Effect of Heart Rate Variability Biofeedback Sessions With Resonant Frequency Breathing on Sleep: A Pilot Study Among Family Caregivers of Patients With Cancer.
Heart rate variability biofeedback (HRV-BF) is used as a skill in psychosomatic medicine, but is not yet established in the field of sleep. The present study aimed to evaluate the effect of HRV-BF with resonant frequency breathing (RFB) on sleep performed once every 2 weeks and the usefulness of practice of RFB using a portable device at home before bedtime. Participants were 69 family caregivers of patients with cancer that felt burdened by nursing care. We conducted a randomized controlled trial with an HRV-BF+Home practice group and an HRV-BF group. HRV-BF with RFB was administered to both groups at our medical institution for up to 30 min on the experiment days. Home practice involved RFB using a portable device, which was performed at home each day within 20 min before bedtime. Evaluation items were: change ratio of total score of the Pittsburgh Sleep Quality Index (PSQI) at 28 days after the trial started. In total, 52.2% of participants had insomnia. The two HRV-BF groups had decreased PSQI total scores, which indicated an improvement in PSQI total score near 5.5 on Day 28. The two HRV-BF groups had significantly increased HRV scores on Day 28, and there was correlation between the variation of PSQI total score and the variation of HRV score. The quality of sleep assessed by PSQI scores in the HRV-BF+Home practice group was significantly improved compared with the HRV-BF group on Day 28 (p = 0.001). This suggests HRV-BF may be a useful skill for enhancing sleep among family caregivers of patients with cancer, as well as supporting their autonomic nervous function. Additional actual regular practice of RFB (using a portable device at home before bedtime) may further enhance the effect.


The iRoCS Toolbox--3D analysis of the plant root apical meristem at cellular resolution.
To achieve a detailed understanding of processes in biological systems, cellular features must be quantified in the three-dimensional (3D) context of cells and organs. We described use of the intrinsic root coordinate system (iRoCS) as a reference model for the root apical meristem of plants. iRoCS enables direct and quantitative comparison between the root tips of plant populations at single-cell resolution. The iRoCS Toolbox automatically fits standardized coordinates to raw 3D image data. It detects nuclei or segments cells, automatically fits the coordinate system, and groups the nuclei/cells into the root's tissue layers. The division status of each nucleus may also be determined. The only manual step required is to mark the quiescent centre. All intermediate outputs may be refined if necessary. The ability to learn the visual appearance of nuclei by example allows the iRoCS Toolbox to be easily adapted to various phenotypes. The iRoCS Toolbox is provided as an open-source software package, licensed under the GNU General Public License, to make it accessible to a broad community. To demonstrate the power of the technique, we measured subtle changes in cell division patterns caused by modified auxin flux within the Arabidopsis thaliana root apical meristem.


Occupancy classification of position weight matrix-inferred transcription factor binding sites.
Computational prediction of Transcription Factor Binding Sites (TFBS) from sequence data alone is difficult and error-prone. Machine learning techniques utilizing additional environmental information about a predicted binding site (such as distances from the site to particular chromatin features) to determine its occupancy/functionality class show promise as methods to achieve more accurate prediction of true TFBS in silico. We evaluate the Bayesian Network (BN) and Support Vector Machine (SVM) machine learning techniques on four distinct TFBS data sets and analyze their performance. We describe the features that are most useful for classification and contrast and compare these feature sets between the factors. Our results demonstrate good performance of classifiers both on TFBS for transcription factors used for initial training and for TFBS for other factors in cross-classification experiments. We find that distances to chromatin modifications (specifically, histone modification islands) as well as distances between such modifications to be effective predictors of TFBS occupancy, though the impact of individual predictors is largely TF specific. In our experiments, Bayesian network classifiers outperform SVM classifiers. Our results demonstrate good performance of machine learning techniques on the problem of occupancy classification, and demonstrate that effective classification can be achieved using distances to chromatin features. We additionally demonstrate that cross-classification of TFBS is possible, suggesting the possibility of constructing a generalizable occupancy classifier capable of handling TFBS for many different transcription factors.


