RNA-Seq Based Identification of Candidate Parasitism Genes of Cereal Cyst Nematode (Heterodera avenae) during Incompatible Infection to Aegilops variabilis.
One of the reasons for the progressive yield decline observed in cereals production is the rapid build-up of populations of the cereal cyst nematode (CCN, Heterodera avenae). These nematodes secrete so-call effectors into their host plant to suppress the plant defense responses, alter plant signaling pathways and then induce the formation of syncytium after infection. However, little is known about its molecular mechanism and parasitism during incompatible infection. To gain insight into its repertoire of parasitism genes, we investigated the transcriptome of the early parasitic second-stage (30 hours, 3 days and 9 days post infection) juveniles of the CCN as well as the CCN infected tissue of the host Aegilops variabilis by Illumina sequencing. Among all assembled unigenes, 681 putative genes of parasitic nematode were found, in which 56 putative effectors were identified, including novel pioneer genes and genes corresponding to previously reported effectors. All the 681 CCN unigenes were mapped to 229 GO terms and 200 KEGG pathways, including growth, development and several stimulus-related signaling pathways. Sixteen clusters were involved in the CCN unigene expression atlas at the early stages during infection process, and three of which were significantly gene-enriched. Besides, the protein-protein interaction network analysis revealed 35 node unigenes which may play an important role in the plant-CCN interaction. Moreover, in a comparison of differentially expressed genes between the pre-parasitic juveniles and the early parasitic juveniles, we found that hydrolase activity was up-regulated in pre J2s whereas binding activity was upregulated in infective J2s. RT-qPCR analysis on some selected genes showed detectable expression, indicating possible secretion of the proteins and putative role in infection. This study provided better insights into the incompatible interaction between H. avenae and the host plant Ae. varabilis. Moreover, RNAi targets with potential lethality were screened out and primarily validated, which provide candidates for engineering-based control of cereal cyst nematode in crops breeding.


Influencing the importance of health, partners, and hygiene among Zambian women.
Intravaginal practices (IVPs) are common in Zambia and are usually practiced for hygiene, partner pleasure, and health. IVPs are associated with HIV acquisition, changes in the vaginal flora, and bacterial vaginosis (BV), making it important to understand the decision-making process behind IVP engagement. The Women's and Sexual Health (WASH) intervention decreased IVP engagement among HIV-infected Zambian women, though change in reasons for engagement has not been assessed. We used conjoint analysis (CA) to quantify the decision-making process of IVP engagement and evaluated how the WASH intervention impacted these factors. Participants were N = 84 women (37 ± 8 years old) randomized to WASH (n = 46) or standard of care plus (SOC+; n = 38) who completed demographic measures and a CA questionnaire at baseline, six months, and 12 months to quantify the importance placed on hygiene, partner pleasure, and health. The importance placed on health increased from baseline to six months (15.5 versus 25.1; p < 0.001) and from baseline to 12 months (15.5 versus 50.5; p < 0.001), and was higher in SOC+ at six months (19.9 versus 30.3; p = 0.003). Hygiene importance decreased from baseline (63.6) to six months (50.3), and from baseline to 12 months (26.1), and was higher in the experimental arm at six months (56.1) compared to SOC+ (44.6; p = 0.029). Importance placed on partner pleasure did not change over time in either group. Findings suggest that both groups exhibited an increase in the importance placed on health and a decrease on hygiene importance for IVP engagement, suggesting that SOC+ may be sufficient to promote attitude changes that may facilitate IVP discontinuation and may prove to be more cost effective by using fewer monetary resources. Findings highlight the potential of interventions to influence attitudes toward IVPs and provide novel avenues for research to improve the design and conduct of interventions aimed at reducing IVPs among Zambian women and contribute to HIV prevention efforts.


Proteomic and genetic analysis of wheat endosperm albumins and globulins using deletion lines of cultivar Chinese Spring.
Albumins and globulins from the endosperm of Triticum aestivum L. cv Chinese Spring (CS) were analysed to establish a proteome reference map for this standard wheat cultivar. Approximately, 1,145 Coomassie-stained spots were detected by two-dimensional gel electrophoresis (2DE), 410 of which were identified using mass spectrometry and data mining. Salt-soluble endosperm proteins from 67 CS deletion lines were also separated by 2DE (four gels per line). Image analysis of the 268 2DE gels as compared to the CS reference proteome allowed the detection of qualitative and quantitative variations in endosperm proteins due to chromosomal deletions. This differential analysis of spots allowed structural or regulatory genes, encoding 211 proteins, to be located on segments of the 21 wheat chromosomes. In addition, variance analysis of quantitative variations in spot volume showed that the expression of 391 proteins is controlled by one or more chromosome bins with 262 significant increases and 196 significant decreases in spot volume. The spot volume of several proteins was increased or decreased by numerous chromosomal regions and homoeologous-like regulation was revealed for some proteins. Quantitative or qualitative variation in a total of 386 proteins was influenced by genes assigned to at least one chromosomal region, while 66 % of all stained proteins were not found to be influenced by chromosome bins. Proteomics of deletion lines can, therefore, be used to simultaneously analyse the composition and genetics of a complex tissue, such as the wheat endosperm.


Design for the optical retardation in broadband zero-order half-wave plates.
This paper presents a novel design for broadband zero-order half-wave plates to eliminate the first-order or up to second-order wavelength-dependent birefringent phase retardation (BPR) with 2 or 3 different birefringent materials. The residual BPRs of the plates increase monotonously with the wavelength deviation from a selected wavelength, so the plates are applicable to the broadband light pulses which gather most of the light energy around their central wavelengths. The model chooses the materials by the birefringent dispersion coefficient and evaluates the performances of the plates by the weighted average of the absolute value of residual BPR in order to emphasize the contributions of the incident spectral components whose possess higher energies.


Electron microscopy findings on an intraocular lens in the uveitis, glaucoma, hyphaema syndrome.
To report the electron microscopic findings on an explanted intraocular lens in a patient with the uveitis, glaucoma, hyphaema syndrome. Scanning and transmission electron microscopy were undertaken on a coccoon of cellular material from the tip of the intraocular lens haptic. Scanning electron micrographs showed densely packed coccoid-like structures on the haptic surface. By transmission electron microscopy these structures proved to be melanosomes. The scanning electron micrographs described in this report are similar to those reported in patients with chronic post-operative uveitis, but to our knowledge have not been shown before in association with the uveitis, glaucoma, hyphaema syndrome. Transmission electron microscopy determined that the coccoid-like structures were melanosomes. The melanosomes are probably derived from damaged pigment epithelial cells or iris stromal melanocytes secondary to recurrent chafing of the haptic against the posterior surface of the iris.


Cellular differentiation and individuality in the 'minor' multicellular taxa.
Biology needs a concept of individuality in order to distinguish organisms from parts of organisms and from groups of organisms, to count individuals and compare traits across taxa, and to distinguish growth from reproduction. Most of the proposed criteria for individuality were designed for 'unitary' or 'paradigm' organisms: contiguous, functionally and physiologically integrated, obligately sexually reproducing multicellular organisms with a germ line sequestered early in development. However, the vast majority of the diversity of life on Earth does not conform to all of these criteria. We consider the issue of individuality in the 'minor' multicellular taxa, which collectively span a large portion of the eukaryotic tree of life, reviewing their general features and focusing on a model species for each group. When the criteria designed for unitary organisms are applied to other groups, they often give conflicting answers or no answer at all to the question of whether or not a given unit is an individual. Complex life cycles, intimate bacterial symbioses, aggregative development, and strange genetic features complicate the picture. The great age of some of the groups considered shows that 'intermediate' forms, those with some but not all of the traits traditionally associated with individuality, cannot reasonably be considered ephemeral or assumed transitional. We discuss a handful of recent attempts to reconcile the many proposed criteria for individuality and to provide criteria that can be applied across all the domains of life. Finally, we argue that individuality should be defined without reference to any particular taxon and that understanding the emergence of new kinds of individuals requires recognizing individuality as a matter of degree.


Microsatellite characterization of Andean races of common bean (Phaseolus vulgaris L.).
The Andean gene pool of common bean (Phaseolus vulgaris L.) has high levels of morphological diversity in terms of seed color and size, growth habit and agro-ecological adaptation, but previously was characterized by low levels of molecular marker diversity. Three races have been described within the Andean gene pool: Chile, Nueva Granada and Peru. The objective of this study was to characterize a collection of 123 genotypes representing Andean bean diversity with 33 microsatellite markers that have been useful for characterizing race structure in common beans. The genotypes were from both the primary center of origin as well as secondary centers of diversity to which Andean beans spread and represented all three races of the gene pool. In addition we evaluated a collection of landraces from Colombia to determine if the Nueva Granada and Peru races could be distinguished in genotypes from the northern range of the primary center. Multiple correspondence analyses of the Andean race representatives identified two predominant groups corresponding to the Nueva Granada and Peru races. Some of the Chile race representatives formed a separate group but several that had been defined previously as from this race grouped with the other races. Gene flow was more notable between Nueva Granada and Peru races than between these races and the Chile race. Among the Colombian genotypes, the Nueva Granada and Peru races were identified and introgression between these two races was especially notable. The genetic diversity within the Colombian genotypes was high, reaffirming the importance of this region as an important source of germplasm. Results of this study suggest that the morphological classification of all climbing beans as Peru race genotypes and all bush beans as Nueva Granada race genotypes is erroneous and that growth habit traits have been mixed in both races, requiring a re-adjustment in the concept of morphological races in Andean beans.


