The prevalence and impact of accommodations on the employment of persons 51-61 years of age with musculoskeletal conditions.
To provide estimates of the frequency with which persons 51 to 61 years of age with musculoskeletal conditions receive workplace accommodations from their employers and to determine if the receipt of such accommodations is associated with higher rates of employment two years later. The estimates derive from the Health and Retirement Survey, a national probability sample of 8,781 respondents who were interviewed both in 1992 and 1994 and who were between the ages of 51 and 61 years, of whom 5,495 reported one or more musculoskeletal conditions. We tabulated the frequency of accommodations provided in 1992 and then estimated the impact of accommodations and demographic and medical characteristics on 1994 employment status, using logistic regression. In 1992, about 14.40 million persons aged 51-61 years reported a musculoskeletal condition. Of these, 1.32 million (9.2%) reported a disability and were employed, the target population for accommodations. Overall, fewer than 1 in 5 persons with musculoskeletal conditions who had a disability and were employed indicated that they had received any form of accommodation on their current jobs. Although no form of accommodation was reported with great frequency, the most commonly used ones included getting someone to help do one's job (12.1%), scheduling more breaks during the work day (9.5%), changing the time that the work day started and stopped (6.3%), having a shorter work day (5.6%), getting special equipment (5.3%), and changing the work tasks (5.3%). Persons with one or more accommodations in 1992, however, were no more likely to be working in 1994 than those with none. Only one specific accommodation--getting someone to help do one's job--was associated with a higher rate of employment in 1994. Receipt of employment accommodations occurred infrequently, and was not generally associated with an improvement in the employment rate of persons with musculoskeletal conditions and disabilities.


[Clinical practice guideline for the diagnosis and treatment of hyperprolactinemia].
Hyperprolactinemia is a common finding within clinical practice in both endocrinology and general practice fields, amongst other specialties. The general practitioner and other specialists must know the indications and serum prolactin determination parameters in order to, once detected, derive the patient for a correct assessment and begin treatment. Formulate a clinical practice guideline evidence-based for the diagnosis and treatment of hyperprolactinemia. It took the participation of eight gynecologists, two pathologists and a pharmacologist in the elaboration of this guideline due their experience and clinical judgement. These recommendations were based upon diagnostic criteria and levels of evidence from treatment guidelines previously established, controlled clinical trials and standardized guides for adolescent and adult population with hyperprolactinemia. During the conformation of this guideline each specialist reviewed and updated a specific topic and established the evidence existent over different topics according their field of best clinical expertise, being enriched by the opinion of other experts. At the end, all the evidence and decisions taken were unified in the document presented here. It is presented the recommendations established by the panel of experts for diagnosis and treatment of patients with high levels of prolactin; also the level of evidence for the diagnosis of hyperprolactinemia, handling drug-induced hyperprolactinemia and prolactinomas in pregnant and non-pregnant patients.


Chromosome numbers in Chihuahuan Desert Cactaceae. III. Trans-Pecos Texas.
Chromosome numbers are reported for 112 collections of Cactaceae, including 102 collections of Opuntia. Reports are presented for 33 species in five genera and a total of 36 taxa. Two specimens were sterile. Emphasis was given to the documentation of intraspecific ploidy-level consistencies and differences, because of the current poor state of knowledge about the populational integrity of chromosome numbers in Trans-Pecos cacti and because information about ploidy levels is taxonomically significant particularly in certain genera of Cactaceae. First reports are presented for six taxa, including Opuntia aureispina (2n = 11 II), O. tortispina (2n = 33 II), and Ancistrocactus tobuschii (2n = 11 II). Chromosome numbers are now known for all but one or two of the ∼104 currently recognized cactus taxa in Trans-Pecos Texas.


Multiple Sclerosis: What Methods are Available for the Assessment of Subclinical Visual System Damage?
We aimed to assess the visual fields and optical coherence tomography (OCT) measurements in patients with multiple sclerosis (MS) to detect subclinical visual system disease. The study included 15 MS patients with previous optic neuritis (Group I), 17 MS patients without previous optic neuritis (Group II), and 14 healthy controls (Group III). Each subject underwent standard automated perimetry (SAP), frequency doubling technology perimetry (FDTP), and OCT. The mean deviation of SAP in Group I was lower than those in Groups II (p = .018) and III (p = .001). The pattern standard deviation of SAP in Group I was higher than those in Group III (p < .0001). The mean deviation of FDTP in Groups I and II was lower than those in Group III (p = .0001 and p = .016, respectively). The temporal quadrant of the retinal nerve fibre layer in Group I was thinner than those in Groups II and III (p = .005 and p = .003, respectively). The mean macular volume in Group I was thinner than those in Groups II and III (p = .004 and p = .002, respectively). A single method is inadequate for establishing early and/or mild visual impairment in MS. All conventional and non-conventional techniques are complementary in demonstrating subclinical visual damage in MS.


Transgene insertion into the plastid genome alters expression of adjacent native chloroplast genes at the transcriptional and translational levels.
In plant biotechnology and basic research, chloroplasts have been used as chassis for the expression of various transgenes. However, potential unintended side effects of transgene insertion and high-level transgene expression on the expression of native chloroplast genes are often ignored and have not been studied comprehensively. Here, we examined expression of the chloroplast genome at both the transcriptional and translational levels in five transplastomic tobacco (Nicotiana tabacum) lines carrying the identical aadA resistance marker cassette in diverse genomic positions. Although none of the lines exhibits a pronounced visible phenotype, the analysis of three lines that contain the aadA insertion in different locations within the petL-petG-psaJ-rpl33-rps18 transcription unit demonstrates that transcriptional read-through from the aadA resistance marker is unavoidable, and regularly causes overexpression of downstream sense-oriented chloroplast genes at the transcriptional and translational levels. Investigation of additional lines that harbour the aadA intergenically and outside of chloroplast transcription units revealed that expression of the resistance marker can also cause antisense effects by interference with transcription/transcript accumulation and/or translation of downstream antisense-oriented genes. In addition, we provide evidence for a previously suggested role of genomically encoded tRNAs in chloroplast transcription termination and/or transcript processing. Together, our data uncover principles of neighbouring effects of chloroplast transgenes and suggest general strategies for the choice of transgene insertion sites and expression elements to minimize unintended consequences of transgene expression on the transcription and translation of native chloroplast genes.


Elucidation of Surface Functional Groups Deposited by Electrochemical Surface Treatment of Discontinuous Carbon Fiber by NEXAFS and XPS.
Control of carbon fiber heteroatom (oxygen and nitrogen) functionalization using electrochemical oxidation is explored in a variety of electrolyte solutions. Results of X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy indicate that most electrolytes in aqueous and anodic conditions are limited to heteroatom surface content of no more than 13 atomic percent (at %) with a majority C-O and/or C-N moieties; the remaining moieties include an oxidative sequence of carbon (alcohol to ketone to carboxylate) and more complex O- and N-containing groups. The pH of the electrolyte solution was found to be crucial in controlling the ratio of the amount of oxygen to nitrogen functionalities, with the increased basicity of solution resulting in higher nitrogen deposition. The oxidative (and/or thermal) decomposition of many electrolytes during electrochemical treatment can have a major impact on functionalization through changes to pH. Oxidation of carbon fiber in some electrolyte solutions showed higher surface concentrations of heteroatoms (25-30 at %) than most electrolytes (13 at %). Mechanisms were proposed to explain how some electrolytes can exceed 13 at % of heteroatom deposition. Specifically, we hypothesized that electrolytes that contain organic ions with chelation capabilities and moieties that produce additional sites of functionalization can overcome that threshold.


Multiplexing cytokine analysis: towards reducing sample volume needs in clinical diagnostics.
The trend for improved more precise diagnostics and management of disease heavily relies on the measurement of panels of biomarkers in physiological samples of patients. Ideally, the ultimate goal would be to detect as many clinically relevant biomarkers as possible in a single drop of blood, achieving quick, sensitive, reproducible, and affordable detection in small volume physiological samples. Bioluminescent (BL) proteins provide many of the desired characteristics required for such labels, including detection at extremely low concentrations, no interference from physiological fluids leading to excellent detection limits, and compatibility with many miniaturized systems. However, to date the use of BL proteins has been restricted by their limited multiplexing capabilities. BL proteins typically exhibit a single emission profile and decay kinetics making the simultaneous detection of multiple analytes difficult. Recent progresses in this area include the use of two different engineered luminescent proteins to achieve resolved signals via one-dimensional time resolution. This approach, however, to date only lead to a dual analyte detection. Herein, we have demonstrated that using a two-dimensional approach that combines both temporal and spatial resolution, we can expand the multiplexing capabilities of bioluminescent proteins. To that end, the photoprotein aequorin (AEQ) has been employed for the simultaneous detection of three separate analytes in a single well, differentiated through the use of three discrete time/wavelength windows. Through a combination of site-specific mutations and synthetic coelenterazines "semi-synthetic" AEQ variants have been developed with altered emission profiles and decay kinetics. In this study, two AEQ mutant proteins were genetically conjugated to three pro-inflammatory cytokines (tumor necrosis factor alpha, interleukins 6 and 8) resulting in AEQ-labeled cytokines. These fusion proteins were combined with synthetic coelenterazines resulting in proteins with differing emission maxima and half-lives to allow for the simultaneous detection of all three cytokines in a single sample. The validity of the assay was demonstrated in serum by employing human physiological samples and comparing our results with commercially available individual tests for each of the three cytokines.


Community nurses' talk of equality and the discursive constitution of selves.
The aim of this paper is to explore how stories revealed the discursive constitution of particular selves and to consider the implications for future understandings of equality and practice. Equality has long been an objective of most Western healthcare systems, as enshrined in the principles of equal rights to access, treatment and care. Service users, however, continue to experience inequities, oppression and discrimination. These continuing inequalities have resulted in demands for nurses to tackle discrimination and oppression and promote equality in their practice. Semi-structured interviews were conducted with 14 community nurse students and 14 practice teachers from two universities in England in 1998. Discourse analysis was used to interpret the narratives. Community nurses were actively positioning themselves and were being positioned through dominant and competing discourses. Their narratives revealed stories of equality in health care that were contingent upon complex discursively constituted selves. They were found to take up, rework and in some cases subvert and reject dominant subject positions. The implications of these selves are considered in relation to the development of equality and practice. Educationalists and practitioners need to engage with these discourses and diverse selves and begin to develop approaches which remain open to scrutiny and challenge so that specific and localized understandings of equality and practice can evolve.


