Local energy pattern for texture classification using self-adaptive quantization thresholds.
Local energy pattern, a statistical histogram-based representation, is proposed for texture classification. First, we use normalized local-oriented energies to generate local feature vectors, which describe the local structures distinctively and are less sensitive to imaging conditions. Then, each local feature vector is quantized by self-adaptive quantization thresholds determined in the learning stage using histogram specification, and the quantized local feature vector is transformed to a number by N-nary coding, which helps to preserve more structure information during vector quantization. Finally, the frequency histogram is used as the representation feature. The performance is benchmarked by material categorization on KTH-TIPS and KTH-TIPS2-a databases. Our method is compared with typical statistical approaches, such as basic image features, local binary pattern (LBP), local ternary pattern, completed LBP, Weber local descriptor, and VZ algorithms (VZ-MR8 and VZ-Joint). The results show that our method is superior to other methods on the KTH-TIPS2-a database, and achieving competitive performance on the KTH-TIPS database. Furthermore, we extend the representation from static image to dynamic texture, and achieve favorable recognition results on the University of California at Los Angeles (UCLA) dynamic texture database.


Dissecting force interactions in cellulose deconstruction reveals the required solvent versatility for overcoming biomass recalcitrance.
Pretreatment for deconstructing the multifaceted interaction network in crystalline cellulose is a limiting step in making fuels from lignocellulosic biomass. Not soluble in water and most organic solvents, cellulose was found to dissolve in certain classes of ionic liquids (ILs). To elucidate the underlying mechanisms, we simulated cellulose deconstruction by peeling off an 11-residue glucan chain from a cellulose microfibril and computed the free-energy profile in water and in 1-butyl-3-methylimidazolium chloride (BmimCl) IL. For this deconstruction process, the calculated free-energy cost/reduction in water/BmimCl is ∼2 kcal/mol per glucose residue, respectively. To unravel the molecular origin of solvent-induced differences, we devised a coarse graining scheme to dissect force interactions in simulation models by a force-matching method. The results establish that solvent-glucan interactions are dependent on the deconstruction state of cellulose. Water couples to the hydroxyl and side-chain groups of glucose residues more strongly in the peeled-off state but lacks driving forces to interact with sugar rings and linker oxygens. Conversely, BmimCl demonstrates versatility in targeting glucose residues in cellulose. Anions strongly interact with hydroxyl groups, and the coupling of cations to side chains and linker oxygens is stronger in the peeled-off state. Other than enhancing anion-hydroxyl group coupling, coarse-grain analysis of force interactions identifies configuring cations to target side chains and linker oxygens as a useful design strategy for pretreatment ILs. Furthermore, the state dependence of solvent-glucan interactions highlights specific stabilization and/or frustration of the different structure states of cellulose as important design parameters for pretreatment solvents.


Clinical efficacy of chloroquine in young children with uncomplicated falciparum malaria--a community-based study in rural Burkina Faso.
We report on a 14-day study on the efficacy of chloroquine for treating uncomplicated falciparum malaria in young children of a malaria holoendemic area in rural Burkina Faso. In this community-based study, the overall treatment failure rate was 12/120 (10%), with no differences between villages. This supports the evidence for a still sufficient efficacy of chloroquine in north-western Burkina Faso.


Paced activation mapping reveals organization of myocardial fibers: a simulation study.
A three-dimensional bidomain model of a block section of both the right and left ventricular walls that included rotational anisotropy and fiber curvature was used to investigate potential distributions generated during paced activation mapping. Unlike previous large-scale tissue models, the extracellular stimulus was included. The model was used to test the hypothesis that information about the underlying tissue structure (surface fiber angle gradients, amount of fiber rotation per unit depth, and anisotropy) can be extracted from surface potential distributions during stimulation. Results from distributions during stimulation were compared to those obtained using the distributions during activation. To better correlate results to possible experimental measurements, the analysis was performed using a 21 X 21 grid of "electrode" sites, each separated by 1 mm. Fiber orientation was estimated from the surface data by: (1) curve-fitting the elliptical shape of the epicardial potential distribution during stimulation; (2) identifying the location of the potential maxima leading the wavefront during early activation; and (3) for epicardial stimuli, curve-fitting the elliptical shape of the activation isochrones. Results show that surface potential distributions from the stimulus can be used to estimate fiber orientation; however, the accuracy of the reconstruction is highly dependent on the amount of fiber rotation per unit depth. Extracellular potential data during and after stimulation is shown to reflect the organization of myocardial fibers and, as such, could be used to characterize the three-dimensional anisotropic electrical properties in situ.


Surface wettability of plasma SiOx:H nanocoating-induced endothelial cells' migration and the associated FAK-Rho GTPases signalling pathways.
Vascular endothelial cell (EC) adhesion and migration are essential processes in re-endothelialization of implanted biomaterials. There is no clear relationship and mechanism between EC adhesion and migration behaviour on surfaces with varying wettabilities. As model substrates, plasma SiO(x):H nanocoatings with well-controlled surface wettability (with water contact angles in the range of 98.5 ± 2.3° to 26.3 ± 4.0°) were used in this study to investigate the effects of surface wettability on cell adhesion/migration and associated protein expressions in FAK-Rho GTPases signalling pathways. It was found that EC adhesion/migration showed opposite behaviour on the hydrophilic and hydrophobic surfaces (i.e. hydrophobic surfaces promoted EC migration but were anti-adhesions). The number of adherent ECs showed a maximum on hydrophilic surfaces, while cells adhered to hydrophobic surfaces exhibited a tendency for cell migration. The focal adhesion kinase (FAK) inhibitor targeting the Y-397 site of FAK could significantly inhibit cell adhesion/migration, suggesting that EC adhesion and migration on surfaces with different wettabilities involve (p)FAK and its downstream signalling pathways. Western blot results suggested that the FAK-Rho GTPases signalling pathways were correlative to EC migration on hydrophobic plasma SiO(x):H surfaces, but uncertain to hydrophilic surfaces. This work demonstrated that surface wettability could induce cellular behaviours that were associated with different cellular signalling events.


Understanding the effects of universal test and treat on longitudinal HIV care outcomes among South African youth: a retrospective cohort study.
Little is known about the effects of universal test and treat (UTT) policies on HIV care outcomes among youth living with HIV (YLHIV). Moreover, there is a paucity of information regarding when YLHIV are most susceptible to disengagement from care under the newest treatment guidelines. The longitudinal HIV care continuum is an underutilized tool that can provide a holistic understanding of population-level HIV care trajectories and be used to compare treatment outcomes across groups. We aimed to explore effects of the UTT policy on longitudinal outcomes among South African YLHIV and identify temporally precise opportunities for re-engaging this priority population in the UTT era. Using medical record data, we conducted a retrospective cohort study among youth aged 18-24 diagnosed with HIV from August 2015-December 2018 in nine health care facilities in South Africa. We used Fine and Gray sub-distribution proportional hazards models to characterize longitudinal care continuum outcomes in the population overall and stratified by treatment era of diagnosis. We estimated the proportion of individuals in each stage of the continuum over time and the restricted mean time spent in each stage in the first year following diagnosis. Sub-group estimates were compared using differences. A total of 420 YLHIV were included. By day 365 following diagnosis, just 23% of individuals had no 90-or-more-day lapse in care and were virally suppressed. Those diagnosed in the UTT era spent less time as ART-naïve (mean difference=-19.3 days; 95% CI: -27.7, -10.9) and more time virally suppressed (mean difference = 17.7; 95% CI: 1.0, 34.4) compared to those diagnosed pre-UTT. Most individuals who were diagnosed in the UTT era and experienced a 90-or-more-day lapse in care disengaged between diagnosis and linkage to care or ART initiation and viral suppression. Implementation of UTT yielded modest improvements in time spent on ART and virally suppressed among South African YLHIV- however, meeting UNAIDS' 95-95-95 targets remains a challenge. Retention in care and re-engagement interventions that can be implemented between diagnosis and linkage to care and between ART initiation and viral suppression (e.g., longitudinal counseling) may be particularly important to improving care outcomes among South African YLHIV in the UTT era.


Bronchopleural fistula after lower lobectomy of the right lung following thoracic endovascular aortic repair.
A 77-year old male patient was admitted for the treatment of a thoracic aortic aneurysm (TAA) and primary lung cancer. A saccular aneurysm, 4.8 cm in diameter, located in the proximal segment of the descending thoracic aorta and a pulmonary tumour, 3 cm in diameter, located at the right lower lobe, with lymph node swelling, were detected simultaneously. First, a thoracic endovascular aortic repair (TEVAR) was performed for TAA, and then 45 days later, a lobectomy and radical lymph node dissection by open thoracotomy were performed safely for primary lung cancer. The postoperative course was complicated by a bronchopleural fistula (BPF). Massive necrotic changes to the bronchial stump and the intercostal muscle flap were observed during an open window thoracotomy. Both the chronic use of corticosteroids and TEVAR may have been among the predisposing factors for the occurrence of the fistula. The patient died as a result of respiratory failure 68 days after the lobectomy. This is a first case report of a BPF after a staged operation of TEVAR and major lung surgery. We reviewed and discussed the surgical strategy and timing for both the primary lung cancer and the thoracic aortic aneurysm.


Endocytosis sustains release at photoreceptor ribbon synapses by restoring fusion competence.
Endocytosis is an essential process at sites of synaptic release. Not only are synaptic vesicles recycled by endocytosis, but the removal of proteins and lipids by endocytosis is needed to restore release site function at active zones after vesicle fusion. Synaptic exocytosis from vertebrate photoreceptors involves synaptic ribbons that serve to cluster vesicles near the presynaptic membrane. In this study, we hypothesize that this clustering increases the likelihood that exocytosis at one ribbon release site may disrupt release at an adjacent site and therefore that endocytosis may be particularly important for restoring release site competence at photoreceptor ribbon synapses. To test this, we combined optical and electrophysiological techniques in salamander rods. Pharmacological inhibition of dynamin-dependent endocytosis rapidly inhibits release from synaptic ribbons and slows recovery of ribbon-mediated release from paired pulse synaptic depression. Inhibiting endocytosis impairs the ability of second-order horizontal cells to follow rod light responses at frequencies as low as 2 Hz. Inhibition of endocytosis also increases lateral membrane mobility of individual Ca2+ channels, showing that it changes release site structure. Visualization of single synaptic vesicles by total internal reflection fluorescence microscopy reveals that inhibition of endocytosis reduces the likelihood of fusion among vesicles docked near ribbons and increases the likelihood that they will retreat from the membrane without fusion. Vesicle advance toward the membrane is also reduced, but the number of membrane-associated vesicles is not. Endocytosis therefore appears to be more important for restoring later steps in vesicle fusion than for restoring docking. Unlike conventional synapses in which endocytic restoration of release sites is evident only at high frequencies, endocytosis is needed to maintain release from rod ribbon synapses even at modest frequencies.


