Predominance of anger in depressive disorders compared with anxiety disorders and somatoform disorders.
The object of this study was to make a comparison regarding various dimensions of anger between depressive disorder and anxiety disorder or somatoform disorder. The subjects included 73 patients with depressive disorders, 67 patients with anxiety disorders, 47 patients with somatoform disorders, and 215 healthy controls (diagnoses made according to DSM-IV criteria). Anger measures--the Anger Expression Scale, the hostility subscale of the Symptom Checklist-90-Revised (SCL-90-R), and the anger and aggression subscales of the Stress Response Inventory--were used to assess the anger levels. The severity of depression, anxiety, phobia, and somatization was assessed using the SCL-90-R. The depressive disorder group showed significantly higher levels of anger on the Stress Response Inventory than the anxiety disorder, somatoform disorder, and control groups (p < .05). The depressive disorder group scored significantly higher on the anger-out and anger-total subscales of the Anger Expression Scale than the somatoform disorder group (p < .05). On the SCL-90-R hostility subscale, the depressive disorder group also scored significantly higher than the anxiety disorder group (p < .05). Within the depressive disorder group, the severity of depression was significantly positively correlated with the anger-out score (r = 0.49, p < .001), whereas, in the somatoform and anxiety disorder groups, the severity of depression was significantly positively correlated with the anger-in score (somatoform disorder: r = 0.51, p < .001; anxiety disorder: r = 0.57, p < .001). These results suggest that depressive disorder patients are more likely to have anger than anxiety disorder or somatoform disorder patients and that depressive disorder may be more relevant to anger expression than somatoform disorder.


Improving Initial Sepsis Management Through a Nurse-Driven Rapid Response Team Protocol.
Rapid identification and timely management of sepsis improve survival. Therefore, a bundled approach to care is recommended. In an acute care area of the study institution, a 2016 internal evaluation of 27 patients with sepsis showed a median time to first-dose antibiotic administration of 269 minutes, with no patients receiving antibiotics within the 60-minute target time. Additionally, only one-third of patients received appropriate fluid resuscitation (30-mL/kg bolus of intravenous crystalloids). Given poor bundle compliance, a nurse-driven rapid response team protocol for suspected sepsis was implemented. The purpose of this project was to assess the protocol's impact on the timeliness of treatment for sepsis. This retrospective quality improvement evaluation involved patients aged 18 years or older for whom the suspected sepsis protocol was initiated during their acute care area admission. The evaluation focused on improvements in time to intravenous antibiotic administration and volume of fluid resuscitation compared with before protocol implementation. The protocol empowers the rapid response team to initiate sepsis management and includes pertinent laboratory tests, blood cultures, intravenous broad-spectrum antibiotic administration, and a crystalloid bolus (30 mL/kg) if indicated. A total of 32 patients were evaluated. Time to first-dose antibiotic administration was reduced by half (from 269 to 135 minutes). Eighteen patients met criteria for fluid resuscitation, with twice as many receiving appropriate fluid volumes compared with before protocol implementation. Implementation of the suspected sepsis protocol demonstrates the substantial role nurses have in optimizing patient care, especially in the timely treatment of sepsis.


Managing Lung Cancer with Comorbid Interstitial Pneumonia.
Systemic therapy for advanced non-small cell lung cancer (NSCLC) has dramatically changed in the latest 15 years. Molecular-targeted therapy has brought about an era of precision medicine, and immune checkpoint inhibitors have brought hope for a cure for advanced NSCLC. In the wake of this remarkable advancement, lung cancer with comorbid interstitial pneumonia (IP) has been completely left behind, as most clinical trials exclude patients with comorbid IP. IP, especially idiopathic pulmonary fibrosis (IPF), is often accompanied by lung cancer, and acute exacerbation can develop during various cancer therapies, including surgery, radiotherapy and pharmacotherapy. In this review, we focus on the clinical questions concerning pharmacotherapy in cases of advanced lung cancer with comorbid IP and discuss what we can do with the currently available data.


Effect of chlorella and its fractions on blood pressure, cerebral stroke lesions, and life-span in stroke-prone spontaneously hypertensive rats.
Effects of Chlorella regularis (dried cell powder)--cultured axenically under heterotrophic conditions, and provided as a dietary supplement--and its fractions on the blood pressure, cerebral stroke lesions, and life-span of stroke-prone spontaneously hypertensive rats (SHRSP/Izm) were investigated. When SHRSP were fed on diets with supplemented Chlorella to a commercial diet (Funabashi SP), elevation of blood pressure was significantly lower in the Chlorella groups than in the control group. At 21 wk of feeding, serum total cholesterol was significantly lower in the Chlorella groups than in the control group. Histopathological examination revealed cerebral vascular accidents in the brains of the control group, but those of Chlorella groups showed apparently low incidence compared to the control group. The average life-span of the Chlorella groups were significantly longer than that of the control group (p < 0.001). Chlorella powder was fractionated into three fractions, lipid-soluble, hot water-soluble, and residual fractions. The diets supplemented with lipid or residual fractions equivalent to 10% Chlorella significantly suppressed elevation of blood pressure in SHRSP, and then decreased the incidence rate of cerebral vessel lesions compared to the control group. Chemical analysis revealed that the lipid fraction contained large quantities of antioxidants, including carotenoids (especially lutein) and others, and phospholipids involved in aorta collagen and elastin metabolism; the residual fraction contained high concentrations of arginine, enhancing the function of blood vessels. The control diet contained only a little these substances. These experimental results suggest that the beneficial effect of Chlorella on SHRSP is caused by the synergistic action of several ingredients of Chlorella, which play a role in sustention of a vascular function of rats.


Cost Analyses of Genomic Sequencing: Lessons Learned from the MedSeq Project.
To summarize lessons learned while analyzing the costs of integrating whole genome sequencing into the care of cardiology and primary care patients in the MedSeq Project by conducting the first randomized controlled trial of whole genome sequencing in general and specialty medicine. Case study that describes key methodological and data challenges that were encountered or are likely to emerge in future work, describes the pros and cons of approaches considered by the study team, and summarizes the solutions that were implemented. Major methodological challenges included defining whole genome sequencing, structuring an appropriate comparator, measuring downstream costs, and examining clinical outcomes. Discussions about solutions addressed conceptual and practical issues that arose because of definitions and analyses around the cost of genomic sequencing in trial-based studies. The MedSeq Project provides an instructive example of how to conduct a cost analysis of whole genome sequencing that feasibly incorporates best practices while being sensitive to the varied applications and diversity of results it may produce. Findings provide guidance for researchers to consider when conducting or analyzing economic analyses of whole genome sequencing and other next-generation sequencing tests, particularly regarding costs.


Distinct enough? A national examination of Catholic hospital affiliation and patient perceptions of care.
Catholic hospitals play a critical role in the provision of health care in the United States; yet, empirical evidence of patient outcomes in these institutions is practically absent in the literature. The purpose of this study was to determine whether patient perceptions of care are more favorable in Catholic hospitals as compared with non-Catholic hospitals in a national sample of hospitals. This cross-sectional secondary analysis used linked data from the 2008 American Hospital Association Annual Survey, the 2008 Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, the 2008 Medicare Case Mix Index file, and the 2010 Religious Congregations and Membership Study. The study included over 3,400 hospitals nationwide, including 494 Catholic hospitals. Propensity score matching and ordinary least-squares regression models were used to examine the relationship between Catholic affiliation and various HCAHPS measures. Our findings revealed that patients treated in Catholic hospitals appear to rate their hospital experience similar to patients treated in non-Catholic hospitals. Catholic hospitals maintain a very slight advantage above their non-Catholic peers on five HCAHPS measures related to nurse communication, receipt of discharge information, quietness of the room at night, overall rating, and recommendation of the hospital; yet, these differences were minimal. If the survival of Catholic health care services is contingent upon how its provision of care is distinct, administrators of Catholic hospitals must show differences more clearly. Given the great importance of Catholic hospitals to the health of millions of patients in the United States, this study provides Catholic hospitals with a set of targeted areas on which to focus improvement efforts, especially in light of current pay-for-performance initiatives.


Genetics of stroke: a review of recent advances.
Stroke is a multifactorial disease responsible for nearly 10% of deaths each year in industrialized countries. While some monogenic forms of stroke have been described, the vast majority result from the common polygenic form of the disease. Progress in molecular genetics has allowed the identification, through genome-wide linkage analysis, of various candidate genes, including the genes encoding PDE4D and ALOX5AP. Since then, genetic research has been extensively performed from single candidate genes to whole-genome scan studies, in parallel with the development of high-throughput technologies in molecular diagnostics. Additionally, the safety and efficacy of tissue plasminogen activator, the only approved therapy for the acute phase of stroke, is modulated by genetic background associated with the occurrence of hemorrhagic transformations and with the revascularization of the cerebral arteries. In the near future, understanding the contribution of stroke genetic factors will lead to improvements in prevention and treatments for neurovascular diseases.


Changes in factor XIII level during pregnancy.
Pregnancy is associated with significant haemostatic changes, with a progressive rise in most clotting factors. There is limited data on the changes of factor XIII (FXIII) level during pregnancy. This study assesses changes in FXIII activity during normal pregnancy and establish FXIII reference range during each trimester of pregnancy and immediate postnatal period. This is a cross sectional study of 376 women with normal uneventful pregnancies. Plasma FXIII activity was measured during first (weeks 0-12, n = 116), second (weeks 13-28, n = 132), third trimester (weeks 29-42, n = 128) and postnatal (day 0-3; n = 30). Samples were also collected from non-pregnant women (n = 25) as a control group. FXIII was assayed on CS-5100 analyser using chromogenic reagent. The mean ± SD FXIII activity was 112 ± 29 IU dL(-1) during first trimester, 96 ± 26 IU dL(-1) during second trimester, 83 ± 21 IU dL(-1) during third trimester, 90 ± 19 IU dL(-1) during postnatal period, and 113 ± 26 IU dL(-1) in the control. The reference range was calculated during the first (55-169 IU dL(-1)), second (45-147 IU dL(-1)), third trimester (42-125 IU dL(-1)) and postnatal period (61-137 IU dL(-1)). There was a significant reduction in the mean FXIII activity during the second and third trimester compared to the first trimester and control group (P < 0.0001). During the immediate postnatal period, the mean FXIII activity was not statistically different compared to the third and second trimester levels but was significantly lower compared to the first trimester (P < 0.0001) level and the control group (P = 0.0002). This study establishes the reference range for FXIII activity during the three trimesters of normal pregnancy and immediate postnatal period. Women have a significantly decreased level of FXIII activity during a normal uneventful pregnancy.


