Uncovering sexual abuse: evaluation of the effectiveness of The Victims of Violence and Abuse Prevention Programme.
Discusses factors inhibiting open talk around a client's history of abuse including gender, age and diagnosis. * Evaluates the helpfulness of a training course designed to reduce and overcome these factors. * Aim of the evaluation is to help replicate the training nationally, following the positive impact found. Abstract Despite the high prevalence of sexual abuse among users of mental health services, it appears that mental health professionals are frequently unaware of clients' abuse histories. In order to address this, a Mental Health Trusts Collaboration Project of nine trusts was formed, which piloted delivering the Department of Health's Victims of Violence & Abuse Prevention Programme one-day education and training course regarding enquiring about histories of sexual abuse to various mental health practitioners. This hoped to educate practitioners in factors associated with victims and offenders, improve confidence and competence in asking about client's history of abuse and to increase awareness of the importance of asking. The purpose of this paper is to describe the impact of this course on mental health professionals' practice and attitudes in one of these nine trusts. It was found that since the delivery of the course, 44% (n= x) of professionals had been asking about abuse in 75-100% of cases. Gender, age and diagnosis of both the service users and the practitioners were all identified as factors potentially affecting practitioners' willingness to ask about abuse. Most importantly, 93% (n= x) of participants were found to feel they have the skills and knowledge to enquire about abuse and respond to disclosure in the appropriate way and 77% (n= x) of participants felt that this training had changed their clinical practice. The aim of this evaluation is to prove the effectiveness of the Department of Health's education and training course, which will help towards replicating the project nationally.


Accounting for animal movement improves vaccination strategies against wildlife disease in heterogeneous landscapes.
Oral baiting is used to deliver vaccines to wildlife to prevent, control, and eliminate infectious diseases. A central challenge is how to spatially distribute baits to maximize encounters by target animal populations, particularly in urban and suburban areas where wildlife such as raccoons (Procyon lotor) are abundant and baits are delivered along roads. Methods from movement ecology that quantify movement and habitat selection could help to optimize baiting strategies by more effectively targeting wildlife populations across space. We developed a spatially explicit, individual-based model of raccoon movement and oral rabies vaccine seroconversion to examine whether and when baiting strategies that match raccoon movement patterns perform better than currently used baiting strategies in an oral rabies vaccination zone in greater Burlington, Vermont, USA. Habitat selection patterns estimated from locally radio-collared raccoons were used to parameterize movement simulations. We then used our simulations to estimate raccoon population rabies seroprevalence under currently used baiting strategies (actual baiting) relative to habitat selection-based baiting strategies (habitat baiting). We conducted simulations on the Burlington landscape and artificial landscapes that varied in heterogeneity relative to Burlington in the proportion and patch size of preferred habitats. We found that the benefits of habitat baiting strongly depended on the magnitude and variability of raccoon habitat selection and the degree of landscape heterogeneity within the baiting area. Habitat baiting improved seroprevalence over actual baiting for raccoons characterized as habitat specialists but not for raccoons that displayed weak habitat selection similar to radiocollared individuals, except when baits were delivered off roads where preferred habitat coverage and complexity was more pronounced. In contrast, in artificial landscapes with either more strongly juxtaposed favored habitats and/or higher proportions of favored habitats, habitat baiting performed better than actual baiting, even when raccoons displayed weak habitat preferences and where baiting was constrained to roads. Our results suggest that habitat selection-based baiting could increase raccoon population seroprevalence in urban-suburban areas, where practical, given the heterogeneity and availability of preferred habitat types in those areas. Our novel simulation approach provides a flexible framework to test alternative baiting strategies in multiclass landscapes to optimize bait-distribution strategies.


In vitro death of jimpy oligodendrocytes: correlation with onset of DM-20/PLP expression and resistance to oligodendrogliotrophic factors.
Severe hypomyelination in the jimpy (jp) mouse mutation results from premature death of most oligodendrocytes (OCs). We have applied an immunopanning technique to successfully purify oligodendroblasts (OBs) directly from neonatal jp brainstem in order to determine if their death during differentiation into OCs is preventable in culture by diffusible oligodendrogliotrophic factors. No significant differences in the yield (0.9-1.1 x 10(5) cells/brainstem) or viability (approximately 90%) of OB populations from jp and wild-type (wt) littermates were observed, indicating that cell death occurs at a later stage in the mutant lineage. When cultured in a basally defined, insulin-containing medium, wt and jp OBs died 1-2 days later as their differentiation into GalC+ OCs began. Survival was not enhanced by known trophic factors (ciliary neurotrophic factor, leukemia inhibitory factor, neurotrophin-3) for differentiating rat OCs. In medium conditioned by neonatally derived rat or wt mouse astrocytes, however, wt OBs survived terminal OC differentiation, expressing first GalC, then DM-20/PLP on their surface 1-2 days later, before elaborating myelin-like membrane. By contrast, jp OBs in sister cultures survived differentiation initially as well as their normal counterparts did but rapidly died thereafter, beginning at the time when PLP/DM-20 immunoreactivity became detectable on premature wt GalC+ OCs. Additionally under these conditions, there survived a minor population (<5%) of jp cells, including mature OCs, which expressed stunted membranes and DM-20/PLP immunoreactivity in their cytoplasm, and undifferentiated progenitors. This model supports the concept that OC death in jp is effected by an intrinsic program, one mechanistically related to jp PLP/DM-20 gene expression and refractory to trophic cues in the environment.


Chlamydia trachomatis remodels stable microtubules to coordinate Golgi stack recruitment to the chlamydial inclusion surface.
Chlamydia trachomatis (Ctr), an obligate intracellular bacterium, survives and replicates within a membrane-bound vacuole, termed the inclusion, which intercepts host exocytic pathways to acquire nutrients. Ctr subverts cellular trafficking pathways from the Golgi by targeting small GTPases, including Rab proteins, to sustain intracellular bacterial replication; however, the precise mechanisms involved remain incompletely understood. Here, we show that Chlamydia infection in human epithelial cells induces microtubule remodeling, in particular the formation of detyrosinated stable MTs, to recruit Golgi ministacks, but not recycling endosomes, to the inclusion. These stable microtubules show increased resistance to chemically induced depolymerization, and their selective depletion results in reduced bacterial infectivity. Rab6 knockdown reversibly prevented not only Golgi ministack formation but also detyrosinated microtubule association with the inclusion. Our data demonstrate that Chlamydia co-opts the function of stable microtubules to support its development.


Beta-adrenergic receptor activation inhibits keratinocyte migration via a cyclic adenosine monophosphate-independent mechanism.
There is increasing evidence that G-protein-coupled receptors cross-talk with growth factor receptor-mediated signal transduction in a variety of cell types. We have investigated mechanisms by which the activation of beta-adrenergic receptors, classically GTP-binding proteins coupled receptors, influence the migration of cultured human keratinocytes. We found that iso-proterenol, a beta-adrenergic receptor-selective agonist, inhibited cell migration stimulated by either epidermal growth factor, or extracellular Ca2+ in a concentration-dependent manner. This was prevented by pretreatment of the cells with the beta-adrenergic receptor-selective antagonist timolol. Interestingly, isoproterenol, at a concentration of 1 nm, did not measurably increase intracellular cyclic adenosine monophosphate concentrations yet inhibited cell migration by 50%. To test further if isoproterenol's actions were mediated via activation of adenylyl cyclase, two inhibitors of its activity, 2'5'-dideoxyadenosine and SQ22536, were used. Both compounds significantly diminished iso-proterenol-induced increases in intracellular cyclic adenosine monophosphate concentrations but did not attenuate isoproterenol-induced inhibition of cell migration. Also, forskolin (1 microm) markedly increased intracellular cyclic adenosine monophosphate concentrations but did not significantly inhibit cell migration. As mitogen-activated protein kinases are known to signal growth factor-stimulated cell migration, we examined whether beta-adrenergic receptor-mediated inhibition of keratinocyte migration might occur via inactivation of mitogen-activated protein kinases. We found that isoproterenol inhibited phosphorylation of extracellular signal-regulated kinase mitogen-activated protein kinase in a concentration-dependent manner but had no effect on the phosphorylation of the stress mitogen-activated protein kinases c-jun N-terminal kinase and stress-activated protein kinase-2. Neither forskolin nor a membrane permeable cyclic adenosine monophosphate analog inhibited phosphorylation of any of these mitogen-activated protein kinases. These findings suggest that beta-adrenergic receptor-induced inhibition of keratinocyte migration is mediated through inhibition of the extracellular signal-regulated kinase mitogen-activated protein kinase signaling in a cyclic adenosine monophosphate-independent manner.


The roles of laminin and fibronectin in the development of the lens capsule.
This study examines the distribution of laminin and fibronectin in the rat lens capsule during development. Both these extracellular matrix glycoproteins are localised in the interspace between presumptive lens and presumptive retina as well as in their basal laminae. The lens capsule arises from multilayering of the basal lamina of the lens cells. Immunofluorescence localises both laminin and fibronectin in the capsule at 16 days of embryonic development, although reactivity for fibronectin is much weaker than for laminin. In the 19 day embryo only laminin is detected. This indicates that during embryonic development fibronectin becomes a minor component of lens cell ECM and is not accumulated in the developing capsule. The roles of laminin and fibronectin in promoting cell migration during development were analysed in explant cultures. Lens epithelial explants from 16, 17 and 19 day old embryos and neonatal rats were grown on a laminin or fibronectin substratum. Lens cells from all ages of rats migrated on the laminin substratum, whereas lens cells progressively lost the ability to migrate on a fibronectin substratum as the age of the donor increased. This developmental loss of ability to migrate on fibronectin in vitro coincides with the developmental loss of fibronectin from the lens capsule in vivo. Therefore, we propose that whilst both laminin and fibronectin may be important for promoting migration of lens cells on their substratum at early stages of lens morphogenesis, during development laminin takes over as the key molecule that promotes migration on the capsule.