Diagnosing deep vein thrombosis in cancer patients with suspected symptoms: An individual participant data meta-analysis.
A previous individual participant data (IPD) meta-analysis showed that the Wells rule and D-dimer testing cannot exclude suspected deep vein thrombosis (DVT) in cancer patients. To explore reasons for this reduced diagnostic accuracy and to optimize the diagnostic pathway for cancer patients suspected of DVT. Using IPD from 13 studies in patients with suspected DVT, DVT prevalence and the predictive value of the Wells rule items and D-dimer testing were compared between patients with and without cancer. Next, we developed a prediction model with five variables selected from all available diagnostic predictors. Among the 10 002 suspected DVT patients, there were 834 patients with cancer. The median prevalence of DVT in these patients with cancer was 37.5% (interquartile range [IQR], 30.8-45.5), whereas it was 15.1% (IQR, 11.5-16.7) in patients without cancer. Diagnostic performance of individual Wells rule items and D-dimer testing was similar across patients with and without cancer, except "immobility" and "history of DVT." The newly developed rule showed a pooled c-statistic 0.80 (95% confidence interval [CI], 0.75-0.83) and good calibration. However, using this model, still only 4.3% (95% CI, 3.0-5.7) of the suspected patients with cancer could be identified with a predicted DVT posttest probability of <2%. Likely because of the high prevalence of DVT, clinical models followed by D-dimer testing fail to rule out DVT efficiently in cancer patients suspected of DVT. Direct referral for compression ultrasonography appears to be the preferred approach for diagnosis of suspected DVT in cancer patients.


In-vitro Application of a Qatari Burkholderia cepacia strain (QBC03) in the Biocontrol of Mycotoxigenic Fungi and in the Reduction of Ochratoxin A biosynthesis by Aspergillus carbonarius.
Mycotoxins are secondary metabolites produced by certain filamentous fungi, causing human and animal health issues upon the ingestion of contaminated food and feed. Among the safest approaches to the control of mycotoxigenic fungi and mycotoxin detoxification is the application of microbial biocontrol agents. Burkholderiacepacia is known for producing metabolites active against a broad number of pathogenic fungi. In this study, the antifungal potential of a Qatari strain of Burkholderia cepacia (QBC03) was explored. QBC03 exhibited antifungal activity against a wide range of mycotoxigenic, as well as phytopathogenic, fungal genera and species. The QBC03 culture supernatant significantly inhibited the growth of Aspergillus carbonarius, Fusarium culmorum and Penicillium verrucosum in PDA medium, as well as A. carbonarius and P. verrucosum biomass in PDB medium. The QBC03 culture supernatant was found to dramatically reduce the synthesis of ochratoxin A (OTA) by A. carbonarius, in addition to inducing mycelia malformation. The antifungal activity of QBC03's culture extract was retained following thermal treatment at 100 °C for 30 min. The findings of the present study advocate that QBC03 is a suitable biocontrol agent against toxigenic fungi, due to the inhibitory activity of its thermostable metabolites.


New dammarane-type glycosides from the roots of Gynostemma pentaphyllum.
Twelve new dammarane-type glycosides ( 1- 12) were isolated from the ethanol extract from the roots of a wild-type of Gynostemma pentaphyllum. The structures of the compounds were elucidated by 1D and 2D NMR spectroscopic analysis as well as by chemical degradation. The compounds contained six structurally diverse aglycons similar to those of the reported ginseng saponins with differences in the oligosaccharide moieties.


Two fossil species of Metrosideros (Myrtaceae) from the Oligo-Miocene Golden Fleece locality in Tasmania, Australia.
The capsular-fruited genus Metrosideros (Myrtaceae) is one of the most widely distributed flowering plant genera in the Pacific but is extinct in Australia today. The center of geographic origin for the genus and the reason for and timing of its extinction in Australia remain uncertain. We identify fossil Metrosideros fruits from the newly discovered Golden Fleece fossil flora in the Oligo-Miocene of Tasmania, Australia, shedding further light on these problems. Standard paleopalynological techniques were used to date the fossil-bearing sediments. Scanning electron microscopy and an auto-montage camera system were used to take high-resolution images of fossil and extant fruits taken from herbarium specimens. Fossils are identified using a nearest-living-relative approach. The fossil-bearing sediments are palynostratigraphically dated as being Proteacidites tuberculatus Zone Equivalent (ca. 33-16 Ma) in age and provide a confident Oligo-Miocene age for the macrofossils. Two new fossil species of Metrosideros are described and are here named Metrosideros dawsonii sp. nov. and Metrosideros wrightii sp. nov. These newly described fossil species of Metrosideros provide a second record of the genus in the Cenozoic of Australia, placing them in the late Early Oligocene to late Early Miocene. It is now apparent not only that Metrosideros was present in Australia, where the genus is now extinct, but that at least several Metrosideros species were present during the Cenozoic. These fossils further strengthen the case for an Australian origin of the genus.


Effect of aspirin, warfarin, and proton-pump inhibitors on performance of fecal immunochemical test in colorectal cancer screening: a systematic review and meta-analysis.
This study aims to investigate the impact of antithrombotic agents and proton-pump inhibitors (PPIs) on fecal immunochemical test (FIT). PubMed, EMBASE, Web of Science, Cochrane Central, and Google Scholar were searched from inception until September 3, 2023. Studies comparing the diagnostic performance of FIT between medicine users and non-users in average-risk colorectal cancer screening populations were included. Pooled sensitivity, specificity, and positive predictive values (PPVs) for advanced neoplasia (AN) of FIT were compared by reporting pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a random-effects model. Twenty-two studies enrolling 5,572,367 individuals were included. For aspirin, pooled sensitivity and specificity for AN were 57.2% and 88.4% in users versus 60.2% and 93.2% in non-users; while pooled ORs were 1.49 (95% CI 0.89-2.48, P = 0.13) and 0.72 (95% CI 0.62-0.83, P < 0.001), respectively. In subgroup analysis, there was no difference in sensitivity and specificity between the two groups at the cutoff of 20 μg Hb/g (P = 0.57 and 0.29, respectively) but a significantly lower specificity in users compared with non-users at lower cutoffs (P < 0.001). Moreover, a significantly lower PPVAN in users compared with non-users was observed after matching age and sex confounders (P = 0.001). Warfarin had no significant influence on PPVAN of FIT (P = 0.43). PPIs were associated with a significantly lower PPVAN in users (P < 0.001). Aspirin use was associated with lower specificity and PPV of FIT. Aspirin discontinuation before FIT to reduce false-positive results should be interpreted with caution given concerns about cardiovascular events. Increasing cutoff values of FIT in aspirin users may be another possible approach. Additionally, warfarin withdrawal before FIT is unnecessary but PPIs withdrawal before FIT is recommended to reduce false-positive results.


Ethanol-induced increase in drug acetylation in man and isolated rat liver cells.
Sixteen healthy volunteers took part in a cross-over study examining the effect of ethanol on the rate of sulphadimidine acetylation (blood ethanol concentration about 1 g/1). In both rapid and slow acetylators the apparent half life of the drug decreased by about 20% after ethanol (mean reduction 39 +/- SE 8 min) and the amount of drug acetylated, measured in blood and urine, increased. In three slow acetylators the rate of acetylation in blood increased so noticeably after ethanol that they would otherwise have been classified as rapid acetylators. Suspensions of isolated rat liver cells showed an increase of about 30% in the rate of sulphadimidine acetylation after the addition of ethanol (2 g/1). Patients' usual alcohol consumption should be taken into account in determining their acetylator status.


Linking departmental priorities to knowledge management: the experiences of Santa Cruz County's Human Services Department.
Federal welfare reform, local service collaborations, and the evolution of statewide information systems inspired agency interest in evidence-informed practice and knowledge sharing systems. Four agency leaders, including the Director, Deputy Director, Director of Planning and Evaluation, and Staff Development Program Manager championed the development of a learning organization based on knowledge management throughout the agency. Internal department restructuring helped to strengthen the Planning and Evaluation, Staff Development, and Personnel units, which have become central to supporting knowledge sharing activities. The Four Pillars of Knowledge framework was designed to capture agency directions in relationship to future knowledge management goals. Featuring People, Practice, Technology and Budget, the framework links the agency's services, mission and goals to the process of becoming a learning organization. Built through an iterative process, the framework was created by observing existing activities in each department rather than being designed from the top down. Knowledge management can help the department to fulfill its mission despite reduced resources.


Consensus approach for 3D joint space width of metacarpophalangeal joints of rheumatoid arthritis patients using high-resolution peripheral quantitative computed tomography.
Joint space assessment for rheumatoid arthritis (RA) by ordinal conventional radiographic scales is susceptible to floor and ceiling effects. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides superior resolution, and may detect earlier changes. The goal of this work was to compare existing 3D methods to calculate joint space width (JSW) metrics in human metacarpophalangeal (MCP) joints with HR-pQCT and reach consensus for future studies. Using the consensus method, we established reproducibility with repositioning as well as feasibility for use in second-generation HR-pQCT scanners. Three published JSW methods were compared using datasets from individuals with RA from three research centers. A SPECTRA consensus method was developed to take advantage of strengths of the individual methods. Using the SPECTRA method, reproducibility after repositioning was tested and agreement between scanner generations was also established. When comparing existing JSW methods, excellent agreement was shown for JSW minimum and mean (ICC 0.987-0.996) but not maximum and volume (ICC 0.000-0.897). Differences were identified as variations in volume definitions and algorithmic differences that generated high sensitivity to boundary conditions. The SPECTRA consensus method reduced this sensitivity, demonstrating good scan-rescan reliability (ICC >0.911) except for minimum JSW (ICC 0.656). There was strong agreement between results from first- and second-generation HR-pQCT (ICC >0.833). The SPECTRA consensus method combines unique strengths of three independently-developed algorithms and leverages underlying software updates to provide a mature analysis to measure 3D JSW. This method is robust with respect to repositioning and scanner generations, suggesting its suitability for detecting change.