Mutated genes and driver pathways involved in myelodysplastic syndromes—a transcriptome sequencing based approach.
Myelodysplastic syndromes are a heterogeneous group of clonal disorders of hematopoietic progenitors and have potentiality to progress into acute myelogenous leukemia. Development of effective treatments has been impeded by limited insight into pathogenic pathways. In this study, we applied RNA-seq technology to study the transcriptome on 20 MDS patients and 5 age-matched controls, and developed a pipeline for analyzing this data. After analysis, we identified 38 mutated genes contributing to MDS pathogenesis. 37 out of 38 genes have not been reported previously, suggesting our pipeline is critical for identifying novel mutated genes in MDS. The most recurrent mutation happened in gene IFRD1, which involved 30% of patient samples. Biological relationships among these mutated genes were mined using Ingenuity Pathway Analysis, and the results demonstrated that top two networks with highest scores were highly associated with cancer and hematological diseases, indicating that the mutated genes identified by our method were highly relevant to MDS. We then integrated the pathways in KEGG database and the identified mutated genes using our novel rule-based mutated driver pathway scoring approach for detecting mutated driver pathways. The results indicated two mutated driver pathways are important for the pathogenesis of MDS: pathway in cancer and in regulation of actin cytoskeleton. The latter, which likely contributes to the hallmark morphologic dysplasia observed in MDS, has not been reported, to the best of our knowledge. These results provide us new insights into the pathogenesis of MDS, which, in turn, may lead to novel therapeutics for this disease.


Rehabilitation after Rotator Cuff Repair.
Rotator cuff tears are a very common condition that is often incapacitating. Whether non-surgical or surgical, successful management of rotator cuff disease is dependent on appropriate rehabilitation. If conservative management is insufficient, surgical repair is often indicated. Postsurgical outcomes for patients having had rotator cuff repair can be quite good. A successful outcome is much dependent on surgical technique as it is on rehabilitation. Numerous rehabilitation protocols for the management of rotator cuff disease are based primarily on clinical experience and expert opinion. This article describes the different rehabilitation protocols that aim to protect the repair in the immediate postoperative period, minimize postoperative stiffness and muscle atrophy. A review of currently available literature on rehabilitation after arthroscopic rotator cuff tear repair was performed to illustrate the available evidence behind various postoperative treatment modalities. There were no statistically significant differences between a conservative and an accelerated rehabilitation protocol . Early passive range of motion (ROM) following arthroscopic cuff repair is thought to decrease postoperative stiffness and improve functionality. However, early aggressive rehabilitation may compromise repair integrity. The currently available literature did not identify any significant differences in functional outcomes and relative risks of re-tears between delayed and early motion in patients undergoing arthroscopic rotator cuff repairs. A gentle rehabilitation protocol with limits in range of motion and exercise times after arthroscopic rotator cuff repair would be better for tendon healing without taking any substantial risks. A close communication between the surgeon, the patient and the physical therapy team is important and should continue throughout the whole recovery process.


Sexual behavior and HPV infection in British women, by postal questionnaires and telephone interviews.
Sexually transmitted human papillomaviruses (HPVs), most frequently HPV 16, are the primary cause of cervical carcinogenesis. The aim of this study was to evaluate the relationship between sexual behavior and prevalence and acquisition of HPV infection among British women attending regular cervical screening who responded to postal questionnaires and/or telephone interviews. A total of 1,880 women who had been tested for HPV in the ARTISTIC (A Randomized Trial In Screening To Improve Cytology) trial were randomized to three methods of data collection: group 1 (questionnaire including sexual history, no interview), group 2 (questionnaire excluding sexual history, short interview including sexual history), and group 3 (questionnaire and long interview including sexual history in both). Questions on sexual history included age at first sexual intercourse, sexually transmitted diseases, lifetime (total and regular) sexual partners, and number of partners in the last 5 years (total and new). Demographics, reproductive, cervical screening, and smoking history were also collected in questionnaires. The overall participation rate was 35%. There was good agreement (87.4-95.5%) on sexual behavior answers in questionnaires and interviews in women in group 3 and no significant differences between data obtained by questionnaire or interview. Odds ratios (OR) for both HPV prevalence and acquisition increased consistently with increasing numbers of lifetime sexual partners, regular partners, and new partners in the last 5 years (recent partners). No significant association was found for other characteristics investigated. The effect of recent sexual partners on HPV acquisition (OR for 2+ recent partners: 4.4, 95% CI: 1.7-11.2) was stronger than that of earlier (> 5 years ago) partners (OR for 2+ earlier partners: 2.2, 95% CI: 0.7-6.7) suggesting that most incident HPV infections are newly acquired rather than recurrent.


Task-Space Synergies for Reaching Using Upper-Limb Prostheses.
Synergistic prostheses enable the coordinated movement of the human-prosthetic arm, as required by activities of daily living. This is achieved by coupling the motion of the prosthesis to the human command, such as the residual limb movement in motion-based interfaces. Previous studies demonstrated that developing human-prosthetic synergies in joint-space must consider individual motor behaviour and the intended task to be performed, requiring personalisation and task calibration. In this work, an alternative synergy-based strategy, utilising a synergistic relationship expressed in task-space, is proposed. This task-space synergy has the potential to replace the need for personalisation and task calibration with a model-based approach requiring knowledge of the individual user's arm kinematics, the anticipated hand motion during the task and voluntary information from the prosthetic user. The proposed method is compared with surface electromyography-based and joint-space synergy-based prosthetic interfaces in a study of motor behaviour and task performance on able-bodied subjects using a VR-based transhumeral prosthesis. Experimental results showed that for a set of forward reaching tasks the proposed task-space synergy achieves comparable performance to joint-space synergies without the need to rely on time-consuming calibration processes or human motor learning. Case study results with an amputee subject motivate the further development of the proposed task-space synergy method.


What can we learn from consumer reports on psychiatric adverse drug reactions with antidepressant medication? Experiences from reports to a consumer association.
According to the World Health Organization (WHO) the cost of adverse drug reactions (ADRs) in the general population is high and under-reporting by health professionals is a well-recognized problem. Another way to increase ADR reporting is to let the consumers themselves report directly to the authorities. In Sweden it is mandatory for prescribers to report serious ADRs to the Medical Products Agency (MPA), but there are no such regulations for consumers. The non-profit and independent organization Consumer Association for Medicines and Health, KILEN has launched the possibility for consumers to report their perceptions and experiences from their use of medicines in order to strengthen consumer rights within the health care sector. This study aimed to analyze these consumer reports. All reports submitted from January 2002 to April 2009 to an open web site in Sweden where anyone could report their experience with the use of pharmaceuticals were analyzed with focus on common psychiatric side effects related to antidepressant usage. More than one ADR for a specific drug could be reported. In total 665 reports were made during the period. 442 reports concerned antidepressant medications and the individual antidepressant reports represented 2392 ADRs and 878 (37%) of these were psychiatric ADRs. 75% of the individual reports concerned serotonin-reuptake inhibitor (SSRI) and the rest serotonin-norepinephrine reuptake inhibitor (SNRI). Women reported more antidepressant psychiatric ADRs (71%) compared to men (24%). More potentially serious psychiatric ADRs were frequently reported to KILEN and withdrawal symptoms during discontinuation were also reported as a common issue. The present study indicates that consumer reports may contribute with important information regarding more serious psychiatric ADRs following antidepressant treatment. Consumer reporting may be considered a complement to traditional ADR reporting.


An Improved Method for Measuring Quantitative Resistance to the Wheat Pathogen Zymoseptoria tritici Using High-Throughput Automated Image Analysis.
Zymoseptoria tritici causes Septoria tritici blotch (STB) on wheat. An improved method of quantifying STB symptoms was developed based on automated analysis of diseased leaf images made using a flatbed scanner. Naturally infected leaves (n = 949) sampled from fungicide-treated field plots comprising 39 wheat cultivars grown in Switzerland and 9 recombinant inbred lines (RIL) grown in Oregon were included in these analyses. Measures of quantitative resistance were percent leaf area covered by lesions, pycnidia size and gray value, and pycnidia density per leaf and lesion. These measures were obtained automatically with a batch-processing macro utilizing the image-processing software ImageJ. All phenotypes in both locations showed a continuous distribution, as expected for a quantitative trait. The trait distributions at both sites were largely overlapping even though the field and host environments were quite different. Cultivars and RILs could be assigned to two or more statistically different groups for each measured phenotype. Traditional visual assessments of field resistance were highly correlated with quantitative resistance measures based on image analysis for the Oregon RILs. These results show that automated image analysis provides a promising tool for assessing quantitative resistance to Z. tritici under field conditions.


CMV immune evasion and manipulation of the immune system with aging.
Human cytomegalovirus (HCMV) encodes numerous proteins and microRNAs that function to evade the immune response and allow the virus to replicate and disseminate in the face of a competent innate and acquired immune system. The establishment of a latent infection by CMV, which if completely quiescent at the level of viral gene expression would represent an ultimate in immune evasion strategies, is not sufficient for lifelong persistence and dissemination of the virus. CMV needs to reactivate and replicate in a lytic cycle of infection in order to disseminate further, which occurs in the face of a fully primed secondary immune response. Without reactivation, latency itself would be redundant for the virus. It is also becoming clear that latency is not a totally quiescent state, but is characterized by limited viral gene expression. Therefore, the virus also needs immune evasion strategies during latency. An effective immune response to CMV is required or viral replication will cause morbidity and ultimately mortality in the host. There is clearly a complex balance between virus immune evasion and host immune recognition over a lifetime. This poses the important question of whether long-term evasion or manipulation of the immune response driven by CMV is detrimental to health. In this meeting report, three groups used the murine model of CMV (MCMV) to examine if the contribution of the virus to immune senescence is set by the (i) initial viral inoculum, (ii) inflation of T cell responses, (iii) or the balance between functionally distinct effector CD4+ T cells. The work of other groups studying the CMV response in humans is discussed. Their work asks whether the ability to make immune responses to new antigens is compromised by (i) age and HCMV carriage, (ii) long-term exposure to HCMV giving rise to an overall immunosuppressive environment and increased levels of latent virus, or (iii) adapted virus mutants (used as potential vaccines) that have the capacity to elicit conventional and unconventional T cell responses.


α-Helical peptide vesicles with chiral membranes as enantioselective nanoreactors.
We report peptide vesicles with chiral membranes as enantioselective nanoreactors. The peptide vesicles are able to selectively encapsulate only a single enantiomer from a racemic mixture solution through preferential diffusion across the membranes. Notably, the confined space of the vesicle acts as an enantioselective nanoreactor for the encapsulated enantiomer which undergoes further chemical transformations to yield a highly enantiopure product.


