of the head.


Parathyroid hormone monotherapy and cotherapy with antiresorptive agents restore vertebral bone mass and strength in aged ovariectomized rats.
Previous studies have shown that parathyroid hormone (PTH) monotherapy and cotherapy with estrogen or risedronate augment vertebral bone mass and bone strength in young, ovariectomized (OVX) rats. The current study was designed to determine whether PTH has similar bone anabolic effects in aged OVX rats at a much later stage of estrogen depletion. Female Sprague Dawley rats were subjected to sham surgery or bilateral ovariectomy at three months of age and maintained untreated for one year after surgery to allow for the development of vertebral osteopenia in OVX rats. Groups of baseline control and OVX rats were sacrificed at the end of this pretreatment period. The remaining OVX rats were then treated for ten weeks with vehicle, antiresorptive agents alone (estrogen, risedronate, or calcitonin), or PTH alone. Other groups of OVX rats were treated concurrently with PTH and each of the antiresorptive agents. The first and fourth lumbar vertebral bodies were processed undecalcified for quantitative bone histomorphometry and biomechanical testing, respectively. As expected, bone mass and compressive strength were decreased in the lumbar vertebral body of baseline OVX rats compared to baseline control rats. This bone loss was associated with decreases in trabecular number and width and an increase in trabecular separation. Treatment with estrogen, risedronate, or calcitonin alone failed to reverse the changes in bone mass, structure, and strength induced by ovariectomy. In contrast, treatment of OVX rats with PTH alone restored vertebral cancellous bone volume and ash density to the level of vehicle-treated control rats and increased vertebral maximum load, stress, and normalized load to well above this level.(ABSTRACT TRUNCATED AT 250 WORDS)


Odontogenic lesions in a pediatric population: Review of the literature and presentation of 745 cases.
Pediatric odontogenic lesions are rare clinical entities and are not well addressed in the otolaryngology literature. Knowledge of the biologic and clinical behavior of these lesions and their basic features such as location and age are key aspects for otolaryngologists in developing an early clinical differential diagnosis, such that they can provide adequate treatment. Six thousand histologically-diagnosed odontogenic lesions from a 40-year period were reviewed. Pediatric patients (745 cases, 12.7%) aged up to 17 years were selected and reevaluated. The patients were divided into three age groups according to dentition periods: primary dentition (0-5 years), mixed dentition (6-12 years), and permanent dentition (13-17 years). Clinical data, including age, sex, and location, were collected from pathology records. Of the total of 745 cases, 596 specimens (80%) were diagnosed as odontogenic cysts and 149 specimens (20%) were diagnosed as odontogenic tumors. The most frequent odontogenic cysts were radicular cysts (48.4%), followed by dentigerous cysts (16.7%). The most common odontogenic tumor was odontoma (8.05%). This study shows that all odontogenic lesions in the pediatric group are benign. Odontogenic tumors are relatively rare in this age group. Knowledge of the biological and histopathological behaviors of odontogenic lesions and their basic features such as location and age is a key aspect for developing an early clinical differential diagnosis and providing adequate treatment.


Innovation Born in Isolation: Rapid Transformation of an In-Person Medical Student Radiology Elective to a Remote Learning Experience During the COVID-19 Pandemic.
With social distancing measures in place both nationally and globally, the current COVID-19 pandemic has forced the cancellation of in-person classes at universities and medical schools across the country. This has presented unique challenges for educators in all fields as they have embarked, many for the first time, on the journey into remote education in order to provide distance learning opportunities for students. In this article we will review our approach to rapidly converting an in-person diagnostic radiology elective to an entirely remote learning experience for medical students at our institution, including modification of course structure, software tools and materials utilized, and strategies for learner engagement and collaboration. Development of an online elective led to a 10-fold increase in student enrollment compared to the traditional course offering, providing a unique opportunity to reach a broad number of students, many of whom were in the early clinical stages of their medical school career. Lastly, we will review faculty feedback after participating in the remote course as well as lessons learned from the transition to distance learning and its implications for future work CONCLUSION: The current state of technology makes radiology particularly well-suited for distance learning, and with the proper tools and approaches, effective remote radiology instruction can be achieved.


Cost-effectiveness of two-dose human papillomavirus vaccination in Singapore.
Cervical cancer is the tenth most common cancer and the eighth most frequent cause of death among women in Singapore. As human papillomavirus (HPV) infection is the necessary cause of cervical cancer, the risk of cervical cancer can be substantially reduced through vaccination. This study was conducted to evaluate the cost-effectiveness of two-dose HPV vaccination as part of a national vaccination programme for 12-year-old girls in Singapore, from the perspective of the healthcare payer. A lifetime Markov cohort model was used to evaluate the cost-effectiveness of introducing the AS04-adjuvanted HPV-16/18 vaccine (AS04-HPV-16/18v) to the current cervical screening programme in Singapore. Furthermore, the cost-effectiveness of the AS04-HPV-16/18v was compared with the HPV-6/11/16/18 vaccine (4vHPV). Model inputs were derived from local data, where possible, and validated by clinical experts in Singapore. Introduction of the AS04-HPV-16/18v in Singapore was shown to prevent 137 cervical cancer cases and 48 cervical cancer deaths when compared with screening alone. This resulted in an incremental cost-effectiveness ratio of SGD 12,645 per quality-adjusted life year (QALY) gained, which is cost-effective according to the World Health Organization threshold for Singapore. When discounted at 3%, AS04-HPV-16/18v was dominant over 4vHPV, with cost savings of SGD 80,559 and 28 additional QALYs gained. In the one-way sensitivity analysis, AS04-HPV-16/18v remained cost-effective compared with screening alone and dominant compared with 4vHPV. AS04-HPV-16/18v is the most cost-effective choice for reducing the burden of cervical cancer through universal mass vaccination for 12-year-old girls in Singapore.


The effect of visual frame of reference on a judgement of plane stimulus orientation by children.
Three studies are reported with children aged 4 1/2 to 9 1/2 years and also with educationally subnormal children, in which it was found that up to about 7 years children's selection of one of a pair of line stimuli as 'falling over' is affected by the nature of the visual surround contours provided. Both the form of the stimulus surround and the presence or absence of a baseline tilted 45 degrees relative to the horizontal were found to affect the children's judgements. The plane (horizontal or vertical) in which the stimuli were presented had no effect on the results. It is argued that while the results show the influence of the visual surround on children's comprehension of 'falling over', this may not be wholly explicable in terms of surround contour matching, as conventionally correct judgements were obtained in the absence of all straight line contours in the immediate surround.


Effect of gelatin on the cyclic AMP response of primocultured hog thyroid cells to acute thyrotropin stimulation.
The cyclic AMP response of cultured hog thyroid cells to acute thyrotropin stimulation was shown to be under a dual regulatory control by thyrotropin: both positive and negative regulation have been described. When added to the culture medium, gelatin (0.25%) promoted the reorganization of the cells into folicle-like structures, as does thyrotropin. Unlike thyrotropin, gelatin did not induce an increase in intracellular cyclic AMP but enhanced the acute cyclic AMP response to thyrotropin in cells cultured in gelatin-containing medium. When both gelatin and thyrotropin were present, the positive effect of low concentrations of hormone (less than 50 microU/ml) was increased whereas the refractory process observed in the presence of higher concentrations of hormone (greater than 50 microU/ml) was unchanged. These effects of gelatin might be mediated by interaction of the denatured collagen molecules with external proteins of the plasma membrane of thyroid cells.


Human embryonic stem cell-derived cardiomyocytes engraft but do not alter cardiac remodeling after chronic infarction in rats.
Previous studies indicated that, in an acute myocardial infarction model, human embryonic stem cell-derived cardiomyocytes (hESC-CM) injected with a pro-survival cocktail (PSC) can preserve contractile function. Because patients with established heart failure may also benefit from cell transplantation, we evaluated the physiological effects of hESC-CM transplanted into a chronic model of myocardial infarction. Intramyocardial injection of hESC-CM with PSC was performed in nude rats at 1 month following ischemia-reperfusion. The left ventricular function of hESC-CM injected rats was evaluated at 1, 2 and 3 months after the cell injection procedure and was compared to 3 control groups (rats injected with serum-free media, PSC only, or non-cardiac human cells in PSC). Histology at 3 months revealed that human cardiomyocytes survive, develop increased sarcomere organization and are still proliferating. Despite successful engraftment, both echocardiography and MRI analyses showed no significant difference in left ventricular structure or function between these 4 groups at any time point of the study, suggesting that human cardiomyocytes do not affect cardiac remodeling in a rat model of chronic myocardial infarction. When injected into a chronic infarct model, hESC-CM can engraft, survive and form grafts with striated cardiomyocytes at least as well as was previously observed in an acute myocardial infarction model. However, although hESC-CM transplantation can attenuate the progression of heart failure in an acute model, the same hESC-CM injection protocol is insufficient to restore heart function or to alter adverse remodeling of a chronic myocardial infarction model.