Proton detection and breathing regulation by the retrotrapezoid nucleus.
We discuss recent evidence which suggests that the principal central respiratory chemoreceptors are located within the retrotrapezoid nucleus (RTN) and that RTN neurons are directly sensitive to [H(+) ]. RTN neurons are glutamatergic. In vitro, their activation by [H(+) ] requires expression of a proton-activated G protein-coupled receptor (GPR4) and a proton-modulated potassium channel (TASK-2) whose transcripts are undetectable in astrocytes and the rest of the lower brainstem respiratory network. The pH response of RTN neurons is modulated by surrounding astrocytes but genetic deletion of RTN neurons or deletion of both GPR4 and TASK-2 virtually eliminates the central respiratory chemoreflex. Thus, although this reflex is regulated by innumerable brain pathways, it seems to operate predominantly by modulating the discharge rate of RTN neurons, and the activation of RTN neurons by hypercapnia may ultimately derive from their intrinsic pH sensitivity. RTN neurons increase lung ventilation by stimulating multiple aspects of breathing simultaneously. They stimulate breathing about equally during quiet wake and non-rapid eye movement (REM) sleep, and to a lesser degree during REM sleep. The activity of RTN neurons is regulated by inhibitory feedback and by excitatory inputs, notably from the carotid bodies. The latter input operates during normo- or hypercapnia but fails to activate RTN neurons under hypocapnic conditions. RTN inhibition probably limits the degree of hyperventilation produced by hypocapnic hypoxia. RTN neurons are also activated by inputs from serotonergic neurons and hypothalamic neurons. The absence of RTN neurons probably underlies the sleep apnoea and lack of chemoreflex that characterize congenital central hypoventilation syndrome.


Internet addiction and psychological well-being among college students: A cross-sectional study from Central India.
Internet provides tremendous educational benefits for college students and also provided better opportunities for communication, information, and social interaction for young adults; however, excessive internet use can lead to negative psychological well-being (PWB). The present study was conducted with the objective to find out the relationship between internet addiction and PWB of college students. A multicenter cross-sectional study was carried out in college students of Jabalpur city of Madhya Pradesh, India. A total of 461 college students, using internet for at least past 6 months were included in this study. Young's Internet addiction scale, consisting of 20-item, based on five-point Likert scale was used to calculate internet addiction scores and 42-item version of the Ryff's PWB scale based on six-point scale was used in this study. A total of 440 questionnaire forms were analyzed. The mean age of students was 19.11 (±1.540) years, and 62.3% were male. Internet addiction was significantly negatively correlated to PWB (r = -0.572, P < 0.01) and subdimensions of PWB. Students with higher levels of internet addiction are more likely to be low in PWB. Simple linear regression showed that internet addiction was a significant negative predictor of PWB. PWB of college students negatively affected by internet addiction. Hence, it is essential to develop strategies for prevention of internet addiction which is very important for promoting PWB of college students.


Calcium absorption across epithelia.
Ca(2+) is an essential ion in all organisms, where it plays a crucial role in processes ranging from the formation and maintenance of the skeleton to the temporal and spatial regulation of neuronal function. The Ca(2+) balance is maintained by the concerted action of three organ systems, including the gastrointestinal tract, bone, and kidney. An adult ingests on average 1 g Ca(2+) daily from which 0.35 g is absorbed in the small intestine by a mechanism that is controlled primarily by the calciotropic hormones. To maintain the Ca(2+) balance, the kidney must excrete the same amount of Ca(2+) that the small intestine absorbs. This is accomplished by a combination of filtration of Ca(2+) across the glomeruli and subsequent reabsorption of the filtered Ca(2+) along the renal tubules. Bone turnover is a continuous process involving both resorption of existing bone and deposition of new bone. The above-mentioned Ca(2+) fluxes are stimulated by the synergistic actions of active vitamin D (1,25-dihydroxyvitamin D(3)) and parathyroid hormone. Until recently, the mechanism by which Ca(2+) enter the absorptive epithelia was unknown. A major breakthrough in completing the molecular details of these pathways was the identification of the epithelial Ca(2+) channel family consisting of two members: TRPV5 and TRPV6. Functional analysis indicated that these Ca(2+) channels constitute the rate-limiting step in Ca(2+)-transporting epithelia. They form the prime target for hormonal control of the active Ca(2+) flux from the intestinal lumen or urine space to the blood compartment. This review describes the characteristics of epithelial Ca(2+) transport in general and highlights in particular the distinctive features and the physiological relevance of the new epithelial Ca(2+) channels accumulating in a comprehensive model for epithelial Ca(2+) absorption.


Programmed Proteolysis of Chemotaxis Proteins in Sinorhizobium meliloti: Features in the C-Terminal Region Control McpU Degradation.
Chemotaxis and motility are important traits that support bacterial survival in various ecological niches and in pathogenic and symbiotic host interaction. Chemotactic stimuli are sensed by chemoreceptors or methyl-accepting chemotaxis proteins (MCPs), which direct the swimming behavior of the bacterial cell. In this study, we present evidence that the cellular abundance of chemoreceptors in the plant symbiont Sinorhizobium meliloti can be altered by the addition of several to as few as one amino acid residues and by including common epitope tags such as 3×FLAG and 6×His at their C termini. To further dissect this phenomenon and its underlying molecular mechanism, we focused on a detailed analysis of the amino acid sensor McpU. Controlled proteolysis is important for the maintenance of an appropriate stoichiometry of chemoreceptors and between chemoreceptors and chemotactic signaling proteins, which is essential for an optimal chemotactic response. We hypothesized that enhanced stability is due to interference with protease binding, thus affecting proteolytic efficacy. Location of the protease recognition site was defined through McpU stability measurements in a series of deletion and amino acid substitution mutants. Deletions in the putative protease recognition site had similar effects on McpU abundance, as did extensions at the C terminus. Our results provide evidence that the programmed proteolysis of chemotaxis proteins in S. meliloti is cell cycle regulated. This posttranslational control, together with regulatory pathways on the transcriptional level, limits the chemotaxis machinery to the early exponential growth phase. Our study identified parallels to cell cycle-dependent processes during asymmetric cell division in Caulobacter crescentusIMPORTANCE The symbiotic bacterium Sinorhizobium meliloti contributes greatly to growth of the agriculturally valuable host plant alfalfa by fixing atmospheric nitrogen. Chemotaxis of S. meliloti cells toward alfalfa roots mediates this symbiosis. The present study establishes programmed proteolysis as a factor in the maintenance of the S. meliloti chemotaxis system. Knowledge about cell cycle-dependent, targeted, and selective proteolysis in S. meliloti is important to understand the molecular mechanisms of maintaining a suitable chemotaxis response. While the role of regulated protein turnover in the cell cycle progression of Caulobacter crescentus is well understood, these pathways are just beginning to be characterized in S. meliloti In addition, our study should alert about the cautionary use of epitope tags for protein quantification.


Beta-blockade prevents recurrent gastrointestinal bleeding in well-compensated patients with alcoholic cirrhosis: a multicenter randomized controlled trial.
To assess the efficacy of beta-blockers in preventing rebleeding in selected cirrhotic patients and to compare the tolerance, safety and patient compliance of a selective and a nonselective beta-blocker, 94 patients were randomly assigned to propranolol (32 patients), atenolol (32 patients) or placebo (30 patients). Randomization was made at least 15 days after the bleeding episode. Propranolol was given orally at increasing doses until the resting pulse rate was reduced by approximately 25%. Atenolol was given at a fixed dose of 100 mg per day. Patients were followed up for a mean of 357 days. Rebleeding occurred in 14 patients in the placebo group, 10 in the atenolol group and eight in the propranolol group. The incidence of rebleeding was significantly lower in patients receiving propranolol than in those on placebo (propranolol vs. placebo: p = 0.01, logrank test). Atenolol was less effective than propranolol (atenolol vs. placebo: p = 0.065, logrank test). Bleeding-free survival was better for patients on active drugs than for those on placebo (propranolol vs. placebo = p = 0.01, atenolol vs. placebo: p = 0.05, logrank test). Retrospective analysis revealed that, whatever the type of treatment, abstinence from alcohol was crucial in preventing rebleeding. We conclude that beta-blocker treatment is effective in preventing rebleeding from esophageal varices in carefully selected alcoholic cirrhotic patients who survive at least 2 weeks after acute variceal hemorrhage and stop drinking.


Alternative bearing couples in total hip replacements: Solutions for young patients.
;There is now considerable clinical concern about the effect of polyethylene wear debris induced osteolysis in long term failure of hip replacements. This paper compares the wear of stabilised and crosslinked polyethylene to alternative hard on hard bearings. The volumetric wear rates of stabilised and moderately crosslinked polyethylene 50 to 35 mm3/million cycles were less than previously reported for historical gamma irradiated in air polyethylene, but still of a level that in the long term could cause osteolysis. The moderately crosslinked polyethylene produced less wear than non-crosslinked polyethylene, but particles were smaller and more reactive resulting in little change in the osteolytic potential. Alumina ceramic on ceramic produced substantially less wear and osteolytic potential. Metal on metal also produced less wear than polyethylene but the particles adversely influence cell viability.


A survey of advancements in nucleic acid-based logic gates and computing for applications in biotechnology and biomedicine.
Nucleic acid-based logic devices were first introduced in 1994. Since then, science has seen the emergence of new logic systems for mimicking mathematical functions, diagnosing disease and even imitating biological systems. The unique features of nucleic acids, such as facile and high-throughput synthesis, Watson-Crick complementary base pairing, and predictable structures, together with the aid of programming design, have led to the widespread applications of nucleic acids (NA) for logic gate and computing in biotechnology and biomedicine. In this feature article, the development of in vitro NA logic systems will be discussed, as well as the expansion of such systems using various input molecules for potential cellular, or even in vivo, applications.


On the frequency-locked orbits of two particles in a paul trap.
Calculations are presented that show frequency-locking to be a prominent phenomenon in the dynamics of two ions in a Paul trap, provided that damping is linear and small. The frequency-locked attractors that exist when dissipation is present correspond to stable, periodic orbits of the underlying Hamiltonian system, which appear to be infinite in number. The accuracy of the calculations is illustrated by comparing an orbit observed in a Paul trap for microspheres with the solution of the equations of motion.


