Pre- and Postcopulatory Traits of Salvator Male Lizards in Allopatry and Sympatry.
The reproductive traits of males are under influence of sexual pressures before and after copulation. The strength of sexual selection varies across populations because they undergo varying competition for mating opportunities. Besides intraspecific pressures, individuals seem to be subjected to pressures driven by interspecific interactions in sympatry. Lizards may vary their reproductive strategies through varying sexual characters, body size, gonadal investment, and sperm traits. We evaluated the reproductive traits, involved in pre- and postcopulatory competition, in allopatric and sympatric populations of Salvator lizards. We observed a spatial gradient of male competition among populations, with the following order: allopatric zone of S. rufescens; sympatric zone; and allopatric zone of S. merianae. Accordingly, variation in secondary sexual character, the relative testis mass, and the length of sperm component was observed between allopatry and sympatry in each species, suggesting differences in the investment of reproductive traits. However, we found that these two Salvator species did not differ in secondary sexual characters in sympatry. Interestingly, the trade-off between testes and muscle varied differently from allopatry to sympatry between these Salvator species, suggesting that the influence of social context on reproductive traits investment would affect lizard species differently.


Pharmacokinetic factors in sex differences in Delta 9-tetrahydrocannabinol-induced behavioral effects in rats.
Cannabinoids have been shown to produce greater behavioral effects in female than in male rats. Sex differences in the metabolism of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) have also been demonstrated in one study. The goal of this study was to determine if sex differences in Delta(9)-THC disposition or metabolism could explain sex differences in Delta(9)-THC-induced behavioral effects. [(3)H]-Delta(9)-THC was administered intraperitoneally (i.p.) to rats and the presence of [(3)H]-Delta(9)-THC and metabolites in serum and brain tissue were compared at multiple times post-injection in male versus female rats. Serum levels of Delta(9)-THC and its metabolites were similar in males and females. In brain tissue, [(3)H]-Delta(9)-THC levels also were similar in males and females. In contrast, levels of Delta(9)-THC metabolites in brain tissue, including 11-hydroxy-Delta(9)-THC, the major active metabolite, were higher in females than in males. To further investigate if greater production of active metabolites by females explained the greater Delta(9)-THC-induced behavioral effects observed in females, i.p. Delta(9)-THC-induced antinociception (50 degrees C warm water tail withdrawal assay) and catalepsy (bar test) were compared in male and female rats following pretreatment with saline or SKF525A, a cytochrome P450 inhibitor. SKF525A did not affect basal responding in the tail withdrawal assay or bar test in either sex. SKF525A significantly attenuated Delta(9)-THC-induced antinociception only in females. A similar sex difference was observed in the effects of SKF525A on Delta(9)-THC-induced catalepsy. These results suggest that the greater levels of active Delta(9)-THC metabolites produced by females contribute to greater behavioral effects of Delta(9)-THC in female compared to male rats.


Effects of hyperbaric oxygen treatment on axonal outgrowth in sciatic nerve grafts in rats.
We studied the effect of hyperbaric oxygen treatment on axonal outgrowth in grafts of sciatic nerves in 40 rats. The sciatic nerve was transsected and a 10 mm long segment from the opposite side was immediately sutured in as a nerve graft. Postoperatively 17 animals were treated with 100% oxygen at 3.2 atmospheres absolute pressure for 45 minutes and the treatment was repeated at four and eight hours postoperatively and then every eight hours until evaluation. At seven days the axonal outgrowth was evaluated by immunohistochemical staining of neurofilaments in the nerve grafts. The axonal outgrowth was significantly longer in animals treated with hyperbaric oxygen. We conclude that hyperbaric oxygen can improve nerve regeneration in sciatic nerve grafts in rats.


Rho kinase inhibition rescues the endothelial cell cerebral cavernous malformation phenotype.
Cerebral cavernous malformations (CCM) are vascular lesions causing seizures and stroke. Mutations causing inactivation of one of three genes, ccm1, -2, or -3, are sufficient to induce vascular endothelial cell defects resulting in CCM. Herein, we show that loss of expression of the CCM1, -2, or -3 proteins causes a marked increase in expression of the GTPase RhoA. Live cell imaging with a RhoA-specific biosensor demonstrates increased RhoA activity with loss of CCM1, -2, or -3, with an especially pronounced RhoA activation in both the cytosol and the nucleus with loss of CCM1 expression. Increased RhoA activation was associated with Rho kinase-dependent phosphorylation of myosin light chain 2. Functionally, loss of CCM1, -2, or -3 inhibited endothelial cell vessel-like tube formation and extracellular matrix invasion, each of which is rescued by chemical inhibition or short hairpin RNA knockdown of Rho kinase. The findings, for the first time, define a signaling network for CCM1, -2, and -3 in CCM pathology, whereby loss of CCM1, -2, or -3 protein expression results in increased RhoA activity, with the activation of Rho kinase responsible for endothelial cell dysregulation. The results define Rho kinase as a therapeutic target to rescue endothelial cells from loss of CCM protein function.


Alcohol consumption and blood pressure in a New Zealand community study.
The relationship between stated alcohol consumption and blood pressure was investigated in 901 adults who participated in a multiphasic health survey in Milton in May 1981. Subjects taking oral contraceptives or drugs which could lower blood pressure were excluded. Eighty-five percent of men and 52% of women reported taking some alcohol at least once a month. The percentage using alcohol was highest (96%) in men aged 20-29 years. The reported mean weekly intake by users was 171 g for men and 56 g for women. After adjustment for age and body mass index, there was a positive association between alcohol intake and blood pressure for men. The mean systolic and diastolic pressures of male heavy alcohol users (300 g or more alcohol per week) were, respectively, 9.8 and 8.9 mmHg higher than those of male non-drinkers. No relationship between alcohol intake and blood pressure was found in the women.


The 'Bodywise' initiative.
Young people want access to good information in suitable settings so they can discuss sexual matters openly. Services are needed to bridge the gap between paediatric and adult health services. Interprofessional collaboration can provide effective, integrated and supportive services for users and providers. Static and outreach services are essential to facilitate young people's access to the services.


Vision-Related Quality of Life among Adult Patients with Visual Impairment at University of Gondar, Northwest Ethiopia.
The purpose of this study was to assess vision-related quality of life and associated factors among adult patients with visual impairment at the University of Gondar Tertiary Eye Care and Training Center, Northwest Ethiopia. The institution-based cross-sectional study was conducted from April 24 to May 12, 2017, at the University of Gondar Tertiary Eye Care and Training Center among 484 patients with visual impairment. Pretested, structured National Eye Institute Visual Function Questionnaire-25 was used to collect data by interviewing. Data were entered using EPI-INFO version 3.5.1 and analyzed with SPSS version 20. Binary logistic regression was used to determine factors associated with vision-related quality of life. Variables with p value <0.05 in multivariable logistic regression were considered as statistically significant. A total of 484 study subjects participated with a response rate of 98.9%. The median age of the participants was 60 years with the interquartile range of 25 years. The proportion of poor vision-related quality of life was 238 (49.2%) (95% CI: 44.2%-53.3%). Age >75 years (AOR = 1.87 (95% CI: 1.02-3.40)), rural residency (AOR = 1.71 (95% CI: 1.13-2.60)), severe visual impairment/blindness (AOR = 2.76 (95% CI: 1.80-4.23)), and history of visual impairment longer than 3 years (AOR = 2.85 (95% CI: 1.61-5.04)) had statistically significant association with poor vision-related quality of life. Almost half of the patients with visual impairment had poor vision-related quality of life. Severe visual impairment/blindness, long duration of visual impairment, older age, and rural residency had a statistically significant association with poor vision-related quality of life.


Fluorescence Guidance in Surgical Oncology: Challenges, Opportunities, and Translation.
Surgical resection continues to function as the primary treatment option for most solid tumors. However, the detection of cancerous tissue remains predominantly subjective and reliant on the expertise of the surgeon. Surgery that is guided by fluorescence imaging has shown clinical relevance as a new approach to detecting the primary tumor, tumor margins, and metastatic lymph nodes. It is a technique to reduce recurrence and increase the possibility of a curative resection. While significant progress has been made in developing this emerging technology as a tool to assist the surgeon, further improvements are still necessary. Refining imaging agents and tumor targeting strategies to be a precise and reliable surgical strategy is essential in order to translate this technology into patient care settings. This review seeks to provide a comprehensive update on the most recent progress of fluorescence-guided surgery and its translation into the clinic. By highlighting the current status and recent developments of fluorescence image-guided surgery in the field of surgical oncology, we aim to offer insight into the challenges and opportunities that require further investigation.


Expression of connexin36 in the adult and developing rat brain.
The distribution of connexin36 (Cx36) in the adult rat brain and retina has been analysed at the protein (immunofluorescence) and mRNA (in situ hybridization) level. Cx36 immunoreactivity, consisting primarily of round or elongated puncta, is highly enriched in specific brain regions (inferior olive and the olfactory bulb), in the retina, in the anterior pituitary and in the pineal gland, in agreement with the high levels of Cx36 mRNA in the same regions. A lower density of immunoreactive puncta can be observed in several brain regions, where only scattered subpopulations of cells express Cx36 mRNA. By combining in situ hybridization for Cx36 mRNA with immunohistochemistry for a general neuronal marker (NeuN), we found that neuronal cells are responsible for the expression of Cx36 mRNA in inferior olive, cerebellum, striatum, hippocampus and cerebral cortex. Cx36 mRNA was also demonstrated in parvalbumin-containing GABAergic interneurons of cerebral cortex, striatum, hippocampus and cerebellar cortex. Analysis of developing brain further revealed that Cx36 reaches a peak of expression in the first two weeks of postnatal life, and decreases sharply during the third week. Moreover, in these early stages of postnatal development Cx36 is detectable in neuronal populations that are devoid of Cx36 mRNA at the adult stage. The developmental changes of Cx36 expression suggest a participation of this connexin in the extensive interneuronal coupling which takes place in several regions of the early postnatal brain.