Gas exchange and ventilation imaging of healthy and COPD subjects using hyperpolarized xenon-129 MRI and a 3D alveolar gas-exchange model.
To investigate the utility of hyperpolarized xenon-129 (HPX) gas-exchange magnetic resonance imaging (MRI) and modeling in a chronic obstructive pulmonary disease (COPD) cohort in comparison to a minimal CT-diagnosed emphysema (MCTE) cohort and a healthy cohort. A total of 25 subjects were involved in this study including COPD (n = 8), MCTE (n = 3), and healthy (n = 14) subjects. The COPD subjects were scanned using HPX ventilation, gas-exchange MRI, and volumetric CT. The healthy subjects were scanned using the same HPX gas-exchange MRI protocol with 9 of them scanned twice, 3 weeks apart. The coefficient of variation (CV) was used to quantify image heterogeneities. A three-dimensional computational fluid dynamic (CFD) model of gas exchange was used to derive functional volumes of pulmonary tissue, capillaries, and veins. The CVs of gas distributions in the images showed that there was a statistically significant difference between the COPD and healthy subjects (p < 0.0001). The functional volumes of pulmonary tissue, capillaries, and veins were significantly lower in the subjects with COPD than in the healthy subjects (p < 0.001). The functional volume of pulmonary tissue was found to be (i) statistically different between the healthy and MCTE groups (p = 0.02) and (ii) dependent on the age of the subjects in the healthy group (p = 0.0008) while their CVs (p = 0.13) were not. The novel HPX gas-exchange MRI and CFD model distinguished the healthy cohort from the MCTE and COPD cohorts. The proposed technique also showed that the functional volume of pulmonary tissue decreases with aging in the healthy group. • The ventilation and gas-exchange imaging with hyperpolarized xenon-129 MRI has enabled the identification of gas-exchange variation between COPD and healthy groups. • This novel technique was promising to be sensitive to minimal CT-diagnosed emphysema and age-related changes in gas-exchange parameter in a small pilot cohort.


Computational studies of photophysical properties of porphin, tetraphenylporphyrin and tetrabenzoporphyrin.
The molecular photonics of porphyrins are studied using a combination of first-principle and semi-empirical calculations. The applicability of the approach is demonstrated by calculations on free-base porphyrin, tetraphenylporphyrin, and tetrabenzoporphyrin. The method uses excitation energies and oscillator strengths calculated at the linear-response time-dependent density functional theory (TDDFT) or the corresponding values calculated at the linear-response approximate second-order coupled-cluster (CC2) levels. The lowest singlet excitation energies obtained in the TDDFT and CC2 calculations are 0.0-0.28 eV and 0.18-0.47 eV larger than the experimental values, respectively. The excitation energies for the first triplet state calculated at the TDDFT level are in excellent agreement with experiment, whereas the corresponding CC2 values have larger deviations from experiment of 0.420.66 eV. The matrix elements of the spin-orbit and non-adiabatic coupling operators have been calculated at the semi-empirical intermediate neglect of differential overlap (INDO) level using a spectroscopic parameterization. The calculations yield rate constants for internal conversion and intersystem crossing processes as well as quantum yields for fluorescence and phosphorescence. The main mechanism for the quenching of fluorescence in tetraphenylporphyrin and tetrabenzoporphyrin is the internal conversion, whereas for free-base porphyrin both the internal conversion and the intersystem crossing processes reduce the fluorescence intensity. The phosphorescence is quenched by a fast internal conversion from the triplet to the ground state.


