Analysis of homosexual behavior characteristics and influencing factors of male college students in Zhejiang Province.
The purpose of this study was to understand the homosexual behavior characteristics and influencing factors of male college students and to provide scientific evidence for the prevention of HIV infection in college students.A self-made online questionnaire was used to collect information on demographic characteristics, sexual attitudes, sexual behaviors, and interventions of the respondents. The χ2 test was performed on the constituent ratios of different groups, and whether homosexual behavior occurred was the dependent variable. Logistic regression was subsequently used to analyze the influencing factors of male homosexual behavior.A total of 2665 students were surveyed, including 219 men who have sex with men, accounting for 8.22% of the sample population. Multivariate analysis revealed the following independent influencing factors of homosexual behavior among male college students: the student's household registration was Zhejiang Province, the hometown was in the city, accepted male homosexual sex, had temporary sex in the last year, and awareness that the correct use of condoms can reduce the spread and risk of acquired immunodeficiency syndrome.Various measures should be enacted to promote human immunodeficiency virus/acquired immunodeficiency syndrome education and intervention among college students, especially emphasizing making friends and advocating safe sex to prevent the spread of the disease.


[Clinical aspects of capillary malformations].
Capillary malformations (CM) are defects of the dermal capillary bed. These slow-flow malformations can affect any part of the body and are always lateralized, despite Unna's naevus. Present at birth, they grow proportionally with the child. In rare instance, they can be part of a more complex syndrome such as Sturge-Weber syndrome. Ectatic CMs of telangiectatic types can be cutaneous, isolated, multiples, diffuse or generalized. In rare instance, they can be associated with epidermal modifications. They can also be part of a syndrome such as Fabry disease, Osler-Weber-Rendu disorder or Cutis marmorata telangiectatica congenita (CMTC). This chapter details the various clinical aspects of CMs.


Mental health of aging immigrants and native-born men across 11 European countries.
Though working-age immigrants exhibit lower mortality compared with those domestic-born immigrants, consequences of immigration for mental health remain unclear. We examine whether older immigrants exhibit a mental advantage and whether factors believed to underlie immigrant vulnerability explain disparities. The sample includes 12,247 noninstitutionalized men more than 50 years in 11 European countries. Multivariate logistic regression models estimated the impact of physical health, health behaviors, availability of social support, social participation, citizenship, time since immigration, socioeconomic status (SES), and employment on the mental health of immigrants. Immigrants face 1.60 increased odds of depression despite a physical health advantage, evidenced by 0.74 lower odds of chronic illness. SES and availability of social support were predictive, though acculturation measures were not. Decomposition analysis revealed that only approximately 20% of the variation in depression rates between immigrants and native-born peers were explained by commonly cited risk factors. Despite physical health advantages, older immigrants suffer substantially higher depression rates. Time since immigration does not appear to mitigate depressive symptoms.


Stable Sparse Classifiers Identify qEEG Signatures that Predict Learning Disabilities (NOS) Severity.
In this paper, we present a novel methodology to solve the classification problem, based on sparse (data-driven) regressions, combined with techniques for ensuring stability, especially useful for high-dimensional datasets and small samples number. The sensitivity and specificity of the classifiers are assessed by a stable ROC procedure, which uses a non-parametric algorithm for estimating the area under the ROC curve. This method allows assessing the performance of the classification by the ROC technique, when more than two groups are involved in the classification problem, i.e., when the gold standard is not binary. We apply this methodology to the EEG spectral signatures to find biomarkers that allow discriminating between (and predicting pertinence to) different subgroups of children diagnosed as Not Otherwise Specified Learning Disabilities (LD-NOS) disorder. Children with LD-NOS have notable learning difficulties, which affect education but are not able to be put into some specific category as reading (Dyslexia), Mathematics (Dyscalculia), or Writing (Dysgraphia). By using the EEG spectra, we aim to identify EEG patterns that may be related to specific learning disabilities in an individual case. This could be useful to develop subject-based methods of therapy, based on information provided by the EEG. Here we study 85 LD-NOS children, divided in three subgroups previously selected by a clustering technique over the scores of cognitive tests. The classification equation produced stable marginal areas under the ROC of 0.71 for discrimination between Group 1 vs. Group 2; 0.91 for Group 1 vs. Group 3; and 0.75 for Group 2 vs. Group1. A discussion of the EEG characteristics of each group related to the cognitive scores is also presented.


Bortezomib-induced Severe Congestive Heart Failure.
The clinical manifestations of anti-cancer drug associated cardiac side effects are diverse and can range from acutely induced cardiac arrhythmias to severe contractile dysfunction, and potentially fatal heart failure. Anthracyclines and trastuzumab cardiac toxicity have been well described and left ventricular ejection fraction (LVEF) evaluation is commonly performed before their use. Bortezomib (Velcade), a potent, specific and reversible proteasome inhibitor is approved for treatment of multiple myeloma (MM). The incidence of cardiac failure associated with bortezomib therapy in clinical trials remains incidental. Acute exacerbation of pre-existing congestive cardiac failure has been associated with this therapy but de novo cardiomyopathy has been reported in only one patient receiving bortezomib for small cell lung cancer. As a result, cardiac evaluation is not normally ordered before its use. We describe a 50-year-old female with newly diagnosed MM and no risk factors for cardiac disease that unexpectedly developed florid heart failure after 2 cycles of bortezomib and low-dose dexamethasone. 2-D echocardiogram showed dilated cardiomyopathy with severely decreased LVEF; no changes consistent with amyloid deposits or myocardial scarring were described. Coronary angiogram ruled out coronary artery disease. The mechanism of bortezomib-induced cardiomyopathy has been postulated to be through fluid retention. Based on literature review we hypothesize that the disruption of the ubiquitin-proteasome system by bortezomib may cause cardiomyopathy and severe cardiac failure. As Bortezomib is a new and promising therapy for MM patients, we recommend routinely monitoring cardiac parameters in patients undergoing this treatment.


[Directed evolution of antibody molecules in phage-displayed combinatorial libraries].
Advances in methods for conformational prediction, structural analysis and site-directed mutagenesis of proteins and peptides have contributed to the understanding of their structure and function. However, with the exception of a few successes, the generation of practical functional molecules solely by rational design remains a difficult challenge. The aim of our study is to investigate molecular design relying on evolutionary processes, called as "directed evolution", to generate a novel class of biofunctional molecules. This evolutionary approach consists of three steps; 1) constructions of protein/peptide libraries based on structural information, 2) expressions of the libraries on phage particles, and 3) selections with investigator-imposed selective pressures. In this work, we study on directed evolution with antibody libraries. We have succeeded in generating highly active catalytic antibodies in phage-displayed antibody (Fab) libraries. To evolve catalytic antibodies toward higher catalytic activity, we have mimicked an enzyme-evolutional process, in which an enzyme has evolved their ability to use binding energies for catalysis by increasing the affinity for the transition state of a reaction and decreasing the affinity for the ground state. Thus, phage-displayed libraries derived from an original catalytic antibody were selected against a newly-devised TSA, which was programmed to optimize the differential affinity for the transition state relative to the ground state, to provide variants with improved reaction rates (k(cat)). The in vitro evolution has great potential for generating novel catalysts as well as for providing opportunities to examine the evolutionary dynamics of enzymes.


The natural history of interferon-alpha2b-induced thyroiditis and its exclusivity in a cohort of patients with chronic hepatitis C infection.
Interferon-alpha2b (IFN-alpha2b) is well known to cause both hyper- and hypo-thyroidism. In the former, the commonest aetiology is thyroiditis. As there is no previous data to fully characterize the entity of IFN-related thyroiditis, the aim of this study is to document in detail its evolution in a cohort of hepatitis C patients treated with pegylated IFN-alpha2b and Ribavirin (RBV). A prospective observational study was conducted in patients who developed thyroid diseases whilst receiving combination of pegylated IFN-alpha2b and RBV for hepatitis C. The patients were followed with monthly thyrotropin (TSH). Where TSH was undetectable, free tetra- (fT4) and tri-iodothyronine (fT3) were added. Anti-thyroperoxidase (TPO), anti-thyroglobulin (Tg) and thyroid stimulating immunoglobulin (TSI) levels were also performed at diagnosis, during and at the end of IFN therapy. All patients were assessed and followed up closely with monthly TSH, fT4 and fT3 levels until the completion, after 6 and 12 months of treatment. There were seven females and four males over a 30-month period. All patients were found to have thyroiditis. On average, the time to the development of thyroid disease was 10 weeks and duration of disease 9 weeks. All patients eventually recovered normal biochemical thyroid function although two required short-term supplementation. Thyroiditis was found exclusively in our patients. Both the hyper- and hypo-thyroid phase can be short lived, extreme and transient in nature which warrants strict monthly TSH monitoring. Careful follow-up of all patients is mandatory as complete recovery is expected.


Cervical cord compression due to delayed scarring around epidural electrodes used in spinal cord stimulation.
The authors report on 2 cases of delayed compression of the cervical spinal cord by dense scar tissue forming around epidural electrodes implanted for spinal cord stimulation (SCS). This complication has not been previously reported. Myelopathy developed in 2 patients 5 and 16 years after the surgical placement of a cervical epidural electrode. Prior to myelopathy, both patients experienced a tolerance phenomenon. Magnetic resonance imaging in both cases showed severe compression of the spinal cord by the electrode. At surgery, thick scar tissue surrounding the electrode and compressing the posterior aspect of the cord was discovered. Both patients experienced a full recovery following the removal of both scar tissue and the electrode. Medical and paramedical staff dealing with SCS should be aware of this severe and delayed complication. In addition, the development of epidural fibrosis can explain the occurrence of tolerance.