Comparison of wide-field fluorescein angiography and 9-field montage angiography in uveitis.
To compare qualitatively and quantitatively Optos fundus camera fluorescein angiographic images of retinal vascular leakage with 9-field montage Topcon fluorescein angiography (FA) images in patients with uveitis. We hypothesized that Optos images reveal more leakage in patients with uveitis. Retrospective, observational case series. Images of all patients with uveitis imaged with same-sitting Optos FA and 9-field montage FA during a 9-month period at a single institution (52 eyes of 31 patients) were graded for the total area of retinal vascular leakage. The main outcome measure was area of fluorescein leakage. The area of apparent FA leakage was greater in Optos images than in 9-field montage images (median 22.5 mm(2) vs 4.8 mm(2), P < 0.0001). Of the 49 (45%) eyes with gradable photos, 22 had at least 25% more leakage in the Optos image than in the montage image; 2 (4.1%) had at least 25% less leakage in Optos; and 25 (51%) were similar in the 2 modalities. There were 2 eyes that had no apparent retinal vascular leakage in 9-field montage but were found to have apparent leakage in Optos images. Of the 49 eyes, 23 had posterior pole leakage, and of these, 17 (73.9%) showed more posterior pole leakage in the Optos image. A single 200-degree Optos FA image captured a mean 1.50× the area captured by montage photography. More retinal vascular pathology, in both the periphery and the posterior pole, is seen with Optos FA in patients with uveitis when compared with 9-field montage. The clinical implications of Optos FA findings have yet to be determined.


The quintessence of quality in the clinical laboratory.
Providing quality service is the goal of laboratory managers. The quintessence of clinical laboratory quality is the provision of an appropriate service--either medical information or some other service--that can be shown to measurably satisfy a patient's medical need and can be tied to patient outcome. Traditional quality measures, such as laboratory inspections and proficiency testing surveys as used by CLIA'88, are not the optimal yardsticks to apply. More effective programs are needed, such as the CAP's Q-Probes, that link laboratory operations with documented desired patient outcome. Only when a laboratory can define quality in a way that allows it to be quantitatively assessed in terms of patient care can it really know if it is providing optimal service.


PTEN loss does not predict for response to RAD001 (Everolimus) in a glioblastoma orthotopic xenograft test panel.
Hyperactivation of the phosphatidylinositol 3-kinase/Akt signaling through disruption of PTEN function is common in glioblastoma multiforme, and these genetic changes are predicted to enhance sensitivity to mammalian target of rapamycin (mTOR) inhibitors such as RAD001 (everolimus). To test whether PTEN loss could be used as a predictive marker for mTOR inhibitor sensitivity, the response of 17 serially transplantable glioblastoma multiforme xenografts was evaluated in an orthotopic therapy evaluation model. Of these 17 xenograft lines, 7 have either genomic deletion or mutation of PTEN. Consistent with activation of Akt signaling, there was a good correlation between loss of PTEN function and elevated levels of Akt phosphorylation. However, of the 7 lines with disrupted PTEN function, only 1 tumor line (GBM10) was significantly sensitive to RAD001 therapy (25% prolongation in median survival), whereas 1 of 10 xenograft lines with wild-type PTEN was significantly sensitive to RAD001 (GS22; 34% prolongation in survival). Relative to placebo, 5 days of RAD001 treatment was associated with a marked 66% reduction in the MIB1 proliferation index in the sensitive GBM10 line (deleted PTEN) compared with a 25% and 7% reduction in MIB1 labeling index in the insensitive GBM14 (mutant PTEN) and GBM15 (wild-type PTEN) lines, respectively. Consistent with a cytostatic antitumor effect, bioluminescent imaging of luciferase-transduced intracranial GBM10 xenografts showed slowed tumor growth without significant tumor regression during RAD001 therapy. These data suggest that loss of PTEN function is insufficient to adequately predict responsiveness to mTOR inhibitors in glioblastoma multiforme.


Impact of Moderate Calorie Restriction on the Reproductive Neuroendocrine Axis of Male Rhesus Macaques.
The impact of moderate calorie restriction on reproductive neuroendocrine function was investigated in young adult male rhesus macaques (Macaca mulatta). The animals were subjected to either 30% calorie restriction (CR; n=5), or were fed a standard control diet (CON; n=5), starting during their peripubertal period. Plasma LH and testosterone concentrations were examined after 7 years of differential dietary treatment, and were found to be similar in both groups, both during the day and during the night. Microarray profiling of pituitary gland and testicular gene expression was performed after 8 years of treatment, using GeneChip® Rhesus Macaque Genome Arrays (Affymetrix), and showed very little effect of caloric restriction. Using a 1.5-fold difference threshold, our microarray analysis revealed differential expression of only 145 probesets in the pituitary gland and 260 in the testes, out of a total of >54,000. Semi-quantitative RT-PCR performed on pituitary gland mRNA corroborated the microarray findings for selected modulated genes, including TSH receptor (TSHR) and sperm-specific antigen 2 (SSFA2). Most notably, significantly lower expression of TSH receptor mRNA was observed in the pituitary of CR compared to CON animals. Also, significantly lower expression of the glycoprotein hormone alpha subunit (CGA) was observed in CR animals, and this finding was further corroborated using quantitative real-time RT-PCR. No significant diet-induced changes were detected in the testis for genes associated with reproduction, circadian clocks, or oxidative stress. There is mounting evidence that CR may promote health and longevity in a wide range of organisms, including nonhuman primates. Importantly, our data suggest that moderate CR has no obvious lasting detrimental effect on the reproductive neuroendocrine axis of long-lived primates, and has only a modest influence on pituitary and testicular gene expression.


Interventional endoscopy.
This review provides an updated summary of gastric interventional endoscopy. Relevant original articles and topic reviews are highlighted in the areas of infection control, light sedation, hemostasis, endoscopic mucosal resection, and endoscopic placement of enteric devices. Several key findings are worth noting: the increased use of propofol by nonanesthesiologists for deep sedation with minimal adverse side effects, the adaptation of tissue adhesive agents for the treatment of bleeding gastric varices, the successful treatment of early gastric cancer by endoscopic mucosal resection, and the development of direct percutaneous endoscopic jejunostomy tubes for patients at high risk of aspiration. These recent developments in the field of interventional endoscopy have already made a great impact on clinical care. More advanced procedures can be performed safely while the patient is under deep sedation. Yet, these developments have not slowed down the need for improvement in interventional endoscopy. Researchers continue to look for smaller instruments, better optics, and more advanced accessories. This constant state of flux marks the field of interventional endoscopy and ensures its progress.


Study on tar generated from downdraft gasification of oil palm fronds.
One of the most challenging issues concerning the gasification of oil palm fronds (OPF) is the presence of tar and particulates formed during the process considering its high volatile matter content. In this study, a tar sampling train custom built based on standard tar sampling protocols was used to quantify the gravimetric concentration of tar (g/Nm3) in syngas produced from downdraft gasification of OPF. The amount of char, ash, and solid tar produced from the gasification process was measured in order to account for the mass and carbon conversion efficiency. Elemental analysis of the char and solid tar samples was done using ultimate analysis machine, while the relative concentration of the different compounds in the liquid tar was determined making use of a liquid gas chromatography (GC) unit. Average tar concentration of 4.928 g/Nm3 and 1.923 g/Nm3 was obtained for raw gas and cleaned gas samples, respectively. Tar concentration in the raw gas sample was found to be higher compared to results for other biomass materials, which could be attributed to the higher volatile matter percentage of OPF. Average cleaning efficiency of 61% which is comparable to that of sand bed filter and venturi scrubber cleaning systems reported in the literature was obtained for the cleaning system proposed in the current study.


Reversible electrical breakdown of lipid bilayers: formation and evolution of pores.
The mechanism of reversible electric breakdown of lipid membranes is studied. The following stages of the process of pore development are substantiated. Hydrophobic pores are formed in the lipid bilayer by spontaneous fluctuations. If these water-filled defects extend to a radius of 0.3 to 0.5 nm, a hydrophilic pore is formed by reorientation of the lipid molecules. This process is favoured by a potential difference across the membrane. The conductivity of the pores depends on membrane voltage, and the type of this dependence changes with the radius of the pore. Hydrophilic pores of an effective radius of 0.6 up to more than 1 nm are formed, which account for the membrane conductivity increase observed. The characteristic times of changes in average radius and number of pores during the voltage pulse and after it are investigated.


Compliance with San Francisco's flavoured tobacco sales prohibition.
In June 2018, San Francisco voters upheld the first comprehensive prohibition on sales of flavoured tobacco products (all products including menthol, everywhere in the city with no exceptions). This paper used data collected by the San Francisco Department of Public Health as part of its implementation and enforcement of San Francisco's city-wide ban on the sale of flavoured tobacco products. Every licensed tobacco retailer was visited and inspected. The San Francisco Department of Public Health and volunteers conducted an educational campaign from September 2018 to December 2018, including emailing all licensed tobacco retailers about the law, mailing a fact sheet poster, conducting four listening sessions and visiting permitted tobacco retailers to educate them about the law and solicit questions. Compliance inspections started in December 2018, which found that compliance was 17%. Compliance increased in January 2019 and averaged 80% between January 2019 and December 2019. After the phase-in period, all retailers were visited as part of routine inspections. This effort resulted in 80% compliance. Including retailer education prior to enforcement can result in compliance with a comprehensive ban on the sale of menthol and other flavoured tobacco products.


Psychiatry residency education in Canada: past, present and future.
OBJECTIVE This article provides a brief overview of the history of psychiatry residency training in Canada, and outlines the rationale for the current training requirements, changes to the final certification examination, and factors influencing future trends in psychiatry education and training. METHOD The author compiled findings and reports on residency education in Canada from current and historical sources. RESULTS Residency training in psychiatry in Canada has undergone significant change in the past 5 years, moving from an "apprenticeship" model to a competency-based curriculum with explicit expectations for the acquisition of key, defined competencies. CONCLUSION Continuous evaluation of teaching methodologies, increasing use of innovative and creative medical education techniques, flexible curricula, and increasingly rigorous standards of accreditation are some of the factors likely to continue to shape the future.


Analysis of selected herbicide metabolites in surface and ground water of the United States.
One of the primary goals of the US Geological Survey (USGS) Laboratory in Lawrence, Kansas, is to develop analytical methods for the analysis of herbicide metabolites in surface and ground water that are vital to the study of herbicide fate and degradation pathways in the environment. Methods to measure metabolite concentrations from three major classes of herbicides--triazine, chloroacetanilide and phenyl-urea--have been developed. Methods for triazine metabolite detection cover nine compounds: six compounds are detected by gas chromatography/mass spectrometry; one is detected by high-performance liquid chromatography with diode-array detection; and eight are detected by liquid chromatography/mass spectrometry. Two metabolites of the chloroacetanilide herbicides--ethane sulfonic acid and oxanilic acid--are detected by high-performance liquid chromatography with diode-array detection and liquid chromatography/mass spectrometry. Alachlor ethane sulfonic acid also has been detected by solid-phase extraction and enzyme-linked immunosorbent assay. Six phenylurea metabolites are all detected by liquid chromatography/mass spectrometry; four of the six metabolites also are detected by gas chromatography/mass spectrometry. Additionally, surveys of herbicides and their metabolites in surface water, ground water, lakes, reservoirs, and rainfall have been conducted through the USGS laboratory in Lawrence. These surveys have been useful in determining herbicide and metabolite occurrence and temporal distribution and have shown that metabolites may be useful in evaluation of non-point-source contamination.


