Proctosigmoidoscopy and rectal biopsy in infants and children.
The medical records of all patients ages 0 to 21 years who underwent proctosigmoidoscopy and/or rectal biopsy over a 27 month period of time were reviewed to determine the efficacy and safety of these procedures in pediatric patients. One hundred twenty-one patients underwent proctosigmoidoscopy; 91 of these also had rectal biopsies. Median age was two years; 21% were less than six months and 8% less than one month of age. Depth of examination was 10 to 15 cm in most patients greater than 10 years of age. Induced friability was the most frequently observed mucosal abnormality. Abnormal findings were almost always present in patients with bloody diarrhea and were quite common in those with rectal bleeding, but less common in those with chronic diarrhea and abdominal pain. Colitis of various causes was the most common cause of blood in the stool; anal fissures were found in only four of 23 patients with rectal bleeding. Both proctosigmoidoscopy and rectal biopsy were needed to exclude the presence of colitis. Mobidity was 0% with proctosigmoidoscopy and 0.34% with rectal suction biopsy.


A Bayesian extreme value theory modelling framework to assess corridor-wide pedestrian safety using autonomous vehicle sensor data.
Pedestrians are a vulnerable road user group, and their crashes are generally spread across the network rather than in a concentrated location. As such, understanding and modelling pedestrian crash risk at a corridor level becomes paramount. Studies on pedestrian crash risks, particularly with the traffic conflict data, are limited to single or multiple but scattered intersections. A lack of proper modelling techniques and the difficulties in capturing pedestrian interaction at the network or corridor level are two main challenges in this regard. With autonomous vehicles trialled on public roads generating massive (and unprecedented) datasets, utilising such rich information for corridor-wide safety analysis is somewhat limited where it appears to be most relevant. This study proposes an extreme value theory modelling framework to estimate corridor-wide pedestrian crash risk using autonomous vehicle sensor/probe data. Two types of models were developed in the Bayesian framework, including the block maxima sampling-based model corresponding to Generalised Extreme Value distribution and the peak over threshold sampling-based model corresponding to Generalised Pareto distribution. The proposed framework was applied to autonomous vehicle data from Argoverse-a Ford Motors subsidiary. This autonomous vehicle fleet of Agro AI (owner of Argoverse dataset) is equipped with two 64 beams synchronised LiDAR sensors, a cluster of seven high-resolution cameras, and a pair of stereo-vison high-resolution cameras to capture surrounding road users' information within a range of 200 meters. A subset of the Argoverse dataset, focussing on an arterial corridor in Miami, USA, was used to extract pedestrian and vehicle trajectories. From these trajectories, vehicle-pedestrian conflicts were identified and measured using post encroachment time. The non-stationarity of extremes was captured by vehicle volume, pedestrian volume, average vehicle speed, and average pedestrian speed in the extreme value model. Both block maxima and peak over threshold sampling-based models were found to provide a reasonable estimate of historical pedestrian crash frequencies. Notably, the block maxima sampling-based model was more accurate than the peak over threshold sampling-based model based on mean crash estimates and confidence intervals. This study demonstrates the potential of using autonomous vehicle sensor data for network-level safety, enabling an efficient identification of pedestrian crash risk zones in a transport network.


A transcriptome for the study of early processes of retinal regeneration in the adult newt, Cynops pyrrhogaster.
Retinal regeneration in the adult newt is a useful system to uncover essential mechanisms underlying the regeneration of body parts of this animal as well as to find clues to treat retinal disorders such as proliferative vitreoretinopathy. Here, to facilitate the study of early processes of retinal regeneration, we provide a de novo assembly transcriptome and inferred proteome of the Japanese fire bellied newt (Cynops pyrrhogaster), which was obtained from eyeball samples of day 0-14 after surgical removal of the lens and neural retina. This transcriptome (237,120 in silico transcripts) contains most information of cDNAs/ESTs which has been reported in newts (C. pyrrhogaster, Pleurodeles waltl and Notophthalmus viridescence) thus far. On the other hand, de novo assembly transcriptomes reported lately for N. viridescence only covered 16-31% of this transcriptome, suggesting that most constituents of this transcriptome are specific to the regenerating eye tissues of C. pyrrhogaster. A total of 87,102 in silico transcripts of this transcriptome were functionally annotated. Coding sequence prediction in combination with functional annotation revealed that 76,968 in silico transcripts encode protein/peptides recorded in public databases so far, whereas 17,316 might be unique. qPCR and Sanger sequencing demonstrated that this transcriptome contains much information pertaining to genes that are regulated in association with cell reprogramming, cell-cycle re-entry/proliferation, and tissue patterning in an early phase of retinal regeneration. This data also provides important insight for further investigations addressing cellular mechanisms and molecular networks underlying retinal regeneration as well as differences between retinal regeneration and disorders. This transcriptome can be applied to ensuing comprehensive gene screening steps, providing candidate genes, regardless of whether annotated or unique, to uncover essential mechanisms underlying early processes of retinal regeneration.


Pulmonary venous flow velocity: relation to hemodynamics, mitral flow velocity and left atrial volume, and ejection fraction.
Abnormal pulmonary venous flow velocity patterns are present in multiple cardiac disease states, but the determinants of pulmonary venous flow velocity have not been fully elucidated. To determine the relative importance of several proposed factors that could influence pulmonary venous flow, anatomic, hemodynamic, and Doppler mitral and pulmonary venous flow velocity data were compared in 50 consecutive patients undergoing cardiac catheterization for clinical reasons. Pulmonary venous diastolic flow velocity was most strongly related to left ventricular isovolumetric relaxation time (r = -0.59), left ventricular end-diastolic pressure (LVEDP, r = 0.50), left atrial minimum volume (r = 0.50), mitral deceleration time (r = -0.50), and early diastolic mitral flow velocity (r = 0.45). Pulmonary venous systolic flow velocity related best with left atrial minimum volume (r = -0.45) and left atrial ejection fraction (r = 0.44). Pulmonary venous systolic flow velocity integral also showed the strongest relation with left atrial minimum volume (r = -0.48). Relations between pulmonary venous flow velocity and velocity time integrals and other variables were sometimes significantly different, apparently caused in part to differences in heart rate. These results suggest that pulmonary venous diastolic flow velocity is influenced by the same factors that influence early left ventricular diastolic filling; pulmonary venous systolic flow velocity relates best to left atrial volume and atrial ejection fraction and does not relate to left ventricular ejection fraction. Future studies analyzing pulmonary venous flow velocity variables should include data on both peak velocities and velocity time integrals as well as left atrial size and function.


The LIG4 Ile658Val polymorphism does not affect the risk of cervical carcinoma.
The aim of this study was to investigate whether gene LIG4 genetic polymorphism affects the risk of cervical carcinoma. We studied 500 cervical carcinoma patients and 800 normal women as controls. Demographic and epidemiologic risk factors were recorded. Single nucleotide polymorphisms (SNPs) (LIG4 Ile658Val) were genotyped. Compared to LIG4 Ile658Ile (AA) genotype, LIG4 Ile658Val (AG) did not increase or decrease the risk of cervical carcinoma or cervical squamous cell carcinoma [ORs and 95% CIs being 1.07 (0.70-1.63) and 1.01 (0.65-1.55)], while no homozygous LIG4 Val658Val (GG) was found in the cervical carcinoma group. Analyzing the risk of variant LIG4 Ile658Val genotypes for cervical carcinoma of different histologic types or HPV infection status, we found striking similarities between the squamous cell carcinoma group and the HPV-positive group and the overall carcinoma. In conclusion, in the Chinese population, LIG4 Ile658Val has only a slight impact on the risk of developing cervical carcinoma.


The role of actin in spindle orientation changes during the Saccharomyces cerevisiae cell cycle.
In the budding yeast Saccharomyces cerevisiae, the mitotic spindle must align along the mother-bud axis to accurately partition the sister chromatids into daughter cells. Previous studies showed that spindle orientation required both astral microtubules and the actin cytoskeleton. We now report that maintenance of correct spindle orientation does not depend on F-actin during G2/M phase of the cell cycle. Depolymerization of F-actin using Latrunculin-A did not perturb spindle orientation after this stage. Even an early step in spindle orientation, the migration of the spindle pole body (SPB), became actin-independent if it was delayed until late in the cell cycle. Early in the cell cycle, both SPB migration and spindle orientation were very sensitive to perturbation of F-actin. Selective disruption of actin cables using a conditional tropomyosin double-mutant also led to defects in spindle orientation, even though cortical actin patches were still polarized. This suggests that actin cables are important for either guiding astral microtubules into the bud or anchoring them in the bud. In addition, F-actin was required early in the cell cycle for the development of the actin-independent spindle orientation capability later in the cell cycle. Finally, neither SPB migration nor the switch from actin-dependent to actin-independent spindle behavior required B-type cyclins.


First-order gradients of skew rays of axis-symmetrical optical systems.
Current commercial software for analysis and design of optical systems use finite difference (FD) approximation methodology to estimate the gradient matrix of a ray with respect to system variables. However, FD estimates are intrinsically inaccurate, subject to gross error when the denominator is excessively small relative to the numerator. We avoid these problems and determine these gradients by the application of Snell's law. We give the background and basics for determining the first-order gradients of skew rays of optical systems, whereby the differential vector of any ray can be estimated by the product of the developed gradient matrix and differential changes of system variables. The most important application is for optical design by use of optimization methods where the merit function is defined as the spot size. FD used for such optimization is slow for large systems and subject to inaccuracy. The presented methodology is shown to be accurate and computationally faster than traditional FD. Two illustrative examples are provided to validate the proposed method.