In silico Screening for Identification of Novel Anti-malarial Inhibitors by Molecular Docking, Pharmacophore Modeling and Virtual Screening.
Drug resistance from affordable drugs has increased the number of deaths from malaria globally. This problem has raised the requirement to design new drugs against multidrug-resistant Plasmodium falciparum parasite. In the current project, we have focused on four important proteins of Plasmodium falciparum and used them as receptors against a dataset of four anti-malarial drugs. In silico analysis of these receptors and ligand dataset was carried out using Autodock 4.2. A pharmacophore model was also established using Ligandscout. Analysis of docking experiments showed that all ligands bind efficiently to four proteins of Plasmodium falciparum. We have used ligand-based pharmacophore modeling and developed a pharmacophore model that has three hydrophobic regions, two aromatic rings, one hydrogen acceptor and one hydrogen donor. Using this pharmacophore model, we have screened a library of 50,000 compounds. The compounds that shared features of our pharmacophore model and exhibited interactions with the four proteins of our receptors dataset are short-listed. As there is a need of more anti-malarial drugs, therefore, this research will be helpful in identifying novel anti-malarial drugs that exhibited bindings with four important proteins of Plasmodium falciparum. The hits obtained in this study can be considered as useful leads in anti-malarial drug discovery.


Forefoot pathology in relation to plantar pressure distribution in patients with rheumatoid arthritis: A cross-sectional study in the Amsterdam Foot cohort.
In patients with rheumatoid arthritis (RA), both high and low forefoot plantar pressures have been reported. Better understanding of pathology in the forefoot associated with altered pressure distribution in patients with RA could help to better formulate and specify goals for treatment with foot orthoses or therapeutic footwear. To investigate the association of plantar pressure with disease activity and deformity in the forefoot in patients with rheumatoid arthritis and forefoot symptoms. A cross sectional study, using data of 172 patients with rheumatoid arthritis and forefoot symptoms, was conducted. Peak pressure (PP) and pressure time integral (PTI) in the forefoot were measured with a pressure platform. Forefoot deformity was assessed using the Platto score. Forefoot disease activity was defined as swelling and/or pain assessed by palpation of the metatarsophalangeal joints. The forefoot was divided in a medial, central and lateral region, in which the following conditions could be present: 1) no pathology, 2) disease activity, 3) deformity or 4) disease activity and deformity. A multilevel analysis was performed using condition per forefoot region as independent variable and PP or PTI in the corresponding region as dependent variable. Statistically significant higher plantar pressures were found in forefoot regions with deformities (RR 1.2, CI 1.1-1.3, P<0.0001), compared to forefoot regions without forefoot pathology. No significant differences in plantar pressures were found when solely forefoot disease activity was present in forefoot regions. Forefoot deformities are related to higher plantar pressures measured in the corresponding forefoot regions. The absence of an association between local disease activity and plantar pressure might be explained by the low prevalence of metatarsophalangeal joint pain or swelling. Future research with sensitive imaging measures to detect disease activity is recommended to reveal the effect of forefoot disease activity on plantar pressure.


Deep brain stimulation: are astrocytes a key driver behind the scene?
Despite its widespread use, the underlying mechanism of deep brain stimulation (DBS) remains unknown. Once thought to impart a "functional inactivation", there is now increasing evidence showing that DBS actually can both inhibit neurons and activate axons, generating a wide range of effects. This implies that the mechanisms that underlie DBS work not only locally but also at the network level. Therefore, not only may DBS induce membrane or synaptic plastic changes in neurons over a wide network, but it may also trigger cellular and molecular changes in other cells, especially astrocytes, where, together, the glial-neuronal interactions may explain effects that are not clearly rationalized by simple activation/inhibition theories alone. Recent studies suggest that (1) high-frequency stimulation (HFS) activates astrocytes and leads to the release of gliotransmitters that can regulate surrounding neurons at the synapse; (2) activated astrocytes modulate synaptic activity and increase axonal activation; (3) activated astrocytes can signal further astrocytes across large networks, contributing to observed network effects induced by DBS; (4) activated astrocytes can help explain the disparate effects of activation and inhibition induced by HFS at different sites; (5) astrocytes contribute to synaptic plasticity through long-term potentiation (LTP) and depression (LTD), possibly helping to mediate the long-term effects of DBS; and (6) DBS may increase delta-opioid receptor activity in astrcoytes to confer neuroprotection. Together, the plastic changes in these glial-neuronal interactions network-wide likely underlie the range of effects seen, from the variable temporal latencies to observed effect to global activation patterns. This article reviews recent research progress in the literature on how astrocytes play a key role in DBS efficacy.


[(H2O)Zn(Imidazole)n]2+: the vital roles of coordination number and geometry in Zn-OH2 acidity and catalytic hydrolysis.
The Zn(ii)-(Imidazole(ate))n coordination motif occurs in numerous biochemical systems, including carbonic anhydrase and the matrix metalloproteinases (MMPs). Additionally, it has been used in synthetic materials, such as the zinc-based zeolitic imidazolate framework (ZIF) structures. Zinc centers in these systems typically act as Lewis acids that form complexes with small molecules, such as H2O, which is activated catalytically toward a number of important and useful hydrolysis reactions. The results reported herein from density functional theory (M05-2X) and ab initio (MP2 and CCSD(T)) calculations demonstrate that both the coordination number and the molecular geometry have a sizable impact on the binding strength, deprotonation energy, and acidity of the Zn(ii) coordinated water. Through a series of quantum mechanical calculations on [(ImH)nZn-OH2]2+ complexes (n = 1-5), both the solution-phase pKa and the gas-phase proton dissociation energy significantly increase as n increases. While this should not be too surprising, the Zn-OH2 bond dissociation energies and bond lengths don't necessarily undergo a concurrent decrease, and therefore would be of limited use as a prediction tool regarding Zn-OH2 acidity. In an effort to dissect the impacts of coordination number and molecular geometry on these thermodynamic parameters, we performed constrained geometry optimizations on the three- (n = 2) and four-coordinate (n = 3) complexes. These calculations surprisingly reveal a marked impact on the pKa and proton dissociation energy of the coordinated water, upon exclusive changes in the Zn(ii) coordination geometry, whether in the gas-phase or in aqueous solution. We discuss the relevance of these results to the catalytic peptide hydrolysis mechanism of the MMPs and possible implications for catalytic activity within or on the surfaces of ZIFs.


ADP-ribosyltransferase in Plasmodium (malaria parasites).
The nuclei of Plasmodium yoelii nigeriensis contain an enzyme, ADP-ribosyltransferase, that will incorporate the ADP-ribose moiety of NAD+ into acid-insoluble product. The time, pH and temperature optima of this incorporation are 30 min, 8.5 and 25 degrees C respectively. Maximum stimulation of the enzyme activity is obtained with 1.0 mM-dithiothreitol or 2.0 mM-2-mercaptoethanol. Ca2+ and Mg2+ ions at optimum concentrations of 5 mM and 10 mM respectively stimulated the activity of the enzyme by 21% and 91%. The enzyme activity is, however, inhibited by 24% in the presence of 10 mM-MnSO4. The substrate, NAD+, exhibits an apparent Km of 500 microM, and the activity of the enzyme is inhibited by four chemical classes of inhibitors: nicotinamides, methylxanthines, thymidine and aromatic amides. The inhibitors are effective in the following increasing order: nicotinamide less than 3-aminobenzamide less than thymidine less than 5-methylnicotinamide less than theophylline less than m-methoxybenzamide less than theobromine. The enzyme activity is also inhibited by some DNA-binding anti-malarial drugs.


Decreased muscle strength relates to self-reported stooping, crouching, or kneeling difficulty in older adults.
Bending down and kneeling are fundamental tasks of daily living, yet nearly a quarter of older adults report having difficulty performing or being unable to perform these movements. Older adults with stooping, crouching, or kneeling (SCK) difficulty have demonstrated an increased fall risk. Strength (force-generating capacity) measures may be useful for determining both SCK difficulty and fall risk. The purposes of this study were: (1) to examine muscle strength differences in older adults with and without SCK difficulty and (2) to examine the relative contributions of trunk and leg muscle strength to SCK difficulty. This was a cross-sectional observational study. Community-dwelling older adults (age [X+/-SD]=75.5+/-6.0 years) with SCK difficulty (n=27) or without SCK difficulty (n=21) were tested for leg and trunk strength and functional mobility. Isometric strength at the trunk, hip, knee, and ankle also was normalized by body weight and height. Compared with older adults with no SCK difficulty, those with SCK difficulty had significant decreases in normalized trunk extensor, knee extensor, and ankle dorsiflexor and plantar-flexor strength. In 2 separate multivariate analyses, raw ankle plantar-flexor strength (odds ratio [OR]=0.97, 95% confidence interval [CI]=0.95-0.99) and normalized knee extensor strength (OR=0.61, 95% CI=0.44-0.82) were significantly associated with SCK difficulty. Stooping, crouching, and kneeling difficulty also correlated with measures of functional balance and falls. Although muscle groups that were key to rising from SCK were examined, there are other muscle groups that may contribute to safe SCK performance. Decreased muscle strength, particularly when normalized for body size, predicts SCK difficulty. These data emphasize the importance of strength measurement at multiple levels in predicting self-reported functional impairment.


Care of the patient receiving epidural analgesia.
Epidural analgesia is a common technique used to manage acute pain after major surgery and is viewed as the 'gold standard'. When managed effectively, epidural analgesia is known to reduce the risk of adverse outcomes following major surgery. There are two main classes of medications used in epidural analgesia: opioids and local anaesthetics. Both of these drugs are beneficial in reducing or eliminating pain, but are also responsible for the common side effects associated with this method of pain relief. There are also some rare and potentially fatal side effects of epidural therapy. The nurse's role is to assess and monitor patients carefully and report and respond to any concerns.