Validation of gallium-67-citrate single-photon emission computed tomography in biopsy-confirmed residual Hodgkin's disease in the mediastinum.
In a retrospective study of a series of 30 adult patients during restaging of Hodgkin's disease after therapy, computed tomography (CT) and biopsy results were correlated with 67Ga SPECT in order to determine the value of SPECT imaging in monitoring recurrent mediastinal Hodgkin's disease. SPECT had an overall accuracy of 93% (28/30) and correctly identified active disease in 24 of 25, 96% of histopathologically proven recurrent Hodgkin's disease. Thus in this post-therapy setting, we have confirmed the high sensitivity of 67GA SPECT scans in patients selected for biopsy. Gallium-67 may prove particularly useful in detecting residual disease activity in patients in whom biopsy was positive but the interpretations of the CT scans were uncertain in regard to presence of tumors [8/30 (27%)]. In this group of patients, we found SPECT particularly helpful. A larger prospective series is under way to assess this possibility.


Unconventional interlayer exchange coupling via chiral phonons in synthetic magnetic oxide heterostructures.
Chiral symmetry breaking of phonons plays an essential role in emergent quantum phenomena owing to its strong coupling to spin degree of freedom. However, direct experimental evidence of the chiral phonon-spin coupling is lacking. In this study, we report a chiral phonon-mediated interlayer exchange interaction in atomically controlled ferromagnetic metal (SrRuO3)-nonmagnetic insulator (SrTiO3) heterostructures. Owing to the unconventional interlayer exchange interaction, we have observed rotation of spins as a function of nonmagnetic insulating spacer thickness, resulting in a spin spiral state. The chiral phonon-spin coupling is further confirmed by phonon Zeeman effect. The existence of the chiral phonons and their interplay with spins along with our atomic-scale heterostructure approach unveil the crucial roles of chiral phonons in magnetic materials.


Clinical performance of the EMIT vancomycin assay.
In evaluating the EMIT system for vancomycin used in the Cobas Bio centrifugal analyzer, we found two potential problems, each of which may have important clinical ramifications. First, precision, though acceptable in concentrations up to 30 mg/L, was marginal in the range above 30 mg/L. Second, when EMIT values were compared with those by fluorescent polarization immunoassay (TDx), we found a good correlation but a significant proportional bias: [EMIT] = (0.877)[TDx] + 0.435 mg/L (r = 0.971). The proportional bias was much more pronounced in specimens with high creatinine values than in specimens with normal values for creatinine. It remains to be determined which method is more nearly accurate. This imprecision and proportional bias in specimens with increased creatinines lead us to conclude that the EMIT vancomycin system should be used with caution.


Aging is associated with cardiac autonomic nerve fiber depletion and reduced cardiac and circulating BDNF levels.
Aging is a multifactorial process associated with an impairment of autonomic nervous system (ANS) function. Progressive ANS remodeling includes upregulation of expression of circulating catecholamines and depletion of cardiac autonomic nerve fibers, and it is responsible, in part, for the increased susceptibility to cardiac diseases observed in elderly subjects. Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), are involved in synaptogenesis and neurite outgrowth processes, supporting neuronal cell differentiation and maturation. However, whether and how these factors and their downstream signaling are involved in cardiac aging remains unclear. Here, we tested whether, in the aged heart, the overall extent of autonomic fibers is reduced, owing to lower production of trophic factors such as BDNF and NGF. In vivo, we used young (age: 3 months; n = 10) and old (age: 24 months; n = 11) male Fisher rats, whereas, we used human neuroblastoma (SH-SY5Y) cells in vitro. Compared to the young rats, old rats displayed a marked reduction in the overall ANS fiber density, affecting both sympathetic and cholinergic compartments, as indicated by dopamine β-hydroxylase (dβh) and vesicular acetylcholine transporter (VaChT) immunohistochemical staining. In addition, a marked downregulation of GAP-43 and BDNF protein was observed in the left ventricular lysates of old rats compared to those of young rats. Interestingly, we did not find any significant difference in cardiac NGF levels between the young and old groups. To further explore the impact of aging on ANS fibers, we treated SH-SY5Y cells in vitro with serum obtained from young and old rats. Sera from both groups induced a remarkable increase in neuronal sprouting, as evidenced by a crystal violet assay. However, this effect was blunted in cells cultured with old rat serum and was accompanied by a marked reduction in GAP-43 and BDNF protein levels. Our data indicate that physiological aging is associated with an impairment of ANS structure and function and that reduced BDNF levels are responsible, at least in part, for these phenomena.


Urinary tetrahydrocannabinol is associated with poorer working memory performance and alterations in associated brain activity.
Worldwide, cannabis is one of the most widely used psychoactive substances and cannabis use has been implicated in poorer performance in several cognitive domains, including working memory (WM). However, the neural mechanisms underlying these WM decrements are not well understood and the current study investigated the association of cannabis involvement with WM performance and associated neural activation in the Human Connectome Project (N = 1038). Multiple indicators of cannabis involvement were examined in relation to behavioral performance and brain activity in a visual N-back task using functional magnetic resonance imaging. A positive urine drug screen for tetrahydocannabinol (THC+ status), the principal psychoactive constituent in cannabis, was associated with worse WM performance and differential brain response in areas previously linked to WM performance. Furthermore, decreases in blood-activation-level-dependent (BOLD) signal in WM task-positive brain regions and increases in task-negative regions mediated the relationship between THC+ status and WM performance. In contrast, WM performance and BOLD response during the N-back task were not associated with total lifetime cannabis use, age of first use, or other indicators of involvement, suggesting that the effects of cannabis on WM were short-term residual effects, rather than long-term persistent effects. These findings elucidate differential influences of cannabis involvement on neurocognition and have significant potential implications for occupational performance in diverse settings.


Cervicovaginal Fungi and Bacteria Associated With Cervical Intraepithelial Neoplasia and High-Risk Human Papillomavirus Infections in a Hispanic Population.
The human cervicovaginal microbiota resides at an interface between the host and the environment and may affect susceptibility to disease. Puerto Rican women have high human papillomavirus (HPV) infection and cervical cancer rates. We hypothesized that the population structure of the cervicovaginal bacterial and fungal biota changed with cervical squamous intraepithelial lesions and HPV infections. DNA was extracted from cervix, introitus, and anal sites of 62 patients attending high-risk San Juan clinics. The 16S rRNA V4 region and ITS-2 fungal regions were amplified and sequenced using Illumina technology. HPV genotyping was determined by reverse hybridization with the HPV SPF10-LiPA25 kit. HPV prevalence was 84% of which ∼44% subjects were infected with high-risk HPV, ∼35% were co-infected with as many as 9 HPV types and ∼5% were infected with exclusively low-risk HPV types. HPV diversity did not change with cervical dysplasia. Cervical bacteria were more diverse in patients with CIN3 pre-cancerous lesions. We found enrichment of Atopobium vaginae and Gardnerella vaginalis in patients with CIN3 lesions. We found no significant bacterial biomarkers associated with HPV infections. Fungal diversity was significantly higher in cervical samples with high-risk HPV and introitus samples of patients with Atypical Squamous Cells of Undetermined Significance (ASCUS). Fungal biomarker signatures for vagina and cervix include Sporidiobolaceae and Sacharomyces for ASCUS, and Malassezia for high-risk HPV infections. Our combined data suggests that specific cervicovaginal bacterial and fungal populations are related to the host epithelial microenvironment, and could play roles in cervical dysplasia.


Seasonal occurrence of immature mosquitoes in swimming pools in Buenos Aires, Argentina.
The seasonal variation in the density of swimming pools and the occurrence of immature mosquitoes in these habitats were studied in the temperate city of Buenos Aires, Argentina. The density of swimming pools was highest in the summer (6.0 pools/ha) when temporal pools predominated; it was lowest in the winter (0.9 pools/ha) when only permanent pools were recorded. The presence of immature stages of mosquitoes was mainly associated with the lack of use and maintenance of the pools in the fall season, when temporal pools were still assembled but not intensively used. Seven mosquito species were recorded, among which Culex pipiens and Culex apicinus were the most frequent.


Prognostic value of pretreatment 18F-fluorodeoxyglucose uptake in patients with cervical cancer treated with definitive chemoradiotherapy.
We analyzed the correlation of F-fluorodeoxyglucose (FDG) uptake into primary tumors using the maximum standardized uptake value (SUVmax) and clinicopathological factors of disease. The impact of the pretreatment SUVmax of the primary tumor on survival was investigated. The records of 149 patients with biopsy-proven cervical cancer treated with definitive chemoradiotherapy (ChRT) were reviewed. All patients underwent pretreatment FDG positron emission tomography with computed tomography, and posttherapy FDG positron emission tomography with computed tomography was performed within a median interval of 4.2 months (range, 3.0-11.2 months) after the completion of chemoradiotherapy. The mean SUVmax in patients with lymph node metastasis was significantly higher than that in patients without metastasis (19.7 ± 8.2 vs 16.4 ± 8.2, respectively; P = 0.01). A significant difference existed between tumor size (<4 vs ≥4 cm) and the primary tumor SUVmax (14.7 ± 6.6 vs 18.7 ± 8.5, respectively; P = 0.02). The primary tumor pretreatment SUVmax for patients with complete remission was significantly lower than that of patients with partial response or progressive disease (15.6 ± 5.7 vs 28.0 ± 9.9, respectively; P < 0.001). The relationship between primary tumor FDG uptake and survival was evaluated by the cutoff value determined by receiver operating characteristic curve analysis. The area under the curve was 0.901 (P < 0.001; 95% confidence interval, 0.848-0.954), and 15.6 was determined as the SUVmax cutoff value. The 4-year actuarial overall survival (OS) and disease-free survival for SUVmax of less than 15.6 compared with SUVmax of 15.6 or greater were 85% vs 34% (P < 0.001) and 80% vs 29%, respectively (P < 0.001). In multivariate analysis, age, SUVmax of 15.6 or greater, and lymph node metastasis were independent prognostic factors of OS, and International Federation of Gynecology and Obstetrics stage IIB or higher, SUVmax of 15.6 or greater, and lymph node metastasis were significant factors for disease-free survival. The primary tumor pretreatment SUVmax is correlated with increased tumor size and lymph node involvement at diagnosis, how well the primary tumor responds to treatment, the likelihood of disease recurrence, and OS.