HR23B is a biomarker for tumor sensitivity to HDAC inhibitor-based therapy.
Histone deacetylase (HDAC) inhibitors are emergent cancer drugs. HR23B is a candidate cancer biomarker identified in a genome-wide loss-of-function screen which influences sensitivity to HDAC inhibitors. Because HDAC inhibitors have found clinical utility in cutaneous T-cell lymphoma (CTCL), we evaluated the role of HR23B in CTCL cells. Our results show that HR23B governs the sensitivity of CTCL cells to HDAC inhibitors. Furthermore, proteasome activity is deregulated in HDAC inhibitor-treated CTCL cells through a mechanism dependent upon HR23B, and HDAC inhibitors sensitize CTCL cells to the effects of proteasome inhibitors. The predictive power of HR23B for clinical response to HDAC inhibitors was investigated through an analysis of a unique collection of CTCL biopsies taken from a phase II clinical trial, where there was a frequent coincidence between HR23B expression and clinical response to HDAC inhibitor. Our study supports the personalized medicine approach for treating cancer and the increasing drive to translate laboratory-based findings into clinical utility.


Macroprolactinomas: serial MR imaging in long-term bromocriptine therapy.
To study the changes in macroprolactinomas during long-term bromocriptine therapy by means of serial MR imaging, and to correlate the findings to the serum prolactin (S-PRL) levels. Thirteen patients with macroprolactinomas were studied before and during bromocriptine therapy; six to 11 MR examinations were performed with a duration of follow-up of 22 to 74 months. Tumor size, extension, relationship to adjacent structures, and signal intensity patterns were evaluated. Signal intensity ratios and T2 values were calculated in areas of apparently solid tumor tissue. Bromocriptine effectively reduced the size of all tumors; the size reduction was already significant at 1 week, but often continued for several years. Reenlargement during therapy was seen in three cases. The development of chiasmal herniation parallel to increasing cisternal invagination into the sella was a common finding, but was not correlated to visual symptoms. Signal intensity patterns corresponding to hemorrhage, cysts or necrosis were frequently observed, and transitions from one pattern to another were common. Hemorrhage occurred mainly in tumors corresponding to high initial serum prolactin levels. After 1 year of therapy, there was a significant increase in T2 values, indicating an increased water content in residual solid tumor tissue. MR is valuable for follow-up in bromocriptine therapy of macroprolactinomas, and provides new information on the tumor size changes, the inner structure of the tumors, and the optic chiasm.


IgG antibody responses in mice coinfected with Toxocara canis and other helminths or protozoan parasites.
The immune response expressed by IgG antibodies in BALB/c mice experimentally infected with Toxocara canis, was studied with the aim of verifying the possible in vivo cross-reactivity between antigens of T. canis and other parasites (Ascaris suum, Taenia crassiceps, Schistosoma mansoni, Strongyloides venezuelensis and Toxoplasma gondii). Experiments included three groups of mice: one infected only by T. canis, another with one of the other species of parasites and a third concomitantly infected with T. canis and the other species in question. Animals were bled by orbital plexus at 23, 38 and 70 days post infection (p.i.). Sera were analyzed for anti-Toxocara antibodies by ELISA and Immunoblotting, using excretion-secretion antigens (ES), obtained from culture of third-stage larvae of T. canis. For all experiments a control group comprised by ten non-infected mice was used. Only in the case of A. suum infection, in these experimental conditions, the occurrence of cross-reactivity with T. canis was observed. However, in the case of co-infection of T. canis - S. mansoni, T. canis - S. venezuelensis and T. canis - T. crassiceps the production of anti-Toxocara antibodies was found at levels significantly lower than those found in mice infected with T. canis only. Co-infection with S. mansoni or S. venezuelensis showed lower mortality rates compared to what occurred in the animals with single infections. Results obtained in mice infected with T. canis and T. gondii showed significant differences between the mean levels of the optical densities of animals infected with T. canis and concomitantly infected with the protozoan only in the 23rd day p.i.


Ten-year incidence of retinal vein occlusion in an older population: the Blue Mountains Eye Study.
To assess the 10-year incidence of retinal vein occlusion (RVO) and its predictors in an older population. The Blue Mountains Eye Study examined 3654 residents aged 49 years and older (82.4% response) from 1992 to 1994, reexamined 2335 residents (75.1% of survivors) from 1997 to 1999, and reexamined 1952 residents (75.6% of survivors) from 2002 to 2004. Incident RVO was assessed from stereoscopic retinal photographs. Kaplan-Meier cumulative 10-year incidence was calculated. After excluding 47 residents with RVO at baseline and 171 residents with no photographs at either follow-up examination, 2346 residents were considered at risk of developing RVO. The cumulative 10-year incidence of RVO was 1.6%. Age was significantly associated with the incidence of RVO (P = .03, Mantel-Haenszel chi(2) test for trend). Factors predicting the incidence of RVO included mean arterial blood pressure (age-adjusted odds ratio [OR], 1.41 per 10-mm Hg increase), ocular perfusion pressure (OR, 1.71 per 10-mm Hg increase), obesity (OR, 2.16), and presence of retinal arteriolar wall signs (focal narrowing: OR, 3.37; arteriovenous nicking: OR, 4.09; and opacification: OR, 4.89). Older age (> or =70 years), increasing mean arterial blood pressure, and atherosclerotic retinal vessel signs were significant predictors of incident RVO.


Relative survival benefit and morbidity with fluids in severe sepsis - a network meta-analysis of alternative therapies.
Fluid resuscitation is widely practiced in intensive care units for the treatment of sepsis. A comparison of the evidence base of different fluids may inform therapeutic choice. The risks of mortality and morbidity (the need for renal replacement therapies (RRT)) were assessed in patients with severe sepsis. A network meta-analysis compared trials for crystalloids, albumin and hydroxyethyl starch (HES). A literature search of human randomized clinical trials was conducted in databases, the bibliographies of other recent relevant systematic reviews and data reported at recent conferences. Mortality outcomes and RRT data with the longest follow up period were compared. A Bayesian network meta-analysis assessed the risk of mortality and a pair-wise metaanalysis assessed RRT using crystalloids as the reference treatment. 13 studies were identified. A fixed-effects meta-analysis of mortality data in the trials demonstrated an odds-ratio (OR) of 0.90 between crystalloids and albumin, 1.25 between crystalloids and HES and 1.40 between albumin and HES. The probability that albumin is associated with the highest survival was 96.4% followed by crystalloid at 3.6%, with a negligible probability for HES. Sub-group analyses demonstrated the robustness of this result to variations in fluid composition, study source and origin of septic shock. A random-effects pairwise comparison for the risk of RRT provided an OR of 1.52 favoring crystalloid over HES. Fluid therapy with albumin was associated with the highest survival benefit. The higher morbidity with HES may affect mortality and requires consideration by prescribers.


The influence of ecology on chimpanzee (Pan troglodytes) cultural behavior: a case study of five Ugandan chimpanzee communities.
The influence of ecology on the development of behavioral traditions in animals is controversial, particularly for chimpanzees (Pan troglodytes), for which it is difficult to rule out environmental influences as a cause of widely observed community-specific behavioral differences. Here, we investigated 3 potential scenarios that could explain the natural variation in a key extractive tool behavior, "fluid-dip," among several communities of chimpanzees of the Pan troglodytes schweinfurthii subspecies in Uganda. We compared data from previous behavioral ecological studies, field experiments, and long-term records of chimpanzee tool-using behavior. We focused on the quality of the available food, dietary preferences, and tool sets of 5 different communities, and carried out a standardized field experiment to test systematically for the presence of fluid-dip in 4 of these communities. Our results revealed major differences in habitat, available diet, and tool use behavior between geographically close communities. However, these differences in ecology and feeding behavior failed to explain the differences in tool use across communities. We conclude that ecological variables may lead both to innovation and loss of behavioral traditions, while contributing little to their transmission within the community. Instead, as soon as a behavioral tradition is established, sociocognitive factors likely play a key maintenance role as long as the ecological conditions do not change sufficiently for the tradition to be abandoned.


MobileODT: a case study of a novel approach to an mHealth-based model of sustainable impact.
A persistent challenge facing global health actors is ensuring that time-bound interventions are ultimately adopted and integrated into local health systems for long term health system strengthening and capacity building. This level of sustainability is rarely achieved with current models of global health intervention that rely on continuous injection of resources or persistent external presence on the ground. Presented here is a case study of a flipped approach to creating capacity and adoption through an engagement strategy centered around an innovative mHealth device and connected service. Through an impact-oriented business model, this mHealth solution engages stakeholders in a cohesive and interdependent network by appealing to the pain points for each actor throughout the health system. This particular intervention centers around the MobileODT, Inc. Enhanced Visual Assessment (EVA) System for enhanced visualization. While focused on challenges to cervical cancer screening and treatment services, the lessons learned are offered as a model for lateral translation into adjacent health condition verticals.


Mechanistic Investigation of Bis(imino)pyridine Manganese Catalyzed Carbonyl and Carboxylate Hydrosilylation.
We recently reported a bis(imino)pyridine (or pyridine diimine, PDI) manganese precatalyst, (Ph2PPrPDI)Mn (1), that is active for the hydrosilylation of ketones and dihydrosilylation of esters. In this contribution, we reveal an expanded scope for 1-mediated hydrosilylation and propose two different mechanisms through which catalysis is achieved. Aldehyde hydrosilylation turnover frequencies (TOFs) of up to 4900 min-1 have been realized, the highest reported for first row metal-catalyzed carbonyl hydrosilylation. Additionally, 1 has been shown to mediate formate dihydrosilylation with leading TOFs of up to 330 min-1. Under stoichiometric and catalytic conditions, addition of PhSiH3 to (Ph2PPrPDI)Mn was found to result in partial conversion to a new diamagnetic hydride compound. Independent preparation of (Ph2PPrPDI)MnH (2) was achieved upon adding NaEt3BH to (Ph2PPrPDI)MnCl2 and single-crystal X-ray diffraction analysis revealed this complex to possess a capped trigonal bipyramidal solid-state geometry. When 2,2,2-trifluoroacetophenone was added to 1, radical transfer yielded (Ph2PPrPDI·)Mn(OC·(Ph)(CF3)) (3), which undergoes intermolecular C-C bond formation to produce the respective Mn(II) dimer, [(μ-O,Npy-4-OC(CF3)(Ph)-4-H-Ph2PPrPDI)Mn]2 (4). Upon finding 3 to be inefficient and 4 to be inactive, kinetic trials were conducted to elucidate the mechanisms of 1- and 2-mediated hydrosilylation. Varying the concentration of 1, substrate, and PhSiH3 revealed a first order dependence on each reagent. Furthermore, a kinetic isotope effect (KIE) of 2.2 ± 0.1 was observed for 1-catalyzed hydrosilylation of diisopropyl ketone, while a KIE of 4.2 ± 0.6 was determined using 2, suggesting 1 and 2 operate through different mechanisms. Although kinetic trials reveal 1 to be the more active precatalyst for carbonyl hydrosilylation, a concurrent 2-mediated pathway is more efficient for carboxylate hydrosilylation. Considering these observations, 1-catalyzed hydrosilylation is believed to proceed through a modified Ojima mechanism, while 2-mediated hydrosilylation occurs via insertion.