Moderated Test Statistics to Detect Differential Deuteration in Hydrogen/Deuterium Exchange Mass Spectrometry Experiments.
With differential hydrogen/deuterium exchange, differences in the structure and dynamics of protein states can be studied. Detecting statistically significant differentially deuterated peptides is crucial to draw meaningful conclusions about the distinct conformations and dynamics of the protein under study. Here, we introduced a linear model in combination with an empirical Bayes approach to detect differentially deuterated peptides. Using a linear model allows one to test for differences in deuteration between two (two-sample t-test) or more groups (F-statistic), while potentially controlling for the effects of other variables that are not of interest. The empirical Bayes approach improves the estimation of deuteration-level variances, especially in experiments with a low number of replicates. As a consequence, the two sample t-tests and the F-statistic become moderated, resulting in a lower number of false positive and false negative findings. Furthermore, we introduce a thresholded-moderated t-statistic to test if the observed deuteration differences are larger than a specified, biologically relevant difference. Finally, we underline the importance of having a sufficient number of replicates, and the effect of the number of replicates on the power of the statistical significance tests. The R-code for the proposed moderated test statistics is available upon request.


Impact of fluoridation in a private pedodontic practice: thirty years later.
For years, dental practitioners, educators, and researchers have sought to reduce the incidence of dental caries and periodontal disease. The efforts to prevent dental caries have focused on the promotion of community water fluoridation, school fluoride-rinse-programs, topical fluoride treatments, fluoridated toothpastes, and plaque-and-diet control. It is not until recently that the striking results of these efforts have become evident. Surveys such as this one, showing the diminished severity of caries in the child population, confirm the impression of many private practitioners. The dental profession should not be surprised by the effectiveness of our preventive programs, nor be unprepared for the future needs of our patients. We should accelerate our preventive efforts, while at the same time anticipating the future with appropriate adjustments in dental curricula, manpower, and practice.


Regulation of pdx-1 gene expression.
The homeodomain-containing transcription factor pancreatic duodenal homeobox 1 (PDX-1) plays a key role in pancreas development and in beta-cell function. Upstream sequences of the gene up to about -6 kb show islet-specific activity in transgenic mice. Attempts to identify functional regulatory elements involved in the controlled expression of the pdx-1 gene led to the identification of distinct distal beta-cell-specific enhancers in human and rat genes. Three additional sequences, conserved between the mouse and the human 5'-flanking regions, two of which are also found in the chicken gene, conferred beta-cell-specific expression on a reporter gene, albeit to different extents. A number of transcription factors binding to and modulating the transcriptional activity of the regulatory elements were identified, such as hepatocyte nuclear factor (HNF)-3beta, HNF-1alpha, SP1/3, and, interestingly, PDX-1 itself. A fourth conserved region was localized to the proximal promoter around an E-box motif and was found to bind members of the upstream stimulatory factor (USF) family of transcription factors. We postulate that disruption of pdx-1 cis-acting regulatory sequences and/or mutations or functional impairment of transcription factors controlling the expression of the gene can lead to diabetes.


Legionella confirmation using real-time PCR and SYTO9 is an alternative to current methodology.
The currently accepted culture techniques for the detection of Legionella spp. in water samples (AS/NZS 3896:1998 and ISO 11731 standard methods) are slow and laborious, requiring from 7 to 14 days for a result. We describe a fully validated rapid confirmation technique that uses real-time PCR incorporating the intercalating dye SYTO9 for the direct identification of primary cultures, significantly decreasing turnaround time and allowing faster remedial action to be taken by the industry.


Multiband enhanced second-harmonic generation via plasmon hybridization.
Boosting nonlinear frequency-conversion efficiencies in hybrid metal-dielectric nanostructures generally requires the enhancement of optical fields that interact constructively with nonlinear dielectrics. Inevitably for localized surface plasmons, spectra subject to this enhancement tend to span narrowly. As a result, because of the spectral mismatch of resonant modes at frequencies participating in nonlinear optical processes, strong nonlinear signal generations endure the disadvantage of rapid degradations. Here, we experimentally design a multiband enhanced second-harmonic generation platform of three-dimensional metal-dielectric-metal nanocavities that consist of thin ZnO films integrated with silver mushroom arrays. Varying geometric parameters, we demonstrate that the introduction of ZnO materials in intracavity regions enables us to modulate fundamental-frequency-related resonant modes, resulting in strong coupling induced plasmon hybridization between localized and propagating surface plasmons. Meanwhile, ZnO materials can also serve as an efficient nonlinear dielectric, which provides a potential to obtain a well-defined coherent interplay between hybridized resonant modes and nonlinear susceptibilities of dielectric materials at multi-frequency. Finally, not only is the conversion efficiency of ZnO materials increased by almost two orders of magnitude with respect to hybrid un-pattered systems at several wavelengths over a 100-nm spectral range but also a hybrid plasmon-light coupling scheme in three-dimensional nanostructures can be developed.


Overview: fungal infections in the transplant patient.
Fungal infection remains a major hurdle in solid organ transplantation. A variety of new antifungal agents have become available and new diagnostic tools are in development. This conference was convened to review current approaches to the prevention and treatment of fungal infection in transplantation. Among the keys to successful management of fungal infection are identification of patients at risk for infection (stratification), eradication or control of established infection in advance of transplantation, the demonstration of cure by radiologic and histopathologic means, and the use of surgical debridement, reduction in immune suppression, and fungicidal therapies whenever possible. The absence of sensitive diagnostic tools and standardization of antifungal susceptibility testing for the filamentous fungi are identified as major impediments to care in this area.


Ligand-independent and agonist-mediated degradation of estrogen receptor-alpha in breast carcinoma cells: evidence for distinct degradative pathways.
Molecular chaperones and co-chaperones, such as heat-shock proteins (Hsp's), play a pivotal role in the adequate folding and the stability of steroid hormone receptors. As shown by immunofluorescence staining and immunoblot analysis, the Hsp90 inhibitor radicicol induced a rapid (within hours) depletion of estrogen receptor-alpha (ER) in MCF-7 and IBEP-2 breast carcinoma cells. Inhibition of proteasomes (MG-132, LLnL) or of protein synthesis (cycloheximide), which both suppressed E(2)-induced downregulation of ER, failed to modify ER degradation caused by radicicol. On the other hand, partial antiestrogens, such as hydroxytamoxifen (a triphenylethylene) and LY 117,018 (a benzothiophene) stabilized ER, making it immune to radicicol-induced degradation. Furthermore, radicicol did not interfere with ER upregulation induced by hydroxytamoxifen. Thus, the current study points to possible variation in the mechanism/pathway of ER breakdown. Besides, the protective effect of partial antiestrogens suggests that ER stability is only compromized by Hsp90 disruption when the receptor is in its native, unliganded form.


Innovations in surgical training: exploring the role of artificial intelligence and large language models (LLM).
The landscape of surgical training is rapidly evolving with the advent of artificial intelligence (AI) and its integration into education and simulation. This manuscript aims to explore the potential applications and benefits of AI-assisted surgical training, particularly the use of large language models (LLMs), in enhancing communication, personalizing feedback, and promoting skill development. We discuss the advancements in simulation-based training, AI-driven assessment tools, video-based assessment systems, virtual reality (VR) and augmented reality (AR) platforms, and the potential role of LLMs in the transcription, translation, and summarization of feedback. Despite the promising opportunities presented by AI integration, several challenges must be addressed, including accuracy and reliability, ethical and privacy concerns, bias in AI models, integration with existing training systems, and training and adoption of AI-assisted tools. By proactively addressing these challenges and harnessing the potential of AI, the future of surgical training may be reshaped to provide a more comprehensive, safe, and effective learning experience for trainees, ultimately leading to better patient outcomes. .


Exploring Readiness for Birth Control in Improving Women Health Status: Factors Influencing the Adoption of Modern Contraceptives Methods for Family Planning Practices.
Pakistan is the world's sixth most populated country, with a population of approximately 208 million people. Despite this, just 25% of legitimate couples say they have used modern contraceptive methods. A large body of literature has indicated that sexual satisfaction is a complex and multifaceted concept, since it involves physical and cultural components. The purpose of this study is to investigate the impact of influencing factors in terms of contraceptive self-efficacy (CSE), contraceptive knowledge, and spousal communication on the adoption of modern contraceptive methods for family planning (FP) under the moderating role of perceived barriers. Data were collected using an adopted questionnaire issued to married women of reproductive age belonging to the Rawalpindi and Neelum Valley regions in Pakistan. The sample consisted of 250 married women of reproductive age. SPSS was used to analyze the respondents' feedback. The findings draw public attention towards CSE, contraceptive knowledge, and spousal communication, because these factors can increase the usage of modern methods for FP among couples, leading to a reduction in unwanted pregnancies and associated risks. Regarding the significant moderation effect of perceived barriers, if individuals (women) are highly motivated (CSE) to overcome perceived barriers by convincing their husbands to use contraceptives, the probability to adopt modern contraceptive methods for FP practices is increased. Policymakers should formulate strategies for the involvement of males by designing male-oriented FP program interventions and incorporating male FP workers to reduce communication barriers between couples. Future research should address several other important variables, such as the desire for additional child, myths/misconceptions, fear of side effects, and partner/friend discouragement, which also affect the adoption of modern contraceptive methods for FP practices.


Adipose-Tumor Crosstalk contributes to CXCL5 Mediated Immune Evasion in PDAC.
CXCR1/2 inhibitors are being implemented with immunotherapies in PDAC clinical trials. Cytokines responsible for stimulating these receptors include CXCL ligands, typically secreted by activated immune cells, fibroblasts, and even adipocytes. Obesity has been linked to poor patient outcome and altered anti-tumor immunity. Adipose-derived cytokines and chemokines have been implicated as potential drivers of tumor cell immune evasion, suggesting a possibility of susceptibility to targeting specifically in the context of obesity. RNA-sequencing of human PDAC cell lines was used to assess differential influences on the cancer cell transcriptome after treatment with conditioned media from peri-pancreatic adipose tissue of lean and obese PDAC patients. The adipose-induced secretome of PDAC cells was then assessed by cytokine arrays and ELISAs. Lentiviral transduction and CRISPR-Cas9 was used to knock out CXCL5 from a murine PDAC cell line for orthotopic tumor studies in diet-induced obese, syngeneic mice. Flow cytometry was used to define the immune profiles of tumors. Anti-PD-1 immune checkpoint blockade therapy was administered to alleviate T cell exhaustion and invoke an immune response, while the mice were monitored at endpoint for differences in tumor size. The chemokine CXCL5 was secreted in response to stimulation of PDAC cells with human adipose conditioned media (hAT-CM). PDAC CXCL5 secretion was induced by either IL-1β or TNF, but neutralization of both was required to limit secretion. Ablation of CXCL5 from tumors promoted an immune phenotype susceptible to PD-1 inhibitor therapy. While application of anti-PD-1 treatment to control tumors failed to alter tumor growth, knockout CXCL5 tumors were diminished. In summary, our findings show that known adipokines TNF and IL-1β can stimulate CXCL5 release from PDAC cells in vitro. In vivo , CXCL5 depletion alone is sufficient to promote T cell infiltration into tumors in an obese setting, but requires checkpoint blockade inhibition to alleviate tumor burden. Raw and processed RNAseq data will be further described in the GEO accession database ( awaiting approval from GEO for PRJ number ). Additional raw data is included in the supplemental material and available upon reasonable request. Obesity is linked to a worsened patient outcome and immunogenic tumor profile in PDAC. CXCR1/2 inhibitors have begun to be implemented in combination with immune checkpoint blockade therapies to promote T cell infiltration under the premise of targeting the myeloid rich TME. Using in vitro/ex vivo cell and tissue culture-based assays with in vivo mouse models we have identified that adipose derived IL-1β and TNF can promote tumor secretion of CXCL5 which acts as a critical deterrent to CD8 T cell tumor infiltration, but loss of CXCL5 also leads to a more immune suppressive myeloid profile. This study highlights a mechanism and emphasizes the efficacy of single CXCR1/2 ligand targeting that could be beneficial to overcoming tumor immune-evasion even in the obese PDAC patient population.