Persistent Trigeminal Artery Variant Terminating in the Ipsilateral Superior Cerebellar Artery.
Persistent trigeminal artery (PTA) represent an unusual remnant of the fetal carotid-basilar anastomosis. Persistent trigeminal artery variant (PTAV) is a rare anastomosis between the internal carotid artery and cerebellar artery, without an interposing basilar artery segment. We report the case of 49-year-old female with an incidentally discovered, rare variation of PTA that directly terminated in the ipsilateral superior cerebellar artery. The variation was observed on CT angiography, digital subtraction angiography, and MR angiography. Additionally, we reviewed the embryogenesis of PTA and PTAV and discussed the clinical implications of this variation.


Quantitative dental measurements by use of simultaneous frequency-domain laser infrared photothermal radiometry and luminescence.
Modulated (frequency-domain) infrared photothermal radiometry (PTR) is used as a dynamic quantitative dental inspection tool complementary to modulated luminescence (LM) to quantify sound enamel or dentin. A dynamic high-spatial-resolution experimental imaging setup, which can provide simultaneous measurements of laser-induced modulated PTR and LM signals from defects in teeth, has been developed. Following optical absorption of laser photons, the experimental setup can monitor simultaneously and independently the nonradiative (optical-to-thermal) energy conversion by infrared PTR and the radiative deexcitation by LM emission. The relaxation lifetimes (tau1, tau2) and optical absorption, scattering, and spectrally averaged infrared emission coefficients (mu(alpha), mu(s), mu(IR)) of enamel are then determined with realistic three-dimensional LM and photothermal models for turbid media followed by multiparameter fits to the data. A quantitative band of values for healthy enamel with respect to these parameters can be generated so as to provide an explicit criterion for the assessment of healthy enamel and, in a future extension, to facilitate the diagnosis of the onset of demineralization in carious enamel.


Shoulder ring complaints as a rare first symptom of malignant pleural mesothelioma.
The prevalence of malignant pleural mesothelioma is often encountered in the areas highly exposed to asbestos. The aim of this paper was a retrospective analysis of shoulder pain as a rare, first symptom of pleural mesothelioma, which constitutes an interdisciplinary diagnostic problem concerning both orthopedics and pulmonology. The research was based on a retrospective review of the patients' medical records. The considered period of time included the years 2006-2012. The study group included a total of 49 patients. Seven patients (14.3%) presented a complain of shoulder pain, as the first symptom of mesothelioma. The remaining 42 mesothelioma patients, without this symptom, constituted a reference group. The intensity of shoulder pain was, on average, 4/10 on an analog scale. A concomitant limitation of mobility was observed in five out of the seven subjects. In one case, limitation of motion and dysfunction of the shoulder joint were at an advanced stage. Neuralgia of upper limbs was found in two cases. We conclude that shoulder pain may be a manifesting symptom of malignant pleural mesothelioma. The neoplasm appears to have a pleiotropic effect on human body, reflected in different ways of its primary manifestation which may also include the motor system.


How sense-of-direction and learning intentionality relate to spatial knowledge acquisition in the environment.
People's impression of their own "sense-of-direction" (SOD) is related to their ability to effectively find their way through environments, such as neighborhoods and cities, but is also related to the speed and accuracy with which they learn new environments. In the current literature, it is unclear whether the cognitive skills underlying SOD require intentional cognitive effort to produce accurate knowledge of a new environment. The cognitive skills underlying SOD could exert their influence automatically-without conscious intention-or they might need to be intentionally and effortfully applied. Determining the intentionality of acquiring environmental spatial knowledge would shed light on whether individuals with a poor SOD can be trained to use the skill set of an individual with good SOD, thereby improving their wayfinding and spatial learning. Therefore, this research investigates the accuracy of spatial knowledge acquisition during a walk through a previously unfamiliar neighborhood by individuals with differing levels of self-assessed SOD, as a function of whether their spatial learning was intentional or incidental. After walking a route through the neighborhood, participants completed landmark, route, and survey knowledge tasks. SOD was related to the accuracy of acquired spatial knowledge, as has been found previously. However, learning intentionality did not affect spatial knowledge acquisition, neither as a main effect nor in interaction with SOD. This research reveals that while the accuracy of spatial knowledge acquired via direct travel through an environment is validly measured by self-reported SOD, the spatial skills behind a good SOD appear to operate with or without intentional application.


Femtosecond fiber CPA system based on picosecond master oscillator and power amplifier with CCC fiber.
Results of numerical and experimental investigations of the simple fiber CPA system seeded by nearly bandwidth-limited pulses from the picosecond oscillator are presented. We utilized self-phase modulation in a stretcher fiber to broaden the pulse spectrum and dispersion of the fiber to stretch pulses in time. During amplification in the ytterbium-doped CCC fiber, gain-shaping and self-phase modulation effects were observed, which improved pulse compression with a bulk diffraction grating compressor. After compression with spectral filtering, pulses with the duration of 400 fs and energy as high as 50 µJ were achieved, and the output beam quality was nearly diffraction-limited.


Endoscopic endonasal minimal access approach to the clivus: case series and technical nuances.
The endoscopic endonasal transclival approach is a novel minimal-access method of managing clival pathology. Limited cases have been published. To summarize our clinical experience with this approach and discuss technical nuances. We retrospectively reviewed a prospective database of 250 endoscopic, endonasal skull base surgeries. Patients in whom a transclival approach was performed were identified. Extent of resection, complications, and clinical outcome were analyzed. Seventeen patients underwent 21 procedures. Pathology included chordoma, meningioma, hemangiopericytoma, enterogenous cyst, epidermoid, and metastasis. Lumbar drain was placed intraoperatively in 9 cases and maintained for approximately 2 days postoperatively. Mean operative time was 252.8 minutes. Intraoperative cerebrospinal fluid (CSF) leak occurred in 10 cases. Greater than 95% resection was achieved in 11 of 12 cases (92%) in which it was the surgical goal. The risk of postoperative CSF leak was 4.8% for all procedures, 9.1% for procedures with large skull base defect, and 0% if a gasket-seal closure was achieved. A nasoseptal flap was used in 2 patients. There was one perioperative infarct, one case of deep vein thrombosis, and one postoperative pulmonary embolus. Mean follow-up was 8.5 months. All but one patient with preoperative cranial nerve deficits improved at last follow-up. All patients were free of disease progression at last follow-up. The endonasal endoscopic transclival approach provides a minimal-access approach to the ventral midline posterior fossa skull base. The risk of CSF leak is low if appropriate closure techniques are applied.


Comparative Gut Microbiota of 59 Neotropical Bird Species.
The gut microbiota of vertebrates are essential to host health. Most non-model vertebrates, however, lack even a basic description of natural gut microbiota biodiversity. Here, we sampled 116 intestines from 59 Neotropical bird species and used the V6 region of the 16S rRNA molecule as a microbial fingerprint (average coverage per bird ~80,000 reads). A core microbiota of Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria was identified, as well as several gut-associated genera. We tested 18 categorical variables associated with each bird for significant correlation to the gut microbiota; host taxonomic categories were most frequently significant and explained the most variation. Ecological variables (e.g., diet, foraging stratum) were also frequently significant but explained less variation. Little evidence was found for a significant influence of geographic space. Finally, we suggest that microbial sampling during field collection of organisms would propel biological understanding of evolutionary history and ecological significance of host-associated microbiota.


Shape matching using relaxation techniques.
The problem of finding approximate matches of pieces of shapes to parts of larger shapes is investigated. The shapes are represented by polygonal approximations. Initially, figures of merit are assigned to the matches between pairs of angles on the two shapes. Relaxation methods are then used to find acceptable combinations of these matches. This approach was tested on a data base consisting of digitized coastlines in various map projections. In nearly all cases, all matches except the correct one were eliminated by the relaxation processes.


Application of WHONET for the surveillance of antimicrobial resistance.
World over antimicrobial resistance is a major public health problem. The WHONET software program puts each laboratory data into a common code and file format, which can be merged for national or global collaboration of antimicrobial resistance surveillance. In this study, antimicrobial sensitivity of 4,289 bacterial isolates was studied by Kirby-Bauer disk diffusion method. -lactamase production was assessed by iodometric test method. Extended spectrum -lactamase (ESBLs) were screened by ceftazidime disk sensitivity. Drug resistance was high in most of the isolates. It was maximum (80-94%) for ampicillin, nalidixic acid and cotrimoxazole. It varied between 40-60% for gentamicin, clindamycin, fluoroquinolones and coamoxyclav. It ranged from 21 to 38% for amikacin and third generation cephalosporins. Constitutive -lactamase production was highest in S.aureus (28.9%) and ESBL production was maximum in Klebsiella spp. (53.6%). WHONET software has in-built analysis program which helps in forming hospital drug policy, identification of hospital outbreaks and recognition of quality control problems in the laboratory.


Antigen-induced TCR-CD3 down-modulation does not require CD3delta or CD3gamma cytoplasmic domains, necessary in response to anti-CD3 antibody.
We studied cytotoxic T lymphocyte (CTL) clones expressing cytoplasmic domain-deleted CD3delta and CD3gamma chains. These cells retained efficient antigen-specific cytolysis. Because the cytoplasmic domains of native CD3delta and CD3gamma chains contain a dileucine-based and a tyrosine-based motif thought to be important for receptor endocytosis, we compared TCR-CD3 down-modulation on the CTL clones expressing or not these domains. We found that antigen-induced TCR-CD3 down-modulation was not dependent on either the CD3delta or CD3gamma cytoplasmic domains. This contrasts with phorbol ester- and anti-CD3 mAb (soluble or plastic-coated)-induced TCR-CD3 down-modulation, that are respectively dependent on CD3gamma and on either CD3delta or CD3gamma cytoplasmic domains, suggesting that differences may exist between the mechanisms of TCR-CD3 down-modulation in response to the three stimuli. TCR-CD3 down-modulation in response to antigen was demonstrated by confocal microscopy to be associated with TCRbeta chain internalization, whether CD3delta and CD3gamma were native or truncated. Inhibition by the protein tyrosine kinase inhibitor PP1 of TCR-CD3 down-modulation in response to antigen was also similar whether CD3delta and CD3gamma cytoplasmic domains were present or not. These properties of receptor down-modulation are discussed with respect to the requirements for TCR engagement on antigen-presenting cells.