Karyotypic evolution in human malignant melanoma.
Chromosome studies were performed on direct preparations, early passage cultures, and cell lines derived from melanocytic lesions of 37 patients. There were six congenital or common acquired nevi, six dysplastic nevi, one early primary melanoma (radial growth phase), three complex melanomas (RGP with foci of vertical growth phase), six advanced primary melanomas (VGP), and 26 metastases. The karyotype was normal in the six common nevi. A chromosomally abnormal clone with a single karyotypic alteration was found in two dysplastic nevi. All melanomas had clones with multiple cytogenetic changes. Nonrandom abnormalities involving translocations or deletions in the short arm of chromosome #1, either arm of chromosome #6, and/or extra copies of the short arm of chromosome #7 were present in all melanomas. These were not obviously associated with a particular stage of disease, except that the only nonrandom alteration in the early (RGP) melanoma involved chromosome #6. In four cases, cytogenetic data were available on both a primary melanoma and its metastases. In each instance there were common alterations (demonstrating the clonality of the disease), as well as additional changes in the metastases. Our findings indicate that demonstrable somatic genetic abnormalities increase in severity with clinical progression of melanocytic disease, but additional data are required to establish the significance of specific karyotypic changes (and the involved genes) in the clinical evolution of these disorders.


Unexpected hormonal activity of a catechol equine estrogen metabolite reveals reversible glutathione conjugation.
4-Hydroxyequilenin (4-OHEN) is a major phase I metabolite of the equine estrogens present in widely prescribed hormone replacement formulations. 4-OHEN is autoxidized to an electrophilic o-quinone that has been shown to redox cycle, generating ROS, and to covalently modify proteins and DNA and thus potentially to act as a chemical carcinogen. To establish the ability of 4-OHEN to act as a hormonal carcinogen at the estrogen receptor (ER), estrogen responsive gene expression and proliferation were studied in ER(+) breast cancer cells. Recruitment by 4-OHEN of ER to estrogen responsive elements (ERE) of DNA in MCF-7 cells was also studied and observed. 4-OHEN was a potent estrogen, with additional weak activity associated with binding to the arylhydrocarbon receptor (AhR). The potency of 4-OHEN toward classical ERalpha mediated activity was unexpected given the reported rapid autoxidation and trapping of the resultant quinone by GSH. Addition of thiols to cell cultures did not attenuate the estrogenic activity of 4-OHEN, and preformed thiol conjugates added to cell incubations only marginally reduced ERE-luciferase induction. On reaction of the 4OHEN-GSH conjugate with NADPH, 4-OHEN was observed to be regenerated at a rate dependent upon NADPH concentration, indicating that intracellular nonenzymatic and enzymatic regeneration of 4-OHEN accounts for the observed estrogenic activity of 4-OHEN. 4-OHEN is therefore capable of inducing chemical and hormonal pathways that may contribute to estrogen-dependent carcinogenesis, and trapping by cellular thiols does not provide a mechanism of termination of these pathways.


Impact of low birth weight and cardiovascular risk factors on endothelial function in early adult life.
Low birth weight is related to increased risk of coronary heart disease in adults and recently has been associated with vascular endothelial dysfunction in children. We investigated whether the relation between birth weight and endothelial function was still present in early adult life and whether there was an interaction with emerging risk factors. In 315 adults (165 women, 150 men, aged 20 to 28 years), high-resolution ultrasound was used to determine endothelium-dependent and -independent vascular responses of the brachial artery. Vascular measures were related to classic risk factors (smoking history, lipid profile, blood pressure, fasting insulin, exercise capacity, body mass index, and combined risk score) and birth weight. Low birth weight was associated with reduced flow-mediated dilation (coefficient=0.18 kg(-1), 95% CI 0.004 to 0.35, P:=0.04) but not with endothelium-independent dilation. The difference in flow-mediated dilation between the top and bottom fifths of birth weight was the same as between smokers and nonsmokers. Increasing levels of acquired risk factors overwhelmed the association, and there was a significant interaction of risk score with the birth weight-endothelial function relation (coefficient of interaction term [birth weightxrisk score] = -0.12, 95% CI -0.22 to -0.03, P:=0.01). Low birth weight is associated with endothelial dysfunction in young adults. This is most marked in individuals with lower risk factor profiles and may be relevant to the pathogenesis of atherosclerosis in later life.