Everolimus in de novo cardiac transplantation: pharmacokinetics, therapeutic range, and influence on cyclosporine exposure.
We evaluated exposure, safety, and efficacy data from an international Phase 3 trial of everolimus in de novo heart transplantation to characterize the longitudinal pharmacokinetics of everolimus and cyclosporine and to identify a therapeutic concentration range for everolimus. We randomized 634 patients to receive either 0.75 mg everolimus twice daily, 1.5 mg everolimus twice daily, or azathioprine in addition to corticosteroids and cyclosporine. At 8 visits during the first 6 months after transplantation, we obtained 2,328 everolimus trough levels (Cmin) and 129 area-under-the-curve (AUC) profiles over the dosing interval in patients treated with everolimus; we collected 3,258 cyclosporine trough concentrations and 174 profiles in all 3 treatment arms. We used median-effect analysis to characterize exposure-response associations between everolimus average Cmin vs freedom from biopsy-confirmed acute rejection; maximum cholesterol, low density lipoprotein, triglyceride, and creatinine levels; and minimum leukocyte and platelet counts. Everolimus Cmins averaged 5.2 +/- 3.8 ng/ml and 9.4 +/- 6.3 ng/ml at the lower and upper dose levels. A 17% underproportionality was noted in Cmins; however, peak exposure and AUC were consistent with dose proportionality. Everolimus exposure was stable during the 6-month period. Interindividual variability was 37% for AUC and 40% for Cmin. The latter parameter was not influenced to a clinically relevant extent by sex, age, or weight. The Cmin was well correlated with AUC (r2 = 0.81). Everolimus Cmin was significantly related to freedom from rejection (p = 0.02) with 3 ng/ml being an informative lower threshold for efficacy. Thrombocytopenia, defined as <75 x 10(9)/liter, was related significantly to Cmin (p = 0.03); however, the incidence in this study was too low to establish an upper end for the therapeutic range. Lower doses of cyclosporine (by 15% to 19%) were used in patients treated with everolimus to achieve cyclosporine Cmins and AUCs similar to those in patients treated with azathioprine. Everolimus exposure was dose proportional and stable during the first 6 months after transplantation. Interindividual pharmacokinetic variability was high but not influenced by common demographic covariates. We observed a significantly increased risk of acute rejection at everolimus trough levels <3 ng/ml, which constitutes the lower therapeutic concentration limit when everolimus is used with conventionally dosed cyclosporine. Everolimus-related adverse events were manageable up to the highest troughs (22 ng/ml) observed in this population. We could not derive a precise upper therapeutic concentration limit from these data.


Dynamic change of neural cell adhesion molecule polysialylation on human neuroblastoma (IMR-32) and rat pheochromocytoma (PC-12) cells during growth and differentiation.
Polysialic acid (PSA) is a regulatory epitope of neural cell adhesion molecule (NCAM) in homophilic adhesion of neural cells mediated by NCAM, is also known to be re-expressed in several human tumors, thus serves as an oncodevelopmental antigen. In this study, using a recently developed ultrasensitive chemical method in addition to immunochemical methods, growth stage-dependent and retinoic acid (RA)-induced differentiation-dependent changes of PSA expression in human neuroblastoma (IMR-32) and rat pheochromocytoma (PC-12) cells were analyzed both qualitatively and quantitatively. Both IMR-32 and PC-12 cells expressed PSA on NCAM, and the level of PSA expressed per unit weight of cells increased with post-inoculation incubation time. The most prominent feature was seen at the full confluence stage. RA induced neuronal differentiation in both IMR-32 and CP-12 cells that paralleled the change in the PSA level. Chemical analysis revealed the presence of NCAM glycoforms differing in the degree of polymerization (DP) of oligo/polysialyl chains, whose DP was smaller than 40. DP distribution of PSA was different between the cell lines and was changed by the growth stage and the RA treatment. Thus DP analysis of PSA is important in understanding both mechanism and biological significance of its regulated expression.


From Pituitary Adenoma to Pituitary Neuroendocrine Tumors: How Molecular Pathways may Impact the Therapeutic Management?
The classification of adeno-pituitary tumor was deeply revised over the last 20 years, in order to better describe the variable and complex biological and clinical behavior of these neoplasia and to identify prognostic markers of aggressiveness and poor prognosis. Recently, the International Pituitary Pathology Club proposed to replace the term "pituitary adenoma" with "pituitary neuroendocrine tumour" (PitNET), to reflect similarities of adeno-pituitary tumours with neuroendocrine neoplasia of other organs, underling better the variable behaviour of adeno-pituitary neoplasia. A definitive consensus was not reached on this issue. In this review, we will describe how molecular and biological marker can predict aggressiveness of PitNETs and impact on therapeutic management of PitNETs.


The curvature sensitivity of a membrane-binding amphipathic helix can be modulated by the charge on a flanking region.
Membrane-induced amphipathic helices (m-AH) can act as membrane curvature sensors by binding preferentially to hydrophobic lipid packing defects enriched in curved surfaces. Reliance on hydrophobicity and membrane curvature for binding is enhanced when electrostatic interactions are weak. We probed the role of modifying membrane and protein charge on the curvature sensing of two m-AH-containing proteins, CTP:phosphocholine cytidylyltransferase (CCT) and α-synuclein (α-syn). The m-AH domains in both proteins are flanked by disordered tails with multiple phosphoserines (CCT) or acidic residues (α-syn), which we mutated to glutamate or serine to modify protein charge. Analysis of binding to vesicles of varying curvature showed that increasing the negative charge of the tail region decreased the binding strength and augmented the curvature dependence, especially for CCT. We attribute this to charge repulsion. Conversely, increasing the membrane negative charge dampened the curvature dependence. Our data suggest that discrimination of curved versus flat membranes with high negative charge could be modulated by phosphorylation.


Stabilizing the regionalisation of the developing vertebrate central nervous system.
During embryonic development, a number of tissues are patterned by their subdivision into domains with distinct regional identity. An important question is how sharp interfaces are established and maintained between adjacent domains despite the potential for scrambling due to cell intermingling during tissue growth. Two mechanisms have been found to underlie the maintenance of sharp interfaces: the specific restriction of cell mixing across boundaries, or the switching of identity of cells that cross between domains. We review the evidence for these mechanisms at distinct boundaries in the developing vertebrate central nervous system, and discuss what is known about their molecular mediators.


Comparison of two methods of seminal plasma removal on buffalo (Bubalus bubalis) sperm cryopreservation.
Cryopreservation causes damage to spermatozoa, and methods minimizing this damage are therefore needed. Although much discussed, seminal plasma removal has become an alternative to improve sperm quality and viability after freezing and has been applied to different species in attempt to obtain good results. The objective of this study was to evaluate semen quality in buffaloes submitted to two methods for seminal plasma removal (filtration and centrifugation). Semen samples were collected from seven Murrah buffalo bulls (Bubalus bubalis) once a week for 8 weeks. Each ejaculate was divided into three groups: control (presence of seminal plasma), centrifugation and filtration. Sperm kinetics was evaluated with the computer-assisted sperm analysis (CASA) system. Plasmalemma and acrosomal membrane integrity, mitochondrial membrane potential and reactive oxygen species (ROS) were measured by flow cytometry, and lipid peroxidation was evaluated by the thiobarbituric acid reactive substances (TBARS) assay. Seminal plasma removal did not improve sperm kinetics compared to the control group. Centrifugation increased the number of cells with damaged acrosomal membranes (0.77 ± 0.05) and filtration caused greater plasmalemma and acrosomal membrane damage (22.18 ± 1.07). No difference in the mitochondrial membrane potential was observed between groups. In contrast, ROS production was higher in the centrifugation group compared to the control and filtration groups, although no differences in TBARS formation were detected. In conclusion, seminal plasma removal did not improve the quality of thawed buffalo semen compared to control in terms of sperm kinetics, membrane integrity, mitochondrial membrane potential or lipid peroxidation.


Decreased neonatal serum bilirubin with plain agar: a meta-analysis.
Neonatal jaundice is one of the most common problems leading to prolonged hospitalization of the newborn. Therefore, an effective low-risk, low-cost therapy reducing hospitalization is highly desirable. Plain dried agar, an extract of seaweed, is low cost and low risk; it can bind bilirubin in the gut, decreasing its enterohepatic circulation, thereby decreasing serum levels. Because of conflicting conclusions in the studies of agar's effectiveness in the prevention and treatment of neonatal jaundice, a meta-analysis of their methodologies was done. Criteria for assessing prospective controlled therapeutic trials of agar were established in six areas: hypothesis and clinical outcome, patient selection, treatment group allocation, therapeutic maneuver, use of cotherapies, and data analysis. Nine prospective clinical trials of agar therapy were evaluated using these six criteria. The seven studies with negative conclusions regarding agar's efficacy failed to meet the criteria in several categories: patient selection, therapeutic maneuver, use of cotherapies, or data analysis. All of the studies, including the positive studies, were at risk for biased treatment allocation. Although the pooled data analysis suggests that prophylactic agar treatment is associated with reduced peak serum bilirubin levels, this observation must be interpreted cautiously in light of heterogenous patient populations and the methodologic problems described. Based on this meta-analysis, agar therapy for neonatal jaundice can neither be recommended nor rejected. The methodologic analysis gives clear guidance for future research concerning the effectiveness of agar in treating neonatal jaundice and provides a model for meta-analysis of other prospective trials in pediatrics.


Positive influencers for early initiation of breastfeeding.
The practice of newborns being put to the breasts soon after birth results in a reduction in neonatal mortality. Factors such as antenatal care attendance, delivery at the Baby Friendly Hospital Initiative (BFHI) facility, mode of delivery, number of children, and various socio-cultural practices are found to have a positive impact on the early initiation of breastfeeding. The present study was performed to determine the socio-demographic, maternal, and neonatal factors affecting the early initiation of breastfeeding. A hospital-based cross-sectional study was performed at the Immunization Clinic and Nursery situated in a government tertiary care hospital for assessing the pattern of breastfeeding initiation. Children born at the hospital and also those reporting to the clinic from outside were included in the study. Breastfeeding initiation within 1 hour after delivery was only 30%, and 9% did not initiate breastfeeding at all. About half of the reasons for not initiating breastfeeding were related to mothers, followed by 30% related to babies. Upon regression analysis, it was found that urban residence, higher educational status of the mothers, and those mothers who were not counselled on breastfeeding during antenatal visits had higher odds of not initiating breastfeeding and that was statistically significant.