Quantifying rapid changes in cardiovascular state with a moving ensemble average.
MEAP, the moving ensemble analysis pipeline, is a new open-source tool designed to perform multisubject preprocessing and analysis of cardiovascular data, including electrocardiogram (ECG), impedance cardiogram (ICG), and continuous blood pressure (BP). In addition to traditional ensemble averaging, MEAP implements a moving ensemble averaging method that allows for the continuous estimation of indices related to cardiovascular state, including cardiac output, preejection period, heart rate variability, and total peripheral resistance, among others. Here, we define the moving ensemble technique mathematically, highlighting its differences from fixed-window ensemble averaging. We describe MEAP's interface and features for signal processing, artifact correction, and cardiovascular-based fMRI analysis. We demonstrate the accuracy of MEAP's novel B point detection algorithm on a large collection of hand-labeled ICG waveforms. As a proof of concept, two subjects completed a series of four physical and cognitive tasks (cold pressor, Valsalva maneuver, video game, random dot kinetogram) on 3 separate days while ECG, ICG, and BP were recorded. Critically, the moving ensemble method reliably captures the rapid cyclical cardiovascular changes related to the baroreflex during the Valsalva maneuver and the classic cold pressor response. Cardiovascular measures were seen to vary considerably within repetitions of the same cognitive task for each individual, suggesting that a carefully designed paradigm could be used to capture fast-acting event-related changes in cardiovascular state.


Surface-confined 2D polymerization of a brominated copper-tetraphenylporphyrin on Au(111).
A coupling-limited approach for the Ullmann reaction-like on-surface synthesis of a two-dimensional covalent organic network starting from a halogenated metallo-porphyrin is demonstrated. Copper-octabromo-tetraphenylporphyrin molecules can diffuse and self-assemble when adsorbed on the inert Au(111) surface. Splitting-off of bromine atoms bonded at the macrocyclic core of the porphyrin starts at room temperature after the deposition and is monitored by X-ray photoelectron spectroscopy for different annealing steps. Direct coupling between the reactive carbon sites of the molecules is, however, hindered by the molecular shape. This leads initially to an ordered non-covalently interconnected supramolecular structure. Further heating to 300 °C and an additional hydrogen dissociation step is required to link the molecular macrocycles via a phenyl group and form large ordered polymeric networks. This approach leads to a close-packed covalently bonded network of overall good quality. The structures are characterized using scanning tunneling microscopy. Different kinds of lattice defects and, furthermore, the impact of polymerization on the HOMO-LUMO gap are discussed. Density functional theory calculations corroborate the interpretations and give further insight into the adsorption of the debrominated molecule on the surface and the geometry and coupling reaction of the polymeric structure.


The application of augmented reality-based navigation for accurate target acquisition of deep brain sites: advances in neurosurgical guidance.
The objective of this study is to quantify the navigational accuracy of an advanced augmented reality (AR)-based guidance system for neurological surgery, biopsy, and/or other minimally invasive neurological surgical procedures. Five burr holes were drilled through a plastic cranium, and 5 optical fiducials (AprilTags) printed with CT-visible ink were placed on the frontal, temporal, and parietal bones of a human skull model. Three 0.5-mm-diameter targets were mounted in the interior of the skull on nylon posts near the level of the tentorium cerebelli and the pituitary fossa. The skull was filled with ballistic gelatin to simulate brain tissue. A CT scan was taken and virtual needle tracts were annotated on the preoperative 3D workstation for the combination of 3 targets and 5 access holes (15 target tracts). The resulting annotated study was uploaded to and launched by VisAR software operating on the HoloLens 2 holographic visor by viewing an encrypted, printed QR code assigned to the study by the preoperative workstation. The DICOM images were converted to 3D holograms and registered to the skull by alignment of the holographic fiducials with the AprilTags attached to the skull. Five volunteers, familiar with the VisAR, used the software/visor combination to navigate an 18-gauge needle/trocar through the series of burr holes to the target, resulting in 70 data points (15 for 4 users and 10 for 1 user). After each attempt the needle was left in the skull, supported by the ballistic gelatin, and a high-resolution CT was taken. Radial error and angle of error were determined using vector coordinates. Summary statistics were calculated individually and collectively. The combined angle of error of was 2.30° ± 1.28°. The mean radial error for users was 3.62 ± 1.71 mm. The mean target depth was 85.41 mm. The mean radial error and angle of error with the associated variance measures demonstrates that VisAR navigation may have utility for guiding a small needle to neural lesions, or targets within an accuracy of 3.62 mm. These values are sufficiently accurate for the navigation of many neurological procedures such as ventriculostomy.


Learning from the Longitudinal Outcomes of Children with Hearing Impairment (LOCHI) study: summary of 5-year findings and implications.
This article summarises findings of the Longitudinal Outcomes of Children with Hearing Impairment (LOCHI) study, and discusses implications of the findings for research and clinical practice. A population-based study on outcomes of children with hearing loss. Evaluations were conducted at five years of age. Participants were 470 children born with hearing loss between 2002 and 2007 in New South Wales, Victoria and Queensland in Australia, and who first received amplification or cochlear implantation by three years of age. The earlier hearing aids or cochlear implants were fitted, the better the speech, language and functional performance outcomes. Better speech perception was also associated with better language and higher cognitive abilities. Better psychosocial development was associated with better language and functional performance. Higher maternal education level was also associated with better outcomes. Qualitative analyses of parental perspectives revealed the multiple facets of their involvement in intervention. The LOCHI study has shown that early fitting of hearing devices is key to achieving better speech, language and functional performance outcomes for children with hearing loss. The findings are discussed in relation to changes in clinical practice and directions for future research.


Coregistered Spectral Optical Coherence Tomography and Two-Photon Microscopy for Multimodal Near-Instantaneous Deep-Tissue Imaging.
Two-photon microscopy (2PM) has brought unique insight into the mechanisms underlying immune system dynamics and function since it enables monitoring of cellular motility and communication in complex systems within their genuine environment-the living organism. However, use of 2PM in clinical settings is limited. In contrast, optical coherence tomography (OCT), a noninvasive label-free diagnostic imaging method, which allows monitoring morphologic changes of large tissue regions in vivo, has found broad application in the clinic. Here we developed a combined multimodal technology to achieve near-instantaneous coregistered OCT, 2PM, and second harmonic generation (SHG) imaging over large volumes (up to 1,000 × 1,000 × 300 μm3 ) of tendons and other tissue compartments in mouse paws, as well as in mouse lymph nodes, spleens, and femurs. Using our multimodal imaging approach, we found differences in macrophage cell shape and motility behavior depending on whether they are located in tendons or in the surrounding tissue compartments of the mouse paw. The cellular shape of tissue-resident macrophages, indicative for their role in tissue, correlated with the supramolecular organization of collagen as revealed by SHG and OCT. Hence, the here-presented approach of coregistered OCT and 2PM has the potential to link specific cellular phenotypes and functions (as revealed by 2PM) to tissue morphology (as highlighted by OCT) and thus, to build a bridge between basic research knowledge and clinical observations. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.


Which factors influence quality of life in acne patients?
The factors that impact quality of life in acne patient are not fully understood. The purpose of this study was to assess the relationship between quality of life with (i) acne severity; (ii) the duration of this cutaneous disease; and (iii) the gender. Leeds scale to quantify acne severity, and Assessment of the Psychological and Social Effects of Acne (APSEA) score to evaluate quality of life were used. An unselected consecutive group of 50 males and 50 females affected by facial acne filled in the APSEA questionnaire during the first visit and after 3 months of treatment. (i) At the beginning of the treatment, APSEA score correlated with acne severity, but at the end of it, the reduction of APSEA score was less marked than the reduction of acne severity. (ii) Acne duration does not significantly influence APSEA score. (iii) Before treatment, acne severity was comparable between females and males, whereas APSEA score was significantly higher in females than in males. The quality life of acne patients could be influenced by social and emotional factors. The discrepancy of the results reported in literature regarding the correlation of the quality of life with acne severity and duration probably depends on the sensitivity and specificity of the questionnaire used to assess the quality of life. Among the different available scores to measure quality of life in acne patients, in the authors' experience, APSEA score is a valuable one.


Stereotactic Bragg peak proton beam radiosurgery for cerebral arteriovenous malformations.
A series of 709 patients with inaccessible AVMs treated with the proton beam is reported. There is a follow-up time of over 2 years for 92% of the patients. AVMs have slightly lower thresholds for proton injury than does normal brain tissue. Proton beam therapy involves very low risk. However, the risks of treatment failure grow with inadequate therapeutic doses.


Subclinical hyperthyroidism is a risk factor for poor functional outcome after ischemic stroke.
Subclinical hyperthyroidism is associated with adverse cardiovascular events, including stroke and atrial fibrillation. However, its impact on functional outcome after stroke remains unexplored. A total of 165 consecutively recruited patients admitted for ischemic stroke were included in this observational prospective study. Blood samples were taken in the morning within 3 days after symptom onset, and patients were divided into the following 3 groups: subclinical hyperthyroidism (0.1< thyroid-stimulating hormone ≤ 0.44 μU/mL), subclinical hypothyroidism (2.5 ≤ thyroid-stimulating hormone <20 μU/mL), and euthyroid state (0.44< thyroid-stimulating hormone <2.5 μU/mL). Patients with overt thyroid dysfunction were excluded. Follow-up took place 3 months after stroke. Primary outcome was functional disability (modified Rankin Scale), and secondary outcome was level of dependency (Barthel Index). Ordinal logistic regression analysis was used to adjust for possible confounders. Variables previously reported to be affected by thyroid function, such as atrial fibrillation, total cholesterol, or body mass index, were included in an additional model. Nineteen patients (11.5%) had subclinical hyperthyroidism, and 23 patients (13.9%) had subclinical hypothyroidism. Patients with subclinical hyperthyroidism had a substantially increased risk of functional disability 3 months after stroke compared with subjects with euthyroid state (odds ratio, 2.63; 95% confidence interval, 1.02-6.82, adjusted for age, sex, smoking status, and time of blood sampling). The association remained significant, when including the baseline NIHSS, TIA, serum CRP, atrial fibrillation, body mass index, and total cholesterol as additional variables (odds ratio, 3.95; 95% confidence interval, 1.25-12.47), and was confirmed by the secondary outcome (Barthel Index: odds ratio, 9.12; 95% confidence interval, 2.08-39.89). Subclinical hyperthyroidism is a risk factor for poor outcome 3 months after ischemic stroke.