Detection of longitudinal lung structural and functional changes after diagnosis of radiation-induced lung injury using hyperpolarized 3He magnetic resonance imaging.
Therapeutic radiation doses for thoracic tumors are significantly restricted to decrease the risk of nontumor tissue damage, yet radiation-induced lung injury (RILI) still occurs in over 1/3 of thoracic radiation treatment cases. Although RILI can be clinically monitored using pulmonary function measurements, the regional functional effects of the injury are not well understood. Hyperpolarized 3He magnetic resonance imaging provides measurements of regional lung function and structure with high spatial and temporal resolution; the authors use this tool longitudinally for the first time in seven subjects after clinical diagnosis of RILI in order to better understand regional changes in lung function and structure post-RILI. All subjects underwent spirometry, plethysmography, and MRI at 3.0 T 35.1 +/- 12.2 weeks after radiation therapy commenced. Thoracic 1H, static 3He ventilation, and 3He diffusion-weighted images were acquired to generate the 3He apparent diffusion coefficient (ADC) and 3He percent ventilated volume (PVV). Four subjects returned 22.0 +/- 0.8 weeks after baseline imaging for follow-up spirometry and 3He MRI measurements of ADC and PVV. At baseline, PVV was significantly different (p = 0.025) and lower in the ipsilateral diseased lung (55 +/- 29%) compared to the contralateral nondiseased lung (88 +/- 5%). Longitudinally, significant increases were observed for 3He MRI PVV (16% +/- 6%, p = 0.012) and 3He MRI ADC (0.02 +/- 0.01 cm2/s, p = 0.003) in the contralateral lung only, in the four subjects who returned for follow-up, while no changes in the ipsilateral lung were reported. Hyperpolarized 3He MRI was well tolerated in all subjects with moderate to severe RILI. Functional improvements and microstructural changes were observed in the contralateral lung, while the ipsilateral lung remained stable, suggesting that functional compensatory changes may have occurred in the contralateral lung due to ipsilateral lung radiation-induced injury.


High Enrichment [13 C]-Labeling of Plants Grown Hydroponically from Seed to Seed in a Controlled 13 C-Carbon Dioxide Atmosphere Enclosure.
In vivo isotopic labeling empowers proteomic and metabolomic analyses to resolve relationships between the molecular composition, environment, and phenotype of an organism. Carbon-13 is particularly useful for plant labeling as it can be introduced via 13 CO2 gas and readily assimilated into plant metabolic systems through natural carbon fixation. While short-term labeling experiments can be performed within a simple sealed enclosure, long-term growth in an isolated environment raises many challenges beyond nutrient availability and buildup of metabolic waste. Viable growth conditions must be maintained by means that do not compromise the integrity of the carbon-13 enrichment. To address these issues, an automated growth chamber equipped with countermeasures to neutralize stresses and ensure high isotopic enrichment throughout the life cycle of the plant has been developed. The following describes this growth chamber and its use in an example 130-day growth of ten soybean plants to full maturity, achieving 100% carbon-13 enrichment of new seed tissue. © 2018 by John Wiley & Sons, Inc.


Personalized Cancer Monitoring Assay for the Detection of ctDNA in Patients with Solid Tumors.
Highly sensitive molecular assays have been developed to detect plasma-based circulating tumor DNA (ctDNA), and emerging evidence suggests their clinical utility for monitoring minimal residual disease and recurrent disease, providing prognostic information, and monitoring therapy responses in patients with solid tumors. The Invitae Personalized Cancer Monitoring™ assay uses a patient-specific, tumor-informed variant signature identified through whole exome sequencing to detect ctDNA in peripheral blood of patients with solid tumors. The assay's tumor whole exome sequencing and ctDNA detection components were analytically validated using 250 unique human specimens and nine commercial reference samples that generated 1349 whole exome sequencing and cell-free DNA (cfDNA)-derived libraries. A comparison of tumor and germline whole exome sequencing was used to identify patient-specific tumor variant signatures and generate patient-specific panels, followed by targeted next-generation sequencing of plasma-derived cfDNA using the patient-specific panels with anchored multiplex polymerase chain reaction chemistry leveraging unique molecular identifiers. Whole exome sequencing resulted in overall sensitivity of 99.8% and specificity of > 99.9%. Patient-specific panels were successfully designed for all 63 samples (100%) with ≥ 20% tumor content and 24 (80%) of 30 samples with ≥ 10% tumor content. Limit of blank studies using 30 histologically normal, formalin-fixed paraffin-embedded specimens resulted in 100% expected panel design failure. The ctDNA detection component demonstrated specificity of > 99.9% and sensitivity of 96.3% for a combination of 10 ng of cfDNA input, 0.008% allele frequency, 50 variants on the patient-specific panels, and a baseline threshold. Limit of detection ranged from 0.008% allele frequency when utilizing 60 ng of cfDNA input with 18-50 variants in the patient-specific panels (> 99.9% sensitivity) with a baseline threshold, to 0.05% allele frequency when using 10 ng of cfDNA input with an 18-variant panel with a monitoring threshold (> 99.9% sensitivity). The Invitae Personalized Cancer Monitoring assay, featuring a flexible patient-specific panel design with 18-50 variants, demonstrated high sensitivity and specificity for detecting ctDNA at variant allele frequencies as low as 0.008%. This assay may support patient prognostic stratification, provide real-time data on therapy responses, and enable early detection of residual/recurrent disease.