Predictors of survival in recurrent rectal cancer after resection and intraoperative radiotherapy.
This study was designed to determine predictors of survival after surgery and intraoperative radiotherapy for recurrent rectal cancer. From a prospective database, 634 patients undergoing resection for recurrent rectal cancer between January 1990 and June 2000 were identified. Of these, 111 received intraoperative radiotherapy with curative intent, and 100 were available for follow-up. Clinicopathologic variables from both the primary and recurrent operations were evaluated as predictors of disease-free and disease-specific survival by multivariate Cox regression and log-rank test. There were 54 males and 46 females, with a median age of 57 (range, 37-83) years. With a median follow-up of 23.2 months, 60 patients (60 percent) recurred: 20 (33 percent) locally, 27 (45 percent) distantly, and 13 (22 percent) at both sites. Of all variables analyzed, only complete resection with microscopically negative margins and the absence of vascular invasion in the recurrent specimen predicted improved disease-free and disease-specific survival (P < 0.01 for all). Median disease-free survival and median disease-specific survival were 31.2 and 66.1 months, respectively, for complete resection compared with 7.9 and 22.8 months for resection with microscopic or grossly positive margins (P < 0.01 for both). Median disease-free survival and median disease-specific survival were 6.4 and 16.1 months, respectively, in the presence of vascular invasion in the recurrent specimen compared with 23.3 and 57.3 months in the absence of vascular invasion (P < 0.01 and P < 0.05, respectively). Complete resection and the absence of vascular invasion were the only predictors of improved local control as well (P < 0.05 and P < 0.01, respectively). Resection with negative microscopic margins and absence of vascular invasion are independent predictors of local control and improved survival after resection and intraoperative radiotherapy for recurrent rectal cancer.


A Dual Associated-Functional Fluorescent Switch: From Alternate Detection Cycle for Fe(III) and pH to Molecular Logic Operations.
With the expansion and deepening of scientific research, dual-functional or multifunctional materials are urgently needed to replace those for single application. Herein, a fluorescence sensing system based on an In(III)-organic complex with in situ Lewis acid sites has been constructed, exhibiting high sensitivity for the detection of Fe(III) ions with a low detection limit of 3.95 μM and a short response time of within 10 s. It is noteworthy that the quenched fluorescence of the Fe(III)-incorporated sample could be reopened linearly with an increase of alkalinity, followed by the reactivation of its functionality to identify Fe(III) ions, forming an alternate detection cycle for Fe(III) and pH with off-on-off fluorescent switch characteristics. Considering its unique molecular recognition capability, an advanced three-input (Fe(III), EDTA, and OH-) and two-output (B440 and G489) Boolean logic operation comprising BUFF, NOT, OR, and AND logic gates was integrated, possessing potential applications in intelligent multianalyte sensing systems.


Fluorous-Core Nanoparticle-Embedded Hydrogel Synthesized via Tandem Photo-Controlled Radical Polymerization: Facilitating the Separation of Perfluorinated Alkyl Substances from Water.
Per- and polyfluorinated alkyl substances (PFASs) are broadly used as surfactants and water/oil repellents for many decades. However, they are toxic, environmental persistence, and widely detected in water sources. In this work, we developed a fluorous-core nanoparticle-embedded hydrogel (FCH) synthesized by the metal-free tandem photocontrolled radical polymerization under visible-light irradiation. With the FCH material, the scope of absorbable PFASs has been expanded to neutral, anionic, cationic and zwitterionic PFASs with the same adsorbent for the first time. The fluorous nanoparticles exhibited strong and selective affinity toward PFASs without being dramatically influenced by pH levels and background ions, enabling efficient removing of PFASs at high to environmentally relevant concentrations (10 mg/L to 1 μg/L). Furthermore, the FCH network has shown good mechanical performance, facilitating the separation, regeneration, and recycling of adsorbent for multiple runs. These results demonstrate the promise of the FCH material for PFASs separation and adsorbent recycling toward sustainable environment.


Effects of Nd:YAG and CO2 lasers on cerebral microvasculature. Study in normal rabbit brain.
The effect of Nd:YAG and CO2 laser beams on cerebral microvasculature was examined in experimental animals. Soft x-ray microangiography and histological examination of the brain after Nd:YAG laser exposure revealed broad avascular or oligovascular zones in the irradiated and the surrounding edematous tissue, in which the surviving vessels were narrowed and tapered without significant leakage of blood. After CO2 laser exposure, a wedge-shaped tissue defect surrounded by layers of charring, coagulation, and edema was observed. The main finding in the surrounding coagulation and edematous layers was dilatation of the vessels. Hemorrhage was sometimes observed, mainly in the edematous layer. These findings seem to explain the effective hemostatic capability of the Nd:YAG laser and the occasional hemorrhage following CO2 laser exposure, especially at high energy output.


Degree of polarization uniformity with high noise immunity using polarization-sensitive optical coherence tomography.
A new metric representing polarization uniformity is presented. Noise corrected degree of polarization uniformity (DOPU) is computed from polarization-sensitive optical coherence tomography (OCT), and selectively visualizes tissue with the multiple scattering, such as highly pigmented tissues. The new metric is designed to be minimally sensitive to systematic additive noise. The performance of this new metric is analyzed by numerical simulation and in vivo human retinal imaging, using Jones matrix OCT. The new metric exhibited only a small dependency on the signal-to-noise ratio. Selective in vivo visualization of pigmented tissues in the human retina is demonstrated, with cross sectional and en-face images.


An evaluation of a high resolution closed-circuit television link in a hospital radiology department.
We have installed and developed a high resolution closed-circuit television system for transmission of radiographic film images from the emergency room in our hospital to the reading room in our radiology department. Using this system, the radiologist can consult promptly on all films and he has increased efficiency. To transmit high detail images, our television system uses a high resolution vidicon camera with a scan rate of 1029 lines and with a limiting resolution of 1200 TV lines. To further increase the overall diagnostic value of our system, we have added remote controls for changing the magnification, illumination and position of the film. In a preliminary clinical trial, seven radiologists were each shown 27 patient film sets transmitted through the television system and then viewed directly on a conventional view box. An analysis of variance of the accuracy rates in each method showed a statistical difference in methods. Even though the error rate was slightly higher using closed-circuit system, radiologist performance was of acceptable accuracy when considering the advantages of the system. In addition, many of the factors reducing the TV system performance have been eliminated or controlled, and further experiments should reflect an even smaller difference between the two methods.


MMPI-2-RF characteristics of individuals with interstitial cystitis.
This study aimed to describe the psychological functioning of interstitial cystitis/bladder pain syndrome patients utilizing MMPI-2-RF scoring. The MMPI-2 was administered to 60 individuals who reported a diagnosis of IC. Responses were scored in the MMPI-2-RF format. Fifty-one protocols were deemed valid. Elevations were discovered on scales FBS-r (symptom validity), RC1 (somatic complaints), and MLS (malaise). Participants were split into two groups based on extreme elevations on RC1; the high RC1 group produced higher scores on 39 scales including clinically significant elevations on 17 scales. Over 25% of this sample had an emotional component to their physical concerns. This knowledge about the psychological characteristics of IC patients may have clinical utility for physicians and other treatment providers. The results argue strongly for psychological evaluation as a component of IC diagnosis and treatment. Those with significant emotional overlay to their somatic complaints may be best managed through psychological interventions and minimally invasive treatments.


Missed ectopic pregnancies: a report of three cases.
Presented here are three cases of missed ectopic pregnancy which occurred within a four month period in Alabama. In two cases the patients expired. In the third case, following a D&C, continued pelvic pain prompted a repeat pregnancy test and ultrasound, during which ectopic pregnancy was diagnosed. All three of the patients had state of the art ultrasound examinations. An emphasis is placed on interpretation of the examinations and correlation with clinical data.


Biological Invasion Influences the Outcome of Plant-Soil Feedback in the Invasive Plant Species from the Brazilian Semi-arid.
Plant-soil feedback is recognized as the mutual interaction between plants and soil microorganisms, but its role on the biological invasion of the Brazilian tropical seasonal dry forest by invasive plants still remains unclear. Here, we analyzed and compared the arbuscular mycorrhizal fungi (AMF) communities and soil characteristics from the root zone of invasive and native plants, and tested how these AMF communities affect the development of four invasive plant species (Cryptostegia madagascariensis, Parkinsonia aculeata, Prosopis juliflora, and Sesbania virgata). Our field sampling revealed that AMF diversity and frequency of the Order Diversisporales were positively correlated with the root zone of the native plants, whereas AMF dominance and frequency of the Order Glomerales were positively correlated with the root zone of invasive plants. We grew the invasive plants in soil inoculated with AMF species from the root zone of invasive (I changed) and native (I unaltered) plant species. We also performed a third treatment with sterilized soil inoculum (control). We examined the effects of these three AMF inoculums on plant dry biomass, root colonization, plant phosphorous concentration, and plant responsiveness to mycorrhizas. We found that I unaltered and I changed promoted the growth of all invasive plants and led to a higher plant dry biomass, mycorrhizal colonization, and P uptake than control, but I changed showed better results on these variables than I unaltered. For plant responsiveness to mycorrhizas and fungal inoculum effect on plant P concentration, we found positive feedback between changed-AMF community (I changed) and three of the studied invasive plants: C. madagascariensis, P. aculeata, and S. virgata.


Synthesis of chiral polyazamacrocycles of variable ring size.
Synthesis and structure elucidation of optically active tri-, tetra-, and penta-azamacrocycles having 4-methoxyphenyl pendants are described. Regioselective ring opening of a nosylaziridine with secondary benzyl amines was repeatedly performed to afford the cyclization precursors. Intramolecular N-alkylation of N-(omega-haloalkyl) nosylamide provided tri-, tetra-, and penta-azamacrocycles. On the basis of our study of the tetra-azamacrocycle previously elucidated by X-ray single-crystal analysis and in solution by NMR analysis, we conclude that the tri-azamacrocycle does not mainly have a vase-type conformation because of the steric hindrance of the 4-methoxyphenyl groups but the penta-azamacrocycle has a vase-type conformation in CDCl(3) and in CD(2)Cl(2). The vase-type conformation of the penta-azamacrocycle is, however, not as much stable as that observed in the tetra-azamacrocycle because conformational flexibility of the penta-azamacrocycle was observed in deuterated benzene.


Determination and Prediction of Time-Varying Parameters of Mooney-Rivlin Model of Rubber Material Used in Natural Rubber Bearing under Alternating of Aging and Seawater Erosion.
In this paper, we examined the parameters of the Mooney-Rivlin model based on the effects of alternative aging and sea corrosion tests for natural rubber bearings and rubber materials in seawater. The model parameters for rubber material used in natural rubber bearings were determined using the least-squares method. Meanwhile, the time-varying law formula of the Mooney-Rivlin model parameters of rubber were fitted, and the fitting and calculated values were compared. Both fitting values and calculated values coincide with each other well. Then, the rubber material parameters were predicted based on the calculated results and combined with nonlinear auto-regressive (NAR). The predicted values were compared with both the fitting and calculated values. The average deviations between predicted and fitting values for C10 and C01 were 2.6% and 5.1%, respectively, and average deviations between predicted and calculated values for C10 and C01 were 5.2% and 4.1%. Compared results show that the predicted values are in good agreement with both the fitting and calculated values; meanwhile, the proposed time-varying law formula of the Mooney-Rivlin model parameters of rubber material have been well verified.