Protein kinase substrate profiling with a high-density peptide microarray.
We describe a powerful peptide microarray for profiling protein kinase substrates that combines the merits of chemoselective immobilization of peptides to achieve high density spots with the advantages of fluorescence-based analysis of phosphorylation for nonhazardous detection. For detection of on-chip phosphorylation, we used a fluorescence-labeled antiphosphotyrosine antibody to detect phosphotyrosine and a biotinylated Phostag, which was subsequently bound with a fluorescence-labeled streptavidin for phosphoserine/threonine. More than 290 kinds of Tyr peptides and over 1,100 kinds of Ser/Thr peptides were chemoselectively immobilized onto a glass surface in a high-density format to profile a panel of protein kinases, including c-Src, c-Abl, EGFR, JNK1, ERK2, p38α, and PKA. Many novel, highly reactive and specific peptides were identified as substrates for each protein kinase. Most substrates had the consensus motifs that have been reported previously but some new motifs were also found. The identification of two designed peptides that have higher reactivity than the famous PKA substrate (Kemptide) indicates that analysis of the amino acid biases of substrates is very helpful to the design of new substrates with high reactivity. Thus, the high-density peptide microarray is expected to be a powerful approach for high-throughput discovery of potential substrates for protein kinases.


Stereology of human fetal adrenal medulla.
Stereological studies were performed on 27 pairs of adrenal glands of human fetuses (9-38 weeks of intra-uterine development). Medullary chromaffin cells were identified by immunostaining for chromogranin-A. The volume of adrenal medulla, average cell volume, and the number of chromaffin cells were calculated. The volume of adrenal medulla increased slowly up to the 20th week and afterwards it enlarged rapidly to the 31 st week of the fetal period. A gradual, linear increase in the number of chromaffin cells of developing adrenal medulla was observed during the studied period. On the contrary, the average volume of the adrenal medullary cells remained quite constant until the 17th week of the development. Afterwards, a gradual, linear increase in the cell volume was observed until the 31 st week, reaching a plateau by the end of intra-uterine development.


The impact of maternal gestational weight gain on cardiometabolic risk factors in children.
Accumulating evidence suggests an impact of gestational weight gain (GWG) on pregnancy outcomes; however, data on cardiometabolic risk factors later in life have not been comprehensively studied. This study aimed to evaluate the relationship between GWG and cardiometabolic risk in offspring aged 7 years. We included a total of 905 mother-child pairs who enrolled in the follow-up visit of the multicentre Hyperglycemia and Adverse Pregnancy Outcome study, at the Hong Kong Centre. Women were classified as having gained weight below, within or exceeding the 2009 Institute of Medicine (IOM) guidelines. A standardised GWG according to pre-pregnancy BMI categories was calculated to explore for any quadratic relationship. Independent of pre-pregnancy BMI, gestational hyperglycaemia and other confounders, women who gained more weight than the IOM recommendations had offspring with a larger body size and increased odds of adiposity, hypertension and insulin resistance (range of p values of all the traits: 4.6 × 10-9 < p < 0.0390) than women who were within the recommended range of weight gain during pregnancy. Meanwhile, women who gained less weight than outlined in the recommendations had offspring with increased risks of hypertension and insulin resistance, compared with those who gained weight within the recommended range (7.9 × 10-3 < p < 0.0477). Quadratic relationships for diastolic blood pressure, AUC for insulin, pancreatic beta cell function and insulin sensitivity index were confirmed in the analysis of standardised GWG (1.4 × 10-3 < pquadratic < 0.0282). Further adjustment for current BMI noticeably attenuated the observed associations. Both excessive and inadequate GWG have independent and significant impacts on childhood adiposity, hypertension and insulin resistance. Our findings support the notion that adverse intrauterine exposures are associated with persistent cardiometabolic risk in the offspring.


Comparison of quantitative PCR and digital PCR assays for quantitative detection of infectious bronchitis virus (IBV) genome.
The quantitative polymerase chain reaction (qPCR) technique is an extensively used molecular tool for the detection and quantification of viral genome load. However, since qPCR is a relative quantification method that relies on an external calibration curve it has a lower assay precision and sensitivity. The digital PCR (dPCR) technique is a good alternative to the qPCR assay as it offers highly precise and direct quantification of viral genome load in samples. In this study, performance characteristics such as the quantification range, sensitivity, precision, and specificity of the dPCR technique was compared to qPCR technique for the detection and quantification of IBV genome loads in serial dilutions of IBV positive plasmid DNA, and IBV infected chicken tissue and swab samples. The quantification range of the qPCR assay was wider than that of the dPCR assay, however dPCR had a higher sensitivity compared to qPCR. The precision of quantification of DNA in plasmid samples in terms of repeatability and reproducibility of results was higher when using the dPCR assay compared to qPCR assay. The quantification results of IBV genome load in infected samples by the qPCR and dPCR assays displayed a high correlation. Hence, our findings suggest that dPCR could be used in avian virology research for improved precision and sensitivity in detection and quantification of viral genome loads.


From single to multiple atomic layers: a unique approach to the systematic tuning of structures and properties of inorganic-organic hybrid nanostructured semiconductors.
In order to systematically tailor the structures and properties of a unique family of inorganic-organic hybrid nanostructured materials based on II-VI semiconductors, we have designed and engineered a new group of two-dimensional crystalline [(M2Q2)(L)] nanostreuctures (where M = Zn, Cd; Q = S, Se; and L = ethylamine, n-propylamine, n-butylamine, n-amylamine, n-hexylamine). These compounds are composed of double atomic layers of M2Q2 separated by organic monoamines. The crystal structures of 2D-[(M2Q2)(L)] are characterized by powder X-ray diffraction (PXRD) analysis. The crystal structures of these compounds are similar to the 2D-[(MQ)(L)] series that we reported earlier, in that they also contain II-VI slabs sandwiched by organic monoamines. The main difference is in the thickness of the II-VI slabs, where they are single-layer (n = 1) in 2D-[(MQ)(L)] but double-layer (n = 2) in 2D-[(M2Q2)(L)]. Optical absorption experiments show that all double-layer compounds exhibit a blue shift in their absorption edge (0.6-1.2 eV), due to the quantum confinement effect (QCE). However, the extent of such a blue shift is significantly less than that of the single-layer 2D-[(MQ)(L)] systems (1.0-2.0 eV) as a result of the difference in their layer thickness. Thermogravimetric (TG) analysis has revealed nanosized II-VI (MQ) particles as the post-TG product of all double-layer hybrids.


A Review of Challenges and Opportunities in Machine Learning for Health.
Modern electronic health records (EHRs) provide data to answer clinically meaningful questions. The growing data in EHRs makes healthcare ripe for the use of machine learning. However, learning in a clinical setting presents unique challenges that complicate the use of common machine learning methodologies. For example, diseases in EHRs are poorly labeled, conditions can encompass multiple underlying endotypes, and healthy individuals are underrepresented. This article serves as a primer to illuminate these challenges and highlights opportunities for members of the machine learning community to contribute to healthcare.


Immunomodulation by Entinostat in Renal Cell Carcinoma Patients Receiving High-Dose Interleukin 2: A Multicenter, Single-Arm, Phase I/II Trial (NCI-CTEP#7870).
Purpose: On the basis of preclinical data suggesting that the class I selective HDAC inhibitor entinostat exerts a synergistic antitumor effect in combination with high-dose IL2 in a renal cell carcinoma model by downregulating Foxp3 expression and function of regulatory T cells (Treg), we conducted a phase I/II clinical study with entinostat and high-dose IL2 in patients with metastatic clear cell renal cell carcinoma (ccRCC).Experimental Design: Clear cell histology, no prior treatments, and being sufficiently fit to receive high-dose IL2 were the main eligibility criteria. The phase I portion consisted of two dose levels of entinostat (3 and 5 mg, orally every 14 days) and a fixed standard dose of IL2 (600,000 U/kg i.v.). Each cycle was 85 days. The primary endpoint was objective response rate and toxicity. Secondary endpoints included progression-free survival and overall survival.Results: Forty-seven patients were enrolled. At a median follow-up of 21.9 months, the objective response rate was 37% [95% confidence interval (CI), 22%-53%], the median progression-free survival was 13.8 months (95% CI, 6.0-18.8), and the median overall survival was 65.3 months (95% CI, 52.6.-65.3). The most common grade 3/4 toxicities were hypophosphatemia (16%), lymphopenia (15%), and hypocalcemia (7%), and all were transient. Decreased Tregs were observed following treatment with entinostat, and lower numbers were associated with response (P = 0.03).Conclusions: This trial suggests a promising clinical activity for entinostat in combination with high-dose IL2 in ccRCC patients and provides the first example of an epigenetic agent being rationally combined with immunotherapy. Clin Cancer Res; 23(23); 7199-208. ©2017 AACR.


CLASP promotes microtubule bundling in metaphase spindle independently of Ase1/PRC1 in fission yeast.
Microtubules in the mitotic spindle are organised by microtubule-associated proteins. In the late stage of mitosis, spindle microtubules are robustly organised through bundling by the antiparallel microtubule bundler Ase1/PRC1. In early mitosis, however, it is not well characterised as to whether spindle microtubules are actively bundled, as Ase1 does not particularly localise to the spindle at that stage. Here we show that the conserved microtubule-associated protein CLASP (fission yeast Peg1/Cls1) facilitates bundling of spindle microtubules in early mitosis. The peg1 mutant displayed a fragile spindle with unbundled microtubules, which eventually resulted in collapse of the metaphase spindle and abnormal segregation of chromosomes. Peg1 is known to be recruited to the spindle by Ase1 to stabilise antiparallel microtubules in late mitosis. However, we demonstrate that the function of Peg1 in early mitosis does not rely on Ase1. The unbundled spindle phenotype of the peg1 mutant was not seen in the ase1 mutant, and Peg1 preferentially localised to the spindle even in early mitosis unlike Ase1. Moreover, artificial overexpression of Ase1 in the peg1 mutant partially suppressed unbundled microtubules. We thus conclude that Peg1 bundles microtubules in early mitosis, in a distinct manner from its conventional Ase1-dependent functions in other cell cycle stages.