Evidence for the sequential assembly of cytochrome oxidase subunits in rat liver mitochondria.
The assembly of cytochrome oxidase was studied in isolated rat liver mitochondria and isolated rat hepatocytes labelled in vitro with L-[35S]methionine. This was achieved by studying the temporal association of radioactive subunits which are immunoabsorbed with antibodies against subunits I, II and the holoenzyme. Antibodies against the holoenzyme were shown to be highly specific for subunit V. The results show that subunit I appears in the holoenzyme late in the assembly process. No radioactive subunit I is absorbed with antiserum against subunit II or the holoenzyme (subunit V) after a 30 min pulse in either isolated mitochondria or hepatocytes. However, both antisera absorb radioactive subunits I after a 150 min chase in isolated hepatocytes. This was confirmed using antibodies against subunit I, which absorbed only radioactive subunit I after a 30 min pulse but absorbed radioactive subunits I-III and VI after a 150 min chase. Thus, the late assembly of radioactive subunit I is explained by a temporal sequence in the assembly process and not by the presence of a large, non-radioactive pool of subunit I. Using the above approach and the three specific antisera, the following temporal sequence in the assembly of cytochrome oxidase was established. Subunits II and III assemble rapidly with each other or with cytoplasmically translated subunit VI. This complex of three peptides in turn assembles slowly with subunit I or with the other cytoplasmically translated subunits. The early association of subunit VI with the mitochondrially translated subunits II and III suggests a possible role of the former in integration of the holoenzyme.


A Heterogeneous Network Based Method for Identifying GBM-Related Genes by Integrating Multi-Dimensional Data.
The emergence of multi-dimensional data offers opportunities for more comprehensive analysis of the molecular characteristics of human diseases and therefore improving diagnosis, treatment, and prevention. In this study, we proposed a heterogeneous network based method by integrating multi-dimensional data (HNMD) to identify GBM-related genes. The novelty of the method lies in that the multi-dimensional data of GBM from TCGA dataset that provide comprehensive information of genes, are combined with protein-protein interactions to construct a weighted heterogeneous network, which reflects both the general and disease-specific relationships between genes. In addition, a propagation algorithm with resistance is introduced to precisely score and rank GBM-related genes. The results of comprehensive performance evaluation show that the proposed method significantly outperforms the network based methods with single-dimensional data and other existing approaches. Subsequent analysis of the top ranked genes suggests they may be functionally implicated in GBM, which further corroborates the superiority of the proposed method. The source code and the results of HNMD can be downloaded from the following URL: http://bioinformatics.ustc.edu.cn/hnmd/ .


Immunosuppression in progressive multiple sclerosis with high dose intravenous cyclophosphamide and monoclonal antibodies.
Our work with multiple sclerosis has demonstrated a favorable effect on the course of chronic progressive multiple sclerosis in two-thirds of patients treated with cyclophosphamide/ACTH. However, alternative methods of therapy, or repeated treatments with cyclophosphamide and ACTH are required for longer term control of the illness. We are attempting to assess the efficacy of outpatient maintenance cyclophosphamide, but do not as yet have any data to support the use of this form of treatment. Cyclophosphamide and ACTH can be given to multiple sclerosis patients without significant serious toxicity. Monoclonal antibody therapy of multiple sclerosis is in its beginning stages. The treatment appears to be safe and has produced some interesting data indicating that rapid entry of some labeled lymphocytes into the nervous system can be measured by this technique. Since these are phase one pilot trials designed to assess immune parameters and only small numbers of patients have been treated, no clinical results have been obtained. No adverse effects of monoclonal antibody therapy were observed.


Minimal growth temperature, sodium chloride tolerance, pH sensitivity, and toxin production of marine and terrestrial strains of Clostridium botulinum type C.
Minimal growth temperatures of four marine and two terrestrial strains of Clostridium botulinum type C were determined in a laboratory culture medium, fortified egg meat medium (FEM), and in ground haddock. The inoculum equaled 2 x 10(6) viable spores per tube with five-tube replicate sets. The spores were preheated in aqueous suspension at 71 C for 15 min prior to inoculation to reduce toxin carry-over. Similar results were obtained in both substrates. Both the marine and the terrestrial strains grew at 15.6 C, but only the terrestrial strains grew at 12.8 C. None of the strains grew at 10 C during prolonged incubation. The sodium chloride tolerance and the pH sensitivity of the marine and the terrestrial strains were determined at 30 C. The basal medium consisted of beef infusion broth. The inoculum level equaled 2 x 10(6) unheated spores per replicate. Growth was inhibited at salt concentrations from 2.5 to 3.0%. The terrestrial strains were more pH-sensitive than the marine strains. Whereas the terrestrial strains failed to grow below pH 5.62, three of the marine strains grew at pH 5.10, but not at pH 4.96, during extended incubation. One marine strain grew at pH 5.25, but not below. FEM and proteose peptone-Trypticase-yeast extract-glucose medium permitted the production of high levels of botulinum toxin among four media tested. Toxin produced by the marine and terrestrial strains showed no increase in toxicity after incubation with trypsin.


Posttreatment assessment of women at risk of developing high-grade cervical disease: proposal for new guidelines based on data from the Netherlands.
Women treated for high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or grade 3 [CIN2/3]) face a significant risk of developing post-treatment disease. Therefore, in most European countries, they are monitored by cytologic testing at 6, 12, and 24 months after treatment. Although testing for high-risk types of the human papillomavirus (hrHPV) in the follow-up seems to be a valuable supplementary method, its use is not yet fully explored. Besides reviewing the literature, we completed a long-term follow-up study describing the cumulative risk for CIN2/3 or cancer (CIN2+) of different hrHPV and cytology test results after treatment. High-risk HPV testing improves the sensitivity to detect posttreatment CIN2/3 (relative sensitivity=1.15, 95% confidence interval [CI]=1.06-1.25), but the highest sensitivity (95%, 95% CI=91%-98%) is reached by performing cotesting (both cytology and hrHPV). The CIN2+ risk after a single negative cotesting result taken 6 months after treatments was similar to the risk after 3 consecutive negative cytologic test results (5-y CIN2+ risk being 3.0% [95% CI=1.5%-6.1%] and 2.9% [95% CI=1.2%-7.1%], respectively). Women who test negative for cotesting at both 6 and 24 months after treatment have a minimal risk of developing CIN3+ in the next 5 years (0.0%, 95% CI=0.0%-3.0%). We propose a new posttreatment surveillance protocol, consisting of combined testing with both cytology and hrHPV at 6 and 24 months after treatment. After 2 negative cotesting results, women should be retested after 5 years.


The use of clinical profiles in the investigation of foodborne outbreaks in restaurants: United States, 1982-1997.
Improving the efficiency of outbreak investigation in restaurants is critical to reducing outbreak-associated illness and improving prevention strategies. Because clinical characteristics of outbreaks are usually available before results of laboratory testing, we examined their use for determining contributing factors in outbreaks caused by restaurants. All confirmed foodborne outbreaks reported to the Centers for Disease Control and Prevention (CDC) from 1982 to 1997 were reviewed. Clinical profiles were developed based on outbreak characteristics. We compared the percentage of contributing factors by known agent and clinical profile to their occurrence in outbreaks of unclassified aetiology. In total, 2246 foodborne outbreaks were included: 697 (31%) with known aetiology and 1549 (69%) with aetiology undetermined. Salmonella accounted for 65% of outbreaks with a known aetiology. Norovirus-like clinical profiles were noted in 54% of outbreaks with undetermined aetiology. Improper holding times and temperatures were associated with outbreaks caused by Clostridium perfringens, Bacillus cereus, Staphylococcus aureus, and Salmonella, and also with outbreaks of undetermined aetiology that fitted diarrhoea-toxin and vomiting-toxin clinical profiles. Poor personal hygiene was associated with norovirus, Shigella, and Salmonella, and also with outbreaks that fitted norovirus-like and vomiting-toxin clinical profiles. Contributing factors were similar for outbreaks with known aetiology and for those where aetiology was assigned by corresponding clinical profile. Rapidly categorizing outbreaks by clinical profile, before results of laboratory testing are available, can help identification of factors which contributed to the occurrence of the outbreak and will promote timely and efficient outbreak investigations.


Resting state cortical connectivity reflected in EEG coherence in individuals with autism.
Theoretical conceptions of autism spectrum disorder (ASD) and experimental studies of cerebral blood flow suggest abnormalities in connections among distributed neural systems in ASD. Functional connectivity was assessed with electroencephalographic coherence between pairs of electrodes in a high-density electrode array in narrow frequency bands among 18 adults with ASD and 18 control adults in an eyes closed resting state. In the theta (3-6 Hz) frequency range, locally elevated coherence was evident for the ASD group, especially within left hemisphere frontal and temporal regions. In the lower alpha range (8-10 Hz), globally reduced coherence was evident for the ASD group within frontal regions and between frontal and all other scalp regions. The ASD group exhibited significantly greater relative power between 3 and 6 Hz and 13-17 Hz and significantly less relative power between 9 and 10 Hz. Robust patterns of over- and under-connectivity are apparent at distinct spatial and temporal scales in ASD subjects in the eyes closed resting state.


Correlates of Dementia and Mild Cognitive Impairment in Patients With Atrial Fibrillation: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).
Atrial fibrillation (AF) has been associated with faster cognitive decline and increased dementia risk. Factors associated with dementia in patients with AF have been seldom studied. We studied 6432 individuals from the ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive Study). In 2011 to 2013, participants underwent a physical exam, echocardiography, detailed cognitive assessments, and a subset, brain magnetic resonance imaging. Dementia and mild cognitive impairment (MCI), as well as etiology of MCI/dementia, Alzheimer's disease-related or vascular, were adjudicated by an expert panel. AF was defined by study ECGs and past hospitalizations. We used logistic regression to estimate odds ratios and 95% CI of MCI/dementia by AF status and to assess cross-sectional correlates of MCI/dementia in patients with AF. Among 6432 participants, 611 (9.5%) had prevalent AF. AF was associated with increased odds of dementia and MCI (odds ratio, 95% CI, 2.25, 1.64-3.10, and 1.28, 1.04-1.56, respectively). Prevalence of Alzheimer's disease-related MCI/dementia and vascular MCI/dementia were higher in participants with AF than without AF (odds ratio, 95% CI, 1.29, 1.04-1.61, and 1.50, 0.99-2.25, respectively). In multivariable analyses, older age, lower body mass index, diabetes mellitus, stroke, and APOE genotype were associated with dementia prevalence in participants with AF. In models evaluating MCI/dementia subtypes, diabetes mellitus was associated with Alzheimer's disease-related MCI/dementia, whereas male sex and stroke were risk factors for vascular MCI/dementia. In a large, community-based study, AF was associated with higher prevalence of MCI and dementia. Controlling cardiometabolic risk factors is a potential target for prevention of adverse cognitive outcomes in AF patients.