Bringing the patient back in: behavioral decision-making and choice in medical economics.
We explore the behavioral methodology and "revolution" in economics through the lens of medical economics. We address two questions: (1) Are mainstream economic assumptions of utility-maximization realistic approximations of people's actual behavior? (2) Do people maximize subjective expected utility, particularly in choosing from among the available options? In doing so, we illustrate-in terms of a hypothetical experimental sample of patients with dry eye diagnosis-why and how utility in pharmacoeconomic assessments might be valued differently by patients when subjective psychological, social, cognitive, and emotional factors are considered. While experimentally-observed or surveyed behavior yields stated (rather than revealed) preferences, behaviorism offers a robust toolset in understanding drug, medical device, and treatment-related decisions compared to the optimizing calculus assumed by mainstream economists. It might also do so more perilously than economists have previously understood, in light of the intractable uncertainties, information asymmetries, insulated third-party agents, entry barriers, and externalities that characterize healthcare. Behavioral work has been carried out in many sub-fields of economics. Only recently has it been extended to healthcare. This offers medical economists both the challenge and opportunity of balancing efficiency presumptions with relatively autonomous patient choices, notwithstanding their predictable, yet seemingly consistent, irrationality. Despite its comparative youth and limitations, the scientific contributions of behaviorism are secure and its future in medical economics appears to be promising.


Maternal weight correction of maternal serum PAPP-A and free beta-hCG MoM when screening for trisomy 21 in the first trimester of pregnancy.
To assess the suitability of either the log-linear or reciprocal-linear regression procedure for maternal weight correction of biochemical marker MoMs in the first trimester. Data from two prospective first-trimester OSCAR screening programmes including 32,010 women with first-trimester maternal serum-free beta-hCG and PAPP-A measured by the Kryptor analyser was analysed by regression analysis to provide parameters for the log-linear and reciprocal-linear MoM correction procedures. Assessment was made by goodness of fit to the data. The impact on detection rate and false-positive rate of the different correction procedures was assessed using statistical modelling with biochemical markers alone. Both log-linear and reciprocal-linear correction were shown to fit the data well. For free beta-hCG, the log-linear procedure was marginally superior to the reciprocal-linear procedure (r2=0.986 v 0.980), whilst for PAPP-A the reciprocal-linear procedure was marginally better (r2=0.991 v 0.985). Log-linear correction reduced the variance for both markers more than did the reciprocal-linear procedure. For free beta-hCG, the sd was reduced from 0.2675 to 0.2605 and for PAPP-A, it was reduced from 0.2545 to 0.2336. Correcting for maternal weight was shown to reduce the population false-positive rate from 7.0 to 6.5%, whilst maintaining the same detection rate at a risk cut-off of 1 in a 100. At individual levels, a two-fold variation in risk was demonstrated depending upon the individual's weight. To provide accurate individual patient-specific risks for trisomy 21, maternal weight must be taken into account and should be a mandatory data item for screening programmes. Maternal weight correction in the first trimester using free beta-hCG and PAPP-A can be best achieved using the log-linear procedure.


Mechanisms and regulations of ferroptosis.
Regulation of cell mortality for disease treatment has been the focus of research. Ferroptosis is an iron-dependent regulated cell death whose mechanism has been extensively studied since its discovery. A large number of studies have shown that regulation of ferroptosis brings new strategies for the treatment of various benign and malignant diseases. Iron excess and lipid peroxidation are its primary metabolic features. Therefore, genes involved in iron metabolism and lipid metabolism can regulate iron overload and lipid peroxidation through direct or indirect pathways, thereby regulating ferroptosis. In addition, glutathione (GSH) is the body's primary non-enzymatic antioxidants and plays a pivotal role in the struggle against lipid peroxidation. GSH functions as an auxiliary substance for glutathione peroxidase 4 (GPX4) to convert toxic lipid peroxides to their corresponding alcohols. Here, we reviewed the researches on the mechanism of ferroptosis in recent years, and comprehensively analyzed the mechanism and regulatory process of ferroptosis from iron metabolism and lipid metabolism, and then described in detail the metabolism of GPX4 and the main non-enzymatic antioxidant GSH in vivo.


Surveillance of antibiotic and analgesic use in the Oral Surgery Department of the University Dentistry Clinical Center of Kosovo.
Because Kosovo has no reliable information on antimicrobial and analgesic use in dental practice, the survey reported here evaluated the antibiotic and analgesic prescriptions in the Oral Surgery Department of the University Dentistry Clinical Center of Kosovo (UDCCK). The data of 2,442 registered patients for a 1-year period were screened and analyzed concerning antibiotic and analgesic use as per standards of rational prescription. Dentistry doctors prescribed antibiotics significantly more often than analgesics. Antibiotics were prescribed in 8.11% of all cases, while only 1.35% of total prescriptions were for analgesics. The total consumption of antibiotic drugs in the UDCCK was 4.53 Defined Daily Doses [DDD]/1,000 inhabitants/day, compared with only 0.216 DDD/1,000 inhabitants/day for analgesics. From a total number of 117 patients, 32 patients received combinations of two antibiotics. Pharmacotherapy analysis showed that the prescription rates of antibiotics and analgesics in the UDCCK are not rational in terms of the qualitative aspects of treatment. For the qualitative improvement of prescription of these drug groups, we recommend the implementation of treatment guidelines following rational standards.


Penetrating injury of the tuberculum sellae.
An unusual case of perforation of the tuberculum sellae and right ethmoid bone by a 10-in. serrated bread knife is described. The patient survived with no neurological or endocrine deficit. The importance of preoperative angiography and control of the proximal and distal vasculature is stressed.


The role of myocardial fibrosis in determining the success rate of ablation for the treatment of atrial fibrillation.
Atrial fibrillation is the most common sustained cardiac arrhythmia and with an aging population its prevalence will increase. In addition to appropriate anticoagulation to reduce the thromboembolic risk, there has been an increasing need for a personalized approach in identifying which patients are likely to benefit more from atrial fibrillation ablation procedures. This review will discuss the role of myocardial fibrosis in patients with atrial fibrillation, its mechanistic role, association with biomarkers and how this could potentially be of use in the development of a risk score identifying the success of maintaining sinus rhythm following an electrophysiological ablation.


[CLINGING LESSER TROCHANTER OSTEOTOMY WITH WAGNER CONE IN TREATMENT OF CROWE TYPE IV DEVELOPMENTAL DYSPLASIA OF THE HIP IN ADULT].
To investigate the effectivness of the clinging lesser trochanter osteotomy with the Wagner cone in total hip arthroplasty (THA) for Crowe type IV developmental dysplasia of the hip (DDH) in adult. Between November 2009 and September 2012, 7 female patients (9 hips) with Crowe type IV DDH were treated by THA procedures of clinging lesser trochanter osteotomy with Wagner cone, aged 24-62 years (mean, 42 years). All patients experienced severe pain and claudication. The left hip was involved in 2 cases, the right hip in 3 cases, and bilateral hips in 2 cases. The Harris score of involved hip was 50.00?7.04. The both limps were discrepancy with an average length difference of 3.4 cm (range, 3-4 cm). The results of Trendelenburg sign were positive. X-ray films showed high complete dislocation of the involved hips. The incisions healed by first intention. There was no complication such as infection, dislocation, prosthesis loosening, neurovascular injury. The average follow-up was 36.4 months (range, 25-48 months). Pain and claudication were improved and all patients could restore to work. The Harris score was improved to 83.42 +/- 6.47, showing significant difference when compared with preoperative score (t=8.90, P=0.00). The results of Trendelenburg sign were negative. X-ray films showed that all patients got a bony union at osteotomy site of greater trochanter at 3-6 months after operation. And the interface between prosthesis and bone was stable. There was no prosthesis loosening or sinking during the follow-up. Clinging lesser trochanter osteotomy with Wagner cone could be an option to shorten the femur in THA for patients with Crowe type IV DDH. It is effective in decreasing the risk of neurovascular injury.


Synthesis and identification of hydroxylated metabolites of the anti-estrogenic agent cyclofenil.
The detection of metabolites of the anti-estrogenic substance cyclofenil, listed on the World Anti-Doping Agency (WADA) Prohibited List since 2004 is described. Target substances are hydroxylated metabolites, bearing an aliphatic hydroxyl group either in the 2-, 3- or 4-position of the aliphatic ring, in addition to the phenolic functions on the aromatic rings. Structural identification used NMR as well as high-resolution mass spectrometry after nano-electrospray ionisation (ESI). Unambiguous detection of all three synthesised cyclofenil metabolites M1-M3 was done using gas chromatography for separation and electron ionisation mass spectrometry for detection of the per-silylated compounds in comparison with a reference urine deriving from an excretion study within the WADA 2007 Educational Programme.


Engineering a Bifunctional Phr60-Rap60-Spo0A Quorum-Sensing Molecular Switch for Dynamic Fine-Tuning of Menaquinone-7 Synthesis in Bacillus subtilis.
Quorum sensing (QS)-based dynamic regulation has been widely used as basic tool for fine-tuning gene expression in response to cell density changes without adding expensive inducers. However, most reported QS systems primarily relied on down-regulation rather than up-regulation of gene expression, significantly limiting its potential as a molecular switch to control metabolic flux. To solve this challenge, we developed a bifunctional and modular Phr60-Rap60-Spo0A QS system, based on two native promoters, PabrB (down-regulation by Spo0A-P) and PspoiiA (up-regulation by Spo0A-P). We constructed a library of promoters with different capacities to implement down-regulation and up-regulation by changing the location, number, and sequences of the binding sites for Spo0A-P. The QS system can dynamically balance the relationship between efficient synthesis of the target product and cell growth. Finally, we validated the usefulness of this strategy by dynamic control of menaquinone-7 (MK-7) synthesis in Bacillus subtilis 168, a model Gram-positive bacterium, with the bifunctional Phr60-Rap60-Spo0A quorum sensing system. Our dynamic pathway regulation led to a 40-fold improvement of MK-7 production from 9 to 360 mg/L in shake flasks and 200 mg/L in 15-L bioreactor. Taken together, our bilayer QS system has been successfully integrated with biocatalytic functions to achieve dynamic pathway regulation in B. subtilis 168, which may be extended for use in other microbes to fine-tune gene expression and improve metabolites production.