Relative effects of flurbiprofen on platelet 12-hydroxy-eicosatetraenoic acid and thromboxane A2 production: influence on collagen-induced platelet aggregation and adhesion.
Flurbiprofen has been shown to inhibit cyclo-oxygenase metabolism of arachidonic acid to thromboxane A2 (TxA2), resulting in the inhibition of platelet aggregation. Recently, our laboratory reported that the "irreversible" phase of platelet aggregation and adhesion were regulated, in part, by the lipoxygenase metabolism of arachidonic acid to 12-hydroxy-eicosatetraenoic acid (12-HETE) in platelets, and that selective inhibition of one enzyme i.e. either cyclo-oxygenase or lipoxygenase, resulted in paradoxical effects on the metabolism of arachidonic acid and platelet response related to the other pathway. Therefore, we performed experiments to assess the relative effects of flurbiprofen on TxA2 and 12-HETE synthesis, and on collagen-induced platelet aggregation and platelet adhesion to collagen-coated surfaces. "Irreversible" collagen-induced platelet aggregation was only partially inhibited by pre-incubation with 1 x 10(-6) M flurbiprofen, while TxA2 production was elevated and 12-HETE production was maximally inhibited in these platelets. At this concentration of flurbiprofen (1 x 10(-6)M), collagen-induced platelet adhesion was also reduced by 50%. At higher concentrations of flurbiprofen, both platelet aggregation and adhesion were further reduced, with a corresponding inhibition of TxA2 production. Thus it appears that the lipoxygenase pathway of arachidonic acid metabolism in platelets is not only inhibited by flurbiprofen, but is more sensitive to inhibition by flurbiprofen than the cyclo-oxygenase pathway. This differential effect of flurbiprofen on arachidonic acid metabolism in the platelet is related to differential effects on platelet function.


Effects of supervised cardiovascular training program on exercise tolerance, aerobic capacity, and quality of life in patients with systemic lupus erythematosus.
To determine if supervised cardiovascular training improves exercise tolerance, aerobic capacity, depression, functional capacity, and quality of life in patients with systemic lupus erythematosus (SLE). Sixty women with SLE (ages 18-55 years) were evaluated using Short Form 36, visual analog scale for pain, scale for fatigue, Beck Depression Inventory, and Health Assessment Questionnaire (HAQ), and participated in a training protocol of incremental load on a treadmill with computed gas metabolic analysis. Maximum oxygen consumption (VO(2max)) and anaerobic threshold VO(2) were calculated with a SensorMedics Vmax29C analyzer (Sensor Medics, Yorba Linda, CA), and heart rate was measured by electrocardiogram. Patients were divided into 2 groups: a training group (41 patients) that participated in the supervised cardiovascular training program and a control group (19 patients) that did not participate in the program. All variables were analyzed at baseline and after 12 weeks for both groups. The training program occurred in the morning for 60 minutes, 3 times a week for 12 weeks. Statistical analysis included Wilcoxon's rank sum test, Mann-Whitney U test, chi-square test, and Fisher's exact test. P values <0.05 were considered to be statistically significant. The 2 groups were homogeneous and comparable at baseline. The training group showed a significant improvement of aerobic capacity measured by anaerobic threshold VO(2) (14.67 +/- 3.03 versus 17.08 +/- 3.35 ml/kg/minute, P < 0.001). Comparison of the training group and control group after 12 weeks showed a significant difference relating to VO(2max) (24.31 +/- 4.61 versus 21.21 +/- 3.88 ml/kg/minute, P = 0.01) and anaerobic threshold VO(2) (17.08 +/- 3.35 versus 13.66 +/- 2.82 ml/kg/minute, P < 0.0001). After cardiovascular training, we found a significant improvement of Beck inventory score (8.37 +/- 12.79 versus 2.90 +/- 3.00, P < 0.001) and HAQ score (0.14 +/- 0.21 versus 0.06 +/- 0.19, P < 0.01) in the training group. This study showed significant improvement in exercise tolerance, aerobic capacity, quality of life, and depression after a supervised cardiovascular training program in patients with SLE.


A Gd3+-based magnetic resonance imaging contrast agent sensitive to beta-galactosidase activity utilizing a receptor-induced magnetization enhancement (RIME) phenomenon.
Magnetic resonance imaging (MRI) permits noninvasive three-dimensional imaging of opaque organisms. Gadolinium (Gd(3+)) complexes have become important imaging tools as MRI contrast agents for MRI studies, though most of them are nonspecific and report solely on anatomy. Recently, MRI contrast agents have been reported whose ability to relax water protons is triggered or greatly enhanced by recognition of a particular biomolecule. This new class of MRI contrast agents could open up the possibility of reporting on the physiological state or metabolic activity deep within living specimens. One possible strategy for this purpose is to utilize the increase in the longitudinal water proton r(1) relaxivity that occurs upon slowing the molecular rotation of a small paramagnetic complex, a phenomenon which is known as receptor-induced magnetization enhancement (RIME), by either binding to a macromolecule or polymerization of the agent itself. Here we describe the design and synthesis of a novel beta-galactosidase-activated MRI contrast agent, the Gd(3+) complex [Gd-5], by using the RIME approach. beta-Galactosidase is commonly used as a marker gene to monitor gene expression. This newly synthesized compound exhibited a 57% increase in the r(1) relaxivity in phosphate-buffered saline (PBS) with 4.5% w/v human serum albumin (HSA) in the presence of beta-galactosidase. Detailed investigations revealed that RIME is the dominant factor in this increase of the observed r(1) relaxivity, based on analysis of Gd(3+) complexes [Gd-5] and [Gd-8], which is generated from [Gd-5] by the activity of beta-galactosidase, and spectroscopic analysis of their corresponding Tb(3+) complexes, [Tb-5] and [Tb-8].


Operant Behavior during Sleep.
Operant-conditioning techniques were employed to produce organized behavior during sleep as defined by the electroencephalographic record. Patterned responding was found in so-called "light" and "deeper" electroencephalograph stages as well as in the awake record. Results suggest that the use of the electroencephalographic record as a reliable indicator of the sleep-awakefulness continuum be re-examined.


Amsacta moorei entomopoxvirus encodes a functional DNA photolyase (AMV025).
The major damage induced in DNA by ultraviolet light is the induction of cyclobutane pyrimidine dimers (CPDs). Amsacta moorei entomopoxvirus (AMEV) encodes a CPD photolyase (AMV025) with a putative role in converting these dimers back into monomers. In infected Lymantria dispar cells transcription of the AMV025 gene started 8h post inoculation (p.i.) and continued through 38hp.i. Transcription was inhibited by a DNA synthesis blocker. Transient expression in an Escherichia coli strain that lacks its endogenous photolyase, rescued growth of the UV-irradiated bacteria in a light-dependent manner, showing that AMV025 encodes a functional DNA photolyase.


Sex reversal and ontogeny under climate change and chemical pollution: are there interactions between the effects of elevated temperature and a xenoestrogen on early development in agile frogs?
Anthropogenic environmental change poses a special threat to species in which genetic sex determination can be overwritten by the thermal and chemical environment. Endocrine disrupting chemicals as well as extreme temperatures can induce sex reversal in such species, with potentially wide-ranging consequences for fitness, demography, population viability and evolution. Despite accumulating evidence suggesting that chemical and thermal effects may interact in ecological contexts, little is known about their combined effects on sex reversal. Here we assessed the simultaneous effects of high temperature (female-to-male sex-reversing agent) and 17α-ethinylestradiol (EE2), a widespread xenoestrogen (male-to-female sex-reversing agent), on sexual development and fitness-related traits in agile frogs (Rana dalmatina). We exposed tadpoles to a six-days heat wave (30 °C) and/or an ecologically relevant concentration of EE2 (30 ng/L) in one of three consecutive larval periods, and diagnosed sex reversals two months after metamorphosis using species-specific markers for genetic sexing. We found that high temperature induced female-to-male sex reversal, decreased survival, delayed metamorphosis, decreased body mass at metamorphosis, and increased the proportion of animals that had no fat bodies, while EE2 had no effect on these traits. Simultaneous exposure to heat and EE2 had non-additive effects on juvenile body mass, which were dependent on treatment timing and further complicated by a negative effect of sex reversal on body mass. These results show that environmentally relevant exposure to EE2 does not diminish the female-to-male sex-reversing effects of high temperature. Instead, our findings on growth suggest that climate change and chemical pollution may have complex consequences for individual fitness and population persistence in species with environment-sensitive sex determination.


Sustained ventricular fibrillation in an alert patient: preserved hemodynamics with a left ventricular assist device.
Emergency medical services (EMS) encountered an alert patient with sustained ventricular fibrillation with preserved hemodynamics via a left ventricular assist device (LVAD). Multiple firings of the patient's implantable defibrillator were the only sign that this patient was experiencing the usually fatal ventricular arrhythmia. Initial attempts at rhythm conversion with amiodarone and 200-J biphasic shocks were unsuccessful. The patient was finally defibrillated to normal sinus rhythm after a 360-J biphasic shock. This case conference highlights the increasing prevalence of LVADs. These devices are used not only as a bridge to cardiac transplantation, but also as definitive therapy for patients in end-stage cardiac failure. Ventricular fibrillation has been shown to be well tolerated in patients with LVADs, and we discuss a standard of care for these patients. The occurrence of sustained ventricular fibrillation in patients with ventricular assist devices represents a challenging situation for EMS and emergency department providers and one that will be increasingly encountered in the future.


How central are clients in sexual networks created by commercial sex?
Sex workers are traditionally considered important vectors of transmission of sexually transmitted infections (STI). The role of clients is commonly overlooked, partially due to the lack of evidence on clients' position in the sexual network created by commercial sex. Contrasting the diffusion importance of sex workers and their clients in the map of their sexual encounters in twoWeb-mediated communities, we find that from diffusion perspective, clients are as important as sex workers. Their diffusion importance is closely linked to the geography of the sexual encounters: as a result of different movement patterns, travelling clients shorten network distances between distant network neighborhoods and thus facilitate contagion among them more than sex workers, and find themselves more often in the core of the network by which they could contribute to the persistence of STIs in the community. These findings position clients into the set of the key actors and highlight the role of human mobility in the transmission of STIs in commercial sexual networks.