Filamin A is required for T cell activation mediated by protein kinase C-theta.
Induction of T cell responses following engagement of the Ag-specific TCR depends on TCR-initiated rearrangements of the cellular actin cytoskeleton and highly coordinated and tightly regulated interactions and of diverse intracellular signaling proteins. In this study, we show that filamin A (FLNa), an actin-binding and signal mediator scaffolding protein, is required for T cell activation. Following Ag stimulation, FLNa was recruited to the T cell-APC contact area, where it colocalized with protein kinase C-theta (PKCtheta). Depletion of FLNa by RNA interference did not affect TCR-induced early tyrosine phosphorylation or actin polymerization but, nevertheless, resulted in impaired IL-2 expression by human primary T cells and reduced activation of NF-kappaB, AP-1, and NFAT reporter genes in transfected T cells. TCR stimulation induced stable physical association of FLNa with PKCtheta. Furthermore, the TCR/CD28-induced membrane translocation of PKCtheta was inhibited in FLNa-depleted T cells. These results reveal novel role for FLNa in the TCR/CD28 signaling pathway leading to transcription factor activation and IL-2 production, and suggest that this role is mediated, in part, through the inducible interaction of FLNa with PKCtheta.


A Clinical Tool to Identify Candidates for Stress-First Myocardial Perfusion Imaging.
This study sought to develop a clinical model that identifies a lower-risk population for coronary artery disease that could benefit from stress-first myocardial perfusion imaging (MPI) protocols and that can be used at point of care to risk stratify patients. There is an increasing interest in stress-first and stress-only imaging to reduce patient radiation exposure and improve patient workflow and experience. A secondary analysis was conducted on a single-center cohort of patients undergoing single-photon emission computed tomography (SPECT) and positron emission tomography (PET) studies. Normal MPI was defined by the absence of perfusion abnormalities and other ischemic markers and the presence of normal left ventricular wall motion and left ventricular ejection fraction. A model was derived using a cohort of 18,389 consecutive patients who underwent SPECT and was validated in a separate cohort of patients who underwent SPECT (n = 5,819), 1 internal cohort of patients who underwent PET (n=4,631), and 1 external PET cohort (n = 7,028). Final models were made for men and women and consisted of 9 variables including age, smoking, hypertension, diabetes, dyslipidemia, typical angina, prior percutaneous coronary intervention, prior coronary artery bypass graft, and prior myocardial infarction. Patients with a score ≤1 were stratified as low risk. The model was robust with areas under the curve of 0.684 (95% confidence interval [CI]: 0.674 to 0.694) and 0.681 (95% CI: 0.666 to 0.696) in the derivation cohort, 0.745 (95% CI: 0.728 to 0.762) and 0.701 (95% CI: 0.673 to 0.728) in the SPECT validation cohort, 0.672 (95% CI: 0.649 to 0.696) and 0.686 (95% CI: 0.663 to 0.710) in the internal PET validation cohort, and 0.756 (95% CI: 0.740 to 0.772) and 0.737 (95% CI: 0.716 to 0.757) in the external PET validation cohort in men and women, respectively. Men and women who scored ≤1 had negative likelihood ratios of 0.48 and 0.52, respectively. A novel model, based on easily obtained clinical variables, is proposed to identify patients with low probability of having abnormal MPI results. This point-of-care tool may be used to identify a population that might qualify for stress-first MPI protocols.


Incorporating antagonistic pleiotropy into models for molecular replicators.
In modern cells, chromosomal genes composed of DNA encode multi-subunit protein/RNA complexes that catalyze the replication of the chromosome and cell. One prevailing theory for the origin of life posits an early stage involving self-replicating macromolecules called replicators, which can be considered genes capable of self-replication. One prevailing theory for the genetics of aging in humans and other organisms is antagonistic pleiotropy, which posits that a gene can be beneficial in one context, and detrimental in another context. We previously reported that the conceptual simplicity of molecular replicators facilitates the generation of two simple models involving antagonistic pleiotropy. Here a third model is proposed, and each of the three models is presented with improved definition of the time variable. Computer simulations were used to calculate the proliferation of a hypothetical two-subunit replicator (AB), when one of the two subunits (B) exhibits antagonistic pleiotropy, leading to an advantage for B to be unstable. In model 1, instability of B yields free A subunits, which in turn stimulate the activity of other AB replicators. In model 2, B is lost and sometimes replaced by a more active mutant form, B'. In model 3, B becomes damaged and loses activity, and its instability allows it to be replaced by a new B. For each model, conditions were identified where instability of B was detrimental, and where instability of B was beneficial. The results are consistent with the hypothesis that antagonistic pleiotropy can promote molecular instability and system complexity, and provide further support for a model linking aging and evolution.


Photophobia in migraine does not apply to green light, which may lessen headache severity.
A narrow band of green light could hold the key to defeating migraines, a new study suggests.


A Bayesian evaluation of six diagnostic tests for foot-and-mouth disease for vaccinated and non-vaccinated cattle.
The sensitivity and specificity of six ELISA tests for foot-and-mouth disease (FMD) to discriminate between sero-converted (for non-structural FMD virus proteins) and non-sero-converted cattle were evaluated for vaccinated and unvaccinated cattle. Since none of the tests could be considered as a proper reference test and for about half of the tested sera the true status (sero-converted or not for non-structural proteins, i.e. presence of antibodies) of the animals was unknown, a Bayesian analysis employing a latent class model was used that did not rely on the use of a reference test or gold standard. Prior information about prevalence for subsets of the data and specificity of the tests was incorporated into the analysis. The specificity of the six tests for vaccinated and non-vaccinated cattle ranged from 96 to 99%. For vaccinated cattle, one test stood out with an estimated sensitivity of 94% (95% CI from 89.8 to 98.1%). Second best for vaccinated cattle were two tests with estimated sensitivities of 85% (95% CI from 78.9 to 89.7%) and 92% (95% CI from 86.2 to 95.6%). For non-vaccinated cattle, the sensitivities of these three tests were around 97%. The remaining three tests showed lower estimated sensitivity for vaccinated cattle, ranging from 57 to 79%.


Percutaneous video angioscopy in peripheral vascular disease.
Percutaneous video angioscopy was performed using high resolution thin angioscopes in 12 peripheral arteries in 10 patients with peripheral vascular disease, to study the intraluminal appearance before and after dynamic, laser and conventional balloon angioplasty. Clear blood free views of the whole length of artery instrumented were obtained in 10 arteries with the remaining two arteries being partially visualised. The angioscopic appearances were compared to angiography. Clinically significant findings were detected in all the arteries by angioscopy that were not found by angiography. These included thrombus in the artery and vascular sheath, intimal flaps and fractured atheroma. The angioscopic findings helped to assess the effects of angioplasty in different types of occlusion. The findings demonstrate the potential of percutaneous angioscopy as an aid to percutaneous angioplasty as well as being a powerful diagnostic procedure.


Vibrational spectroscopy and solubility study of the mineral stringhamite CaCuSiO₄·H₂O.
Stringhamite CaCuSiO(4)·H(2)O is a hydrated calcium copper silicate and is commonly known as a significant 'healing' mineral and is potentially a semi-precious jewel. Stringhamite is a neosilicate with Cu(2+) in square planar coordination. Vibrational spectroscopy has been used to characterise the molecular structure of stringhamite. The intense sharp Raman band at 956 cm(-1) is assigned to the ν(1) (A(1g)) symmetric stretching vibration. Raman bands at 980, 997, 1061 cm(-1) are assigned to the ν(3) (A(2u), B(1g)) antisymmetric stretching vibrations. Splitting of the ν(3) vibrational mode supports the concept that the stringhamite SiO(4) tetrahedron is strongly distorted. The intense bands at 505 and 519 cm(-1) and at 570 cm(-1) are assigned to the ν(2) and ν(4) vibrational modes. The question arises as to whether the mineral stringhamite can actually function as a healing mineral. An estimation of the solubility product at pH<5 shows that the cupric ion can be released. The copper ion is a very powerful antibiological agent and thus the mineral stringhamite may well function as a healing mineral.