Lexical knowledge and lexical use in autism.
One aspect of autistic language that has been infrequently researched is vocabulary and the conceptual knowledge underpinning individual words or word types. In this descriptive study we investigate anomalous vocabulary use in a 70,000-word corpus of conversational autistic language and examine evidence that concept formation, and hence vocabulary, is abnormal in autism. Particular attention is paid to the expression of artifact and temporal concepts which some believe may develop abnormally in autism. Little evidence is found of anomalous use of artifact terms, though errors with temporal (and also spatial) expressions are relatively common. We discuss why this may be and consider several potential explanations for why underlying lexical knowledge in autism may not necessarily be reflected in lexical use.


PrP(C) regulates epidermal growth factor receptor function and cell shape dynamics in Neuro2a cells.
The prion protein (PrP) plays a key role in prion disease pathogenesis. Although the misfolded and pathologic variant of this protein (PrP(SC)) has been studied in depth, the physiological role of PrP(C) remains elusive and controversial. PrP(C) is a cell-surface glycoprotein involved in multiple cellular functions at the plasma membrane, where it interacts with a myriad of partners and regulates several intracellular signal transduction cascades. However, little is known about the gene expression changes modulated by PrP(C) in animals and in cellular models. In this article, we present PrP(C)-dependent gene expression signature in N2a cells and its implication in the most overrepresented functions: cell cycle, cell growth and proliferation, and maintenance of cell shape. PrP(C) over-expression enhances cell proliferation and cell cycle re-entrance after serum stimulation, while PrP(C) silencing slows down cell cycle progression. In addition, MAP kinase and protein kinase B (AKT) pathway activation are under the regulation of PrP(C) in asynchronous cells and following mitogenic stimulation. These effects are due in part to the modulation of epidermal growth factor receptor (EGFR) by PrP(C) in the plasma membrane, where the two proteins interact in a multimeric complex. We also describe how PrP(C) over-expression modulates filopodia formation by Rho GTPase regulation mainly in an AKT-Cdc42-N-WASP-dependent pathway.


Development of a submaximal test to predict elliptical cross-trainer VO2max.
The purpose of this study was to develop an equation to predict VO2max from a submaximal elliptical cross-trainer test. Fifty-four apparently healthy subjects (25 men and 29 women, mean +/- SD age: 29.5 +/- 7.1 years, height: 173.3 +/- 12.6 cm, weight: 72.3 +/- 7.9 kg, percent body fat: 17.3 +/- 5.0%, and elliptical cross-trainer VO2max: 43.9 +/- 7.2 ml x kg(-1) x min(-1)) participated in the study and were randomly assigned to an original sample group (n = 40) and a cross-validation group (n = 14). Each subject completed an elliptical cross-trainer submaximal (3 5-minute submaximal stages) and a VO2max test on the same day, with a 15-minute rest period in between. Stepwise multiple regression analyses were used to develop an equation for estimating elliptical cross-trainer VO2max from the data of the original sample group. The accuracy of the equation was tested by using data from the cross-validation group. Because there was no shrinkage in R2 between the original sample group and the cross-validation group, data were combined in the final prediction equation (R2 = 0.732, standard error of the estimate = 3.91 ml x kg(-1) x min(-1), p < 0.05): VO2max = 73.676 + 7.383(gender) - 0.317(weight) + 0.003957(age x cadence) - 0.006452(age x heart rate at stage 2). The correlation coefficient between the predicted and measured VO2max values was r = 0.86. Dependent t-tests resulted in no significant differences (p > 0.05) between predicted (43.8 ml x kg(-1) x min(-1)) and measured (43.9 ml x kg(-1) x min(-1)) VO2max measurements. Results indicate that the protocol and equation developed in the current study can be used by exercise professionals to provide acceptably accurate estimates of VO2max in non-laboratory-based settings.


Angiogenic factors in laryngeal carcinomas: do they have prognostic relevance?
Angiogenesis is a cascade-like mechanism essential for tumour growth and metastasis. Recently developed inhibitors of angiogenesis have already proven their benefit in anticancer treatment. Therefore the existence of angiogenic molecules in individual tumours is of major interest. The factors most frequently contributing to angiogenesis are basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and some matrix metalloproteinases (MMPs). In order to evaluate the prognostic significance of these molecules we investigated the distribution pattern of VEGF, bFGF, MMP-2 and MMP-9 in 41 laryngeal carcinomas using immunohistochemical methods. The results were correlated with clinicopathological parameters, i.e. T and N stage, histological grading, freedom from disease, overall survival and microvessel density (MVD). Only VEGF revealed a correlation with MVD (p = 0.01) and a weak association with histological grading (p = 0.06). Even though there is controversy about published data on the prognostic relevance of angiogenic factors, our results suggest that the factors examined in this study are not suitable for prognosis in larynx cancer patients.


[The need for human health protection from climate changes].
The occurring climate changes have a considerable impact on human health. The higher frequency of different natural disasters, including flood and typhoons, deteriorates the epidemiological situation. Evidence is provided for the importance of climate warming as a risk factor for a number of communicable diseases, including West Nile fever in the Astrakhan and Volgograd Regions. The paper presents the results of analytical epidemiological surveys, by using the time-series analysis, in Tver and Moscow, which indicate an increase in the number of fatal outcomes particularly among the elderly during temperature heat and cold waves. The specific features of the impact of climate warming on human health in the northern and southern regions of the country are considered. The need for developing the National Plan of Actions to prevent the population's health from climate changes is warranted.


Oral-health-related quality of life in patients with cancer: cultural adaptation and the psychometric testing of the Persian version of EORTC QLQ-OH17.
To evaluate the validity, reliability, responsiveness to treatment, and gender invariance of the Persian version of the European Organization for Research and Treatment of Cancer Oral Health Questionnaire (QLQ-OH17) among Iranian cancer patients. Cancer patients (n = 729) from three oncology centers in Tehran and Qazvin were recruited. A forward and backward translation procedure was performed to develop a culturally acceptable version of Persian QLQ-OH17. Internal consistency and test-retest reliability of the QLQ-OH17 was assessed. In addition, convergent and discriminant validity, concurrent validity, construct validity, and known-groups validity were evaluated. The factor structure of the questionnaire was examined by exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Responsiveness to change was measured in an independent sample of patients with head and neck cancer undergoing radiotherapy. Finally, factorial invariance of the QLQ-OH17 was assessed across gender. The Persian version of QLQ-OH17 showed good internal consistency (Cronbach's alpha coefficients of 0.71-0.83) and reliability on repeated administration (intraclass correlation coefficients of 0.85-0.94). Persian QLQ-OH17 exhibited the original four-factor structure. Patients who perceived good oral health and satisfaction with their mouth reported significantly better oral-health-related quality of life (OHRQoL) than those who perceived poor oral health and dissatisfied with their mouth. Similarly, those who perceived a need for dental treatment reported significantly poorer OHRQoL than those who have not perceived any treatment need. Older patients, females, and those experiencing greater caries had poorer QoL than their comparative counterparts. All QLQ-OH17 subscales were correlated with QLQ-C30 subscales and global QoL. Both male and female patients with cancer interpreted items on the QLQ-OH17 in a similar manner. The QLQ-OH17 was found to be responsive to treatment in a sample of head and neck cancer patients. The Persian version of QLQ-OH17 is a valid and reliable questionnaire for assessing OHRQoL in Iranian patients with various cancers.


Business responds to AIDS program--December 1992-February 1993.
Of all acquired immunodeficiency syndrome (AIDS) cases reported through 1991 in the United States, 76% occurred among persons aged 25-44 years; persons aged 15-44 years comprise approximately 50% of the United States workforce. On December 1, 1992, CDC introduced "Business Responds to AIDS" (BRTA)--a new program for the primary prevention of human immunodeficiency virus (HIV)/AIDS. BRTA, which was introduced by satellite teleconference, encourages business and labor leaders in U.S. communities to develop comprehensive workplace HIV-prevention education programs (3). This report describes BRTA and summarizes the response--from December 1, 1992, through February 5, 1993--to the launch of the national program.


Crystallization and preliminary X-ray analysis of methylamine-treated alpha 2-macroglobulin and 3 alpha 2-macroglobulin-proteinase complexes.
Crystals of methylamine-treated alpha 2-macroglobulin (alpha 2M-MA), alpha 2-macroglobulin in complex with two molecules of trypsin, alpha 2M-T2, one molecule of plasmin, alpha 2M-PL, and one molecule of plasmin followed by methylamine-treatment, alpha 2M-PL(MA), have reproducibly been obtained using ammonium sulfate or magnesium sulfate as precipitants. The crystals are fragile tetragonal bipyramids of up to 1.5 mm in length. Crystals of alpha 2M-MA diffracted to at least 9 A resolution, crystals of alpha 2M-T2 diffracted to 10 A resolution and crystals of alpha 2M-PL and alpha 2M-PL(MA) diffracted to 11 A resolution. For alpha 2M-MA the cell parameters were determined as: a=b=257 A, c=555 A; and for alpha 2M-T2 as: a=b=247 A, c=559 A. For both preparations the space group was I4(1)22. As estimated from density measurements, the crystals of alpha 2M-MA and alpha 2M-T2 contain one 360 kDa alpha 2M dimer per asymmetric unit. The volume of the asymmetric unit/molecular weight, Vm, was estimated at 5.6 A3/Da. The crystal parameters of alpha 2M-PL and alpha 2M-PL(MA) were not determined.