Impaired sperm function in infertile men relies on the membrane sterol pattern.
Membrane cholesterol removal appears a key step for the gain of fertility potential during sperm maturation. However, the membrane sterol pattern in sperm cells from infertile patients, with impaired sperm parameters, has been poorly investigated. To elucidate a causative link between sperm membrane composition in male fertility, here we have investigated the levels of cholesterol and its oxidized derivatives 7β-hydroxycholesterol and 7-keto-cholesterol in sixteen infertile patients with oligo-asthenozoospermia and 16 normozoospermic (N) fertile subjects. Furthermore, ten of 16 N fertile subjects agreed to receive a defined testicular thermal challenge by adhering to a programme of sauna sessions for 1 month. Semen samples were obtained from each of the participants, and sperm parameters were assessed according to the World Health Organization criteria. Sperm levels of cholesterol, 7β-hydroxycholesterol and 7-keto-cholesterol were quantified by ultra-pressure liquid chromatography mass spectrometry. The results showed that oligo-asthenozoospermia patients had a huge amount of cholesterol content compared with fertile subjects (12.40 ± 6.05 μg/106 cells vs. 0.45 ± 0.28 μg/106 cells, p < 0.001, N and oligo-asthenozoospermia, respectively). Also, oxidized derivatives were significantly higher in oligo-asthenozoospermia patients (7β-hydroxycholesterol: 1.96 ± 1.03 ng/106 cells vs. 0.075 ± 0.05 ng/106 cells, p < 0.001 and 7-keto-cholesterol: 1.11 ± 0.72 ng/106 cells vs. 0.005 ± 0.003 ng/106 cells, p < 0.001). Moreover, sauna exposure, in parallel with a progressive worsening of sperm motility parameters, was associated with a reversible increase in sperm cholesterol after the third and fourth week of treatment, whilst 7β-hydroxycholesterol and 7-keto-cholesterol levels showed an earlier enhancement starting from the second week. Our data show for the first time in humans a strong difference in the cholesterol and its oxidized derivatives of infertile and fertile subjects. These findings suggest a strict biochemical link relating testis function, sperm membrane status and male fertility potential.


MPS-1 is a K+ channel beta-subunit and a serine/threonine kinase.
We report the first example of a K+ channel beta-subunit that is also a serine/threonine kinase. MPS-1 is a single-transmembrane domain protein that coassembles with voltage-gated K+ channel KVS-1 in the nervous system of the nematode Caenorhabditis elegans. Biochemical analysis shows that MPS-1 can phosphorylate KVS-1 and other substrates. Electrophysiological analysis in Chinese hamster ovary (CHO) cells demonstrates that MPS-1 activity leads to a significant decrease in the macroscopic current. Single-channel analysis and biotinylation assays indicate that MPS-1 reduces the macroscopic current by lowering the open probability of the channel. These data are consistent with a model that predicts that the MPS-1-dependent phosphorylation of KVS-1 sustains cell excitability by controlling K+ flux.


Polymorphic changes of mannitol during freeze-drying: effect of surface-active agents.
The effect of polysorbate 80 on the crystalline properties of mannitol during freeze-drying was studied. Crystallinity and polymorphism play an important role in, e.g., the solubility and stability of freeze-dried products. Polysorbate 80 had an effect on both the polymorphism and the crystallinity of freeze-dried mannitol.


Expression of plasminogen activator as a marker of stimulation in tumor-associated macrophages.
Tumor-associated macrophages (TAM) are a peculiar subpopulation of resident phagocytes with activities possibly important at the tumor host interface. Among these activities the production of proteases could obviously influence tumor cell detachment and migration from the primary. We have evaluated the expression of plasminogen activator (PA) in different types of murine tumors with differing immunogenic capacity. In TAM from all tumors studied the expression of PA was markedly greater than that of resident peritoneal macrophages. The fact that PA was similarly enhanced in peritoneal macrophages responding to a standard stimulation (thioglycolate) and in TAM suggests that the expression of PA is part of a more general cellular inflammatory response to injury.


Speech and non-speech processing in hemispherectomised children: an event-related potential study.
Although hemispherectomy is now used as a radical treatment for intractable seizures in a number of centres, there have been limited electrophysiological studies investigating post-procedure auditory-speech processing and recovery or reorganisation. We therefore recorded auditory event-related potentials (ERPs) evoked by pure tones and syllables employing a 51-channel electrode array concentrated over the functional hemisphere in 17 patients (nine males, mean age 14.2 years) who had undergone hemispherectomy for intractable seizures; eight of the patients had congenital brain damage and nine had sustained their initial insult at an age of 1 year or older. For comparison, recordings were made from 10 controls (five males, mean age 13.5 years). Responses from patients consisted of five small amplitude components restricted to the functional hemisphere whose scalp polarity was opposite to the ERPs observed in control subjects. The topography of the auditory ERPs in the patients was localised to the centro-temporal regions of the functional hemisphere in comparison to the midline distribution observed in control subjects. As in the control subjects, the latencies of the components evoked by tones were shorter than those evoked by syllables in both left and right hemispherectomised children. In addition, further analysis of the N1 and P2 component revealed increased syllable latencies in left hemispherectomised children only. The results of this study suggest that the left hemisphere alone may be more efficient at processing both pure tones and syllables compared to the right or both together.


Induction of Sestrin2 by pterostilbene suppresses ethanol-triggered hepatocyte senescence by degrading CCN1 via p62-dependent selective autophagy.
Hepatocyte senescence is a key event participating in the progression of alcoholic liver disease. Autophagy is a critical biological process that controls cell fates by affecting cell behaviors like senescence. Pterostilbene is a natural compound with hepatoprotective potential; however, its implication for alcoholic liver disease was not understood. This study was aimed to investigate the therapeutic effect of pterostilbene on alcoholic liver disease and elucidate the potential mechanism. Our results showed that pterostilbene alleviated ethanol-triggered hepatocyte damage and senescence. Intriguingly, pterostilbene decreased the protein abundance of cellular communication network factor 1 (CCN1) in ethanol-exposed hepatocytes, which was essential for pterostilbene to execute its anti-senescent function. In vivo studies verified the anti-senescent effect of pterostilbene on hepatocytes of alcohol-intoxicated mice. Pterostilbene also relieved senescence-associated secretory phenotype (SASP), redox imbalance, and steatosis by suppressing hepatic CCN1 expression. Mechanistically, pterostilbene-forced CCN1 reduction was dependent on posttranscriptional regulation via autophagy machinery but not transcriptional regulation. To be specific, pterostilbene restored autophagic flux in damaged hepatocytes and activated p62-mediated selective autophagy to recognize and lead CCN1 to autolysosomes for degradation. The protein abundance of Sestrin2 (SESN2), a core upstream modulator of autophagy pathway, was decreased in ethanol-administrated hepatocytes but rescued by co-treatment with pterostilbene. Induction of SESN2 protein by pterostilbene rescued ethanol-triggered autophagic dysfunction in hepatocytes, which then reduced senescence-associated markers, postponed hepatocyte senescence, and relieved alcohol-caused liver injury and inflammation. In conclusion, this work discovered a novel compound pterostilbene with therapeutic implications for alcoholic liver disease and uncover its underlying mechanism.


A High-Throughput Screening Strategy to Identify Inhibitors of SSB Protein-Protein Interactions in an Academic Screening Facility.
Antibiotic-resistant bacterial infections are increasingly prevalent worldwide, and there is an urgent need for novel classes of antibiotics capable of overcoming existing resistance mechanisms. One potential antibiotic target is the bacterial single-stranded DNA binding protein (SSB), which serves as a hub for DNA repair, recombination, and replication. Eight highly conserved residues at the C-terminus of SSB use direct protein-protein interactions (PPIs) to recruit more than a dozen important genome maintenance proteins to single-stranded DNA. Mutations that disrupt PPIs with the C-terminal tail of SSB are lethal, suggesting that small-molecule inhibitors of these critical SSB PPIs could be effective antibacterial agents. As a first step toward implementing this strategy, we have developed orthogonal high-throughput screening assays to identify small-molecule inhibitors of the Klebsiella pneumonia SSB-PriA interaction. Hits were identified from an initial screen of 72,474 compounds using an AlphaScreen (AS) primary screen, and their activity was subsequently confirmed in an orthogonal fluorescence polarization (FP) assay. As an additional control, an FP assay targeted against an unrelated eukaryotic PPI was used to confirm specificity for the SSB-PriA interaction. Nine potent and selective inhibitors produced concentration-response curves with IC50 values of <40 μM, and two compounds were observed to directly bind to PriA, demonstrating the success of this screen strategy.


Sexual transmission of SIVagm in wild grivet monkeys.
This study reports the prevalence of simian immunodeficiency virus and the relationship of serostatus to age and sex among a wild population of Ethiopian grivet monkeys (Cercopithecus aethiops aethiops). Seropositivity paralleled patterns of sexual activity, being nearly universal in females of reproductive age, and absent in all males except those that were fully adult. One female seroconverted between two capture seasons at an age consistent with first breeding. Our findings support a predominantly sexual mode of transmission among SIVagm infected grivets.


It's Time to Stop Kicking People Out of Addiction Treatment.
Interventions by professional helpers that are later recognized as ineffective or even harmful have a long and colorful history. Some of the most widely practiced of such interventions have left later generations pondering, "What on earth were they thinking?" Lectures on the history of addiction treatment stir feelings of enlightened condescension amidst tales of treating morphine addiction with cocaine and other such idiocies, but occasionally a conference attendee asks the tough question: "How will the current era of addiction treatment be judged in the future?" And, of course, that is the rub, because it is so difficult to clearly see our own professional miscues and mistakes without the benefit of historical hindsight. This essay explores one practice-administratively discharging clients from addiction treatment-that we suspect will be judged harshly by historians of the not so distant future.