Demographic Representation and Collective Storytelling in the Me Too Twitter Hashtag Activism Movement.
The #MeToo movement on Twitter has drawn attention to the pervasive nature of sexual harassment and violence. While #MeToo has been praised for providing support for self-disclosures of harassment or violence and shifting societal response, it has also been criticized for exemplifying how women of color have been discounted for their historical contributions to and excluded from feminist movements. Through an analysis of over 600,000 tweets from over 256,000 unique users, we examine online #MeToo conversations across gender and racial/ethnic identities and the topics that each demographic emphasized. We found that tweets authored by white women were overrepresented in the movement compared to other demographics, aligning with criticism of unequal representation. We found that intersected identities contributed differing narratives to frame the movement, co-opted the movement to raise visibility in parallel ongoing movements, employed the same hashtags both critically and supportively, and revived and created new hashtags in response to pivotal moments. Notably, tweets authored by black women often expressed emotional support and were critical about differential treatment in the justice system and by police. In comparison, tweets authored by white women and men often highlighted sexual harassment and violence by public figures and weaved in more general political discussions. We discuss the implications of this work for digital activism research and design, including suggestions to raise visibility by those who were under-represented in this hashtag activism movement. Content warning: this article discusses issues of sexual harassment and violence.


[Immunomodulation in cancer. What do we do and where do we go?].
In the last few years we have witnessed a reorientation process in the diagnosis and treatment of cancer, and advances in cancer research point to the need for selective or specific immunomodulation therapies. In this article we remark on generalities of the immune response against tumors, highlighting both: mechanisms that underlie immune evasion by tumors and host defense mechanisms against malignancies. We also discuss current experience with the use of biological response modifiers in cancer and of immunomodulation therapies, in terms of accumulated effectiveness and adverse events of new biological response modifiers. We conclude that therapies with BRMs are hopeful and effective strategies to treat cancer, either alone or in combination with chemotherapy, surgery or radiations. Immunomodulation seem to be one of the most promising therapies for the control of malignant diseases.


Distinguishing Pathovars from Nonpathovars: Escherichia coli.
Escherichia coli is one of the most well-adapted and pathogenically versatile bacterial organisms. It causes a variety of human infections, including gastrointestinal illnesses and extraintestinal infections. It is also part of the intestinal commensal flora of humans and other mammals. Groups of E. coli that cause diarrhea are often described as intestinal pathogenic E. coli (IPEC), while those that cause infections outside of the gut are called extraintestinal pathogenic E. coli (ExPEC). IPEC can cause a variety of diarrheal illnesses as well as extraintestinal syndromes such as hemolytic-uremic syndrome. ExPEC cause urinary tract infections, bloodstream infection, sepsis, and neonatal meningitis. IPEC and ExPEC have thus come to be referred to as pathogenic variants of E. coli or pathovars. While IPEC can be distinguished from commensal E. coli based on their characteristic virulence factors responsible for their associated clinical manifestations, ExPEC cannot be so easily distinguished. IPEC most likely have reservoirs outside of the human intestine but it is unclear if ExPEC represent nothing more than commensal E. coli that breach a sterile barrier to cause extraintestinal infections. This question has become more complicated by the advent of whole genome sequencing (WGS) that has raised a new question about the taxonomic characterization of E. coli based on traditional clinical microbiologic and phylogenetic methods. This review discusses how molecular epidemiologic approaches have been used to address these questions, and how answers to these questions may contribute to our better understanding of the epidemiology of infections caused by E. coli. *This article is part of a curated collection.


AdipoR-increased intracellular ROS promotes cPLA2 and COX-2 expressions via activation of PKC and p300 in adiponectin-stimulated human alveolar type II cells.
Adiponectin, an adipokine, accumulated in lung system via T-cadherin after allergens/ozone challenge. However, the roles of adiponectin on lung pathologies were controversial. Here we reported that adiponectin stimulated expression of inflammatory proteins, cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and production of reactive oxygen species (ROS) in human alveolar type II A549 cells. AdipoR1/2 involved in adiponectin-activated NADPH oxidase and mitochondria, which further promoted intracellular ROS accumulation. Protein kinase C (PKC) may involve an adiponectin-activated NADPH oxidase. Similarly, p300 phosphorylation and histone H4 acetylation occurred in adiponectin-challenged A549 cells. Moreover, adiponectin-upregulated cPLA2 and COX-2 expression was significantly abrogated by ROS scavenger (N-acetylcysteine) or the inhibitors of NADPH oxidase (apocynin), mitochondrial complex I (rotenone), PKC (Ro31-8220, Gö-6976, and rottlerin), and p300 (garcinol). Briefly, we reported that adiponectin stimulated cPLA2 and COX-2 expression via AdipoR1/2-dependent activation of PKC/NADPH oxidase/mitochondria resulting in ROS accumulation, p300 phosphorylation, and histone H4 acetylation. These results suggested that adiponectin promoted lung inflammation, resulting in exacerbation of pulmonary diseases via upregulating cPLA2 and COX-2 expression together with intracellular ROS production. Understanding the adiponectin signaling pathways on regulating cPLA2 and COX-2 may help develop therapeutic strategies on pulmonary diseases.


Epidemiology of nonkeratinocytic skin cancers among persons with AIDS in the United States.
Immunosuppression may increase risk for some skin cancers. We evaluated skin cancer epidemiology among persons with AIDS. We linked data from population-based US AIDS and cancer registries to evaluate risk of nonkeratinocytic skin cancers (melanoma, Merkel cell carcinoma, and appendageal carcinomas, including sebaceous carcinoma) in 497 142 persons with AIDS. Standardized incidence ratios (SIRs) were calculated to relate skin cancer risk to that in the general population. We used logistic regression to compare risk according to demographic factors, CD4 cell count, and a geographic index of ultraviolet radiation exposure. From 60 months before to 60 months after AIDS onset, persons with AIDS had elevated risks of melanoma (SIR = 1.3, 95% confidence interval 1.1-1.4, n = 292 cases) and, more strongly, of Merkel cell carcinoma (SIR = 11, 95% confidence interval 6.3-17, n = 17) and sebaceous carcinoma (SIR = 8.1, 95% confidence interval 3.2-17, n = 7). Risk for appendageal carcinomas increased with progressive time relative to AIDS onset (P trend = 0.03). Risk of these skin cancers was higher in non-Hispanic whites than other racial/ethnic groups, and melanoma risk was highest among men who have sex with men. Melanoma risk was unrelated to CD4 cell count at AIDS onset (P = 0.32). Risks for melanoma and appendageal carcinomas rose with increasing ultraviolet radiation exposure (P trend <10 and P trend = 10, respectively). Among persons with AIDS, there is a modest excess risk of melanoma, which is not strongly related to immunosuppression and may relate to ultraviolet radiation exposure. In contrast, the greatly increased risks for Merkel cell and sebaceous carcinoma suggest an etiologic role for immunosuppression.


Anthroposophic therapy for chronic depression: a four-year prospective cohort study.
Depressive disorders are common, cause considerable disability, and do not always respond to standard therapy (psychotherapy, antidepressants). Anthroposophic treatment for depression differs from ordinary treatment in the use of artistic and physical therapies and special medication. We studied clinical outcomes of anthroposophic therapy for depression. 97 outpatients from 42 medical practices in Germany participated in a prospective cohort study. Patients were aged 20-69 years and were referred to anthroposophic therapies (art, eurythmy movement exercises, or rhythmical massage) or started physician-provided anthroposophic therapy (counselling, medication) for depression: depressed mood, at least two of six further depressive symptoms, minimum duration six months, Center for Epidemiological Studies Depression Scale, German version (CES-D, range 0-60 points) of at least 24 points. Outcomes were CES-D (primary outcome) and SF-36 after 3, 6, 12, 18, 24, and 48 months. Data were collected from July 1998 to March 2005. Median number of art/eurythmy/massage sessions was 14 (interquartile range 12-22), median therapy duration was 137 (91-212) days. All outcomes improved significantly between baseline and all subsequent follow-ups. Improvements from baseline to 12 months were: CES-D from mean (standard deviation) 34.77 (8.21) to 19.55 (13.12) (p < 0.001), SF-36 Mental Component Summary from 26.11 (7.98) to 39.15 (12.08) (p < 0.001), and SF-36 Physical Component Summary from 43.78 (9.46) to 48.79 (9.00) (p < 0.001). All these improvements were maintained until last follow-up. At 12-month follow-up and later, 52%-56% of evaluable patients (35%-42% of all patients) were improved by at least 50% of baseline CES-D scores. CES-D improved similarly in patients not using antidepressants or psychotherapy during the first six study months (55% of patients). In outpatients with chronic depression, anthroposophic therapies were followed by long-term clinical improvement. Although the pre-post design of the present study does not allow for conclusions about comparative effectiveness, study findings suggest that the anthroposophic approach, with its recourse to non-verbal and artistic exercising therapies can be useful for patients motivated for such therapies.


Signals of motor command bias joint position sense in the presence of feedback from proprioceptors.
Joint position sense is believed to be mediated by muscle afferent signals. Because a "phantom" hand produced by a sensory and motor nerve block appears to move in the direction of voluntary effort, signals of "motor command" or "effort" can influence perceived joint position. To determine whether this occurs when sensory signals are available, three studies assessed position sense when motor command and afferent signals were available, but joint movement was prevented. First, the hand was positioned to stop movement at the proximal joint of the middle finger, and movement at the distal joint was impossible because the muscles had been "disengaged". Voluntary efforts produced illusory position changes in the direction of the effort (12.6 +/- 2.0 degrees distal joint; 12.3 +/- 2.3 degrees proximal joint for efforts at 30% maximum; means +/- SD). Second, when subjects attempted to move the index finger under isometric conditions, the index finger appeared to move 7.4 +/- 1.2 degrees in the direction of efforts. These illusions graded with the level of effort (10 or 30% maximum) and far exceeded any real joint movement. Finally, because changes in muscle afferent feedback might have accompanied the voluntary efforts, all forearm and hand muscles were completely paralyzed by locally infused rocuronium. During paralysis, passive wrist position was signaled accurately, but, during attempted efforts (30% maximum), perceived wrist position changed by 9.7 +/- 4.9 degrees . Before paralysis, isometric efforts changed it by 6.7 +/- 3.6 degrees . Thus all studies concur: when joint movement is prevented, signals of motor command contribute to joint position sense.