Dewatering and disinfection of aerobic and anaerobic sludge using an electrokinetic (EK) system.
The objectives of the study were to upgrade sewage sludge to Class A Exceptional Quality biosolids (as defined by US EPA) using an electrokinetics dewatering system. The pathogens monitored were Salmonella spp, and fecal coliforms (FC). Ten bench-scale electrokinetic cells were set up for the disinfection of the following sludges: primary, secondary (attached growth culture and suspended culture), and anaerobically digested sludge. A conditioning liquid was also added to five cells. Blower system to aid in dewatering and drying was used in in four EK cells. Sludge characteristics such as water content, volatile solids content, sulfate and chloride ions concentrations, FC and Salmonella spp. before and after the tests were monitored. The highest total solids content (98% TS) was achieved in the cell with the low voltage gradient, in the presence of the conditioner and with the blower system. An average reduction by 50% of volatile solids was observed. The highest, 11 log-reduction of Salmonella spp. was observed in a cell with anaerobically digested sludge. No fecal coliforms were observed in any of the cells after EK treatment.


Electroencephalogram correlates of higher cortical functions.
By means of two-stage, nonlinear multivariate pattern recognition, electroencephalograms (EEG's) were analyzed during performance of verbal and spatial tasks. Complex scalp distributions of theta-, beta-, and, to a lesser extent, alpha-band spectral intensities discriminated between the two members of a pair of tasks, such as writing sentences and Koh's block design. Small EEG asymmetries were probably attributable to limb movements and other uncontrolled noncognitive aspects of tasks. Significant EEG differences beteeen cognitive tasks were eliminated when controls for inter-task differences in efferent activity, stimulus characteristics, and performance-related factors were introduced. Each controlled task was associated with an approximately 10 percent reduction, as compared with visual fixation, in the magnitude of alpha- and beta-band spectral intensity. This effect occurred bilaterally and was approximately the same over occipital, parietal, and central regions, with some minor difference over the frontal region in the beta band. With these controls, no evidence for lateralization of different cognitive functions was found in the EEG.


New focal plane architecture and transform for fast target recognition.
This paper presents a new concept for recognizing target shapes. The method depends upon establishing a uniform current density in a mesh of interconnected photosensitive pixels and characterizing the target image by potential changes at the mesh boundary. The concept proposes a way to reduce potentially hundreds of thousands of pixel values to a small set of signature values. The concept also removes the traditional time bottleneck of having to read the image off the focal plane before commencing analysis. The method is capable of easily handling target rotation and linear scaling.


Bis(μ-2-hy-droxy-methyl-2-methyl-propane-1,3-diolato)bis-[di-chlorido-titanium(IV)] diethyl ether disolvate.
The title complex, [Ti2Cl4{CH3C(CH2O)2(CH2OH)}2], lies across a centre of symmetry with a diethyl ether solvent mol-ecule hydrogen bonded to the -CH2OH groups on either side of it. The Ti(IV) atom is coordinated in a distorted octa-hedral geometry by a tripodal ligand and two terminal chloride atoms. There are three coordination modes for the tripodal ligand distinguishable on the basis of their very different Ti-O bond lengths. For the terminal alkoxo ligand, the Ti-O distance is 1.760 (1) Å, the asymmetric bridge system has Ti-O bond lengths of 1.911 (1) and 2.048 (1) Å. The Ti-O bond length for the alcohol O atom is the longest at 2.148 (1) Å.


Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso.
Besides existing artemisinin-based combination therapies, alternative safe, effective and affordable drug combinations against falciparum malaria are needed. Methylene blue (MB) was the first synthetic antimalarial drug ever used, and recent studies have been promising with regard to its revival in malaria therapy. The objective of this study was to assess the safety and efficacy of two MB-based malaria combination therapies, MB-artesunate (AS) and MB-amodiaquine (AQ), compared to the local standard of care, AS-AQ, in Burkina Faso. Open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria in Nouna, north-western Burkina Faso. Follow-up was for 28 days and analysis by intention-to-treat. The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. No drug-related serious adverse events and no deaths occurred. MB-containing regimens were associated with mild vomiting and dysuria. No early treatment failures were observed. Parasite clearance time differed significantly among groups and was the shortest with MB-AS. By day 14, the rates of adequate clinical and parasitological response after PCR-based correction for recrudescence were 87% for MB-AS, 100% for MB-AQ (p = 0.004), and 100% for AS-AQ (p = 0.003). By day 28, the respective figure was lowest for MB-AS (62%), intermediate for the standard treatment AS-AQ (82%; p = 0.015), and highest for MB-AQ (95%; p<0.001; p = 0.03). MB-AQ is a promising alternative drug combination against malaria in Africa. Moreover, MB has the potential to further accelerate the rapid parasite clearance of artemisinin-based combination therapies. More than a century after the antimalarial properties of MB had been described, its role in malaria control deserves closer attention. ClinicalTrials.gov NCT00354380.


Location of the abducent nerve within the cavernous sinus.
Knowing the distance between the superior and inferior border of Parkinson's triangle and the location of the abducent nerve within the cavernous sinus is important to decrease the complications which may occur during surgery. We aimed to investigate the cavernous sinus to decrease the complications that may occur during surgery to this area. Fifty MRIs without pituitary gland abnormality were chosen for radiological assessment of CS. These images were from 18 males and 32 females, with ages ranging from 9 to 58 years and a median age of 28 years. We evaluated structures within and on the lateral wall of the cavernous sinus (especially Parkinson's triangle) with magnetic resonance imaging. The position of the abducent nerve and its level according to the cranial nerves running close the lateral wall were examined. At the level of pituitary stalk, the distance between the trochlear nerve and the ophthalmic nerve ranged from 1 to 4 mm bilaterally. The abducent nerve was located between the trochlear and the ophthalmic nerves in 30% cases bilaterally. The knowledge of the position of the abducent nerve will provide a great benefit in minimizing the rate of complications that may occur during the resection of tumors of the cavernous sinus.


Adult Movement Defects Associated with a CORL Mutation in Drosophila Display Behavioral Plasticity.
The CORL family of CNS-specific proteins share a Smad-binding region with mammalian SnoN and c-Ski protooncogenes. In this family Drosophila CORL has two mouse and two human relatives. Roles for the mouse and human CORL proteins are largely unknown. Based on genome-wide association studies linking the human CORL proteins Fussel15 and Fussel18 with ataxia, we tested the hypothesis that dCORL mutations will cause adult movement disorders. For our initial tests, we conducted side by side studies of adults with the small deletion Df(4)dCORL and eight control strains. We found that deletion mutants exhibit three types of behavioral plasticity. First, significant climbing defects attributable to loss of dCORL are eliminated by age. Second, significant phototaxis defects due to loss of dCORL are partially ameliorated by age and are not due to faulty photoreceptors. Third, Df(4)dCORL males raised in groups have a lower courtship index than males raised as singles though this defect is not due to loss of dCORL Subsequent tests showed that the climbing and phototaxis defects were phenocpied by dCORL21B and dCORL23C two CRISPR generated mutations. Overall, the finding that adult movement defects due to loss of dCORL are subject to age-dependent plasticity suggests new hypotheses for CORL functions in flies and mammals.


LPS-induced epithelial-mesenchymal transition of intrahepatic biliary epithelial cells.
Recent studies have revealed that the epithelial-mesenchymal transition (EMT) of bile duct epithelial cells is engaged in hepatic fibrogenesis. However, the association between etiological factors of liver disease such as virus or bacterial infection and EMT remains to be investigated. The present study focuses on the inductive role of endotoxin, the main component of the cell wall's ectoblast of gram-negative bacteria, in the EMT of human intrahepatic biliary epithelial cells (HIBEpiCs). The expressions of E-cadherin, S100A4, α-SMA, TGF-β1, and Smad2/3 in HIBEpiCs cultured with or without lipopolysaccharide LPS, were detected by real-time PCR and Western blotting. We blocked the expression of TGF-β1 using paclitaxel and knocked down Smad2/3 by siRNA to explore the role of TGF-β1/Smad2/3 pathway in the EMT of HIBEpiCs. Resting HIBEpiCs showed epithelioid cobblestone morphology, and underwent a phenotypic change to produce bipolar cells with a fibroblastic morphology when co-cultured with LPS. After LPS stimulation and the up-regulation of mRNA and protein expression of TGF-β1 and Smad2/Smad3, the mRNA and protein expression of mesenchymal markers (S100A and α-SMA) increased significantly. Paclitaxel inhibited the mRNA and protein expression of TGF-β1 in vitro. Knock-down of Smad2/3 by siRNA led to up-regulation of epithelial markers E-cadherin and down-regulation of S100A and α-SMA, indicating a reversal of the EMT. LPS can induce the expression of TGF-ß1 and a subsequent EMT in HIBEpiCs, and the inhibition of TGF-ß1 or Smad 2/3 could reverse this EMT, suggesting that LPS may play a potential role in the EMT of HIBEpiCs.


Protective effect of dexamethasone on osmotic-induced demyelination in rats.
Central pontine myelinolysis (CPM) is a serious demyelination disease commonly associated with the rapid correction of hyponatremia. Although its pathogenesis remains unclear, the disruption of the blood-brain barrier (BBB) as a consequence of a rapid increase in serum sodium concentration is considered to play a critical role. Since glucocorticoids are known to influence BBB permeability and prevent its disruption as a result of hypertension or hyperosmolarity, we investigated whether dexamethasone (DEX) could protect against osmotic demyelination in an animal model of CPM. Hyponatremia was induced in rats by liquid diet feeding and dDAVP infusion. Seven days later, the animals' hyponatremia was rapidly corrected by injecting a bolus of hypertonic saline intraperitoneally. Rats subjected to this treatment displayed serious neurological impairment and 77% died within 5 days of rapid correction of their hyponatremia; demyelinative lesions were observed in various brain regions in these animals. On the other hand, rats that were treated with DEX (2 mg/kg, 0 and 6 h after hypertonic saline injection) exhibited minimal neurological impairment and all were alive after 5 days. Demyelinative lesions were rarely seen in the brains of DEX-treated rats. A marked extravasation of endogenous IgG was observed in the demyelinative lesions in the brains of rats that did not receive DEX, indicating disruption of the BBB, but was not observed in DEX-treated rats. Furthermore, Evans blue injection revealed a significant reduction in staining in the brains of DEX-treated rats (P < 0.05). These results indicate that early DEX treatment can prevent the BBB disruption that is caused by the rapid correction of hyponatremia and its associative demyelinative changes, and suggest that DEX might be effective in preventing CPM.


