Characterization of Several Heterodera glycines mRNA that Encode Small Proteins with Putative Signal Peptides.
Two subtraction libraries were prepared from RNA extracted at early and late stages in the development of soybean cyst nematodes (SCN), Heterodera glycines, in soybean roots. The cDNA from inoculated roots were subtracted with cDNA prepared from non-inoculated roots and SCN eggs, and 384 clones from each library were sequenced. BLAST searches revealed that 191 of the cDNA in the late library were most probably of nematode origin. Alignment of the 191 sequences produced 28 unigenes and 1 singlet. The size of the transcripts for the nematode genes was confirmed by RNA blot hybridization. Thirteen SCN transcripts were selected for further study because they included short open reading frames encoding predicted proteins of <20 kDa with signal peptides at their amino-terminus. Ten of the 13 encode predicted peptides <10 kDa. Although most of the 13 transcripts were fairly abundant in the SCN dbEST, most were of unknown function based on BLAST similarities. Nevertheless, several had characteristics common to anti-microbial peptides, and in situ hybridization indicated that three of the selected transcripts were expressed in the female reproductive system.


Visual adaptation and the amplitude spectra of radiological images.
We examined how visual sensitivity and perception are affected by adaptation to the characteristic amplitude spectra of X-ray mammography images. Because of the transmissive nature of X-ray photons, these images have relatively more low-frequency variability than natural images, a difference that is captured by a steeper slope of the amplitude spectrum (~ - 1.5) compared to the ~ 1/f (slope of - 1) spectra common to natural scenes. Radiologists inspecting these images are therefore exposed to a different balance of spectral components, and we measured how this exposure might alter spatial vision. Observers (who were not radiologists) were adapted to images of normal mammograms or the same images sharpened by filtering the amplitude spectra to shallower slopes. Prior adaptation to the original mammograms significantly biased judgments of image focus relative to the sharpened images, demonstrating that the images are sufficient to induce substantial after-effects. The adaptation also induced strong losses in threshold contrast sensitivity that were selective for lower spatial frequencies, though these losses were very similar to the threshold changes induced by the sharpened images. Visual search for targets (Gaussian blobs) added to the images was also not differentially affected by adaptation to the original or sharper images. These results complement our previous studies examining how observers adapt to the textural properties or phase spectra of mammograms. Like the phase spectrum, adaptation to the amplitude spectrum of mammograms alters spatial sensitivity and visual judgments about the images. However, unlike the phase spectrum, adaptation to the amplitude spectra did not confer a selective performance advantage relative to more natural spectra.


A spectroscopic study of Brazilwood paints in medieval books of hours.
In this work, microspectrofluorimetry was for the first time applied to the identification of the red organic lakes that are characteristic of the lavish illuminations found in 15(th) century books of hours. Microspectrofluorimetry identified those red paints, ranging from opaque pink to dark red glazes, as brazilwood lakes. An unequivocal characterization was achieved by comparison with reference paints produced following recipes from the medieval treatise The Book on How to Make Colours, and was further confirmed by fiber optic reflectance spectroscopy (FORS). For these treasured cultural objects, microspectrofluorimetry and FORS proved to be the only techniques that could identify, in situ or in microsamples, the chromophore responsible for the pinkish hues: a brazilein-Al(3+) complex. Additionally, a multi-analytical approach provided a full characterization of the color paints, including pigments, additives, and binders. Microspectroscopic techniques, based on infrared and X-ray radiation, enabled us to disclose the full palette of these medieval manuscripts, including the elusive greens, for which, besides malachite, basic copper sulfates were found; Raman microscopy suggested a mixture of brochantite and langite. Infrared analysis proved invaluable for a full characterization of the additives that were applied as fillers or whites (chalk, gypsum, and white lead) as well as the proteinaceous and polysaccharide binders that were found pure or in mixture.


Oxidative Stress and Antioxidants in Atherosclerosis Development and Treatment.
Atherosclerosis can be regarded as chronic inflammatory disease affecting the arterial wall. Despite the recent progress in studying the pathogenesis of atherosclerosis, some of the pathogenic mechanisms remain to be fully understood. Among these mechanisms is oxidative stress, which is closely linked to foam cells formation and other key events in atherosclerosis development. Two groups of enzymes are involved in the emergence of oxidative stress: Pro-oxidant (including NADPH oxidases, xanthine oxidases, and endothelial nitric oxide synthase) and antioxidant (such as superoxide dismutase, catalases, and thioredoxins). Pro-oxidant enzymes in normal conditions produce moderate concentrations of reactive oxidant species that play an important role in cell functioning and can be fully utilized by antioxidant enzymes. Under pathological conditions, activities of both pro-oxidant and antioxidant enzymes can be modified by numerous factors that can be relevant for developing novel therapies. Recent studies have explored potential therapeutic properties of antioxidant molecules that are capable to eliminate oxidative damage. However, the results of these studies remain controversial. Other perspective approach is to inhibit the activity of pro-oxidant enzymes and thus to slow down the progression of atherosclerosis. In this review we summarized the current knowledge on oxidative stress in atherosclerosis and potential antioxidant approaches. We discuss several important antioxidant molecules of plant origin that appear to be promising for treatment of atherosclerosis.


Deregulation of MUC4 in gastric adenocarcinoma: potential pathobiological implication in poorly differentiated non-signet ring cell type gastric cancer.
MUC4 is a large, heavily glycosylated transmembrane mucin, that is implicated in the pathogenesis of various types of cancers. To date, no extensive study has been done to check the expression and functional significance of MUC4 in different types of gastric adenocarcinomas. Here, we report the expression profile of MUC4 in gastric adenocarcinomas and its function in poorly differentiated gastric non-signet ring cell carcinoma (non-SRCC) type cells. Immunohistochemical analysis using tissue microarray (TMA) showed a significant difference in MUC4 expression between normal adjacent (n = 45) and gastric adenocarcinoma (n = 83; P < 0.001). MUC4 expression was not associated with tumour type, stage or with the degree of differentiation. To gain further insight into the significance of MUC4 expression in gastric non-SRCC cells, MUC4 was ectopically expressed in AGS, a poorly differentiated gastric non-signet ring cell line. The MUC4 overexpressing cells (AGS-MUC4) showed a significant increase (P < 0.005) in cell motility and a decrease in cellular aggregation as compared with the vector-transfected cells. Furthermore, in vivo tumorigenicity analysis revealed that animals transplanted with the MUC4 overexpressing cells (AGS-MUC4) had a greater incidence of tumours (83%) in comparison to empty vector control (17%). In addition, the expression of MUC4 resulted in enhanced expression of total cellular ErbB2 and phosphorylated ErbB2. In conclusion, our results showed that MUC4 is overexpressed in gastric adenocarcinoma tissues, and that it has a role in promoting aggressive properties in poorly differentiated gastric non-SRCC cells through the activation of the ErbB2 oncoprotein.


Selective slow-wave sleep suppression affects glucose tolerance and melatonin secretion. The role of sleep architecture.
Our study aimed to assess the impact of one night of slow-wave sleep (SWS) suppression on glucose tolerance, and explore whether melatonin plays a role in glucose tolerance impairment after SWS suppression. In sum, 20 volunteers participated in two experimental sessions: a session with SWS suppression during one night's sleep and a session with a regular night's sleep (control). Each session included collecting seven salivary samples. The following morning, an oral glucose tolerance test (OGTT) was performed. SWS suppression effects depended on the individual blood glucose response to the OGTT. During the control session, 'responders' (N = 11), already presented with low glucose tolerance, which further declined after SWS suppression. 'Non-responders' (N = 9) experienced high glucose tolerance in both conditions. Among the responders, SWS suppression led to an increase in melatonin at the moment of awakening, while in non-responders melatonin increased during the first half of the night. In both conditions, responders were characterized by a shorter total sleep time (TST) and less rapid eye movement (REM) sleep. During SWS suppression, they had more non-rapid eye movement (NREM) stage 1 and longer nocturnal wakefulness. Responders and non-responders showed a comparable amount of SWS. This study highlights three key findings: first, SWS suppression leads to an increase in salivary melatonin; second, melatonin's effect on glucose tolerance depends on its secretion timing; and third, durations of REM sleep and nocturnal awakenings, appear to play an important role in melatonin secretion and glucose tolerance, indicating the potential clinical relevance of these findings for type 2 diabetes risk assessment.


Therapeutic potential for protein kinase C inhibitor in vascular restenosis.
Vascular restenosis, an overreaction of biological response to injury, is initialized by thrombosis and inflammation. This response is characterized by increased smooth muscle cell migration and proliferation. Available pharmacological treatments include anticoagulants, antiplatelet agents, immunosuppressants, and antiproliferation agents. Protein kinase C (PKC), a large family of serine/threonine kinases, has been shown to participate in various pathological stages of restenosis. Consequently, PKC inhibitors are expected to exert a wide range of pharmacological activities therapeutically beneficial for restenosis. In this review, the roles of PKC isozymes in platelets, leukocytes, endothelial cells, and smooth muscle cells are discussed, with emphasis given to smooth muscle cells. We will describe cellular and animal studies assessing prevention of restenosis with PKC inhibitors, particularly targeting -α, -β, -δ, and -ζ isozymes. The delivery strategy, efficacy, and safety of such PKC regulators will also be discussed.


Female germ cells of Drosophila require zygotic ovo and otu product for survival in larvae and pupae respectively.
Mutations in the genes ovo or otu can cause abnormal proliferation of XX germ cells, which leads to so-called ovarian tumors, or they can lead to the elimination of XX germ cells, such that adult females possess empty ovaries. Males carrying ovo or otu mutations are unaffected. To find out when this sexual dimorphism affects germ cells, we analyzed the requirement of embryos and larvae for zygotic ovo and otu products. We found that ovo is required for the survival of XX germ cells during larval stages, while XX germ cells lacking otu survive until metamorphosis. Furthermore, we found no sex-transformed mutant larval germ cells and no evidence for an early sex-specific vital process acting in germ cells of the embryo, contrary to what had been suggested earlier.