Nutritional and lifestyle risk behaviors and their association with mental health and violence among Pakistani adolescents: results from the National Survey of 4583 individuals.
Unhealthy behaviors are associated with mental health problems and violence in adolescents, yet their combined association has been understudied. Using the Global School Health Survey, this study examined the association between combined unhealthy behaviors (including fast food, soft drink, smoking, other tobacco products and physical inactivity) and anxiety, suicidal ideation and involvement in physical fight among Pakistani adolescents. Data were obtained from the Global School Health Survey conducted in Pakistan (2009). The study population consisted of school going adolescents aged 13 to 15 years. Association of combined unhealthy behaviors with anxiety, suicidal ideation and involvement in physical fight were studied through secondary analysis. We used univariate and multivariate logistic regression analysis by complex sample method, accounting for cluster sampling technique used for data collection. Of the total 4583 students, weighted percentage and unweighted count for one, two, three and four or more unhealthy behaviors was 39.4% (n = 1770), 22.1% (n = 963), 5.9% (n = 274) and 1.2% (n = 62) respectively. The weighted prevalence for anxiety, suicidal ideation and involvement in physical fight were 8.4%, 7.3% and 37.4% respectively. The results of multivariate logistic regression analysis after adjustment showed that students who had four or more unhealthy behaviors had higher odds of; being anxious (OR 2.45, 95%CI 1.31-4.59, p value 0.004), suicide ideation (OR 4.56, 95%CI 2.58-8.07, p value <0.001) and being involved in physical fight (OR 3.15, 95% CI 1.63-6.08, p value <0.001) as compared to those who had not adopted any unhealthy behaviors. This study suggests that the co-occurrence of unhealthy behaviors is associated with anxiety, suicidal ideation and physical fight among adolescents. These findings should be considered when developing interventions to combat detrimental outcomes of unhealthy behaviors during adolescence.


Genetic and environmental influences on the rate of progression to alcohol dependence in young women.
The development of alcohol dependence (AD) involves transitions through multiple stages of drinking behaviors and is shaped by both heritable and environmental influences. We attempted to capture this dynamic process by characterizing genetic and environmental contributions to the rate at which women progressed through 3 significant transitions along the pathway to AD: nonuse to initiation, initiation to onset of first alcohol-related problem, and first problem to onset of AD. The sample consisted of 3,546 female twins from the Missouri Adolescent Female Twin Study. Participants ranged in age from 18 to 29 years. Retrospective reports of alcohol use histories were collected by telephone diagnostic interview and transition times between drinking milestones were coded ordinally. Standard genetic analyses were conducted in Mx to derive a trivariate model that provided estimates of genetic and environmental influences that were common as well as specific to the 3 transition times. Heritable influences were found for rate of progression across all 3 transitions, accounting for 30 to 47% of the variance in transition times. Shared environmental contributions were evident only in rate of progression from nonuse to initiation (i.e., age at first drink). Heritable contributions to the rate of movement through successive drinking milestones were attributable to a common factor, whereas environmental influences were transition-specific. The current study is unique in its use of a genetically informative design to document the rate of movement between drinking milestones in a female sample and to examine genetic contributions to multiple transition times over the course of AD development. Results indicate that an earlier report of heritability for males in rate of progression from regular drinking to AD generalizes to women and to other alcohol stage transitions. Findings also suggest the need to consider stage-specific environmental contributions to alcohol outcomes in developing interventions.


Transcriptional regulation of the human trefoil factor, TFF1, by gastrin.
This study aimed to identify gastrin-sensitive genes that may mediate the effects of this hormone on gastric epithelial architecture. Gastrin-sensitive genes were identified by messenger RNA (mRNA) differential display of the gastric fundus from gastrin-deficient (GAS-KO) or wild-type mice. Gastrin-stimulated expression of the trefoil peptide TFF1 in mouse fundus and in the gastric cancer cell line AGS-G(R) was determined by Northern blot and real-time polymerase chain reaction. Transcriptional regulation of TFF1 in AGS-G(R) cells was studied using promoter-reporter assays and electrophoretic mobility shift assay. Expression of TFF1 and the cholecystokinin(B) receptor in response to gastric mucosal injury was determined by immunohistochemistry. mRNA differential display identified TFF1 as a gastrin-regulated gene. TFF1 mRNA was reversibly reduced in GAS-KO mice and increased in a hypergastrinemic transgenic strain versus respective background strains. TFF1 mRNA expression was rapidly and potently induced by gastrin in a gastric cancer cell line that expresses the gastrin/cholecystokinin(B) receptor. Gastrin responsiveness of the human TFF1 promoter mapped to a G-C rich region 300 base pairs upstream of the transcriptional start site. This region bound the transcription factors SP3 and MAZ. Gastrin activated transcription through a Raf-, Mek- and Erk-dependent but Ras-independent pathway. TFF1 expression was induced both directly and by transactivation between neighboring cells. Neither direct nor indirect gastrin-induced TFF1 expression required activation of the epidermal growth factor receptor. Gastrin exerts tonic control of TFF1 expression but also has the potential for rapid up-regulation of this trefoil factor. TFF1 is a potential candidate to counterbalance the proliferative effects of gastrin.


Understanding the role of cessation fatigue in the smoking cessation process.
To understand the dynamic process of cessation fatigue (i.e., the tiredness of trying to quit smoking) with respect to its average trend, effect on relapse, time-varying relations with craving and negative affect, and differences among genders and treatment groups. Randomized placebo-controlled clinical trial. Participants received either placebo, monotherapy (bupropion SR, nicotine patch, nicotine lozenge), or combined pharmacotherapy (bupropion SR+nicotine lozenge, nicotine patch+nicotine lozenge). Data were collected from 1504 daily smokers who were motivated to quit smoking. The participants completed baseline assessments and ecological momentary assessments for 2 weeks post-quit. Cessation fatigue reduced the likelihood of 6-month post-quit abstinence (OR=0.97, 95% CI (0.95, 0.99)), and was positively associated with craving and negative affect. After controlling for these two factors, average cessation fatigue increased over time. Compared to men, women experienced greater fatigue (t=-10.69, p<0.0001) and a stronger relation between fatigue and craving (t=-8.80, p<0.0001). The relationship between fatigue and negative affect was significantly stronger in men (t=5.73, p<0.0001). Cessation fatigue was significantly reduced by combined pharmacotherapy (t=-13.4, p<0.0001), as well as monotherapy (t=-6.2, p<0.0001). Cessation fatigue was closely related to craving, negative affect, and cessation outcomes. Women reported greater cessation fatigue than men. Current treatments appeared to reduce fatigue and weaken its relations with craving and negative affect.


CXCR4 overexpression during the course of HIV-1 infection correlates with the emergence of X4 strains.
The factors that determine the emergence of X4 isolates in some HIV-1-infected subjects are unknown. As the level of expression of CXCR4 could favor an R5 to X4 switch, quantitative flow cytometry was used to measure CXCR4 density on CD4 T cells in 200 HIV-1-positive adults, and this was compared with CD4 counts, interleukin-7 (IL-7), and RANTES (regulated on activation, normal T expressed and secreted) plasma levels and the R5/X4 virus phenotype. CD4 T-cell surface CXCR4 densities were increased in infected subjects and inversely correlated with CD4 T-cell count (r=-0.548, P<0.001). Yet, in vitro infection with either R5 or X4 strains and in vivo increases in viral load following interruption of antiretroviral treatment did not induce CXCR4 overexpression. The plasma levels of IL-7 and RANTES, 2 cytokines able to induce CXCR4 expression, did not correlate with CXCR4 density. Finally, higher CXCR4 densities were observed in patients harboring X4 strains (3300, 95% CI 2431-4169 CXCR4 molecules per cell) than in patients harboring only R5 strains (2406, 95% CI 2135-2677, P=0.027). These data suggest that CXCR4 overexpression during the course of the disease in some patients could favor the emergence of X4 strains.


Benzene-1,3,5-tricarb-oxy-lic acid-5-(4-pyrid-yl)pyrimidine (1/1).
In the pyrimidine mol-ecule of the title compound, C(9)H(7)N(3)·C(9)H(6)O(6), the pyridine ring is oriented at 33.26 (11)° with respect to the pyrimidine ring. In the benzene-1,3,5-tricarb-oxy-lic acid mol-ecule, the three carb-oxy groups are twisted by 7.92 (9), 8.68 (10) and 17.07 (10)° relative to the benzene ring. Classical O-H⋯N and O-H⋯O hydrogen bonds and weak C-H⋯O and C-H⋯N hydrogen bonds occur in the crystal structure.


Relationships between parameters describing low-frequency electrical admittance locus plot of human palmar skin.
Using a two-frequency three-electrode method, unipolar electrical admittance was measured in the palmar skin of 48 normal healthy humans. Characteristics of and relationships between the phase angle pi alpha/2, the conductance extrapolated at zero frequency G(O) and ion relaxation time tau obtained from the Cole-Cole equation were examined in a low-frequency region (up to 354 Hz). At base-line resting values, the three admittance parameters were interrelated according to the regression model; log tau i = A + B alpha i + D log G(O)i + epsilon i with R2 > or = 0.7434 (p < or = 0.0001), where A, B and D determined from regression analysis showed inter- and intra-individual variation. Multi-factor analyses of variance showed that alpha was greater in women than men (0.8025 versus 0.7545, p < 0.0023), and log G(O) decreased significantly with age (covariate coefficient = -0.0058 log microS cm-2 per year, p < 0.04). For evoked responses, alpha showed a very small change (maximum < 5%), tau decreased while G(O) increased. With increasing frequency, conductance responses increased in absolute amplitudes but decreased in relative changes (amplitude change divided by static level). Statistical analyses from clinical experimental materials (total 130 subjects) showed that the capacitive behaviour of admittance (due to alpha) presented significant variation between controls and patient groups. This may shed new light on the nature of the skin electrical admittance/impedance.