Clinical Requirements of Future Patient Monitoring in the Intensive Care Unit: Qualitative Study.
In the intensive care unit (ICU), continuous patient monitoring is essential to detect critical changes in patients' health statuses and to guide therapy. The implementation of digital health technologies for patient monitoring may further improve patient safety. However, most monitoring devices today are still based on technologies from the 1970s. The aim of this study was to evaluate statements by ICU staff on the current patient monitoring systems and their expectations for future technological developments in order to investigate clinical requirements and barriers to the implementation of future patient monitoring. This prospective study was conducted at three intensive care units of a German university hospital. Guideline-based interviews with ICU staff-5 physicians, 6 nurses, and 4 respiratory therapists-were recorded, transcribed, and analyzed using the grounded theory approach. Evaluating the current monitoring system, ICU staff put high emphasis on usability factors such as intuitiveness and visualization. Trend analysis was rarely used; inadequate alarm management as well as the entanglement of monitoring cables were rated as potential patient safety issues. For a future system, the importance of high usability was again emphasized; wireless, noninvasive, and interoperable monitoring sensors were desired; mobile phones for remote patient monitoring and alarm management optimization were needed; and clinical decision support systems based on artificial intelligence were considered useful. Among perceived barriers to implementation of novel technology were lack of trust, fear of losing clinical skills, fear of increasing workload, and lack of awareness of available digital technologies. This qualitative study on patient monitoring involves core statements from ICU staff. To promote a rapid and sustainable implementation of digital health solutions in the ICU, all health care stakeholders must focus more on user-derived findings. Results on alarm management or mobile devices may be used to prepare ICU staff to use novel technology, to reduce alarm fatigue, to improve medical device usability, and to advance interoperability standards in intensive care medicine. For digital transformation in health care, increasing the trust and awareness of ICU staff in digital health technology may be an essential prerequisite. ClinicalTrials.gov NCT03514173; https://clinicaltrials.gov/ct2/show/NCT03514173 (Archived by WebCite at http://www.webcitation.org/77T1HwOzk).


Action Planning Mediates Guidance of Visual Attention from Working Memory.
Visual search is impaired when a salient task-irrelevant stimulus is presented together with the target. Recent research has shown that this attentional capture effect is enhanced when the salient stimulus matches working memory (WM) content, arguing in favor of attention guidance from WM. Visual attention was also shown to be closely coupled with action planning. Preparing a movement renders action-relevant perceptual dimensions more salient and thus increases search efficiency for stimuli sharing that dimension. The present study aimed at revealing common underlying mechanisms for selective attention, WM, and action planning. Participants both prepared a specific movement (grasping or pointing) and memorized a color hue. Before the movement was executed towards an object of the memorized color, a visual search task (additional singleton) was performed. Results showed that distraction from target was more pronounced when the additional singleton had a memorized color. This WM-guided attention deployment was more pronounced when participants prepared a grasping movement. We argue that preparing a grasping movement mediates attention guidance from WM content by enhancing representations of memory content that matches the distractor shape (i.e., circles), thus encouraging attentional capture by circle distractors of the memorized color. We conclude that templates for visual search, action planning, and WM compete for resources and thus cause interferences.


Premenopausal sexual dimorphism in lipopolysaccharide-stimulated production and secretion of tumor necrosis factor.
To establish whether sexual dimorphism in tumor necrosis factor (TNF) concentration in lipopolysaccharide (LPS)-stimulated whole blood culture is related to menopausal status or hormone concentrations. Healthy volunteers (72 premenopausal female, 159 male, and 62 postmenopausal female) completed questionnaires and gave peripheral blood specimens for whole blood LPS-stimulated TNF assay and for selected hormone levels. TNFab microsatellite markers were genotyped. Mean LPS-stimulated TNF level in the premenopausal female group was 18% lower than the postmenopausal female mean (1579 +/- 913 pg/ml compared with 2257 +/- 881 in the men and 1965 +/- 950 in the postmenopausal women; p < 0.0003 and p 0.058, respectively). Analyzing a subset for which blood counts were obtained, mean stimulated TNF per monocyte was lower in the premenopausal female group than in the postmenopausal female group and appeared lower than in the male group (2.67 +/- 1.96 pg/ml per 10(3) monocytes vs 4.44 +/- 2.16 and 3.60 +/- 1.40; p = 0.018 and p = 0.12, respectively). Total plasma cortisol was higher in premenopausal women than men, and, in turn, higher in men than postmenopausal women (mean +/- SD 16.1 +/- 5.7, 12.2 +/- 3.6, and 10.4 +/- 4.3 microg/dl, respectively; p < 0.05 for each comparison). Using multiple linear regression to correct for covariates and TNF allelic effects, premenopausal status predicted TNF level independently from potential confounders or TNF genetic markers (covariate-adjusted decrement of 408 pg/ml; p = 0.0241). In the male group, total cortisol predicted lower TNF level (coefficient -67.5 pg/ml for each microg/dl cortisol; p = 0.0006 after stepwise selection), but total testosterone had no effect. In premenopausal women, LPS-stimulated TNF was not related to total estradiol, testosterone, or cortisol level. Premenopausal women had a lower mean whole blood LPS-stimulated TNF level than postmenopausal women, but there was no significant relation to total estradiol, testosterone, or cortisol levels in premenopausal women.


High turnover of tissue factor enables efficient intracellular delivery of antibody-drug conjugates.
Antibody-drug conjugates (ADC) are emerging as powerful cancer treatments that combine antibody-mediated tumor targeting with the potent cytotoxic activity of toxins. We recently reported the development of a novel ADC that delivers the cytotoxic payload monomethyl auristatin E (MMAE) to tumor cells expressing tissue factor (TF). By carefully selecting a TF-specific antibody that interferes with TF:FVIIa-dependent intracellular signaling, but not with the procoagulant activity of TF, an ADC was developed (TF-011-MMAE/HuMax-TF-ADC) that efficiently kills tumor cells, with an acceptable toxicology profile. To gain more insight in the efficacy of TF-directed ADC treatment, we compared the internalization characteristics and intracellular routing of TF with the EGFR and HER2. Both in absence and presence of antibody, TF demonstrated more efficient internalization, lysosomal targeting, and degradation than EGFR and HER2. By conjugating TF, EGFR, and HER2-specific antibodies with duostatin-3, a toxin that induces potent cytotoxicity upon antibody-mediated internalization but lacks the ability to induce bystander killing, we were able to compare cytotoxicity of ADCs with different tumor specificities. TF-ADC demonstrated effective killing against tumor cell lines with variable levels of target expression. In xenograft models, TF-ADC was relatively potent in reducing tumor growth compared with EGFR- and HER2-ADCs. We hypothesize that the constant turnover of TF on tumor cells makes this protein specifically suitable for an ADC approach.


[MR imaging in congenital disorders of the brain].
MR imaging is an excellent tool for use in diagnosing congenital malformations of the brain. Such malformations cannot be reliably recognized or classified without an insight in to the basic processes of the fetal development of the brain. Cortical malformations are classically divided into (1) malformations of neuronal proliferation, i.e. of stem cell proliferation in the periventricular germinal matrix zone, (2) disorders of neuronal migration, i.e. of the radial migration of the neurons from the periventricular germinal matrix zone to the cortical surface, and (3) disorders of cortical organisation. Other cerebral malformations are agenesis or dysgenesis of the corpus callosum, encephaloceles and various kinds of holoprosencephaly. Chiari malformations and disorders on the Dandy-Walker spectrum are relatively common, primarily infratentorial disorders. Rarer infratentorial disorders are Joubert syndrome, rhombencephalosynapsis and Lhermitte Duclos syndrome.


Lippia alba (Verbenaceae): A new tropical autopolyploid complex?
• Premise of the study: Tropical regions have high species diversity, and polyploidization is a major mechanism of speciation in plants. However, few cases of natural polyploidy have been reported in tropical regions. Lippia alba, is a tropical, aromatic shrub with a wide distribution, extensive morphological plasticity, and several chemotypes. The species has long been recognized as a diploid with 2n = 30 chromosomes. Recently, two variations in chromosome number (2n = 60; 2n = 12-60) have been reported, suggesting the occurrence of polyploidy within the species.• Methods: Flow cytometry was used to investigate the genome size in 106 accessions from 14 Brazilian States. Conventional and molecular cytogenetic techniques and pollen viability analysis were employed to characterize each chromosome number observed.• Key results: The DNA 1C-value varied from 1.17 to 3.45 pg, showing a large variation in genome size. Five distinct chromosome numbers were observed (2n = 30, 38, 45, 60, 90); three are cytogenetically described here for the first time. The 5S rDNA signals varied proportionally according to each chromosome number, but 45S rDNA sites did not. High rates of meiotic irregularity were observed, mainly in cytotypes with higher chromosome numbers.• Conclusions: The data provide new support for the occurrence of a polyploid series in Lippia alba. We provide a hypothesis for how this complex may have arisen. Other cryptic polyploid complexes may remain undiscovered in tropical regions.


Optimizing Tailored Health Promotion for Older Adults: Understanding Their Perspectives on Healthy Living.
Objective: This study explores older adults' perspectives on healthy living, and their interactions with professionals regarding healthy living. This perspective is necessary for health professionals when they engage in tailored health promotion in their daily work routines. Method: In a qualitative study, 18 semi-structured interviews were carried out with older adults (aged 55-98) living in the Netherlands. The framework analysis method was used to analyze the transcripts. Results: Three themes emerged from the data-(a) healthy living: daily routines and staying active, (b) enacting healthy living: accepting and adapting, (c) interaction with health professionals with regard to healthy living: autonomy and reciprocity. Discussion: Older adults experience healthy living in a holistic way in which they prefer to live active and independent lives. Health professionals should focus on building an equal relationship of trust and focus on positive health outcomes, such as autonomy and self-sufficiency when communicating about healthy living.