Cancer registry data based estimation of regional cancer incidence: application to breast and colorectal cancer in French administrative regions.
In many countries, cancer registries cover only a small part of the national population. Cancer incidence for the rest of the country has therefore to be estimated. This can be done from mortality data using the relation between incidence and mortality observed in the cancer registry areas. Such an approach was used to study geographical variation and trend of colorectal and breast cancer incidence in France where 10% of the national population is covered by cancer registries. This study applies the incidence/mortality ratios of cancer registry areas to regional mortality data to obtain an estimation of cancer incidence at a given point in time. Age and period effects are included in the statistical models. The incidence estimations are given for 21 administrative regions and three time points (1985, 1990, 1995). The European standardised incidence rates for breast cancer ranged from 86.8 to 128.8. For colorectal cancer, these rates ranged from 48.2 to 79.6 for men, and from 32.5 to 48.8 for women. Breast cancer incidence has increased considerably between 1985 and 1995 with a higher increase in the north than in the south of France. The incidence of colorectal cancer has also increased, albeit to a lesser extent. The incidence estimation method proposed leads to regional incidence rates that are useful for planning health care services on a regional basis and may also be used to study regional differences in incidence. This method is useful when only partial incidence data are available.


In vitro susceptibility of methicillin-resistant Staphylococcus aureus isolates from skin and soft tissue infections to vancomycin, daptomycin, linezolid and tedizolid.
Treatment of multidrug-resistant Gram-positive infections caused by Staphylococcus aureus remains as a clinical challenge due to emergence of new resistance mechanisms. Tedizolid is a next-generation oxazolidinone, recently approved for skin and soft tissues infections. We conducted a study to determine in vitro susceptibility to vancomycin, daptomycin, linezolid and tedizolid in MRSA clinical isolates from adult patients with skin and soft tissue infections. Methicillin-resistant S. aureus isolates were collected in three tertiary-care hospitals of Medellin, Colombia, from February 2008 to June 2010 as part of a previous study. Clinical characteristics were assessed by medical records and MIC values were determined by Epsilometer test. Genotypic analysis included spa typing, MLST, and SCCmec typing. A total of 150 MRSA isolates were evaluated and tedizolid MIC values obtained showed higher in vitro activity than other antimicrobials, with MIC values ranging from 0.13μg/mL to 0.75μg/mL and lower values of MIC50 and MIC90 (0.38μg/mL and 0.5μg/mL). In contrast, vancomycin and linezolid had higher MIC values, which ranged from 0.5μg/mL to 2.0μg/mL and from 0.38μg/mL to 4.0μg/mL, respectively. Tedizolid MICs were 2- to 5-fold lower than those of linezolid. Clinical characteristics showed high previous antimicrobial use and hospitalization history. The majority of the strains belong to the CC8 harboring the SCCmec IVc and were associated with the spa t1610 (29.33%, n=44). In vitro effectiveness of tedizolid was superior for isolates from skin and soft tissue infections in comparison with the other antibiotics evaluated. The above added to its less toxicity, good bioavailability, daily dose and unnecessity of dosage adjustment, make tedizolid in a promising alternative for the treatment of infections caused by MRSA.


A Neural Network-based Method for Predicting Dose to Organs at Risk in Intensity-modulated Radiotherapy for Nasopharyngeal Carcinoma.
A neural network method was used to establish a dose prediction model for organs at risk (OARs) during intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). In total, 103 patients with NPC were randomly selected for IMRT. Suborgans were automatically generated for OARs using ring structures based on distance to the target using a MATLAB program and the corresponding volume of each suborgan was determined. The correlation between the volume of each suborgan and the dose to each OAR was analysed and neural network prediction models of the OAR dose were established using the MATLAB Neural Net Fitting application. The R-value and mean square error in the regression analysis were used to evaluate the prediction model. The OAR dose was related to the volume of the corresponding sub-OAR. The average R-values for the normalised mean dose (Dnmean) to parallel organs and serial organs and the normalised maximum dose (Dn0) to serial organs in the training set were 0.880, 0.927 and 0.905, respectively. The mean square error for each OAR in the prediction model was low (ranging from 1.72 × 10-4 to 7.06 × 10-3). The neural network-based model for predicting OAR dose during IMRT for NPC is simple, reliable and worth further investigation and application.


Treatment timing and the effects of rhythm control strategy in patients with atrial fibrillation: nationwide cohort study.
To investigate whether the results of a rhythm control strategy differ according to the duration between diagnosis of atrial fibrillation and treatment initiation. Longitudinal observational cohort study. Population based cohort from the Korean National Health Insurance Service database. 22 635 adults with atrial fibrillation and cardiovascular conditions, newly treated with rhythm control (antiarrhythmic drugs or ablation) or rate control strategies between 28 July 2011 and 31 December 2015. A composite outcome of death from cardiovascular causes, ischaemic stroke, admission to hospital for heart failure, or acute myocardial infarction. Of the study population, 12 200 (53.9%) were male, the median age was 70, and the median follow-up duration was 2.1 years. Among patients with early treatment for atrial fibrillation (initiated within one year since diagnosis), compared with rate control, rhythm control was associated with a lower risk of the primary composite outcome (weighted incidence rate per 100 person years 7.42 in rhythm control v 9.25 in rate control; hazard ratio 0.81, 95% confidence interval 0.71 to 0.93; P=0.002). No difference in the risk of the primary composite outcome was found between rhythm and rate control (weighted incidence rate per 100 person years 8.67 in rhythm control v 8.99 in rate control; 0.97, 0.78 to 1.20; P=0.76) in patients with late treatment for atrial fibrillation (initiated after one year since diagnosis). No significant differences in safety outcomes were found between the rhythm and rate control strategies across different treatment timings. Earlier initiation of treatment was linearly associated with more favourable cardiovascular outcomes for rhythm control compared with rate control. Early initiation of rhythm control treatment was associated with a lower risk of adverse cardiovascular outcomes than rate control treatment in patients with recently diagnosed atrial fibrillation. This association was not found in patients who had had atrial fibrillation for more than one year.


Costs and benefits of rabies control in wildlife in France.
The author presents an evaluation of the cost of wildlife rabies in France. This study included the vaccination of domestic animals, the reinforcement of epidemiological surveillance networks and the support provided to diagnostic laboratories, the expenses associated with outbreaks of rabies (animal losses and associated economic losses), the clinical observation of those animals which had bitten humans and the preventive vaccination and post-exposure treatment of humans. A substantial percentage (72%) of this cost was the preventive vaccination of domestic animals. In France, as in other European countries in which the red fox (Vulpes vulpes) is the species most affected, to main strategies for controlling the disease at the reservoir level were evaluated, namely: fox depopulation and the oral vaccination of foxes. The combined costs and benefits of rabies and of both strategies were compared and included either the cost of fox culling or the cost of oral vaccination (baits, bait delivery and follow-up to ensure the efficiency of the vaccination). The cumulative annual costs of both strategies remained comparable until the fourth year, after which the oral vaccination strategy became beneficial. This forecast was made in 1988, readjusted in 1993 and confirmed by ex post analysis five years later. The expected benefits of oral vaccination have now been obtained. Fox depopulation has only ever resulted in a transient lull in the occurrence of the disease, while oral vaccination has proved to be capable of eliminating rabies even in situations in which fox populations were increasing.


Synergy between the antinociceptive effects of morphine and NSAIDs.
The intraperitoneal administration of morphine, diclofenac, ketoprofen, meloxicam, metamizol, paracetamol and piroxicam induced dose-dependent antinociception in mice tested with the acetic acid writhing test. The isobolographic analysis of the simultaneous intraperitoneal administration of fractions of the ED50's of morphine with each nonsteroidal anti-inflammatory drug (NSAID) demonstrated the existence of a supra-additive interaction (synergy). The selective antagonist of micro -opioid receptors naltrexone partially reversed the supra-additive interactions to additive interactions; however, the combinations of morphine/metamizol and morphine/paracetamol were completely antagonized, resulting in subadditive interactions. The selective antagonist of delta-opioid receptors naltrindole failed to significantly attenuate the combinations of morphine with ketoprofen, meloxicam and piroxicam, but decreased the activity of the combinations of morphine with diclofenac, metamizol and paracetamol, transforming the interactions from supra-additive to additive. Nor-binaltorphimine was used to evaluate the involvement of kappa-opioid receptors. Nor-binaltorphimine did not modify the supra-additive interaction of morphine and NSAIDs and the additive interaction of the co-administration of morphine and metamizol. The synergy between morphine and NSAIDs could be related to different pathways of pain transmission, probably related to the different intracellular signal transduction mechanisms of action of opioid and non-opioid agents.


Adenosine inhibits voltage-dependent Ca2+ influx in cone photoreceptor terminals of the tiger salamander retina.
Endogenous adenosine has already been shown to inhibit transmitter release from the rod synapse by suppressing Ca(2+) influx through voltage-gated Ca(2+) channels. However, it is not clear how adenosine modulates the cone synapse. Cone photoreceptors, like rod photoreceptors, also possess L-type Ca(2+) channels that regulate the release of L-glutamate. To assess the impact of adenosine on Ca(2+) influx though voltage-gated Ca(2+) channels in cone terminals, whole-cell perforated-patch clamp recording and Ca(2+) imaging with fluo-4 were used on isolated cones and salamander retinal slices. Synaptic markers (VAMP and piccolo) and activity-dependent dye labeling revealed that tiger salamander cone terminals contain a broad, vesicle-filled cytoplasmic extension at the base of the somatic compartment, which is unlike rod terminals that contain one or more thin axons, each terminating in a large bulbous synaptic terminal. The spatiotemporal Ca(2+) responses of the cone terminals do not differ significantly from the Ca(2+) responses of the soma or inner segment like that observed in rods. Whole-cell recording of cone I(Ca) and Ca(2+) imaging of synaptic terminals in cones demonstrate that adenosine inhibited both I(Ca) and the depolarization-evoked Ca(2+) increase in cone terminals in a dose-dependent manner from 1 to 50 muM. These results indicate that, as in rods, adenosine's ability to suppress voltage-dependent Ca(2+) channels at the cone synapse will limit the amount of L-glutamate released. Therefore, adenosine has an inhibitory effect on L-glutamate release at the first synapse, which likely favors elevated adenosine levels in the dark or during dark-adapted conditions.