Systems biology-based analysis indicates that PHO1;H10 positively modulates high light-induced anthocyanin biosynthesis in Arabidopsis leaves.
Arabidopsis PHO1;H10 is a member of the PHO1 gene family with SPX and EXS domains, and its functions remain largely unknown. As shown in PCSD database, the upstream region of PHO1;H10 gene is in the active chromatin states, with high DHS accessibility and binding sites of multiple transcription factors, especially ABI5, SPCH and HY5. Co-expression network and data-mining analyses showed PHO1;H10 and co-expression genes were with activation under high light stress. We did wet-lab experiments, and found that the detached leaves of PHO1;H10 overexpression lines accumulated more anthocyanin than those of WT and mutant under high light treatment. RNA-seq results showed overexpression of PHO1;H10 up-regulated many anthocyanin biosynthetic genes. The GSEA analysis result showed that the functional module related to anthocyanin pathway was significantly enriched. In summary, we conducted systems biology approach, combining dry- and wet-lab analyses, and discovered that PHO1;H10 might play an essential role during modulating high light-induced anthocyanin accumulation in the Arabidopsis detached leaves.


The role of the anterior insular cortex in self-monitoring: A novel study protocol with electrical stimulation mapping and functional magnetic resonance imaging.
Becoming aware of one's own states is a fundamental aspect for self-monitoring, allowing us to adjust our beliefs of the world to the changing context. Previous evidence points out to the key role of the anterior insular cortex (aIC) in evaluating the consequences of our own actions, especially whenever an error has occurred. In the present study, we propose a new multimodal protocol combining electrical stimulation mapping (ESM) and functional magnetic resonance imaging (fMRI) to explore the functional role of the aIC for self-monitoring in patients undergoing awake brain surgery. Our results using a modified version of the Stroop task tackling metacognitive abilities revealed new direct evidence of the involvement of the aIC in monitoring our performance, showing increased difficulties in detecting action-outcome mismatches when stimulating a cortical site located at the most posterior part of the aIC as well as significant BOLD activations at this region during outcome incongruences for self-made actions. Based on these preliminary results, we highlight the importance of assessing the aIC's functioning during tumor resection involving this region to evaluate metacognitive awareness of the self in patients undergoing awake brain surgery. In a similar vein, a better understanding of the aIC's role during self-monitoring may help shed light on action/outcome processing abnormalities reported in several neuropsychiatric disorders such as schizophrenia, anosognosia for hemiplegia or major depression.


Low frequency of GJB2 mutations in thirty-five students with hearing loss in Chinese consanguineous families.
GJB2 mutation is recognized as the prevalent causes of non-syndromic hearing impairment (NSHI) worldwide. However, the mutation profiles of this gene are unknown in deafness probands in the consanguineous pedigrees in China. Therefore, this study aimed to characterize the forms and frequencies of GJB2 mutations in 35 students with hearing loss in the consanguineous families in Hubei province, Central China. Genomic DNA was extracted from blood samples of 35 students with hearing loss. The target fragments were amplified by polymerase chain reaction (PCR) and subjected to sequencing to identify sequence variations. Surprisingly, none of these probands harbored homozygous mutation in GJB2. Three GJB2 heterozygous mutations were identified: a single base pair substitution c.35G>T and c.139G>T, and a 2 bp deletion c.299-300delAT in three probands. The frequency of GJB2 mutation is relatively low in these consanguineous families, most of which were minorities. Our results suggest that screening for responsible genes other than GJB2 may be necessary for NSHI in these minorities.


Radial component of CNS myelin: junctional subunit structure and supramolecular assembly.
The radial component is a structural specialization within CNS myelin that is believed to stabilize the apposition of membranes in the internode. Previous observations on thin sections and freeze-fracture replicas show that this junctional complex consists of linear, particulate strands that run parallel to the nerve fibre axis and radially through the myelin sheath, but details on its molecular organization are lacking. The objective of our current study was to gain further insight into its arrangement and composition by examining its fine-structure and incidence in: myelin with known deficits in protein composition (e.g., shiverer, transgenic shiverer, myelin deficient and jimpy mutant mice); isolated CNS myelin, which has been shown by X-ray diffraction to be more stable than intact CNS myelin; and human white matter, in which this junctional complex has not yet been described. Our results confirm the localization and general appearance of the radial component as previously reported. In addition, we found that: (1) the radial component occurs abundantly in human CNS myelin where it has a complex subunit structure; (2) the constituent junctional unit of this structure is organized as a pair of globular domains (each approximately 40 A diameter) at the extracellular apposition which is linked by approximately 15 A diameter filaments extending through the bilayer to approximately 25 A globular domains in the adjacent cytoplasmic apposition; (3) the radial component is present with apparently normal structure in the sparse, compact myelin of murine mutants containing either different amounts of MBP or no PLP which indicates that neither of these proteins is necessary for junctional integrity; (4) the radial component is present in purified CNS myelin membranes which may account for the stability of these membranes; and (5) the radial component is structurally resistant to Triton, which suggests a method for its further biochemical characterization. Finally, from an analysis of images from tilted transverse and longitudinal sections, we have reconstructed a model of its three-dimensional, supramolecular organization.


High-sensitivity C-reactive protein predicts adverse outcomes after non-ST-segment elevation acute coronary syndrome regardless of GRACE risk score, but not after ST-segment elevation myocardial infarction.
Atherosclerosis is an active process and the inflammatory component appears to be particularly correlated with the development of acute coronary syndromes (ACS). C-reactive protein (CRP) is an acute phase protein that appears in the circulation in response to inflammatory cytokines. The present study investigated the association between high-sensitivity C-reactive protein (hsCRP) on admission and follow-up prognosis after an ACS. We included 151 consecutive patients admitted to the coronary care unit with a diagnosis of ACS (47% ST-segment elevation myocardial infarction [STEMI]). The primary endpoint was the combination of cardiac death and myocardial reinfarction during the follow-up period (median 19.8 months, interquartile range 16.3-23.7 months). The occurrence of follow-up events was significantly related to admission hsCRP level, which was an excellent predictor of cardiac death and reinfarction during follow-up (HR 1.091, 95% CI 1.014-1.174; p=0.019). Stratifying the population based on type of ACS, adjusted by variables associated with cardiac events in univariate analysis (hsCRP, diabetes, depressed ejection fraction and GRACE risk score), hsCRP proved to be an independent predictor of follow-up outcomes only in non-STEMI patients (HR 1.217, 95% CI: 1.093-1.356, p<0.001), not in STEMI patients. The best cutoff level of hsCRP to predict follow-up outcomes was 1.1mg/dl, with sensitivity of 77.8% and specificity of 63.2%. Although the GRACE risk score is routinely used for stratification of patients with ACS, assessment of hsCRP may provide additional prognostic value in the follow-up of non-STEMI patients.


Subcutaneous Immunoglobulin 16.5% (Cutaquig®) in Primary Immunodeficiency Disease: Safety, Tolerability, Efficacy, and Patient Experience with Enhanced Infusion Regimens.
To achieve reductions in infusion time, infusion sites, and frequency, a prospective, open-label, multicenter, Phase 3 study evaluated the safety, efficacy, and tolerability of subcutaneous immunoglobulin (SCIG) 16.5% (Cutaquig®, Octapharma) at enhanced infusion regimens. Three separate cohorts received SCIG 16.5% evaluating volume, rate, and frequency: Cohort 1) volume assessment/site: up to a maximum 100 mL/site; Cohort 2) infusion flow rate/site: up to a maximum of 100 mL/hr/site or the maximum flow rate achievable by the tubing; Cohort 3) infusion frequency: every other week at twice the patient's weekly dose. For Cohort 1 (n = 15), the maximum realized volume per site was 108 mL/site, exceeding the currently labeled (US) maximum (up to 40 mL/site for adults). In Cohort 2 (n = 15), the maximum realized infusion flow rate was 67.5 mL/hr/site which is also higher than the labeled (US) maximum (up to 52 mL/hr/site). In Cohort 3 (n = 34), the mean total trough levels for every other week dosing demonstrated equivalency to weekly dosing (p value = 0.0017). All regimens were well tolerated. There were no serious bacterial infections (SBIs). Most patients had mild (23.4%) or moderate (56.3%) adverse events. The majority of patients found the new infusion regimens to be better or somewhat better than their previous regimens and reported that switching to SCIG 16.5% was easy. SCIG 16.5% (Cutaquig®), infusions are efficacious, safe, and well tolerated with reduced infusion time, fewer infusion sites, and reduced frequency. Further, the majority of patients found the new infusion regimens to be better or somewhat better than their previous regimens.