Water rights reform and water-saving irrigation: evidence from China.
As a market-based water resource management, the water rights reform (WRR) will allocate water rights to water users and allow water users to trade water rights, which can realize the reallocation across water users. In this context, the adoption of water-saving irrigation (WSI) is an important technical form to adapt to the reform. Based on this, this paper studies the impacts of the WRR on WSI using the difference-in-differences (DID) strategy. The results show that the WRR could increase the land area for WSI by an average of 13.63%. The WRR could promote the expansion of high-efficiency irrigation mainly because the WRR could promote the expansion of spray and drip irrigation areas, and micro-irrigation land areas, which are high-efficiency water-saving irrigation technologies. In addition, the WRR also could improve agricultural production by increasing agricultural water productivity and planting area (including the sown area of grain crops and cash crops), but the WRR does not reduce agricultural water extraction. Therefore, the WRR could increase agricultural production without increasing agricultural water extraction.


The mechanism of insertion of a segment of heterologous DNA into the chromosome of Bacillus subtilis.
An Escherichia coli plasmid, p1949, that is derived from pMB9 and pC194, and unable to replicate in Bacillus subtilis, can give rise to stable CmR transformants of the latter species if it is inserted into the bacterial chromosome. A purified segment of the B. subtilis chromosome, with transforming activity against pheA1 and nic-38 recipients, was used to direct the insertion of p1949 into the B. subtilis chromosome. Insertion of the ligated DNA segments occurred in the region of the chromosome from which the purified phe-nic segment was derived. Many of the properties of the resulting CmR transformants of B. subtilis are consistent with the occurrence of a Campbell recombination mechanism leading to integration. However, certain of these properties are more easily explained if it is proposed that integration occurs by a reciprocal recombination event involving a linear ligation product. Evidence is presented suggesting that the inserted sequences may be tandemly duplicated. This may effectively vitiate the use of p1949 as a convenient means for complementation analysis of recessive mutations in B. subtilis.


Review article: from gastrin to gastro-oesophageal reflux disease--a century of acid suppression.
To commemorate Edkins' discovery of gastrin in 1905, we review a century of progress in the physiology and pathobiology of gastrin and acid secretion especially as it pertains to clinical aspects of gastro-oesophageal reflux disease. Although initially ignored, Edkins' observations eventually led to the enthusiastic investigation of gastrin and acid regulation in peptic ulcer disease, culminating in important therapeutic advances in the management of acid peptic disease. Following the improved understanding of gastric secretory physiology, and the development of acid suppressants with increasing efficacy, the use of surgical intervention for peptic ulcer disease was almost eliminated. Surgery became obsolete with the discovery of Helicobacter pylori. Three other advances are also influencing modern practice: the gastrotoxicity of aspirin and non-steroidal anti-inflammatory drugs is now increasingly appreciated, the role of endoscopy in the diagnosis and therapy of upper gastrointestinal bleeding, and the use of intravenous acid-suppressive agents. The major issue for the future resides within the epidemic of gastro-oesophageal reflux disease. How to diagnose, categorize and treat this condition and how to identify and prevent neoplasia, are the challenges of the new century.


Artificial intelligence accurately identifies total hip arthroplasty implants: a tool for revision surgery.
A critical part in preoperative planning for revision arthroplasty surgery involves the identification of the failed implant. Using a predictive artificial neural network (ANN) model, the objectives of this study were: (1) to develop a machine-learning algorithm using operative big data to identify an implant from a radiograph; and (2) to compare algorithms that optimise accuracy in a timely fashion. Using 2116 postoperative anteroposterior (AP) hip radiographs of total hip arthroplasties from 2002 to 2019, 10 artificial neural networks were modeled and trained to classify the radiograph according to the femoral stem implanted. Stem brand and model was confirmed with 1594 operative reports. Model performance was determined by classification accuracy toward a random 706 AP hip radiographs, and again on a consecutive series of 324 radiographs prospectively collected over 2019. The Dense-Net 201 architecture outperformed all others with 100.00% accuracy in training data, 95.15% accuracy on validation data, and 91.16% accuracy in the unique prospective series of patients. This outperformed all other models on the validation (p < 0.0001) and novel series (p < 0.0001). The convolutional neural network also displayed the probability (confidence) of the femoral stem classification for any input radiograph. This neural network averaged a runtime of 0.96 (SD 0.02) seconds for an iPhone 6 to calculate from a given radiograph when converted to an application. Neural networks offer a useful adjunct to the surgeon in preoperative identification of the prior implant.


Alveolar rhabdomyosarcoma with regional nodal involvement: Results of a combined analysis from two cooperative groups.
Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative groups. In order to define a better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissue sarcoma Study Group (EpSSG) and Children's Oncology Group (COG). We retrospectively identified patients with ARMS N1 enrolled in either EpSSG RMS2005 or in COG ARST0531. Chemotherapy in RMS2005 comprised ifosfamide + vincristine + dactinomycin + doxorubicin (IVADo), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531, it consisted of either vincristine + dactinomycin + cyclophosphamide (VAC) or VAC alternating with vincristine + irinotecan (VI). Local treatment was similar in both protocols. The analysis of the clinical characteristics of 239 patients showed some differences between study groups: in RMS2005, advanced Intergroup Rhabdomyosarcoma Study Group (IRS) and large tumors predominated. There were no differences in outcomes between the two groups: 5-year event-free survival (EFS), 49% (95% confidence interval [CI]: 39-59) and 44% (95% CI: 30-58), and overall survival (OS), 51% (95% CI: 41-61) and 53.6% (95% CI: 40-68) in RMS2005 and ARST0531, respectively. In RMS2005, EFS of patients with FOXO1-positive tumors was significantly inferior to those with FOXO1-negative (49.3% vs 73%, P = .034). In contrast, in ARST0531, EFS of patients with FOXO1-positive tumors was 45% compared with 43.8% for those with FOXO1-negative. The outcome of patients with ARMS N1 was similar in both protocols. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that different strategies of chemotherapy may have an impact in the outcome of this subgroup of patients.


Revalorization of Almond By-Products for the Design of Novel Functional Foods: An Updated Review.
The search for waste minimization and the valorization of by-products are key to good management and improved sustainability in the food industry. The great production of almonds, based on their high nutritional value as food, especially almond kernels, generates tons of waste yearly. The remaining parts (skin, shell, hulls, etc.) are still little explored, even though they have been used as fuel by burning or as livestock feed. The interest in these by-products has been increasing, as they possess beneficial properties, caused by the presence of different bioactive compounds, and can be used as promising sources of new ingredients for the food, cosmetic and pharmaceutical industry. Additionally, the use of almond by-products is being increasingly applied for the fortification of already-existing food products, but there are some limitations, including the presence of allergens and mycotoxins that harden their applicability. This review focuses on the extraction technologies applied to the valorization of almond by-products for the development of new value-added products that would contribute to the reduction of environmental impact and an improvement in the sustainability and competitiveness of the almond industry.


Sequential organ failure assessment score as the determinant of outcome for patients with severe sepsis.
To evaluate the impact of organ dysfunction in severe sepsis and determine the effectiveness of organ dysfunction scores to discriminate outcome after admission to the intensive care unit (ICU). Patients with a diagnosis of severe sepsis and at least one organ dysfunction on the first day in the ICU (n=117) were included in the prospective observational study. The presence of organ dysfunction was assessed using a Sequential Organ Failure Assessment (SOFA). The severity of illness was assessed using a Simplified Acute Physiology Score (SAPS) II during the first 24 hours after the admission to the ICU. The main outcome was survival status on day 28 after admission to the ICU. Most common sites of infection were intra-abdominal and respiratory system (77 and 38 cases, respectively). Median SAPS II score on admission was 47 points (25th-75th quartiles range, 37-57 points). Twenty eight days survival rate was 41%. The best discrimination results were shown for cumulative scores with the highest for the SOFA score on day 3 in the ICU. The ability to discriminate outcome on day 1 was weak for the presence of dysfunction in all organ systems except neurological. The discriminative power of organ dysfunction scores increased during the stay in the ICU. Neurological and cardiovascular dysfunctions were the independent risk factors for mortality. The SOFA scores showed high accuracy in describing the course of organ dysfunction for the patients with severe sepsis. Evolving organ dysfunction following admission to the ICU strongly affected the outcome. Cumulative SOFA scores were better in discriminating outcome compared to single organ dysfunction scores.


Mother-to-child HIV transmissions in Israel, 1985-2011.
Mother-to-child transmission (MTCT) is the leading cause of paediatric HIV-infection in Israel. This study aimed to assess MTCT rates and analyse temporal changes in relation to highly active antiretroviral therapy (HAART) introduction in 1996. This historical prospective study included all HIV-infected women who delivered in Israel between 1988 and 2011. Demographic, clinical, laboratory and therapy characteristics were compared between HIV-infected newborns with all others, and between infants born before and after 1996. Of all 796 infants born in Israel to HIV-infected women, 25 (3·1%) were infected. MTCT rates decreased significantly after HAART introduction compared with infants who were born before 1996 (16·3% vs. 1·7%). Mothers who infected vertically were more likely to be younger, Ethiopian-born, delivered trans-vaginally, not treated with HAART during pregnancy/labour and delivered before 1996 compared with mothers who did not transmit the HIV to their neonates. Newborns who did not receive antiretroviral therapy postpartum were more commonly HIV-infected and their mortality rate was higher. In conclusion, HAART during pregnancy/labour decreased MTCT significantly. Most MTCT in Israel was recorded among Ethiopian migrants, yet, in decreasing rates. Continuous efforts should be employed to encourage early HIV testing and allow effective HAART to pregnant women who belong to a key risk-group.


Routine pelvic examination during front-line chemotherapy for ovarian cancer: should it play a role?
To determine if pelvic examination affected management in patients undergoing first-line chemotherapy for ovarian cancer and to determine a threshold of change in tumor size reliably detectable by pelvic examination. We reviewed 501 encounters among 47 women with ovarian cancer to see if pelvic examination prompted a management change. Clinicians then evaluated synthetic model "tumors" and were retested at intervals of 3-48 hours to determine change needed for reliable detection. The median number of examinations was 3 during 8 cycles of chemotherapy. Fifteen examinations (10.5%) revealed palpable anomalies, attributable to known tumor in 10 instances. The most common events preceding management change were elevation in serum CA-125 (57%) or chemotherapy toxicity (20%). No changes were made based on pelvic examination alone. When assessing "tumor" volume in a model, estimates ranged from 33-309% of actual volume. Determination of volume change following a delay was poor. No reliable threshold of detection of volume change was established. Pelvic examination findings rarely dictated management changes in this study. Further, our results call into question the potential of routine pelvic examination to add significantly to clinical management during initial treatment given the wide range of error in "tumor" size estimates.