Breast Cancer: Model Reconstruction and Image Registration From Segmented Deformed Image Using Visual and Force Based Analysis.
Breast lesion localization using tactile imaging is a new and developing direction in medical science. To achieve the goal, proper image reconstruction and image registration can be a valuable asset. In this paper, a new approach of the segmentation-based image surface reconstruction algorithm is used to reconstruct the surface of a breast phantom. In breast tissue, the sub-dermal vein network is used as a distinguishable pattern for reconstruction. The proposed image capturing device contacts the surface of the phantom, and surface deformation will occur due to applied force at the time of scanning. A novel force based surface rectification system is used to reconstruct a deformed surface image to its original structure. For the construction of the full surface from rectified images, advanced affine scale-invariant feature transform (A-SIFT) is proposed to reduce the affine effect in time when data capturing. Camera position based image stitching approach is applied to construct the final original non-rigid surface. The proposed model is validated in theoretical models and real scenarios, to demonstrate its advantages with respect to competing methods. The result of the proposed method, applied to path reconstruction, ends with a positioning accuracy of 99.7%.


Nanorod-constructed porous Co3O4 nanowires: highly sensitive sensors for the detection of hydrazine.
A highly sensitive, reliable and reproducible sensor for the detection of hydrazine was fabricated using a porous Co3O4 nanowire (NW) electrode. Porous Co3O4 NWs constructed from interconnected nanorod units with a three-dimensional porous network were synthesized via a facile hydrothermal process. The hydrazine sensor based on the Co3O4 NW electrode demonstrated a relatively high sensitivity (28.63 μA mM(-1)) and a rather low detection limit (0.5 μM) due to the fast electro-oxidation of hydrazine catalyzed by Co3O4 NWs. The unique porous structure of Co3O4 NWs offers a promising probe candidate for efficient electrochemical sensors of hydrazine.


Assessing violence risk and psychopathy in juvenile and adult offenders: a survey of clinical practices.
This study surveyed 199 forensic clinicians about the practices that they use in assessing violence risk in juvenile and adult offenders. Results indicated that the use of risk assessment and psychopathy tools was common. Although clinicians reported more routine use of psychopathy measures in adult risk assessments compared with juvenile risks assessments, 79% of clinicians reported using psychopathy measures at least once in a while in juvenile risk assessments. Extremely few clinicians, however, believe that juveniles should be labeled or referred to as psychopaths. Juvenile risk reports were more likely than adult reports to routinely discuss treatment and protective factors, and provide recommendations to reevaluate risk. The implications of these findings are discussed.


Influenza vaccination responses in human systemic lupus erythematosus: impact of clinical and demographic features.
Vaccination against common pathogens, such as influenza, is recommended for patients with systemic lupus erythematosus (SLE) to decrease infections and improve health. However, most reports describing the vaccination response are limited to evaluations of SLE patients with quiescent disease. This study focuses on understanding the clinical, serologic, therapeutic, and demographic factors that influence the response to influenza vaccination in SLE patients with a broad range of disease activity. Blood specimens and information on disease activity were collected from 72 patients with SLE, at baseline and at 2, 6, and 12 weeks after influenza vaccination. Influenza-specific antibody responses were assessed by determining the total serum antibody concentration (B(max)), relative affinity (K(a)), and level of hemagglutination inhibition in the plasma. Using a cumulative score, the patients were evenly divided into groups of high or low vaccine responders. Autoantibody levels were evaluated at each time point using immunofluorescence tests and standard enzyme-linked immunosorbent assays. Compared to high responders, low responders to the vaccine were more likely to have hematologic criteria (P = 0.009), to have more American College of Rheumatology classification criteria for SLE (P = 0.05), and to be receiving concurrent prednisone treatment (P = 0.04). Interestingly, European American patients were more likely to be low responders than were African American patients (P = 0.03). Following vaccination, low responders were more likely to experience disease flares (P = 0.01) and to have increased titers of antinuclear antibodies (P = 0.04). Serum interferon-α activity at baseline was significantly higher in patients in whom a flare occurred after vaccination compared to a matched group of patients who did not experience a disease flare (P = 0.04). Ancestral background, prednisone treatment, hematologic criteria, and evidence of increased likelihood of disease flares were associated with low antibody responses to influenza vaccination in SLE patients.


Octreotide, a somatostatin analogue, in the treatment of chylothorax associated with idiopathic fibrosing mediastinitis.
Fibrosing mediastinitis (FM) is a rare benign disorder that is characterized by excessive fibrotic reactions in the mediastinum. FM is associated with various diseases, including Histoplasma capsulatum infection and IgG4-related disease, and may compromise the airways, great vessels, and other mediastinal structures. Chylothorax is not a common manifestation of FM, and there is no standard treatment for FM or chylothorax. Recently, however, somatostatin and octreotide, a somatostatin analogue, were successfully used for the treatment of chylothorax due to various causes, and they are considered as putative therapeutic interventions for chylothorax. Here, we present a 28-year-old Japanese man with chylothorax due to idiopathic FM, who was successfully treated with octreotide. The patient visited our hospital because of dyspnea on exertion. On admission, chest computed tomography revealed pericardial effusion, bilateral pleural effusion, and a mass in the mediastinum. The right pleural effusion appeared chylous, with the triglyceride level of 253 mg/dl. The biopsy specimen from the mediastinal mass showed collagenous fibers and fibroblasts with moderate infiltration of lymphocytes. Neither fungi nor bacteria were cultured from the biopsy specimen. Steroid therapy was not effective. The patient was then treated with subcutaneous octreotide (100 microg three times daily). Five days after starting the treatment, the drained pleural fluid was decreased to approximately 150 ml/day from approximately 1,000 ml/day. The mediastinal mass decreased in size 2 weeks after the initiation of octreotide treatment. After discharge, the patient has received octreotide treatment for 6 months without serious adverse events. We suggest octreotide as a treatment option for FM.


Effects of SCH-23390 infused into the amygdala or adjacent cortex and basal ganglia on cocaine seeking and self-administration in rats.
Amygdala D1 receptors have been implicated in the motivating effects of cocaine-conditioned cues and cocaine itself, but the specific nucleus involved is unclear. Thus, we infused the D1 antagonist, SCH-23390, into the rostral basolateral amygdala (rBLA), caudal basolateral amygdala (cBLA), or central amygdala (CEA), and tested its effects on self-administration of cocaine, as well as reinstatement of extinguished cocaine-seeking behavior by cocaine-conditioned cues or cocaine itself. Two anatomical controls, the posterior regions of basal ganglia (BG) and somatosensory/insular cortices (CTX), were also examined. Cocaine self-administration was increased and cue and cocaine reinstatement were decreased by SCH-23390 infusion into every region when examined across the hour test session, with the exception that cBLA infusion did not alter cocaine reinstatement. In the first 20 min of the session, when SCH-23390 was more localized in the target sites, self-administration was increased by infusion into the CEA, cBLA, BG, and CTX, with lesser increases in the rBLA. Cocaine reinstatement was attenuated during the first 20 min only by infusion into the CEA, rBLA, and CTX. Cue reinstatement was not reliably observed in the first 20 min, but there was a trend for attenuation by infusion into the cBLA, and surprisingly, significant attenuations in the BG and CTX. The findings suggest that D1 receptors in subregions of the amygdala play differential roles in the reinforcing/motivational effects of cocaine, while the cue reinstatement effects are less clear. Further research is needed to examine the novel findings that neighboring regions of the BG and CTX may play a role in motivation for cocaine.


Radical hysterectomy in obese and morbidly obese women with cervical cancer.
To compare intraoperative and postoperative outcomes, pathologic findings, cancer recurrence, and death rates in normal-weight, overweight, obese, and morbidly obese women undergoing radical hysterectomy and pelvic lymphadenectomy for early-stage cervical cancer. A review of patients who underwent radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer between 1990 and 2006 was performed. On the basis of body mass index (BMI) (calculated as weight [kg]/[height (m)](2)), women were categorized as normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), obese (BMI 30.0-34.9), or morbidly obese (BMI at least 35.0). Four hundred eight women met the inclusion criteria. Of these, 155 (38%) were normal weight, 126 (31%) were overweight, 77 (19%) were obese, and 50 (12%) were morbidly obese. There were no statistically significant differences between these four groups in age, Charlson comorbidity score, smoking history, stage, histologic grade or subtype, tumor size, depth of invasion, transfusion rate, operative time, or intraoperative complications. Higher BMI was significantly correlated with higher estimated operative blood loss (P=.001). There were no statistically significant differences between the groups in pathologic findings, length of postoperative hospital stay, postoperative complications, readmission rate, or proportion of women receiving adjuvant radiotherapy. At a median follow-up time of 64 months, there were no differences between groups in rates of recurrence or death from disease. Radical hysterectomy and pelvic lymphadenectomy is feasible for obese and morbidly obese women with cervical cancer. Obesity alone should not be a contraindication to radical hysterectomy in women with cervical cancer.


Highly stable water-soluble platinum nanoparticles stabilized by hydrophilic N-heterocyclic carbenes.
Controlling the synthesis of stable metal nanoparticles in water is a current challenge in nanochemistry. The strategy presented herein uses sulfonated N-heterocyclic carbene (NHC) ligands to stabilize platinum nanoparticles (PtNPs) in water, under air, for an indefinite time period. The particles were prepared by thermal decomposition of a preformed molecular Pt complex containing the NHC ligand and were then purified by dialysis and characterized by TEM, high-resolution TEM, and spectroscopic techniques. Solid-state NMR studies showed coordination of the carbene ligands to the nanoparticle surface and allowed the determination of a (13)C-(195)Pt coupling constant for the first time in a nanosystem (940 Hz). Additionally, in one case a novel structure was formed in which platinum(II) NHC complexes form a second coordination sphere around the nanoparticle.


Production and characterization of monoclonal antibodies directed against the laminin receptor precursor.
The 67-kDa laminin receptor (67LR) is an important tumor marker whose molecular structure has not yet been fully elucidated. To shed new light on this molecule, we raised a series of eight new monoclonal antibodies, designated MPLR1 to 8, directed against the 37-kDa recombinant laminin receptor precursor (37LRP). Cross-competition experiments demonstrated that the epitopes recognized by MPLR2, 4 and 5 partially overlap, since MPLR4 and 5 compete with labelled MPLR2 for the binding to recombinant 37LRP. These three antibodies belong to the IgG1 class, whereas the other ones are all IgM. Presumably due to the fact that they are directed against partially unfolded antigenic determinants expressed on the recombinant protein, MPLRs did not recognize the native protein. Indeed, they showed no reactivity at the membrane level in cytofluorimetric analysis and they did not work in immunoprecipitation experiments. In contrast, these reagents are valuable tools in immunoblotting, since they clearly identify a 67-kDa protein (the mature laminin receptor) in addition to the 37-kDa precursor form. MPLRs are thus a new powerful tool which could help in the characterization of the still enigmatic 67LR molecule.