Preparation and Characterization of Silver(I) Ethylcellulose Thin Films as Potential Food Packaging Materials.
Ag(I)-containing ethylcellulose (EC) films suitable as antbacterial packaging materials have been prepared and fully characterized. Different preparation methods, including the use of green casting solvents, are proposed. The Ag(I) acylpyrazolonato complexes, [Ag(Qpy,CF3 )(L)], L=benzylimidazole (Bzim) and L=ethylimidazole (EtimH), used as active additives, display different modes of interactions with EC, depending on their structural features. A thorough investigation of the EC liquid-crystalline lyotropic phase and its changes with the introduction of silver additives, has been conducted, revealing either the inclusion of complex molecules into the inner structure of the EC matrix or their dispersion on its surface. Moreover, the bactericidal activity of the prepared Ag(I) films seems to be related to the interaction between silver additives and the polymeric EC matrix. Indeed, the EC-2b films show a particularly good performance even with a low silver content, with a relative bacterial killing of about 100 %. Tests for Ag(I) migration have been performed by using three food stimulants under two assay conditions. Low values of silver release are recorded, particularly at low concentration of silver content, in the case of all new prepared Ag(I) films.


Impaired extinction of cued fear memory and abnormal dendritic morphology in the prelimbic and infralimbic cortices in VPAC2 receptor (VIPR2)-deficient mice.
The structurally related neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have been implicated in stress regulation and learning and memory. Several bodies of research have shown the impact of the PACAP specific receptor PAC1 on fear memory, but the roles of other PACAP receptors in regulating fear stress responses remain to be elucidated. Here we aimed to investigate the effects of genetic deletion of VIPR2 encoding the VPAC2 receptor, which binds both VIP and PACAP, on fear-related memory and on dendritic morphology in the brain regions of the fear circuitry. Male VPAC2 receptor knockout (VPAC2-KO) and littermate wild-type control mice were subjected to Pavlovian fear conditioning paradigm. VPAC2-KO mice displayed normal acquisition of fear conditioning, contextual and cued fear memory, but impaired extinction of cued fear memory. Morphological analyses revealed reductions in cell body size and total branch number and length of apical and basal dendrites of prelimbic cortex neurons in VPAC2-KO mice. In addition, Sholl analysis indicated that the amount of dendritic material distal to the soma was decreased, while proximal dendritic material was increased. In the infralimbic cortex, the amount of apical dendritic material proximal to the soma was increased in VPAC2-KO mice, while other indices of morphology did not differ. Finally, there were no differences in dendritic morphology in basolateral amygdala neurons between genotypes. These findings suggest that the VPAC2 receptor plays an important role in the fear extinction processes and the regulation of the dendritic morphology in the prelimbic and infralimbic cortices.


Interactive effects of nrf2 genotype and oltipraz on benzo[a]pyrene-DNA adducts and tumor yield in mice.
The cancer chemopreventive actions of oltipraz (4-methyl-5-[2-pyrazinyl]-1,2-dithiole-3-thione) have been primarily associated with the induction of phase 2 detoxifying enzymes through transcriptional activation of the antioxidant response element (ARE) in the promoter regions of these genes. The transcription factor Nrf2 has been shown to bind to and activate AREs. Previously, we demonstrated that nrf2-deficient mice had low basal expression of phase 2 enzymes and were substantially more susceptible to benzo[a]pyrene (B[a]P)-induced neoplasia of the forestomach than wild-type. Moreover, loss of Nrf2 abrogated the chemopreventive action of oltipraz, when administered 48 h before B[a]P, an interval allowing maximal induction of many phase 2 enzymes. Oltipraz also inhibits some cytochrome P450s involved in the bioactivation of B[a]P. In the present study we observed that oltipraz had no protective effect on tumor burden in the forestomach of nrf2-deficient mice when administered 1 h before B[a]P, a timeline that selectively optimizes for possible inhibitory effects on cytochrome P450s. To evaluate the role of nrf2 genotype on B[a]P disposition, levels of B[a]P-DNA adducts were measured as tetrols released from DNA isolated from target (forestomach) and non-target tissues (liver) of wild-type and nrf2-deficient mice treated with either vehicle or oltipraz 1 or 48 h before B[a]P. Levels of B[a]P-DNA adducts in forestomach were significantly higher in nrf2-deficient compared with wild-type mice. Oltipraz treatment at 1 or 48 h before B[a]P had no protective effect on forestomach tetrol levels in nrf2-deficient mice, whereas a significant reduction was observed in wild-type mice treated with oltipraz 48 h, but not 1 h, before carcinogen. Combining all treatments and genotypes, there was a strong correlation (R(2) = 0.91) between levels of B[a]P-DNA adducts in forestomach and subsequent yield of tumors. In contrast to the results in forestomach, nrf2 genotype did not modify hepatic B[a]P-DNA adduct levels while both oltipraz treatments were protective, suggesting that Nrf2-independent mechanisms (e.g. P450 inhibition) for oltipraz can also occur in vivo in some tissues.


[Does meditation improve the quality of life for patients living with cancer?].
To determine whether interventions that promote meditation improve quality of life in cancer patients. MEDLINE data bank (1966 to 2004) using the terms "spiritual well-being" and the MeSH terms "meditation", "neoplasm", "cancer", and "spiritual therapies". Clinical trials evaluating the effect of meditation on cancer patients. SYNTHESIS Five studies were retained; none were designed in a way that made it possible to evaluate the effect of meditation exclusively or its effect on quality of life compared with a neutral intervention. Only 1 evaluated spiritual well-being. Four reported a significant improvement in symptoms of depression and anxiety when the study group's preintervention and post-intervention scores were compared. In the 2 studies that included a control intervention, participants preferred the meditation intervention. The design of studies to evaluate the effect of meditation on cancer patients did not make it possible to clearly identify the effect of meditation alone. These studies did show, however, that mood and anxiety parameters tend to improve--something that has been documented in other populations--and that spiritual well-being tends to improve as well. The main biases preventing a generalization of the effects of meditation are simultaneous evaluation of several interventions, "diluting" the effect of meditation; the lack of control groups receiving a comparable intervention; and the selection of study populations favourable to the intervention. There is increasing recognition of the effect of improved spiritual well-being on quality of life, even though most tools for measuring quality of life do not have a section for measuring spiritual well-being. Failing to take this aspect into account could be causing us to miss certain effects of meditation. In order to determine whether meditation should be offered to terminally ill patients, we need studies that do not contain these biases--studies designed to measure spiritual well-being.


Carriage of class 1 integrons and antibiotic resistance in clinical isolates of Acinetobacter baumannii from northern Spain.
A collection of 70 clinical isolates of Acinetobacter baumannii from Bilbao in northern Spain was examined by PCR for the presence of class 1 integron structures. The organisms comprised 21 distinct RAPD genotypes, with 10 distinct antibiogram patterns. Four different integron structures were detected in a total of 59 (84%) of the 70 isolates, with two predominant integron structures found in 20 and 30 isolates each. No clear antibiogram differences could be correlated with the presence or absence of integron structures, but sequence analysis of two of the internal integron regions indicated homology with genes encoding ANT(2'') adenyltransferase activity and AAC(6')-Ib acetyltransferase activity. Phenotypic analysis of aminoglycoside resistance profiles indicated that many isolates produced a combination of aminoglycoside-modifying enzymes, with most of the observed resistance to amikacin being associated with a gene encoding APH(3')-VI phosphotransferase, as detected by PCR. RAPD analysis indicated that all the Bilbao isolates producing APH(3')-VI were distinct from an epidemic integron-carrying and APH(3')-VI-producing Acinetobacter strain found in other regions of Spain. It is concluded that, although class 1 integrons are widely disseminated amongst clinical isolates of A. baumannii from the Bilbao region of Spain, at present they are not playing a major role in the dissemination of antibiotic resistance genes in this region.


1,6-α-L-Fucosidases from Bifidobacterium longum subsp. infantis ATCC 15697 Involved in the Degradation of Core-fucosylated N -Glycan.
Bifidobacterium longum subsp. infantis ATCC 15697 possesses five α-L-fucosidases, which have been previously characterized toward fucosylated human milk oligosaccharides containing α1,2/3/4-linked fucose [Sela et al.: Appl. Environ. Microbiol., 78, 795-803 (2012)]. In this study, two glycoside hydrolase family 29 α-L-fucosidases out of five (Blon_0426 and Blon_0248) were found to be 1,6-α-L-fucosidases acting on core α1,6-fucose on the N-glycan of glycoproteins. These enzymes readily hydrolyzed p-nitrophenyl-α-L-fucoside and Fucα1-6GlcNAc, but hardly hydrolyzed Fucα1-6(GlcNAcβ1-4)GlcNAc, suggesting that they de-fucosylate Fucα1-6GlcNAcβ1-Asn-peptides/proteins generated by the action of endo-β- N-acetylglucosaminidase. We demonstrated that Blon_0426 can de-fucosylate Fucα1-6GlcNAc-IgG prepared from Rituximab using Endo-CoM from Cordyceps militaris. To generate homogenous non-fucosylated N-glycan-containing IgG with high antibody-dependent cellular cytotoxicity (ADCC) activity, the resulting GlcNAc-IgG has a potential to be a good acceptor substrate for the glycosynthase mutant of Endo-M from Mucor hiemalis. Collectively, our results strongly suggest that Blon_0426 and Blon_0248 are useful for glycoprotein glycan remodeling.