Effect of frequency of boar exposure and adjusted mating times on measures of reproductive performance in weaned sows.
In weaned sows, reduced reproductive performance can result from failure or delayed return to estrus or improper timing of insemination. This experiment evaluated the effect of increased frequency of boar exposure and adjusted mating times on reproductive performance. Sows of mixed parity were weaned approximately 18.7 d after parturition and allotted by genotype, parity, and lactation length to boar exposure frequency of once daily (1X, n = 66), twice daily every 12 h (2X, n = 61), or three times daily exposure at 8-h intervals (3X, n = 60). Sows were weaned into crates and boar exposure was initiated 3 d after weaning. Once estrus was detected, ultrasound was performed every 8 h to determine time of ovulation. All sows were artificially inseminated twice in the 1X group at 0 and 24 h, in the 2X group at 12 and 24 h, and in the 3X group at 16 and 32 h after onset of estrus. The weaning-to-estrus interval was not influenced by treatment and averaged 4.5 d. The percentage of sows expressing estrus in 8 d was higher (P < 0.05) for 1X (97.3%) compared with 2X (92.8%) but not the 3X group (94.0%). The percentage of sows ovulating after estrus was not influenced by treatment (P > 0.10) and averaged 96.5%. Estrus-to-ovulation interval was not affected by treatment (44.7 h) but was influenced by weaning-to-estrus interval (P < 0.0001). Length of estrus was influenced by treatment (P < 0.001), with estrus in the 1X (46.6 h) shorter than in the 2X (60.0 h) and 3X (67.0 h) treatments, and also by weaning-to-estrus interval (P < 0.001). The percentage of first inseminations occurring within 24 h before ovulation was increased (P < 0.001) in the 2X (62%) and 3X (66%) groups compared with the 1X group (28%) and was also influenced by parity (P < 0.001) and weaning-to-estrus interval (P < 0.05). The percentage of second services within 24 h before ovulation was not increased by any factor and averaged 78%. Farrowing rates were not increased (P > 0.10) for 2X (87.2%) and 3X (83.1%) treatments compared with 1X (75.0%). Total pigs born was also not affected by treatment, although 2X (11.2) and 3X (10.7) numbers were greater than 1X (10.0). It appears that once-daily estrus detection combined with delayed mating could achieve optimal reproductive performance.


Analysis of Factors Affecting Patients' Compliance to Topical Antiglaucoma Medications in Egypt as a Developing Country Model.
Purpose. To study factors affecting patients' compliance to antiglaucoma medications in Egypt where there are unique factors as a developing country. Patients and Methods. A cross-sectional descriptive study on 440 Egyptian patients with open angle glaucoma (OAG) recruited for over two years. The patients were thoroughly interviewed about their age, education level, duration of glaucoma, difficulty in instilling the drops, medication regimens, a family history of glaucoma, knowledge of the disease, and the presence of medical insurance. Results. 236 (53.6%) were noncompliant compared to 204 (46.4%) who were compliant. Females had a tendency for higher compliance (p=0.061). Patient age above 50 years and low level of education and negative family history of glaucoma were factors significantly associated with poor compliance (p < 0.0001). Polytherapy and lack of medical insurance could be contributing factors. Conclusion. Egyptian patients have a high rate of noncompliance compared to the average in literature. Great effort is needed in educating patients about the importance of medications and the risk and the prognosis of this disease. Economic factors must also be taken into consideration in developing countries with large number of poor patients. We recommend simplifying drug regimens, incorporating electronic dose monitors, and creating reminders for follow-up visits of glaucoma patients.


"Language Breathes Life"-Barngarla Community Perspectives on the Wellbeing Impacts of Reclaiming a Dormant Australian Aboriginal Language.
Traditional languages are a key element of Indigenous peoples' identity, cultural expression, autonomy, spiritual and intellectual sovereignty, and wellbeing. While the links between Indigenous language loss and poor mental health have been demonstrated in several settings, little research has sought to identify the potential psychological benefits that may derive from language reclamation. The revival of the Barngarla language on the Eyre Peninsula, South Australia, offers a unique opportunity to examine whether improvements in mental health and social and emotional wellbeing can occur during and following the language reclamation process. This paper presents findings from 16 semi-structured interviews conducted with Barngarla community members describing their own experienced or observed mental health and wellbeing impacts of language reclamation activities. Aligning with a social and emotional wellbeing framework from an Aboriginal and Torres Strait Islander perspective, key themes included connection to spirituality and ancestors; connection to Country; connection to culture; connection to community; connection to family and kinship; connection to mind and emotions; and impacts upon identity and cultural pride at an individual level. These themes will form the foundation of assessment of the impacts of language reclamation in future stages of the project.


The addition of bicalutamide 150 mg to radiotherapy significantly improves overall survival in men with locally advanced prostate cancer.
Castration therapy adjuvant to radiotherapy can significantly improve overall survival compared with radiotherapy alone in patients with locally advanced prostate cancer. Although many of the adverse effects of castration therapy are manageable, they can have a detrimental effect on quality of life. Here we evaluate the efficacy and tolerability of the non-castration-based therapy bicalutamide ('Casodex') 150 mg adjuvant to radiotherapy in patients with T1-4, M0, any n prostate cancer. The subset of patients within the early prostate cancer (EPC) program who received radiotherapy with curative intent (n = 1,370) were included in the analysis. These patients were randomized to receive oral bicalutamide 150 mg once daily (n = 699) or placebo (n = 671). The median follow-up for patients included in this analysis was 7.2 years. In patients with locally advanced disease (n = 305), bicalutamide adjuvant to radiotherapy significantly improved: progression-free survival (PFS), reducing the risk of objective progression by 44% compared with radiotherapy alone [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.40, 0.78; P < 0.001). Prostate-specific antigen (PSA)-PFS, reducing the risk of PSA progression by 59% compared with radiotherapy alone (HR 0.41; 95% CI 0.30, 0.55; P < 0.001). Overall survival, reducing the risk of death by 35% compared with radiotherapy alone (HR 0.65; 95% CI 0.44, 0.95; P = 0.03). This significant overall survival benefit for bicalutamide was driven by a lower risk of prostate cancer-related deaths (16.1 vs 24.3%, respectively). There was no significant difference in PFS or overall survival in patients with localized disease (n = 1,065). In patients with locally advanced disease, bicalutamide 150 mg adjuvant to radiotherapy demonstrates significant clinical benefits in terms of overall survival, PFS and PSA-PFS compared with radiotherapy alone. The overall survival benefit in these patients is consistent with prior studies evaluating castration-based therapies adjuvant to radiotherapy (Bolla et al. in Lancet 360:103-108, 2002; Pilepich et al. in Int J Radiat Oncol Biol Phys 61:1285-1290, 2005). In addition, the clinical benefit of bicalutamide 150 mg in locally advanced patients, but not in those with localized disease, is consistent with the overall results from the EPC program (McLeod et al. BJU Int 97:247-254, 2006). Given the quality-of-life advantages of bicalutamide relative to castration, bicalutamide 150 mg adjuvant to radiotherapy is an attractive alternative for men with locally advanced prostate cancer.


Exogenous taurine administration abates reproductive dysfunction in male rats exposed to silver nanoparticles.
The broad contemporary applications of silver nanoparticles (AgNPs) have been associated with various toxicities including reproductive toxicity. Taurine is well acknowledged for its potent pharmacological role in numerous disease models and chemically-mediated toxicity. We investigated the effect of taurine on AgNPs-induced reproductive toxicity in male rats. The animals were intraperitoneally injected with AgNPs (200 μg/kg) alone or co-administered with taurine at 50 and 100 mg/kg for 21 successive days. Exogenous taurine administration significantly abated AgNPs-induced oxidative injury by decreasing the levels of oxidative stress indices while boosting antioxidant enzymes activities and glutathione level in the hypothalamus, testes and epididymis of exposed animals. Taurine administration alleviated AgNPs-induced inflammatory response and caspase-3 activity, an apoptotic biomarker. Moreover, taurine significantly improved spermiogram, reproductive hormones and the marker enzymes of testicular function in AgNPs-treated animals. The ameliorative effect of taurine on pathological lesions induced by AgNPs in the exposed animals was substantiated by histopathological data. This study provides the first mechanistic evidence that taurine supplementation affords therapeutic effect against reproductive dysfunction associated with AgNPs exposure in male rats.


Regulator of G protein signaling 2 differentially regulates nicotine-induced anxiolytic- and antidepressant-like effects in mice.
This study assessed the role of regulator of G protein signaling 2 (RGS2) in nicotine-induced anxiolytic- and antidepressant-like effects using RGS2 wildtype (WT) and RGS2 knockout (KO) mice. RGS2 negatively regulates monoaminergic neurotransmission, which is implicated in the pathology of anxiety and depression. We hypothesized that deletion of RGS2 would enhance nicotine-induced anxiolytic- and antidepressant-like effects, which were assessed using the elevated plus maze and tail suspension tests, respectively. Anxiolytic-like effects were observed in both RGS2 WT and KO mice after administration of low dose of nicotine (0.05 mg/kg, base) compared to respective saline controls. Additionally, administration of nicotine (0.1 mg/kg, base) compared to saline resulted in anxiolytic-like effects in RGS2 KO mice, but not RGS2 WT mice, suggesting genetic deletion of RGS2 facilitated anxiolytic-like effects of nicotine. Administration of nicotine (0.5 and 1 mg/kg, base) compared to saline resulted in antidepressant-like effects in RGS2 WT mice. Antidepressant-like effects were observed in RGS2 KO mice only at the highest tested dose of nicotine (1 mg/kg, base) compared to saline controls, suggesting that genetic deletion of RGS2 decreased sensitivity to antidepressant-like effects of nicotine. Together, the data suggest that RGS2 differentially regulated nicotine-induced affective behavioral responses. These data suggest that individuals with RGS2 polymorphisms may experience differential affective responses to tobacco smoking, which may make them vulnerable to developing nicotine addiction.