Innovative use of increasing the width of attached gingiva using chorion membrane along with platelet rich fibrin membrane.
Width of attached gingiva plays an important role in maintaining periodontal health, provides stabilization of the gingival margin against frictional forces and aids in dissipating physiological forces exerted by the muscular fibers of the alveolar mucosa on the gingival tissues. Inadequate width of attached gingiva leads to attachment loss, soft tissue recession, and impedes oral hygiene measures. Hence, procedures using autografts and allografts have been proposed to augment the attached gingiva. Allografts like chorionic membrane (CM) are known to enhance release of growth factors, promote neovascularization, healing and enhance biotype. To assess the efficacy of CM in increasing the width of attached gingiva, vestibular depth and gingival thickness. Fifteen patients with inadequate attached gingival width were included in the study. Patients were randomly allocated to each group: Control group, CM group and CM + platelet rich fibrin (PRF) group. Attached gingiva width, vestibular depth, and gingival thickness were measured at baseline and 4 weeks post procedure. The control, CM and CM + PRF groups showed an increase in all parameters from baseline to 4 weeks. The increase in the attached gingiva (p = 0.042) width, vestibular depth (p = 0.043) and gingival thickness (p = 0.034) were statistically significant at 4 weeks for CM group and CM + PRF group respectively. The CM + PRF group showed better results compared to other groups. CM and PRF can be effectively incorporated to increase the width of attached gingiva and depth of vestibule.


Alignment of worm-like micelles at intermediate and high shear rates.
Rheology combined with Small-Angle Neutron Scattering (Rheo-SANS) can determine the local structural order in Worm-Like Micelle (WLM) solutions when the shear rate increases beyond the ending of the gradient shear banding. There, micelles are supposedly aligned, but viscosity reveals a transition regime as the shear rate increases. The mixture of 3-[dimethyl(tetradecyl)azaniumyl]propane-1-sulfonate (TDPS), sodium dodecylsulfate (SDS) (R = [SDS]/[TDPS] = 0.55), and a water solution of NaCl (0.2 mol/L), was studied with mechanical rheology and Small-Angle Neutron Scattering (SANS) in the quiescent fluid and under flow. The system self-assembles in WLMs and presents gradient shear banding. SANS patterns of the bands formed during the shear banding were obtained in a Couette geometry along the 1-2 plane, as well as the orientation parameter along the gap. At very high shear rates, in the paranematic phase, we found an apparent transition on the flow curves with its corresponding change in the orientation parameter. The origin of this transition is unclear, but we present possible explanations of why we observe it.


Secondary metabolic effects in complex I deficiency.
The objective of this study was to investigate clinical, biochemical, and genetic features in 7 probands (a total of 11 patients) with nicotine-amide adenine dinucleotide (NADH) dehydrogenase (complex I) deficiency. We screened the mitochondrial DNA for mutations and found pathogenic mutations in complex I genes (mitochondrial NADH dehydrogenase subunit (MTND) genes) in three probands. The 10191T>C mutation in MTND3 and the 14487T>C mutation in MTND6 were present in two probands with Leigh's-like and Leigh's syndrome, respectively. Four siblings with a syndrome consisting of encephalomyopathy with hearing impairment, optic nerve atrophy, and cardiac involvement had the 11778G>A mutation in MTND4, previously associated with Leber hereditary optic neuropathy. These findings demonstrate that mutations in MTND genes are relatively frequent in patients with complex I deficiency. Biochemical measurements of respiratory chain function in muscle mitochondria showed that all patients had a moderate decrease of the mitochondrial adenosine triphosphate production rate. Interestingly, the complex I deficiency caused secondary metabolic alterations with decreased oxaloacetate-induced inhibition of succinate dehydrogenase (complex II) and excretion of Krebs cycle intermediates in the urine. Our results thus suggest that altered regulation of metabolism may play an important role in the pathogenesis of complex I deficiency.


Simultaneous investigations of elemental changes in individual cells of the stria vascularis and in endolymph.
Using the microprobe for energy dispersive X-ray microanalysis, the elemental compositions of both the individual cells of the stria vascularis and of the endolymph were followed simultaneously under normal conditions and after the administration of 120 mg/kg ethacrynic acid (EA). Marginal cells and intermediate cells showed reversible increases in potassium and decreases in sodium concentrations. Shifts in the ionic composition of endolymph occurred later than after elemental changes in the strial cells. The present results indicate that the marginal and the intermediate cells are the primary target for EA-induced ototoxicity. However, generalized toxic effects of EA are also indicated, with a general leakage of different elements occurring during the 30-60 min period after EA administration.


Particulated articular cartilage for symptomatic chondral defects of the knee.
The treatment of focal cartilage defects in the knee remains a challenging clinical problem. One relatively new unique treatment option is particulated articular cartilage, which includes autograft and off-the-shelf allogeneic juvenile grafts. The use of particulated cartilage has the advantage of being a single-stage procedure. In the case of autograft, it is cost efficient, while in the juvenile allograft form, it may have increased proliferative and restorative potentials. Laboratory and clinical data are limited for particulated cartilage grafts; however, there are promising histologic and clinical outcomes. This review provides a summary of the indications, surgical technique, and most up-to-date research on particulated cartilage for the repair of symptomatic chondral defects in the knee.


Phosphoinositide 3-kinase pathway mediates early aldosterone action on morphology and epithelial sodium channel in mammalian renal epithelia.
Involvement of phosphoinositide 3-kinases (PI3Ks) in early aldosterone action on epithelial sodium channel (ENaC) in mammalian renal epithelia was investigated by hopping probe ion conductance microscopy combined with patch-clamping in this study. Aldosterone treatment enlarged the cell volume and elevated the apical membrane of renal mpkCCDc14 epithelia, which resulted in enhancing the open probability of ENaC. Inhibition of PI3K pathway by LY294002 obviously suppressed these aldosterone-induced changes in both cell morphology and ENaC activity. These results indicated the important role of PI3K pathway in early aldosterone action and the close relationship between cell morphology and ENaC activity in mammalian renal epithelia.


Social Behavior and Group Formation in Male Asian Elephants (Elephas maximus): The Effects of Age and Musth in Wild and Zoo-Housed Animals.
Asian elephants are endangered, and the long-term viability of the species depends on integrative approaches to address the sustainability of in-situ and ex-situ populations. Growing evidence shows that male elephants exhibit extensive and flexible social behavior that rivals the complexity of that of females. Male elephant sociality is expected to change dramatically around the unique sexual state of musth. However, data related to male Asian elephant sociality is lacking. Here, we conducted complementary observations in Wasgamuwa National Park, Sri Lanka, and North American zoos of male Asian elephant social behavior. Age and musth status, along with other factors, were associated with variation in social behavior and group formation of males. In wild male elephants, both musth status and age impacted elephant associations within all-male and mixed-sex groups: non-musth elephants were generally sighted less often in mixed-sex groups as they aged, while the inverse occurred with musth elephants. Musth status interacted with age to predict the number of conspecifics with which a wild male elephant associated: younger males were observed with more females during non-musth (but the opposite was true during musth), and male elephants between 20 and 30 years were observed with the highest number of male conspecifics except during musth. Finally, we found variation in aggression, prosocial behavior, and submissive behavior was influenced by intrinsic (age and musth status) and extrinsic factors (group size and type) in similar ways in both populations; prosocial behavior was most common and was influenced by the number of conspecifics present (both populations), and age, group type, and musth status (zoo population), while aggression was rare, especially among older elephants. We suggest that longitudinal studies of this threatened species will be particularly helpful to promote the reproduction and conservation of Asian elephants in in-situ and ex-situ environments.


The molecular and crystal structure of (+/-)-1-methyl-7-oxa-norborn-5-ene-2exo,3exo-dicarboxylic acid-anhydride and its enantiodifferentiation in 1H NMR spectroscopy.
The Diels-Alder reaction between 2-methylfuran and maleic anhydride leads to the formation of known racemic title adduct 3. The structure of this compound was confirmed by X-ray crystallography. An efficient enantiodifferentiation of 3 in 1H NMR spectroscopy was observed upon treatment with Eu(hfc)3.