Colors of thermal pools at Yellowstone National Park.
The brilliant visible colors of various hot springs and pools in Yellowstone National Park are explained with a combination of scattering from the water and from microbial mats that coat the bottoms of these thermal features. A simple 1D radiative transfer model was used to simulate the colors recorded in visible photographs and the spectrum of light making up these colors. The model includes attenuation in water by absorption and molecular scattering as well as reflection characteristics of the microbial mats and surface reflection of the water. Pool geometries are simulated as simple rough cones scaled to have depths and widths that match published data. Thermal images are also used to record the spatial distribution of water skin temperature. The measurements and simulations confirm that colors observed from shallow-water features arise primarily from the spectral properties of the microbial mat, which is related to the water temperature, while colors observed from deeper water arise primarily from the wavelength-dependent absorption and scattering in the water.


Autonomous in situ measurements of seawater alkalinity.
Total alkalinity (AT) is an important parameter for describing the marine inorganic carbon system and understanding the effects of atmospheric CO2 on the oceans. Measurements of AT are limited, however, because of the laborious process of collecting and analyzing samples. In this work we evaluate the performance of an autonomous instrument for high temporal resolution measurements of seawater AT. The Submersible Autonomous Moored Instrument for alkalinity (SAMI-alk) uses a novel tracer monitored titration method where a colorimetric pH indicator quantifies both pH and relative volumes of sample and titrant, circumventing the need for gravimetric or volumetric measurements. The SAMI-alk performance was validated in the laboratory and in situ during two field studies. Overall in situ accuracy was -2.2 ± 13.1 μmol kg(-1) (n = 86), on the basis of comparison to discrete samples. Precision on duplicate analyses of a carbonate standard was ±4.7 μmol kg(-1) (n = 22). This prototype instrument can measure in situ AT hourly for one month, limited by consumption of reagent and standard solutions.


Measuring nurses' impact on health care quality: progress, challenges, and future directions.
Quality measurement is central in efforts to improve health care delivery and financing. The Interdisciplinary Nursing Quality Research Initiative supported interdisciplinary research teams to address gaps in measuring the contributions of nursing to quality care. To summarize the research of 4 interdisciplinary teams funded by The Interdisciplinary Nursing Quality Research Initiative and reflect on challenges and future directions to improving quality measurement. Each team summarized their work including the targeted gap in measurement, the methods used, key results, and next steps. The authors discussed key challenges and recommended future directions. These exemplar projects addressed cross-cutting issues related to quality; developed measures of patient experience; tested new ways to model the important relationships between structure, process, and outcome; measured care across the continuum; focused on positive aspects of care; examined the relationship of nursing care with outcomes; and measured both nursing and interdisciplinary care. Challenges include: measuring care delivery from multiple perspectives; determining the dose of care delivered; and measuring the entire care process. Meaningful measures that are simple, feasible, affordable, and integrated into the care delivery system and electronic health record are needed. Advances in health information systems create opportunities to advance quality measurement in innovative ways. These findings and products add to the robust set of measures needed to measure nurses' contributions to the care of hospitalized patients. The implementation of these projects has been rich with lessons about the ongoing challenges related to quality measurement.


Pseudohypoparathyroidism type 1a and insulin resistance in a child.
Background. A 5-year-old white girl with a history of hypothyroidism in infancy presented to the endocrinology clinic of a tertiary hospital. Her physical examination noted a stocky physique, broad chest, short neck and short digits. Two years later, skin examination revealed subcutaneous nodules and acanthosis nigricans.Investigations. Measurement of levels of serum phosphate, parathyroid hormone, ionized calcium and insulin; measurement of peak growth hormone by the arginine-levodopa stimulation test; calculation of homeostasis model assessment of insulin resistance; assessment of bone age; DNA analysis of the GNAS gene.Diagnosis. Pseudohypoparathyroidism type 1a in a patient with Albright hereditary osteodystrophy, characterized by hypocalcemia, hypothyroidism, growth-hormone deficiency and insulin resistance.Management. The child continued to take levothyroxine 25 microg once daily, and at 5 years of age she was started on 40 mg/kg elemental calcium as calcium carbonate daily, and calcitriol (active vitamin D) 0.25 microg twice daily. Lifestyle modifications were also recommended for weight control. At 6 years and 4 months of age, treatment with growth hormone was initiated at a dose of 0.3 mg/kg weekly.


Bricks-and-mortar and patient safety culture.
Purpose Building a new hospital requires a major investment in capital infrastructure. The purpose of this paper is to investigate the impact of bricks-and-mortar on patient safety culture before and two years after the move of a large tertiary hospital to a greenfield site. The difference in patient safety perceptions between clinical and non-clinical staff is also explored. Design/methodology/approach This research uses data collected from the same workforce across two time periods (2013 and 2015) in a large Australian healthcare service. Validated surveys of patient safety culture ( n=306 and 246) were analysed using descriptive and inferential statistics. Findings Using two-way analysis of variance, the authors found that perceived patient safety culture remains unchanged for staff despite a major relocation and upgrade of services and different perceptions of patient safety culture between staff groups remains the same throughout change. Practical implications A dramatic change in physical context, such as moving an entire hospital, made no measurable impact on perceived patient safety culture by major groups of staff. Improving patient safety culture requires more than investment in buildings and infrastructure. Understanding differences in professional perspectives of patient safety culture may inform organisational management approaches, and enhance the targeting of specific strategies. Originality/value The authors believe this to be the first empirically based paper that investigates the impact of a large investment into hospital capital and a subsequent relocation of services on clinical and non-clinical staff perceptions of patient safety culture.


Computer-based de novo designs of tripeptides as novel neuraminidase inhibitors.
The latest influenza A (H1N1) pandemic attracted worldwide attention and called for the urgent development of novel antiviral drugs. Here, seven tripeptides are designed and explored as neuraminidase (NA) inhibitors on the structural basis of known inhibitors. Their interactions with NA are studied and compared with each other, using flexible docking and molecular dynamics simulations. The various composed tripeptides have respective binding specificities and their interaction energies with NA decrease in the order of FRI > FRV > FRT > FHV > FRS > FRG > YRV (letters corresponding to amino acid code). The Arg and Phe portions of the tripeptides play important roles during the binding process: Arg has strong electrostatic interactions with the key residues Asp151, Glu119, Glu227 and Glu277, whereas Phe fits well in the hydrophobic cave within the NA active site. Owing to the introduction of hydrophobic property, the interaction energies of FRV and FRI are larger; in particular, FRI demonstrates the best binding quality and shows potential as a lead compound. In addition, the influence of the chemical states of the terminal amino acids are clarified: it is revealed that the charged states of the N-terminus (NH(3) (+)) and C-terminus (COO(-)) are crucial for the tripeptide inhibitory activities and longer peptides may not be appropriate. In addition, the medium inhibiting activity by acetylation of the N-terminus indicates the possible chemical modifications of FRI. Experimental efforts are expected in order to actualize the tripeptides as potent NA inhibitors in the near future.


[Comparison of reproducibility measurements for calibration of dental caries epidemiological surveys].
This study compares three measurements (Kappa, general agreement percentage, or GAP, and dice index) used to determine the reproducibility of caries diagnosis in epidemiological surveys under different clinical diagnostic thresholds. Eleven examiners with previous experience in epidemiological surveys were submitted to a theoretical and clinical calibration process. Data analysis used two caries detection thresholds: World Health Organization (WHO) and WHO with the inclusion of initial enamel lesions (WHO + IL). Twenty-three children 6-7 years of age were examined, with and without caries. Mean values for Kappa index, GAP, and Dice were considered high (> 0.90), except for the dice index for the WHO + IL threshold (0.69). Since Kappa is an adjusted agreement index, it can be considered the instrument of choice for calibration of examiners. However, when it is impossible to use, the GAP is recommended together with the dice index in order to orient and improve examiners when examining caries lesions.


What is the normal intra-abdominal pressure in critically ill children and how should we measure it?
The intravesical method has been validated and is considered the gold standard for indirect intra-abdominal pressure (IAP) measurements. In adults, a standard volume (25 mL) is instilled into the bladder to measure IAP. However, the optimal volume for accurate IAP measurements in children has not been well studied and using inappropriate volumes could give erroneous IAP readings. To determine the normal IAP in critically ill children and the optimal volume for IAP measurement by the intravesical method in this population. Prospective observational study. Tertiary pediatric intensive care unit. Ninety-six mechanically ventilated children younger than 18 yrs of age with no clinical evidence of intra-abdominal hypertension. Graduated volumes of normal saline in increments of 3-50 mL were instilled in the bladder via a urethral catheter. IAP was recorded by using the AbViser device (WolfeTory Medical, Inc., Salt Lake City, UT) with each instillation. A pressure-volume curve was generated for every patient, and the minimum and mean optimal volumes were determined from this curve. Data were analyzed by stratification of patients according to weights 0-10 kg, >10-20 kg, and >20-50 kg. Descriptive statistics was used for statistical analysis. Normal IAP for critically ill children was 7 +/- 3 and was similar in the different weight groups (p = .745). Although the mean optimal volume to measure accurate IAP was variable in the different weight groups, the minimum optimal volume was 3 mL irrespective of weight. Mean IAP in critically ill children is 7 +/- 3 mm Hg. The minimum optimal volume needed to accurately measure IAP by the intravesical method in children is 3 mL. We recommend that 3 mL be the standard instillation volume for IAP measurement by the intravesical method in children. IAP >10 mm Hg should be considered elevated in children.


When fear is near: threat imminence elicits prefrontal-periaqueductal gray shifts in humans.
Humans, like other animals, alter their behavior depending on whether a threat is close or distant. We investigated spatial imminence of threat by developing an active avoidance paradigm in which volunteers were pursued through a maze by a virtual predator endowed with an ability to chase, capture, and inflict pain. Using functional magnetic resonance imaging, we found that as the virtual predator grew closer, brain activity shifted from the ventromedial prefrontal cortex to the periaqueductal gray. This shift showed maximal expression when a high degree of pain was anticipated. Moreover, imminence-driven periaqueductal gray activity correlated with increased subjective degree of dread and decreased confidence of escape. Our findings cast light on the neural dynamics of threat anticipation and have implications for the neurobiology of human anxiety-related disorders.


Antiplatelet drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment.