Human TOLLIP regulates TLR2 and TLR4 signaling and its polymorphisms are associated with susceptibility to tuberculosis.
Tuberculosis, one of the leading causes of death worldwide, stimulates inflammatory responses with beneficial and pathologic consequences. The regulation and nature of an optimal inflammatory response to Mycobacterium tuberculosis remains poorly understood in humans. Insight into mechanisms of negative regulation of the TLR-mediated innate immune response to M. tuberculosis could provide significant breakthroughs in the design of new vaccines and drugs. We hypothesized that TOLLIP and its common variants negatively regulate TLR signaling in human monocytes and are associated with susceptibility to tuberculosis. Using short hairpin RNA knockdown of TOLLIP in peripheral blood human monocytes, we found that TOLLIP suppresses TNF and IL-6 production after stimulation with TLR2 and TLR4 ligands. In contrast, secretion of the anti-inflammatory cytokine IL-10 was induced by TOLLIP. We also discovered two common polymorphisms that are associated with either decreased levels of mRNA expression (rs3750920) or increased IL-6 production (rs5743899) in a sample of 56 healthy volunteers. Furthermore, in a case-population study in Vietnam with 760 cord blood samples and 671 TB case patients, we found that SNPs rs3750920 and rs5743899 were associated with susceptibility to tuberculosis (p = 7.03 × 10(-16) and 6.97 × 10(-7), respectively). These data demonstrate that TOLLIP has an anti-inflammatory effect on TLR signaling in humans and that TOLLIP deficiency is associated with an increased risk of tuberculosis. To our knowledge, these data also show the first associations of TOLLIP polymorphisms with any infectious disease. These data also implicate an unexpected mechanism of negative regulation of TLR signaling in human tuberculosis pathogenesis.


Bladder cancer and seroreactivity to BK, JC and Merkel cell polyomaviruses: the Spanish bladder cancer study.
An infectious etiology for bladder cancer has long been suspected. Merkel cell virus (MCV), BKV and JCV polyomaviruses are possible causative agents but data remain scarce. Therefore, we evaluated the seroresponse to these three polyomaviruses in association with bladder cancer risk. 1,135 incident bladder cancer subjects from five Spanish regions and 982 hospital controls matched by sex, age and region were included. 99% of cases were urothelial-cell carcinomas. Antibody response against MCV, BKV and JCV was measured by enzyme immunoassay using Virus-Like-Particles. Our results show a similar seroprevalence in cases and controls: 64/60% for BKV, 83/82% for MCV and 87/83% for JCV. However, among seropositive subjects, higher median seroreactivities were observed in cases compared to controls for BKV (0.84 vs. 0.70, p-value = 0.009) and MCV (1.81 vs. 0.65, p-value < 0.001). Increased bladder cancer risk was observed for BKV (OR = 1.4, 95%CI 1.04-1.8) and for MCV (OR = 1.5, 95%CI 1.2-1.9), when comparing highest to lowest seroreactivity tertiles. The associations of BKV and MCV with bladder cancer were independent of each other and neither smoking status nor disease stage and grade modified them. Furthermore, no association was observed between seroresponse to JCV and bladder cancer. Therefore, we conclude that BKV and MCV polyomavirus infection could be related to an increased bladder cancer risk.


The prodromal phase of hereditary spastic paraplegia type 4: the preSPG4 cohort study.
This cohort study aimed to characterize the prodromal phase of hereditary spastic paraplegia type 4 (SPG4) using biomarkers and clinical signs and symptoms that develop before manifest gait abnormalities. Fifty-six first-degree relatives at risk of developing SPG4 underwent blinded genotyping and standardized phenotyping, including the Spastic Paraplegia Rating Scale (SPRS), complicating symptoms, non-motor affection, Three-Minute Walk, and neurophysiological assessment. Automated MR image analysis was used to compare volumetric properties. CSF of 33 probands was analysed for neurofilament light chain (NfL), tau, and amyloid-β (Aβ). Thirty participants turned out to be SPAST mutation carriers, whereas 26 did not inherit a SPAST mutation. Increased reflexes, ankle clonus, and hip abduction weakness were more frequent in prodromal mutation carriers but were also observed in non-mutation carriers. Only Babinski's sign differentiated reliably between the two groups. Timed walk and non-motor symptoms did not differ between groups. Whereas most mutation carriers had total SPRS scores of 2 points or more, only two non-mutation carriers reached more than 1 point. Motor evoked potentials revealed no differences between mutation and non-mutation carriers. We found NfL but not tau or Aβ to rise in CSF of mutation carriers when approaching the time point of predicted disease manifestation. Serum NfL did not differ between groups. Volumetric MRI analyses did not reveal group differences apart from a smaller cingulate gyrus in mutation carriers. This study depicts subtle clinical signs which develop before gait abnormalities in SPG4. Long-term follow-up is needed to study the evolution of SPG4 in the prodromal stage and conversion into manifest disease. NfL in CSF is a promising fluid biomarker that may indicate disease activity in prodromal SPG4 but needs further evaluation in longitudinal studies.


Interpretation of two-stage experiments in animal studies.
Two-stage experiments allow results to be analysed at the end of the first stage and the second stage to be omitted if the preliminary conclusions are clear-cut. They thus offer the potential to reduce the number of experimental animals. However, using standard P values to assess the significance of results at the end of either stage will lead to an increase in risk of false positive conclusions. This paper provides a possible protocol for two-stage experiments and a method for adjusting P values. It is shown that, for experiments with reasonable power (>80%), the expected reduction in animal numbers will be at least 20%.


Abuse of Hispanic elders.
The nature, extent, and consequences of Hispanic elder abuse are described infrequently and often underconsidered. We reviewed information of 16,677 Hispanic elders living in the community who were abused between 1991 and 1995; these were based on valid cases reported to the Adult Protective Services (APS) office in Texas. Data did not include nursing home victims. Hispanic elders accounted for 20.6% of all elderly cases reported to APS. A 10% to 20% annual increase was seen over each of the past 5 years. Self-neglect was the most commonly identified form of abuse (63.2%). Cases with more than 1 allegation were common. The most common perpetrators (excluding self) were adult children (44.6%). Women were twice as likely as men to suffer abuse of any kind. Reluctance of victims to become involved in services to ameliorate their situations is a major barrier to effective intervention. Strategies to prevent abuse of Hispanic elders are needed and should focus on known characteristics of the abused and abusers.


Malabsorption of antimycobacterial drugs as a cause of treatment failure in tuberculosis.
Malabsorption of oral antimycobacterial drugs is a rare cause of treatment failure in tuberculosis (TB). Several predisposing comorbidities have been recognised. HIV infection is the most important risk factor referred in the literature. There are few reports about antimycobacterial drugs malabsorption, particularly in the absence of predisposing comorbidities. The authors present a clinical case of oral treatment failure in TB due to malabsorption; however, what caused the failure remained unclear. Possible causes of malabsorption are discussed under various sections. Purpose of this case report is to point to this rare situation that can easily go unnoticed unless a very high level of suspicion is present.


Body mass index, cigarette smoking, and alcohol consumption and cancers of the oral cavity, pharynx, and larynx: modeling odds ratios in pooled case-control data.
Odds ratios for head and neck cancer increase with greater cigarette and alcohol use and lower body mass index (BMI; weight (kg)/height(2) (m(2))). Using data from the International Head and Neck Cancer Epidemiology Consortium, the authors conducted a formal analysis of BMI as a modifier of smoking- and alcohol-related effects. Analysis of never and current smokers included 6,333 cases, while analysis of never drinkers and consumers of < or =10 drinks/day included 8,452 cases. There were 8,000 or more controls, depending on the analysis. Odds ratios for all sites increased with lower BMI, greater smoking, and greater drinking. In polytomous regression, odds ratios for BMI (P = 0.65), smoking (P = 0.52), and drinking (P = 0.73) were homogeneous for oral cavity and pharyngeal cancers. Odds ratios for BMI and drinking were greater for oral cavity/pharyngeal cancer (P < 0.01), while smoking odds ratios were greater for laryngeal cancer (P < 0.01). Lower BMI enhanced smoking- and drinking-related odds ratios for oral cavity/pharyngeal cancer (P < 0.01), while BMI did not modify smoking and drinking odds ratios for laryngeal cancer. The increased odds ratios for all sites with low BMI may suggest related carcinogenic mechanisms; however, BMI modification of smoking and drinking odds ratios for cancer of the oral cavity/pharynx but not larynx cancer suggests additional factors specific to oral cavity/pharynx cancer.


Survey of senescent cell markers with age in human tissues.
Cellular senescence, triggered by sublethal damage, is characterized by indefinite growth arrest, altered gene expression patterns, and a senescence-associated secretory phenotype. While the accumulation of senescent cells during aging decreases tissue function and promotes many age-related diseases, at present there is no universal marker to detect senescent cells in tissues. Cyclin-dependent kinase inhibitors 2A (p16/CDKN2A) and 1A (p21/CDKN1A) can identify senescent cells, but few studies have examined the numbers of cells expressing these markers in different organs as a function of age. Here, we investigated systematically p16- and p21-positive cells in tissue arrays designed to include normal organs from persons across a broad spectrum of ages. Increased numbers of p21-positive and p16-positive cells with donor age were found in skin (epidermis), pancreas, and kidney, while p16-expressing cells increased in brain cortex, liver, spleen and intestine (colon), and p21-expressing cells increased in skin (dermis). The numbers of cells expressing p16 or p21 in lung did not change with age, and muscle did not appear to have p21- or p16-positive cells. In summary, different organs display different levels of the senescent proteins p16 and p21 as a function of age across the human life span.


Effects of mango and mint pod-based e-cigarette aerosol inhalation on inflammatory states of the brain, lung, heart, and colon in mice.
While health effects of conventional tobacco are well defined, data on vaping devices, including one of the most popular e-cigarettes which have high nicotine levels, are less established. Prior acute e-cigarette studies have demonstrated inflammatory and cardiopulmonary physiology changes while chronic studies have demonstrated extra-pulmonary effects, including neurotransmitter alterations in reward pathways. In this study we investigated the impact of inhalation of aerosols produced from pod-based, flavored e-cigarettes (JUUL) aerosols three times daily for 3 months on inflammatory markers in the brain, lung, heart, and colon. JUUL aerosol exposure induced upregulation of cytokine and chemokine gene expression and increased HMGB1 and RAGE in the nucleus accumbens in the central nervous system. Inflammatory gene expression increased in the colon, while gene expression was more broadly altered by e-cigarette aerosol inhalation in the lung. Cardiopulmonary inflammatory responses to acute lung injury with lipopolysaccharide were exacerbated in the heart. Flavor-specific findings were detected across these studies. Our findings suggest that daily e-cigarette use may cause neuroinflammation, which may contribute to behavioral changes and mood disorders. In addition, e-cigarette use may cause gut inflammation, which has been tied to poor systemic health, and cardiac inflammation, which leads to cardiovascular disease.