Vaccine-preventable disease susceptibility in a British paediatric assessment unit.
Aims: To evaluate practice within a paediatric secondary-care centre before and after introduction of simple interventions to improve identification of under-immunised children and facilitate catch-up immunisations. Methods: The population-based child health database was used to check immunisation status for two cohorts of 200 consecutive admissions before and after routine printing of immunisation histories from the database and raising staff awareness. Vaccine-preventable disease (VPD) susceptibility burdens were calculated for each child. Case notes were assessed for accuracy and documentation of ward-based interventions. Results: Fourteen per cent of all children were under-immunised on admission and 27% of these were more than five years behind schedule. Under-immunised children's VPD susceptibility burdens ranged from 0-40,858 days and in 59% exceeded 1,000 days. Over one month the paediatric admission unit saw children with a combined VPD susceptibility burden of 1,323 child-years. Positive identification of under-immunised children increased by 40% (95% confidence interval: 12-62, p=0.002) following the introduction of routine database printouts. Conclusion: Children presenting to British secondary care units have large VPD susceptibility burdens. Positive identification of under-immunised children substantially improved after the introduction of routine database printouts, but catch-up immunisation rates did not increase.


Geometric and dosimetric effects of image co-registration workflows for Gamma Knife frameless radiosurgery.
The Gamma Knife® Icon™ CBCT facilitates frameless radiosurgery. In the vendor-recommended workflow, MRI is co-registered directly to CBCT for planning. Alternatively, MRI is co-registered to a diagnostic CT, which is then co-registered to CBCT. Our objective is to evaluate if this additional CT is necessary for more accurate registrations. Nine small spherical targets were generated onto 14 patient data-sets. Single-shot treatment plans were created. Geometric and dosimetric differences between the two workflows were determined. Mean target displacement was 0.5±0.3mm; average PTV coverage loss was 4.3±5.0%. For 19 clinical targets in 14 patients, the mean displacement and coverage change was 0.6±0.4mm and 1.3±1.6%. Eleven surrogate landmarks were contoured on a phantom MRI and registered to the CBCT using both workflows. The registration uncertainty was 0.50±0.65mm and 0.32±0.47mm for the MRI-CT-CBCT and MRI-CBCT respectively. As neither workflow was significantly more accurate, the additional CT is unnecessary for most cases.


Functional characterization of a vitamin B12-dependent methylmalonyl pathway in Mycobacterium tuberculosis: implications for propionate metabolism during growth on fatty acids.
Mycobacterium tuberculosis is predicted to subsist on alternative carbon sources during persistence within the human host. Catabolism of odd- and branched-chain fatty acids, branched-chain amino acids, and cholesterol generates propionyl-coenzyme A (CoA) as a terminal, three-carbon (C(3)) product. Propionate constitutes a key precursor in lipid biosynthesis but is toxic if accumulated, potentially implicating its metabolism in M. tuberculosis pathogenesis. In addition to the well-characterized methylcitrate cycle, the M. tuberculosis genome contains a complete methylmalonyl pathway, including a mutAB-encoded methylmalonyl-CoA mutase (MCM) that requires a vitamin B(12)-derived cofactor for activity. Here, we demonstrate the ability of M. tuberculosis to utilize propionate as the sole carbon source in the absence of a functional methylcitrate cycle, provided that vitamin B(12) is supplied exogenously. We show that this ability is dependent on mutAB and, furthermore, that an active methylmalonyl pathway allows the bypass of the glyoxylate cycle during growth on propionate in vitro. Importantly, although the glyoxylate and methylcitrate cycles supported robust growth of M. tuberculosis on the C(17) fatty acid heptadecanoate, growth on valerate (C(5)) was significantly enhanced through vitamin B(12) supplementation. Moreover, both wild-type and methylcitrate cycle mutant strains grew on B(12)-supplemented valerate in the presence of 3-nitropropionate, an inhibitor of the glyoxylate cycle enzyme isocitrate lyase, indicating an anaplerotic role for the methylmalonyl pathway. The demonstrated functionality of MCM reinforces the potential relevance of vitamin B(12) to mycobacterial pathogenesis and suggests that vitamin B(12) availability in vivo might resolve the paradoxical dispensability of the methylcitrate cycle for the growth and persistence of M. tuberculosis in mice.


Prevalence, Gender and Age Differences of Dating Aggression Among Italian Adolescents.
The present study represents an effort to expand and deepen the scant literature on Adolescent Dating Aggression (ADA) within the Italian context; adolescent dating aggression is a public health issue of interest due to its increasing frequency among adolescents. The prevalence of verbal-emotional and physical ADA was examined as well as gender and age differences in a sample of Italian adolescents. Participants included 436 adolescents (47.7% males; 52.3% females) living in northern Italy, aged 16 to 18 years (M = 17.11). Participants completed the Conflict in Adolescent Dating Relationships Inventory measuring abusive behaviors between adolescent dating partners. Non-parametric analyses were computed. Verbal-emotional ADA perpetration and victimization were much more common than physical ADA perpetration and victimization. Females reported higher levels of verbal-emotional and physical ADA perpetration than males. To fully investigate gender differences single behaviors were analyzed and described. Finally, age differences emerged only for perpetrated verbal-emotional abuse with such aggression being highest at age 18. This research suggests that in order to prevent the onset of dating aggression in teens in northern Italy, prevention programs may need to begin earlier than previously provided in junior high school. Another core conclusion is that physical aggression against partners is a problem for both males and females, thus intervention for the empowerment of interpersonal skills are needed.


Inferring pandemic growth rates from sequence data.
Using sequence data to infer population dynamics is playing an increasing role in the analysis of outbreaks. The most common methods in use, based on coalescent inference, have been widely used but not extensively tested against simulated epidemics. Here, we use simulated data to test the ability of both parametric and non-parametric methods for inference of effective population size (coded in the popular BEAST package) to reconstruct epidemic dynamics. We consider a range of simulations centred on scenarios considered plausible for pandemic influenza, but our conclusions are generic for any exponentially growing epidemic. We highlight systematic biases in non-parametric effective population size estimation. The most prominent such bias leads to the false inference of slowing of epidemic spread in the recent past even when the real epidemic is growing exponentially. We suggest some sampling strategies that could reduce (but not eliminate) some of the biases. Parametric methods can correct for these biases if the infected population size is large. We also explore how some poor sampling strategies (e.g. that over-represent epidemiologically linked clusters of cases) could dramatically exacerbate bias in an uncontrolled manner. Finally, we present a simple diagnostic indicator, based on coalescent density and which can easily be applied to reconstructed phylogenies, that identifies time-periods for which effective population size estimates are less likely to be biased. We illustrate this with an application to the 2009 H1N1 pandemic.


Parity status and the development of rheumatoid arthritis.
Rheumatoid arthritis (RA) is one of a number of autoimmune diseases with a marked female excess in incidence, particularly during the reproductive years. It is of interest to investigate whether reproductive factors are important in determining susceptibility to RA. However, difficulties in dating the pathological onset of the disease can make it difficult to distinguish between the reproductive influence history on disease and the influence of (subclinical) disease on reproduction. In women with RA compared to controls, there is no excess of being unmarried. Most but not all studies, show an increase in nulliparity, whereas parity rates in fertile RA women are unchanged. There is an increased rate of onset postpartum, particularly in the first three months after delivery. There is no unifying biological explanation for these epidemiological findings, and it is likely that the apparently obvious link between reproductive experience and pregnancy is complex.


Protective effect of ginsenoside Rh3 against anticancer drug-induced apoptosis in LLC-PK1 kidney cells.
Ginsenosides are active components of Panax ginseng that exert various health benefits including kidney protection effect. The medicinal activity of ginsenosides can be enhanced by modulating their stereospecificity by heat processing. Ginsenosides Rk2 and Rh3 represent positional isomers of the double bond at C-20(21) or C-20(22). The present study investigated the kidney-protective effects of ginsenosides Rk2 and Rh3 against cisplatin, a platinum based anticancer drug, induced apoptotic damage in renal proximal LLC-PK1 cells. As a result, ginsenoside Rh3 shows a stronger protective effect than that shown by Rk2. Cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), p38, and cleaved caspase-3 decreased after cotreatment with ginsenoside Rh3. The increase in the percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment also significantly reduced after cotreatment with ginsenoside Rh3. These results demonstrate that inhibition of the JNK and ERK mitogen-activated protein kinase signaling cascade plays a critical role in mediating the renoprotective effect of ginsenoside Rh3.