Tail docking in dogs: a review of the issues.
Different groups in our community hold strong views about tail docking in domestic dogs. These range from veterinary associations and welfare organisations, which typically want the practice banned, to purebred dog associations, which vigorously oppose the introduction of antidocking legislation. An evaluation of the tail docking issue, which is informed and nonemotive, requires the integration of moral views with biological and behavioural facts. In recent years, much data have been accumulated concerning the welfare implications of tail docking. Unfortunately, however, there has been limited transfer of this knowledge to people interested in the issue. In this review some of the main arguments for and against canine tail docking are presented and evaluated.


Measuring muscle protein synthesis in humans and the influence of nutritional state.
In 1982 and 2011, Clinical Science published papers that used infusion of stable isotope-labeled amino acids to assess skeletal muscle protein synthesis in the fasted and fed state and before and after a period of increased intake of omega-3 fatty acids, respectively; both of these papers have been highly cited. An overview of the study designs, key findings and novel features, and a consideration of the lasting impact of these two papers is presented. The earlier paper introduced stable isotope tracer approaches in humans that showed consuming a meal will increase whole body oxidation, synthesis, and breakdown of protein, but that protein synthesis is greater than breakdown resulting in net accumulation of protein. The paper also demonstrated that consuming a meal promotes net protein synthesis in skeletal muscle. The later paper introduced the concept that omega-3 polyunsaturated fatty acids are able to improve anabolism by reporting that 8 weeks consumption of high-dose omega-3 fatty acids by healthy young and middle-aged adults increased skeletal muscle protein synthesis during a hyperaminoacidemic-hyperinsulinemic clamp compared with what was seen during the clamp at study entry. Omega-3 fatty acids also increased the phosphorylation of important signaling proteins in muscle, including mammalian target of rapamycin, p70s6k, and Akt, during the clamp. These two papers remain relevant because they offer experimental approaches to study human (patho)physiology in different contexts, they present novel insights into the impact of nutritional state (feeding) and specific nutrients (omega-3 fatty acids) on muscle protein synthesis, and they suggest ways to explore the potential of interventions to help prevent and reverse the age-, disease-, and disuse-associated decline in muscle mass.


Epithelial-mesenchymal transition markers in lymph node metastases and primary breast tumors - relation to dissemination and proliferation.
Epithelial-mesenchymal transition (EMT) was shown to enhance metastatic abilities of cancer cells, but it remains elusive in clinical samples. Moreover, EMT is rarely studied in lymph node metastases (LNM), thus limiting our understanding of its role outside of the primary tumors (PT). We collected a set of samples including triplets - PT, circulating tumor cells (CTCs)-enriched blood samples and LNM from 108 early breast cancer patients. With immunohistochemistry we analyzed levels of EMT effectors - E-cadherin, vimentin and N-cadherin in LNM, central areas and margins of PT. Additionally, expression of EMT core regulators TWIST1, SNAI1, SNAI2 was measured with RT-qPCR. Patients with E-cadherin loss had CTCs in 45% of the cases in comparison to 23% with normal E-cadherin level (P = 0.05). Mesenchymal phenotype of CTCs-enriched blood fractions was five-times more frequent in patients with E-cadherin loss in PT compared to PT with normal E-cadherin levels (P = 0.01). Epithelial/mesenchymal status of matched samples at different stages of dissemination was frequently discordant, especially for pairs involving CTCs, indicating high plasticity of tumor cells. LNM showed increased expression of TWIST1, SNAI1, SNAI2 accompanied by decreased Ki67 labeling index, with median Ki67 of 15% in PT and 10% in LNM (P = 0.0002). Our findings demonstrate that E-cadherin loss, not only in PT margin, might lead to seeding of especially malignant CTCs with mesenchymal phenotype. In comparison to PT, cells in LNM re-express E-cadherin, upregulate EMT transcription factors and reduce cell division rate, which could be viewed as their long-term survival strategy.


A tale of two pandemics: The enduring partisan differences in actions, attitudes, and beliefs during the coronavirus pandemic.
Early in the new coronavirus disease (COVID-19) pandemic, scholars and journalists noted partisan differences in behaviors, attitudes, and beliefs. Based on location data from a large sample of smartphones, as well as 13,334 responses to a proprietary survey spanning 10 months from April 1, 2020 to February 15, 2021, we document that the partisan gap has persisted over time and that the lack of convergence occurs even among individuals who were at heightened risk of death. Our results point to the existence and persistence of the interaction of partisanship and information acquisition and highlight the need for mandates and targeted informational campaigns towards those with high health risks.


Assessment for returning to work after spinal cord injuries and patient's vocational preferences.
Returning to work after spinal cord injury (SCI) is a complex process due to the nature of injury and its devastating effect on all aspects of patients. This case study report is based on a spinal cord injury centre of Bangladesh. The evaluation examined vocational assessment process and vocational interest of persons with SCI undergoing rehabilitation program in the center. Occupational Therapists were interviewed to understand the existing vocational assessment services. This study also used data from 183 vocational assessment forms to find out the association of vocational interests and other demographic factors. The vocational assessment conducted to gathered information on the physical capacity of the patient and physical environment of patients living area only. The most preferred vocational interest was shop management 39%, and returning to previous job 38%. Vocational trades with the lowest level of interest were computer (2%) and electronics (3%), and 10% of patients at the time of assessment were undecided. A statistically significant association between interest to return to previous job and gender, age, occupation before injury and living area were found. Patients go through a complex process to adapt to a new life after experiencing SCI which is significantly influenced by the rehabilitation professionals around him/her. A comprehensive assessment including psychosocial information and therapist's expertise on facilitations making vocational decision based on the variables can optimize the rehabilitation outcome.


Correlation of psychomotor findings and the outcome of a physical therapy program to treat scapular dyskinesis.
This pilot study was performed to investigate the influence of psychomotor skills on the outcome of a specific nonoperative program (scapular dyskinesis-program) to treat scapular dyskinesis. Fifteen patients (group A) with positive and 11 patients (group B) with a negative outcome after physical therapy were included. To test the psychomotor skills of the patients the Motorische Leistungsserie (MLS) was used. The test results of the patients of group A were then compared with those of group B. For 2 parameters, a significant correlation could be detected. However, due to the small sample size, a clear but statistically insignificant difference could be found for several other factors. We, therefore, hypothesize that psychomotor skills testing is a potential method to predict the outcome of nonoperative treatment for scapular dyskinesis. Further investigations with a larger sample size are necessary to confirm this assumption.


Ocular syphilis, a case of acute posterior placoid chorioretinitis.
To report a case of acute posterior placoid chorioretinitis, a rare manifestation of ocular syphilis. The patient was examined at age 59 with symptoms of subacute severe unilateral vision loss of the right eye. He underwent fundus examination, automated perimetry, optical coherence tomography imaging and fluorescein angiography. There was a close follow-up for 3 months. At time of presentation, the visual acuity in the right eye was hand movement. Fundus examination showed a central retinal placoid yellowish lesion going beyond the temporal vascular arcades. Optical coherence tomography showed thickening of the neuroretina and disappearance of the inner and outer segment junction. Fluorescein angiography showed in the early phase areas of hypofluorescence followed by hyperfluorescence and late staining. Serologic examinations were positive for secondary syphilis. After treatment with intravenous ceftriaxone 2g/d for 2 weeks there was a complete functional recovery with regression of the fundus lesion. Acute syphilitic posterior placoid chorioretinitis has been described as a rare chorioretinal manifestation in patients with syphilis. The pathogenesis of this entity still remains unknown. Since there are no pathognomonic features of ocular syphilis, findings may often mimic those of other diseases. Maintaining an awareness of the different manifestations of this disease allows ophthalmologists to play a key role in the early diagnosis of syphilis.


[Determination of the sample size and distribution of the ABO and Rh blood groups in Botucatu, Sã Paulo, Brazil (author's transl)].
In the present paper some statistical aspects referred to the distribution of the ABO and Rh blood groups were studied. The sample included 4,037 data, about white and no white persons, of both sexes, living in Botucatu. The results are presented with a calculation of the frequencies of the alleles responsible for the polymorphisms studied, the sample frequencies of the blood groups and their populations confidence-intervals estimates. The possibles interdependences for sex and color with the blood groups were verified by the chi2 test. The principal aim of the present study was to determine the ideal sample size. It was elaborated a table where are given populations sizes, samples sizes and the percentual relations between these values.


Arthropathy associated with cystic acne, hidradenitis suppurativa, and perifolliculitis capitis abscedens et suffodiens: treatment with isotretinoin.
A patient with arthropathy associated with cystic acne, hidradenitis suppurativa, and perifolliculitis capitis abscedens et suffodiens who showed a dramatic response to isotretinoin is described. This, to our knowledge, is the first report documenting effective treatment of this condition, whose nosologic position with respect to other spondyloarthropathies associated with cutaneous disease is considered.


Inhibition of tobacco mosaic virus movement by expression of an actin-binding protein.
The tobacco mosaic virus (TMV) movement protein (MP) required for the cell-to-cell spread of viral RNA interacts with the endoplasmic reticulum (ER) as well as with the cytoskeleton during infection. Whereas associations of MP with ER and microtubules have been intensely investigated, research on the role of actin has been rather scarce. We demonstrate that Nicotiana benthamiana plants transgenic for the actin-binding domain 2 of Arabidopsis (Arabidopsis thaliana) fimbrin (AtFIM1) fused to green fluorescent protein (ABD2:GFP) exhibit a dynamic ABD2:GFP-labeled actin cytoskeleton and myosin-dependent Golgi trafficking. These plants also support the movement of TMV. In contrast, both myosin-dependent Golgi trafficking and TMV movement are dominantly inhibited when ABD2:GFP is expressed transiently. Inhibition is mediated through binding of ABD2:GFP to actin filaments, since TMV movement is restored upon disruption of the ABD2:GFP-labeled actin network with latrunculin B. Latrunculin B shows no significant effect on the spread of TMV infection in either wild-type plants or ABD2:GFP transgenic plants under our treatment conditions. We did not observe any binding of MP along the length of actin filaments. Collectively, these observations demonstrate that TMV movement does not require an intact actomyosin system. Nevertheless, actin-binding proteins appear to have the potential to exert control over TMV movement through the inhibition of myosin-associated protein trafficking along the ER membrane.