Retinal mesopic adaptation model for brightness perception under transient glare.
A glare source in the visual field modifies the brightness of a test patch surrounded by a mesopic background. In this study, we investigated the effect of two levels of transient glare on brightness perception for several combinations of mesopic reference test luminances (Lts) and background luminances (Lbs). While brightness perception was affected by Lb, there were no appreciable effects for changes in the Lt. The highest brightness reduction was found for Lbs in the low mesopic range. Considering the main proposal that brightness can be inferred from contrast and the Lb sets the mesopic luminance adaptation, we hypothesized that contrast gain and retinal adaptation mechanisms would act when a transient glare source was present in the visual field. A physiology-based model that adequately fitted the present and previous results was developed.


Increasing maternal body mass index is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways.
Obese pregnant women have increased levels of proinflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated proinflammatory cytokines in maternal and fetal circulations and increased activation of placental inflammatory pathways. A total of 60 women of varying pre-/early pregnancy BMI, undergoing delivery by Cesarean section at term, were studied. Maternal and fetal (cord) plasma were collected for analysis of insulin, leptin, IL-1beta, IL-6, IL-8, monocyte chemoattractant protein (MCP) 1, and TNFalpha by multiplex ELISA. Activation of the inflammatory pathways in the placenta was investigated by measuring the phosphorylated and total protein expression of p38-mitogen-activated protein kinase (MAPK), c-Jun-N-terminal kinase (JNK)-MAPK, signal transducer-activated transcription factor (STAT) 3, caspase-1, IL-1beta, IkappaB-alpha protein, and p65 DNA-binding activity. To determine the link between activated placental inflammatory pathways and elevated maternal cytokines, cultured primary human trophoblast (PHT) cells were treated with physiological concentrations of insulin, MCP-1, and TNFalpha, and inflammatory signaling analyzed by Western blot. Maternal BMI was positively correlated with maternal insulin, leptin, MCP-1, and TNFalpha, whereas only fetal leptin was increased with BMI. Placental phosphorylation of p38-MAPK and STAT3, and the expression of IL-1beta protein, were increased with maternal BMI; phosphorylation of p38-MAPK was also correlated with birth weight. In contrast, placental NFkappaB, JNK and caspase-1 signaling, and fetal cytokine levels were unaffected by maternal BMI. In PHT cells, p38-MAPK was activated by MCP-1 and TNFalpha, whereas STAT3 phosphorylation was increased following TNFalpha treatment. Maternal BMI is associated with elevated maternal cytokines and activation of placental p38-MAPK and STAT3 inflammatory pathways, without changes in fetal systemic inflammatory profile. Activation of p38-MAPK by MCP-1 and TNFalpha, and STAT3 by TNFalpha, suggests a link between elevated proinflammatory cytokines in maternal plasma and activation of placental inflammatory pathways. We suggest that inflammatory processes associated with elevated maternal BMI may influence fetal growth by altering placental function.


Comparison of mean on-scene times: road versus air transportation of critically ill patients in the Western Cape of South Africa.
The South African setting lends itself to the extensive use of air transport. There is a perception with healthcare providers that flight crews spend too much time with a patient before departure. The main advantage of aero medical transport is to minimise the delay to definitive care and prolonged on-scene time defies this objective. A study was carried out to examine the mean on-scene times of aero medical and road transport of critically ill patients in the Western Cape of South Africa. In this retrospective observational study, all critically ill patients transported in the Western Cape between September 2005 and May 2006 were evaluated. The mean on-scene time for each transport mode was calculated. Road transport was compared with air transport (rotor and fixed wing). Every transport mode was further divided into mission types: "scene" missions (scene to a healthcare facility) or "inter-facility" missions (from one healthcare facility to another). A total of 7924 transports were included in the study, 7580 of which (95.7%) were road transports. The air transport group spent 53.2 min (95% CI 51.1 to 55.4) at the scene compared with 27.9 min (95% CI 27.5 to 28.4) for the road transport group. There was a significant difference between scene and inter-facility missions in the air transport group (mean 31.7 min for scene missions vs 58.7 min for inter-facility missions; p<0.001). A significant difference was also found in the road transport (mean 24.6 min for scene missions vs 31.9 min for inter-facility missions; p<0.001). The on-scene time for transport missions by road is significantly less than for those done by air. There are significant differences between scene and inter-facility missions in both transport modes. Capacity building programmes with ongoing education and training of staff at referring facilities should be implemented.


From an Fe2P3 complex to FeP nanoparticles as efficient electrocatalysts for water-splitting.
In large-scale, hydrogen production from water-splitting represents the most promising solution for a clean, recyclable, and low-cost energy source. The realization of viable technological solutions requires suitable efficient electrochemical catalysts with low overpotentials and long-term stability for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) based on cheap and nontoxic materials. Herein, we present a unique molecular approach to monodispersed, ultra-small, and superiorly active iron phosphide (FeP) electrocatalysts for bifunctional OER, HER, and overall water-splitting. They result from transformation of a molecular iron phosphide precursor, containing a [Fe2P3] core with mixed-valence FeIIFeIII sites bridged by an asymmetric cyclo-P(2+1) 3- ligand. The as-synthesized FeP nanoparticles act as long-lasting electrocatalysts for OER and HER with low overpotential and high current densities that render them one of the best-performing electrocatalysts hitherto known. The fabricated alkaline electrolyzer delivered low cell voltage with durability over weeks, representing an attractive catalyst for large-scale water-splitting technologies.


Additional resources and the default mode network: Evidence of increased connectivity and decreased white matter integrity in amyotrophic lateral sclerosis.
In amyotrophic lateral sclerosis (ALS), cognition is affected. Cortical atrophy in frontal and temporal areas has been associated with the cognitive profile of patients. Additionally, reduced metabolic turnover and regional cerebral blood flow in frontal areas indicative of reduced neural activity have been reported for ALS. We hypothesize that functional connectivity in non-task associated functional default mode network (DMN) is associated with cognitive profile and white matter integrity. This study focused on specific cognitive tasks known to be impaired in ALS such as verbal fluency and attention, and the relationship with functional connectivity in the DMN and white matter integrity. Nine patients and 11 controls were measured with an extensive neuropsychological battery. Resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were acquired. Results showed that ALS patients performed significantly worse in attention and verbal fluency task. Patients showed increased functional connectivity in parahippocampal and parietal areas of the non-task associated DMN compared to controls. The more pronounced the cognitive deficits, the stronger the increase in functional connectivity in those areas. White matter integrity was reduced in frontal areas in the patients. In conclusion, increased connectivity in the DMN in parahippocampal and parietal areas might represent recruitment of accessory brain regions to compensate for dysfunctional frontal networks.


Time course and spacial distribution of UV effects on human skin in organ culture.
Apoptosis plays an important role in eliminating cells from populations when cells have been exposed to UV irradiation and damaged. Studies of cells in culture have provided some details of the mechanisms involved when stress response genes act after exposure to UV irradiation and other environmental stresses. However, little is known about the responses of intact sections of human skin growing in organ culture to UV irradiation. In the work reported here, it was found that the response of organ-cultured human skin after exposure to UV irradiation is different than the response of cultured cells. At wavelengths below 300 nm, the action spectrum obtained from organ-cultured skin samples showed a lower sensitivity than that observed at 300 nm, indicating that the overlying stratum corneum and upper epidermal cell layers had probably caused a selective absorption of incident UV radiation at some wavelengths. At 3 hours after UV irradiation, p53 was phosphorylated at Ser 15 and Ser 46, and accumulated in the cell nuclei, notably after exposure to 280-320 nm wavelengths. Accumulations of Bax, active Caspase-3 and cleaved PARP were detected in apoptotic cells at 24 hours post-exposure, along with a reduction of Bcl-2 levels, notably after exposure to 300-365 nm light. This difference in apoptotic responses may result from the characteristics of the different irradiation wavelengths used, and from details in the skin's structure. The data obtained in this study using an organ-culture system utilized direct measurements of the biological effects of different wavelengths of UV lights.


Comparative genomic hybridisation in malignant deciduoid mesothelioma.
Malignant deciduoid mesothelioma is a rare variant of epithelioid mesothelioma. This tumour generally has poor prognosis, and can be asbestos related. To identify peculiar genetic changes responsible for critical phases in pathogenesis of malignant deciduoid mesothelioma and their prognostic relevance. Comparative genomic hybridisation was carried out in six cases of malignant pleural deciduoid mesothelioma, four sporadic and two familial. All cases were found to be asbestos related. Four patients died during follow-up and the mean survival was 29.5 (SD 14.2, range 12-43) months. Genetic abnormalities were found in all the tumour tissues, the most frequent being chromosomal gains at 1p, 12q, 17, 8q, 19 and 20 and losses at 13q, 6q and 9p. Survival was found to be longer in those patients who presented a smaller number of losses (< or =2) in the tumorous chromosomes. Although numerous genetic changes are presented by deciduoid mesotheliomas, certain chromosomal regions are preferentially affected. The clinical outcome for this mesothelioma subtype is predicted by the number of losses.


Mentorship Initiatives in Radiation Oncology: A Scoping Review of the Literature.
Although mentorship is described extensively in academic medical literature, there are few descriptions of mentorship specific to radiation oncology. The goal of the current study was to investigate the state of mentorship in radiation oncology through a scoping review of the literature. A search protocol was defined according to Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for scoping reviews (PRISMA-ScR) guidelines. Predefined search terms and medical subject headings were used to search PubMed for English language articles published after January 1, 1990, on mentorship in radiation oncology. Additionally, in-press articles from major radiation oncology and medical education journals were searched. Three reviewers determined article eligibility. Included articles were classified based on predefined evaluation criteria. Fourteen publications from 2008 to 2019 met inclusion criteria. The most commonly described form of mentorship was the dyad (64.3%), followed by team (14.3%) and peer (7.1%); 2 articles did not specify mentorship type (14.3%). The most commonly mentored participants were residents (35.7%), followed by medical students (35.7%) and attendings (21.4%); 1 study included participants of all levels (7.1%). Thirteen studies (92.9%) identified an experimental study design, most of which were cross-sectional (42.9%), followed by cohort studies (28.6%) and before/after (21.4%). Median sample size, reported in 12 of 13 experimental studies, was 132 (coefficient of variation, 1.06). Although outcomes varied widely, the majority described successful implementation of mentorship initiatives with high levels of participant satisfaction. Although few initiatives are currently reported, the present study suggests that these initiatives are successful in promoting career development and increasing professional satisfaction. The interventions overwhelmingly described mentorship dyads; other forms of mentorship are either less common or understudied. Limitations included interventions not being evaluated in a controlled setting, and many were assessed using surveys with low response rates. This review highlights rich opportunities for future scholarship to develop, evaluate, and disseminate radiation oncology mentorship initiatives.