Updated CDC recommendations for the management of hepatitis B virus-infected health-care providers and students.
This report updates the 1991 CDC recommendations for the management of hepatitis B virus (HBV)-infected health-care providers and students to reduce risk for transmitting HBV to patients during the conduct of exposure-prone invasive procedures (CDC. Recommendations for preventing transmission of human immunodeficiency virus and hepatitis B virus to patients during exposure-prone invasive procedures. MMWR 1991;40[No. RR-8]). This update reflects changes in the epidemiology of HBV infection in the United States and advances in the medical management of chronic HBV infection and policy directives issued by health authorities since 1991. The primary goal of this report is to promote patient safety while providing risk management and practice guidance to HBV-infected health-care providers and students, particularly those performing exposure-prone procedures such as certain types of surgery. Because percutaneous injuries sustained by health-care personnel during certain surgical, obstetrical, and dental procedures provide a potential route of HBV transmission to patients as well as providers, this report emphasizes prevention of operator injuries and blood exposures during exposure-prone surgical, obstetrical, and dental procedures. These updated recommendations reaffirm the 1991 CDC recommendation that HBV infection alone should not disqualify infected persons from the practice or study of surgery, dentistry, medicine, or allied health fields. The previous recommendations have been updated to include the following changes: no prenotification of patients of a health-care provider's or student's HBV status; use of HBV DNA serum levels rather than hepatitis B e-antigen status to monitor infectivity; and, for those health-care professionals requiring oversight, specific suggestions for composition of expert review panels and threshold value of serum HBV DNA considered "safe" for practice (<1,000 IU/ml). These recommendations also explicitly address the issue of medical and dental students who are discovered to have chronic HBV infection. For most chronically HBV-infected providers and students who conform to current standards for infection control, HBV infection status alone does not require any curtailing of their practices or supervised learning experiences. These updated recommendations outline the criteria for safe clinical practice of HBV-infected providers and students that can be used by the appropriate occupational or student health authorities to develop their own institutional policies. These recommendations also can be used by an institutional expert panel that monitors providers who perform exposure-prone procedures.


Developments in life expectancy in Germany. Current trends.
Since the beginning of the 1990s, life expectancy in Germany has increased by 4.2 years among women (to 83.2 years), and by 5.9 years among men (to 78.4 years). This rise is related to the increasing convergence of life expectancy in Germany's new and old federal states. Recently, life expectancy among women in the new federal states has even risen slightly above the level found in the old federal states. In addition, differences between socioeconomic groups continue to be observed in Germany. Women in the highest income group have a 4.4-year longer life expectancy than women in the lowest income group. Similarly, an 8.6-year difference exists between men in the highest income group and men in the lowest income group. Influenza waves can adversely affect the development of life expectancy in certain calendar years. In comparison to other European countries, Germany has a mid-range life expectancy: the current difference between life expectancy in Germany and Switzerland (the European country with the highest life expectancy) is 2.7 years.


Semen collection in rhinoceroses (Rhinoceros unicornis, Diceros bicornis, Ceratotherium simum) by electroejaculation with a uniquely designed probe.
Electroejaculation in rhinoceroses has historically yielded inconsistent results, with the collection of high-quality, sperm-rich samples rare. The goal of this study was to develop a reliable method of electroejaculation in the rhinoceros by designing a rectal probe that appropriately fits the anatomy of this taxon and refining the procedure. A curved probe handle ending in an oblate, ellipsoid head was built using readily available supplies. A combination of rectal massage, penile massage, and electrical stimulation with a specially designed probe was employed in attempts to collect semen on 14 occasions from greater one-horned rhinoceroses (Rhinoceros unicornis; n = 4), black rhinoceroses (Diceros bicornis; n = 2) and a southern white rhinoceros (Ceratotherium simum; n = 1). During 13 of the 14 attempts, ejaculates were collected in multiple fractions. All but one of the ejaculates contained spermatozoa, and seven ejaculates contained good-quality fractions of semen (-60% sperm motility; > or =20 x 106 spermatozoa/ml) suitable for sperm banking and assisted reproduction procedures. Mean (+/-SEM) values for volume, pH, osmolality, and total sperm number for ejaculates containing good-quality fractions (98.2 +/-21.8 ml, 8.5+/-0.1, 290.4+/-6.7 mOsm, and 37.1+/-12.0 x 10(9), respectively) did not differ (P > 0.05) from those containing only poor-quality samples. Urine and/or erythrocyte contamination was not uncommon in fractions of both ejaculate types. Males producing good-quality samples ranged in age from 7 to 34 yr. None of the samples contained > or =75% morphologically normal spermatozoa. Electroejaculation with a uniquely designed probe consistently produced ejaculates in the rhinoceros. However, the production of high-quality samples continued to be challenging, occurring in only 50% of collection attempts. Regardless, the technology has progressed to a stage at which good-quality semen samples can be produced for sperm banking and assisted reproduction, and thereby can be integrated into intensive rhinoceros management strategies for the ultimate survival of this taxon.


The protective effect of inflammatory monocytes during systemic C. albicans infection is dependent on collaboration between C-type lectin-like receptors.
Invasive candidiasis, mainly caused by Candida albicans, is a serious healthcare problem with high mortality rates, particularly in immunocompromised patients. Innate immune cells express pathogen recognition receptors (PRRs) including C-type lectin-like receptors (CLRs) that bind C. albicans to initiate an immune response. Multiple CLRs including Dectin-1, Dectin-2 and Mincle have been proposed individually to contribute to the immune response to C. albicans. However how these receptors collaborate to clear a fungal infection is unknown. Herein, we used novel multi-CLR knockout (KO) mice to decipher the individual, collaborative and collective roles of Dectin-1, Dectin-2 and Mincle during systemic C. albicans infection. These studies revealed an unappreciated and profound role for CLR co-operation in anti-fungal immunity. The protective effect of multiple CLRs was markedly greater than any single receptor, and was mediated through inflammatory monocytes via recognition and phagocytosis of C. albicans, and production of C. albicans-induced cytokines and chemokines. These CLRs were dispensable for mediating similar responses from neutrophils, likely due to lower expression of these CLRs on neutrophils compared to inflammatory monocytes. Concurrent deletion of Dectin-1 and Dectin-2, or all three CLRs, resulted in dramatically increased susceptibility to systemic C. albicans infection compared to mice lacking a single CLR. Multi-CLR KO mice were unable to control fungal growth due to an inadequate early inflammatory monocyte-mediated response. In response to excessive fungal growth, the multi-CLR KO mice mounted a hyper-inflammatory response, likely leading to multiple organ failure. Thus, these data reveal a critical role for CLR co-operation in the effective control of C. albicans and maintenance of organ function during infection.


Stimulation of sperm production by human luteinizing hormone in gonadotropin-suppressed normal men.
The relative roles of FSH and LH in the control of human spermatogenesis are not well established. We previously reported that supraphysiological doses of hCG can stimulate sperm production in gonadotropin-suppressed normal men despite prepubertal FSH levels. To determine whether more nearly physiological levels of human LH (hLH) also can stimulate spermatogenesis when FSH levels are suppressed, we administered hLH to normal men whose endogenous gonadotropin levels and sperm production were suppressed by exogenous testosterone enanthate (T). After a 3-month control period, 11 normal men received 200 mg T, im, weekly to suppress LH and FSH. T administration alone was continued for 3-4 months until 3 successive sperm concentrations (performed twice monthly) revealed azoospermia or severe oligospermia (sperm concentrations, less than 4 million/ml). Then, while continuing T, 4 of the 11 men (experimental subjects) simultaneously received 1100 IU hLH, sc, daily for 4-6 months to replace LH activity, leaving FSH activity suppressed. The effect on sperm production of the selective FSH deficiency produced by hLH plus T administration was determined. The remaining 7 men (control subjects) continued to receive T alone at the same dosage, without gonadotropin replacement, for an additional 6 months. In the four experimental subjects, sperm concentrations increased significantly from 0.7 +/- 0.7 million/ml (mean +/- SEM) during T treatment alone to 19 +/- 4 million/ml during hLH plus T administration (P less than 0.001). However, none of the men achieved sperm concentrations consistently in their own pretreatment range. Sperm motilities and morphologies were normal in all four subjects by the end of hLH plus T administration. In contrast, sperm concentrations in the seven control subjects remained suppressed (less than 3 million/ml) throughout the entire period of prolonged T administration alone. Serum LH bioactivity, determined monthly by in vitro mouse Leydig cell bioassay in all four experimental subjects, was markedly suppressed during T administration alone (120 +/- 10 ng/ml) compared to that during the control period (390 +/- 20 ng/ml; P less than 0.001). With the addition of hLH to T, LH bioactivity returned to control levels (400 +/- 40 ng/ml; P = NS compared to control value). Serum FSH levels determined monthly by RIA were reduced from 98 +/- 12 ng/ml during the control period to undetectable levels (less than 25 ng/ml) during the T alone and the hLH plus T periods (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)


An overview of current evaluation methods of postgraduate dental specialty residents.
A lack of contemporary dental literature exists on evaluating dental residents in postgraduate education, with no standardized criteria or information on technology adoption. This study aims to understand current evaluation methods in dental residency programs and compare them to existing literature. A survey with 22 questions was sent to program directors of 749 ADA/CODA (American Dental Association/Commission on Dental Accreditation)-accredited postgraduate dental residencies. The questions focused on evaluation frequency, faculty involvement, submission methods, and electronic software usage. The survey response rate was 30.2% (226 responses). Results show that 98% of program directors are involved in evaluations, but require more support from auxiliary faculty. Evaluations are typically submitted twice or four times a year, with 12% of programs wanting increased frequency. Face-to-face delivery of feedback is considered crucial. While desktop computers are widely used for evaluation submission, 55% of programs utilize mobile devices, which correlates with higher program director satisfaction. The most popular evaluation software includes New Innovations, MEd Hub, and Qualtrics. Overall, 86.96% of program directors are satisfied with current evaluation practices. Areas needing improvement are non-program director faculty involvement, resident response/feedback, and software navigation. This study found that a majority of program directors of the postgraduate dental education system are using electronic technology for their resident evaluation systems and are satisfied with their current mechanism of evaluation.