Electrophysiological responses of interfascicular neurons of the rat anterior commissure to activation from the anterior olfactory nucleus, medial frontal cortex, and posterior nucleus of the amygdala.
Interfascicular neurons (IFNs) of the anterior commissure (AC) include short-axon and projection types which receive inputs from commissural collaterals. Therefore, it was proposed that IFNs may play a role in processing nerve impulses arising from the forebrain and delivered by these collaterals [Brain Res. 931 (2002) 81-91]. To determine possible inputs from the forebrain to IFNs we performed extracellular recordings of 25 neurons from anesthetized adult rats. Short-latency evoked potentials in IFNs were elicited by electrical stimulation of the anterior olfactory, posterior amygdaloid nuclei (PA), and medial frontal cortex. The IFN responses showed three distinct patterns, namely, a single action potential (AP) followed by what appear to be spontaneous discharge; a burst of high-frequency APs, and a single AP followed by a period devoid of APs. The latter response which was elicited by stimulation of the PA, may be explained by an intervening inhibitory interneuron, perhaps GABAergic in nature. Finally, IFNs seem not to project back to any of these three forebrain areas, as we failed to demonstrate antidromic activation.


Testing the 'seizure scaffold': What can experimental simulation tell us about functional seizures?
It has been suggested for over 100 years that patterns of neurological symptoms and signs in functional neurological disorders may be shaped at a neural level by underlying ideas or preconceptions how neurological symptoms present. This study used experimental simulation to probe ideas about seizures in healthy volunteers, with a view to compare with features commonly observed in functional and epileptic seizure disorders. Sixty healthy volunteers were instructed to simulate an epileptic seizure. The episodes were video-recorded and assessed by three qualified markers for the presence of clinical features commonly observed in functional seizures (FS), epileptic seizures, and syncope. Simulated seizures were hyperkinetic (83%), hypokinetic (7%), or staring (10%). Fifty-two percent had their eyes open and 45% eyes closed. Tremor was observed in 70%, while clonic jerking was only present in 17%. The majority of volunteers maintained a normal or floppy body posture. Head shaking side-to-side was observed in 38%, while guttural cries, stertorous breathing, tearfulness, and hyperventilation were absent in all volunteers. Our results suggest that simulated seizures not only resemble FS more closely than epileptic seizures but also show some important differences. Subjective seizure experiences in people with FS, not captured by this experimental simulation, remain a core determinant of semiology.


Acute normovolemic hemodilution in moderate blood loss surgery: a randomized controlled trial.
The risks associated with allogeneic blood transfusion are increasingly recognized. More blood is cross-matched for moderate blood loss surgery than any other indication. The role of acute normovolemic hemodilution (ANH) as a blood transfusion strategy was evaluated in a prospective randomized controlled trial. A total of 155 patients undergoing elective hip surgery were randomly assigned to either "ANH" (n = 78) or "standard transfusion" (n = 77). ANH on induction of anesthesia was to a target hemoglobin (Hb) level of 110 g per L with return of autologous blood on wound closure. Allogeneic blood was prescribed by an objective transfusion trigger based on an Hb level of less than 80 g per L. Transfusion requirements and postoperative complications were recorded. Allogeneic transfusion was necessary in 22 (29%) standard transfusion patients and 15 (19%) ANH (odds ratio [OR], 0.6; 95% CI, 0.28-1.3; p = 0.23) with 63 and 33 units transfused, respectively (p = 0.1). Significant postoperative complications occurred in 30 (38%) standard transfusion patients compared with 14 (18%) of those randomly assigned to ANH (OR, 0.3; 95% CI, 0.14-0.65; p = 0.009). The major difference between the groups was the frequency of infective complications. Despite modest allogeneic transfusion requirements in hip surgery, ANH reduced postoperative complications.


Occurrence of a binding protein for 11-cis-retinal in retina.
A binding protein for retinal has been found in the soluble protein fraction of bovine retina. It was separable from the intracellular retinol- and retinoic acid-binding proteins by gel filtration on Sephadex G-100 and appeared to have a molecular weight of about 50,000. The new binding protein did not bind retinol or retinoic acid. The binding protein neither oxidized retinal in the presence of reduced pyridine nucleotides and is presumed, therefore, not to be a dehydrogenase. Bound retinal was reduced to retinol in the presence of liver alcohol dehydrogenase and NADH, indicating that the functional group remained accessible when in the protein complex. The binding protein bound cis isomers of retinal preferentially. Bound ligand was displaced most effectively by 11-cis-retinal. When individual cis-trans isomers of retinal were presented to the binding protein, binding was maximal with the 11-cis isomer. It is proposed that the protein be referred to as 11-cis-retinal-binding protein.


Tracheal chondrosarcoma with an overview of other tumors of the trachea.
Chondrosarcomas of the trachea are extraordinarily rare tumors, with only four cases documented in the English literature. An additional case is reported with conventional and computed tomography correlation. Because primary tumors of the trachea are such rare neoplasms, a review of the subject is presented to put chondrosarcomas of the trachea into perspective. Malignant tumors are slightly more common than benign tumors of the trachea and occur more frequently in adults. The most common tumor involving the trachea is carcinoma, accounting for 80 to 90% of all cases. This, however, represents only 0.2% of all malignancies of the respiratory tract.


Bioinspired and self-restorable alginate-tyramine hydrogels with plasma reinforcement for arthritis treatment.
Long-standing administration of disease-modifying antirheumatic drugs confirms their clinical value for managing rheumatoid arthritis (RA). Nevertheless, there are emergent worries over unwanted adverse risks of systemic drug administration. Hence, a novel strategy that can be used in a drug-free manner while diminishing side effects is immediately needed, but challenges persist in the therapy for RA. To this end, herein we conjugated tyramine (TYR) with alginate (ALG) to form ALG-TYR and then treated it for 5 min with oxygen plasma (ALG-TYR + P/5 min). It was shown that the ALG-TYR + P/5 min hydrogel exhibited favorable viscoelastic, morphological, mechanical, biocompatible, and cellular heat-shock protein amplification behaviors. A thorough physical and structural analysis was conducted on the ALG-TYR + P/5 min hydrogel, revealing favorable physical characteristics and uniform porous structural features within the hydrogel. Moreover, ALG-TYR + P/5 min not only effectively inhibited inflammation of RA but also potentially regulated lesion immunity. Once ALG-TYR + P/5 min was intra-articularly administered to joints of rats with zymosan-induced arthritis, we observed that ALG-TYR + P/5 min could ameliorate syndromes of RA joint. This bioinspired and self-restorable ALG-TYR + P/5 min hydrogel can thus serve as a promising system to provide prospective outcomes to potentiate RA therapy.


Solvation driven conformational transitions in the second transmembrane domain of mycobacteriophage holin.
Holins are pore-forming membrane proteins synthesized by lytic phages. The second transmembrane domain (TM2) of Mycobacteriophage D29 holin presents an Ala- and Gly-rich sequence, with a currently unknown structure and function. In this study, we present the spectroscopic characterization of synthetic TM2 in various solvents, detergents, and lipids. We find that TM2 adopts α-helical conformation under conditions that promote intra-strand hydrogen bonding, such as organic solvents and detergent micelles. When we transfer the peptide to a well-hydrated environment, a polyproline II-like structure is obtained. Surprisingly, we find that the polyproline II-like conformation is retained in lipid vesicles. Based on our results, we present a putative role for TM2 in the process of pore formation by holin. © 2016 The Authors. Peptide Science Published by Wiley Periodicals, Inc. Biopolymers (Pept Sci) 108: 1-10, 2017.


Tetherin/BST-2: Restriction Factor or Immunomodulator?
Cell-mediated immune (CMI) responses are critical for the control of HIV-1 infection and their importance was highlighted by the existence of viral proteins, particularly Vpu and Nef, that antagonize these responses. Pandemic HIV-1 Vpu counteracts Tetherin/BST-2, a host factor that could prevent the release of HIV-1 virions by tethering virions on the cell surface, but a link between Tetherin and HIV-1 CMI responses has not yet been demonstrated in vivo. In vitro, the virological and immunological impact of Tetherin-mediated accumulation of virions ranged from enhanced or diminished cell-to-cell spread to enhanced recognition by virus-specific antibodies for natural killer cellmediated lysis. However, Tetherin-restricted virions could be internalized through an endocytosis motif in the Tetherin cytoplasmic tail. Given the uncertainties on which in vitro results manifest in vivo and the dearth of knowledge on how Tetherin influences retroviral immunity, in vivo retrovirus infections in mice encoding wild-type, null and endocytosis-defective Tetherin were performed. Here, we review and highlight the results from these in vivo studies. Current data suggests that endocytosis-defective Tetherin functions as a potent innate restriction factor. By contrast, endocytosis-competent Tetherin, the form found in most mammals including humans and the form counteracted by HIV-1 Vpu, was linked to stronger CMI responses in mice. We propose that the main role of endocytosis-competent Tetherin is not to directly restrict retroviral replication, but to promote a more effective CMI response against retroviruses.