The interaction of canine plasminogen with Streptococcus pyogenes enolase: they bind to one another but what is the nature of the structures involved?
For years it has been clear that plasminogen from different sources and enolase from different sources interact strongly. What is less clear is the nature of the structures required for them to interact. This work examines the interaction between canine plasminogen (dPgn) and Streptococcus pyogenes enolase (Str enolase) using analytical ultracentrifugation (AUC), surface plasmon resonance (SPR), fluorescence polarization, dynamic light scattering (DLS), isothermal titration calorimetry (ITC), and simple pull-down reactions. Overall, our data indicate that a non-native structure of the octameric Str enolase (monomers or multimers) is an important determinant of its surface-mediated interaction with host plasminogen. Interestingly, a non-native structure of plasminogen is capable of interacting with native enolase. As far as we can tell, the native structures resist forming stable mixed complexes.


[Serum polypeptides in peptic ulcer patients].
Fifty-four healthy subjects and 56 peptic ulcer patients were examined for blood serum polypeptides, their toxicity and antigenicity. It was discovered that in the peptic ulcer patients, the blood polypeptide content was 1.5-3-fold higher than in healthy subjects. The increased content of polypeptides in the patients was caused by a high supply of polypeptides from the gastrointestinal tract. Polypeptides isolated from the patients' blood had toxic and antigenic properties. Antibodies against polypeptides were detected in 82% of the peptic ulcer patients and in 10% of the healthy persons. A direct correlation was found between the titer of antibodies against polypeptides and IgG content. It is suggested that polypeptides are involved in the development of peptic ulcer.


Neuroencorine Tumor Arising within a Tailgut Cyst in an Adolescent Boy.
Neuroendocrine tumors (NET) within tailgut cysts (TC) are usually seen in middle-aged females. A 14 year-old boy who underwent surgical excision of NET within TC is presented to discuss the clinical features, diagnosis and treatment options. A 14-year-old boy with rectal bleeding and constipation had a 5 × 4 cm mass detected upon rectal examination. The cystic mass was totally excised. The histopathological evaluation revealed a low-grade NET within mucularis layer of the cyst showing a positive immunhistochemical staining for cytokeratin and synaptophysin. Although, the malignant transition of TC is commonly observed in middle age females, males and children can also be affected. This is first report of a pediatric TC with malignant transformation. Total surgical excision of cysts is mandatory for local control of the disease and chemotherapy should be reserved for the patients who have positive surgical margins.


Effect of ancestry on interleukin-10 haplotypes in chronic periodontitis.
Chronic periodontitis is caused by an inflammatory reaction of the periodontal tissues and alveolar bone. This inflammation is caused by periodontopathic bacteria located in the subgingival biofilm, resulting in inflammatory reactions that may lead to loss of attachment. This tissue destruction is a consequence of host immune and inflammatory responses to specific periodontal pathogens and their metabolic products. Cytokines modulate the immune response, altering its efficiency in the competition against pathogens and increasing periodontal susceptibility. This study investigated genetic polymorphisms in Interleukin 10 (A-1082G, C-819T and C-592A) in 205 individuals from an admixed Brazilian population. A significantly increased risk of developing chronic periodontitis was observed in individuals with low IL-10 production and Amerindian ancestry. These results suggest that the polymorphisms A-1082G, C-819T, and C-592A, which are associated with ancestry, are involved in the susceptibility to the development of chronic periodontitis in an admixed northern Brazilian population.


Chemical characteristics of the L-glutamate receptor on the Onchidium neuron.
Application of L-glutamate (L-glu) to particular neurons (G-H cells) in the esophageal ganglia of Onchidium produced hyperpolarization associated with an increase in K+ permeability. The reversal potential (Erev) for this response, was -60 mV. The ED50, an indicator of affinity between L-glu and its receptive site, was 5.3 mM, and the Hill coefficient n, an indicator of cooperativity, was 2. Other chemicals, structurally analogous to L-glu, were also examined on G-H cells. The responses of L-aspartate were similar to those of L-glu with respect to Erev, ED50, and n. However, the G-H cells responded differently to D-glutamate (D-glu) and kainic acid. The D-glu response had an Erev = -37.5 mV, ED50 = 29.4 mM, and n = 1; that of kainic acid had an Erev = 0 mV, ED50 = 1.5 mM, and n = 1. L-glutamine and GABA elicited very small responses, amplitudes of which were less than 10% of the L-glu response. The structure-activity relationship between L-glu and its analogues, estimated from Erev, ED50, and Hill coefficient during each drug application, indicates that the presence of alpha-NH2, alpha-COOH, and gamma-COOH groups is essential for the L-glu response and that the response characteristics may be closely related to the relative positions of these groups.


Alkane and wax ester production from lignin-related aromatic compounds.
Lignin has potential as a sustainable feedstock for microbial production of industrially relevant molecules. However, the required lignin depolymerization yields a heterogenic mixture of aromatic monomers that are challenging substrates for the microorganisms commonly used in the industry. Here, we investigated the properties of lignin-related aromatic compounds (LRAs), namely coumarate, ferulate, and caffeate, in the synthesis of biomass and products in an LRA-utilizing bacterial host Acinetobacter baylyi ADP1. The biosynthesis products, wax esters, and alkanes are relevant compounds for the chemical and fuel industries. Here, wax esters were produced by a native pathway of ADP1, whereas alkanes were produced by a synthetic pathway introduced to the host. Using individual LRAs as substrates, the growth and product formation were monitored with internal biosensors and off-line analytics. Of the tested LRAs, coumarate was the most propitious in terms of product synthesis. Wax esters were produced from coumarate with yield and titer of 37 mg/gcoumarate and 202 mg/L, whereas alkanes were produced with a yield of 62.3 µg /gcoumarate and titer of 152 µg/L. This study demonstrates the microbial preference for certain LRAs and highlights the potential of A. baylyi ADP1 as a host for LRA upgrading to value-added products.


Hepatocellular Carcinoma in Diabetic Patients - a Single Center Experience.
Hepatocellular carcinoma (HCC) represents a major health concern worldwide; identifying risk factors and associated conditions that may lead to its development are therefore of utmost importance to the medical community. An association between diabetes mellitus (DM) and development of HCC on underlying liver conditions has been previously suggested. The aim of our study is to reveal possible significant statistical correlations between the two entities, which might warrant further study of the pathophysiological mechanisms behind this association. We have prospectively included consecutive cirrhotic patients admitted to our medical clinic over a period of four years, between 2010 and 2014. Diagnostic was established using the EASL criteria. We have documented history of hyperglycemia and any changes of serum values in these patients, evaluating DM patients within the LC lot. From these patients we have selected all patients with imaging suggestive for HCC and established positive diagnosis on the criteria established in the latest EASL guidelines. We have used statistical tests to identify possible correlations between these pathologies. We have identified 2718 consecutive patients with LC and successfully included 2556. Of these, 164 also had HCC. A total of 371 patients had DM - 54 also had HCC while 317 remained cancer-free through our study period. We found positive correlations between the presence of DM and HCC. Subgroup analysis of the HCC cohort revealed a positive association between DM and liver cirrhosis and chronic hepatitis. We did not find positive relationships between DM and overall liver conditions, splenomegaly, hepatomegaly, other significant symptoms, substance abuse and main serum values. We have found several significant correlations between DM and underlying liver conditions in a HCC cohort. Our study, however, did not reveal other significant associations regarding these diseases. Further studies are required to determine the precise role this disease plays in the development and severity of liver diseases.


Impact of hypomanic personality traits on brain functional connectivity during a dynamic theory-of-mind task.
Hypomanic personality traits are present in the general population and represent a risk factor for developing bipolar disorder. This personality style, notably its social component, is linked to difficulties in theory of mind (i.e., ability to infer mental states). Exploring the neural correlates of mental states' inference in individuals with these personality traits can provide meaningful insights into the development of bipolar disorder. The aim of the present study was therefore to investigate the potential impact of hypomanic traits on brain activation and task-based connectivity strength during a dynamic theory of mind task in a nonclinical population. A total of 52 nonclinical participants were recruited, and hypomanic traits were assessed with the Hypomanic Personality Scale. The severity of hypomanic traits was positively associated with right middle and inferior frontal gyri activations (in high vs. low inference in nonemotional condition and emotion vs. no emotion in high inference, respectively). It was also associated with stronger connectivity between the salience network (i.e., bilateral putamen and pallidum) and bilateral superior temporal gyri (high inference in nonemotional condition), and between cerebellar and temporal areas (high inference in emotional condition). These changes may either reflect adaptations or differential processing, and further studies are therefore mandatory.


Bilateral deficits in postural control following lateral ankle sprain.
Although postural control deficits have been identified after lateral ankle sprains, objective and subjective comparisons of data before and after injury are limited. The purpose of this project was to prospectively assess and compare the changes in postural control and self-reported functional status in athletes who suffer acute lateral ankle sprains. We evaluated postural control and self-reported functional status before injury and at 1, 7, 14, 21, and 28 days after acute lateral ankle sprain. Postural control in single-limb stance and self-reported functional status were evaluated in 460 collegiate athletes during preseason examinations. Twenty-eight athletes suffered a lateral ankle sprain during the competitive season and participated in testing at 1, 7, 14, 21, and 28 days after injury. Significant deficits in postural control were noted in both the injured and the uninjured ankles at 1 day after injury compared to the baseline measurements taken during the preseason examinations. Significant differences (p < .05) also were noted between the uninjured and injured ankles at 1, 7, and 21 days after injury. After lateral ankle sprain, postural control deficits occur in the injured and uninjured ankles, suggesting a central impairment in neuromuscular control. Changes in self-reported functional status followed a trend of deficit and improvement that was similar to that shown by the postural control data taken after injury, but the two measures did not strongly correlate.