Putting politics first.
The greatest lesson of the failure of comprehensive health reform in the early 1990s is that politics comes first. Even the best-laid policy plans are worthless if they lack the political support to pass. Putting politics first means avoiding the overarching mistake of the Clinton reformers: envisioning a grand policy compromise rather than hammering out a real political compromise. It also means addressing the inevitable fears of those who believe that they are well protected by our eroding employment-based system. And it means formulating political strategies that are premised on the contemporary realities of the hyperpolarized U.S. political environment, rather than wistfully recalled images of the bipartisan politics of old.


Antioxidants and Other Micronutrients in Complementary Oncology.
Many patients being treated for cancer use micronutrient supplements, with the intention to complement their cancer treatment or help them cope with the therapy- and disease-associated side effects. The majority are adding antioxidants without the knowledge of the treating physician. There are many concerns that antioxidants might decrease the effectiveness of chemotherapy, but increasing evidence suggests a benefit when antioxidants are added to conventional cytotoxic therapies. However, it is imperative that physicians explore the use of antioxidant and other micronutrient supplements with their cancer patients and educate them about potentially negative as well as potentially beneficial effects.


Frequency downshift of Nd:YAG lasers and terahertz radiation.
The interaction between an intense laser and a cotraveling relativistic dense electron beam could result in the downshifting of the laser frequency. It is theoretically analyzed that this process can generate a coherent terahertz radiation. The radiation energy could reach the order of 1 mJ per shot in the duration of 100 ps, or a temporal radiation power of 10 MW, with a set of practically relevant parameters.


'I Didn't Know What to Expect': Describing Parents' Expectations in Children's Rehabilitation Services.
Aims: The aim of this paper is to provide a holistic description of the nature, formation and impact of parents' therapy related expectations.Methods: This qualitative descriptive study drew from initial and follow up interviews with 20 parents of children ≤ 6 years who had a developmental disability or delay and used therapy services at a children's treatment center in Ontario, Canada. Conventional content analysis was used to inductively generate themes and investigator triangulation was completed.Results: Parent's child related expectations focused on whether the child would receive a diagnosis and what they might achieve. Parents held expectations about the availability of service and how it would be offered. Parents' expectations of service providers included their knowledge, skills, relationships and communication with the children and parents. Parents held expectations of themselves related to attendance and roles in therapy sessions and home practice. These expectations are described according to how they are shaped and changed them over time. The impact of matched/mismatched expectations is explored.Conclusion: Service providers can improve family-centred care and collaboration with parents by explicitly discussing parents' expectations when beginning, and throughout, therapy. Parent satisfaction and therapy engagement may improve if parents and service providers negotiate and agree upon expectations.


The quantity of protein-bound [32P]phosphotyrosine in hepatocytes and fibroblasts. The effects of tyrosine protein kinase activating agents.
Tyrosine protein kinase activities have been demonstrated in transformed and normal cell systems. So far, few data on the quantity of protein-bound phosphotyrosine in intact cells have been published. A knowledge of the stoichiometric increase in phosphotyrosine in cells after hormonal induction could be of interest when evaluating the importance of the tyrosine protein kinase activities found. By the addition of a known amount of unlabeled phosphotyrosine to the precipitated protein of 32P-phosphate-labeled cells it was possible after alkaline hydrolysis to spectrophotometrically follow the phosphotyrosine during consecutive chromatographies of the material. From the specific radioactivity of the purified phosphotyrosine the initial concentration of [32P]phosphotyrosine could be calculated. The method proved to be useful for the determination of [32P]phosphotyrosine is small amounts of cells. The minimum detectable amount of [32P]phosphotyrosine was about 1 pmol, and as an example, only 2.5 X 10(6) fibroblasts were needed. By this method it was shown that platelet-derived growth factor increased protein-bound [32P]phosphotyrosine from 600 to 3,200 pmol/g of fibroblasts, while insulin only increased the [32P]phosphotyrosine from 110 to 120 pmol/g of hepatocytes.


Epidural Spinal Stimulation to Improve Bladder, Bowel, and Sexual Function in Individuals With Spinal Cord Injuries: A Framework for Clinical Research.
While some recent studies that apply epidural spinal cord stimulation (SCS) have demonstrated a breakthrough in improvement of the health and quality of the life of persons with spinal cord injury (SCI), the numbers of people who have received SCS are small. This is in sharp contrast to the thousands of persons worldwide living with SCI who have no practical recourse or hope of recovery of lost functions. Thus, the vision is to understand the full potential of this new intervention and to determine if it is safe and effective in a larger cohort, and if it is scalable so that it can be made available to all those who might benefit. To achieve this vision, the National Institute of Biomedical Imaging and Bioengineering called for and organized a consortium of multiple stakeholder groups: foundations addressing paralysis, federal and public agencies, industrial partners, academicians, and researchers, all interested in the same goal. Based on input from consortium participants, we have reasoned that a first step is to define a scalable SCS approach that is effective in restoring lost autonomic physiology, specifically bladder, bowel, and sexual function. These functions are most critical for improving the quality of life of persons living with SCI. This report outlines a framework for conducting the research needed to define such an effective SCS procedure that might seek Food and Drug Administration approval and be implemented at the population level.


Application of a modified 203Hg binding assay for metallothionein.
A sensitive and rapid method to estimate concentrations of functional metallothionein in small biological samples, based upon the acid stability of 203Hg binding and solubility of this protein in trichloroacetic acid is described. Sephadex G-10 minicolumns supported in centrifuge tubes afforded separation and quantitation of isotope bound metallothionein from unbound metal. Elution of metallothionein bound 203Hg was achieved by short term-low speed centrifugation that segregated chelator-ligand complex into the eluate while unbound ligand remained in the gel. A well characterized standard of pure metallothionein protein was utilized to verify the specificity and sensitivity of the modified assay. Metallothionein levels were estimated by 203Hg binding in extracts of wild type and cadmium resistant Chinese hamster ovary cells treated with maximum tolerable concentrations of CdCl2. Similar separation methods demonstrated [35S]-cysteine incorporation into induced metallothionein. Additionally, induction of metallothionein was observed after treatment with particulate CdS but not crystalline NiS particles. These results demonstrate that the modified assay system is easily applied to serial measurement of metallothionein levels in multiple small biological samples.


Development of shyness across adolescence: Reactivity, regulation, or both?
The reactivity-regulation model suggests that the origins and maintenance of shyness results from relatively high levels of reactivity in combination with relatively low levels of regulation. Although this model has received some empirical support, there are still issues regarding directionality of the relations among variables and a dearth of studies examining the joint influence of reactivity and regulation on the prospective development of shyness. Using a longitudinal design, we first examined whether the relations among reactivity, regulation, and shyness were unidirectional or bidirectional in a sample of 1284 children (49.8% female, 84.1% White; mean parental education fell between associate degree/diploma and undergraduate degree) assessed annually across three waves from late childhood and early adolescence (Mage = 10.72 years) to adolescence (Mage = 12.42 years) and then examined whether reactivity and regulation interacted to influence the development of shyness over time. At Wave 1, shyness was related to higher levels of reactivity and lower levels of regulation at Wave 2, but neither reactivity nor regulation at Wave 1 predicted shyness at Wave 2. At Wave 2, shyness predicted greater reactivity at Wave 3, but shyness at Wave 3 was only predicted by lower levels of regulation at Wave 2. Contrary to the reactivity-regulation model of shyness, we found that relatively high levels of reactivity and low levels of regulation predicted a steep decrease in shyness over 3 years. These results are discussed in the context of the socioemotional difficulties experienced by shy individuals and demonstrate the importance of empirically evaluating long-standing models of personality development. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Symptomatic bilateral discoid menisci in children: a comparison with unilaterally symptomatic patients.
In previous studies, 5% to 20% of patients with a discoid lateral meniscus eventually require surgery bilaterally for symptomatic discoid menisci. However, there are little published data specifically on children who require treatment for discoid menisci in both knees. The purpose of this study is to identify differences in clinical and arthroscopic findings between children who require bilateral versus unilateral treatment for symptomatic discoid lateral menisci. We retrospectively reviewed the records of all patients aged 18 years or younger requiring treatment of discoid lateral meniscus between 1998 and 2007. Data were collected on 16 patients (32 knees) with symptomatic bilateral discoid menisci and 60 patients treated unilaterally with an asymptomatic contralateral knee. At initial presentation, children who were treated bilaterally for discoid menisci were younger than those treated unilaterally (10.4 vs. 12.5 y; P=0.021). Patients under 12 years of age were 4.6 times more likely to eventually require surgery on both knees (P=0.015). Watanabe classification was as follows: complete, 65% bilateral versus 30% unilateral; incomplete, 22% bilateral versus 68% unilateral; and Wrisberg, 13% bilateral versus 2% unilateral (P<0.001). The odds of current or future bilateral symptoms requiring treatment were 4.5 times higher in patients with a complete discoid meniscus (P=0.0017) and 8.4 times higher in those with a Wrisberg type (P=0.048). A tear of the lateral meniscus was more likely to be found intraoperatively in unilateral knees than bilateral (90% vs. 72%; P=0.037). Patient education and long-term follow-up are important for children who present with a discoid meniscus at a young age or with a complete or Wrisberg type, as these patients may be at increased odds of symptomatic discoid meniscus in the contralateral knee, even several years later. Furthermore, evaluation and treatment of discoid lateral meniscus requires vigilance for meniscal tears. Prognostic study, level III.


Analyzing bowtie structures with sharp tips by a vertical mode expansion method.
Bowtie structures of metallic nanoparticles are very effective in producing strong local fields needed in many applications. Existing numerical studies on bowtie structures are limited to those with rounded tips. Due to the field singularities at sharp edges and corners, accurate numerical solutions for bowtie structures with mathematically sharp tips are difficult to obtain. Based on an improved vertical mode expansion method (VMEM) that incorporates boundary integral equation techniques for domains with corners, we analyze bowtie structures with truly sharp tips. Numerical results are presented to reveal the effects of a few key factors including the distance between the tips, the apex angle and the substrate.