Outcomes of Elderly Patients Undergoing Emergency Surgery for Complicated Colorectal Cancer: A Retrospective Cohort Study.
Colorectal cancer is one of the most frequent types of malignant neoplasms. Age is a risk factor for this disease, with 75% of cases diagnosed in patients older than 65 years. Complications such as obstruction, hemorrhage, and perforation are present in more than one-third of cases and require emergency treatment. We aim to analyze the profile of elderly patients undergoing surgery for complicated colorectal cancer, and to evaluate factors related to worse short-term prognosis. A retrospective analysis of patients who underwent emergency surgical treatment for complicated colorectal cancer was performed. Demographics, clinical, radiological and histological data were collected. Sixty-seven patients were analyzed. The median age was 72 years, and almost half (46%) of the patients were female. Obstruction was the most prevalent complication at initial presentation (72%). The most common sites of neoplasia were the left and sigmoid colon in 22 patients (32.8%), and the right colon in 17 patients (25.4%). Resection was performed in 88% of cases, followed by primary anastomosis in almost half. The most frequent clinical stages were II (48%) and III (22%). Forty-three patients (65.7%) had some form of postoperative complication. Clavien-Dindo grades 1, 2, and 4, were the most frequent. Complete oncologic resection was observed in 80% of the cases. The thirty-day mortality rate was 10.4%. Advanced age was associated with worse morbidity and mortality. Elderly patients with complicated colorectal cancer undergoing emergency surgery have high morbidity and mortality rates. Advanced age is significantly associated with worse outcomes.


Longitudinal analysis of communication repair skills across three neurodevelopmental disabilities.
This study is a longitudinal follow-up to prior work examining the important pragmatic skill of communication repair (i.e., the ability to respond effectively to a request for clarification of an unclear message) across three neurodevelopmental disabilities in which language skills are impaired: fragile X syndrome with and without autism spectrum disorder (FXS-ASD; FXS-O), idiopathic ASD (ASD-O), Down syndrome (DS) and controls with typical development (TD). Prior work examining communication repair skills at younger ages indicated impairments in boys with FXS-ASD and ASD-O, with females performing comparably with each other across groups. To characterize communication repair skills in young individuals with FXS-ASD, FXS-O, ASD-O, DS and TD, across groups and over development. A secondary aim included documenting sex differences in FXS (with and without ASD) and DS. Sixty young individuals with FXS-ASD (49 males, 11 females), 38 with FXS-O (13 males, 25 females), 38 with ASD-O (males only), 42 with DS (21 males, 21 females) and 41 with TD (21 males, 20 females) participated in the study, with a subsample reported on here who were retested at a second time point 2.7 years later on average. Participants completed a structured, picture-based task designed to assess the ability to repair breakdowns in communication. Participants' responses were compared across groups and sexes at the second time point, and interpreted with respect to previously published (Time 1) findings. Key findings included that, with age, male groups (including those with FXS-ASD and ASD-O, who showed difficulty at Time 1) performed more comparably, decreasing their use of inappropriate responses, in spite of relatively little change observed in general cognitive or structural language abilities in the clinical groups. However, girls with FXS and DS became more non-responsive with age, and differences between boys and girls with FXS-ASD emerged over time as well. Findings suggest that impairments in a critical pragmatic skill-the ability to repair communication breakdown-show significant change with age across three neurodevelopmental disabilities, with important sex-specific patterns. These developments were often observed in spite of a relative plateau in cognitive and language growth, suggesting that repair skills may be more malleable and therefore an excellent target for intervention. Findings not only inform the nature of pragmatic impairment across groups but also can importantly inform clinical practice, suggesting that clinicians should monitor pragmatic skills such as repairs throughout development and also consider the role of sex in clinical efforts.


Late-life shift in caloric intake affects fly metabolism and longevity.
The prevalence of obesity is increasing in older adults and contributes to age-related decline. Caloric restriction (CR) alleviates obesity phenotypes and delays the onset of age-related changes. However, how late in life organisms benefit from switching from a high-(H) to a low-calorie (L) diet is unclear. We transferred male flies from a H to a L (HL) diet or vice versa (LH) at different times during life. Both shifts immediately change fly rate of aging even when applied late in life. HL shift rapidly reduces fly mortality rate to briefly lower rate than in flies on a constant L diet, and extends lifespan. Transcriptomic analysis uncovers that flies aged on H diet have acquired increased stress response, which may have temporal advantage over flies aged on L diet and leads to rapid decrease in mortality rate after HL switch. Conversely, a LH shift increases mortality rate, which is temporarily higher than in flies aged on a H diet, and shortens lifespan. Unexpectedly, more abundant transcriptomic changes accompanied LH shift, including increase in ribosome biogenesis, stress response and growth. These changes reflect protection from sudden release of ROS, energy storage, and use of energy to growth, which all likely contribute to higher mortality rate. As the beneficial effects of CR on physiology and lifespan are conserved across many organisms, our study provides framework to study underlying mechanisms of CR interventions that counteract the detrimental effects of H diets and reduce rate of aging even when initiated later in life.


Inferring the population history of Kyrgyz in Xinjiang, Northwest China from genome-wide array genotyping.
Xinjiang plays a vital role in the trans-Eurasian population migration, language diffusion, and culture and technology exchange. However, the underrepresentation of Xinjiang's genomes has hindered a more comprehensive understanding of Xinjiang's genetic structure and population history. We collected and genotyped 70 southern Xinjiang's Kyrgyz (SXJK) individuals and combined the data with modern and ancient Eurasians published. We used allele-frequency methods, including PCA, ADMIXTURE, f-statistics, qpWave/qpAdm, ALDER, Treemix, and haplotype-shared methods including shared-IBD segments, fineSTRUCTURE, and GLOBETROTTER to unveil the fine-scale population structure and reconstruct admixture history. We identified genetic substructure within the SXJK population with subgroups showing different genetic affinities to West and East Eurasians. All SXJK subgroups were suggested to have close genetic relationships with surrounding Turkic-speaking groups that is, Uyghur, Kyrgyz from north Xinjiang and Tajikistan, and Chinese Kazakh, suggesting a shared ancestry among those populations. Outgroup-f3 and symmetrical f4 statistics showed a high genetic affinity of SXJK to present-day Tungusic, Mongolic-speaking populations and Ancient Northeast Asian (ANA) related groups. Allele sharing and haplotype sharing profiles revealed the east-west admixture pattern of SXJK. The qpAdm-based admixture models showed that SXJK derived ancestry from East Eurasian (ANA and East Asian, 42.7%-83.3%) and West Eurasian (Western Steppe herders and Central Asian, 16.7%-57.3%), the recent east-west admixture event could be traced to 1000 years ago based on ALDER and GLOBETROTTER analysis. The high genetic affinity of SXJK to present-day Tungusic and Mongolic-speaking populations and short-shared IBD segments indicated their shared common ancestry. SXJK harbored a close genetic affinity to ANA-related populations, indicating the Northeast Asian origin of SXJK. The West and East Eurasian admixture models observed in SXJK further provided evidence of the dynamic admixture history in Xinjiang. The east-west admixture pattern and the identified ancestral makeup of SXJK suggested a genetic continuity from some Iron Age Xinjiang populations to present-day SXJK.


Defining the molecular basis of tumor metabolism: a continuing challenge since Warburg's discovery.
Cancer cells are the product of genetic disorders that alter crucial intracellular signaling pathways associated with the regulation of cell survival, proliferation, differentiation and death mechanisms. The role of oncogene activation and tumor suppressor inhibition in the onset of cancer is well established. Traditional antitumor therapies target specific molecules, the action/expression of which is altered in cancer cells. However, since the physiology of normal cells involves the same signaling pathways that are disturbed in cancer cells, targeted therapies have to deal with side effects and multidrug resistance, the main causes of therapy failure. Since the pioneering work of Otto Warburg, over 80 years ago, the subversion of normal metabolism displayed by cancer cells has been highlighted by many studies. Recently, the study of tumor metabolism has received much attention because metabolic transformation is a crucial cancer hallmark and a direct consequence of disturbances in the activities of oncogenes and tumor suppressors. In this review we discuss tumor metabolism from the molecular perspective of oncogenes, tumor suppressors and protein signaling pathways relevant to metabolic transformation and tumorigenesis. We also identify the principal unanswered questions surrounding this issue and the attempts to relate these to their potential for future cancer treatment. As will be made clear, tumor metabolism is still only partly understood and the metabolic aspects of transformation constitute a major challenge for science. Nevertheless, cancer metabolism can be exploited to devise novel avenues for the rational treatment of this disease.


Competitiveness and conflict behavior in simulation of a social dilemma.
This experiment examined the competitive behavior in a seven-choice Prisoner's Dilemma game of 108 adult students (68 women, 40 men) classified as high, average, or low in competitiveness based on their scores on the Competitiveness Index. Participants were then presented one of three preprogrammed response conditions representing (1) Competitive, (2) De-escalating, or (3) Noncompetitive conflict behavior from a simulated opponent. Participants high in competitiveness engaged in more competitive behavior and reported higher satisfaction with the task than those low in competitiveness. As expected, the Competitive conditions elicited more competitive behavior than Noncompetitive conditions. The results suggest competitive individuals may be particularly susceptible to social cues that trigger competitive behavior.


Point-of-care antimicrobial coating protects orthopaedic implants from bacterial challenge.
Implant related infections are the most common cause of joint arthroplasty failure, requiring revision surgeries and a new implant, resulting in a cost of $8.6 billion annually. To address this problem, we created a class of coating technology that is applied in the operating room, in a procedure that takes less than 10 min, and can incorporate any desired antibiotic. Our coating technology uses an in situ coupling reaction of branched poly(ethylene glycol) and poly(allyl mercaptan) (PEG-PAM) polymers to generate an amphiphilic polymeric coating. We show in vivo efficacy in preventing implant infection in both post-arthroplasty infection and post-spinal surgery infection mouse models. Our technology displays efficacy with or without systemic antibiotics, the standard of care. Our coating technology is applied in a clinically relevant time frame, does not require modification of implant manufacturing process, and does not change the implant shelf life.