Evaluating the presence of SARS-CoV-2 in the intraocular fluid of COVID-19 patients.
To detect the presence of SARS-CoV-2 in aqueous and vitreous humor of COVID-19 patients in a pilot study. : Consecutive patients planned for emergency ophthalmic surgeries after ocular trauma were subjected to naso-oropharyngeal RT-PCR test for SARS-CoV-2. Laboratory-confirmed cases were enrolled for the study. During surgery, 0.1 mL aqueous and vitreous each was aspirated. The vitreous tap was collected on clinical suspicion of endophthalmitis. RT-PCR test was used to detect SARS-COV-2 nucleotide in the samples. Cycle threshold (Ct) for E gene of ≤35 along with confirmatory results on one of the two target genes (RdRp or ORF1b) was considered as positive. : One hundred and thirty two patients were found positive on naso-oropharyngeal RT-PCR test for SARS-CoV-2 preoperatively. Seven patients with ocular trauma were studied. The mean age was 31.8 years. There were six male and one female patient. Two patients had symptoms of mild COVID-19 disease and the rest were asymptomatic. The mean Ct value of the E gene on naso-oropharyngeal RT-PCR was 23.14 ± 4.7. Corneal and corneoscleral laceration repair was done in five patients, intracorneal wooden foreign body was removed in one patient, and injection of intravitreal antibiotics was done in one patient. Aqueous and vitreous tap was collected in 7 and 5 patients, respectively. None of the aqueous or vitreous samples was found positive for SARS-CoV-2. : SARS-CoV-2 was not detected by RT-PCR in aqueous or vitreous humor in this pilot study. Future studies with a larger sample size are needed to further explore the presence of SARS-CoV-2 in intraocular fluids.


Structure and function of the papillomavirus E6 protein and its interacting proteins.
Infection by high risk papillomavirus causes various forms of anogenital cancer including squamous cell carcinoma of the cervix. A primary step in the carcinogenesis includes formation of a complex of viral E6 protein and a human E3 ubiquitin ligase. This complex is competent to cause degradation and inactivation of several target proteins including human tumor suppressors which contributes to hyperproliferation of infected cells. Great insight on the mechanism by which E6 binds target proteins has recently been provided by determination of structures of interacting peptides and a E6 domain. These data have also provided a basis for the discovery of small molecules that can inhibit E6. However, there is still a need to further solve the structures of additional interacting complexes to identify the structural relationship that exists between proteins that simultaneously bind E6, such as E6AP and p53 or E6AP and PDZ domain-containing proteins, and to provide a clear picture of the interface between E6 and its ubiquitin ligase.


Adiabatic evolution of plasma equilibrium.
A new theory of plasma equilibrium is introduced in which adiabatic constraints are specified. This leads to a mathematically nonstandard structure, as compared to the usual equilibrium theory, in which prescription of pressure and current profiles leads to an elliptic partial differential equation. Topologically complex configurations require further generalization of the concept of adiabaticity to allow irreversible mixing of plasma and magnetic flux among islands. Matching conditions across a boundary layer at the separatrix are obtained from appropriate conservation laws. Applications are made to configurations with planned islands (as in Doublet) and accidental islands (as in Tokamaks). Two-dimensional, axially symmetric, helically symmetric, and closed line equilibria are included.


Effect of AdGDNF on dopaminergic neurotransmission in the striatum of 6-OHDA-treated rats.
We have previously observed that the delivery of an adenoviral vector encoding for glial cell line-derived neurotrophic factor (AdGDNF) into the substantia nigra (SN) 7 days after intrastriatal administration of 6-hydroxydopamine (6-OHDA) protects dopamine (DA)-dependent behaviors, tyrosine hydroxylase immunoreactive (TH+) cells in SN, and amphetamine-induced c-fos induction in striatum. In the present study, we sought to determine if the behavioral protection observed in 6-OHDA-treated rats receiving AdGDNF was associated with an increase in DA availability in the striatum as measured by microdialysis. Rats received intrastriatal 6-OHDA (16 microg/2.8 microl) or vehicle followed 7 days later by intranigral AdGDNF (3.2x10(7) pfu/2 microl), AdLacZ (3.2 x 10(7) pfu/2 microl), or phosphate buffered saline (PBS). Three weeks later, microdialysis samples were collected from the same striatal region under basal conditions, following KCl (100 mM) or amphetamine (250 microM) administered via the striatal microdialysis probe, or amphetamine administered systemically (6.8 mg/kg i.p). Animals given 6-OHDA followed by either PBS or AdLacZ showed a decrease in basal extracellular striatal DA levels to 24% of control. In contrast, basal extracellular DA in 6-OHDA-lesioned rats with a nigral injection of AdGDNF was almost 3-fold higher than 6-OHDA-vehicle treated animals, 65% of control DA levels. Moreover, although KCl and amphetamine produced no increase in striatal DA release in 6-OHDA-treated rats that subsequently were given either PBS or AdLacZ, these manipulations increased DA levels significantly in 6-OHDA-treated rats later given AdGDNF. Thus, DA neurotransmission within the striatum of 6-OHDA treated rats appears to be enhanced by increased expression of GDNF in the nigra.


[Features of the ECG in acute altitude sickness].
Using the Minnesota Code, we analysed ECGs of 58 subjects with smooth adaptation to high altitude (3.600 m) and of 70 patients with acute mountain sickness. In both groups, the 30-day sojourn at high altitude was characterized by ECG signs of the right heart overload; these signs were more marked in patients with acute mountain sickness. It was demonstrated that baseline ECGs (recorded before the ascent) of subjects predisposed to the development of acute mountain sickness showed a higher incidence of right-ventricular hypertrophy, right-atrial hypertrophy, and tachycardia. These ECG features can be used in the prognosis of acute mountain sickness.


A two-equation coupled system model for determination of liver tissue temperature during radio frequency ablation.
A model is presented that is an alternative approach to the bio-heat equation for use in radio frequency heating of the liver. The model comprises both a tissue subvolume and a blood subvolume. Separate bio-heat equations are determined for each subvolume, but with an additional term exchanging heat between them, thus creating a coupled system. The derivation for the two coupled differential equations is outlined and sample simulations are presented to demonstrate the importance of considering the two subvolumes separately, even when the blood subvolume is a small fraction of the tissue subvolume.


A novel C-terminal proteolytic processing of cytosolic pyruvate kinase, its phosphorylation and degradation by the proteasome in developing soybean seeds.
Cytosolic pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 22.214.171.124) is an important glycolytic enzyme, but the post-translational regulation of this enzyme is poorly understood. Sequence analysis of the soybean seed enzyme suggested the potential for two phosphorylation sites: site-1 (FVRKGS220DLVN) and site-2 (VLTRGGS407TAKL). Sequence- and phosphorylation state-specific antipeptide antibodies established that cytosolic pyruvate kinase (PyrKinc) is phosphorylated at both sites in vivo. However, by SDS-PAGE, the phosphorylated polypeptides were found to be smaller (20-51 kDa) than the full length (55 kDa). Biochemical separations of seed proteins by size exclusion chromatography and sucrose-density gradient centrifugation revealed that the phosphorylated polypeptides were associated with 26S proteasomes. The 26S proteasome particle in developing seeds was determined to be of approximately 1900 kDa. In vitro, the 26S proteasome degraded associated PyrKinc polypeptides, and this was blocked by proteasome-specific inhibitors such as MG132 and NLVS. By immunoprecipitation, we found that some part of the phosphorylated PyrKinc was conjugated to ubiquitin and shifted to high molecular mass forms in vivo. Moreover, recombinant wild-type PyrKinc was ubiquitinated in vitro to a much greater extent than the S220A and S407A mutant proteins, suggesting a link between phosphorylation and ubiquitination. In addition, during seed development, a progressive accumulation of a C-terminally truncated polypeptide of approximately 51 kDa was observed that was in parallel with a loss of the full-length 55 kDa polypeptide. Interestingly, the C-terminal 51 kDa truncation showed not only pyruvate kinase activity but also activation by aspartate. Collectively, the results suggest that there are two pathways for PyrKinc modification at the post-translational level. One involves partial C-terminal truncation to generate a 51 kDa pyruvate kinase subunit which might have altered regulatory properties and the other involves phosphorylation and ubiquitin conjugation that targets the protein to the 26S proteasome for complete degradation.


In vivo strain of the medial vs. lateral quadriceps tendon in patellofemoral pain syndrome.
Patellofemoral pain (PFP) is thought to be related to patellar maltracking due to imbalances in the knee extensor. However, no study has evaluated the in vivo biomechanical properties of the quadriceps tendon in PFP syndrome. Our purpose was to compare the biomechanical properties of the quadriceps tendons in vivo and noninvasively in patients with PFP syndrome to those of control subjects. The null hypothesis was that the quadriceps tendons of PFP subjects would have significantly decreased strain compared with control subjects. Fourteen subjects (7 control, 7 PFP) performed voluntary ramp isometric contractions to a range of torque levels, while quadriceps tendon elongation was measured using ultrasonography. Tendon strain was calculated for the vastus medialis obliquus (VMO) and vastus lateralis (VL) portion of the quadriceps tendon and compared between subjects (control vs. PFP) and within subjects (VMO vs. VL). PFP subjects showed significantly less VMO tendon strain than control subjects (P<0.001), but there was no difference in VL tendon strain between PFP and control subjects (P=0.100). Relative weakness of the VMO is the most likely cause of the decreased tendon strain seen in subjects with PFP. VMO weakness not only explains the decreased medial tendon strain but also explains the presence of increased lateral patellar translation and lateral patellar spin (distal pole rotates laterally) reported in the literature in this population. This technique can potentially be used in a clinical setting to evaluate quadriceps tendon properties and infer the presence of muscle weakness in PFP.