Response to trametinib in recurrent low-grade serous ovarian cancer with NRAS mutation: A case report.
Low-grade serous ovarian cancer represents a minority of ovarian cancers and has distinctive features from high grade epithelial ovarian cancer. While less aggressive, in advanced stage they can be poorly chemo-responsive and incur a treatment challenge. Next generation sequencing of tumors has allowed for the potential for targeted therapy in cancer treatment, which can allow for avoidance of traditional cytotoxic chemotherapy. We present a case of a 56 year old female with advanced recurrent low grade serous ovarian cancer found to have NRAS mutation who underwent targeted therapy with trametinib with immediate and sustained disease response. We review the response and toxicity experienced by the patient, as well as treatment for her toxicity.


Estimating Canadian sodium intakes and the health impact of meeting national and WHO recommended sodium intake levels: A macrosimulation modelling study.
Cardiovascular diseases (CVDs) are the second leading cause of total deaths in Canada. High blood pressure is the main metabolic risk factor for developing CVDs. It has been well established that excess consumption of sodium adversely affects blood pressure. Canadians' mean sodium intakes are well above recommended levels. Reducing dietary sodium intake through food reformulation has been identified as a cost-effective intervention, however, dietary sodium intake and the potential health impact of meeting recommended sodium intake levels due to food reformulation have not been determined in Canada. This study aimed to 1) obtain robust estimates of Canadians' usual sodium intakes, 2) model sodium intakes had foods been reformulated to align with Health Canada's sodium reduction targets, and 3) estimate the number of CVD deaths that could be averted or delayed if Canadian adults were to reduce their mean sodium intake to recommended levels under three scenarios: A) 2,300 mg/d-driven by a reduction of sodium levels in packaged foods to meet Health Canada targets (reformulation); B) 2,000 mg/d to meet the World Health Organization (WHO) recommendation; and C) 1,500 mg/d to meet the Adequate Intake recommendation. Foods in the University of Toronto's Food Label Information Program 2017, a Canadian branded food composition database, were linked to nationally representative food intake data from the 2015 Canadian Community Health Survey-Nutrition to estimate sodium intakes (and intakes had Health Canada's reformulation strategy been fully implemented). The Preventable Risk Integrated ModEl (PRIME) was used to estimate potential health impact. Overall, mean sodium intake was 2758 mg/day, varying by age and sex group. Based on 'reformulation' scenario A, mean sodium intakes were reduced by 459 mg/day, to 2299 mg/day. Reducing Canadians' sodium intake to recommended levels under scenarios A, B and C could have averted or delayed 2,176 (95% UI 869-3,687), 3,252 (95% UI 1,380-5,321), and 5,296 (95% UI 2,190-8,311) deaths due to CVDs, respectively, mainly from ischaemic heart disease, stroke, and hypertensive disease. This represents 3.7%, 5.6%, and 9.1%, respectively, of the total number of CVDs deaths observed in Canada in 2019. Results suggest that reducing sodium intake to recommended levels could prevent or postpone a substantial number of CVD deaths in Canada. Reduced sodium intakes could be achieved through reformulation of the Canadian food supply. However, it will require higher compliance from the food industry to achieve Health Canada's voluntary benchmark sodium reduction targets.


Cytochemical discrimination between catalases and peroxidases using diaminobenzidine.
The influence on diaminobenzidine staining of four variables: prefixation in aldehyde, temperature and pH of incubation, and H2O2 concentration, was investigated in catalase-, as well as in peroxydase-containing material. Catalase from five different sources and five types of peroxidase were examined. It is concluded: (a) when cells are incubated without prior fixation, in a DAB medium at room temperature and pH 7.3 with 0.003% H2O2, peroxidases produce a visible cytochemical stain, while catalases do not; (b) the cytochemical reaction elicited by catalases is stimulated by prior aldehyde fixation in specified conditions, and incubation at 45 degrees C and pH 9.7 with 0.06% H2O2; (c) under the latter circumstances several peroxidases also stain. Ultrastructural preservation is satisfactory in tissues incubated prior to fixation.


Field evaluation of Bt cotton crop impact on nontarget pests: cotton aphid and boll weevil.
Bt cotton plants expressing Cry1Ac protein have high specificity for the control of lepidopteran larvae. However, studies conducted in several countries have shown these plants have a differential impact on nontarget herbivores. The aim of this study was to compare the colonization rates and population abundance of the cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae) and the boll weevil, Anthonomus grandis Boheman (Coleoptera: Curculionidae), in plots of Bt (Nuopal) and non-Bt cotton (Delta Opal) in an experimental field in Brasilia, DF, Brazil. No difference was observed in the preference and colonization by winged aphids to plants from the two treatments. There was no significant difference in abundance of wingless aphids or in the production of winged aphids between treatments. Apparently, the parameters that control factors such as fecundity, survival, and dispersal were similar on both Bt and non-Bt plants. Monitoring of plants for coccinellids, a specialist predator of aphids, and ants that act on the dispersal of aphids among plants showed no significant difference between Bt and non-Bt plants, supporting the inference above. Regarding the effect on boll weevil, there was also no significant difference between treatments in the total number of fruiting structures attacked in each plot, the percentage of fruiting structures attacked per plant or on the number of weevils emerging from fruits with boll weevil damage from egg-laying, when damaged fruit samples were held in the laboratory. Based on these results, we conclude that there is no impact of Bt cotton crop expressing Cry1Ac on the nontarget herbivores tested under field conditions.


A single-step aerosol process for in-situ surface modification of nanoparticles: Preparation of stable aqueous nanoparticle suspensions.
Surface modification of nanoparticles during aerosol or gas-phase synthesis, followed by direct transfer into liquid media can be used to produce stable water-dispersed nanoparticle suspensions. This work investigates a single-step, aerosol process for in-situ surface-modification of nanoparticles. Previous studies have used a two-step sublimation-condensation mechanism following droplet drying, for surface modification, while the present process uses a liquid precursor containing two solutes, a matrix lipid and a surface modifying agent. A precursor solution in chloroform, of stearic acid lipid, with 4 %w/w of surface-active, physiological molecules [1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol)-sodium salt (DPPG) or 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol) 2000]-ammonium salt (DPPE-PEG)] was processed in an aerosol reactor at a low gas temperatures. The surface modified nanoparticles were characterized for morphology, surface composition and suspension properties. Spherical, surface-modified lipid nanoparticles with median mobility diameters in the range of 105-150nm and unimodal size distributions were obtained. Fourier transform infra-red spectroscopy (FTIR) measurements confirmed the presence of surface-active molecules on external surfaces of modified lipid nanoparticles. Surface modified nanoparticles exhibited improved suspension stability, compared to that of pure lipid nanoparticles for a period of 30days. Lowest aggregation was observed in DPPE-PEG modified nanoparticles from combined electrostatic and steric effects. The study provides a single-step aerosol method for in-situ surface modification of nanoparticles, using minimal amounts of surface active agents, to make stable, aqueous nanoparticle suspensions.


Miku's mask: Fictional encounters in children's costume play.
Children's engagement with Japanese toys and fictional characters has taken on new significance in the age of YouTube. Drawing on ethnographic research on technology-mediated play among 8- and 9-year-olds in Norway, this article shows how boundaries between "real" humans and "fake" non-humans are blurred and undermined when children take on the perspective of a fictional pop star known as Miku. I argue that YouTube provides a platform for children's playful experimentation with posthuman subjectivities, where they orient themselves toward the future not in terms of becoming adult but in terms of multiple becomings.


Keeping Cool When Things Heat Up During a Malignant Hyperthermia Crisis.
This article describes the experience of a health care team at a maternity center during their care for a woman exhibiting an atypical presentation of malignant hyperthermia and outlines the steps taken to rapidly identify the condition and begin treatment to save her life. Key components in ensuring a positive outcome in a malignant hyperthermia crisis include increased awareness and readiness to effectively treat and reverse the signs and symptoms of this condition.


Valsartan and hydrochlorothiazide in patients with essential hypertension. A multiple dose, double-blind, placebo controlled trial comparing combination therapy with monotherapy.
This study compares the antihypertensive efficacy and tolerability of valsartan, a novel angiotensin II antagonist, given with hydrochlorothiazide (HCTZ) vs placebo or vs valsartan or HCTZ alone. 871 adult out-patients with essential hypertension participated in this double-blind study. Patients were randomised in equal number to receive either combination therapy of valsartan (80 mg or 160 mg) and HCTZ (12.5 mg or 25 mg), or valsartan (80 mg or 160 mg) or HCTZ (12.5 mg or 25 mg) alone, or placebo. Patients were treated once daily for 8 weeks and assessed at 2, 4 and 8 weeks after randomisation. The primary efficacy variable was change from baseline in mean sitting diastolic blood pressure (MSDBP) at end-point. The secondary variable was change in mean sitting systolic blood pressure (MSSBP) from baseline to end-point. All active treatments produced a statistically significant difference in MSDBP (P < 0.001) from baseline to end-point compared with placebo. Similar results were obtained for MSSBP. All combination regimens produced a statistically significantly greater reduction in MSDPB and MSSBP than the corresponding monotherapies. Dizziness and headache were the most common treatment-related adverse experiences reported. Hypokalaemia, associated with the use of thiazide diuretics, was more commonly reported in the higher dose HCTZ 25 mg groups. Valsartan 80 mg and 160 mg act additively with HCTZ 12.5 mg or 25 mg to lower MSDBP and MSSBP in patients with essential hypertension. The addition of HCTZ to valsartan 80 mg or 160 mg was well tolerated.