M2-Macrophage-Induced Chronic Inflammation Promotes Reversible Mesenchymal Stromal Cell Senescence and Reduces Their Anti-Fibrotic Properties.
Fibrosis and the associated decline in organ functionality lead to an almost 50% mortality rate in developed countries. Multipotent mesenchymal stromal cells (MSC) were shown to suppress the development and progression of fibrosis through secreted factors including specific non-coding RNAs transferred within extracellular vesicles (EV). However, age-associated chronic inflammation can provoke MSC senescence and change secretome composition, thereby affecting their antifibrotic properties. Alternatively activated macrophages (M2-type) are key players in chronic inflammation that may interact with MSC through paracrine mechanisms and decrease their antifibrotic functions. To confirm this hypothesis, we evaluated the M2-macrophage conditioned medium (CM-M2) effect on human adipose-tissue-derived MSC senescence in vitro. We found that CM-M2, as well as a pro-senescence agent, hydrogen peroxide (H2O2), increased p21+-MSC number and secretion of IL-6 and MCP-1, which are considered main senescence-associated secretory phenotype (SASP) components. Thus, both exposures led to the senescent phenotype acquisition of MSC. EV from both CM-M2 and H2O2-exposed MSC, which showed a decreased effect on the suppression of TGFβ-induced fibroblast-to-myofibroblast differentiation compared to EV from control MSC according to αSMA level and the αSMA+-stress fiber reduction. After two weeks of subsequent cultivation under standard conditions, MSC demonstrated a decrease in senescence hallmarks and fibroblast differentiation suppression via EV. These results suggest that M2-macrophage-induced chronic inflammation can reversibly induce MSC senescence, which reduces the MSC's ability to inhibit fibroblast-to-myofibroblast differentiation.


Bovine leucosis virus contamination of a vaccine produced in vivo against bovine babesiosis and anaplasmosis.
Contamination of a batch of tick fever (babesiosis and anaplasmosis) vaccine with bovine leucosis virus (BLV) was detected when a herd, in the final stages of an enzootic bovine leucosis (EBL) accreditation program, developed a large number of seropositive cattle following use of tick fever vaccine. Investigations incriminated a single calf used to produce Anaplasma centrale vaccine from which 13,959 doses were distributed. The failure of this calf to give a positive agar gel immunodiffusion (AGID) test before use was not fully explained. A total of 22,627 cattle from 111 herds receiving contaminated vaccine was tested to validate claims for compensation. Results showed infection rates of 62% and 51.8% in vaccinated dairy and beef cattle, respectively, compared with 6.1% and 1.5% in non-vaccinated cattle in the same herds. The results also indicated that infection did not spread from vaccinated to non-vaccinated in-contact cattle. Heavy reliance is now placed on purchase of calves for vaccine production from EBL accredited-free herds and on transmission tests from the calves to sheep to prevent a recurrence of contamination. The need for a BLV antigen detection test, with the sensitivity of the sheep transmission test but simpler and faster to perform, is evident.


Advantages and Disadvantages of the Patient-Centered Medical Home: A Critical Analysis and Lessons Learned.
This article provides a detailed examination of the pros and cons associated with patient-centered medical homes (PCMHs). Opinions and findings from those who have studied PCMHs and those who have been directly involved with this type of health care model are outlined. Key lessons from providers are detailed, and critical success factors are highlighted. This synthesized analysis serves to lend evidence to health care managers and providers who are considering implementation of the PCMH model.


Orbital Infarction Syndrome Following Mechanical Thrombectomy Secondary to Embolization in New Territory.
Orbital infarction syndrome (OIS) is a rare entity defined as ischemia of all intraorbital and intraoccular structures including the optic nerve, extraocular muscles, and orbital fat. This entity is rare due to rich anastomotic orbital vascularization from both the internal carotid artery and external carotid artery. We report a case of a patient who suffered emboli to previously nonaffected territories to the ophthalmic artery and external carotid artery, which resulted in orbital infarction syndrome, and describe techniques to avoid such complications. A 66-year-old male presented to our institution with an acute ischemic stroke secondary to occlusion of the internal carotid artery terminus and M1 segment. The vessel was revascularized after 1 pass using a stent retriever. Postoperative angiography demonstrated sluggish flow in the distal right ophthalmic artery, as well as occlusion of the distal external carotid artery. Twenty-four hours following the procedure, the patient was noted to have complete ophthalmoplegia of the right eye, proptosis, and conjunctival chemosis. Computed tomography angiography demonstrated persistent occlusion of the distal right ophthalmic artery and external carotid artery. The right optic nerve was swollen, as were all extraocular muscles. A final diagnosis of orbital infarction syndrome was made given the clinical presentation, imaging findings, and occlusion of all vascular supply to the orbit on both conventional angiography and 24-hour computed tomography angiography. OIS is a rare entity that has not been previously described as a complication of mechanical thrombectomy for acute ischemic stroke. OIS should be considered when patients present with blindness, orbital pain, and total ophthalmoplegia post thrombectomy.


Single crowns in the posterior maxilla supported by either 11-mm long implants with sinus floor augmentation or by 6-mm long implants: A 10-year randomized controlled trial.
To compare the clinical performance of single crowns in the posterior maxilla supported by either 11-mm long implants combined with maxillary sinus floor augmentation (MSFA) surgery or by 6-mm long implants during a 10-year follow-up period. Subjects were randomly allocated to receive one 11-mm long implant in combination MFSA or to receive one 6-mm long implant without any grafting. Twenty-one implants in 20 patients were placed in the 6-mm group and 20 implants in 18 patients were placed in the 11-mm group. Both groups were followed by clinical and radiographic examinations up to 10 years. Patients' satisfaction was also scored before treatment. Two patients died and eight patients moved during the follow-up. Two patients lost an implant in the 6-mm group and one implant was lost in the 11-mm group (implant survival 89.5% and 90.9%, respectively). From loading to 10 years' follow-up, mean ± SE marginal bone loss in the 6-mm group and 11-mm group was 0.18 ± 0.10 mm and 0.26 ± 0.12 mm, respectively, without a significant difference between the groups at 10 years (p = .650). In both groups, indices scores for plaque, calculus, gingiva and bleeding were low as well as mean pocket probing depth. Patients' satisfaction at 10 years was high in both groups; mean overall satisfaction in the 6-mm group and 11-mm group was 9.6 ± 0.6 and 9.2 ± 0.8, respectively (p = .168). Placement of 6-mm implants or 11-mm implants combined MFSA are equally successful during a 10-year follow-up period when applied for supporting a single restoration.


The role of secondary cytoreduction in the management of the first relapse in epithelial ovarian cancer.
The aim of this study was to investigate the benefit of secondary cytoreduction (SCR) in the first relapse in epithelial ovarian cancer and to attempt to define selection criteria for SCR. A retrospective population-based study on recorded information from 789 patients treated at the Norwegian Radium Hospital during 1985-2000 for their initial recurrence. In all, 217 had SCR and 572 were treated with chemotherapy alone. Median survival time (MST) was 1.1 years for the chemotherapy group. Complete optimal cytoreduction (COC) was achieved in 35% of all 217 patients, in 49% of the patients operated with debulking intent and in 52% if bowel surgery was done with debulking intent. MST was 4.5 versus 0.7 years for 0 versus>2 cm residual disease, respectively. Residual disease after SCR, treatment-free interval (TFI) and age were found to be prognostic factors for overall survival (OS) in multivariate analysis. Localised tumour was found to be the only significant factor to predict COC. SCR followed by chemotherapy gives a clear survival benefit compared with chemotherapy and should be offered when the tumour is localised. The combination of COC, TFI >24 months and age </=39 years identifies a group of patients with the best OS.


cagA and vacA genotype of Helicobacter pylori associated with gastric diseases in Xi'an area.
To establish stock of clinical Helicobacter pylori (H. pylori) isolates, to perform cagA and vacA typing of these isolates, to evaluate the relationship between genotypes of cagA and vacA and upper gastrointestinal diseases and to assess the association of vacA genotypes with presence of the pathogenicity marker-cagA. Clinical H.pylori strains were isolated from the antrum of 259 patients in Clumbia agar. The isolated H.pylori strains were identified by histology, and16SrRNA PCR. CagA genotypes were detected by colony hybridization, the probe was derived from the cloned plasmid PcagA, and digested by EcoRI-HindIII and the isolated PcagA DNA fragment was radioactively labelled by the random priming method. vacA genes types (s,m)and subtypes (s1a, s1b, s2) were typed by PCR. Vacuolating toxin was detected with neutral red absorb test. The results were treated statistically by chi(2) test, t test, and rank sum test. A total of 192 clinical H.pylori strains were isolated and the stock of Helicobacter pylori was established. The total positive rate of cagA was 87 % in all gastric diseases, and 95 % in gastric cancer group. There was a difference between gastric cancer group and the other groups (P<0.05) except duodenal ulcer group. The expression of type s1 of vacA was more than type s2 (P<0.05), and, the expression of type m1 was equal to type m2. In gastric cancer group, there was a difference between s1a and s1b (P<0.05), and s1a was more than s1b. Vacuolating toxins were more in Xi'an area isolates. The cagA(+) vacA type s1 clinical isolates are more in Xi'an area, but this can not serve as an index to predict gastric cancer.


Increasing CRTC1 function in the dentate gyrus during memory formation or reactivation increases memory strength without compromising memory quality.
Memory stabilization following encoding (synaptic consolidation) or memory reactivation (reconsolidation) requires gene expression and protein synthesis (Dudai and Eisenberg, 2004; Tronson and Taylor, 2007; Nader and Einarsson, 2010; Alberini, 2011). Although consolidation and reconsolidation may be mediated by distinct molecular mechanisms (Lee et al., 2004), disrupting the function of the transcription factor CREB impairs both processes (Kida et al., 2002; Mamiya et al., 2009). Phosphorylation of CREB at Ser133 recruits CREB binding protein (CBP)/p300 coactivators to activate transcription (Chrivia et al., 1993; Parker et al., 1996). In addition to this well known mechanism, CREB regulated transcription coactivators (CRTCs), previously called transducers of regulated CREB (TORC) activity, stimulate CREB-mediated transcription, even in the absence of CREB phosphorylation. Recently, CRTC1 has been shown to undergo activity-dependent trafficking from synapses and dendrites to the nucleus in excitatory hippocampal neurons (Ch'ng et al., 2012). Despite being a powerful and specific coactivator of CREB, the role of CRTC in memory is virtually unexplored. To examine the effects of increasing CRTC levels, we used viral vectors to locally and acutely increase CRTC1 in the dorsal hippocampus dentate gyrus region of mice before training or memory reactivation in context fear conditioning. Overexpressing CRTC1 enhanced both memory consolidation and reconsolidation; CRTC1-mediated memory facilitation was context specific (did not generalize to nontrained context) and long lasting (observed after virally expressed CRTC1 dissipated). CREB overexpression produced strikingly similar effects. Therefore, increasing CRTC1 or CREB function is sufficient to enhance the strength of new, as well as established reactivated, memories without compromising memory quality.