Lipoprotein(a) as a strong indicator for cerebrovascular disease.
To evaluate the role of lipoprotein(a) (Lp(a] in patients with cerebrovascular disease (CVD), lipid parameters were compared with a control group (CO). Additionally, the Lp(a) serum levels were investigated in a coronary artery disease (CAD) group. The CO was made up of 37 healthy persons (age: 54.5 +/- 7.7, 26 males and 11 females), the CVD group included 46 patients with sustained transient ischemic attack (TIA) prolonged reversible ischemic neurologic deficits (PRIND) and cerebral infarction (CI) (age: 53.6 +/- 9.7, 32 males and 14 females), and the CAD group was made up of 28 survivors of myocardial infarctions (age: 52.5 +/- 8.1, 18 males and 10 females). The median values of Lp(a) in CVD were significantly higher than in the CO (p less than 0.01) and did not differ significantly from the CAD. Total TC, HDL-C, TG, LDL-C and the ratio of LDL-C/HDL-C did not show any significant difference between the control and cerebrovascular disease group. For quantification of the vascular lesions of the carotid system, a Duplex Doppler score system was used. The score correlated with Lp(a) in patients between 40 to 65 years of age (r = 0.34, p less than 0.01). Thus, we conclude that Lp(a) is not only a risk factor for CAD but also for CVD.


Engineering fungal secondary metabolism: a roadmap to novel compounds.
Natural products play important roles not only in the environment but also as useful compounds in various applications like in medicine or plant protection. An enormous number of such compounds have derived from microorganisms colonizing various habitats. Traditionally, new isolates of bacteria or fungi have been screened for their potential to produce biologically active compounds. In the post genomic era, however, there is a growing number of novel methods based on genetic engineering to obtain new metabolites. In this review, we summarize the recent progress made in the development of novel promising approaches for natural product discovery in fungi using genome mining, activation of silent gene clusters, heterologous expression of biosynthesis genes, exchange of enzyme modules as well as redesign of metabolic flux.


The influence of cultural dimensions when implementing fun in the workplace approach as a driver of creativity.
Creativity is essential for success in business, especially in the contemporary world where innovations are a cornerstone of competitive advantage. A large body of literature has examined many factors which influence creative abilities with the work environment being the factor of increasing importance. Creativity has been associated with the work environment through a number of theoretical frameworks and empirical studies. However, the relationship between the work environment and creativity in different cultures has not been explored sufficiently. This paper addresses this gap in the literature by linking the concept of a creativity-supporting work environment and culture. To that end, elements of the work environment (physical, socio-organisational, and fun in the workplace) and creative personality have been analysed on multinational samples. The results clearly point that the relationship exists between dimensions of the national culture (individualism, uncertainty avoidance, masculinity, and power distance) and specific elements of a creativity-supporting work environment. Practitioner summary: Companies experience high pressure for generating creative ideas. As a result, stimulating employees' creativity has become a key strategic aim. This study, through cross-cultural primary research, provides clear managerial implications and practical advice for successful implementation and quality adoption of the creativity-supporting work environment worldwide. Abbreviations: A-FOs: activity-based flexible offices; AVG: average; CDQS: creativity development quick scan; CP: creative personality; CPS: creative personality scale; FWP: fun in the workplace; HF/E: human factors and ergonomics; IDV: individualism; MAS: masculinity; MBA: Master of Business Administration; PDI: power distance; PWE: physical work environment; SWE: socio-organisational work environment; UAI: uncertainty avoidance; USA: United States of America; WE: work environment.


Multidrug resistance: molecular mechanisms and clinical relevance.
Multidrug resistance (MDR) describes the phenomenon of simultaneous resistance to unrelated drugs. It has been a decade since the P-glycoprotein (Pgp) gene, which is associated with a form of MDR caused by reduced drug accumulation, was cloned. Thus, this would seem to be an appropriate time to evaluate our understanding of this form of MDR. The two MDR genes identified in humans to date (the MDR-associated protein [MRP] and Pgp genes) are structurally similar and both are members of the ATP-binding cassette (ABC) transporter family. Although the physiological role of MRP is not yet understood, one Pgp gene (mdr1) plays an important role in the blood-tissue barrier and the other (mdr2/3) is involved in phospholipid transport in the liver. A variety of compounds (chemosensitizing agents) can interfere with Pgp and MRP function; such agents may improve the efficacy of conventional therapy when used in combination with such regimens. Determining the roles cellular MDR mechanisms play in patients' response to chemotherapy is a major challenge. Using Pgp and MRP as molecular markers to detect MDR tumor cells is technically demanding, and solid tumors in particular contain heterogeneous cell populations. Since MDR requires Pgp or MRP gene expression, clinically relevant gene expression thresholds need to be established; sequential samples from individual patients are valuable for correlating MDR gene expression with the clinical course of disease. Studies in leukemias, myelomas, and some childhood cancers show that Pgp expression correlates with poor response to chemotherapy. However, in some cases, inclusion of a reversing or chemosensitizing agent such as verapamil or cyclosporin A has improved clinical efficacy. Such agents may inactivate Pgp in tumor cells or affect Pgp function in normal cells, resulting in altered pharmacokinetics. It would be interesting to determine whether patients who fail treatment in the presence of chemosensitizing agents acquire other MDR mechanisms. The ABC transporter superfamily in prokaryotes and eukaryotes is involved in the transport of substrates ranging from ions to large proteins. Of the 15 or more ABC transporter genes characterized in human cells, two (Pgp and MRP) cause MDR. Therefore, it would be relevant to determine the number of such genes present in the human genome; however, extrapolating from the number of ABC transporter genes in bacteria, the human gene probably contains a minimum of 200 ABC transporter superfamily members. Thus, tumor cells can potentially use many ABC transporters to mount resistance to known and future therapeutic agents. The challenge will be to determine which ABC transporters are clinically relevant. Despite the potential of tumor cells to protect themselves, a variety of malignancies can be successfully treated with chemotherapy. This may provide unique insights.


Antioxidant and Anti-Inflammatory Activities of Stellera chamaejasme L. Roots and Aerial Parts Extracts.
Natural products, mainly plants, have a crucial role in folk medicine. Particularly, Stellera chamaejasme L. has been traditionally used in Mongolian medicine to treat various diseases, including chronic tracheitis, tuberculosis, and psoriasis. In this study, ethanol (EtOH) and dichloromethane (DCM) extracts of its roots (R) and aerial parts (AP) were evaluated for their antioxidant and anti-inflammatory activities. Thin-layer chromatography demonstrated the presence of flavonoids, namely kaempferol and quercetin-3-O-glucopyranoside, only in the EtOH-AP. Conversely, it showed that kaempferol, quercetin-3-O-glucopyranoside, coumarin, luteolin, rutin, morin, and riboflavin were not present in the other three extracts. The S. chamaejasme extracts exhibited strong antioxidant activity. In addition, the roots extracts presented the highest antioxidant activity against peroxyl radicals, with the EtOH-R being the most potent (IC50 = 0.90 ± 0.07 µg/mL). S. chamaejasme extracts also efficiently inhibited the production of one of the main pro-inflammatory cytokines, interleukin (IL)-6, in a dose-dependent manner by lipopolysaccharide-stimulated macrophages. Particularly, DCM-R was the strongest extract, reducing ≈ 91.5% of the IL-6 production. Since this extract was the most effective, gas chromatography-mass spectrometry (GC-MS) analyses were performed and demonstrated the presence of two fatty acids (palmitic acid and 9-octadecenoic acid), one fatty alcohol (1-hexadecanol), and one triterpenoid (squalene) that can contribute to the observed bioactivity. Herewith, S. chamaejasme extracts, mainly DCM-R, exhibit antioxidant and anti-inflammatory activities that could be applied as new and innovative natural formulations for the treatment of chronic inflammatory diseases.


Pharmacokinetic properties and antitumor efficacy of the 5-fluorouracil loaded PEG-hydrogel.
We have studied the in vitro and in vivo utility of polyethylene glycol (PEG)-hydrogels for the development of an anticancer drug 5-fluorouracil (5-FU) delivery system. A 5-FU-loaded PEG-hydrogel was implanted subcutaneously to evaluate the drug retention time and the anticancer effect. For the pharmacokinetic study, two groups of male rats were administered either an aqueous solution of 5-FU (control group)/or a 5-FU-loaded PEG-hydrogel (treated group) at a dose of 100 mg/kg. For the pharmacodynamic study, a human non-small-cell lung adenocarcinoma (NSCLC) cell line, A549 was inoculated to male nude mice with a cell density of 3 x 10(6). Once tumors start growing, the mice were injected with 5-FU/or 5-FU-loaded PEG-hydrogel once a week for 4 weeks. The growth of the tumors was monitored by measuring the tumor volume and calculating the tumor inhibition rate (IR) over the duration of the study. In the pharmacokinetic study, the 5-FU-loaded PEG-hydrogel gave a mean residence time (MRT) of 8.0 h and the elimination half-life of 0.9 h; these values were 14- and 6-fold, respectively, longer than those for the free solution of 5-FU (p < 0.05). In the pharmacodynamic study, A549 tumor growth was significantly inhibited in the 5-FU-loaded PEG-hydrogel group in comparison to the untreated group beginning on Day 14 (p < 0.05-0.01). Moreover, the 5-FU-loaded PEG-hydrogel group had a significantly enhanced tumor IR (p < 0.05) compared to the free 5-FU drug treatment group. We suggest that 5-FU-loaded PEG-hydrogels could provide a useful tool for the development of an anticancer drug delivery system.


Stomatal control and leaf thermal and hydraulic capacitances under rapid environmental fluctuations.
Leaves within a canopy may experience rapid and extreme fluctuations in ambient conditions. A shaded leaf, for example, may become exposed to an order of magnitude increase in solar radiation within a few seconds, due to sunflecks or canopy motions. Considering typical time scales for stomatal adjustments, (2 to 60 minutes), the gap between these two time scales raised the question whether leaves rely on their hydraulic and thermal capacitances for passive protection from hydraulic failure or over-heating until stomata have adjusted. We employed a physically based model to systematically study effects of short-term fluctuations in irradiance on leaf temperatures and transpiration rates. Considering typical amplitudes and time scales of such fluctuations, the importance of leaf heat and water capacities for avoiding damaging leaf temperatures and hydraulic failure were investigated. The results suggest that common leaf heat capacities are not sufficient to protect a non-transpiring leaf from over-heating during sunflecks of several minutes duration whereas transpirative cooling provides effective protection. A comparison of the simulated time scales for heat damage in the absence of evaporative cooling with observed stomatal response times suggested that stomata must be already open before arrival of a sunfleck to avoid over-heating to critical leaf temperatures. This is consistent with measured stomatal conductances in shaded leaves and has implications for water use efficiency of deep canopy leaves and vulnerability to heat damage during drought. Our results also suggest that typical leaf water contents could sustain several minutes of evaporative cooling during a sunfleck without increasing the xylem water supply and thus risking embolism. We thus submit that shaded leaves rely on hydraulic capacitance and evaporative cooling to avoid over-heating and hydraulic failure during exposure to typical sunflecks, whereas thermal capacitance provides limited protection for very short sunflecks (tens of seconds).