Tracking the fingerprints and combined TOC-black carbon mediated soil-air partitioning of polychlorinated naphthalenes (PCNs) in the Indus River Basin of Pakistan.
This study reports the first investigation of polychlorinated naphthalenes (PCNs) in air and soil samples from ecologically important sites of the Indus River Basin, Pakistan. The concentrations of ∑39-PCNs in air and soil were found in a range between 1-1588 pg m(-3) and 0.02-23 ng g(-1) while the mean TEQ values were calculated to be 5.4E(-04) pg TEQ m(-3) and 1.6E(+01) pg TEQ g(-1), respectively. Spatially, air and soil PCN concentrations were found to be high at Rahim Yar Khan (agricultural region). Lower-medium chlorinated PCNs (sum of tri-, tetra- and penta-CNs) predominated in both air and soil, altogether constituting 87 and 86% of total PCNs in the two environmental matrices, respectively. According to the data, soil-air partitioning of PCNs was interpreted to be similarly controlled by the combined effect of black carbon and organic matter in the Indus River Basin, with no preferential implication of the recalcitrant organic form.


Trends in medical information retrieval on Internet.
Information on the World Wide Web is unstructured, distributed, multimedia and multilingual. Many tools have been developed to help users search for useful information: subject hierarchies, general search engines, browsers and search assistants. Although helpful, they present serious limitations, mainly in terms of precision, multilingual indexing and distribution. In this paper, we cover some on-line solutions to medical information discovery and present our own approach, the MARVIN (multi-agent retrieval vagabond on information network) project, which tackles medical information research with specialized cooperative retrieval agents. We also draw some outlines for future extensions.


S2-alar-iliac screw and S1 pedicle screw fixation for the treatment of non-osteoporotic sacral fractures: a finite element study.
Five different sacral fracture fixation methods were compared using finite element (FE) analysis to study their biomechanical characteristics. Denis type I sacral fractures were created by FE modeling. Five different fixation methods for the posterior pelvic ring were simulated: sacroiliac screw (SIS), lumbopelvic fixation (LPF), transiliac internal fixator (TIFI), S2-alar-iliac (S2AI) screw and S1 pedicle screw fixation (S2AI-S1) and S2AI screw and contralateral S1 pedicle screw fixation (S2AI-CS1). Four different loading methods were implemented in sequence to simulate the force in standing, flexion, right bending and left twisting, respectively. Vertical stiffness, relative displacement and change in relative displacement were recorded and analyzed. As predicted by the FE model, the vertical stiffness of the five groups in descending order was S2AI-S1, SIS, S2AI-CS1, LPF and TIFI. In terms of relative displacement, groups S2AI-S1 and S2AI-CS1 displayed a lower mean relative displacement, although group S2AI-CS1 exhibited greater displacement in the upper sacrum than group S2AI-S1. Group SIS displayed a moderate mean relative displacement, although the displacement of the upper sacrum was smaller than the corresponding displacement in group S2AI-CS1, while groups LPF and TIFI displayed larger mean relative displacements. Finally, in terms of change in relative displacement, groups TIFI and LPF displayed the greatest fluctuations in their motion, while groups SIS, S2AI-S1 and S2AI-CS1 displayed smaller fluctuations. Compared with SIS, unilateral LPF and TIFI, group S2AI-S1 displayed the greatest biomechanical stability of the Denis type I sacral fracture FE models. When the S1 pedicle screw insertion point on the affected side is damaged, S2AI-CS1 can be used as an appropriate alternative to S2AI-S1.


Psychological impact of anti-VEGF treatments for wet macular degeneration-a review.
To review the current literature on the psychological impact of anti-VEGF treatments for wet age-related macular degeneration (wAMD), in terms of patients' experiences of receiving these treatments, and the impact of these treatments for patients' mental health and quality of life. We critically analyzed current literature evaluating psychological impact of anti-VEGF treatments for wAMD. Primary searches of PubMed, Science Direct, and Web of Science were conducted in July and August of 2015. We reviewed all papers on the topic published until August 5, 2015. Our literature search found 14 papers addressing the psychological impact of anti-VEGF treatments for wAMD. Results highlighted potential anxieties and experiences of pain caused by receiving regular intravitreal injections. A positive visual outcome of anti-VEGF therapy is associated with positive vision-related QOL outcomes, although such association seems to be dependent on improvements on visual acuity. In the literature reviewed, patients receiving anti-VEGF treatments showed a prevalence rate of depression between 20 and 26 %. Although anti-VEGF treatments can cause some anxiety and being experienced as a stressful event, especially in the beginning of the treatment, preliminary findings suggest a potential benefit for long-term vision-related quality of life. Further longitudinal and qualitative research should bring more evidence on the positive and negative effects of these treatments on patients' long-term mental health.


Lamin misexpression upregulates three distinct ubiquitin ligase systems that degrade ATR kinase in HeLa cells.
Lamins are the major structural components of the nucleus and mutations in the human lamin A gene cause a number of genetic diseases collectively termed laminopathies. At the cellular level, lamin A mutations cause aberrant nuclear morphology and defects in nuclear functions such as the response to DNA damage. We have investigated the mechanism of depletion of a key damage sensor, ATR (Ataxia-telangiectasia-mutated-and-Rad3-related) kinase, in HeLa cells expressing lamin A mutants or lamin A shRNA. The degradation of ATR kinase in these cells was through the proteasomal pathway as it was reversed by the proteasomal inhibitor MG132. Expression of lamin A mutants or shRNA led to transcriptional activation of three ubiquitin ligase components, namely, RNF123 (ring finger protein 123), HECW2 (HECT domain ligase W2) and the F-box protein FBXW10. Ectopic expression of RNF123, HECW2 or FBXW10 directly resulted in proteasomal degradation of ATR kinase and the ring domain of RNF123 was required for this degradation. However, these ligases did not alter the stability of DNA-dependent protein kinase, which is not depleted upon lamin misexpression. Although degradation of ATR kinase was reversed by MG132, it was not affected by the nuclear export inhibitor, leptomycin B, suggesting that ATR kinase is degraded within the nucleus. Our findings indicate that lamin misexpression can lead to deleterious effects on the stability of the key DNA damage sensor, ATR kinase by upregulation of specific components of the ubiquitination pathway.


Cerebrolysin combined with rehabilitation promotes motor recovery in patients with severe motor impairment after stroke.
Cerebrolysin is a neuropeptide preparation with neuroprotective and neurorestorative effects. Combining Cerebrolysin treatment with a standardized rehabilitation program may have a potential synergistic effect in the subacute stage of stroke. This study aims to evaluate whether Cerebrolysin provides additional motor recovery on top of rehabilitation therapy in the subacute stroke patients with moderate to severe motor impairment. This phase IV trial was designed as a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. A total of 70 patients (Cerebrolysin n = 35, placebo n = 35) with moderate to severe motor function impairment were included within 7 days after stroke onset and were randomized to receive a 21-day treatment course of either Cerebrolysin or placebo, given in addition to standardized rehabilitation therapy. Assessments were performed at baseline, immediately after treatment as well as 2 and 3 months after stroke onset. The plasticity of motor system was assessed by diffusion tensor imaging and with resting state functional magnetic resonance imaging. Both groups demonstrated significant improvement in motor function (p < 0.05); however, no significant difference was found between the two groups. In the stroke patients with severe motor impairment, the Cerebrolysin group exhibited significantly more improvement in motor function compared with the placebo group (p < 0.05). Effects of Cerebrolysin were demonstrated as restricted increments of corticospinal diffusivity and as recovery of the sensorimotor connectivity. The combination of standard rehabilitation therapy with Cerebrolysin treatment in the subacute stroke has shown additional benefit on motor recovery and plastic changes of the corticospinal tract in patients with severe motor impairment. NCT01996761 (November 5, 2013).


Identification of Arcanobacterium (Trueperella) abortisuis, a novel species of veterinary importance, by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).
In the present study A. (T.) abortisuis isolated from pigs and bovines could be reliably identified by determination of phenotypic properties, genotypically by polymerase chain reaction with the help of A. (T.) abortisuis 16s-23S rDNA intergenic spacer region specific oligonucleotide primer and by Matrix-Assisted Laser Desorption Ionization-Time Of Flight mass spectrometry (MALDI-TOF MS). The latter appeared to be a promising tool for fast and cost effective identification of this species and might help to elucidate the role A. (T.) abortisuis plays in infections of pigs, bovines, possibly other animals or humans.