Medical and Health Data Classification Method Based on Machine Learning.
The information defined in medical health data is researched based on machine learning-related algorithms. Also, this paper used random forest and other related algorithms to perform health data training and fitting. Research shows that the algorithm proposed in the paper can improve the progress of health data classification. The algorithm can provide technical support for the improvement of medical data classification.


Visual field defects may not affect safe driving.
In Quebec a driver whose acquired visual field defect renders them ineligible for a driver's permit renewal may request an exemption from the visual field standard by demonstrating safe driving despite the defect. For safety reasons it was decided to attempt to identify predictors of failure on the road test in order to avoid placing driving evaluators in potentially dangerous situations when evaluating drivers with visual field defects. During a 4-month period in 2009 all requests for exemptions from the visual field standard were collected and analyzed. All available medical and visual field data were collated for 103 individuals, of whom 91 successfully completed the evaluation process and obtained a waiver. The collated data included age, sex, type of visual field defect, visual field characteristics, and concomitant medical problems. No single factor, or combination of factors, could predict failure of the road test. All 5 failures of the road test had cognitive problems but 6 of the successful drivers also had known cognitive problems. Thus, cognitive problems influence the risk of failure but do not predict certain failure. Most of the applicants for an exemption were able to complete the evaluation process successfully, thereby demonstrating safe driving despite their handicap. Consequently, jurisdictions that have visual field standards for their driving permit should implement procedures to evaluate drivers with visual field defects that render them unable to meet the standard but who wish to continue driving.


Stimulatory and synergistic effects of luteinising hormone and insulin like growth factor 1 on the secretion of vascular endothelial growth factor and progesterone of cultured bovine granulosa cells.
Vascular endothelial growth factor (VEGF) is the most important factor in the regulation of angiogenesis. Associated with luteinisation and formation of corpus luteum (CL) are alterations in luteal vascularity. The aim of the study was to test under in vitro conditions the stimulation of VEGF and progesterone (P) secretion of bovine granulosa cells by LH, IGF1 (insulin like growth factor) or by factors known to be produced by luteinised granulosa cells or in the early CL. Localisation of VEGF protein in preovulatory follicle and early CL were achieved by immunohistochemistry. LH and IGF1 stimulated dose dependently and significantly P and VEGF when tested alone. Both hormones added simultaneously had clear additive and even more interesting far greater (synergistic) effects on P with LH (0.1 ng/ml) plus 5 or 10 ng IGF1. In contrast, VEGF was stimulated only additively with 0.1 ng/ml of LH plus 5 or 10 ng IGF1. But with the higher dose of LH (1 ng/ml) additionally to the additive effect a tendency for a synergistic action (which was significant with 1 ng LH plus 5 ng IGF1/ml) was observed. Endothelin, oxytocin, progesterone, atrial natiuretic peptide, angiotensin II, prostaglandin F2 alpha alpha, prostaglandin E2, cortisol, fibroblast growth factor 1 and 2 and growth hormone showed no effect neither on P nor on VEGF. Tumour necrosis factor alpha (TNF alpha) stimulated (P < 0.05) VEGF with 10 or 100 ng/ml but not P. TPA (12-0 tetra decaenoyl-phorbol-13-acetate) or Ca2+ ionophore did not show a stimulatory effect in contrast to forskolin which increased P and VEGF secretion dose dependently. The VEGF protein was localised in follicle (granulosa cells, theca cells and some endothelial cells) and early (about 24 h after ovulation) CL (granulosa-lutein cells and endothelial cells). The same signalling pathway by stimulation of cAMP production and proteinkinase A activation for luteinisation and neo-vascularisation demonstrates a close temporal and spatial relationship of these normal physiological processes.


Isolation and enzyme determination of Candida tropicalis mutants for DCA production.
Techniques, named two-step enrichment and double-time replica-plating method (TEDR), are described that allow a mutated population of Candida tropicalis to be enriched efficiently for mutants deficient in the alkane degradation pathway (Alk(-)) and to be selected easily for mutants increasing in the DCA (dicarboxylic acids) excretion pathway. After C. tropicalis was mutated with ethyl methane sulphonate and ultraviolet, the Alk(-) mutants were enriched (the first step enrichment, up to eightfold in one round of enrichment) by treatment with nystatin in medium SEL1-1. The mutagen-treated cells were then cultured in medium YPD containing chlorpromazine for further enriching (the second-step enrichment, up to threefold in one round) the mutants with an increasing capacity of alpha- and omega-oxidation. On the other hand, the Alk(-) mutants were readily isolated by the SEL1 replica-plating method by using alkane or glucose as the sole carbon source. A total of 43 Alk(-) mutants were isolated from 2x10(8) mutagen-treated cells. In the following steps, by using SEL2 replica plating, the screening studies showed that of the 43 Alk(-) mutants, 11 strains could accumulate DCA greatly from alkane, and strains 1-12 and 1-3, especially, could produce nearly three times as much DCA as the wild-type organism could. The results showed that the strains had more cytochrome P450 activity and a higher converting capacity of alkane.


Approximate derivative calculated by using continuous wavelet transform.
A novel method of calculating approximate derivative of signals in analytical chemistry by using the continuous wavelet transform (CWT) is proposed. As compared with numerical differentiation, FT method and DWT method, fast calculation, and simple mathematical operation are remarkable advantages of CWT method. The signal-to-noise ratio (SNR) of approximate derivative of signals calculated by CWT method is easily enhanced only through appropriately adjusting the dilation, even in the case of very low SNR. Therefore, CWT method is a powerful tool for performing the approximate derivative calculation of signals in analytical chemistry. Additionally, the approximate second derivative evaluated via CWT method can be used to determine the peak potentials of the overlapping square wave voltammogram (SWV) of Cd(II) and In(III), and the results are very satisfactory.


Language networks in children: evidence from functional MRI studies.
The purpose of our study was to review functional MRI and other neuroimaging studies of language skills in children from infancy to adulthood. Functional MRI (fMRI) and other neuroimaging studies show developmental changes in the networks of brain regions supporting language, which can be affected by brain injuries or neurologic disorders. Particular aspects of language rely on networks that lateralize to the dominant hemisphere; others rely on bilateral or nondominant mechanisms. Multiple fMRI tasks for pediatric patients characterize functional brain reorganization that may accompany language deficits.


Molecular imaging for theranostics in gastroenterology: one stone to kill two birds.
Molecular imaging in gastroenterology has become more feasible with recent advances in imaging technology, molecular genetics, and next-generation biochemistry, in addition to advances in endoscopic imaging techniques including magnified high-resolution endoscopy, narrow band imaging or autofluorescence imaging, flexible spectral imaging color enhancement, and confocal laser endomicroscopy. These developments have the potential to serve as "red flag" techniques enabling the earlier and accurate detection of mucosal abnormalities (such as precancerous lesions) beyond biomarkers, virtual histology of detected lesions, and molecular targeted therapy-the strategy of "one stone to kill two or three birds"; however, more effort should be done to be "blue ocean" benefit. This review deals with the introduction of Raman spectroscopy endoscopy, imaging mass spectroscopy, and nanomolecule development for theranostics. Imaging of molecular pathological changes in cells/tissues/organs might open the "royal road" to either convincing diagnosis of diseases that otherwise would only be detected in the advanced stages or novel therapeutic methods targeted to personalized medicine.


MRI Aspects of Neuro-Vascular Conflict of the VIII Nerve.
The vascular cross compression syndrome of the vestibule-cochlear nerve is an abnormal contact between the VIII nerve and a vessel leading to tinnitus and/or vertigo due to the nerve irritation. MRI is an important diagnostic tool as it will display the whole course of the nerve and identify the site and the type of neuro-vascular contact. However, MR findings are not specific and diagnosis can only be made on the basis of clinical and otolaryngologic features, after ruling out other possible diseases causing the same symptomatology. We describe 15 patients with neuro-vascular conflict disclosed by MRI examination which was associated with non specific neuro-othologic symptoms.


Prognostic value of OCT4 in primary intracranial germinoma: a single institute analysis of 31 cases.
OCT4 expresses variably in primary intracranial germinomas. In this study, we tested our hypothesis that such variation of OCT4 is predictive of outcome in primary intracranial germinomas. Thirty-one histologically identified CNS germinoma patients were enrolled in our study. We collected medical data, immunohistochemically evaluated the OCT4 expression level, and followed up all patients from April 2001 to May 2010. We found that 7 of the 31 patients expressed OCT4 weakly, 11 expressed OCT4 moderately, and 13 expressed OCT4 strongly. No significant correlation between the OCT4 expression level and clinicopathological characteristics was observed. WV-CS combined treatment modality showed a better 5-year progression-free survival (PFS) rate than other treatment modalities and a low expression level of OCT4 showed a significantly better 5-year PFS. In both the WV-CS combined treatment modality and other treatments modality group, patients received a better 5-year PFS and had a lower level of OCT4 expression. As a result, we suggest OCT4 as a probable prognostic marker for intracranial germinoma.


Mouse mutant embryos overexpressing IGF-II exhibit phenotypic features of the Beckwith-Wiedemann and Simpson-Golabi-Behmel syndromes.
In mice, the imprinted Igf2 gene (expressed from the paternal allele), which encodes a growth-promoting factor (IGF-II), is linked closely to the reciprocally imprinted H19 locus on chromosome 7. Also imprinted (expressed from the maternal allele) is the Igf2r gene on chromsome 17 encoding the type 2 IGF receptor that is involved in degradation of excess IGF-II. Double mutant embryos carrying a deletion around the H19 region and also a targeted Igf2r allele, both inherited maternally, have extremely high levels of IGF-II (7- and 11-fold higher than normal in tissues and serum, respectively) as a result of biallelic Igf2 expression (imprint relaxation by deletion of H19-associated sequence) in combination with lack of the IGF2R-mediated IGF-II turnover. This excess of IGF-II causes somatic overgrowth, visceromegaly, placentomegaly, omphalocele, and cardiac and adrenal defects, which are also features of the Beckwith-Wiedemann syndrome (BWS), a genetically complex human disorder associated with chromosomal abnormalities in the 11p15.5 region where the IGF2 gene resides. In addition, the double mutant mouse embryos exhibit skeletal defects and cleft palate, which are manifestations observed frequently in the Simpson-Golabi-Behmel syndrome, another overgrowth disorder overlapping phenotypically, but not genetically, with BWS.