Biphasic kinetics of growth and bacteriocin production with Lactobacillus amylovorus DCE 471 occur under stress conditions.
Micro-organisms used during the production of fermented foods are subjected to several abiotic stresses. Microbial survival during these processes strongly depends on the ability of the cells to adapt and become more tolerant to the environmental conditions. Cultivation of Lactobacillus amylovorus DCE 471, a potential strain for use during type II sourdough fermentations, at low temperatures, unfavourable pH and high salt concentrations resulted in biphasic growth patterns. In addition, two separate bacteriocin peaks, as well as a dramatic change in cellular morphology, were observed. In general, an increase of the specific bacteriocin production occurred during the second growth phase. Finally, the observed sugar consumption profiles were affected by the applied fermentation temperature. Moreover, the highest bacteriocin activity occurred during maltose consumption at a low constant temperature of 28 degrees C and a constant pH of 5.4. Plate counts from both growth phases revealed the existence of two colony types. Irregular colonies were found to outnumber smoother colonies during the first growth phase, while the second growth phase was characterized by a greater number of smooth colonies. Electron microscopy was used to investigate the observed morphological switch at the single-cell level. Single, rod-shaped cells changed into elongated cells that grew in chains. Colony and cell morphology changes coincided with the biphasic growth pattern.


Advanced forms of MPNs are accompanied by chromosomal abnormalities that lead to dysregulation of TP53.
The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and the prefibrotic form of primary myelofibrosis (PMF), frequently progress to more overt forms of MF and a type of acute leukemia termed MPN-accelerated phase/blast phase (MPN-AP/BP). Recent evidence indicates that dysregulation of the tumor suppressor tumor protein p53 (TP53) commonly occurs in the MPNs. The proteins MDM2 and MDM4 alter the cellular levels of TP53. We investigated in 1,294 patients whether abnormalities involving chromosomes 1 and 12, which harbor the genes for MDM4 and MDM2, respectively, and chromosome 17, where the gene for TP53 is located, are associated with MPN disease progression. Gain of 1q occurred not only in individuals with MPN-BP but also in patients with PV and ET, who, with further follow-up, eventually evolve to either MF and/or MPN-BP. These gains of 1q were most prevalent in patients with a history of PV and those who possessed the JAK2V617F driver mutation. The gains of 1q were accompanied by increased transcript levels of MDM4 In contrast, 12q chromosomal abnormalities were exclusively detected in patients who presented with MF or MPN-BP, but were not accompanied by further increases in MDM2/MDM4 transcript levels. Furthermore, all patients with a loss of 17p13, which leads to a deletion of TP53, had either MF or MPN-AP/BP. These findings suggest that gain of 1q, as well as deletions of 17p, are associated with perturbations of the TP53 pathway, which contribute to MPN disease progression.


An estimator for functional data with application to MRI.
We propose a method for restoring the underlying true signal in noisy functional images. The Nadaraya-Watson (NW) estimator described in, e.g., [1] is a classical nonparametric estimator for this problem. Since the true scene in many applications contains abrupt changes between pixels of different types, a modification of the NW estimator is needed. In the data we study, the characteristics of each pixel are given as a function of time. This means that a curve of data points is observed at each pixel. Utilizing this time information, the NW weights can be modified to obtain a weighted average over pixels with the same true value. Theoretical results showing the estimator's properties are developed. Several parameters play an important role for the restoration result. Practical guidelines are given for how these parameters can be selected. Finally, we demonstrate how the method can be successfully applied both to artificial data and Magnetic Resonance Images.


Low-fat diet management strategy for chylothorax after pulmonary resection and lymph node dissection for primary lung cancer.
We reviewed our experience of iatrogenic chylothorax after pulmonary resection for primary lung cancer to evaluate a low-fat diet management strategy. From October 2003 to March 2010, 1580 patients underwent lobectomy or greater resection and systematic mediastinal lymph node dissection for primary lung cancer at our institution. Chylothorax was diagnosed on the basis of chylous leakage from the chest tube and was confirmed by presence of triglycerides (>110 mg/dL) in the drainage fluid. We initially treated the patients with chylothorax conservatively with a low-fat diet (fat intake <10 g/day). If chest tube drainage produced >500 mL of chylous fluid during the first 24 hours after the initiation of the low-fat diet, surgical intervention was performed. If chest tube drainage produced >300 mL/day of chylous fluid after 3 days of a low-fat diet, we performed pleurodesis by injecting a preparation of OK-432, a penicillin-treated lyophilized preparation of a Streptococcus strain into the thoracic cavity through a chest tube. Postoperative chylothorax developed in 37 patients (2.3%), 33 men and 4 women, with a median age of 69 years (range, 44-84). The initial procedures were pneumonectomy in 1 patient and lobectomy in 36 patients. In 23 patients (62%), their condition resolved with the low-fat diet only. A total of 10 patients underwent OK-432 pleurodesis, and 8 of these were cured with continuation of the low-fat diet. These 31 patients who responded to conservative treatment (84%) resumed a normal diet at a median of 10 days (range, 5-27) after the chylothorax diagnosis. The remaining 6 patients (16%) underwent reoperation and were discharged at a median of 18 days (range, 14-33) after the initial surgery. A low-fat diet and OK-432 pleurodesis achieved positive results in >80% of patients with chylothorax after pulmonary resection with systematic mediastinal lymph node dissection within 4 weeks after the initial surgery. More than 500 mL of chylous fluid during the first 24 hours after the initiation of the low-fat diet was valid as an indication of the need for surgical intervention.


Carbohydrate tolerance in pregnant Nigerian women--comparison of 75 gms and 100 gms glucose loads.
Oral glucose tolerance tests (OGTT) with 75 gms. and 100 gms. glucose loads were performed two weeks apart in each of 20 healthy Nigerian women in the third trimester of pregnancy. The mean (+/- SD) blood glucose values (venous whole blood in mgs/100 ml) during the tests with the two loads were as follows: 75 gms. -fasting -71.1 (12.6), 30 min. -96.9 (19.1), 60 mins. -99.5 (19.8), 120 mins. -92.3 (19.3), 180 mins. -79.6 (17.2); 100 gms. -fasting -60.5 (7.4), 30 mins. -93.4 (13.8), 60 mins. -94.9 (21.7), 120 mins. -82.3 (10.3), 180 mins. -72.7 (12.2). The differences were statistically significant for the fasting and 120 mins. values, p less than 0.05. These results suggest that increasing the glucose load above 75 gms. does not necessarily increase the maximum glycemic response. Therefore, criteria for the interpretation of the OGTT in pregnancy based on a 75 gms. dose. It would be desirable to establish reliable criteria for the diagnosis of diabetes in pregnancy based on a 75 gms. dose OGTT. This would foster a uniform standard for the performance of this test in all adult population groups and it may also mean a little saving in cost for those working in the less developed countries of the world.


Renin angiotensin system deregulation as renal cancer risk factor.
For numerous years, the non-cardiovascular role of the renin-angiotensin system (RAS) was underestimated, but recent studies have advanced the understanding of its function in various processes, including carcinogenesis. Numerous evidence comes from preclinical and clinical studies on the use of antihypertensive agents targeting the RAS, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers. It has been demonstrated that the use of ACEIs can alter the incidence of renal cell carcinoma (RCC) and may have a positive effect by prolonging patient survival. It has an effect on the complex action of ACEI, resulting in decreased angiotensin II (Ang-II) production and altered levels of bradykinin or Ang 1-7. The present review discusses the existing knowledge on the effects of ACE and its inhibitors on RCC cell lines, xenograft models, and patient survival in clinical studies. A brief introduction to molecular pathways aids in understanding the non-cardiovascular effects of RAS inhibitors and enables the conduction of studies on combined cancer treatment with the application of ACEIs. Recent evidence regarding the treatment of hypertension associated with tyrosine kinase inhibitors, one of the most pronounced and common side effects in modern RCC treatment, are also outlined. Captopril, an ACEI, may be used to lower blood pressure in patients, particularly due to its additional renoprotective actions.


Use of trichloroacetic acid for management of oral lesions caused by human papillomavirus.
The human papillomavirus (HPV) has an affinity for squamous cells of stratified keratinized epithelium, thus affecting the lower genital, nasal, and oral tracts. In the oral cavity, HPV is associated with pathoses such as the verruca vulgaris (common wart), squamous cell papilloma, condyloma acuminatum (venereal wart), and focal epithelial hyperplasia (Heck disease). Among the treatments available for these lesions are cryotherapy, electrosurgery, surgical removal, laser therapy, and trichloroacetic acid (TCA). The objective of this research was to determine the behavior of HPV-associated oral pathoses treated with TCA. A prospective cohort study was performed in 20 patients who attended a dental consultation at 2 universities in Cartagena, Colombia. Among the patients, 65% were diagnosed as having focal epithelial hyperplasia, 20% as having verrucae vulgares, and 15% as having condylomata acuminata. Application of TCA to HPV-associated oral lesions proved to be a useful nonsurgical alternative treatment, as the resolution of the lesions was achieved atraumatically in a span of 45 days with 3 applications of 30-60 seconds each.


Ventilatory and cardiovascular actions of centrally administered trout tachykinins in the unanesthetized trout.
The brains of teleost fish contain members of the tachykinin family that are the products of orthologous genes expressed in mammalian nervous tissues, but little is known regarding the physiological effects of these peptides in their species of origin. The present study compares the central actions of trout neuropeptide gamma (NPgamma), substance P (SP) and neurokinin A (NKA) (5-250 pmol) on ventilatory and cardiovascular parameters in the unanesthetized rainbow trout Oncorhynchus mykiss. Intracerebroventricular (ICV) injection of NPgamma evoked a dose-dependent elevation of the ventilation rate (f(V)) but a reduction of the ventilation amplitude (V(AMP)) that was caused by a reduction of the magnitude of the adduction phase of the ventilatory signal. The net effect of NPgamma was to produce an hypoventilatory response since the total ventilation (V(TOT)) was significantly reduced. The minimum effective dose for a significant effect of NPgamma on f(V) and V(AMP) was 50 pmol. SP evoked a significant elevation of f(V), a concomitant depression of V(AMP), and a resultant decrease in V(TOT) but only at the highest dose (250 pmol). NKA was without action on f(V) but significantly decreased V(AMP) at only the highest dose tested. In this case also, the net effect of NKA was to reduce V(TOT). When injected centrally, none of the three peptides, at any dose tested, produced changes in heart rate or mean dorsal aortic blood pressure (P(DA)). Intra-arterial injection of the three tachykinins (250 pmol) produced a significant (P<0.05) increase in P(DA), but only SP and NKA induced concomitant bradycardia. None of the three peptides produced any change in f(V) or V(AMP). In conclusion, our results demonstrate that centrally injected tachykinins, particularly NPgamma, produce a strong hypoventilatory response in a teleost fish and so suggest that endogenous tachykinins may be differentially implicated in neuroregulatory control of ventilation.