Porous nitrogen-doped carbon microspheres as anode materials for lithium ion batteries.
Nitrogen-doped carbon microspheres (NCSs) were fabricated via a simple, fast and energy-saving microwave-assisted method followed by thermal treatment under an ammonia atmosphere. NCSs thermally treated at different temperatures were investigated as anode materials for lithium ion batteries (LIBs). The results show that NCSs treated at 900 °C exhibit a maximum reversible capacity of 816 mA h g(-1) at a current density of 50 mA g(-1) and preserve a capacity of 660 mA h g(-1) after 50 cycles, and even at a high current density of 1000 mA g(-1), a capacity of 255 mA h g(-1) is maintained. The excellent electrochemical performance of NCSs is due to their porous structure and nitrogen-doping. The present NCSs should be promising low-cost anode materials with a high capacity and good cycle stability for LIBs.


The role of steric hindrance in 3TC resistance of human immunodeficiency virus type-1 reverse transcriptase.
Treating HIV infections with drugs that block viral replication selects for drug-resistant strains of the virus. Particular inhibitors select characteristic resistance mutations. In the case of the nucleoside analogs 3TC and FTC, resistant viruses are selected with mutations at amino acid residue 184 of reverse transcriptase (RT). The initial change is usually to M184I; this virus is rapidly replaced by a variant carrying the mutation M184V. 3TC and FTC are taken up by cells and converted into 3TCTP and FTCTP. The triphosphate forms of these nucleoside analogs are incorporated into DNA by HIV-1 RT and act as chain terminators. Both of the mutations, M184I and M184V, provide very high levels of resistance in vivo; purified HIV-1 RT carrying M184V and M184I also shows resistance to 3TCTP and FTCTP in in vitro polymerase assays. Amino acid M184 is part of the dNTP binding site of HIV-1 RT. Structural studies suggest that the mechanism of resistance of HIV-1 RTs carrying the M184V or M184I mutation involves steric hindrance, which could either completely block the binding of 3TCTP and FTCTP or allow binding of these nucleoside triphosphate molecules but only in a configuration that would prevent incorporation. The available kinetic data are ambiguous: one group has reported that the primary effect of the mutations is at the level of 3TCTP binding; another, at the level of incorporation. We have approached this problem using assays that monitor the ability of HIV-1 RT to undergo a conformational change upon binding a dNTP. These studies show that both wild-type RT and the drug-resistant variants can bind 3TCTP at the polymerase active site; however, the binding to M184V and M184I is somewhat weaker and is sensitive to salt. We propose that the drug-resistant variants bind 3TCTP in a strained configuration that is salt-sensitive and is not catalytically competent.


A novel truncating AIP mutation, p.W279*, in a familial isolated pituitary adenoma (FIPA) kindred.
Familial isolated pituitary adenomas (FIPA) constitute 2-3% of pituitary tumours. AIP is the most commonly mutated gene in FIPA. We herein report a novel germline mutation of the AIP gene in a family with FIPA. We present two patients, a father and his 12-year-old daughter, diagnosed clinically and using laboratory measures with acromegaly-gigantism. Both underwent transsphenoidal hypophyseal surgery for macroadenomas. We initially detected a novel heterozygous germline AIP mutation, c.836G>A (p.W279*), in the father's DNA. We then found the same mutation in his affected daughter. Pituitary adenomas associated with AIP mutations mostly present as FIPA (68%) at an early age (78% occur at <30 years old). They are often growth hormone (GH) - or prolactin - secreting macroadenomas (88%) that have already extended beyond the sella at the time of diagnosis. Acromegalic cases are resistant to somatostatin analogues and multimodal management is frequently essential to control the disease. Our patients had normalized GH/IGF-1 values soon after surgery, although enough time may not have elapsed to reach final cure. While penetrance of the disease can be as low as 10% in FIPA, especially children and young patients with somatotropinoma and prolactinoma should be surveyed for inactivating mutations or deletions in AIP. Determining the causative mutations may be of assistance in early diagnosis, treatment success, and genetic counseling.


Overcoming the barriers of teaching physical examination at the bedside: more than just curriculum design.
Physicians in training must achieve a high degree of proficiency in performing physical examinations and must strive to become experts in the field. Concerns are emerging about physicians' abilities to perform these basic skills, essential for clinical decision making. Learning at the bedside has the potential to support skill acquisition through deliberate practice. Previous skills improvement programs, targeted at teaching physical examinations, have been successful at increasing the frequency of performing and teaching physical examinations. It remains unclear what barriers might persist after such program implementation. This study explores residents' and physicians' perceptions of physical examinations teaching at the bedside following the implementation of a new structured bedside curriculum: What are the potentially persisting barriers and proposed solutions for improvement? The study used a constructivist approach using a qualitative inductive thematic analysis that was oriented to construct an understanding of the barriers and facilitators of physical examination teaching in the context of a new bedside curriculum. Participants took part in individual interviews and subsequently focus groups. Transcripts were coded and themes were identified. Data analyses yielded three main themes: (1) the culture of teaching physical examination at the bedside is shaped and threatened by the lack of hospital support, physicians' motivation and expertise, residents' attitudes and dependence on technology, (2) the hospital environment makes bedside teaching difficult because of its chaotic nature, time constraints and conflicting responsibilities, and finally (3) structured physical examination curricula create missed opportunities in being restrictive and pose difficulties in identifying patients with findings. Despite the implementation of a structured bedside curriculum for physical examination teaching, our study suggests that cultural, environmental and curriculum-related barriers remain important issues to be addressed. Institutions wishing to develop and implement similar bedside curricula should prioritize recruitment of expert clinical teachers, recognizing their time and efforts. Teaching should be delivered in a protected environment, away from clinical duties, and with patients with real findings. Physicians must value teaching and learning of physical examination skills, with multiple hands-on opportunities for direct role modeling, coaching, observation and deliberate practice. Ideally, clinical teachers should master the art of combining both patient care and educational activities.


Treat to target in inflammatory bowel disease: a survey of treatment strategies amongst Portuguese doctors.
treatment goals in inflammatory bowel disease have changed over the last few years and have shifted from a mainly symptom-based management to objective endpoints, such as mucosal healing and deep remission. A treat-to-target strategy to achieve these goals has been proposed by several experts, although the real-life clinical data is still lacking. This study aimed to investigate the current practices among Portuguese gastroenterologists who treat inflammatory bowel disease patients. Portuguese gastroenterologists were asked to participate in an anonymous online survey. The questions focused on opinions and current practice with regard to treatment targets in inflammatory bowel disease. sixty-two physicians agreed to participate in the survey, 40 were gastroenterology specialists and 22 (35.5%) were fellows. Deep remission was considered as the main treatment goal for Crohn's disease and ulcerative colitis by 82% and 83.9% of the participants, respectively. Mucosal healing as a treatment target was used by 95% and 80% of participants in ulcerative colitis and Crohn's disease, respectively; 71% intensified the treatment to achieve mucosal healing after clinical remission. The most common definition of mucosal healing in Crohn's disease and ulcerative colitis was the absence of mucosal ulceration (32.3%) and a Mayo endoscopic sub-score of 0 (41.9%). Only 3.2% escalated treatment with the aim to achieve histologic remission in ulcerative colitis. a treat-to-target strategy to achieve mucosal healing and deep remission is currently accepted by a substantial number of Portuguese gastroenterologists.


A systematic review and meta-analysis of acupuncture in in vitro fertilisation.
Numerous randomised studies have reported pregnancy outcome in women who received acupuncture during their in vitro fertilisation (IVF) treatment cycle. The objective of this study was to conduct a systematic review with meta-analysis of the trials of acupuncture during IVF treatment on the outcomes of clinical pregnancy and live birth rates. Searches were conducted in MEDLINE, EMBASE, Cochrane Library, ISI Proceedings and SCISEARCH. All randomised controlled trials that evaluated the effects of acupuncture compared with no treatment or sham acupuncture in women undergoing IVF-intracytoplasmic sperm injection treatment were included. Study selection, quality appraisal and data extraction were performed independently and in duplicate. A sensitivity analysis was conducted where the meta-analysis was restricted to trials in which sham acupuncture was used in the control group. Meta-regression analysis was used to explore the association between study characteristics and pregnancy rates. Thirteen relevant trials, including a total of 2500 women randomised to either acupuncture or control group, were identified. No evidence of publication bias was found (Begg's test, P = 0.50). Five trials (n = 877) evaluated IVF outcome when acupuncture was performed around the time of transvaginal oocyte retrieval, while eight trials (n = 1623) reported IVF outcome when acupuncture was performed around the time of embryo transfer (ET). Meta-analysis of the five studies of acupuncture around the time of egg collection did not show a significant difference in clinical pregnancy (relative risks [RR] = 1.06, 95% CI 0.82-1.37, P = 0.65). Meta-analysis of the eight studies of acupuncture around the time of ET showed no difference in the clinical pregnancy rate (RR = 1.23, 95% CI 0.96-1.58, P = 0.1). Live birth data were available from five of the eight studies of acupuncture around the time of ET. Meta-analysis of these studies did not show a significant increase in live birth rate with acupuncture (RR = 1.34, 95% CI 0.85-2.11). Using meta-regression, no significant association between any of the studied covariates and clinical pregnancy rate was found (P > 0.05 for all covariates). Currently available literature does not provide sufficient evidence that adjuvant acupuncture improves IVF clinical pregnancy rate.


Gold nanocages with dual modality for image-guided therapeutics.
Numerous studies have demonstrated that microRNAs are very important in cancer development and progression. However, the complex relationship between the size of microRNA delivery systems, cellular uptake, biodistribution and therapeutic efficiency remains unclear. Herein, we have successfully constructed a series of differently-sized microRNA delivery systems, miR-26a-loaded, hyaluronic acid-modified, polyetherimide-conjugated PEGylated gold nanocage ternary nanocomplexes (PPHAuNCs-TNCs), which can be monitored optically by fluorescence and photoacoustic tomography imaging. We evaluated the effect of the particle size on the cellular uptake and biodistribution in the BEL-7402 cell line in vitro and in the subcutaneous and orthotopic hepatocellular carcinoma (HCC) mouse models. Our findings showed that the cellular uptake and biodistribution were optimal for cancer therapy with the PPHAuNCs-30-TNCs (30 nm AuNCs in edge length) in comparison with their 50 nm and 70 nm counterparts. PPHAuNCs-30-TNCs could accumulate in the liver for a longer time in an orthotopic mouse model of HCC than that in normal mice and could considerably restrain tumor growth in an orthotopic HCC mouse model under near-infrared radiation. This study may provide insightful information for developing novel non-viral microRNA vectors, and PPHAuNCs-30-TNCs have great potential for application in tumor diagnosis and cancer therapy in the future.