Holographic representations of space-variant systems using phase-coded reference beams.
A new holographic implementation of a sampling technique permits, in principle, a straightforward representation of 2-D space-variant optical systems. The set of sample transfer functions required for the representation is recorded on a single holographic plate by utilizing phase coded reference beams. Because this approach does not depend on volume effects in the recording medium in an essential way, the holograms can be produced digitally, as well as optically. Basic concepts and preliminary experimental investigations related to this approach are presented and discussed.


[Ehrlichiosis and human anaplasmosis].
Human ehrlichiosis and anaplasmosis are acute febrile tick-borne diseases caused by various species of the genera Ehrlichia and Anaplasma (Anaplasmataceae). To date, only cases of human granulocytic anaplasmosis (HGA) caused by Anaplasma phagocytophilum (formerly human granulocytic Ehrlichia, Ehrlichia phagocytophila, and E. equi) have been diagnosed in Europe. HGA and Lyme borreliosis are closely related diseases that share vector and reservoirs. In addition to HGA, human monocytic ehrlichiosis caused by E. chaffeensis has been reported in North America, as well as cases of infection due to E. ewingii in immunocompromised hosts. Ehrlichia spp. and A. phagocytophilum have tropism for blood cells, especially leukocytes and platelets, causing a considerable decrease of both components in these patients. HGA should be suspected in tick-bitten patients or those who have visited an endemic area and show symptoms of flu-like fever, leukopenia and thrombocytopenia.


Heat stress and dehydration in adapting for performance: Good, bad, both, or neither?
Physiological systems respond acutely to stress to minimize homeostatic disturbance, and typically adapt to chronic stress to enhance tolerance to that or a related stressor. It is legitimate to ask whether dehydration is a valuable stressor in stimulating adaptation per se. While hypoxia has had long-standing interest by athletes and researchers as an ergogenic aid, heat and nutritional stressors have had little interest until the past decade. Heat and dehydration are highly interlinked in their causation and the physiological strain they induce, so their individual roles in adaptation are difficult to delineate. The effectiveness of heat acclimation as an ergogenic aid remains unclear for team sport and endurance athletes despite several recent studies on this topic. Very few studies have examined the potential ergogenic (or ergolytic) adaptations to ecologically-valid dehydration as a stressor in its own right, despite longstanding evidence of relevant fluid-regulatory adaptations from short-term hypohydration. Transient and self-limiting dehydration (e.g., as constrained by thirst), as with most forms of stress, might have a time and a place in physiological or behavioral adaptations independently or by exacerbating other stressors (esp. heat); it cannot be dismissed without the appropriate evidence. The present review did not identify such evidence. Future research should identify how the magnitude and timing of dehydration might augment or interfere with the adaptive processes in behaviorally constrained versus unconstrained humans.


Effect of periodontal surgery on oral health-related quality of life in patients who have completed initial periodontal therapy.
Patient-centered assessments are particularly important in periodontal treatment in which their concerns may differ from the traditional clinical endpoints. However, information is limited regarding the influence of periodontal surgery on patients' quality of life (QoL). The aim of the present study was to investigate the impact of surgical periodontal therapy on the oral health-related QoL of patients who have received initial periodontal therapy. A three-center prospective clinical study design was used, with the study participants comprising patients with moderate to severe periodontitis. Following initial periodontal therapy, the participants received either surgical or non-surgical periodontal treatment. The Oral Health-related Quality of Life Model for Dental Hygiene (OHRQL instrument), was used to assess participants' oral health-related QoL at each periodontal assessment interval: baseline (phase I), after initial therapy (phase II) and after surgery or during supportive periodontal therapy (phase III). Seventy-six patients (26 non-surgery, 50 surgery) completed the third phase of OHRQL assessment and were subjected to data analysis. From phase II to III, an improvement was achieved in all clinical parameters (p < 0.05-0.001) in the surgery group, whereas no such improvement was observed in the non-surgery group. In both groups, a significant difference in total OHRQL score was noted between phases I and III (p < 0.001 for surgery and p < 0.05 for non-surgery). The OHRQL domain scores for pain and eating/chewing function showed a significant improvement between these time points. However, no further significant improvement in OHRQL scores was achieved from phase II to III. A significant improvement in oral health-related QoL was noted between phases I and III in the surgery and non-surgery groups. Such improvement was less pronounced in the non-surgery vs. the surgery group. From phase II to III, neither surgery nor non-surgical treatment yielded significant improvement in oral health-related QoL.


Rupture of a pseudo aneurysm of the abdominal aorta in a patient with human immunodeficiency virus infection.
Human immunodeficiency virus (HIV) infection has an impact on all systems of the body, including the cardiovascular system. A 54-year-old man presented with abdominal pain. Enhanced computed tomography revealed rupture of a pseudoaneurysm of the abdominal aorta. After surgery, the patient tested positive for HIV. Histological examination of the resected aorta showed leukocytoclastic vasculitis, a characteristic feature of HIV-related vasculitis.


A novel temporal calibration method for 3-D ultrasound.
This paper examines a novel approach for temporal calibration of a three-dimensional (3-D) freehand ultrasound system. A localization system fixed on the probe gives the position and orientation of the probe. For quantitative use, calibration is needed to correctly localize a B-scan in four-dimensional (4-D) (3-D+t) space. Temporal latency estimation is defined in a general robust formulation using no specific probe motion constraints. Experiments were performed on synthetic and real data using a 3-D freehand ultrasound system. The achieved precision is lower than the image acquisition rate (40 ms). A validation study using a calibration phantom has been performed to evaluate the influence of incorrect latency estimation on the 3-D reconstruction procedure. We showed that for latency estimation errors less than 40 ms, the 3-D reconstruction errors are negligible for volume estimation.


Increasing access to cholesterol screening in rural communities catalyzes cardiovascular disease prevention.
Despite increasing frequency, little evidence guides cholesterol screening in less traditional health care settings, such as rural health fairs. The Miller School of Medicine Department of Community Service (DOCS) is a student-run organization providing free basic health care to underserved South Florida communities. We retrospectively reviewed all new patients seen at 2007 DOCS rural fairs to describe their low-density lipoprotein (LDL) and high-density lipoprotein (HDL) values. In addition, we assessed if patient characteristics were associated with cholesterol abnormalities and whether patients with abnormalities who returned to a subsequent fair in 2008 or 2009 improved their cholesterol. Of 252 patients, 145 (58%) had an LDL cholesterol over 129 mg/dL and 61 (24%) had an HDL cholesterol below 40 mg/dL or 50 mg/dL for males and females, respectively. Baseline LDL cholesterol was not associated with body-mass index (BMI), age over 60 years, gender, healthy lifestyle habits, or insurance status. Of 36 patients with elevated LDL cholesterol and a follow-up screening, 24 (67%) reduced their LDL cholesterol by at least 16 mg/dL though reductions were not associated with BMI reduction, and 22 (61%) increased their HDL cholesterol by at least 5 mg/dL, trending with BMI reduction. Cholesterol screening at rural fairs can identify a high proportion of patients with abnormal cholesterol, including those who might not be considered at high risk. Although this may catalyze favorable cholesterol changes, the lack of an association with weight loss suggests patients seek additional medical care, which should be considered before offering cholesterol screening at fairs.


Small-Area, Resistive Volatile Organic Compound (VOC) Sensors Using Metal-Polymer Hybrid Film Based on Oxidative Chemical Vapor Deposition (oCVD).
We report a novel room temperature methanol sensor comprised of gold nanoparticles covalently attached to the surface of conducting copolymer films. The copolymer films are synthesized by oxidative chemical vapor deposition (oCVD), allowing substrate-independent deposition, good polymer conductivity and stability. Two different oCVD copolymers are examined: poly(3,4-ethylenedioxythiophene-co-thiophene-3-aceticacid)[poly(EDOT-co-TAA)] and poly(3,4-ehylenedioxythiophene-co-thiophene-3-ethanol)[poly(EDOT-co-3-TE)]. Covalent attachment of gold nanoparticles to the functional groups of the oCVD films results in a hybrid system with efficient sensing response to methanol. The response of the poly(EDOT-co-TAA)/Au devices is found to be superior to that of the other copolymer, confirming the importance of the linker molecules (4-aminothiophenol) in the sensing behavior. Selectivity of the sensor to methanol over n-pentane, acetone, and toluene is demonstrated. Direct fabrication on a printed circuit board (PCB) is achieved, resulting in an improved electrical contact of the organic resistor to the metal circuitry and thus enhanced sensing properties. The simplicity and low fabrication cost of the resistive element, mild working temperature, together with its compatibility with PCB substrates pave the way for its straightforward integration into electronic devices, such as wireless sensor networks.


Effect of treatment gaps in elderly patients with dementia treated with cholinesterase inhibitors.
To determine the effect of treatment gaps on the risk of institutionalization or death among community-dwelling elderly patients treated with cholinesterase inhibitors (ChIs). A survival analysis was conducted among a cohort of community-dwelling elderly patients (age 66+) newly treated with ChIs identified in the Quebec drug claims databases (Régie de l'Assurance Maladie du Québec [RAMQ]) between January 1, 2000, and December 31, 2007. Treatment nonpersistence during the year following ChI initiation was defined as treatment discontinuation or gaps of at least 6 weeks. To account for reverse causality, Cox proportional hazard modeling was conducted only among patients who did not discontinue treatment, in order to assess the association between treatment nonpersistence and institutionalization or death. Among the 24,394 elderly ChI users, 4,108 (16.8) experienced a treatment gap during the year following ChI treatment initiation while 596 (2.4%) discontinued their treatment within the first 3 months (early stoppers) and 4,038 (16.6%) after 3 months of treatment (late stoppers). Of all treated patients, 4,409 (18.1%) were institutionalized or died during follow-up. In patients who did not stop their treatment, the risk of institutionalization or death appeared lower in patients who experienced a treatment gap (hazard ratio 0.91; 95% confidence interval 0.86-0.96). Our results suggest that, contrary to what was previously reported in clinical trials, treatment gaps do not compromise the outcome of patients treated with ChIs in a real-life setting.