Illness representation of arterial hypertension in a sample of health professionals and the general public.
This work studies the illness representation of high blood pressure in a sample of primary health care professionals and the general public in order to identify possible differences. The examination of illness representation was carried out using a Spanish adaptation of Turk et al.'s ( 1986 ) Implicit Model of Illness Questionnaire. This questionnaire assesses nine components: identity, cause, incapacity, cure, personal responsibility, controllability, changeability and chance. The results showed statistically significant differences between the general public and doctors in all the components except controllability. Results also show that nurses' responses are closer to those of the general public in the social and psychological aspects, but not in the technical knowledge of hypertension.


The abnormal glandular smear: cytologic prediction, colposcopic correlation and clinical management.
We reviewed recent cytological reporting of abnormal glandular cells on cervical smears in order to assess the predictive value of these reports and the contribution of colposcopy in the assessment of these abnormalities. The study consisted of a 5-year retrospective review of the clinical management of 80 women with abnormal glandular cells on a cervical smear, with clinical and histopathological data available for review in the interval 1992-1996. There were two groups of women: (i) those referred with gynaecological symptoms and (ii) those with screen detected abnormalities who were asymptomatic and significantly younger than the first group. The predictive value of a glandular smear for malignancy was 42.5% and for premalignancy 28.8%. The most common lesions detected were cervical intraepithelial neoplasia (CIN) (13), endometrial cancer (13), cervical adenocarcinoma (10) and cervical intraepithelial glandular neoplasia (CIGN) (8). Four cases of endometrial carcinoma presented through screening. In the remainder a variety of benign conditions were identified as responsible for the abnormal smear. Failure to find an explanation for the abnormal smear only occurred in 8.8%. In developing a protocol for abnormal glandular smears, our observations indicate that: (a) those with abnormal bleeding require endometrial sampling; (b) for those with screen detected abnormality, colposcopy is valuable as it is a sensitive predictor of early invasion and can predict glandular abnormality; (c)diseases of the entire genital tract, non-gynaecological viscera and metastatic cancer can generate cytological abnormality; (d) screen detected borderline abnormality in endocervical cells is associated with CIN III.


Lipid rafts, pseudotyping, and virus-like particles: relevance of a novel, configurable, and modular antigen-presenting platform.
Antigen presentation by professional antigen-presenting cells (APC) is the first step towards the initiation of an adaptive immune response carried out by naïve T lymphocytes. For this purpose, antigens are presented in the form of peptide/major histocompatibility complexes (pMHC) on APC to the antigen receptor of T cells. For sustained T cell activation to occur, numerous additional molecules specifically expressed on the surface of APC have to synergize with pMHC to stimulate a given T lymphocyte. Moreover, soluble factors such as cytokines critically contribute to the specific milieu during T cell activation. APC 'talk' to T cells only when they engage in intimate physical interaction. The cell biological correlate of this APC-T cell interaction is commonly referred to as the formation of an immunological synapse. In this review we aim to provide an overview of a novel cell-free antigen-presenting platform, i.e. virus-like particles (VLP) decorated with immune receptors of choice, which was devised to overcome the molecular and cell biological complexity of the APC side of the immunological synapse. In the past we have demonstrated that immune receptor-decorated VLP are able to activate, modulate, or abrogate antigen-specific T lymphocyte responses. Thus, antigen-specific VLP represent a valuable tool which might help to explore and understand the function of antigen-specific T lymphocytes in more detail and might thus open new avenues for the modulation of pathologic T lymphocyte responses, e.g. for the treatment of allergic diseases.


Cognitive assessment of the handicapped infant: the need for an alternative approach.
Traditional developmental protocols based on neurological or sensorimotor models frequently underestimate the cognitive status of physically handicapped infants. A critical review of current clinical practices in the area of infant assessment is followed by a discussion of an alternative approach and the presentation of an illustrative case.


History of guide dog use by veterans.
The first guide dog school was established in Germany during World War I to care for German soldiers blinded in that war. Other schools in Germany followed. Observation by an American at one of the schools led to the creation of the first guide dog school in the United States in 1929, "The Seeing Eye." Additional U.S. schools were opened during and after World War II. This article discusses the history of guide dog use by veterans, including the formation of the first guide dog schools in response to aiding blinded servicemen, and the involvement of federal agencies and guide dog schools in providing assistance to blinded veterans.


Erythroderma and extensive poikiloderma - a rare initial presentation of dermatomyositis: a case report.
Dermatomyositis is a humoral-mediated inflammatory myopathy with symmetrical proximal muscle weakness and dermatological manifestations such as Gottron's papules, heliotrope rash, periungual abnormalities, and flagellate erythema. Erythroderma is a severe and potentially life-threatening dermatological condition with diffuse erythema and scaling involving more than 90% of the skin surface area. Poikiloderma vasculare atrophicans refers to mottled hyperpigmentation and hypopigmentation of the skin with in-between telangiectases and areas of atrophy and is considered a variant of mycosis fungoides. Poikilodermatomyositis is the term given to the condition with poikiloderma and inflammatory myopathy. Only a few cases are reported on erythroderma in dermatomyositis and poikilodermatomyositis. Erythrodermal pattern of dermatomyositis transforming into poikilodermatomyositis is a recognized rare manifestation of dermatomyositis and we could find only one case report in the literature. A 53-year-old Sri Lankan woman presented with intermittent fever of 5 months' duration with erythroderma. Later she developed progressive, symmetrical proximal muscle weakness. Following a short course of small dose steroids, erythroderma settled but changed to extensive poikiloderma involving more than 90% of her skin with her face being relatively spared. She had an early heliotrope rash, shawl sign, and Gottron papules. Electromyography and muscle biopsy were supportive of inflammatory myositis and skin biopsy showed evidence of dermatomyositis. Inflammatory markers and muscle enzymes were also elevated. Autoimmune antibodies and myositis-specific autoantibodies were negative. She was started on orally administered prednisolone 1 mg/kg per day with methotrexate 10 mg once a week and had a good response to treatment with resolution of the skin condition and improvement of muscle power. Imaging studies, endoscopies, and tumor markers did not reveal any malignancy. This case illustrates a rare presentation of dermatomyositis initially presenting as fever, erythroderma, and proximal muscle weakness and later developing poikiloderma involving more than 90% of the skin. It is important to be aware of this rare presentation to avoid misdiagnosis. With the currently available literature it is not possible to conclude that erythroderma is a bad prognostic factor in dermatomyositis or a predictive factor for a malignancy. Patients have a good response to steroids with a combination of immunosuppressants.


Chromatin structure and control of beta-like globin gene switching.
The human beta-globin locus is a complex genetic system widely used for analysis of eukaryotic gene expression. The locus consists of five functional beta-like globin genes, epsilon, (G)gamma, (A)gamma, delta, and beta, arrayed on the chromosome in the order that they are expressed during ontogeny. Globin gene expression is regulated, in part, by the locus control region, which physically consists of five DNaseI-hypersensitive sites located 6-22 Kb upstream of the epsilon -globin gene. During ontogeny two switches occur in beta-globin gene expression that reflect the changing oxygen requirements of the fetus. The first switch from embryonic epsilon - to fetal gamma-globin occurs at six weeks of gestation. The second switch from gamma- to adult delta- and beta-globin occurs shortly after birth. Throughout the locus, cis-acting elements exist that are dynamically bound by trans-acting proteins, including transcription factors, co-activators, repressors, and chromatin modifiers. Discovery of novel erythroid-specific transcription factors and a role for chromatin structure in gene expression have enhanced our understanding of the mechanism of globin gene switching. However, the hierarchy of events regulating gene expression during development, from extracellular signaling to transcriptional activation or repression, is complex. In this review we attempt to unify the current knowledge regarding the interplay of cis-acting elements, transcription factors, and chromatin modifiers into a comprehensive overview of globin gene switching.


Analgesia Nociception Index (ANI) to predict intraoperative haemodynamic changes: results of a pilot investigation.
The Analgesia Nociception Index has been described to reflect different levels of intraoperative nociceptive stimulation during total intravenous anaesthesia. The association between this index and haemodynamic changes during sevoflurane-based anaesthesia was investigated in 30 patients with the hypothesis that changes in the Analgesia Nociception Index may coincide with or even predict haemodynamic changes. The Analgesia Nociception Index as well as blood pressure and heart rate were observed during induction, at skin incision, at times of an Analgesia Noceception Index decrease > 20% ('event') and pre-/post-fentanyl administration. The Analgesia Nociception Index decreased with airway manipulation [mean: 52 (before) vs. 33 (after); P < 0.005] and after skin incision [mean: 63 (before) vs. 38 (after); P < 0.001], and it increased after fentanyl administration [53 (before) vs. 59 (after); P < 0.05]. However, its predictive probability to indicate heart rate and blood pressure increases of >10% was low (heart rate 0.61; blood pressure 0.59). The Analgesia Nociception Index appears to reflect different levels of stimulation during sevoflurane-based general anaesthesia. However, it was of little predictive value to pre-empt significant haemodynamic changes.


The Effect of Genetically Modified Food on Infertility Indices: A Systematic Review Study.
Background and Objectives. With the increase in the growth of genetically modified (GM) crops, concerns as to the adverse effects of GM crops have risen in the community. The present systematic review seeks to assess the GM plants' potential impacts on the sperm parameters, including sperm head, sperm motility, sperm abnormality, and fertility index. Materials and Methods. A structured literature search was independently performed by three authors on Scopus, Web of Science, PubMed, and Embase in January 2019. A total of 1467 publications were obtained by the search strategy after eliminating the duplicates. Moreover, the review only included articles written in English language. Other pertinent peer-reviewed publications were chosen ("snowballing") from the reference lists in the selected publications. To assess the GM crop effects on infertility, experimental studies designed with the control group were selected. On the basis of abstract screening and full-text reviewing, 39 relevant publications were selected, seven of which were used in our review. To access the quality of articles, we used the Cochrane checklist. The collected articles were scored independently by three authors, and the publications with the eligibility criteria were included in our review. No article was excluded due to quality assessment. Results and Conclusion. Our findings indicated that GM products had no adverse effects on infertility indices such as the sperm head, sperm motility, sperm abnormality, and fertility indices. Long-term research still seems to be strongly necessary to ensure that the use of GM plants does not cause any harm to consumers, especially in infertility area.