Topographic organization of somatosensory corticotectal influences in cat.
Using electrophysiological techniques, the present study demonstrated that substantial direct somatosensory cortical influences on the superior colliculus (SC) originate from three areas: a) SIV, b) para-SIV (the cortex adjacent to SIV but deeper in the anterior ectosylvian sulcus (AES) and for which no topography has yet been described), and c) the rostral suprasylvian sulcus. Influences also appeared to originate from SI and SII, but these may have been indirect. Detailed examination of the AES revealed that these corticotectal projections are topographically organized, and stimulation of a given cortical locus was observed to affect only those cells in the SC whose receptive fields overlapped those of cells at the stimulation site. A similar receptive-field register was found between the suprasylvian sulcus and the SC. Within this topographic pattern, considerable convergence was evident and an individual SC cell could be influenced from a surprisingly large cortical area. This was particularly evident within the representation of the forelimb. Thus, an SC cell with a receptive field covering the forelimb and paw could receive convergent input from many cortical cells with receptive fields covering all or restricted portions of this body region. Considerable corticotectal divergence also was observed within this general topographic scheme. For example, a given corticotectal site representing the digits sent projections to many different SC cells that included the digits within their receptive fields. These data are more consistent with a block-to-block than a point-to-point corticotectal projection. Somatosensory corticotectal projections excited only those SC cells that could also be activated by peripheral somatosensory stimuli. Similarly, the caudal AES, which contains auditory cells, excited only those SC cells activated also by peripheral auditory stimuli. Yet convergent influences from both auditory and somatosensory regions of the AES were observed in the SC cells that could be activated by both auditory and somatosensory stimuli. These data indicate that the AES is a major source of excitatory input to cells of the deep laminae of the SC. Since it is these deep laminae cells that project to premotor regions of the brain stem and the spinal cord, it is reasonable to suppose that the AES has a significant impact on the output signals of the SC that initiate the orientation responses to peripheral sensory stimulation.


Automated identification of depsipeptide natural products by an informatic search algorithm.
Nonribosomal depsipeptides are a class of potent microbial natural products, which include several clinically approved pharmaceutical agents. Genome sequencing has revealed a large number of uninvestigated natural-product biosynthetic gene clusters. However, while novel informatic search methods to access these gene clusters have been developed to identify peptide natural products, depsipeptide detection has proven challenging. Herein, we present an improved version of our informatic search algorithm for natural products (iSNAP), which facilitates the detection of known and genetically predicted depsipeptides in complex microbial culture extracts. We validated this technology by identifying several depsipeptides from novel producers, and located a large number of novel depsipeptide gene clusters for future study. This approach highlights the value of chemoinformatic search methods for the discovery of genetically encoded metabolites by targeting specific areas of chemical space.


A Phase II Study of Pazopanib in Patients with Malignant Pleural Mesothelioma: NCCTG N0623 (Alliance).
Preclinical and clinical data have shown promise in using antiangiogenic agents to treat malignant pleural mesothelioma (MPM). We conducted this phase II study to evaluate the efficacy and toxicity of single-agent pazopanib in patients with MPM. Patients with MPM who had received 0-1 prior chemotherapy regimens were eligible to receive pazopanib at a dose of 800 mg daily. The primary endpoint was progression-free survival rate at 6 months (PFS6), with a preplanned interim analysis for futility. Secondary endpoints included overall survival (OS), PFS, adverse events assessment and clinical benefit (complete response, partial response [PR], and stable disease [SD]). Thirty-four evaluable patients were enrolled, with a median age of 73 years (49-84). The trial was closed early because of lack of efficacy at the preplanned interim analysis. Only 8 patients (28.6%; 95% confidence interval [CI], 13.2-48.7%) in the first 28 evaluable were progression-free at 6 months. PFS6 was 32.4% (95% CI, 17.4-50.5). There were 2 PR (5.9%) and 16 SD (47.1%). The overall median PFS and OS were 4.2 months (95% CI, 2.0-6.0) and 11.5 months (95% CI: 5.3-18.2), respectively. The median PFS and OS for the previously untreated patients was 5.4 months (95% CI, 2.7-8.5) and 16.6 months (95% CI, 6.6-30.6), respectively; and 2.0 months (95% CI, 1.3-4.2) and 5.0 months (95% CI: 3.0-11.9), respectively, for the previously treated patients. Grade 3 or higher adverse events were observed in 23 patients (67.6%). Single-agent pazopanib was poorly tolerated in patients with MPM. The primary endpoint of PFS6 was not achieved in the current study. ClinicalTrials.gov identification number. NCT00459862. Single-agent pazopanib did not meet its endpoint in this phase II trial in malignant mesothelioma. Pazopanib is well tolerated in mesothelioma patients with a manageable toxicity profile. There is a need to better identify signals of angiogenesis that can be targeted in mesothelioma. Encouraging findings in frontline treatment warrant further investigations in combination with chemotherapy or immunotherapy.


The influence of childhood sexual abuse on adolescent outcomes: the roles of gender, poverty, and revictimization.
Research on child sexual abuse has focused on adult revictimization and outcomes. This article examines the rate of child maltreatment revictimization among male and female children reported to child protective services for child sexual abuse and whether revictimization impacts outcomes. Using longitudinal administrative data, Cox regressions were used to examine relationships between initial report of child sexual abuse, maltreatment revictimization, and adolescent outcomes among children from poor and nonpoor families. Despite no significant differences in child sexual abuse rates between poor and nonpoor families, poor child sexual abuse victims were significantly more likely to have re-reports for maltreatment. Children with multiple reports were more likely to have negative outcomes. Interventions for child sexual abuse survivors should focus on preventing maltreatment recurrence generally and not ignore needs of male victims.


Adaptive neural mechanism for listing's law revealed in patients with fourth nerve palsy.
During fixation and saccades, human eye movements obey Listing's law, which specifies the eye's torsional angle as a function of its horizontal and vertical position. Torsion of the eye is in part controlled by the fourth nerve. This study investigates whether the brain adapts to defective torsional control after fourth nerve palsy. Thirteen patients with fourth nerve palsy (11 chronic, 2 acute), and 10 normal subjects were studied with scleral search coils. With the head immobile, subjects made saccades to a target that moved between straight ahead and eight eccentric positions. At each target position, fixation was maintained for 3 seconds before the next saccade. From the eye position data, we computed the plane of best fit, referred to as Listing's plane. Violations of Listing's law were quantified by computing the "thickness" of this plane, defined as the SD of the distances to the plane from the data points. Both the paretic and nonparetic eyes in patients with chronic fourth nerve palsy obeyed Listing's law during fixation and saccades. However, Listing's planes in both eyes had abnormal orientations, being rotated temporally, meaning the eye excyclotorted during downgaze and incyclotorted during upgaze. In contrast, the paretic eye of patients with acute fourth nerve palsy violated Listing's law during saccades. During downward saccades, transient torsional deviations moved the paretic eye out of Listing's plane. Torsional drifts returned the paretic eye to Listing's plane during subsequent fixation. During saccades, acute fourth nerve palsy violates Listing's law, whereas chronic palsy obeys it, indicating that neural adaptation can restore Listing's law by adjusting the innervations to the remaining extraocular muscles, even when one eye muscle remains paretic. The transient torsional deviations during downward saccades in acute palsy are attributed to pulse-step mismatch, as a result of lesions in the trochlear nerve that lead to an imbalance of phasic and tonic signals reaching the muscles.


Intraocular Pressure-Related Events After Anti-Vascular Endothelial Growth Factor Therapy for Macular Edema Due to Central Retinal Vein Occlusion or Hemiretinal Vein Occlusion: SCORE2 Report 16 on a Secondary Analysis of a Randomized Clinical Trial.
Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are used to treat a variety of posterior segment conditions, including some associated with glaucoma, such as macular edema due to central retinal vein occlusion (CRVO). Therefore, information regarding intraocular pressure (IOP)-related events associated with anti-VEGF therapies is important to help balance the risks and benefits over the course of therapy. To investigate IOP-related events among participants in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2). Secondary analysis of a randomized clinical trial that included 312 participants with macular edema secondary to CRVO or hemiretinal vein occlusion (HRVO) who were not taking IOP-lowering medications at baseline. First randomization occurred on September 14, 2014, and contained data through data freeze on April 1, 2020. Analysis took place from April 2020 through December 2020. Study participants were initially randomized to 6 monthly intravitreal injections of aflibercept or bevacizumab. At month 6, protocol-defined good responders were rerandomized to continued monthly or treat-and-extend dosing of their originally assigned study drug, and protocol-defined poor or marginal responders were switched to alternative treatment. After month 12, participants were treated as per investigator discretion. Three different outcomes: (1) IOP elevation more than 10 mm Hg from baseline, (2) IOP to a level higher than 35 mm Hg, and (3) IOP-lowering incisional or laser surgery. Of the 312 participants meeting inclusion criteria (138 [44.2%] were female; mean [SD] age, 67.8 [12.1] years), 25 (8.0%) had IOP elevation more than 10 mm Hg over baseline through month 60, and 5 (1.6%) had IOP higher than 35 mm Hg. The 60-month Kaplan-Meier cumulative incidence of IOP elevation more than 10 mm Hg over baseline was 0.13 (95% CI, 0.08-0.19), and the 60-month Kaplan-Meier cumulative incidence of IOP higher than 35 mm Hg was 0.02 (95% CI, 0.01-0.06), and did not differ among participants initially randomly assigned to receive aflibercept or bevacizumab. Three participants (1.0%) underwent IOP-lowering incisional surgery, and 3 participants (1.0%) underwent IOP-lowering glaucoma laser surgery. Intravitreal anti-VEGF injections are used to treat some conditions associated with glaucoma, such as macular edema due to CRVO, and the rates of IOP-related events in this trial support monitoring IOP in eyes treated with anti-VEGF therapy for macular edema associated with CRVO or HRVO for up to 60 months. ClinicalTrials.gov Identifier: NCT01969708.