Dual-purpose, compact spectrometer and fiber-coupled laser wavemeter based on a wollaston prism.
A fiber-coupled, compact laser wavemeter based on a modified Wollaston prism has been constructed and evaluated. The path difference between orthogonal polarization states of the input light varies smoothly across the aperture of the prism forming an interferogram in the spatial domain that is recorded with a CCD detector array. A Fourier transform of this interferogram gives the spectral distribution of the incident light. Alternatively, for a narrow-linewidth source a fringe period measurement technique is used to obtain precision measurement of the center wavelength. Using 752 interferogram data points we obtain a wavelength precision of 1 part in 10(6). The elimination of moving parts from the design makes the recorded interferogram inherently stable.


Surface and Structural Properties of Novel Titanium Phosphates
Two novel fibrous framework titanium phosphates having a similar formula, Ti2O(PO4)2·H2O, and a layered titanium phosphate, Ti2O3(H2PO4)2·2H2O, were synthesized and their properties were characterized with physicochemical methods, such as elemental analysis, thermogravimetry, nitrogen adsorption, X-ray diffraction, and 31P solid-state NMR. Nitrogen adsorption isotherms were measured on synthesized titanium phosphates in order to characterize their surface and structural properties. The specific surface area and total pore volume of the titanium phosphates studied were determined. The low-pressure nitrogen adsorption isotherms were used to evaluate surface heterogeneity of the synthesized materials by employing an advanced numerical procedure based on the regularization method.


Altered amygdala-prefrontal connectivity during emotion perception in schizophrenia.
Individuals with schizophrenia evidence impaired emotional functioning. Abnormal amygdala activity has been identified as an etiological factor underlying affective impairment in this population, but the exact nature remains unclear. The current study utilized psychophysiological interaction analyses to examine functional connectivity between the amygdala and medial prefrontal cortex (mPFC) during an emotion perception task. Participants with schizophrenia (SZ) and healthy controls (HC) viewed and rated positive, negative, and neutral images while undergoing functional neuroimaging. Results revealed a significant group difference in right amygdala-mPFC connectivity during perception of negative versus neutral images. Specifically, HC participants demonstrated positive functional coupling between the amygdala and mPFC, consistent with co-active processing of salient information. In contrast, SZ participants evidenced negative functional coupling, consistent with top-down inhibition of the amygdala by the mPFC. A significant positive correlation between connectivity strength during negative image perception and clinician-rated social functioning was also observed in SZ participants, such that weaker right amygdala-mPFC coupling during negative compared to neutral image perception was associated with poorer social functioning. Overall, results suggest that emotional dysfunction and associated deficits in functional outcome in schizophrenia may relate to abnormal interactions between the amygdala and mPFC during perception of emotional stimuli. This study adds to the growing literature on abnormal functional connections in schizophrenia and supports the functional disconnection hypothesis of schizophrenia.


Convergent innovation for affordable nutrition, health, and health care: the global pulse roadmap.
The paper outlines how the principles of convergent innovation (CI) can be applied to bring about a transformation in the pulse value chain. The paper presents three pioneering CI initiatives--two in conception and one in operation--by various actors in the pulse ecosystem, which are delivering economic and human development impact in particular segments of the pulse value chain. It goes on to propose the way forward to scale up these efforts and connect them into a roadmap so as to achieve transformation throughout society, calling into action a number of actors in the ecosystem.


Cost-effectiveness of on-site versus off-site collaborative care for depression in rural FQHCs.
Collaborative care for depression in primary care settings is effective and cost-effective. However, there is minimal evidence to support the choice of on-site versus off-site models. This study examined the cost-effectiveness of on-site practice-based collaborative care (PBCC) versus off-site telemedicine-based collaborative care (TBCC) for depression in federally qualified health centers (FQHCs). In a multisite, randomized, pragmatic comparative cost-effectiveness trial, 19,285 patients were screened for depression, 2,863 (14.8%) screened positive, and 364 were enrolled. Telephone interview data were collected at baseline and at six, 12, and 18 months. Base case analysis used Arkansas FQHC health care costs, and secondary analysis used national cost estimates. Effectiveness measures were depression-free days and quality-adjusted life years (QALYs) derived from depression-free days, the 12-Item Short-Form Survey, and the Quality of Well-Being (QWB) Scale. Nonparametric bootstrap with replacement methods were used to generate an empirical joint distribution of incremental costs and QALYs and acceptability curves. The TBCC intervention resulted in more depression-free days and QALYs but at a greater cost than the PBCC intervention. The disease-specific (depression-free day) and generic (QALY) incremental cost-effectiveness ratios (ICERs) were below their respective ICER thresholds for implementation, suggesting that the TBCC intervention was more cost effective than the PBCC intervention. These results support the cost-effectiveness of TBCC in medically underserved primary care settings. Information about whether to insource (make) or outsource (buy) depression care management is important, given the current interest in patient-centered medical homes, value-based purchasing, and bundled payments for depression care.


Human eukaryotic initiation factor 4G (eIF4G) protein binds to eIF3c, -d, and -e to promote mRNA recruitment to the ribosome.
Recruitment of mRNA to the 40S ribosomal subunit requires the coordinated interaction of a large number of translation initiation factors. In mammals, the direct interaction between eukaryotic initiation factor 4G (eIF4G) and eIF3 is thought to act as the molecular bridge between the mRNA cap-binding complex and the 40S subunit. A discrete ∼90 amino acid domain in eIF4G is responsible for binding to eIF3, but the identity of the eIF3 subunit(s) involved is less clear. The eIF3e subunit has been shown to directly bind eIF4G, but the potential role of other eIF3 subunits in stabilizing this interaction has not been investigated. It is also not clear if the eIF4A helicase plays a role in stabilizing the interaction between eIF4G and eIF3. Here, we have used a fluorescence anisotropy assay to demonstrate that eIF4G binds to eIF3 independently of eIF4A binding to the middle region of eIF4G. By using a site-specific cross-linking approach, we unexpectedly show that the eIF4G-binding surface in eIF3 is comprised of the -c, -d and -e subunits. Screening multiple cross-linker positions reveals that eIF4G contains two distinct eIF3-binding subdomains within the previously identified eIF3-binding domain. Finally, by employing an eIF4G-dependent translation assay, we establish that both of these subdomains are required for efficient mRNA recruitment to the ribosome and stimulate translation. Our study reveals unexpected complexity to the eIF3-eIF4G interaction that provides new insight into the regulation of mRNA recruitment to the human ribosome.


Corrections and clarifications.
In the article "Light emission from silicon" by S. S. Iyer and Y.-H. Xie (2 Apr., p. 40), the title in reference 33 on page 46 should have read, "Extended Abstracts of the 1992 Solid-State Devices and Materials Conference."


Change in Insurance Status and Cost-related Medication Non-adherence among Older U.S. Adults with Diabetes from 2010 to 2014.
Cost-related medication non-adherence (CRN) is a persistent challenge in health care in the U.S. Insurance coverage is a key determinant of access to medical care. We seek to examine the CRN rates among the older diabetes adult population in the U.S. from 2010 to 2014 when the major provisions of the Affordable Care Act came into force. Data from the 2010 and 2014 Health and Retirement Study (HRS) were used for this study. CRN is identified if a respondent indicated taking less medication than was prescribed because of the cost, while diabetes is self-reported. We assessed the change in CRN rates by insurance status using multivariable logistic regression analysis. A total of 4,741 and 4,505 diabetes adults aged 50 or older in 2010 and 2014 were included in the analyses, representing 18.8 million and 19.1 million older adults with diabetes respectively. Overall, the percentage of dual-eligible diabetes patients increased from 8% to 10% and the uninsured decreased from 6% to 4% based on weighted population estimates. The CRN rates decreased from 27% to 21% and from 12% to 10% for those between 50 and 64, and 65 or older, respectively from 2010 to 2014. Race (African American) became a less significant factor for variations in CRN rates in 2014 (p=0.24). There is an encouraging reduction in CRN rates after implementation of the ACA. However, CRN rates among diabetes patients between 50 and 65 of age remained high.


Characterization of alterations in plasma lipoprotein lipid and apoprotein profiles accompanying hepatoma-induced hyperlipidemia in rats.
Alterations in plasma lipoprotein lipid and apoprotein accompanying the hyperlipidemia of rats bearing Morris hepatoma 7288C were characterized. In tumor-bearing animals all plasma lipid classes except cholesterol ester (CE) were elevated, particularly free cholesterol (FC) and triglyceride (TG), which increased by 57 and 63%, respectively. Fasting only partially reduced the tumor-induced hyperlipidemia and had no effect on the ratios of FC/CE and TG/CE. Analysis of plasma lipoproteins revealed an elevation of VLDL, IDL, and LDL in host rats, with more than a 2-fold increase in both lipid and protein of VLDL. In contrast, the three high density fractions, HDL2, HDL3, and d greater than 1.21 g/ml, were reduced. The inverse changes in concentration of host lipoproteins of lower versus higher density indicate a defective catabolism of TG-rich lipoprotein. This possibility is supported by the analysis of apolipoprotein. The percentage of total apoprotein contributed by apo C-I and C-II was reduced in all host fractions except HDL2, while the C-IIIs remained unchanged except for a small decrease in C-III-3 of host VLDL and a slight increase in the combined C-IIIs of HDL2. These changes were reflected in the decreased C-I+C-II/C-III ratios of all host lipoprotein fractions. Apo E levels remained similar to control values except for a significant decrease in HDL2. Host VLDL showed increased apo A-IV and A-I content, while A-IV was decreased in HDL2. Changes in apo B profiles were also observed.