Persistent pollutants: focus on perfluorinated compounds and kidney.
There is increasing interest in the environmental and human damage caused by pollutants. Big efforts are continuously made to monitor their levels and identify safe thresholds. For this purpose, an essential step is to prioritize harmful substances and understand their effect on human body. Perfluorinated compounds (PFCs) deserve particular attention because of their wide diffusion and potential correlation with different diseases including glucose intolerance, hyperlipidaemia, thyroid diseases, gestational diabetes mellitus and hypertension, testicular and genitourinary cancer as well as impaired kidney function. This review focuses on the renal effects of PFCs, with the attempt to clarify their occurrence and pathogenetic mechanisms. We reviewed MEDLINE and EMBASE citations between 31 October 2017 and 31 May 2019 and selected human studies measuring PFCs exposure, kidney function markers and the ability of haemodialysis to remove PFCs from the circulating blood. It has been currently clarified that exposure to PFCs is linked with an impaired kidney function and that they can be removed by blood purification. Further studies are required on the potential synergic negative effect of PFCs co-exposure with other pollutants as well as animal studies about the removal capacity of different haemodialysis membranes.


Reverse radial forearm flap as a source of soft tissue and blood supply for thumb reconstruction.
Soft-tissue deficiency is sometimes a major problem in thumb reconstructive cases with toe-to-thumb transfer. In the patient presented, a reverse radial forearm flap was used to provide a vascular pedicle for anastomosis with the second toe vessels. The flap also provided soft-tissue coverage for the metatarsal bone of the transferred toe. The radial artery and concomitant vein were used for the dorsalis pedis artery and vein anastomosis. The skin island of the forearm flap was wrapped around the transferred metatarsal bone. Using this technique, two limiting problems in toe-to-hand transfers were solved at the same time. In the crushed hand, sometimes it is not possible to find enough soft tissue and a good vascular pedicle for a new thumb, and this option seems to be a reasonable choice.


Calcutta metro: is it safe from noise pollution hazards?
A modest assessment of noise was made in Calcutta Metro, India's first ever underground tube rail system, to examine if the range of noise levels present could endanger the hearing sensitivity of workers for the Metro. Sound measuring instruments of a sound level meter, an octave band analyzer, and a sound level calibrator were used for measuring the sound pressure levels in platforms of three stations: Esplanade, Kalighat and Tollygunge. The results indicated that the averaged A-weighted SPLs in these stations were in the range of 84-87 dBA. In the coaches of the moving train the Leq values ranged 92-99 dBA and LNP 105-117 dBA, all exceeding the safe limit of day time noise exposure of 55 dBA and 85 dBA of ACGIH. The SPLs at 4,000 Hz in the coaches were also in excess of safe exposure limit of 79 dB. The findings thus posed a potential threat to the workers.