Pervasive and situational hyperactivity--confounding effect of informant: a research note.
Several studies of children with problems of hyperactivity, impulsivity, and inattention (HIA) have suggested that when such behaviour occurs in more than one setting, associated conduct problems, emotional symptoms, and functional impairment are more serious than when HIA problems are seen in one situation only. Analyses of parent and teacher reports on a community sample of 480 children aged 7-11 are presented to show that in some cases this conclusion may have resulted from a confound between informant and information. When children with situational HIA were divided into 'home situational' and 'school situational' subgroups, their scores on other measures of psychopathology and impairment varied, depending on whether the informant was the parent or the teacher. When the source of information was independent of parents' or teachers' judgments, no differences were found between situationally and pervasively HIA children. Implications for future studies of situational and prevasive HIA are discussed.


A novel "tunnel-like" cyclopalladated arylimine catalyst immobilized on graphene oxide nano-sheet.
A novel "tunnel-like" cyclopalladated arylimine was prepared and immobilized on graphene oxide nano-sheet to form a hybrid catalytic material (denoted as F-GO-Pd) by self-assembly. The F-GO-Pd catalyst was characterized by XRD, FTIR, Raman, XPS, SEM, and TEM. This novel hybrid catalytic material was proven to be an efficient catalyst for the Suzuki-Miyaura coupling reaction of aryl halides (I, Br, Cl) with arylboronic acids in aqueous media under mild conditions with a very low amount of catalyst (0.01 mol%) and a high turnover frequency (TOF) (>20 000 h-1). In particular, high yields also could be obtained at room temperature with prolonged time. F-GO-Pd also showed good stability and recyclability seven times with a superior catalytic activity. The heterogeneous catalytic mechanism was investigated with kinetic studies, hot filtration tests, catalyst poisoning tests, and in situ FTIR spectroscopy with a ReactIR and the deactivation mechanism of the catalysts was proposed through analysis of its chemical stability by TEM, SEM, Raman, and XRD, indicating that a heterogeneous catalytic process occurred on the surface and the changes of the catalytic activity during the recycling were related to the micro-environment of the catalyst surface.


Reactivity of electrophilic chlorine atoms due to σ-holes: a mechanistic assessment of the chemical reduction of a trichloromethyl group by sulfur nucleophiles.
σ-Holes are shown to promote the electrophilic behavior of chlorine atoms in a trichloromethyl group when bound to an electron-withdrawing moiety. A halogen bond-type non-covalent interaction between a chlorine atom and a negatively charged sulfur atom takes place, causing the abstraction of such a chlorine atom while leaving a carbanion, subsequently driving the chemical reduction of the trichloromethyl group to a sulfide in a stepwise process. The mechanism for the model reaction of trichloromethyl pyrimidine 1 with thiophenolate and thiophenol to yield phenylsulfide 4 was followed through 1H-NMR and studied using DFT transition state calculations, and the energy profile for this transformation is fully discussed. MP2 calculations of the electrostatic potential were performed for a series of trichloromethyl compounds in order to assess the presence of σ-holes and quantify them by means of the maximum surface electrostatic potential. Such calculations showed that the chlorine atoms behave as electrophilic leaving groups toward a nucleophilic attack, opening a new possibility in the synthetic chemistry of the trichloromethyl group.


The 26S proteasome: assembly and function of a destructive machine.
The heart of the ubiquitin-mediated degradation pathway, the 26S proteasome, endoproteolytically cleaves most intracellular proteins, thereby maintaining biological homeostasis and regulating many crucial processes in the cell. This hydrolyzing machine comprises more than 30 different subunits, which perform different functions including the recognition, unfolding, translocating and cleavage of protein substrates. Thus, careful assemblage and regulation of the 26S proteasome is essential to ensure correct positioning and function of each subunit, thereby preserving the delicate cellular balance between protein synthesis and degradation. Here, we review the most current research on the 26S proteasome assembly pathway, and describe the mechanism used by the cell to manage the complex structure and functions of the proteasome.


Blueberry prevents bone loss in ovariectomized rat model of postmenopausal osteoporosis.
The objective of the present study was to explore the bone protective role of blueberry in an ovariectomized rat model. Thirty 6-month-old female Sprague-Dawley rats were either sham-operated (Sham) or ovariectomized (Ovx) and divided into three groups: Sham, Ovx (control), Ovx+blueberry (5% blueberry w/w). After 100 days of treatment, rats were euthanized, and blood and tissues were collected. Bone mineral density (BMD) and content of whole body, right tibia, right femur and fourth lumbar vertebra were assessed via dual-energy X-ray absorptiometry. As expected, Ovx resulted in loss of whole-body, tibial, femoral, and 4th lumbar BMD by approximately 6%. Blueberry treatment was able to prevent the loss of whole-body BMD and had an intermediary effect on prevention of tibial and femoral BMD when compared to either Sham or Ovx controls. The bone-protective effects of blueberry may be due to suppression of Ovx-induced increase in bone turnover, as evident by lowered femoral mRNA levels of alkaline phosphatase, collagen type I and tartrate-resistant acid phosphatase to the Sham levels. Similarly, serum osteocalcein levels were also lower in the blueberry group when compared to the Ovx control group, albeit not significantly. In summary, our findings indicate that blueberry can prevent bone loss as seen by the increases in BMD and favorable changes in biomarkers of bone metabolism.


Comparison of children's free-living physical activity derived from wrist and hip raw accelerations during the segmented week.
This study assessed children's physical activity (PA) levels derived from wrist-worn GENEActiv and hip-worn ActiGraph GT3X+ accelerometers and examined the comparability of PA levels between the two devices throughout the segmented week. One hundred and twenty-nine 9-10-year-old children (79 girls) wore a GENEActiv (GAwrist) and ActiGraph GT3X+ (AGhip) accelerometer on the left wrist and right hip, respectively, for 7 days. Mean minutes of light PA (LPA) and moderate-to-vigorous PA (MVPA) per weekday (whole-day, before-school, school and after-school) and weekend day (whole-day, morning and afternoon-evening) segments were calculated, and expressed as percentage of segment time. Repeated measures analysis of variance examined differences in LPA and MVPA between GAwrist and AGhip for each time segment. Bland-Altman plots assessed between-device agreement for LPA and MVPA for whole weekday and whole weekend day segments. Correlations between GAwrist and AGhip were weak for LPA (r = 0.18-0.28), but strong for MVPA (r = 0.80-0.86). LPA and MVPA levels during all weekday and weekend day segments were significantly higher for GAwrist than AGhip (p < 0.001). The largest inter-device percent difference of 26% was observed in LPA during the school day segment. Our data suggest that correction factors are needed to improve raw PA level comparability between GAwrist and AGhip.


Numerical Computation of Anisotropic Thermal Conductivity in Injection Molded Polymer Heat Sink Filled with Graphite Flakes.
The use of polymer composites as a replacement for commonly applied materials in industry has been on the rise in recent decades. Along with the development of computer software, the desire to predict the behavior of new products is thus increasing. Traditional additives in the form of fibers cause anisotropic properties of the whole product. The subject of the presented study is a polymer heat sink prototype with a thermally conductive filler in the form of graphite flakes, which differs from the commonly used fibers. Three simplified approaches are introduced to model the thermal conductivity anisotropy of an entire heat sink. Each model is subjected to an inverse heat conduction problem, the output of which are thermal conductivity values. These are optimized to minimize the difference between simulated and experimental temperatures at selected locations in the model. The approaches are compared with each other with respect to their error against the experimentally obtained results. The goal is to find a sufficiently simplified approach that can be applied to products of various geometries. This would remove the costly and time-consuming need for mold production and experimental testing.


Human immunodeficiency virus and human T-lymphotropic virus type I infection among homosexual men in Kingston, Jamaica.
From August 1985 through January 1986, 125 homosexual or bisexual men from the Kingston area were enrolled in a study to evaluate risk factors for infection with human immunodeficiency virus (HIV) and human T-lymphotropic virus type I (HTLV-I). Twelve men (10%) were seropositive for HIV and 6 (5%) for HTLV-I; 1 man had possible coinfection with HIV and HTLV-I. One third of the men reported having had homosexual encounters with foreign visitors or while travelling outside Jamaica, and sexual contact with men in the U.S. was weakly associated with HIV infection (p = 0.11). The median number of partners was 12 per year (range 0-135) and a greater number of homosexual partners per year was associated with HIV seropositivity (p = 0.01). HIV seropositives also were more likely to have a history of lymphadenopathy (p = 0.07). For HTLV-I, there were no obvious risk factors identified, and age-adjusted seroprevalence was not significantly higher than that of heterosexual men. Compared to studies of homosexual men in the U.S. prior to the advent of extensive AIDS education, the Jamaican homosexual population was more sexually conservative. Despite this circumstance, HIV appears to have entered this population via sexual contact with foreign men and spread efficiently among men with a greater number of sexual partners. The frequency of bisexuality (65/125 men) and the 11% HIV prevalence in bisexual men suggest that secondary infection of female sexual partners may occur.


Effect of Moringa oleifera lectin on development and mortality of Aedes aegypti larvae.
Aedes aegypti larvae have developed tolerance to many insecticides used for mosquito control. Moringa oleifera seeds contain a water-soluble lectin (WSMoL) and this paper reports the effect of M. oleifera seed extracts (MoE(1-15)) and WSMoL on development and survival of A. aegypti larvae. WSMoL peptide from in-gel trypsin digestion is also described. MoE(1-15) showed hemagglutinating activity and WSMoL had similarity with flocculating proteins from M. oleifera seeds. MoE(1) and MoE(3) delayed larval development which stopped in the third instar (L3) in MoE(6) and MoE(15). Significant (p<0.0001) larval mortality was only detected in MoE(15). Native WSMoL showed larvicidal activity (LC(50) 0.197 mg mL(-1)) and heated lectin, without hemagglutinating activity, did not kill fourth instar (L4) larvae. Optical microscopy showed that live L4 from MoE(1) presented underlying epithelium, increased gut lumen and hypertrophic segments; dead L4 from WSMoL were absent of underlying epithelium, had increased gut lumen and hypertrophic segments. The presence of hemagglutinating activity in the extracts suggests that soluble lectin promotes the delay of larval development and mortality; furthermore, the absence of larvicidal activity in heat-denatured WSMoL strengthens the involvement of lectin in this activity mechanism.