Integration of critically appraised topics into evidence-based physical therapist practice.
Physical therapists frequently encounter situations that require complex differential-diagnosis decisions and the ability to consistently screen for serious pathology that may mimic a musculoskeletal complaint. By applying the evidence-based-practice process to diagnosis, screening, and referral, physical therapists can identify diagnostic and screening strategies that positively influence clinical decisions. A critically appraised topic document (a standard 1-page summary of the literature appraisal and clinical relevance in response to a specific clinical question) is a valuable tool in evidence-based practice. The creation of a critically appraised topic makes the educational process cumulative instead of duplicative, allowing the individual clinician to assimilate and consolidate knowledge after a search effort and improving search and appraisal skills. The purpose of this clinical commentary is as follows: (1) to describe the clinical reasoning process of 3 orthopaedic physical therapists that led to the development of specific clinical questions related to screening for nonmusculoskeletal pathology, (2) to describe the search and triage strategy that led each physical therapist to the current best evidence needed to rule out nonmusculoskeletal pathology in the patient, and (3) to discuss the advantages and disadvantages of a critically appraised topic, the implementation of this process, and the tailoring of search strategies to find diagnostic and screening strategies.


Solid-phase extraction of polar organophosphorous pesticides from aqueous samples with oxidized carbon nanotubes.
The development of new sorbents, which are able to trap polar compounds, is a growing research field in solid-phase extraction (SPE). In this study, multi-walled carbon nanotubes (MWCNTs) and single-walled carbon nanotubes (SWCNTs) were oxidized in air at 600 degrees C and 500 degrees C, respectively, for 2 h. MWCNTs, SWCNTs, air oxidized MWCNTs (OMWCNTs) and SWCNTs (OSWCNTs) (200 mg of each) were packed in SPE cartridges. The four cartridges obtained, together with a commercial Oasis HLB cartridge, were used to extract six polar organophosphorous pesticides (OPPs), i.e., dichlorvos, methamidophos, acephate, omethoate, monocrotophos and dimethoate, from an aqueous sample. The results showed that the oxidation process significantly enhanced the adsorption abilities of both SWCNTs and MWCNTs for polar OPPs. A comparative study indicated that OSWCNTs were more effective than Oasis HLB for the extraction of methamidophos and acephate and as effective as Oasis HLB for the other four OPPs from aqueous samples. When 100 mL of a natural sample was spiked with OPPs and extracted with OSWCNTs, the recoveries of five of the six polar OPPs (methamidophos excepted) ranged from 79.1 to 101.9%. The detection limits of the method based on OSWCNTs was found to be 0.07-0.12 microg L(-1).


Lateral shift in photon tunneling studied by the energy streamline method.
The energy streamline method based on the Poynting vector of the coupled forward and backward waves is used to study photon tunneling phenomenon associated with the lateral shift of energy path. Each point on the energy streamline indicates the direction of the net energy flow of a plane wave. In the tunneling configuration, the light energy of the propagating waves is squeezed to the inside of a cone, whereas the streamlines of the coupled evanescent waves go through the barrier inside or outside the cone. This observation provides insight of the photon tunneling phenomenon. A relationship between the energy refraction angle and the incidence angle exists in the proximity limit and can be used to evaluate the lateral shift of the energy path. Furthermore, the energy streamline method can help gain deeper understanding of nanoscale radiation where photon tunneling plays an important role in the heat transfer enhancement.


Fiber Type and Size as Sources of Variation in Human Single Muscle Fiber Passive Elasticity.
Studies on single muscle fiber passive material properties often report relatively large variation in elastic modulus (or normalized stiffness), and it is not clear where this variation arises. This study was designed to determine if the stiffness, normalized to both fiber cross-sectional area and length, is inherently different between types 1 and 2 muscle fibers. Vastus lateralis fibers (n = 93), from ten young men, were mechanically tested using a cumulative stretch-relaxation protocol. SDS-PAGE classified fibers as types 1 or 2. While there was a difference in normalized stiffness between fiber types (p = 0.0019), an unexpected inverse relationship was found between fiber diameter and normalized stiffness (r = -0.64; p < 0.001). As fiber type and diameter are not independent, a one-way analysis of covariance (ANCOVA) including fiber diameter as a covariate was run; this eliminated the effect of fiber type on normalized stiffness (p = 0.1935). To further explore the relationship between fiber size and elastic properties, we tested whether stiffness was linearly related to fiber cross-sectional area, as would be expected for a homogenous material. Passive stiffness was not linearly related to fiber area (p < 0.001), which can occur if single muscle fibers are better represented as composite materials. The rule of mixtures for composite materials was used to explore whether the presence of a stiff perimeter-based fiber component could explain the observed results. The model (R2 = 0.38) predicted a perimeter-based normalized stiffness of 8800 ± 2600 kPa/μm, which is within the range of basement membrane moduli reported in the literature.


Inositol for subfertile women with polycystic ovary syndrome.
Subfertile women are highly motivated to try different adjunctive therapies to have a baby, and the widespread perception is that dietary supplements such as myo-inositol (MI) and D-chiro-insoitol (DCI) are associated with only benefit, and not with harm. Many fertility clinicians currently prescribe MI for subfertile women with polycystic ovary syndrome (PCOS) as pre-treatment to in vitro fertilisation (IVF) or for ovulation induction; however no high-quality evidence is available to support this practice. This review assessed the evidence for the effectiveness of inositol in subfertile women with a diagnosis of PCOS. To evaluate the effectiveness and safety of oral supplementation of inositol for reproductive outcomes among subfertile women with PCOS who are trying to conceive. We searched the following databases (to July 2018): Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and AMED. We also checked reference lists and searched the clinical trials registries. We included randomised controlled trials (RCTs) that compared any type, dose, or combination of oral inositol versus placebo, no treatment/standard treatment, or treatment with another antioxidant, or with a fertility agent, or with another type of inositol, among subfertile women with PCOS. Two review authors independently selected eligible studies, extracted data, and assessed risk of bias. The primary outcomes were live birth and adverse effects; secondary outcomes included clinical pregnancy rates and ovulation rates. We pooled studies using a fixed-effect model, and we calculated odds ratios (ORs) with 95% confidence intervals (CIs). We assessed the overall quality of the evidence by applying GRADE criteria. We included 13 trials involving 1472 subfertile women with PCOS who were receiving myo-inositol as pre-treatment to IVF (11 trials), or during ovulation induction (two trials). These studies compared MI versus placebo, no treatment/standard, melatonin, metformin, clomiphene citrate, or DCI. The evidence was of 'low' to 'very low' quality. The main limitations were serious risk of bias due to poor reporting of methods, inconsistency, and lack of reporting of clinically relevant outcomes such as live birth and adverse events.We are uncertain whether MI improves live birth rates when compared to standard treatment among women undergoing IVF (OR 2.42, 95% CI 0.75 to 7.83; P = 0.14; 2 RCTs; 84 women; I² = 0%). Very low-quality evidence suggests that for subfertile women with PCOS undergoing pre-treatment to IVF who have an expected live birth rate of 12%, the rate among women using MI would be between 9% and 51%.We are uncertain whether MI may be associated with a decrease in miscarriage rate when compared to standard treatment (OR 0.40, 95% CI 0.19 to 0.86; P = 0.02; 4 RCTs; 535 women; I² = 66%; very low-quality evidence). This suggests that among subfertile women with PCOS with an expected miscarriage rate of 9% who are undergoing pre-treatment to IVF, the rate among women using MI would be between 2% and 8%; however this meta-analysis is based primarily on one study, which reported an unusually high miscarriage rate in the control group, and this has resulted in very high heterogeneity. When we removed this trial from the sensitivity analysis, we no longer saw the effect, and we noted no conclusive differences between MI and standard treatment.Low-quality evidence suggests that MI may be associated with little or no difference in multiple pregnancy rates when compared with standard treatment (OR 1.04, 95% CI 0.63 to 1.71; P = 0.89; 2 RCTs; 425 women). This suggests that among subfertile women with PCOS who are undergoing pre-treatment to IVF, with an expected multiple pregnancy rate of 18%, the rate among women using inositol would be between 12% and 27%.We are uncertain whether MI may be associated with an increased clinical pregnancy rate when compared to standard treatment (OR 1.27, 95% CI 0.87 to 1.85; P = 0.22; 4 RCTs; 535 women; I² = 0%; very low-quality evidence). This suggests that among subfertile women with PCOS who are undergoing pre-treatment to IVF, with an expected clinical pregnancy rate of 26%, the rate among women using MI would be between 24% and 40%. Ovulation rates were not reported for this comparison.Other comparisons included only one trial in each, so for the comparisons MI versus antioxidant, MI versus an insulin-sensitising agent, MI versus an ovulation induction agent, and MI versus another DCI, meta-analysis was not possible.No pooled evidence was available for women with PCOS undergoing ovulation induction, as only single trials performed comparison of the insulin-sensitising agent and the ovulation induction agent. In light of available evidence of very low quality, we are uncertain whether MI improves live birth rate or clinical pregnancy rate in subfertile women with PCOS undergoing IVF pre-treatment taking MI compared to standard treatment. We are also uncertain whether MI decreases miscarriage rates or multiple pregnancy rates for these same women taking MI compared to standard treatment. No pooled evidence is available for use of MI versus placebo, another antioxidant, insulin-sensitising agents, ovulation induction agents, or another type of inositol for women with PCOS undergoing pre-treatment to IVF. No pooled evidence is available for use of MI in women undergoing ovulation induction.