New benzo[h]quinoline-based ligands and their pincer Ru and Os complexes for efficient catalytic transfer hydrogenation of carbonyl compounds.
New benzo[h]quinoline ligands (HCN'N) containing a CHRNH2 (R=H (a), Me (b), tBu (c)) function in the 2-position were prepared starting from benzo[h]quinoline N-oxide (in the case of ligand a) and 2-chlorobenzo[h]quinoline (for ligands b and c). These compounds were used to prepare ruthenium and osmium complexes, which are excellent catalysts for the transfer hydrogenation (TH) of ketones. The reaction of a with [RuCl2(PPh3)3] in 2-propanol at reflux afforded the terdentate CN'N complex [RuCl(CN'N)(PPh3)2] (1), whereas the complexes [RuCl(CN'N)(dppb)] (2-4; dppb=Ph2P(CH2)4PPh2) were obtained from [RuCl2(PPh3)(dppb)] with a-c, respectively. Employment of (R,S)-Josiphos, (S,R)-Josiphos*, (S,S)-Skewphos, and (S)-MeO-Biphep in combination with [RuCl2(PPh3)3] and ligand a gave the chiral derivatives [RuCl(CN'N)(PP)] (5-8). The osmium complex [OsCl(CN'N)(dppb)] (12) was prepared by treatment of [OsCl2(PPh3)3] with dppb and ligand a. Reaction of the chloride 2 and 12 with NaOiPr in 2-propanol/toluene afforded the hydride complexes [MH(CN'N)(dppb)] (M=Ru 10, Os 14), through elimination of acetone from [M(OiPr)(CN'N)(dppb)] (M=Ru 9, Os 13). The species 9 and 13 easily reacted with 4,4'-difluorobenzophenone, via 10 and 14, respectively, affording the corresponding isolable alkoxides [M(OR)(CN'N)(dppb)] (M=Ru 11, Os 15). The complexes [MX(CN'N)(P2)] (1-15) (M=Ru, Os; X=Cl, H, OR; P=PPh3 and P2=diphosphane) are efficient catalysts for the TH of carbonyl compounds with 2-propanol in the presence of NaOiPr (2 mol %). Turnover frequency (TOF) values up to 1.8x10(6) h(-1) have been achieved using 0.02-0.001 mol % of catalyst. Much the same activity has been observed for the Ru--Cl, --H, --OR, and the Os--Cl derivatives, whereas the Os--H and Os--OR derivatives display significantly lower activity on account of their high oxygen sensitivity. The chiral Ru complexes 5-8 catalyze the asymmetric TH of methyl-aryl ketones with TOF approximately 10(5) h(-1) at 60 degrees C, up to 97 % enatiomeric excess (ee) and remarkably high productivity (0.005 mol % catalyst loading). High catalytic activity (TOF up to 2.2x10(5) h(-1)) and enantioselectivity (up to 98 % ee) have also been achieved with the in-situ-generated catalysts prepared from [MCl2(PPh3)3], (S,R)-Josiphos or (S,R)-Josiphos*, and the benzo[h]quinoline ligands a-c.


Developing an effective nursing research committee.
If you want to challenge your critical care nurses to participate in nursing research, develop a nursing research committee. Participation on a research committee fosters nurses' research interests and provides an opportunity for them to learn about the research process from a practical perspective.


[Changes in the spectrum of AIDS-defining diseases in Spain].
Since the late 1980s the use of prophylaxis against several AIDS-diagnostic diseases has been recommended. In order to detect the impact of these measures we analyzed the shifts in the spectrum of AIDS-diagnostic diseases in Spain. AIDS cases (CDC-1987) among patients over 12 years of age diagnosed in Spain during the period 1988-1993 were studied. Number and percentage of annual AIDS cases corresponding to each reported AIDS-diagnostic disease were analyzed. Annual percentage trends were assessed by means of chi 2 trend test and logistic regression adjusting for possible changes in distribution by transmission category, sex, and age-group. Annual incidence in most of AIDS-defining diseases rose over the period 1988-1993, although the proportion of cases in which the respective conditions appeared as AIDS-diagnostic diseases exhibited declining trends (p < 0.05) in: invasive candidiasis, Herpes simplex virus infection, isosporidiasis, Pneumocystis carinii pneumonia, extrapulmonary tuberculosis, Salmonella (non-typhoid) septicemia, HIV encephalopathy and wasting syndrome. Increases were observed in the proportion of Mycobacterium avium complex disease and progressive multifocal leukoencephalopathy (p < 0.05). Some shifts in the spectrum of diseases are noted, which could be due to primary prophylaxis. Efforts should be targeted to improve coverage and compliance, and to develop guidelines of prophylaxis against the remaining diseases.


A new look at the WMS-III: new research to guide clinical practice.
The Wechsler Memory Scale, Third Edition (WMS-III) was published in 1997 and marked an ambitious and substantial revision of the traditional memory scale. Since publication, however, clinical experience has led many practitioners to raise questions about the validity and clinical utility of the new subtests and new index scores. The impetus of this special issue was to address some of the questions with which clinicians have been struggling. The articles contained in this special issue present new empirical research on the WMS-III, and several include new methods and scoring techniques that go beyond what has been published in the WAIS-III-WMS-III Technical Manual (The Psychological Corporation, 1997, 2002). It is hoped that the new scores and techniques will prove useful in clinical practice and that this research will benefit future revisions of the Wechsler Memory Scale.


[Studies on toxicity of four kinds of heavy metals in water by synchronous-scan fluorescence].
Spectrofluorometry of chlorella pyrenoidosa was studied by three dimensional excitation-emission (3DEEM) fluorescence spectroscopy and synchronous scan fluorescence spectroscopy with Delta gamma = 20 nm in the stress of Hg+, Cd2+, Cu2+ and Zn2+. The conclusion from two kinds of Spectrofluorometry was the same: after 96h stress by heavy metals, the maximum fluorescence values reduced obviously, chlorophyll-a and chlorophyll-b in the photosynthetic system were seriously damaged by heavy metal. Further analysis of the correlations between heavy metal concentration and fluorescence quenching efficiency I0/I can conclude that the toxicity of heavy metal and the fluorescence quenching efficiency I0/I were positively correlated, and they all increased with the heavy metal concentration and stress time. For one kind of heavy metals, synchronous scan fluorometry is a sensitive method for its toxicity assessment. Compared to 3DEEM fluorescence spectroscopy, synchronous scan fluorescence spectroscopy is less time consuming and of higher selectivity. It is suitable to assess the toxicity of pollutions in water.


Both negative and positive task-irrelevant stimuli contract attentional breadth in individuals with high levels of negative affect.
Emotionally-salient stimuli can capture attention to their spatial location, even when they are not relevant to a prescribed task. Here we tested whether they can influence the spatial breadth of attention. Experiment 1 tested whether small task-irrelevant emotionally-salient stimuli contracted attentional breadth when the task required a broad focus, while Experiment 2 tested whether large task-irrelevant emotionally-salient stimuli expanded attentional breadth when the task required a narrow focus. Both experiments compared the effect of negative and positive emotionally-salient images against neutral, and examined the role of participants' self-reported experiences of negative affect. Both experiments revealed slower responses following large emotionally-salient images, an effect unrelated to attentional breadth. Experiment 1 demonstrated an interaction between accuracy and negative affect, such that individuals with high levels of negative affect were less accurate at identifying global targets following both negative and positive small images, but not following neutral small images. This suggests that these small task-irrelevant emotionally-salient images contracted attentional breadth. Experiment 2 suggested that large task-irrelevant emotionally-salient images did not expand attentional breadth. We discuss how these results cannot be explained by existing models of emotion-based effects on attention and cognition, and the important implications they have for the practicalities of model-testing.


Changes in single K channel behavior induced by a lipid phase transition.
Membrane protein activity is affected by the properties of the lipid bilayer hosting them. These properties are established by both the lipid composition and the thermodynamic state of the bilayer. In the latter case, any parameter that can alter the state of the bilayer is indirectly able to affect the activity of membrane proteins. In a recent study, we have demonstrated that the activity of the KcsA ion channel is strongly related to the thermodynamic state of the lipid bilayer. In particular, when the lipid bilayer is in its main phase transition region, the conductivity of KcsA is increased and all its characteristic times change according to the characteristic times of the lipid bilayer. We propose here that the lipid bilayer can affect the distribution among many conformational substates of the open channel, affecting the corresponding channel conductivity.


The Anti-Apoptotic Role of COX-2 during In Vitro Infection of Human Intestinal Cell Line by Giardia duodenalis and the Potential Regulators.
The protozoan parasite Giardia duodenalis inhabits the upper small intestine of mammals, including humans, and causes a disease known as giardiasis, which can lead to diarrhea, abdominal cramps, and bloating. G. duodenalis was known as a causative factor of intestinal epithelial cell (IEC) apoptosis. Cyclooxygenase-2 (COX-2) has been identified as an influencing factor of pathogen infection by participating in immune response, while its role in host defense against Giardia infection is not clear. Here, we initially observed the involvement of COX-2 in the regulation of Giardia-induced IEC apoptosis. Inhibition of COX-2 activity could promote Giardia-induced reduction of IEC viability, increase of reactive oxygen species (ROS) production, and decrease of nitric oxide (NO) release, which would exacerbate IEC apoptosis. In addition, during Giardia-IEC interactions, COX-2 inhibition was able to accelerate caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage and inhibit the expressions of some anti-apoptotic proteins like cIAP-2 and survivin. In contrast, COX-2 overexpression could reduce Giardia-induced IEC apoptosis. We further investigated the regulatory mechanisms affecting COX-2 expression in terms of anti-apoptosis. The results showed that p38/ERK/AKT/NF-κB signaling could regulate COX-2-mediated ROS/NO production and anti-IEC apoptosis during Giardia infection. We also found that COX-2-mediated anti-IEC apoptosis induced by Giardia was related to Toll-like receptor 4 (TLR4)-dependent activation of p38-NF-κB signaling. Collectively, this study identified COX-2 as a promoter for apoptotic resistance during Giardia-IEC interactions and determined the potential regulators, furthering our knowledge of anti-Giardia host defense mechanisms.