Low-dose streptokinase for selective thrombolysis: systemic effects and complications.
The systemic effects and complications associated with the infusion of low-dose (5,000 U/hr) intravascular streptokinase were reviewed in 159 patients. Eighty-two percent of the patients had a 50% decrease in plasma fibrinogen levels during the first 4 hours of treatment, and 100% of the patients showed the same decline following 12 hours of treatment. The thrombin time was prolonged to at least 1 1/2 times the control thrombin time in 42% of the patients at 4 hours of treatment and in 92% at 24 hours of treatment. The rate or degree of change in fibrinogen levels or prolongation of the thrombin time did not correlate with the incidence of complications. Seventeen patients (10.7%) suffered major complications. Thirteen of the 17 had hemorrhagic complications, three had thrombotic or embolic complications, and one had a false aneurysm. In this series, systemic effects occurred in all patients. It is concluded that, despite precautionary measures, hemorrhagic complications may occur. Steps should be taken to minimize complications, including careful observation of the patient and monitoring of plasma fibrinogen levels until adequate regeneration is complete.


Adhesion of annexin 7 deficient erythrocytes to endothelial cells.
Annexin 7 deficiency has previously been shown to foster suicidal death of erythrocytes or eryptosis, which is triggered by increase of intracellular Ca(2+) concentration ([Ca(2+)](i)) and characterized by cell shrinkage and cell membrane scrambling with subsequent phosphatidylserine exposure at the cell surface. Eryptosis following increase of [Ca(2+)](i) by Ca(2+) ionophore ionomycin, osmotic shock or energy depletion was more pronounced in erythrocytes from annexinA7-deficient mice (anxA7(-/-)) than in erythrocytes from wild type mice (anxA7(+/+)). As phosphatidylserine exposure is considered to mediate adhesion of erythrocytes to the vascular wall, the present study explored adhesion of erythrocytes from anx7(-/-) and anx7(+/+)-mice following increase of [Ca(2+)](i) by Ca(2+) ionophore ionomycin (1 µM for 30 min), hyperosmotic shock (addition of 550 mM sucrose for 2 hours) or energy depletion (removal of glucose for 12 hours). Phosphatidylserine exposing erythrocytes were identified by annexin V binding, cell volume estimated from forward scatter in FACS analysis and adhesion to human umbilical vein endothelial cells (HUVEC) utilizing a flow chamber. As a result, ionomycin, sucrose addition and glucose removal all triggered phosphatidylserine-exposure, decreased forward scatter and enhanced adhesion of erythrocytes to human umbilical vein endothelial cells (HUVEC), effects significantly more pronounced in anx7(-/-) than in anx7(+/+)-erythrocytes. Following ischemia, morphological renal injury was significantly higher in anx7(-/-) than in anx7(+/+)-mice. The present observations demonstrate that enhanced eryptosis of annexin7 deficient cells is paralleled by increased adhesion of erythrocytes to the vascular wall, an effect, which may impact on microcirculation during ischemia.


Acute pancreatitis in a cohort of 129 patients referred for severe hypertriglyceridemia.
The aim of this study was to assess retrospectively the prevalence and the predictive factors of acute pancreatitis (AP) in a population of patients referred in our endocrinology department for evaluation of very high triglyceride (TG) levels. One hundred twenty-nine patients (119 with type IV phenotypes and 10 with type V phenotypes according to Fredrickson's classification) were referred to our hospital between 2000 and 2005. Twenty-six subjects (20.2% of the population) presented with AP. This population was significantly younger at diagnosis of hyperlipidemia (32 vs 40 years, P < 0.001) and at age of investigation (43 vs 48 years, P = 0.05) and had maximum TG levels greater than the population without AP (44.7 vs 24.5, P < 0.001). Subjects of the third tertile of TG levels had a 4.0-fold increased risk (95% confidence interval, 1.3-12.3) of AP compared with the first tertile. Severe pancreatitis (need for intensive care, C-reactive protein >150 mg/L, or Balthazar score >C) was observed in 71.5% of the patients. Twenty percent of patients with severe hypertriglyceridemia experience at least 1 attack of AP. Pancreatitis seems to occur in young patients at higher levels of TG than previously thought (85% of patients >30 g/L) and is associated with a severe clinical course.


Delayed administration of G-CSF until day +7 after autologous peripheral blood stem cell transplant is as effective in accelerating hematopoietic as day 0.
To compare the hematopoietic recovery and the clinical outcome after high dose chemotherapy and peripheral blood stem cell (PBSC) transplant between patients who received recombinant granulocyte colony-stimulating factor (G-CSF) starting on day 0 and those who received it starting on day +7. Thirty-five consecutive patients received high dose chemotherapy with ifosfamide, etoposide and carboplatin (ICE) and autologous PBSC transplant. PBSC mobilization was achieved with G-CSF. In 19 transplants done in 1994, G-CSF was started on day 0 and in 16 procedures done in 1995, G-CSF was started on day +7. In both groups G-CSF was given until the absolute neutrophil count was 1 x 10(9)/L. The median number of days to reach an absolute neutrophil count > 0.1 x 10(9)/L, was 11 in the patients who started the G-CSF on day 0 and 11 days in the patients with delayed administration of G-CSF and to reach > 0.5 x 10(9)/L 14 days and 13 respectively. The median number of days to reach a platelet count > 20 x 10(9)/L was 14 and 13. Comparison of early vs. delayed administration of G-CSF did not show any significant differences regarding the time to achieve platelet independence, number of days with fever, median days of hospital stay, number of red cell or platelet transfusions. Starting G-CSF on day +7 after high dose ICE chemotherapy and autologous transplant of PBSC is as effective in restoring the hematopoietic function as is starting its administration on day 0.


Associations between prevalence of adult atopic dermatitis and occupational characteristics.
To examine the prevalence of adult atopic dermatitis according to occupational status. While atopic dermatitis is more prevalent among children, some adults also suffer from it. The disease causes considerable difficulty in these adults' social lives at school or work, suggesting that they require high-quality health care. Given the chronic nature and environmental determinants of atopic dermatitis, its associations with occupational characteristics must be clarified. An exploratory cross-sectional analysis using secondary data. Participants were 662 people diagnosed with atopic dermatitis, all 19 years old or older; raw data were taken from the Korea National Health and Nutrition Examination Survey V (2010-2012) and VI (2013-2014). Manual workers (adjusted odds ratio 2.50, 95% confidence interval, 1.30-4.83), paid workers (1.70, 1.15-2.51), regular workers (1.83, 1.18-2.85), and full-time workers (1.88, 1.23-2.89) all showed increased odds of currently suffering from atopic dermatitis. Prevalence rates of atopic dermatitis differed by occupational characteristics, which suggests the need for interventions seeking to prevent symptom recurrence that are tailored to occupational characteristics. We expect this study to provide helpful baseline data for better policy-making.


Rapid serodiagnosis of typhoid fever by dot enzyme immunoassay in an endemic area.
A dot enzyme immunoassay (EIA) using 50-kD outer-membrane proteins (OMPs) of Salmonella typhi was compared with the Widal test for the serodiagnosis of typhoid fever in 109 febrile children admitted to a hospital in an endemic area. In the culture-positive typhoid group, the initial dot EIA was positive in 40 of 42 cases and the initial Widal test was positive in 41. In the culture-negative clinical typhoid group, both the dot EIA and the Widal test were positive in 17 of 18 cases. In the nontyphoidal fever group, the dot EIA was negative in all of 49 cases and the Widal test was negative in 44. With culture used as the gold standard, the dot EIA is as sensitive as the Widal test (95% vs. 98%), has a similar high negative predictive value (96% vs. 98%), and is more specific (75% vs. 67%). In addition, the dot EIA offers the advantages of simplicity, speed, early diagnosis, economy, and flexibility (i.e., other diagnostic tests can be conducted simultaneously).


Frequency and phase synchronization in large groups: Low dimensional description of synchronized clapping, firefly flashing, and cricket chirping.
A common observation is that large groups of oscillatory biological units often have the ability to synchronize. A paradigmatic model of such behavior is provided by the Kuramoto model, which achieves synchronization through coupling of the phase dynamics of individual oscillators, while each oscillator maintains a different constant inherent natural frequency. Here we consider the biologically likely possibility that the oscillatory units may be capable of enhancing their synchronization ability by adaptive frequency dynamics. We propose a simple augmentation of the Kuramoto model which does this. We also show that, by the use of a previously developed technique [Ott and Antonsen, Chaos 18, 037113 (2008)], it is possible to reduce the resulting dynamics to a lower dimensional system for the macroscopic evolution of the oscillator ensemble. By employing this reduction, we investigate the dynamics of our system, finding a characteristic hysteretic behavior and enhancement of the quality of the achieved synchronization.


Trait Hostility and Acute Inflammatory Responses to Stress in the Laboratory.
Hostility has been associated with higher basal levels of inflammation. The present study evaluated the association of hostility with acute stress-induced changes in inflammatory activity. One hundred and ninety-nine healthy men and women, aged 19-64 years, were exposed to a stress protocol involving four interpersonal stressors. Participants completed the Cook-Medley Hostility questionnaire and provided two blood samples for the measurement of inflammatory biomarkers (CRP, Il-6, MPO, TNF-α, MCP-1, Il-8, Il-10, and Il-18), prior to and following exposure to a standardized stress protocol. In univariate analyses, hostility was associated with significantly higher TNF-α, but lower Il-8 and Il-18 values post-stress, though only Il-8 remained significant after controlling for baseline differences. In multivariate analyses, a significant Age by Hostility interaction emerged for Il-6, while sex moderated the relation between hostility and Il-10 reactivity. Following stress, hostility was associated with greater pro-inflammatory Il-6 activity among younger individuals and to decreased anti-inflammatory Il-10 activity in women. Future research is needed to replicate these findings and to evaluate their implication for disease.


A20 regulates lymphocyte adhesion in murine neuroinflammation by restricting endothelial ICOSL expression in the CNS.
A20 is a ubiquitin-modifying protein that negatively regulates NF-κB signaling. Mutations in A20/TNFAIP3 are associated with a variety of autoimmune diseases, including multiple sclerosis (MS). We found that deletion of A20 in central nervous system (CNS) endothelial cells (ECs) enhances experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. A20∆CNS-EC mice showed increased numbers of CNS-infiltrating immune cells during neuroinflammation and in the steady state. While the integrity of the blood-brain barrier (BBB) was not impaired, we observed a strong activation of CNS-ECs in these mice, with dramatically increased levels of the adhesion molecules ICAM-1 and VCAM-1. We discovered ICOSL as adhesion molecule expressed by A20-deficient CNS-ECs. Silencing of ICOSL in CNS microvascular ECs partly reversed the phenotype of A20∆CNS-EC mice without reaching statistical significance and delayed the onset of EAE symptoms in wildtype mice. In addition, blocking of ICOSL on primary mouse brain microvascular endothelial cells (pMBMECs) impaired the adhesion of T cells in vitro. Taken together, we here propose that CNS EC-ICOSL contributes to the firm adhesion of T cells to the BBB, promoting their entry into the CNS and eventually driving neuroinflammation.