Long bone fracture characteristics in children with medical conditions linked to bone health.
Knowledge of fracture characteristics among children with medical conditions affecting bone could help to distinguish medical causes from child abuse. Characterize long bone fracture morphology among children diagnosed with medical conditions linked to bone health. Patients <18 years at a single pediatric hospital diagnosed with a medical condition linked to bone health and ≥1 long bone fracture were studied. This retrospective medical record review categorized underlying medical diagnoses as: metabolic bone disease, genetic disorder of connective tissue, neurologic disorder and other chronic disease. A pediatric radiologist reviewed plain films to determine fracture type and location. Descriptive statistics, as well as logistic regression were used to compare fracture types by clinical characteristics. Ninety-four patients were included and their diagnoses were genetic connective disorder (19; 20.2 %), metabolic bone disease (16; 17.0 %), neurologic disorder (27; 28.7 %), and other (32; 34.0 %). A total of 216 long bone fractures were sustained; 52.1 % of children had >1 long bone fracture. Of the 216 fractures, 55 (25.5 %) were in children < 1 year, 118 (54.6 %) were associated with known trauma, and 122 (56.5 %) were in non-ambulatory patients. Lower extremity fractures occurred with greatest frequency and most fractures occurred at the mid-diaphysis. Transverse was the most common fracture type in all diagnostic categories. Children with metabolic disorders had highest odds of transverse fracture (COR 3.55, CI 1.45-8.67; neurologic disorders as reference group). Diseases affecting bone health can influence fracture morphology. Transverse fractures were most common in bones impacted by disease.


Child care subsidies, maternal health, and child-parent interactions: evidence from three nationally representative datasets.
A complete account of the US child care subsidy system requires an understanding of its implications for both parental and child well-being. Although the effects of child care subsidies on maternal employment and child development have been recently studied, many other dimensions of family well-being have received little attention. This paper attempts to fill this gap by examining the impact of child care subsidy receipt on maternal health and the quality of child-parent interactions. The empirical analyses use data from three nationally representative surveys, providing access to numerous measures of family well-being. In addition, we attempt to handle the possibility of non-random selection into subsidy receipt by using several identification strategies both within and across the surveys. Our results consistently indicate that child care subsidies are associated with worse maternal health and poorer interactions between parents and their children. In particular, subsidized mothers report lower levels of overall health and are more likely to show symptoms consistent with anxiety, depression, and parenting stress. Such mothers also reveal more psychological and physical aggression toward their children and are more likely to utilize spanking as a disciplinary tool. Together, these findings suggest that work-based public policies aimed at economically disadvantaged mothers may ultimately undermine family well-being.


Sub-pixel resolving optofluidic microscope for on-chip cell imaging.
We report the implementation of a fully on-chip, lensless, sub-pixel resolving optofluidic microscope (SROFM). The device utilizes microfluidic flow to deliver specimens directly across a complementary metal oxide semiconductor (CMOS) sensor to generate a sequence of low-resolution (LR) projection images, where resolution is limited by the sensor's pixel size. This image sequence is then processed with a pixel super-resolution algorithm to reconstruct a single high resolution (HR) image, where features beyond the Nyquist rate of the LR images are resolved. We demonstrate the device's capabilities by imaging microspheres, protist Euglena gracilis, and Entamoeba invadens cysts with sub-cellular resolution and establish that our prototype has a resolution limit of 0.75 microns. Furthermore, we also apply the same pixel super-resolution algorithm to reconstruct HR videos in which the dynamic interaction between the fluid and the sample, including the in-plane and out-of-plane rotation of the sample within the flow, can be monitored in high resolution. We believe that the powerful combination of both the pixel super-resolution and optofluidic microscopy techniques within our SROFM is a significant step forwards toward a simple, cost-effective, high throughput and highly compact imaging solution for biomedical and bioscience needs.


The non-equilibrium allele frequency spectrum in a Poisson random field framework.
In population genetic studies, the allele frequency spectrum (AFS) efficiently summarizes genome-wide polymorphism data and shapes a variety of allele frequency-based summary statistics. While existing theory typically features equilibrium conditions, emerging methodology requires an analytical understanding of the build-up of the allele frequencies over time. In this work, we use the framework of Poisson random fields to derive new representations of the non-equilibrium AFS for the case of a Wright-Fisher population model with selection. In our approach, the AFS is a scaling-limit of the expectation of a Poisson stochastic integral and the representation of the non-equilibrium AFS arises in terms of a fixation time probability distribution. The known duality between the Wright-Fisher diffusion process and a birth and death process generalizing Kingman's coalescent yields an additional representation. The results carry over to the setting of a random sample drawn from the population and provide the non-equilibrium behavior of sample statistics. Our findings are consistent with and extend a previous approach where the non-equilibrium AFS solves a partial differential forward equation with a non-traditional boundary condition. Moreover, we provide a bridge to previous coalescent-based work, and hence tie several frameworks together. Since frequency-based summary statistics are widely used in population genetics, for example, to identify candidate loci of adaptive evolution, to infer the demographic history of a population, or to improve our understanding of the underlying mechanics of speciation events, the presented results are potentially useful for a broad range of topics.


False expectations? Expectations vs. probabilities for dying.
It is widely recognized that the code of the physician has undergone dramatic changes in the last century--changes which have serious implications for the patient-physician relationship. This is an ethnographic study examining how certain changes in the role and abilities of biomedical physicians have affected patient attitudes and expectations about end-of-life care. In-home interviews were conducted with eighteen persons age fifty-five and older, including a sample of Hemlock Society members. Results indicate a broad spectrum of end-of-life concerns including capacity, autonomy, pain, and burden to loved ones. Most participants reported a reluctance to begin a discussion of death or future deteriorating capacity with their physicians. Instead, when conversations about death were reported, they had been largely limited to the scenarios of catastrophic illness (e.g., hospitalization, ventilator, etc.) and the Living Will. While this discussion does not overlook the utility of the Living Will, it proposes the reliance on this document for preparing patients for end-of-life care is inadequate.


Relationship between photosynthetic phosphorus-use efficiency and foliar phosphorus fractions in tropical tree species.
How plants develop adaptive strategies to efficiently use nutrients on infertile soils is an important topic in plant ecology. It has been suggested that, with decreasing phosphorus (P) availability, plants increase photosynthetic P-use efficiency (PPUE) (i.e., the ratio of instantaneous photosynthetic carbon assimilation rate per unit foliar P). However, the mechanism to increase PPUE remains unclear. In this study, we tested whether high PPUE is explained by an optimized allocation of P in cells among P-containing biochemical compounds (i.e., foliar P fractions). We investigated the relationships among mass-based photosynthetic carbon assimilation rate (A mass), PPUE, total foliar P concentration, and foliar P fractions in 10 tree species in two tropical montane rain forests with differing soil P availability (five species on sedimentary soils and five species on P-poorer ultrabasic serpentine soils) on Mount Kinabalu, Borneo. We chemically fractionated foliar P into the following four fractions: metabolic P, lipid P, nucleic acid P, and residual P. A mass was positively correlated with the concentrations of total foliar P and of metabolic P across 10 tree species. Mean A mass and mean concentrations of total foliar P and of each foliar P fraction were lower on the P-poorer ultrabasic serpentine soils than on the sedimentary soils. There was a negative relationship between the proportion of metabolic P per total P and the proportion of lipid P per total P. PPUE was positively correlated with the ratio of metabolic P to lipid P. High PPUE is explained by the net effect of a relatively greater investment of P into P-containing metabolites and a relatively lesser investment into phospholipids in addition to generally reduced concentrations of all P fractions. We conclude that plants optimize the allocation of P among foliar P fractions for maintaining their productivity and growth and for reducing demand for P as their adaptation to P-poor soils.


The repeatability of cognitive performance: a meta-analysis.
Behavioural and cognitive processes play important roles in mediating an individual's interactions with its environment. Yet, while there is a vast literature on repeatable individual differences in behaviour, relatively little is known about the repeatability of cognitive performance. To further our understanding of the evolution of cognition, we gathered 44 studies on individual performance of 25 species across six animal classes and used meta-analysis to assess whether cognitive performance is repeatable. We compared repeatability (R) in performance (1) on the same task presented at different times (temporal repeatability), and (2) on different tasks that measured the same putative cognitive ability (contextual repeatability). We also addressed whether R estimates were influenced by seven extrinsic factors (moderators): type of cognitive performance measurement, type of cognitive task, delay between tests, origin of the subjects, experimental context, taxonomic class and publication status. We found support for both temporal and contextual repeatability of cognitive performance, with mean R estimates ranging between 0.15 and 0.28. Repeatability estimates were mostly influenced by the type of cognitive performance measures and publication status. Our findings highlight the widespread occurrence of consistent inter-individual variation in cognition across a range of taxa which, like behaviour, may be associated with fitness outcomes.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.


Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture.
Changes in bone density and bone markers suggest that pregnancy is associated with deterioration of bone mass in the mother. The metabolism of calcium resets to allow for the needs imposed by the building of the fetal skeleton. The fetus contributes to the process through the output of regulators from the placenta. Understanding of the whole process is limited, but some changes are unambiguous. There is an increase in the circulating levels of vitamin D, but its functional impact is unclear. Fetal parathyroid hormone (PTH) and PTH-related peptide (PTHrp) play an indirect role through support of a calcium gradient that creates hypercalcemia in the fetus. Placental GH, which increases up to the end of pregnancy, may exert some anabolic effects, either directly or through the regulation of the IGF1 production. Other key regulators of bone metabolism, such as estrogens or prolactin, are elevated during pregnancy, but their role is uncertain. An increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL) to osteoprotegerin (OPG) acts as an additional pro-resorbing factor in bone. The increase in bone resorption may lead to osteoporosis and fragility fracture, which have been diagnosed, although rarely. However, the condition is transitory as long-term studies do not link the number of pregnancies with osteoporosis. Prevention is limited by the lack of identifiable risk factors. When fractures are diagnosed, rest, analgesics, or, when indicated, orthopedic intervention have demonstrated efficacy. Systemic treatment with anti-osteoporotic drugs is effective, but the potential harm to the fetus imposes caution in their use.