VIP Regulates Morphology and F-Actin Distribution of Schlemm's Canal in a Chronic Intraocular Pressure Hypertension Model via the VPAC2 Receptor.
To investigate the roles of vasoactive intestinal peptides (VIPs) in regulating the morphology and F-actin distribution of Schlemm's canal (SC) of rat eyes. Chronic intraocular pressure (IOP) hypertension models with episcleral venous cauterization (EVC) were treated with topical VIP or PG99-465 (vasoactive intestinal peptide receptors 2 [VPAC2] antagonist). IOPs were measured with Tono-Pen, and the SC parameters, including the cross-section area, circumference, and length, were statistically evaluated by hematoxylin-eosin and CD31 immunohistochemical staining. Immunofluorescence was performed to detect the distribution of F-actin in the SC. Moreover, the distribution of filamentous actin (F-actin) and globular actin (G-actin) in human umbilical vein endothelial cells (HUVECs) was studied under a pressure system by immunofluorescence and Western blotting. Increased expressions of VIP and VPAC2 receptors, as well as a disordered distribution of F-actin were found in SC endothelial cells (SCEs) in the EVC model. Moreover, topical VIP maintained the normal distribution of F-actin in SCEs, expanded the collapsed SC, and induced a significant decrease in IOP in the EVC model. In in vitro HUVECs, the F-actin/G-actin ratio increased significantly under stress stimulation for 30 minutes. A total of 50 μM VIP helped maintain the normal F-actin/G-actin ratio of HUVECs against stress stimulation. VIP regulates the distribution of F-actin in SCEs via the VPAC2 receptor in order to induce a decrease in IOP. VIP may represent a new target for antiglaucoma drugs.


DNA recovery from wild chimpanzee tools.
Most of our knowledge of wild chimpanzee behaviour stems from fewer than 10 long-term field sites. This bias limits studies to a potentially unrepresentative set of communities known to show great behavioural diversity on small geographic scales. Here, we introduce a new genetic approach to bridge the gap between behavioural material evidence in unhabituated chimpanzees and genetic advances in the field of primatology. The use of DNA analyses has revolutionised archaeological and primatological fields, whereby extraction of DNA from non-invasively collected samples allows researchers to reconstruct behaviour without ever directly observing individuals. We used commercially available forensic DNA kits to show that termite-fishing by wild chimpanzees (Pan troglodytes schweinfurthii) leaves behind detectable chimpanzee DNA evidence on tools. We then quantified the recovered DNA, compared the yield to that from faecal samples, and performed an initial assessment of mitochondrial and microsatellite markers to identify individuals. From 49 termite-fishing tools from the Issa Valley research site in western Tanzania, we recovered an average of 52 pg/μl chimpanzee DNA, compared to 376.2 pg/μl in faecal DNA extracts. Mitochondrial DNA haplotypes could be assigned to 41 of 49 tools (84%). Twenty-six tool DNA extracts yielded >25 pg/μl DNA and were selected for microsatellite analyses; genotypes were determined with confidence for 18 tools. These tools were used by a minimum of 11 individuals across the study period and termite mounds. These results demonstrate the utility of bio-molecular techniques and a primate archaeology approach in non-invasive monitoring and behavioural reconstruction of unhabituated primate populations.


The promise of open survey questions-The validation of text-based job satisfaction measures.
Recent advances in computer-aided text analysis (CATA) have allowed organizational scientists to construct reliable and convenient measures from open texts. As yet, there is a lack of research into using CATA to analyze responses to open survey questions and constructing text-based measures of psychological constructs. In our study, we demonstrated the potential of CATA methods for the construction of text-based job satisfaction measures based on responses to a completely open and semi-open question. To do this, we employed three sentiment analysis techniques: Linguistic Inquiry and Word Count 2015, SentimentR and SentiStrength, and quantified the forms of measurement error they introduced: specific factor error, algorithm error and transient error. We conducted an initial test of the text-based measures' validity, assessing their convergence with closed-question job satisfaction measures. We adopted a time-lagged survey design (Nwave 1 = 996; Nwave 2 = 116) to test our hypotheses. In line with our hypotheses, we found that specific factor error is higher in the open question text-based measure than in the semi-open question text-based measure. As expected, algorithm error was substantial for both the open and semi-open question text-based measures. Transient error in the text-based measures was higher than expected, as it generally exceeded the transient error in the human-coded and the closed job satisfaction question measures. Our initial test of convergent and discriminant validity indicated that the semi-open question text-based measure is especially suitable for measuring job satisfaction. Our article ends with a discussion of limitations and an agenda for future research.


Psychosocial interventions for children and adolescents after man-made and natural disasters: a meta-analysis and systematic review.
Children and adolescents are a vulnerable group to develop post-traumatic stress symptoms after natural or man-made disasters. In the light of increasing numbers of refugees under the age of 18 years worldwide, there is a significant need for effective treatments. This meta-analytic review investigates specific psychosocial treatments for children and adolescents after man-made and natural disasters. In a systematic literature search using MEDLINE, EMBASE and PsycINFO, as well as hand-searching existing reviews and contacting professional associations, 36 studies were identified. Random- and mixed-effects models were applied to test for average effect sizes and moderating variables. Overall, treatments showed high effect sizes in pre-post comparisons (Hedges' g = 1.34) and medium effect sizes as compared with control conditions (Hedges' g = 0.43). Treatments investigated by at least two studies were cognitive-behavioural therapy (CBT), eye movement desensitization and reprocessing (EMDR), narrative exposure therapy for children (KIDNET) and classroom-based interventions, which showed similar effect sizes. However, studies were very heterogenic with regard to their outcomes. Effects were moderated by type of profession (higher level of training leading to higher effect sizes). A number of effective psychosocial treatments for child and adolescent survivors of disasters exist. CBT, EMDR, KIDNET and classroom-based interventions can be equally recommended. Although disasters require immediate reactions and improvisation, future studies with larger sample sizes and rigorous methodology are needed.


Associative and phonological priming effects after letter search on the prime.
Responses to target words typically are faster and more accurate after associatively related primes (e.g., "orange-juice") than after unrelated primes (e.g., "glue-juice"). This priming effect has been used as an index of semantic activation, and its elimination often is cited as evidence against semantic access. When participants are asked to perform a letter search on the prime, associative priming typically is eliminated, but repetition and morphological priming remain. It is possible that priming survives letter search when it arises from activity in codes that are represented before semantics. This experiment examined associative and phonological priming to determine whether priming from phonologically related rhymes would remain after letter search (e.g., "moose-juice"; rhyming items were orthographically dissimilar). When participants read the primes, equivalent associative and phonological priming effects were obtained; both effects were eliminated after letter search. The impact of letter search on semantic and phonological access and implications for the structural arrangement of lexical and semantic memory are discussed.


Reducing potential mental health issues and alcohol abuse through an early prevention model for victims of peer harassment.
Psychological disability, including alcohol abuse and mental health issues, are associated with numerous interpersonal, intrapersonal, and occupational difficulties. Employers often bear the greatest economic impact of maladaptive behavior due to greater employee turnover, poor work performance, and other negative work outcomes. Despite these negative outcomes, researchers have yet to examine possible benefits of prevention and intervention programs designed specifically to limit adulthood occupational problems. In this paper, an early prevention/intervention model is suggested. Specifically, the authors suggest that early preventions and interventions should target peer victimization in elementary school settings, as peer victimization has been shown to lead to mental health issues and alcohol abuse. Furthermore, the authors suggest that limiting the occurrence of these psychological difficulties would decrease occurrence of substance use and abuse, decrease the occurrence of later mental health problems, and, therefore, decrease negative occupational outcomes. The authors assert that such early prevention/intervention programs have the opportunity to minimize the need for costly, adulthood interventions and may maximize individuals' potential gains.


Food Habits of Older Australians Living Alone in the Australian Capital Territory.
The link between adequate nutrition and quality of life for older persons is well established. With the proportion of older adults increasing, policy regarding support and care for the ageing has shifted emphasis to keeping older adults in their homes for as long as possible. Risk of malnutrition is an issue of importance for this population and, while this risk is well researched within the hospital setting, it is still relatively under-researched within the community-dwelling elderly, particularly with respect to the lived experience. This qualitative study (underpinned by interpretative phenomenology philosophy) explores how the lived experiences of community-dwelling older people living in one-person households in the Australian Capital Territory (ACT) influences dietary patterns, food choices and perceptions about food availability. Using purposeful and snowballing sampling, older people (65 years and over) living alone in the community participated in focus group discussions triangulated with their family/carers. Data were thematically analysed using a previously established approach. Participants (n = 22) were interviewed in three focus groups. Three themes were identified: active and meaningful community connectedness; eating well and behaviours to promote dietary resilience. Of these, community connectedness was pivotal in driving food patterns and choices and was a central component influencing behaviours to eating well and maintaining dietary resilience.


COVID-19 and informal settlements - implications for water, sanitation and health in India and Indonesia.
Informal settlements are home to over 1 billion people worldwide and are characterised by high population densities and poor environmental conditions. The authors identify the impact of COVID-19 on existing water and sanitation practices and potential pathways for the transmission of COVID-19 in informal settlements in India and Indonesia. In the short term, there is an urgent need for mobile and contactless hand washing, washing/bathing facilities and toilets. In the long term, COVID-19 provides an opportunity to invest in centralised water and sanitation networked solutions appropriate for high-density settings to integrate those settlements into cities and improve environmental conditions and health in these cities.


Laser in situ monitoring of combustion processes.
Several examples of laser in situ monitoring of combustion processes are presented. Using a frequency modulated (13)CO(2) waveguide laser, in situ concentrations of NH(3) down to 1 ppm were measured at temperatures up to 600 degrees C in waste incinerators and power or chemical plants. Following ignition of CH(3)OH-O(2) mixtures by a TEA CO(2) laser, gas temperature profiles were measured using rapid scanning tunable diode laser spectroscopy of CO molecules. In laminar CH(4)-air counterflow diffusion flames at atmospheric pressure absolute concentrations, temperatures, and collisional lifetimes of OH radicals were determined by 2-D and picosecond LIF and absorption spectroscopy. Two-dimensional LIF and Mie scattering were used to observe fuel injection and combustion in a diesel engine.