Roux-En-Y gastric bypass following failed fundoplication.
Roux-En-Y gastric bypass (RYGB) is an alternative to reoperative fundoplication. The aim of this study was to expand long-term outcomes of patients undergoing RYGB after failed fundoplication and assess symptom resolution. A single institution prospective study was performed of patients undergoing fundoplication takedown and RYGB between March 2007 and September 2016. Demographics, body mass index (BMI), preoperative symptoms, operative duration and findings, and postoperative outcomes were recorded. Data were assessed using standard statistical methods. 87 patients with failed antireflux surgery underwent RYGB. Median age 58 years (range 25-79 years). Median preoperative BMI 32.4 kg/m2 (range 21.6-50.6 kg/m2). Comorbidities included hypertension (48.3%) and diabetes (11.5%). Sixty-six patients had undergone 1 prior fundoplication, 18 had 2 prior fundoplications, and 3 had 3 prior fundoplications. At least one previous open antireflux procedure had been performed in 16.1% of patients. The most common recurrent symptoms were reflux (85.1%), dysphagia (36.7%), pain (35.6%), and regurgitation (29.9%). Median symptom-free interval from last antireflux surgery was 3 years (range 0-25 years). RYGB was performed laparoscopically in 47.1% of cases, robotically in 44.8% of cases, and open in 5.9%. Operative duration was longer in the robotic group (p = 0.04). During RYGB, 85.1% patients were found to have an associated hiatal hernia, 34.5% had intrathoracic migration of the fundoplication, 32.2% a slipped fundoplication onto proximal stomach, and 13.8% had wrap disruption. Median length of stay (LOS) was 4 days (range 1-33 days). Median follow-up was 35.8 months, 11 patients (12.6%) had recurrent reflux symptoms. Excess body weight loss (%EWL) was 80.4%. There was no mortality but 8 patients required reoperation during follow-up. Fundoplication takedown with RYGB was successful for long-term reflux resolution. Most can be performed via a minimally invasive approach with acceptable perioperative morbidity, symptom resolution, and the additional benefit of %EWL.


A Study on Preparation and Stabilizing Mechanism of Hydrophobic Silica Nanofluids.
Nanofluids have increasingly drawn interest in recent years with their various applications in a number of fields. The method for the preparation of stable nanofluids is a key concern for extending the application of nanofluids. This study focuses on the effect of pH, dosage of surfactant (TX-100), and nanofluid concentration on the stability of a silica nanofluid. Particle size and zeta potential are two important factors to consider in evaluating the stability of the silica nanofluid. Results indicate that the stability of the silica nanofluid highly depends on pH, dosage of surfactant (TX-100), and nanofluid concentration. On the basis of these experiments, the best conditions for the preparation of a silica nanofluid are 0.1 wt. % for the concentration of silica nanoparticles and TX-100 and 10 for pH. A transparent and stable silica nanofluid can thus be obtained.


Interleukin-31 promotes helper T cell type-2 inflammation in children with allergic rhinitis.
Interleukin-31 (IL-31) is a recently described cytokine that is involved in helper T cell type-2 (Th2)-mediated diseases. However, its regulatory effect in the pathogenesis of children allergic rhinitis (AR) needs to be further characterized. This study sought to evaluate the expression and role of IL-31 in children with AR. Sixty children with AR and 20 normal controls were included. IL-31 and Th2 cytokines production in tissue, serum, and nasal lavage was examined by immunohistochemistry, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay, respectively. Peripheral blood mononuclear cells (PBMCs) were purified for in vitro regulation experiment of IL-31. Nasal epithelial cells (NECs) were cultured and stimulated by recombinant IL-31. The IL-31 mRNA and protein levels in both serum and nasal lavage were significantly enhanced in AR compared with normal controls, especially in children with asthma. The nasal IL-31 was associated with enhanced local Th2 cytokines and mucin 5AC (MUC5AC) expression. In vitro study showed that IL-31 promotes Th2 cytokines expression and MUC5AC upregulation and thus amplified Th2 inflammation. Our results demonstrate that IL-31 expression in AR aggravated and amplified Th2 inflammation as well as mucin production, and provide a possible explanation for IL-31's regulatory role in the pathogenesis of AR.


Copy-number variation in control population cohorts.
Copy-number variation (CNV) is the most prevalent type of structural variation in the human genome, and contributes significantly to genetic heterogeneity. It has already been recognized that some CNVs can contribute to human phenotype, including rare genomic disorders and Mendelian diseases. Other CNVs are now amenable to genome-wide association studies so that their influence on human phenotypic diversity and disease susceptibility may soon be more readily determined. Population studies and reference databases for control and disease-associated samples are required to provide an information resource about CNV frequencies and their relative contribution to phenotypic outcomes. The relatively high cost of screening individual samples has tended to limit the number of controls assayed, and use of the data has often been hampered by the variety of technology platforms and analysis techniques. As a result, there is still a paucity of data on population frequency and distribution of CNVs, particularly for those that are rare. Here, we provide an example of how to discover new CNVs from existing genotype data from large-scale genetic epidemiological studies. We also discuss the need to expand surveys of CNV in different population-based cohorts and to apply the information to studies of human variation and disease.


Enhancing the natural folate level in wine using bioengineering and stabilization strategies.
Folate deficiency is linked to many diseases, some of which may have higher probability in individuals with alcohol-induced alterations in one-carbon metabolism. Our study shows that folate content in commercial wine is not related to white or red varieties, but associated with the yeast that is used to produce the wine. The stability of folate in these wines, once opened for consumption, did not correlate with total phenolic or sulfite content. In addition, we employed yeast bioengineering to fortify wine with folate. We confirmed by overexpression that FOL2 was the key gene encoding the rate-limiting step of folate biosynthesis in wine yeast. In this study, we also show that overexpression of other folate biosynthesis genes, including ABZ1, ABZ2, DFR1, FOL1 and FOL3, had no effect on folate levels in wine. Ensuring stability of the increased natural folate in all wines was achieved by the addition of ascorbate.


Imidazolylidene carbene ligated palladium catalysis of the Heck reaction in the presence of air.
Five 1,3-disubstituted imidazolium salts were synthesized. Their Heck reaction activities were evaluated. A convenient, efficient and high yielding procedure based on these compounds for the arylation of olefins was developed. Heck reactions mediated by these palladium-N-heterocyclic carbene complexes were conducted under air and even in the presence of several common oxidants.


Impact of systolic blood pressure on cardiovascular prognosis.
Traditionally, diastolic rather than systolic blood pressure has been regarded as the main risk factor for cardiovascular complications in hypertension. While this remains valid for clinical hypertensive emergencies (accelerated and malignant hypertension), it is becoming increasingly clear that the risk of incurring the more distant cardiovascular complications in chronic 'benign' hypertension is associated with the systolic rather than the diastolic component of arterial pressure. Assessment of increased systolic pressure as a risk factor in its own right has been based on three epidemiological approaches. First, the impact of systolic pressure per se was examined by statistical evaluation of prospectively studied populations with different blood pressures. Second, selected subgroups with 'isolated' systolic hypertension were followed up. A third assessment was based on the results of therapeutic trials. All three assessments confirm that systolic pressure is likely to become the main criterion in the evaluation of hypertension, particularly in the elderly.


[Cytokines and hematopoiesis].
The identification and purification of haemopoietic growth regulators have resulted in a better understanding of control mechanisms. Cloning and expression of the corresponding genes have shown that most of the activities observed correspond to specific glycoproteins produced by cells from numerous tissues, including those of bone marrow stroma and immune system. These cytokines activate the responsive cells through specific receptors expressed on their membranes. They exert an accurate control of haematopoiesis in a network of synergistic and antagonistic factors. The exact identification of their biological activities, together with the possibility of producing them in large amounts by genetic recombination, have already resulted in their therapeutic use with, in certain cases, a remarkable efficiency.


[Experimental studies relative to the persistence of several facultative pathogenic fungi in river water].
Under laboratory conditions survival time of 3 fungi species (Candida albicans, Geotrichum candidum, Rhodotorula rubra) in river water of various quality and temperature has been studied. The mean (and the maximum) survival time was as follows: 82 (240) d for C. albicans, 210 (578) d for G. candidum and 333 (606) d for R. rubra. Differences concerning survival time were recorded in dependence on temperature and quality of water. All the 3 strains were multiplied periodically. Variants of culture character could be noticed during the experiments. The flora of association seems to have a considerable influence on the survival time of the fungi studied. The very long persistence of fungi enables them to become widespread by means of water, and in such a way that they pollute environment.


Fusaric acid inhibits cell proliferation and downregulates expressions of toll-like receptors pathway genes in Ishikawa endometrial cancer cells.
Fusaric acid is a derivative of picolinic acid produced by some Fusarium species. In this study, we aimed to determine the mRNA expression and antiproliferative effects of fusaric acid in Ishikawa endometrium cancer cells in signal pathway genes associated with Toll-like receptors (TLRs). The effect of fusaric acid on the viability of Ishikawa cells was evaluated using XTT. After total RNA was isolated from control and dose group cells, cDNA synthesis was performed, and mRNA expression changes of genes involved in the Toll-like signaling pathway were evaluated by real-time reverse-transcription polymerase chain reaction (RT-PCR). The decrease in viability of Ishikawa cells was observed in a time- and dose-dependent manner. The inhibitory concentration (IC50) dose of fusaric acid at the 72nd hour in the Ishikawa cell line was 142.81 µM. When the dose group treated with 125 µM fusaric acid at the 72nd hour was compared with the control group, significantly decreased toll-like receptor 1 (TLR1), TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, and Myeloid differentiation primary response protein 88 (MYD88) gene expressions were observed. Fusaric acid inhibits cell proliferation and downregulates Toll-like receptors pathway gene expression in Ishikawa endometrial cancer cells.