Deformation of the early glaucomatous monkey optic nerve head connective tissue after acute IOP elevation in 3-D histomorphometric reconstructions.
To retest the hypothesis that monkey ONH connective tissues become hypercompliant in early experimental glaucoma (EEG), by using 3-D histomorphometric reconstructions, and to expand the characterization of EEG connective tissue deformation to nine EEG eyes. Trephinated ONH and peripapillary sclera from both eyes of nine monkeys that were perfusion fixed, with one normal eye at IOP 10 mm Hg and the other EEG eye at 10 (n=3), 30 (n=3), or 45 (n=3) mm Hg were serial sectioned, 3-D reconstructed, 3-D delineated, and quantified with 3-D reconstruction techniques developed in prior studies by the authors. Overall, and for each monkey, intereye differences (EEG eye minus normal eye) for each parameter were calculated and compared by ANOVA. Hypercompliance in the EEG 30 and 45 eyes was assessed by ANOVA, and deformations in all nine EEG eyes were separately compared by region without regard for fixation IOP. Hypercompliant deformation was not significant in the overall ANOVA, but was suggested in a subset of EEG 30/45 eyes. EEG eye deformations included posterior laminar deformation, neural canal expansion, lamina cribrosa thickening, and posterior (outward) bowing of the peripapillary sclera. Maximum posterior laminar deformation and scleral canal expansion co-localized to either the inferior nasal or superior temporal quadrants in the eyes with the least deformation and involved both quadrants in the eyes achieving the greatest deformation. The data suggest that, in monkey EEG, ONH connective tissue hypercompliance may occur only in a subset of eyes and that early ONH connective tissue deformation is maximized in the superior temporal and/or inferior nasal quadrants.


Properties of membrane-incorporated WALP peptides that are anchored on only one end.
Peptides of the "WALP" family, acetyl-GWW(LA)(n)LWWA-[ethanol]amide, have proven to be opportune models for investigating lipid-peptide interactions. Because the average orientations and motional behavior of the N- and C-terminal Trp (W) residues differ, it is of interest to investigate how the positions of the tryptophans influence the properties of the membrane-incorporated peptides. To address this question, we synthesized acetyl-GGWW(LA)(n)-ethanolamide and acetyl-(AL)(n)WWG-ethanolamide, in which n = 4 or 8, which we designate as "N-anchored" and "C-anchored" peptides, respectively. Selected (2)H or (15)N labels were incorporated for solid-state nuclear magnetic resonance (NMR) spectroscopy. These peptides can be considered "half"-anchored WALP peptides, having only one pair of interfacial Trp residues near either the amino or the carboxyl terminus. The hydrophobic lengths of the (n = 8) peptides are similar to that of WALP23. These longer half-anchored WALP peptides incorporate into lipid bilayers as α-helices, as reflected in their circular dichroism spectra. Solid-state NMR experiments indicate that the longer peptide helices assume defined transmembrane orientations with small non-zero average tilt angles and moderate to high dynamic averaging in bilayer membranes of 1,2-dioleoylphosphatidylcholine, 1,2-dimyristoylphosphatidylcholine, and 1,2-dilauroylphosphatidylcholine. The intrinsically small apparent tilt angles suggest that interactions of aromatic residues with lipid headgroups may play an important role in determining the magnitude of the peptide tilt in the bilayer membrane. The shorter (n = 4) peptides, in stark contrast to the longer peptides, display NMR spectra that are characteristic of greatly reduced motional averaging, probably because of peptide aggregation in the bilayer environment, and CD spectra that are characteristic of β-structure.


Prevalence and causes of blindness and low vision in southern Sudan.
Blindness and low vision are thought to be common in southern Sudan. However, the magnitude and geographical distribution are largely unknown. We aimed to estimate the prevalence of blindness and low vision, identify the main causes of blindness and low vision, and estimate targets for blindness prevention programs in Mankien payam (district), southern Sudan. A cross-sectional survey of the population aged 5 y and above was conducted in May 2005 using a two-stage cluster random sampling with probability proportional to size. The Snellen E chart was used to test visual acuity, and participants also underwent basic eye examination. Vision status was defined using World Health Organization categories of visual impairment based on presenting visual acuity (VA). A total of 2,954 persons were enumerated and 2,499 (84.6%) examined. Prevalence of blindness (presenting VA of less than 3/60 in the better eye) was 4.1% (95% confidence interval [CI], 3.4-4.8); prevalence of low vision (presenting VA of at least 3/60 but less than 6/18 [corrected] in the better eye) was 7.7% (95% CI, 6.7-8.7); whereas prevalence of monocular visual impairment (presenting VA of at least 6/18 [corrected] in better eye and VA of less than 6/18 [corrected] in other eye) was 4.4% (95% CI, 3.6-5.3). The main causes of blindness were considered to be cataract (41.2%) and trachoma (35.3%), whereas low vision was mainly caused by trachoma (58.1%) and cataract (29.3%). It is estimated that in Mankien payam 1,154 persons aged 5 y and above (lower and upper bounds = 782-1,799) are blind, and 2,291 persons (lower and upper bounds = 1,820-2,898) have low vision. Blindness is a serious public health problem in Mankien, and there is urgent need to implement comprehensive blindness prevention programs. Further surveys are essential to confirm these tragic findings and estimate prevalence of blindness and low vision in the entire region of southern Sudan in order to facilitate planning of VISION 2020 objectives.


Hepatic drug metabolism in rats: impairment in a dirty environment.
Reduction of aniline hydroxylase activity, ethylmorphine N-dementhylase activity, and cytochrome P-450 content occurred in hepatic microsomes of rats kept under dirty conditions, defined as accumulation for 1 week of urine and feces in pans under the wire mesh cages. In comparison with rats that had urine and feces removed twice daily from such pans, rats kept over Kimpak bedding or over Litter Green, changed twice daily, also showed reduced drug-metabolizing activity in hepatic microsomes, but to a lesser degree than the dirty rats. Placement of a filter top on cages for 1 week also decreased drug-metabolizing activity. These experiments suggest that the relative cleanliness of an animal's environment can influence hepatic microsomal drug metabolism.


Post-acute traumatic brain injury rehabilitation: effects on outcome measures and life care costs.
Rehabilitation is the predominant post-acute treatment for patients with traumatic brain injury (TBI). We retrospectively evaluated the effectiveness of post-acute TBI rehabilitation by comparing outcome measures and life care cost with that of patients with cerebrovascular accident (CVA) who underwent a multidisciplinary rehabilitation program within the same facility. To better assess the effects of rehabilitation, we only included patients with no benefit limitations from the insurance carrier. Functional effectiveness was determined by comparing outcome scales, which included the Disability Rating Scale, Mayo Portland Inventory, Occupational Status Scale, Living Status Scale, and the Centre for Neuro Skills Scale. Cost-effectiveness was determined by having certified life care planners create separate cost projections from the admission and discharge patient files. This allowed us to compare cost projections with and without rehabilitation for each patient. Significant decreases in the cost projections, i.e., rehabilitation savings (RS), were found after rehabilitation for TBI. These RS were equivalent to those of patients with CVA. Likewise, equivalent improvements were found on all of the outcome scales for both brain injury groups. We also evaluated if the latency from TBI to admission in the rehabilitation program had an influence on outcome. Cost and functional effectiveness was more marked when rehabilitation was initiated within the first year after TBI. The effects of age of TBI were also evaluated. Although RS were most marked in younger patients, improvements in outcome measures were observed in all age groups after post-acute rehabilitation.


Identification of Druggable Genes for Asthma by Integrated Genomic Network Analysis.
Asthma is a common and heterogeneous disease characterized by chronic airway inflammation. Currently, the two main types of asthma medicines are inhaled corticosteroids and long-acting β2-adrenoceptor agonists (LABAs). In addition, biological drugs provide another therapeutic option, especially for patients with severe asthma. However, these drugs were less effective in preventing severe asthma exacerbation, and other drug options are still limited. Herein, we extracted asthma-associated single nucleotide polymorphisms (SNPs) from the genome-wide association studies (GWAS) and phenome-wide association studies (PheWAS) catalog and prioritized candidate genes through five functional annotations. Genes enriched in more than two categories were defined as "biological asthma risk genes." Then, DrugBank was used to match target genes with FDA-approved medications and identify candidate drugs for asthma. We discovered 139 biological asthma risk genes and identified 64 drugs targeting 22 of these genes. Seven of them were approved for asthma, including reslizumab, mepolizumab, theophylline, dyphylline, aminophylline, oxtriphylline, and enprofylline. We also found 17 drugs with clinical or preclinical evidence in treating asthma. In addition, eleven of the 40 candidate drugs were further identified as promising asthma therapy. Noteworthy, IL6R is considered a target for asthma drug repurposing based on its high target scores. Through in silico drug repurposing approach, we identified sarilumab and satralizumab as the most promising drug for asthma treatment.


Actin polymerisation during morphogenesis of the acrosome as spermatozoa undergo epididymal maturation in the tammar wallaby (Macropus eugenii).
In the tammar wallaby (Macropus eugenii), post-testicular acrosomal shaping involves a complex infolding and fusion of the anterior and lateral projections of the scoop-shaped acrosome into a compact button-like structure occupying the depression on the anterior end of the sperm nucleus. The present study has generated cytochemical and histological evidence to demonstrate that the occurrence of actin filaments (F-actin, labelled by Phalloidin-FITC) in the acrosome of tammar wallaby spermatozoa is temporally and spatially associated with the process of acrosomal shaping in the epididymis, through a pool of monomeric actin (G-actin, labelled by Rh-DNase I) present in the acrosome throughout all stages of epididymal maturation. F-actin was not detected in the acrosome of testicular spermatozoa, but was found in the infolding and condensing acrosome of caput and corpus epididymal spermatozoa. When the spermatozoa completed acrosome shaping in the cauda epididymidis, F-actin disappeared from the acrosomal area. The strong correlation between the occurrence of F-actin and the events of acrosomal shaping suggested that the post-testicular shaping of the acrosome might depend on a precise succession of assembly and disassembly of F-actin within the acrosome as the spermatozoa transit the epididymis. Thus, actin filaments might play a significant role in the acrosomal transformation, as they are commonly involved in morphological changes in somatic cells.