Characterization and expression of the unique calmodulin gene of Aspergillus nidulans.
Complete cDNA and genomic clones for the unique calmodulin (CaM) gene of the filamentous fungus Aspergillus nidulans have been isolated and characterized. The gene contains five introns, of which three are at unique positions relative to other CaM genes. The A. nidulans CaM gene is transcribed as a single, 0.85-kilobase mRNA species that encodes a predicted protein 84% identical (93% similar if conservative changes are considered) to vertebrate CaM. The complete cDNA was ligated into a lambda PL promoter-regulated bacterial expression vector to allow expression of A. nidulans CaM in Escherichia coli. The expressed protein was purified from bacterial lysates by phenyl-Sepharose chromatography and migrated as a single species on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the presence of Ca2+, A. nidulans CaM exhibited a shift in apparent Mr identical to vertebrate CaM. The bacterially synthesized protein activated vertebrate CaM-dependent phosphodiesterase, CaM-dependent protein kinase II, and myosin light chain kinase with kinetics similar to vertebrate CaM. Isolated conidia (G0 spores) were germinated to induce synchronous cell cycle re-entry and the levels of CaM mRNA and protein determined. Both CaM and its mRNA were regulated during cell cycle re-entry. Calmodulin mRNA levels increased 20-fold as germlings progressed through the G1 phase, while CaM levels increased 2-fold prior to the initiation of DNA synthesis. Messenger RNA levels decreased during S-phase while protein levels increased an additional 2-fold, peaking at the onset of mitosis followed by a subsequent decrease as cells completed mitosis. Disruption of the CaM gene by site-specific homologous recombination was lethal, indicating that CaM is essential for cell cycle progression.


What's under the ROC? An introduction to receiver operating characteristics curves.
It is often necessary to dichotomize a continuous scale to separate respondents into normal and abnormal groups. However, because the distributions of the scores in these 2 groups most often overlap, any cut point that is chosen will result in 2 types of errors: false negatives (that is, abnormal cases judged to be normal) and false positives (that is, normal cases placed in the abnormal group). Changing the cut point will alter the numbers of erroneous judgments but will not eliminate the problem. A technique called receiver operating characteristic (ROC) curves allows us to determine the ability ofa test to discriminate between groups, to choose the optimal cut point, and to compare the performance of 2 or more tests. We discuss how to calculate and compareROC curves and the factors that must be considered in choosing an optimal cut point.


Association Between Mild Cognitive Impairment and Seasonal Rest-Activity Patterns of Older Adults.
Seasonal variation in rest-activity patterns has been observed in healthy adult populations. This study examined seasonal variation in total time spent overnight in the bedroom by cognitively intact older adults and older adults with mild cognitive impairment (MCI). We hypothesize that seasonal variation in rest-activity patterns is observed in the cognitively intact group and that this variation is disturbed in those with MCI. Study participants were 128 older adults; mean age 85.2 years. Ninety-eight were cognitively intact, and 30 had been diagnosed with MCI. All were enrolled in an ongoing longitudinal study using in-home passive monitoring technology. Infrared presence sensors were placed throughout each participant's home to monitor movement and presence in each room of the home. Activity data was collected from the sensors over a period of up to 527 days. Overnight time in bedroom was found to vary seasonally for the cognitively intact group, with longer times spent overnight in the bedroom during the winter months. This seasonal variation was not observed for those with non-amnestic MCI. MCI is associated with an attenuation of seasonal variation in total time spent in the bedroom at night. Detection of changes in infradian sleep patterns may be an early marker of cognitive decline. Which key determinants are driving these disturbed rhythms, such as features intrinsic to changes in the brain or to environmental factors or external cues, remains an important question for ongoing and future studies.


Evaluation of m-T7 agar as a fecal coliform medium.
m-T7 agar, designed to improve recoveries of injured total coliforms, was evaluated for its effectiveness as a fecal coliform medium. The time and temperature of preincubation were found to be crucial to the optimal recovery of fetal coliforms. Isolation rates for fecal coliforms on m-T7 agar from sewage effluents were the highest when plates were preincubated at 37 degrees C for 8 h before transfer to 44.5 degrees C for 12 h. The medium was found to produce consistently higher fecal coliform counts than all the other methods tested. Recoveries were 3.1 times greater than the standard m-FC method and 1.7 times greater than the two-layer enrichment, temperature acclimation procedure. Verification rates for fecal coliforms isolated on m-T7 agar averaged 89.0%, whereas verification rates for m-FC agar averaged only 82.8%. Both media isolated similar fecal coliform populations. The advantages of a single medium, highly effective for the isolation of both total and fecal coliforms, are discussed.


A fully 3D small PET scanner.
A fully 3D small PET scanner based on a novel detection principle for gamma rays is described. It uses BaF2 scintillator and photosensitive wire chambers. Extensive tests with technical prototypes have shown that such a system will have a detection efficiency for gamma rays comparable with what can be obtained with the more traditional approach, and a spatial resolution determined by the size of the crystals. The expected performances of the scanner, based on our measurements and on simulations, are given.


Depression and health-related quality of life after discharge and associated factors in childhood cancer patients in Japan.
We identified the prevalence of depression and quality of life (QOL) of Japanese children with childhood cancer after discharge using the Birleson Depression Self-rating Scale for Children (DSRS-C) and the Pediatric Quality of Life Inventory (PedsQL). Subjects were 118 caregivers who raised children ages 2-18 with childhood cancer; subjects resided in suburban districts of Japan and completed instruments after their children were discharged. Multiple regression analysis of data collected from 105 respondents revealed that lower PedsQL scores correlated with more problems in life at school and at home, an increased frequency of hospital visits, less cooperation within the family, and higher DSRS-C scores. To ensure the QOL of children with childhood cancer, outpatient nurses need to encourage children to psychosocially adapt after discharge, periodically screen children during outpatient treatment using instruments such as the DSRS-C, and conduct preventive interventions for children who meet screening criteria and their families before they suffer from adaptation disorders and offer multilateral psychosocial assistance in cooperation with a multidisciplinary care team.


Cyber security threats: A never-ending challenge for e-commerce.
This study explores the challenge of cyber security threats that e-commerce technology and business are facing. Technology applications for e-commerce are attracting attention from both academia and industry. It has made what was not possible before for the business community and consumers. But it did not come all alone but has brought some challenges, and cyber security challenge is one of them. Cyber security concerns have many forms, but this study focuses on social engineering, denial of services, malware, and attacks on personal data. Firms worldwide spend a lot on addressing cybersecurity issues, which grow each year. However, it seems complicated to overcome the challenge because the attackers continuously search for new vulnerabilities in humans, organizations, and technology. This paper is based on the conceptual analysis of social engineering, denial of services, malware, and attacks on personal data. We argue that implementing modern technology for e-commerce and cybersecurity issues is a never-ending game of cat and mouse. To reduce risks, reliable technology is needed, training of employees and consumer is necessary for using the technology, and a strong policy and regulation is needed at the firm and governmental level.


Sprayable Foams Based on an Amphiphilic Biopolymer for Control of Hemorrhage Without Compression.
Hemorrhage (severe blood loss) from traumatic injury is a leading cause of death for soldiers in combat and for young civilians. In some cases, hemorrhage can be stopped by applying compression of a tourniquet or bandage at the injury site. However, the majority of hemorrhages that prove fatal are "non-compressible", such as those due to an internal injury in the truncal region. Currently, there is no effective way to treat such injuries. In this initial study, we demonstrate that a sprayable polymer-based foam can be effective at treating bleeding from soft tissue without the need for compression. When the foam is sprayed into an open cavity created by injury, it expands and forms a self-supporting barrier that counteracts the expulsion of blood from the cavity. The active material in this foam is the amphiphilic biopolymer, hydrophobically modified chitosan (hmC), which physically connects blood cells into clusters via hydrophobic interactions (the hemostatic mechanism of hmC is thus distinct from the natural clotting cascade, and it works even with heparinized or citrated blood). The amphiphilic nature of hmC also allows it to serve as a stabilizer for the bubbles in the foam. We tested the hmC-based hemostatic foam for its ability to arrest bleeding from an injury to the liver in pigs. Hemostasis was achieved within minutes after application of the hmC foams (without the need for external compression). The total blood loss was 90% lower with the hmC foam relative to controls.


Invasive infections caused by Trichosporon species and Geotrichum capitatum in patients with hematological malignancies: a retrospective multicenter study from Italy and review of the literature.
Trichosporonosis is an uncommon but frequently fatal mycosis in immunocompromised patients. A multicenter retrospective study was conducted to characterize cases of proven or probable invasive trichosporonosis diagnosed over the past 20 years in Italian patients with hematological diseases. Of the 52 cases identified, 17 were classified as Trichosporon sp. infections and 35 were attributed to Geotrichum capitatum. Acute myeloid leukemia accounted for 65.4% of the cases. The incidence rates of Trichosporon sp. and G. capitatum infections in acute leukemia patients were 0.4 and 0.5%, respectively. Overall, 76.9% of cases had positive blood cultures. Pulmonary involvement was documented in 26.9% of cases. Death was reported for 57.1% of G. capitatum infections and for 64.7% of Trichosporon sp. infections. A literature review on trichosporonosis in patients with any underlying disease or condition reveals G. capitatum as a predominantly European pathogen, particularly in certain Mediterranean areas, while Trichosporon sp. infections are seen with similar frequencies on all continents. The majority of published Trichosporon sp. and G. capitatum infections occurred in patients with hematological diseases (62.8 and 91.7%, respectively). Well over half of these were suffering from acute leukemia (68 and 84% of patients with Trichosporon sp. and G. capitatum infections, respectively). Crude mortality rates were 77% for Trichosporon spp. and 55.7% for G. capitatum. The optimal therapy for trichosporonosis has yet to be identified; however, in vitro experiences are providing encouraging evidence of the potential role of the new triazoles, in particular, voriconazole.


Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study.
To determine whether the addition of ifosfamide to cisplatin plus etoposide improves the response rate, time to disease progression, or overall survival in previously untreated patients with extensive-stage small-cell carcinoma of the lung (SCLC). Patients with extensive SCLC with a Karnofsky performance score (KPS) > or = 50 and adequate renal function and bone marrow reserve were eligible. Patients with CNS metastases were eligible and received concurrent whole-brain radiotherapy. Patients were randomized to receive cisplatin (20 mg/m2) plus etoposide (100 mg/m2) (VP) both given intravenously (i.v.) on days 1 to 4 or cisplatin (20 mg/m2), ifosfamide (1.2 g/m2), and etoposide (75 mg/m2) (VIP) all given i.v. on days 1 to 4. Cycles were repeated every 3 weeks for four cycles. From May 1989 through March 1993, 171 patients were randomized (84 to VP and 87 to VIP). The median follow-up duration is 26 months. All patients were assessable for survival; 163 were fully assessable for response and 162 for toxicity. Myelosuppression was greater with VIP. Objective responses were observed in 55 of 82 (67%) and 59 of 81 (73%) assessable patients treated with VP and VIP, respectively (difference not significant). The difference in the median time to progression was statistically different (P = .039). The median survival times on VP and VIP were 7.3 months and 9.0 months, respectively (P = .045 for survival curves by stratified log-rank test) with 2-year survival rates of 5% versus 13%, respectively. VIP combination chemotherapy is associated with an improved time to progression and overall survival over VP therapy in patients with extensive SCLC.


An essential role for Pin1 in Xenopus laevis embryonic development revealed by specific inhibitors.
The peptidyl prolyl cis/trans isomerase (PPIase) Pin1 plays an important role in phosphorylation-dependent events of the cell cycle. This function is linked to its display of two phosphothreonine/phosphoserine-proline binding motifs, one within the type IV WW domain and a second within the parvulin-like catalytic domain. By microinjection of the compound Ac-Phe-D-Thr(PO3H2)-Pip-Nal-Gln-NH2, which inhibits Xenopus laevis Pin1 with a Ki value of 19.4+/-1.5 nM, into the animal pole of X. laevis embryos at the two-cell stage, the impact of Pin1 PPIase activity on cell cycle progression and embryonic development could be analysed, independent of WW domain-mediated phosphoprotein binding. Injected embryos showed a dramatically decreased survival rate at late stages of development that could only be partially compensated by co-injection with mRNAs of enzymatically active Pin1 variants, demonstrating that the phosphorylation-specific PPIase activity of Pin1 is essential for cell division and development in X. laevis.


Soybean phytoestrogen intake and cancer risk.
Because many Western diseases are hormone-dependent cancers, we have postulated that the Western diet, compared with a vegetarian or semi-vegetarian diet, may alter hormone production, metabolism or action at the cellular level. Recently, our interest has been focused on the cancer-protective role of some hormone-like diphenolic phytoestrogens of dietary origin, the lignans and isoflavonoids. The precursors of the biologically active compounds originate in soybean products (mainly isoflavonoids but also lignans), as well as whole grain cereals, seeds, probably berries and nuts (mainly lignans). The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormone-like compounds with weak estrogenic and antioxidative activity; they have now been shown to influence not only sex hormone metabolism and biological activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation and angiogenesis, making them strong candidates for a role as natural cancer protective compounds. Epidemiological investigations support this hypothesis, because the highest levels of these compounds are found in countries or regions with low cancer incidence. This report is a review of results that suggest that the diphenolic isoflavonoids and lignans are natural cancer-protective compounds.


Selective Deletion of the Mechanistic Target of Rapamycin From the Renal Collecting Duct Principal Cell in Mice Down-Regulates the Epithelial Sodium Channel.
The mechanistic target of rapamycin (mTOR), a serine-threonine-specific kinase, is a cellular energy sensor, integrating growth factor and nutrient signaling. In the collecting duct (CD) of the kidney, the epithelial sodium channel (ENaC) essential in the determination of final urine Na+ losses, has been demonstrated to be upregulated by mTOR, using cell culture and mTOR inhibition in ex vivo preparations. We tested whether CD-principal cell (PC) targeted deletion of mTOR using Cre-lox recombination would affect whole-body sodium homeostasis, blood pressure, and ENaC regulation in mice. Male and female CD-PC mTOR knockout (KO) mice and wild-type (WT) littermates (Cre-negative) were generated using aquaporin-2 (AQP2) promoter to drive Cre-recombinase. Under basal conditions, KO mice showed a reduced (∼30%) natriuretic response to benzamil (ENaC) antagonist, suggesting reduced in vivo ENaC activity. WT and KO mice were fed normal sodium (NS, 0.45% Na+) or a very low Na+ (LS, <0.02%) diet for 7-days. Switching from NS to LS resulted in significantly higher urine sodium losses (relative to WT) in the KO with adaptation occurring by day 2. Blood pressures were modestly (∼5-10 mm Hg) but significantly lower in KO mice under both diets. Western blotting showed KO mice had 20-40% reduced protein levels of all three subunits of ENaC under LS or NS diet. Immunohistochemistry (IHC) of kidney showed enhanced apical-vs.-cellular localization of all three subunits with LS, but a reduction in this ratio for γ-ENaC in the KO. Furthermore, the KO kidneys showed increased ubiquitination of α-ENaC and reduced phosphorylation of the serum and glucocorticoid regulated kinase, type 1 [serum glucocorticoid regulated kinase (SGK1)] on serine 422 (mTOR phosphorylation site). Taken together this suggests enhanced degradation as a consequence of reduced mTOR kinase activity and downstream upregulation of ubiquitination may have accounted for the reduction at least in α-ENaC. Overall, our data support a role for mTOR in ENaC activity likely via regulation of SGK1, ubiquitination, ENaC channel turnover and apical membrane residency. These data support a role for mTOR in the collecting duct in the maintenance of body sodium homeostasis.


Endobronchial adenomata in children.
Two cases of carcinoid adenomata of the bronchus in children are added to 25 previously reported cases of bronchial adenomata in children in the literature. Carcinoid tumors represent close to 50 per cent of bronchial adenomata in children, with cylindromas (adenoid cystic) forming 13 per cent and mucoepidermoids two per cent. Over 1/3 of bronchial adenomata have metastases at the time of diagnosis. No cases of carcinoid syndrome have been reported in children. The treatment of choice is lobectomy with sleeve resection or, failing that, pulmonary resection. The overall five-year survival time varies from 50 to 80 per cent and is enhanced by surgical resection.


Medicinal plants used by Tibetans in Shangri-la, Yunnan, China.
Medicinal plants used by the local people in Xizang (Tibet) have been investigated since the 1960s. The others out of Xizang, however, have been less understood, although they may be easily and strongly influenced by the various local herbal practices, diverse environments, local religious beliefs and different prevalent types of diseases. In 2006, two ethnobotanical surveys were organized in the county of Shangri-la, Yunnan Province, SW China, to document the traditional medicinal plants used by the Tibetan people. After literature surveying, four local townships were selected to carry out the field investigation. Three local healers were interviewed as key informants. The methods of ethnobotany, anthropology and participatory rural appraisal (PRA) were used in the field surveys. Plant taxonomic approach was adopted for voucher specimen identification. Sixty-eight medicinal plant species in 64 genera of 40 families were recorded and collected. Among them, 23 species were found to have medicinal values that have not been recorded in any existing Tibetan literatures before, and 31 species were recorded to have traditional prescriptions. Moreover, the traditional preparations of each species and some folk medicinal knowledge were recorded and analyzed. These traditional prescriptions, preparations, new medicinal plants and folk medicinal knowledge and principles were discovered and summarized by local traditional Tibetan healers through times of treatment practices, and were passed down from generation to generation. As a part of the cultural diversity of Tibetan community, these traditional medicinal knowledge and experiences may provide data and information basis for the sustainable utilization and development of Tibetan medicine, and may contribute to the local economic development. However, for many reasons, they are disappearing gradually as time goes by. Our study showed that there were abundant traditional Tibetan medicinal prescriptions and using methods. It implies that more Tibetan medicinal plants and traditional knowledge can be discovered. Further research should be done to save the wealth of these traditional medicinal knowledge and experiences before they are dying out.


Hospice care and resource utilization in Medicare beneficiaries with heart failure.
Although hospice use may be increasing among heart failure patients, its association with both cost and intensity of care in this population has not been well examined. To assess the association of hospice care with resource utilization among a national sample of Medicare beneficiaries with heart failure during the last 6 months of life. We performed a cross-sectional analysis of the 5% sample of Medicare claims data. Negative binomial regression models were used to compare expenditures, hospitalization rates, and intensive care unit (ICU) days between hospice and nonhospice beneficiaries. We used Poisson regression models to compare utilization of certain procedures between hospice and nonhospice beneficiaries. Among 16613 Medicare beneficiaries who died with heart failure in 2007, 6436 (38.7%) received hospice care during the last 6 months of life. The mean total medical expenditures were $31,793 (SD 25,691) among decedents with hospice care, in comparison to $34,067 (SD 40,561) among decedents without hospice care. However, after adjustments for covariates, hospice care was associated with 4% higher expenditures (cost ratio, 1.04; 95% confidence interval, CI: 1.01-1.07). Hospice use was associated with reduced hospitalizations (adjusted incidence rate ratio, 0.87, 95% CI: 0.84-0.89), ICU days (adjusted incidence rate ratio, 0.68, 95% CI: 0.63-0.73), and procedures, including cardiac catheterization, noninvasive ventilation, and mechanical ventilation. Despite lower rates of hospitalization, ICU days, and invasive procedures, hospice care was not associated with reduced expenditures in heart failure. Financial savings related to reduced intensive medical care seems to be offset by the expenditures related to hospice care itself.


Experimental study of chuanxiong on cerebrovascular hemodynamic parameters.
In the experimental rabbit arteriosclerosis, the change of the cerebrovascular hemodynamic parameters (CVHP) and the effect of Chuanxiong (CX) on CVHP were observed. In arteriosclerosis group (AS group), the mean flow (Qmean), mean velocity (Vmean), maximal velocity (Vmax) and minimal velocity (Vmin) of the carotid blood flow and cerebrovascular compliance for zero pressure (CO) were significantly decreased (P < 0.05, 0.01), but the values of cerebrovascular peripheral resistance (R) and characteristic impedance (Zc) were significantly increased (P < 0.05 and 0.01), and the value of R showed significant positive correlation with the extent of carotid lesions (P < 0.01). All indexes of CVHP of the Chuanxiong group (CX group) were close to and had no significant difference from those of the normal group (N group) but Qmean, Vmean, Vmin, CO and R were significantly better than those of the AS group (P < 0.05, 0.01). These results showed that CX can effectively improve cerebrovascular hemodynamics.