Carbonyl Compounds Containing Formaldehyde Produced from the Heated Mouthpiece of Tobacco Sticks for Heated Tobacco Products.
Diverse harmful compounds can be emitted during the heating of tobacco sticks for heated tobacco products (HTPs). In this study, the generation of harmful compounds from the filter, instead of tobacco in tobacco sticks, was confirmed. The heat of a heated tobacco product device can be transferred to the tobacco stick filter, resulting in the generation of harmful compounds from the heated filter. Since the heating materials (tobacco consumable) of the tobacco sticks evaluated in this study were different depending on the brand, the harmful compounds emitted from the heated tobacco stick filters were examined by focusing on the carbonyl compounds, using three different tobacco stick parts. Acetaldehyde and propionaldehyde exhibited the highest concentrations in HTP aerosols produced by heating the tobacco consumable (conventional case) (63.5 ± 18.4 µg/stick and 1.71 ± 0.123 µg/stick, respectively). The aerosols produced by heating tobacco stick filters had higher formaldehyde and acrolein concentrations (0.945 ± 0.214 µg/stick and 0.519 ± 0.379 µg/stick) than the aerosols generated from heated tobacco consumable (0.641 ± 0.092 µg/stick and 0.220 ± 0.102 µg/stick). As such, formaldehyde and acrolein were produced by heating small parts of the mouthpiece of a tobacco stick, regardless of the heated tobacco product brand. In addition, acetone was only detected in the aerosols generated from heated filters (0.580 ± 0.305 µg/stick). Thus, safety evaluations of heated tobacco products should include considerations of the harmful compounds generated by heating tobacco stick mouthpieces for heated tobacco products in addition to those found in heated tobacco product aerosols.


Levels and patterns of neutrophil cell counts over the first 8 years of life in children of HIV-1-infected mothers.
Antiretroviral drugs (ARV) as prophylaxis to prevent mother-to-child transmission of HIV results in decreased haematological parameters during and shortly after exposure, with recent data suggesting a more prolonged inhibition of haematopoiesis until at least 18 months. Data on 156 HIV-infected and 1533 uninfected children in the European Collaborative Study followed from birth until at least 8 years of age. Smoothers and splines were used to elucidate patterns over age; linear mixed effects allowed for repeated measurements. Covariates included the child's HIV-1 infection status, prematurity, gender, race, drug withdrawal symptoms at birth and ARV exposure; effects on neutrophil count were quantified in regression analyses using z-scores (SD from mean) of neutrophil counts obtained after modelling untransformed values using the LMS method. For HIV-infected children, progression to AIDS and ARV therapy were also included. After approximately 4 months of age, neutrophil counts were consistently and substantially lower in HIV-infected children than in uninfected children; in both groups, black children had significantly lower counts than white children across the whole age range. In uninfected children, male gender and ARV exposure were associated with reduced neutrophil count until at least 8 years of age. In HIV-infected children, advanced disease and ARV treatment were significantly associated with neutrophil count. A considerably longer effect of exposure to ARV was shown in uninfected children than previously thought and significant associations were shown between race and gender and neutrophil count, as previously observed for lymphocyte counts. The clinical relevance of these reduced levels of neutrophils requires further investigation.


Metabolism and disposition of [(14)C]1-nitronaphthalene in male Sprague-Dawley rats.
In rats and mice, 1-nitronaphthalene (1-NN) produces both lung and liver toxicity. Even though these toxicities have been reported, the metabolism and disposition of 1-NN have not been elucidated. Therefore, studies were performed to characterize its fate after i.p. and i.v. administration to male Sprague-Dawley rats. After i.p. administration of [(14)C]1-NN (100 mg/kg; 60 microCi/kg), 84% of the dose was eliminated in the urine and feces by 48 h. At 96 h, 60% of the dose was recovered in the urine, 32% in the feces, and 1% collectively in the tissues, blood, and gastrointestinal contents. The terminal phase rate constant (k(term)) of 1-NN was 0.21 h(-1), the terminal phase half-life (T(1/2,term)) was 3.40 h, and the systemic bioavailability was 0.67. When administered i.v. (10 mg/kg; 120 microCi/kg), 85% of the dose was eliminated in the urine and feces by 24 h. At the end of the study (96 h), 56% of the dose was recovered in the urine, 36% in the feces, and 1% collectively in the tissues, blood, and gastrointestinal contents. Interestingly, 88% of the dose was secreted into bile by 8 h. The k(term) was 0.94 h(-1) and the T(1/2,term) was 0.77 h. The major urinary metabolite after both routes of administration was N-acetyl-S-(hydroxy-1-nitro-dihydronaphthalene)-L-cysteine. Other urinary metabolites identified include hydroxylated, dihydroxylated, glucuronidated, sulfated, and reduced metabolites, as well as dihydrodiol. The major biliary metabolite was hydroxy-glutathionyl-1-nitro-dihydronaphthalene. These data show that 1-NN undergoes extensive metabolism and enterohepatic recirculation, and the majority of the dose is eliminated in the urine.


Phenol assisted deaggregation of polyaniline chains: simple route to high quality polyaniline film.
High conducting polyaniline films were readily prepared by in situ chemical oxidative polymerization/deposition of aniline in the presence of a very small amount of organic additive such as phenol. The conductivity of a thin ( approximately 150 nm) polyaniline film synthesized in the presence of 0.01 wt % of phenol ( r-PANI) is an order of magnitude higher (as well as better conducting homogeneity) than that of a film (PANI) obtained from the conventional method without an additive. r-PANI also has better adhesion and electrochemical stability/reversibility, more transparency in the visible-light region, and faster/easier doping/dedoping response compared to PANI. The function of phenol molecule is to avoid the formation of the inter- and/or intrachain hydrogen bonding during the growth of the polyaniline chains. The deaggregation/reducing intrachain hydrogen bonding of polyaniline chains by phenol molecules was revealed with IR, SAXS, and SEM data. All these data supported that phenol does assist the deaggregation of polyaniline chains during the growth of polymer chains or nanorods.


Congenital cytomegalovirus infection in high-risk Canadian infants: Report of a pilot screening study.
Congenital cytomegalovirus (cCMV) is the most common congenital infection; however, the epidemiology in Canada has not been recently examined. The present prospective study pilots tools for a population-based study of cCMV infection in Canada by determining the maternal seroprevalence and risk factors, the clinical characteristics and the incidence of cCMV using a variety of diagnostic tests in a cohort of high-risk infants in northern Alberta. All infants born at the Royal Alexandra Hospital in Edmonton, Alberta, from June 1, 2003, to May 31, 2004, were screened for the study. Eligible infants were those with very low birth weights (VLBWs) or small for gestational age (SGA). Maternal CMV serostatus was determined, and chart review and parental interviews were completed. Neonatal urine and throat cultures, and polymerase chain reaction (PCR) were performed. Dried blood spots (DBS) were tested for CMV by PCR. In total, 213 infants were eligible for the study. Of these, 137 entered the study (79 VLBW and 58 SGA). Some families were not contacted for participation in the study due to neonatal deaths or early discharge. The mean age of the mothers was 27.6 years; 68% of the mothers were Caucasian and 16% were Aboriginal. The maternal CMV seroprevalence was 55%. Seropositivity was significantly associated with ethnicity (First Nations [100%]; Caucasian [34%]) and country of birth (outside Canada [94%]; Canadian born [45%]). The rate of cCMV was two in 137 (1.5%), with a rate of one in 79 (1.3%) for the VLBW infants and one in 58 (1.7%) for the SGA infants. Both had positive throat or urine specimens, but only the symptomatic infant was positive on DBS. A cCMV screening program should be universal and routine to successfully screen all newborns. Maternal CMV seropositivity varies widely within the Canadian population. In the present pilot study, DBS PCR was not a sensitive screening tool and throat swab was the best screening specimen.


Asthma prevalence, knowledge, and perceptions among secondary school pupils in rural and urban coastal districts in Tanzania.
Asthma is a common chronic disease of childhood that is associated with significant morbidity and mortality. We aimed to estimate the prevalence of asthma among secondary school pupils in urban and rural areas of coast districts of Tanzania. The study also aimed to describe pupils' perception towards asthma, and to assess their knowledge on symptoms, triggers, and treatment of asthma. A total of 610 pupils from Ilala district and 619 pupils from Bagamoyo district formed the urban and rural groups, respectively. Using a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, a history of "diagnosed" asthma or the presence of a wheeze in the previous 12 months was obtained from all the studied pupils, along with documentation of their perceptions regarding asthma. Pupils without asthma or wheeze in the prior 12 months were subsequently selected and underwent a free running exercise testing. A ≥ 20% decrease in the post-exercise Peak Expiratory Flow Rate (PEFR) values was the criterion for diagnosing exercise-induced asthma. The mean age of participants was 16.8 (±1.8) years. The prevalence of wheeze in the past 12 months was 12.1% in Bagamoyo district and 23.1% in Ilala district (p < 0.001). Self-reported asthma was found in 17.6% and 6.4% of pupils in Ilala and Bagamoyo districts, respectively (p < 0.001). The prevalence of exercise-induced asthma was 2.4% in Bagamoyo, and 26.3% in Ilala (P < 0.002). In both districts, most information on asthma came from parents, and there was variation in symptoms and triggers of asthma reported by the pupils. Non-asthmatic pupils feared sleeping, playing, and eating with their asthmatic peers. The prevalence rates of self-reported asthma, wheezing in the past 12 months, and exercise-induced asthma were significantly higher among urban than rural pupils. Although bronchial asthma is a common disease, pupils' perceptions about asthma were associated with fear of contact with their asthmatic peers in both rural and urban schools.


Actor vocal training for the habilitation of speech in adolescent users of cochlear implants.
This study examined changes to speech production in adolescents with hearing impairment following a period of actor vocal training. In addition to vocal parameters, the study also investigated changes to psychosocial factors such as confidence, self-esteem, and anxiety. The group were adolescent users of cochlear implants (mean age at commencement of training 15.9 years), with approximately half of the group wearing a hearing aid in the contralateral ear. The mean age of implantation of the group was 7.6 years and the participants displayed a range of speech production abilities. Evaluation of posttraining outcomes was performed via a combination of perceptual and acoustic analyses. Significant posttraining changes to vocal parameters included increased pitch range and variability and decreased speaking rate. From a psychosocial perspective, posttraining stress levels were significantly lowered. This study suggested that actor vocal training may benefit young people with hearing impairment, both in the way in which they use their voices and in the way in which they view themselves.