The bithorax complex of Drosophila an exceptional Hox cluster.
In his 1978 seminal paper, Ed Lewis described a series of mutations that affect the segmental identities of the segments forming the posterior two-thirds of the Drosophila body plan. In each class of mutations, particular segments developed like copies of a more-anterior segment. Genetic mapping of the different classes of mutations led to the discovery that their arrangement along the chromosome paralleled the body segments they affect along the anteroposterior axis of the fly. As all these mutations mapped to the same cytological location, he named this chromosomal locus after its founding mutation. Thus the first homeotic gene (Hox) cluster became known as the bithorax complex (BX-C). Even before the sequencing of the BX-C, the fact that these similar mutations grouped together in a cluster, lead Ed Lewis to propose that the homeotic genes arose through a gene duplication mechanism and that these clusters would be conserved through evolution. With the identification of the homeobox in the early 1980s, Lewis' first prediction was confirmed. The two cloned Drosophila homeotic genes, Antennapedia and Ultrabithorax, were indeed related genes. Using the homeobox as an entry point, homologous genes have since been cloned in many other species. Today, Hox clusters have been discovered in almost all metazoan phyla, confirming Lewis' second prediction. Remarkably, these homologous Hox genes are also arranged in clusters with their order within each cluster reflecting the anterior boundary of their domain of expression along the anterior-posterior axis of the animal. This correlation between the genomic organization and the activity along the anteroposterior body axis is known as the principle of "colinearity." The description of the BX-C inspired decades of developmental and evolutionary biology. And although this first Hox cluster led to the identification of many important features common to all Hox gene clusters, it now turns out that the fly Hox clusters are rather exceptional when compared with the Hox clusters of other animals. In this chapter, we will review the history and salient features of bithorax molecular genetics, in part, emphasizing its unique features relative to the other Hox clusters.


Self-management behavior among patients with diabetic retinopathy in the community: a structural equation model.
Diabetic retinopathy (DR) is an important, chronic complication of diabetes, requiring competent self-management that depends on adherence to behavioral regimens. This study attempted to identify factors influencing self-management behaviors and develop a model illustrating the interdependence of several factors associated with DR patients. In June-December 2012, 368 patients with DR completed questionnaires assessing self-management behavior, diabetes knowledge, health beliefs, social support, and treatment adherence. Structural equation modeling was used to test predicted pathways linking self-management behavior to diabetes knowledge, health beliefs, social support, and treatment adherence. The results indicated that health beliefs, treatment adherence, and duration of diabetes each had a direct impact on diabetes self-management (p < 0.05). Diabetes knowledge only indirectly influenced diabetes self-management, through health beliefs. Social support had a direct impact on diabetes self-management (β = 0.35, p < 0.01), and an indirect influence on diabetes self-management, through treatment adherence (β = 0.77, p < 0.01). Health beliefs, treatment adherence, and social support directly affect diabetes self-management, and diabetes knowledge indirectly affects diabetes self-management. This suggests that enhancing DR patients' health beliefs, treatment adherence, and social support would facilitate their diabetes self-management. Meanwhile, improved health education can strengthen diabetes knowledge, which in turn, can positively affect diabetes self-management.


Consumption of Dairy Yogurt Containing Lactobacillus paracasei ssp. paracasei, Bifidobacterium animalis ssp. lactis and Heat-Treated Lactobacillus plantarum Improves Immune Function Including Natural Killer Cell Activity.
The aim of this study was to investigate the impact of consuming dairy yogurt containing Lactobacillus paracasei ssp. paracasei (L. paracasei), Bifidobacterium animalis ssp. lactis (B. lactis) and heat-treated Lactobacillus plantarum (L. plantarum) on immune function. A randomized, open-label, placebo-controlled study was conducted on 200 nondiabetic subjects. Over a twelve-week period, the test group consumed dairy yogurt containing probiotics each day, whereas the placebo group consumed milk. Natural killer (NK) cell activity, interleukin (IL)-12 and immunoglobulin (Ig) G1 levels were significantly increased in the test group at twelve weeks compared to baseline. Additionally, the test group had significantly greater increases in serum NK cell activity and interferon (IFN)-γ and IgG1 than placebo group. Daily consumption of dairy yogurt containing L. paracasei, B. lactis and heat-treated L. plantarum could be an effective option to improve immune function by enhancing NK cell function and IFN-γ concentration (ClinicalTrials.gov: NCT03051425).


Epidemiology in multiple sclerosis: a pilgrim's progress.
There was more neurology taught under Harold G. Wolff at Cornell University Medical College in New York than perhaps anywhere else in the country when I attended from 1948 to 1952. I took my residency at the Veterans Administration Hospital in the Bronx, New York, a teaching hospital of Cornell, with Wolff as my Director of Training. While a resident, we thought we had found a treatment for multiple sclerosis. To test our conclusion, the first Class 1 treatment trial ever conducted for multiple sclerosis was performed. This showed no effect, but the participants began investigating multiple sclerosis among the 16 million persons at prime age for symptom onset who had served in the military in World War II. This led me to study its epidemiology worldwide, beginning with a detailed review of all published population-based estimates of frequency. Among these were nationwide surveys from Sweden, Denmark, Switzerland and later Norway and Finland, which showed in each country a concentration of the significantly high regions into contiguous areas forming a single 'focus' in each land, maximal in Denmark under the age of 15 years. The primary locus of high frequency multiple sclerosis seemed to be in the south-central inland lake region of Sweden, with spread to its contiguous neighbours. These concentrations in time and space indicated that multiple sclerosis was a disease probably acquired in early adolescence. Migration studies supported this: moves from high to low showed retention of birthplace risk only for those aged >15 years, whereas opposite moves indicated susceptibility limited to some 11-45 year olds. Epidemics of multiple sclerosis would suggest the disease is not only acquired but also infectious. If an infectious origin were true, transmission would have to occur before clinical onset, and would have to involve a much greater number of subjects than clinically involved. I believe there have been epidemics in Iceland, Shetland-Orkney and the Faroe Islands. On the Faroes there were no cases of multiple sclerosis among native-born resident Faroese from 1900 until 1943, when the first of 21 cases had clinical onset, heralding a type 1 epidemic with peak incidence rates >10 per 100,000 for 1945-46. British troops who occupied the islands from April 1940 to September 1945 we believe brought a widespread (because of the scatter of Faroese cases), asymptomatic (because they were healthy troops), persistent infection we called the primary multiple sclerosis affection that involved a large proportion of Faroese, with clinical multiple sclerosis ensuing in a very small proportion. Primary multiple sclerosis affection itself may have been manifest there as a newly introduced cause of acute infectious gastroenteritis and is possibly the underlying cause of multiple sclerosis in general.


Identification of candidate genes in scleroderma-related pulmonary arterial hypertension.
We hypothesize that pulmonary arterial hypertension (PAH)-associated genes identified by expression profiling of peripheral blood mononuclear cells (PBMCs) from patients with idiopathic pulmonary arterial hypertension (IPAH) can also be identified in PBMCs from scleroderma patients with PAH (PAH-SSc). Gene expression profiles of PBMCs collected from IPAH (n = 9), PAH-SSc (n = 10) patients, and healthy controls (n = 5) were generated using HG_U133A_2.0 GeneChips and were processed by the RMA/GCOS_1.4/SAM_1.21 data analysis pipeline. Disease severity in consecutive patients was assessed by functional status and hemodynamic measurements. The expression profiles were analyzed using PAH severity-stratification, and identified candidate genes were validated with real-time polymerase chain reaction (PCR). Transcriptomics of PBMCs from IPAH patients was highly comparable with that of PMBCs from PAH-SSc patients. The PBMC gene expression patterns significantly correlate with right atrium pressure (RA) and cardiac index (CI), which are known predictors of survival in PAH. Array stratification by RA and CI identified 364 PAH-associated candidate genes. Gene ontology (GO) analysis revealed significant (Z(score) > 1.96) alterations in angiogenesis genes according to PAH severity: matrix metalloproteinase 9 (MMP9) and vascular endothelial growth factor (VEGF) were significantly upregulated in mild as compared with severe PAH and healthy controls, as confirmed by real-time PCR. These data demonstrate that PBMCs from patients with PAH-SSc carry distinct transcriptional expression. Furthermore, our findings suggest an association between angiogenesis-related gene expression and severity of PAH in PAH-SSc patients. Deciphering the role of genes involved in vascular remodeling and PAH development may reveal new treatment targets for this devastating disorder.


Is Childhood Overweight/Obesity Perceived as a Health Problem by Mothers of Preschool Aged Children in Bangladesh? A Community Level Cross-Sectional Study.
Childhood obesity is rapidly rising in many developing countries such as Bangladesh; however, the factors responsible for this increase are not well understood. Being the primary caregivers of children, particularly in developing countries, maternal perceptions and knowledge could be important factors influencing the weight status of children. This study aimed to assess maternal perceptions of childhood obesity and associated socio-demographic factors in Bangladesh. A cross-sectional study using stratified random sampling was conducted among 585 mothers whose children aged 4 to 7 years attended preschools in a district town. Body Mass Index of the children was calculated and weight status categorized according to the Centers for Disease Control (CDC) criteria. Maternal perceptions were assessed using a self- or interviewer-administered questionnaire. Multinomial logistic regression was used to obtain crude and adjusted odds ratios. Fourteen percent of children were overweight or obese and approximately 30% were underweight. Only 3.1% of children were perceived as overweight/obese by their mothers. Over one-third (35%) of mothers perceived that childhood overweight/obesity could be a health problem and over two-thirds (68.6%) were not aware of any health consequences of childhood obesity. Maternal perceptions were significantly associated with maternal education, family income, and weight status of the child but were not associated with the sex of the child. We have identified knowledge gaps regarding maternal perception of childhood obesity and its contributing factors in a developing country. These findings can be used to develop and test parent-focused educational interventions for preventing childhood obesity in Bangladesh.


Erythrocyte phosphoinositide metabolism in essential hypertensive patients and their normotensive offspring.
The metabolism of phosphoinositides was investigated in erythrocyte membranes of essential hypertensive patients, normotensive offspring of hypertensive patients and matched controls. Measurement of 32P-labelling of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate revealed no differences in the rate of incorporation of the isotope in essential hypertensive patients compared with controls. In the normotensive offspring of essential hypertensive patients there was a highly significant increase in the rate of 32P incorporation (P less than 0.01), compared with matched controls, indicating a higher rate of metabolic turnover in these subjects. These data demonstrate that phosphoinositide metabolism is enhanced in subjects genetically at risk of hypertension, before the blood pressure has risen, but once the blood pressure is established, it is no different from control values. Abnormal phosphoinositide metabolism may be a further manifestation of a genetically determined defect of membrane physicochemical function underlying essential hypertension.