Depletion of a single nucleoporin, Nup107, prevents the assembly of a subset of nucleoporins into the nuclear pore complex.
The nuclear pore complex (NPC) is a protein assembly that contains several distinct subcomplexes. The mammalian nucleoporin (Nup)-107 is part of a hetero-oligomeric complex, that also contains Nup160, Nup133, Nup96, and the mammalian homolog of yeast Sec13p. We used transfection of HeLa cells with small interfering RNAs to specifically deplete mRNA for Nup107. In a domino effect, Nup107 depletion caused codepletion of a subset of other Nups on their protein but not on their mRNA level. Among the affected Nups was a member of the Nup107 subcomplex, Nup133, whereas two other tested members of this complex, Nup96 and Sec13, were unaffected and assembled into Nup107Nup133-deficient NPCs. We also tested several phenylalanine-glycine repeat-containing Nups that serve as docking sites for karyopherins. Some of these, such as Nup358, Nup214 on the cytoplasmic, and Nup153 on the nucleoplasmic side of the NPC, failed to assemble into Nup107Nup133-depleted NPCs, whereas p62, a Nup at the center of the NPC, was unaffected. Interestingly, the filamentous, NPC-associated protein Tpr also failed to assemble into the NPCs of Nup107-depleted cells. These data indicate that Nup107 functions as a keystone Nup that is required for the assembly of a subset of Nups into the NPC. Despite the depletion of Nup107 and the accompanying effects on other Nups, there was no significant effect on the growth rate of these cells and only a partial inhibition of mRNA export. These data indicate redundancy of Nups in the function of the mammalian NPC.


Japanese lung cancer registry study of 11,663 surgical cases in 2004: demographic and prognosis changes over decade.
The Japan Lung Cancer Society, the Japanese Association for Chest Surgery, and the Japanese Respiratory Society jointly established the Japanese Joint Committee for Lung Cancer Registration, which has regularly conducted lung cancer registries for surgical cases in 5-year periods. We analyzed data obtained in these registries to reveal the most recent surgical outcomes and trends related to lung cancer surgery in Japan. Using data from the registry in 2010 for cases of surgery performed in 2004, demographics, surgical results, and stage-specific prognoses were analyzed. In addition, trends for those parameters over 10 years were assessed. The 5-year survival rate for all cases (n = 11,663, 7369 males, mean age 66.7 years) was 69.6%. The 5-year survival rates by c-stage and p-stage were as follow: IA, 82.0% (n = 6295) and 86.8% (n = 4978); IB, 66.8% (n = 2339) and 73.9% (n = 2552); IIA, 54.5% (n = 819) and 61.6% (n = 941); IIB, 46.4% (n = 648) and 49.8% (n = 848); IIIA, 42.8% (n = 1216) and 40.9% (n = 1804); IIIB, 40.3% (n = 90) and 27.8% (n = 106); and IV, 31.4% (n = 256) and 27.9% (n = 434), respectively. The percentages of female patients, cases with adenocarcinoma, stage I or II disease, and tumors sized less than 2 cm were increased, while those of operative and hospital deaths were decreased. Furthermore, the prognoses of all cases and cases in each stage improved over the decade. In Japanese cases of lung cancer surgery, demographics, surgical results, and stage-specific prognoses changed over the 10-year study period, while the 5-year survival rate for surgical cases improved to 69.6% in 2004.


Shoulder kinematics and spatial pattern of trapezius electromyographic activity in real and virtual environments.
The design of an industrial workstation tends to include ergonomic assessment steps based on a digital mock-up and a virtual reality setup. Lack of interaction and system fidelity is often reported as a main issue in such virtual reality applications. This limitation is a crucial issue as thorough ergonomic analysis is required for an investigation of the biomechanics. In the current study, we investigated the biomechanical responses of the shoulder joint in a simulated assembly task for comparison with the biomechanical responses in virtual environments. Sixteen male healthy novice subjects performed the task on three different platforms: real (RE), virtual (VE), and virtual environment with force feedback (VEF) with low and high precision demands. The subjects repeated the task 12 times (i.e., 12 cycles). High density electromyography from the upper trapezius and rotation angles of the shoulder joint were recorded and split into the cycles. The angular trajectories and velocity profiles of the shoulder joint angles over a cycle were computed in 3D. The inter-subject similarity in terms of normalized mutual information on kinematics and electromyography was investigated. Compared with RE the task in VE and VEF was characterized by lower kinematic maxima. The inter-subject similarity in RE compared with intra-subject similarity across the platforms was lower in terms of movement trajectories and greater in terms of trapezius muscle activation. The precision demand resulted in lower inter- and intra-subject similarity across platforms. The proposed approach identifies biomechanical differences in the shoulder joint in both VE and VEF compared with the RE platform, but these differences are less marked in VE mostly due to technical limitations of co-localizing the force feedback system in the VEF platform.


Electrochemical Synthesis of Allylic Amines from Terminal Alkenes and Secondary Amines.
Allylic amines are valuable synthetic targets en route to diverse biologically active amine products. Current allylic C-H amination strategies remain limited with respect to the viable N-substituents. Herein, we disclose a new electrochemical process to prepare aliphatic allylic amines by coupling two abundant starting materials: secondary amines and unactivated alkenes. This oxidative transformation proceeds via electrochemical generation of an electrophilic adduct between thianthrene and the alkene substrates. Treatment of these adducts with aliphatic amine nucleophiles and base provides allylic amine products in high yield. This synthetic strategy is also amenable to functionalization of feedstock gaseous alkenes at 1 atm. In the case of 1-butene, high Z-selective crotylation is observed. This strategy, however, is not limited to the synthesis of simple building blocks; complex biologically active molecules are suitable as both alkene and amine coupling partners. Preliminary mechanistic studies implicate vinylthianthrenium salts as key reactive intermediates.


Hereditary angioedema: an update on available therapeutic options.
There is no cure for hereditary angioedema (HAE). Therapeutic approaches consist of symptomatic therapy for acute attacks, short-term prophylaxis before surgery, and long-term prophylaxis for those with frequent and severe attacks. In Germany, C1-INH concentrate and icatibant are licensed for acute therapy. C1-INH concentrate, which is obtained from human plasma, is administered intravenously to restore the deficient C1-INH activity. This therapy, which has been available for decades, is effective and well-tolerated. Batch documentation is required by German law. The synthetic decapeptide icatibant is administered subcutaneously. It competes with bradykinin, the responsible inducer of edema formation, for binding to the bradykinin B2 receptor. Icatibant is also effective and well-tolerated, even on repeated administration. An additional human C1-inhibitor, a recombinant human C1-inhibitor and the recombinant inhibitor of kallikrein ecallantide are currently under development. There are no licensed treatment options available in Germany for long- and short-term prophylaxis. Androgen derivatives are established in long-term prophylaxis. However, they are associated with many adverse effects, some of which are severe. Many drug interactions also limit their use. They are contraindicated in pregnancy, lactation, for children and in cases of prostate cancer. Antifibrinolytics have fewer adverse effects but are also less effective than androgens. They are contraindicated in thromboembolic disease and impaired vision. If androgen therapy has too negative an effect on quality of life, it may be worth reducing the dose or discontinuing therapy entirely and treating attacks with acute therapy.


Managing disruptive patients in health care: necessary solutions to a difficult problem.
We sought to describe the components and processes in a violence risk assessment and management system, including electronic record requirements in the Veterans Health Administration (VA). We present information on system-level variation among program elements and their association with perceived and measured effectiveness. We conducted a cross-sectional survey of Chiefs of Staff (COS) at 140 VA hospitals across the United States about specific disruptive behavior program elements, such as committee processes, patient referrals, and outcome patterns. We assessed COS perceived effectiveness of the processes. We compared COS perceptions with employee-reported assault-related incident rates and workers compensation lost time claim rates for assault-related injuries for 2009 and 2010. We found the violence risk assessment and management system is heavily used, often with guidance to provide police protection for providers. COS respondents were generally satisfied with design and performance of the system. Committee processes and perceptions of effectiveness were associated with reduction in assault-related incident rates. VA's system was considered effective by system owners and users may be effective at reducing assaulted-related injuries.


Cryo-EM structure of human rhodopsin bound to an inhibitory G protein.
G-protein-coupled receptors comprise the largest family of mammalian transmembrane receptors. They mediate numerous cellular pathways by coupling with downstream signalling transducers, including the hetrotrimeric G proteins Gs (stimulatory) and Gi (inhibitory) and several arrestin proteins. The structural mechanisms that define how G-protein-coupled receptors selectively couple to a specific type of G protein or arrestin remain unknown. Here, using cryo-electron microscopy, we show that the major interactions between activated rhodopsin and Gi are mediated by the C-terminal helix of the Gi α-subunit, which is wedged into the cytoplasmic cavity of the transmembrane helix bundle and directly contacts the amino terminus of helix 8 of rhodopsin. Structural comparisons of inactive, Gi-bound and arrestin-bound forms of rhodopsin with inactive and Gs-bound forms of the β2-adrenergic receptor provide a foundation to understand the unique structural signatures that are associated with the recognition of Gs, Gi and arrestin by activated G-protein-coupled receptors.


Megaloblastic anaemia due to vitamin B12 deficiency caused by small intestinal bacterial overgrowth: possible role of vitamin B12 analogues.
Megaloblastic anaemia due to bacterial overgrowth of the small intestine is due to vitamin B12 malabsorption. This report describes a patient with bacterial overgrowth of the small intestine who had megaloblastic anaemia and malabsorption of vitamin B12, but persistently normal levels of serum vitamin B12 and normal serum and red cell folate levels. However, there was evidence of vitamin B12 deficiency as shown by an abnormal deoxyuridine suppression test and by the response to treatment with physiological doses of vitamin B12. A relative increase in biologically inactive vitamin B12 analogues may be the explanation for the normal vitamin B12 level in this patient.