Mini Nutritional Assessment (MNA) as a Reliable Tool for Nutritional Assessment of Hemodialysis Patients: A Single-Center Observation.
Objective In this study, we evaluated mini nutritional assessment (MNA) as a tool for the assessment of the nutritional status of end-stage renal disease (ESRD) patients on maintenance hemodialysis (MHD). Methods This prospective cross-sectional study was done from February 2021 till August 2021 on ESRD patients on MHD at our center. Nutritional status was assessed by using MNA score which evaluates four different aspects: anthropometric measures (body mass index [BMI], weight loss, mid-arm and mid-calf circumferences); general assessment (lifestyle, medications, mobility, and signs of depression); short dietary assessment (number of meals, food, and fluid intake) and subjective assessment (self-perception of food and nutrition). Results Out of 195 study subjects, 127 (65.1%) were males and 68 (34.9%) were females. Most women were stay-at-home mothers (57, 29.2% overall and 83.8% among all women), while most men owned their own businesses (44, 22.6% overall). The mean age was 51.2±14 years and the mean duration of hemodialysis was 4.6±4.1 years. Most of our patients belonged to the middle socioeconomic group (110, 56.6%). By using MNA, we found that most are at risk of developing malnutrition (112, 57.4%); however, only 9 (4.6%) patients are malnourished. In our study group, most malnourished patients belonged to the age group of >65 years (5, 56.6%). BMI was found to be significantly associated with MNA (p <0.001). Conclusion MNA is an easy and reliable bedside tool that can be used in ESRD patients on MHD for nutritional assessment. This is helpful in nutritional planning and the prevention of malnutrition.


Effects of Upgrade Versus De Novo Cardiac Resynchronization Therapy on Clinical Response and Long-Term Survival: Results from a Multicenter Study.
Benefits of cardiac resynchronization therapy (CRT) on morbidity and mortality in selected patients are well known. Although the number of upgrade procedures from single- or dual-chamber devices to CRT is increasing, there are only sparse data on the outcomes of upgrade procedures compared with de novo CRT. This study aimed to evaluate clinical response and survival in patients receiving de novo versus upgrade CRT defibrillator therapy. Prospectively collected outcome data were compared in patients undergoing de novo or upgrade CRT defibrillator implantation at 3 implant centers in Germany and Hungary. Clinical response was defined as an improvement by at least one New York Heart Association (NYHA) functional class. CRT implantation was performed in 552 consecutive patients of whom 375 underwent a de novo and 177 an upgrade procedure. Upgrade patients were more often implanted for secondary prevention, suffered more often from atrial fibrillation, chronic kidney disease, diabetes mellitus, and dyslipidemia, and had more often a non-LBBB (left bundle branch block) wide QRS complex, and lower left ventricular ejection fraction. Upgrade procedures were associated with a lower response rate compared to the de novo group (57% versus 69%, P univariate=0.008, P multivariate=0.021). During the follow-up of 37±28 months, survival was worse after upgrade compared with de novo CRT defibrillator implantations (hazard ratio, 1.65; 95% confidence interval, 1.22-2.24; P=0.001) even after careful adjustment for important baseline variables (adjusted hazard ratio, 1.68; 95% confidence interval, 1.20-2.34; P=0.002) and after propensity-score matching (propensity-adjusted hazard ratio, 1.79; 95% confidence interval, 1.08-2.95; P=0.023). Both clinical response and long-term survival were less favorable in patients undergoing CRT upgrade compared to de novo implantations.


Lamin B1 deletion in myeloid neoplasms causes nuclear anomaly and altered hematopoietic stem cell function.
Abnormal nuclear morphology is a hallmark of malignant cells widely used in cancer diagnosis. Pelger-Huët anomaly (PHA) is a common abnormality of neutrophil nuclear morphology of unknown molecular etiology in myeloid neoplasms (MNs). We show that loss of nuclear lamin B1 (LMNB1) encoded on chromosome 5q, which is frequently deleted in MNs, induces defects in nuclear morphology and human hematopoietic stem cell (HSC) function associated with malignancy. LMNB1 deficiency alters genome organization inducing in vitro and in vivo expansion of HSCs, myeloid-biased differentiation with impaired lymphoid commitment, and genome instability due to defective DNA damage repair. Nuclear dysmorphology of neutrophils in patients with MNs is associated with 5q deletions spanning the LMNB1 locus, and lamin B1 loss is both necessary and sufficient to cause PHA in normal and 5q-deleted neutrophils. LMNB1 loss thus causes acquired PHA and links abnormal nuclear morphology with HSCs and progenitor cell fate determination via genome organization.


Antiresorptive medication in oncology: the clinical and dental profile of patients in a reference center.
: The aim of this study was to evaluate the profile of patients on antiresorptive therapies for cancer treatment and assess presence of oral lesions, oral hygiene status, and knowledge regarding medication-related osteonecrosis of the jaw (MRONJ). This was an observational cross-sectional study that evaluated patients treated with antiresorptive medication at a single cancer hospital. Clinical data were collected and oral examination was performed to assess patient oral health. From July 2017 to December 2018, 90 patients were assessed; 64 were female and 26 were male, and the mean age was 61 years. The most common drug was an intravenous bisphosphonate, zoledronic acid. Among the 90 patients, 47 presented with some type of oral disease, isolated or associated. Among these 47 patients, 9 patients (10%) developed osteonecrosis. Oral hygiene was evaluated, and most patients, with or without MRONJ, presented with regular to poor condition. Regarding patient knowledge of the risks of MRONJ and the risks associated with dental surgery, 60% stated that they were not aware of the risks. Identifying the profile of patients and their needs facilitates not only the preventive process, but also the emergence of new therapeutic options. Our study shows that most patients are weakened both by metastatic disease and antineoplastic treatment as well as by issues associated with aging because most were over 60 years of age. Collectively, this information should be considered for management of preventive and therapeutic measures.


Tumor necrosis factor and c-fos expression in human peripheral-blood monocytes: expression is dependent on stage of in vitro differentiation.
The differentiation of monocytes and macrophages both in vitro and in vivo can be characterized by the modulation of specific functional and molecular phenotypes. We have determined in human peripheral-blood monocytes (HPBM) the role of in vitro differentiation on the expression of nonspecific tumoricidal activity, induction of soluble tumor necrosis factor (TNF) activity and TNF-specific mRNA transcription. HPBM were activatable by bacterial lipopolysaccharide (LPS; 1 microgram/ml) for nonspecific cytotoxicity to A375M (human malignant melanoma cell line) only during the first 24 h of in vitro differentiation. Activated supernatants of HPBM were found to be partially neutralizable (75 +/- 7%) by rabbit polyclonal anti-TNF antibody and, in freshly isolated HPBM, the release of soluble TNF activity determined by the L929 assay was found to occur only after activation with LPS. Maximal TNF release occurred at 8 h of LPS stimulation, and required both protein and RNA synthesis as evidenced by the ability of both actinomycin D and cycloheximide to inhibit its release. Neither control untreated HPBM nor recombinant interferon-gamma (rIFN-gamma; 1 U/ml)-treated HPBM alone released soluble TNF activity. Further in vitro culture determined that HPBM were activatable for TNF release out to 72 h of culture after which HPBM became resistant to LPS-mediated TNF release. The expression of TNF and c-fos mRNA was also determined during in vitro differentiation. Both TNF and c-fos mRNA were expressed in freshly isolated HPBM, and returned to baseline by 24 h of in vitro culture. Treatment of HPBM with LPS induced TNF transcription as late as 5 days of in vitro culture with maximal induction occurring during the first 48 h. rIFN-gamma significantly induced TNF transcription at 24 h in the absence of soluble TNF activity, but did not increase transcription at later times. The expression of nonspecific cytolytic activity, the release of soluble bioactive TNF and the induction of TNF and c-fos mRNA are regulated in HPBM by differentiation-determined processes.


Highly efficient siRNA delivery system into human and murine cells using single-wall carbon nanotubes.
Development of RNA interference (RNAi) technology utilizing short interfering RNA sequences (siRNA) has focused on creating methods for delivering siRNAs to cells and for enhancing siRNA stability in vitro and in vivo. Here, we describe a novel approach for siRNA cellular delivery using siRNA coiling into carboxyl-functionalized single-wall carbon nanotubes (SWCNTs). The CNT-siRNA delivery system successfully demonstrates nonspecific toxicity and transfection efficiency greater than 95%. This approach offers the potential for siRNA delivery into different types of cells, including hard-to-transfect cells, such as neuronal cells and cardiomyocytes. We also tested the CNT-siRNA system in a non-metastatic human hepatocellular carcinoma cell line (SKHep1). In all types of cells used in this work the CNT-siRNA delivery system showed high efficiency and apparent no side effects for various in vitro applications.


Cognitive and emotional health risk perceptions among people living in poverty.
Many theories of risk perception and health behavior examine cognitive dimensions of risk (i.e., perceived susceptibility or severity) but not emotional dimensions. To address this gap, the authors examined the emotional component of risk perception (as worry) and its relation to cognitive assessments of risk, self-efficacy and response efficacy, and health protective action. Although people in poverty are at high risk for many health conditions, little is known about how concerned they are about these conditions or how their risk perceptions influence health actions. African Americans and Whites with incomes≤$35,000 were surveyed (N=431). Participants reported their worry level for 10 health risks. Among their highest worry risks, they identified the risk they took the most action and the risk they took the least action to prevent. Worry was low or moderate for each health risk and chronic conditions were of the most concern. For high- and low-action risks, response efficacy moderated the relation between cognitive risk perception and health protective action. For low-action risks, decisions to act were affected independently by cognitive and emotional responses. The results support the Risk Perception Attitude Framework and indicate the importance of using cognitive and emotional dimensions of risk in behavior change models.