[Food consumption surveillance].
This paper analyzes the importance of food consumption surveillance; as food consumption is determined by multiple factors, the difficulties involved in this process are established. Some direct methods used for food consumption assessment and other indirect methods that can be used to infer it, are analyzed and discussed in terms of their advantages and disadvantages. Other methods based on the follow up of food basket cost and purchasing capacity of poor population wages in terms of some selected food commodities, are proposed. The importance of food consumption surveillance as an instrument for decision making is pointed out.


A Systematic Review of Neuromodulation Treatment Effects on Suicidality.
Introduction: Neuromodulation is an important group of therapeutic modalities for neuropsychiatric disorders. Prior studies have focused on efficacy and adverse events associated with neuromodulation. Less is known regarding the influence of neuromodulation treatments on suicidality. This systematic review sought to examine the effects of various neuromodulation techniques on suicidality. Methods: A systematic review of the literature from 1940 to 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was conducted. Any reported suicide-related outcome, including suicidal ideation, suicide intent, suicide attempt, completed suicide in reports were considered as a putative measure of treatment effect on suicidality. Results: The review identified 129 relevant studies. An exploratory analysis of a randomized controlled trial comparing the effects of sertraline and transcranial direct-current stimulation (tDCS) for treating depression reported a decrease in suicidal ideation favoring tDCS vs. placebo and tDCS combined with sertraline vs. placebo. Several studies reported an association between repetitive transcranial magnetic stimulation and improvements in suicidal ideation. In 12 of the studies, suicidality was the primary outcome, ten of which showed a significant improvement in suicidal ideation. Electroconvulsive therapy (ECT) and magnetic seizure therapy was also shown to be associated with lower suicidal ideation and completed suicide rates. There were 11 studies which suicidality was the primary outcome and seven of these showed an improvement in suicidal ideation or suicide intent and fewer suicide attempts or completed suicides in patients treated with ECT. There was limited literature focused on the potential protective effect of vagal nerve stimulation with respect to suicidal ideation. Data were mixed regarding the potential effects of deep brain stimulation on suicidality. Conclusions: Future prospective studies of neuromodulation that focus on the primary outcome of suicidality are urgently needed. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=125599, identifier: CRD42019125599.


Surface plasmon resonance study of the interaction of N-methyl mesoporphyrin IX with G-quadruplex DNA.
Surface plasmon resonance (SPR) was used to investigate the interaction between N-methyl mesoporphyrin IX (NMM) and different G-quadruplex (G4) topologies. The study was associated with circular dichroism analysis (CD) to assess the topology of the G4s when they interacted with NMM. We demonstrate the high selectivity of NMM for the parallel G4 structure with a dissociation constant at least ten times lower than those of other G4 topologies. We also confirm the ability of NMM to shift the G4 conformation from both the hybrid and antiparallel topologies toward the parallel structure.


Flow Arrest in the Plasma Membrane.
The arrangement of receptors in the plasma membrane strongly affects the ability of a cell to sense its environment both in terms of sensitivity and in terms of spatial resolution. The spatial and temporal arrangement of the receptors is affected in turn by the mechanical properties and the structure of the cell membrane. Here, we focus on characterizing the flow of the membrane in response to the motion of a protein embedded in it. We do so by measuring the correlated diffusion of extracellularly tagged transmembrane neurotrophin receptors TrkB and p75 on transfected neuronal cells. In accord with previous reports, we find that the motion of single receptors exhibits transient confinement to submicron domains. We confirm predictions based on hydrodynamics of fluid membranes, finding long-range correlations in the motion of the receptors in the plasma membrane. However, we discover that these correlations do not persist for long ranges, as predicted, but decay exponentially, with a typical decay length on the scale of the average confining domain size.


Virtual endoscopy for planning and simulation of minimally invasive neurosurgery.
This article demonstrates the usefulness and the problems of present-state software for virtual endoscopy as a tool for the planning and simulation of minimally invasive neurosurgical procedures. The software Navigator (General Electric Medical Systems, Buc, France) was applied for virtual endoscopic visualization of three-dimensional magnetic resonance data sets of healthy volunteers and neurosurgical patients, using a clinical magnetic resonance scanner (1.5-T Signa Hispeed; General Electric Medical Systems). Classical approaches for minimally invasive procedures were simulated. Virtual endoscopy provided impressive three-dimensional views of intracranial and intracerebral cavities, with visualization of many anatomic details of the brain's inner and outer surfaces. The method proved to be especially suited for the simulation and planning of operations of intraventricular lesions, for which the technical limitations of the present state of development of this method have fewer implications. However, the present state of technology, as described in this article, has two major shortcomings: 1) the blood vessels cannot be visualized together with the brain tissue and cranial nerves; and 2) different tissue compartments cannot be stained in their original coloring, which would facilitate their recognition and thus orientation in space by anatomic landmarks. Another important disadvantage at this stage is time consumption for many single working steps. Virtual endoscopy is a promising tool for teaching and training in intracranial neuroanatomy as well as for planning and simulation of minimally invasive (e.g., endoscopic), mainly intraventricular, operations. Direct clinical application is, at this stage of development, limited by several technical shortcomings of visualization and quantification of distances and modeling of surfaces.


Oncologists' attitudes toward and practices in giving bad news: an exploratory study.
To examine the attitudes and practices of oncologists in disclosure of unfavorable medical information to cancer patients. A questionnaire was administered to a group of physicians who attended the 1999 Annual Meeting of the American Society of Clinical Oncology. The questionnaire assessed demographic and practice-related information and the frequency of patient encounters in which unfavorable cancer-related information was disclosed. Participants were also asked about difficulties they had when approaching stressful discussions and communication strategies used in giving unfavorable information. The questionnaire was completed by 167 oncologists. Sixty-four percent were medical oncologists. Thirty-eight percent practiced in North America, 26% practiced in Europe, 13% practiced in South America, and 13% practiced in Asia. Participants gave bad news to patients an average of 35 times per month. Discussing no further curative treatment and hospice was reported as most difficult. In disclosing the cancer diagnosis and prognosis, physicians from Western countries were less likely to withhold unfavorable information from the patient at the family's request, avoid the discussion entirely, use euphemisms, and give treatments known not to be effective so as not to destroy hope than physicians from other countries. There was significant variability in opinions regarding the best time to discuss resuscitation, with 18% of respondents believing that it should be done close to the end of life. There was significant variability in how physicians approach information disclosure to cancer patients. Factors such as geographical region and cultural and family variables may be important influences in this process.


The Rapid Evaluation of COVID-19 Vaccination in Emergency Departments for Underserved Patients Study.
Emergency departments (EDs) often serve vulnerable populations who may lack primary care and have suffered disproportionate COVID-19 pandemic effects. Comparing patients having and lacking a regular source of medical care and other ED patient characteristics, we assessed COVID-19 vaccine hesitancy, reasons for not wanting the vaccine, perceived access to vaccine sites, and willingness to get the vaccine as part of ED care. This was a cross-sectional survey conducted from December 10, 2020, to March 7, 2021, at 15 safety net US EDs. Primary outcomes were COVID-19 vaccine hesitancy, reasons for vaccine hesitancy, and sites (including EDs) for potential COVID-19 vaccine receipt. Of 2,575 patients approached, 2,301 (89.4%) participated. Of the 18.4% of respondents who lacked a regular source of medical care, 65% used the ED as their usual source of health care. The overall rate of vaccine hesitancy was 39%; the range among the 15 sites was 28% to 58%. Respondents who lacked a regular source of medical care were more commonly vaccine hesitant than those who had a regular source of medical care (47% versus 38%, 9% difference, 95% confidence interval 4% to 14%). Other characteristics associated with greater vaccine hesitancy were younger age, female sex, Black race, Latinx ethnicity, and not having received an influenza vaccine in the past 5 years. Of the 61% who would accept a COVID-19 vaccine, 21% stated that they lacked a primary physician or clinic at which to receive it; the vast majority (95%) of these respondents would accept the COVID-19 vaccine as part of their care in the ED. ED patients who lack a regular source of medical care are particularly hesitant regarding COVID-19 vaccination. Most COVID-19 vaccine acceptors would accept it as part of their care in the ED. EDs may play pivotal roles in COVID-19 vaccine messaging and delivery to highly vulnerable populations.


Spirulina Extract Enhanced a Protective Effect in Type 1 Diabetes by Anti-Apoptosis and Anti-ROS Production.
Interest in the nutritional value and pharmacological activities of blue-green algae has gradually increased. Spirulina extracts show protective effects against apoptosis and inflammatory damage in various cell types. Here, we investigated the protective effects of extracts from Spirulina maxima in a cytokine-mediated type 1 diabetes model in vitro and in streptozotocin-induced diabetic Wistar rats in vivo. Interleukin-1β and interferon-gamma induced substantial cytotoxicity to RINm5F rat insulinoma cells, increasing nitric oxide (NO) production, nuclear factor-kappa B (NF-κB) activity, the expression of endoplasmic reticulum (ER) stress genes, and activation of mitogen-activated protein kinases and key genes related apoptosis. However, the cytotoxicity of cytokines was significantly attenuated by Spirulina extract, which effectively prevented NO production by inhibiting the synthesis of cytokine-activated NO synthase (iNOS), and apoptosis was suppressed. These results suggest that Spirulina extract might be effective to preserve the viability and function of pancreatic β-cells against cytotoxic conditions. Moreover, diabetic mice orally administered Spirulina extract showed decreased glucose levels, increased insulin, and improvement in liver enzyme markers. The antioxidant effect of Spirulina extract may be helpful in treating type 1 diabetes by enhancing the survival, and reducing or delaying cytokine-mediated β-cells destruction.


The cognitive underpinnings of effective teamwork: a meta-analysis.
Major theories of team effectiveness position emergent collective cognitive processes as central drivers of team performance. We meta-analytically cumulated 231 correlations culled from 65 independent studies of team cognition and its relations to teamwork processes, motivational states, and performance outcomes. We examined both broad relationships among cognition, behavior, motivation, and performance, as well as 3 underpinnings of team cognition as potential moderators of these relationships. Findings reveal there is indeed a cognitive foundation to teamwork; team cognition has strong positive relationships to team behavioral process, motivational states, and team performance. Meta-analytic regressions further indicate that team cognition explains significant incremental variance in team performance after the effects of behavioral and motivational dynamics have been controlled. The nature of emergence, form of cognition, and content of cognition moderate relationships among cognition, process, and performance, as do task interdependence and team type. Taken together, these findings not only cumulate extant research on team cognition but also provide a new interpretation of the impact of underlying dimensions of cognition as a way to frame and extend future research.