[Lúpus erythematosus].
Systemic Lúpus Erythematosus (SLE) is an auto-imune disorder, with multiple organ involvement, characterized by vascular and connective tissue inflammation, as well as antinuclear antibodies (ANA). We report a case of a black teenager with a past of arthritis of knees, fever and astenia during the year previous to this admission. She was admitted to the Pediatric Intensive Care Unit (PICU) for bilateral Streptococcus pneumoniae pneumonia complicated by pleural effusion. She also had generalized edema and macroscopic hematúria. She was started on antibiotics, with improvement. The studies were compatible with active SLE, poliserositis, nephrotic proteinúria, lupic nephritis class IV and serious anemia. During the admission, she had symptomatic hypertension with tonic-clonic seizure. She was transferred to Italy, clinically stable, medicated with steroids, anti-hypertensive and anti-convulsant drugs.


In-office discussions of migraine: results from the American Migraine Communication Study.
Research indicates that successful migraine assessment and treatment depends on information obtained during patient and healthcare professional (HCP) discussions. However, no studies outline how migraine is actually discussed during clinical encounters. Record naturally occurring HCP-migraineur interactions, analyzing frequency and impairment assessment, and preventive treatment discussions. HCPs seeing high volumes of migraineurs were recruited for a communication study. Patients likely to discuss migraine were recruited immediately before their normally scheduled appointment and, once consented, were audio- and video-recorded without a researcher present. Separate post-visit interviews were conducted with patients and HCPs. All interactions were transcribed. Sixty patients (83% female; mean age 41.7) were analyzed. Patients were diagnosed with migraine 14 years and experienced 5 per month, on average. Transcripts were analyzed using sociolinguistic techniques such as number and type of questions asked and post-visit alignment on migraine frequency and impairment. American Migraine Prevalence and Prevention Study guidelines were utilized. Ninety-one percent of HCP-initiated, migraine-specific questions were closed-ended/short answer; assessments focused on frequency and did not focus on attention on impairment. Open-ended questions in patient post-visit interviews yielded robust impairment-related information. Post-visit, 55% of HCP-patient pairs were misaligned regarding frequency; 51% on impairment. Of the 20 (33%) patients who were preventive medication candidates, 80% did not receive it and 50% of their visits lacked discussion of prevention. Sociolinguistic analysis revealed that HCPs often used narrowly focused, closed-ended questions and were often unaware of how migraine affected patients' lives as a result. It is recommended that HCPs assess impairment using open-ended questions in combination with the ask-tell-ask technique.


Monoamine oxidase-inhibition and MPTP-induced neurotoxicity in the non-human primate: comparison of rasagiline (TVP 1012) with selegiline.
The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to induce parkinsonism in man and non-human primates. Monoamine-oxidase B (MAO-B) has been reported to be implicated in both MPTP-induced parkinsonism and Parkinson's disease, since selegiline (L-deprenyl), an irreversible MAO-B inhibitor, prevents MPTP-induced neurotoxicity in numerous species including mice, goldfish and drosophyla. However, one disadvantage of this substance relates to its metabolism to (-)-methamphetamine and (-)-amphetamine. Rasagiline (R-(+)-N-propyl-1-aminoindane) is a novel irrevesible MAO-B-inhibitor, which is not metabolized to metamphetamine and/or amphetamine. The present study compared the effects of high doses of selegiline and rasagiline (10 mg/kg body weight s.c.) on MPTP-induced dopaminergic neurotoxicity in a non-human primate (Callithrix jacchus) model of PD. Groups of four monkeys were assigned to the following six experimental groups: Group I: Saline, Group II: Selegiline/Saline, Group III: Rasagiline/Saline, Group IV: MPTP/Saline, Group V: Rasagiline/MPTP, Group VI: Selegiline/MPTP. Daily treatment with MAO-B-inhibitors (either rasagiline or selegiline, 10 mg/kg body weight s.c.) was initiated four days prior to MPTP-exposure (MPTP-HCl, 2 mg/kg body weight subcutaneously, separated by an interval of 24 hours for a total of four days) and was continued until the end of the experiment, i.e. 7 days after the cessation of the MPTP-injections, when animals were sacrificed. MPTP-treatment caused distinct behavioural, histological, and biochemical alterations: 1. significant reduction of motor activity assessed by clinical rating and by computerized locomotor activity measurements; 2. substantial loss (approx. 40%) of dopaminergic (tyrosine-hydroxylase-positive) cells in the substantia nigra, pars compacta; and 3. putaminal dopamine depletion of 98% and its metabolites DOPAC (88%) and HVA (96%). Treatment with either rasagiline or selegiline markedly attenuated the neurotoxic effects of MPTP at the behavioural, histological, and at the biochemical levels. There were no significant differences between rasagiline/MPTP and selegiline/MPTP-treated animals in respect to signs of motor impairment, the number of dopaminergic cells in the substantia nigra, and striatal dopamine levels. As expected, both inhibitors decreased the metabolism of dopamine, leading to reduced levels of HVA and DOPAC (by >95% and 45% respectively). In conclusion, rasagiline and selegiline at the dosages employed equally protect against MPTP-toxicity in the common marmoset, suggesting that selegiline-derived metabolites are not important for the neuroprotective effects of high dose selegiline in the non-human MPTP-primate model in the experimental design employed. However, unexpectedly, high dose treatment with both MAO-inhibitors caused a decrease of the cell sizes of nigral tyrosine hydroxylase positive neurons. It remains to be determined, if this histological observation represents potential adverse effects of high dose treatment with monoamine oxidase inhibitors.


Trauma and posttraumatic stress symptoms predict alcohol and other drug consequence trajectories in the first year of college.
College matriculation begins a period of transition into adulthood, one that is marked by new freedoms and responsibilities. This transition also is marked by an escalation in heavy drinking and other drug use as well as a variety of use-related negative consequences. Trauma and symptoms of posttraumatic stress disorder (PTSD) may affect alcohol and drug problems and, thus, may be a point of intervention. Yet, no studies have examined trauma, PTSD, and alcohol and drug problem associations during this developmental period. The present study provides such an examination. Matriculating college students (N = 997) completed surveys in September (Time 1) and at 5 subsequent time points (Time 2-Time 6) over their 1st year of college. With latent growth analysis, trajectories of alcohol- and drug-related consequences were modeled to examine how trauma (No Criterion A Trauma, Criterion A Only, No PTSD Symptoms) and PTSD (partial or full) symptom status predicted these trajectories. Results showed substantial risk for alcohol- and other drug-related negative consequences that is conferred by the presence of PTSD at matriculation. Those with both partial and full PTSD started the year with more alcohol and drug consequences. These individuals showed a steeper decrease in consequences in the 1st semester, which leveled off as the year progressed. Both alcohol and drug consequences remained higher for those in the PTSD group throughout the academic year. Hyperarousal symptoms showed unique effects on substance consequence trajectories. Risk patterns were consistent for both partial and full PTSD symptom presentations. Trajectories did not vary by gender. Interventions that offer support and resources to students entering college with PTSD may help to ameliorate problem substance use and may ultimately facilitate a stronger transition into college and beyond.


Why the visual recognition system might encode the effects of illumination.
A key problem in recognition is that the image of an object depends on the lighting conditions. We investigated whether recognition is sensitive to illumination using 3-D objects that were lit from either the left or right, varying both the shading and the cast shadows. In experiments 1 and 2 participants judged whether two sequentially presented objects were the same regardless of illumination. Experiment 1 used six objects that were easily discriminated and that were rendered with cast shadows. While no cost was found in sensitivity, there was a response time cost over a change in lighting direction. Experiment 2 included six additional objects that were similar to the original six objects making recognition more difficult. The objects were rendered with cast shadows, no shadows, and as a control, white shadows. With normal shadows a change in lighting direction produced costs in both sensitivity and response times. With white shadows there was a much larger cost in sensitivity and a comparable cost in response times. Without cast shadows there was no cost in either measure, but the overall performance was poorer. Experiment 3 used a naming task in which names were assigned to six objects rendered with cast shadows. Participants practised identifying the objects in two viewpoints lit from a single lighting direction. Viewpoint and illumination invariance were then tested over new viewpoints and illuminations. Costs in both sensitivity and response time were found for naming the familiar objects in unfamiliar lighting directions regardless of whether the viewpoint was familiar or unfamiliar. Together these results suggest that illumination effects such as shadow edges: (1) affect visual memory; (2) serve the function of making unambigous the three-dimensional shape; and (3) are modeled with respect to object shape, rather than simply encoded in terms of their effects in the image.


Isolation and functional characterization of a novel endogenous inverse agonist of estrogen related receptors (ERRs) from human pregnancy urine.
Estrogen-receptor related receptors (ERRs) which consists of ERRα, ERRβ and ERRγ belong to the orphan nuclear receptor subfamily 3, group B (NR3B) subfamily, and are constitutively active. ERRs have been shown to actively modulate estrogenic responses, and to play an essential role in pregnancy, and are implicated in breast cancer progression. Despite intensive efforts, no endogenous ligand other than the ubiquitous sterol, cholesterol which binds ERRα, has been identified for ERRs so far. The discovery of ligands that bind these orphan receptors will allow the manipulation of this pathway and may lead to novel strategies for the treatment of cancer and other diseases. We previously reported the identification of a novel endogenous estradienolone-like steroid (ED) that is strongly bound to sex hormone binding globulin, in pregnant women. Our recent results show that ED acts as an inverse agonist of ERRα and ERRγ by directly interacting with these receptors, and inhibiting their transcriptional activity. We also demonstrate that ED inhibits the growth of both estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) breast cancer cells in a dose dependent manner, while of displaying a little effect on normal epithelial breast cells. Furthermore, the anti-mitogenic effect of ED in breast cancer cells is ERRα-dependent. These data suggest that ED-ERR interaction may represent a novel physiologically relevant hormone response pathway in the human. The finding that ED inhibits both ER negative and ER positive breast cancer cell growth may have important implications in pathophysiology breast cancer.