Diabetes managed care and clinical outcomes: the Harbor City, California Kaiser Permanente diabetes care system.
To investigate diabetes clinical outcomes in a large patient population by comparing results of computer-supported team care to those of usual care. Patients enrolled in a diabetes care management program were tracked by a computerized system. Their subsequent healthcare outcomes were compared with those of usual-care patients and those of patients who had been discontinued from being managed in this program. Screening rates for glycosylated hemoglobin (GHb), urinary protein, serum lipids, and glycemic and blood pressure control were compared between currently managed and usual-care patients. Hospital days and screening rates in a subset of the currently managed group, long-term managed patients, were compared with those of no longer managed patients. Screening rates for GHb, urinary protein, and serum lipids were higher in currently managed patients than in usual-care patients. Follow-up of initially elevated GHb in currently managed and usual-care patients showed an overall decrease in both groups. Follow-up of initially elevated blood pressure in currently managed patients showed a decrease in both mean systolic and mean diastolic measurements, while follow-up in usual-care patients showed no change in either mean systolic or mean diastolic measurements. Inpatient utilization for the long-term managed patients decreased between 1995 and 1997 and was lower in 1997 for this group than for no longer managed patients. Screening rates for GHb, urinary protein, and serum lipids were higher in the long-term managed patients than in the no longer managed patients. Computer-supported care management by a dedicated team appears to reduce the number of hospitalizations and improve screening rates and glycemic and blood pressure control.


Percutaneous and surgical interventions for in-stent restenosis: long-term outcomes and effect of diabetes mellitus.
We examined long-term outcomes of patients with in-stent restenosis (ISR) who underwent different percutaneous interventions at the discretion of individual operators: balloon angioplasty (BA), repeat stent or rotational atherectomy (RA). We also examined long-term outcomes of patients with ISR who underwent coronary artery bypass surgery (CABG). In-stent restenosis remains a challenging problem, and its optimal management is still unknown. Symptomatic patients (n = 510) with ISR were identified using cardiac catheterization laboratory data. Management for ISR included BA (169 patients), repeat stenting (117 patients), RA (107 patients) or CABG (117 patients). Clinical outcome events of interest included death, myocardial infarction, target vessel revascularization (TVR) and a combined end point of these major adverse cardiovascular events (MACE). Mean follow-up was 19+/-12 months (range = 6 to 61 months). Patients with ISR treated with repeat stent had significantly larger average post-procedure minimal lumen diameter compared with BA or RA (3.3+/-0.4 mm vs. 3.0+/-0.4 vs. 2.9+/-0.5, respectively, p < 0.05). Incidence of TVR and MACE were similar in the BA, stent and RA groups (39%, 40%, 33% for TVR and 43%, 40%, 33% for MACE, p = NS). Patients with diabetes who underwent RA had similar outcomes as patients without diabetes, while patients with diabetes who underwent BA or stent had worse outcomes than patients without diabetes. Patients who underwent CABG for ISR, mainly because of the presence of multivessel disease, had significantly better outcomes than any percutaneous treatment (8% for TVR and 23% for MACE). In this large cohort of patients with ISR and in the subset of patients without diabetes, long-term outcomes were similar in the BA, repeat stent and RA groups. Tissue debulking with RA yielded better results only in diabetic patients. Bypass surgery for patients with multivessel disease and ISR provided the best outcomes.


Inhibition by hydrogen sulfide of rabbit platelet aggregation and calcium mobilization.
Hydrogen sulfide (H2S), a gasotransmitter, plays a variety of roles in the mammalian body including the cardiovascular system. Given evidence that H2S donors including NaHS inhibit human platelet aggregation, we examined and characterized the effects of NaHS on rabbit platelet aggregation and cytosolic Ca(2+) mobilization. Rabbit platelet aggregation was determined in platelet-rich plasma (PRP) and washed platelets. Intracellular Ca(2+) levels were monitored in Fura2-loaded washed platelets. NaHS prevented rabbit platelet aggregation induced by collagen or ADP, and the effective concentration range of NaHS was 0.1-0.3 mM in PRP and 1-3 mM in washed platelets. In washed platelets, NaHS attenuated cytosolic Ca(2+) mobilization induced by collagen or ADP and also reduced platelet aggregation induced by ionomycin, a Ca(2+) ionophore. The anti-platelet effect of NaHS was blocked by an adenylyl cyclase inhibitor and enhanced by a phosphodiesterase inhibitor. H2S thus suppresses rabbit platelet aggregation by interfering with both upstream and downstream signals of cytosolic Ca(2+) mobilization in a cAMP-dependent manner.


Correction: Frequency of co-seropositivities for certain pathogens and their relationship with clinical and histopathological changes and parasite load in dogs infected with Leishmania infantum.
[This corrects the article DOI: 10.1371/journal.pone.0247560.].


The covert orienting of visual attention following severe traumatic brain injury.
Attentional problems have frequently been identified following traumatic brain injuries (TBIs) using both clinical assessments and self-report measures. Unfortunately, most measures of attention do not enable us to determine the underlying basis of these attentional deficits. One exception is Posner's Covert Orienting of Attention Task (COAT), which is designed to identify some of the fundamental mental operations underlying attention. This study sought to determine whether the COAT task could identify discrete attentional deficits following TBI beyond those caused by reduced speed of information processing. Thirty five patients who had sustained a severe TBI were compared to 35 age-matched controls. Results revealed that, although the reaction times of the patients with TBI were significantly slower than the controls, there were no differences between the two groups in terms of their ability to disengage, move, and engage their attention. The introduction of a secondary (language) task produced no significant difference between the two groups on the COAT task. However, there was a significant difference between the two groups on the language-based task, suggesting a deficit in auditory-verbal attention under dual task conditions.


Vitamin D intake and mental health-related quality of life in older women: the Iowa Women's Health Study.
Vitamin D deficiency and mood disorders are both prevalent among the elderly. We evaluated the association between vitamin D intake and mental health-related quality of life (QOL) among elderly women participating in a large population-based study. This study was a cross-sectional analysis of the Iowa Women's Health Study, a prospective study of cancer risk factors among post-menopausal women in Iowa that began in 1986. Additional survey data was collected from the cohort members in 1987, 1989, 1992, 1997, and 2004. Data for this analysis came from the 2004 questionnaire. Mental health-related QOL was assessed using five scales from the Medical Outcomes Study 36-item Short-form Health Survey. QOL scores were analyzed as continuous variables using linear regression, controlling for age, energy intake, BMI, education, smoking, living arrangement, antidepressant usage, comorbidity history, and physical activity. Low vitamin D intake (<400 IU/day) was associated with poorer QOL scores compared to women with higher intake (≥400 IU/day). Differences in QOL scores by vitamin D intake group were attenuated with multivariable adjustment, but a significant overall association between vitamin D and QOL scores persisted. Further adjustment for physical activity attenuated all differences as well as the overall association between vitamin D and QOL scores. Women who consumed <400 IU/day of vitamin D had significantly lower mental health-related QOL compared to those who consumed ≥400 IU/day. Meeting dietary vitamin D recommendations is a potential method for improving QOL among the elderly.


Gender differences in nightmare frequency: a meta-analysis.
Many studies have reported gender differences in nightmare frequency. In order to study this difference systematically, data from 111 independent studies have been included in the meta-analysis reported here. Overall, estimated effect sizes regarding the gender difference in nightmare frequency differed significantly from zero in three age groups of healthy persons (adolescents, young adults, and middle-aged adults), whereas for children and older persons no substantial gender difference in nightmare frequency could be demonstrated. There are several candidate variables like dream recall frequency, depression, childhood trauma, and insomnia which might explain this gender difference because these variables are related to nightmare frequency and show stable gender differences themselves. Systematic research studying the effect of these variables on the gender difference in nightmare frequency, though, is still lacking. In the present study it was found that women tend to report nightmares more often than men but this gender difference was not found in children and older persons. Starting with adolescence, the gender difference narrowed with increasing age. In addition, studies with binary coded items showed a markedly smaller effect size for the gender difference in nightmare frequency compared to the studies using multiple categories in a rating scale. How nightmares were defined did not affect the gender difference. In the analyses of all studies and also in the analysis for the children alone the data source (children vs. parents) turned out to be the most influential variable on the gender difference (reporting, age). Other results are also presented. Investigating factors explaining the gender difference in nightmare frequency might be helpful in deepening the understanding regarding nightmare etiology and possibly gender differences in other mental disorders like depression or posttraumatic stress disorder.


Is interleukin 6 an early marker of injury severity following major trauma in humans?
Interleukin 6 (IL-6), a multifunctional cytokine, is expressed by various cells after many stimuli and underlies complex regulatory control mechanisms. Following major trauma, IL-6 release correlates with injury severity, complications, and mortality. The IL-6 response to injury is supposed to be uniquely consistent and related to injury severity. Therefore, we designed a prospective study starting as early as at the scene of the unintentional injury, to determine the trauma-related release of plasma IL-6 in multiple injured patients. On approval of the local ethics committee, 94 patients were enrolled with different injuries following trauma (Injury Severity Score [ISS] median, 19; range, 3-75). The patients were rescued by a medical helicopter. Subsets were performed according to the severity of trauma--4 groups (ISS, <9, 9-17, 18-30, and >32)-and survival vs nonsurvival. The first blood sample was collected at the scene of the unintentional injury before cardiopulmonary resuscitation, when appropriate. Then, blood samples were collected in hourly to daily intervals. Interleukin 6 plasma levels were determined using a commercial enzyme-linked immunosorbent assay test. The short-term phase protein, C-reactive protein, was measured to characterize the extent of trauma and to relate these results to IL-6 release. As early as immediately after trauma, elevated IL-6 plasma levels occurred. This phenomenon was pronounced in patients with major trauma (ISS, >32). Patients with minor injury had elevated concentrations as well but to a far lesser extent. In surviving patients, IL-6 release correlated with the ISS values best during the first 6 hours after hospital admission. All patients revealed increased C-reactive protein levels within 12 hours following trauma, reflecting the individual injury severity. This was most pronounced in patients with the most severe (ISS, >32) trauma. To our knowledge, this is the first study that elucidates the changes in the IL-6 concentrations following major trauma in humans as early as at the scene of the unintentional injury. The results reveal an early increase of IL-6 immediately after trauma. Moreover, patients with the most severe injuries had the highest IL-6 plasma levels. There is strong evidence that systemic IL-6 plasma concentrations correlate with ISS values at hospital admission. Therefore, IL-6 release can be used to evaluate the impact of injury early regardless of the injury pattern.