Hemodynamic Response Pattern of Spatial Cueing is Different for Social and Symbolic Cues.
Directional social gaze and symbolic arrow cues both serve as spatial cues, causing seemingly reflexive shifts of an observer's attention. However, the underlying neural substrates remain a point at issue. The present study specifically addressed the differences in the activation patterns associated with non-predictive gaze and arrow cues, placing special emphasis on brain regions known to be involved in the processing of social information [superior temporal sulcus (STS), fusiform gyrus (FFG)]. Additionally, the functional connectivity of these brain regions with other areas involved in gaze processing and spatial attention was investigated. Results indicate that gaze and arrow cues recruit several brain regions differently, with gaze cues increasing activation in occipito-temporal regions and arrow cues increasing activation in occipito-parietal regions. Specifically, gaze cues in contrast to arrow cues enhanced activation in the FFG and the STS. Functional connectivity analysis revealed that during gaze cueing the STS was more strongly connected to the intraparietal sulcus (IPS) and the frontal eye fields, whereas the FFG was more strongly connected to the IPS and the amygdala.


Variations in Serratia marcescens differentiation using different primers.
To study primer sequences (1060, 1247, 1254, 1281, 1283, and 1290) for random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR). Twenty-four clinical Serratia marcescens (S. marcescens) isolates were obtained over a 6-month period from April 2002 to September 2002 from hospitals in the Fars province of Iran. Six primers were used due to S. marcescens genome properties, and RAPD-PCR was carried out. The results were subjected to unweighted pair-group method analysis using NTSYSpc 2.02. The primers were blasted with the S. marcescens genome, and the primers efficiency was estimated. The results of blast primers with S. marcescens genome sequence showed that primer 1283 had the highest homology and primer 1290 had the lowest homology. Comparing the resulted dendrograms showed that the pattern of the primers to separate isolates was closely related to their sequence homology with the genome and their amount of guanine and cytosine nucleotide content. There are clear differences in RAPD-PCR results when different primers are used, and it is recommended to consider genomic properties of an organism to design a primer for RAPD-PCR.


Dengue fever.
Dengue fever, and its more serious haemorrhagic form, is increasingly being found among UK travellers to tropical and sub-tropical countries. This Update examines transmission, the main symptoms and nursing care of affected people.


Effects and potential mechanism of dietary vitamin C supplementation on hepatic lipid metabolism in growing laying hens under chronic heat stress.
The adverse effects of chronic heat stress (CHS)-induced fatty liver syndrome on laying hens during the egg-producing stages have been wildly documented. However, until nowadays, the CHS responses of growing laying hens as well as its alleviating effects of vitamin C are rarely reported. In this study, 12-wk-old laying hens were subjected to CHS at 36 °C for 10 h/d for 3 wk with or without dietary supplementation of 300 mg/kg vitamin C. Results showed that CHS significantly impaired the growth performances and the liver functions of birds, as characterized by reduced feed intake and body weight, increased hepatic lipid accumulation and serum concentrations of TG, ALT, and AST, as well as the abnormal expression patterns of the lipid metabolism-related genes. Vitamin C supplementation successfully mitigated the lipid accumulation, while showing no alleviating effect on the serum contents of ALT or AST, which are two key indicators of liver functions. Metabolomic analysis based on UPLC-Q-TOF/MS identified 173 differential metabolites from the HS and HSV group samples, and they are mainly enriched in the pathways related to the cellular components, vitamin and amino acid metabolism and energy substance metabolism. The results indicate that CHS-induced hepatic lipid deposition in growing laying hens is effectively alleviated by dietary supplementation of vitamin C, which is probably resulted from the alterations of hepatocellular metabolic patterns.


Cognitive MMN and P300 in mild cognitive impairment and Alzheimer's disease: A high density EEG-3D vector field tomography approach.
Precise preclinical detection of dementia for effective treatment and stage monitoring is of great importance. Miscellaneous types of biomarkers, e.g., biochemical, genetic, neuroimaging, and physiological, have been proposed to diagnose Alzheimer's disease (AD), the usual suspect behind manifested cognitive decline, and mild cognitive impairment (MCI), a neuropathology prior to AD that does not affect cognitive functions. Event related potential (ERP) methods constitute a non-invasive, inexpensive means of analysis and have been proposed as sensitive biomarkers of cognitive impairment; besides, various ERP components are strongly linked with working memory, attention, sensory processing and motor responses. In this study, an auditory oddball task is employed, to acquire high density electroencephalograhy recordings from healthy elderly controls, MCI and AD patients. The mismatch negativity (MMN) and P300 ERP components are then extracted and their relationship with neurodegeneration is examined. Then, the neural activation at these components is reconstructed using the 3D vector field tomography (3D-VFT) inverse solution. The results reveal a decline of both ERPs amplitude, and a statistically significant prolongation of their latency as cognitive impairment advances. For the MMN, higher brain activation is usually localized in the inferior frontal and superior temporal gyri in the controls. However, in AD, parietal sites exhibit strong activity. Stronger P300 generators are mostly found in the frontal lobe for the controls, but in AD they often shift to the temporal lobe. Reduction in inferior frontal source strength and the switch of the maximum intensity area to parietal and superior temporal sites suggest that these areas, especially the former, are of particular significance when neurodegenerative disorders are investigated. The modulation of MMN and P300 can serve to produce biomarkers of dementia and its progression, and brain imaging can further contribute to the diagnostic efficiency of ERPs.


Subthreshold Activity Underlying the Diversity and Selectivity of the Primary Auditory Cortex Studied by Intracellular Recordings in Awake Marmosets.
Extracellular recording studies have revealed diverse and selective neural responses in the primary auditory cortex (A1) of awake animals. However, we have limited knowledge on subthreshold events that give rise to these responses, especially in non-human primates, as intracellular recordings in awake animals pose substantial technical challenges. We developed a novel intracellular recording technique in awake marmosets to systematically study subthreshold activity of A1 neurons that underlies their diverse and selective spiking responses. Our findings showed that in contrast to predominantly transient depolarization observed in A1 of anesthetized animals, both transient and sustained depolarization (during or beyond the stimulus period) were observed. Comparing with spiking responses, subthreshold responses were often longer lasting in duration and more broadly tuned in frequency, and showed narrower intensity tuning in non-monotonic neurons and lower response threshold in monotonic neurons. These observations demonstrated the enhancement of stimulus selectivity from subthreshold to spiking responses in individual A1 neurons. Furthermore, A1 neurons classified as regular- or fast-spiking subpopulation based on their spike shapes exhibited distinct response properties in frequency and intensity domains. These findings provide valuable insights into cortical integration and transformation of auditory information at the cellular level in auditory cortex of awake non-human primates.


[Suicide attempt by an interstitial cystitis patient : a case report].
We report a suicide attempt by an interstitial cystitis patient. A 68-year-old woman consulted several clinics with complaints of urinary frequency and bladder pain, but her symptoms did not improve. She was admitted to our hospital and diagnosed with interstitial cystitis. Hydrodistention was performed, and the urethral catheter removed one day after surgery. The next day, the patient was afraid that her symptoms had not improved and, due to this physical and mental distress, cut her wrist with a razor. Vascular anastomosis and neuroanastomosis were performed accordingly. Eighteen months after hydrodistention, the patient's symptoms of interstitial cystitis have much improved.


Predator community composition is linked to soil carbon retention across a human land use gradient.
Soil carbon (C) storage is a major component of the carbon cycle. Consensus holds that soil C uptake and storage is regulated by plant-microbe-soil interactions. However, the contribution of animals in aboveground food webs to this process has been overlooked. Using insights from prior long-term experimentation in an old-field ecosystem and mathematical modeling, we predicted that the amount of soil C retention within a field should increase with the proportion of active hunting predators comprising the aboveground community of active hunting and sit-and-wait predators. This comes about because predators with different hunting modes have different cascading effects on plants. Our test of the prediction revealed that the composition of the arthropod predator community and associated cascading effects on the plant community explained 41% of variation in soil C retention among 15 old fields across a human land use gradient. We also evaluated the potential for several other candidate factors to explain variation in soil C retention among fields, independent of among-field variation in the predator community. These included live plant biomass, insect herbivore community composition, soil arthropod decomposer community composition, degree of land use development around the fields, field age, and soil texture. None of these candidate variables significantly explained soil C retention among the fields. The study offers a generalizable understanding of the pathways through which arthropod predator community composition can contribute to old-field ecosystem carbon storage. This insight helps support ongoing efforts to understand and manage the effects of anthropogenic land use change on soil C storage.


Cysteinyl leukotriene receptor antagonists inhibit tumor metastasis by inhibiting capillary permeability.
We explored the possibility of the cysteinyl leukotriene receptor antagonists, pranlukast and montelukast, preventing tumor cell migration through both cerebral and peripheral capillaries. To study tumor cell migration through brain capillaries, male Fisher rats were cannulated via the cisterna magna under pentobarbital anesthesia. RCN9 cells labeled with a fluorescent marker PKH67 were intravenously administered following arachidonic acid administration into the subarachnoid space, and specimens of the central nervous system were collected every 30 min for 8 h. Arachidonic acid increased the fluid volume with elevated white blood cell and RCN9 cell counts. When given 2 h before arachidonic acid administration, pranlukast, but not montelukast, reduced the fluid volume and inhibited white blood cell and RCN9 cell extravasation through the brain capillary. In addition, a Lewis lung carcinoma metastasis model in mice was used to study the inhibitory effect of pranlu kast and montelukast against cancer cell extravasation through general capillaries. When mice were given food containing either pranlukast or montelukast, immediately after paw amputation, tumor metastasis was prevented by both drugs, and their survival was prolonged. These results show that pranlukast can inhibit tumor cell migration through both the brain and peripheral capillaries, whereas montelukast inhibits tumor cell migration only in the peripheral capillaries.


Altered network stability in progressive supranuclear palsy.
The clinical syndromes of Progressive Supranuclear Palsy (PSP) may be mediated by abnormal temporal dynamics of brain networks, due to the impact of atrophy, synapse loss and neurotransmitter deficits. We tested the hypothesis that alterations in signal complexity in neural networks influence short-latency state transitions. Ninety-four participants with PSP and 64 healthy controls were recruited from two independent cohorts. All participants underwent clinical and neuropsychological testing and resting-state functional MRI. Network dynamics were assessed using hidden Markov models and neural signal complexity measured in terms of multiscale entropy. In both cohorts, PSP increased the proportion of time in networks associated with higher cognitive functions. This effect correlated with clinical severity as measured by the PSP-rating-scale, and with reduced neural signal complexity. Regional atrophy influenced abnormal brain-state occupancy, but abnormal network topology and dynamics were not restricted to areas of atrophy. Our findings show that the pathology of PSP causes clinically relevant changes in neural temporal dynamics, leading to a greater proportion of time in inefficient brain-states.