Histochemical staining and quantification of dihydrolipoamide dehydrogenase diaphorase activity using blue native PAGE.
Mammalian mitochondrial dihydrolipoamide dehydrogenase (DLDH, EC 18.104.22.168) catalyzes NAD(+)-dependent oxidation of dihydrolipoamide in vivo and can also act as a diaphorase catalyzing in vitro nicotinamide adenine dinucleotide (reduced form) (NADH)-dependent reduction of electron-accepting molecules such as ubiquinone and nitroblue tetrazolium (NBT). In this paper, we report a gel-based method for histochemical staining and quantification of DLDH diaphorase activity using blue native PAGE (BN-PAGE). Rat brain mitochondrial extracts, used as the source of DLDH, were resolved by nongradient BN-PAGE (9%), which was followed by diaphorase activity staining using NADH as the electron donor and NBT as the electron acceptor. It was shown that activity staining of DLDH diaphorase was both protein amount- and time-dependent. Moreover, this in-gel activity-staining method was demonstrated to be in good agreement with the conventional spectrophotometric method that measures DLDH dehydrogenase activity using dihydrolipoamide as the substrate. The method was applied to determine levels of DLDH diaphorase activity in several rat tissues other than the brain, and the results indicated a similar level of DLDH diaphorase activity for all the tissues examined. Finally, the effects of thiol-reactive reagents such as N-ethylmaleimide (NEM) and nitric oxide donors on DLDH diaphorase activity were evaluated, demonstrating that, with this method, DLDH diaphorase activity can be determined without having to remove these thiol-reactive reagents that may otherwise interfere with spectrophotometric measurement of DLDH dehydrogenase activity. The gel-based method can also be used as a means to isolate mitochondrial DLDH that is to be analyzed by mass spectral techniques in studying DLDH post-translational modifications.


Use of vertebroplasty to prevent proximal junctional fractures in adult deformity surgery: a biomechanical cadaveric study.
Vertebral compression fractures at the proximal junction are common complications of long spinal fusion surgeries that can contribute to the development of proximal junctional kyphosis or proximal junctional failure. To our knowledge, no biomechanical studies have addressed the effect of vertebral augmentation at the proximal junction. To evaluate the effectiveness of prophylactic vertebroplasty in reducing the incidence of vertebral compression fractures at the proximal junction after a long spinal fusion in a cadaveric spine model. Biomechanical cadaveric study. We divided 18 cadaveric spine specimens into three groups of six spines each: a control group, a group treated with one-level prophylactic vertebroplasty at the upper instrumented vertebra, and a group treated with two-level prophylactic vertebroplasty at the upper instrumented vertebra and the supra-adjacent vertebra. In all spines, the pedicles were instrumented from L5 to T10. Using eccentric axial loading, the specimens were then compressed until failure. Failure was defined as a precipitous decrease in load with increasing compression. The effect of augmentation on load-to-failure was checked using linear regression. The effect of augmentation on incidence of adjacent fractures was checked using logistic regression. Differences at the level of p<.05 were considered significant. KyphX cement introducer was donated by Kyphon, and the pedicle screws were donated by DePuy. Fractures occurred in 12 of 18 specimens: five in the control group, six in the one-level group, and only one in the two-level group; these differences were statistically significant. Prophylactic vertebroplasty at the upper instrumented level and its supra-adjacent vertebra reduced the incidence of junctional fractures after long posterior spinal instrumentation in this axially loaded cadaveric model. Additional studies are necessary to determine if these results are translatable to clinical practice.


Mild hypothermia improves recovery of cortical extracellular potassium ion activity and excitability after middle cerebral artery occlusion in the rat.
Mild brain hypothermia significantly alleviates damage after focal ischemia, although the mechanism of this protection remains poorly defined. In the present study, we tested the hypothesis that mild hypothermia would protect cortex from early deterioration of ion homeostasis and loss of excitability associated with reperfusion after focal ischemia. Cortical extracellular potassium ion activity ([K+]o) and the response of [K+]o to direct cortical stimulation was measured both in the ischemic core and in the ischemic penumbra of normothermic and mildly hypothermic (31.5 degrees C to 32 degrees C) rats after distal middle cerebral artery occlusion (MCAO) and reperfusion. The response of [K+]o during MCAO was similar in normothermic and hypothermic animals. However, within 1 hour of reperfusion, [K+]o in the ischemic core region of normothermic animals showed incomplete recovery and was refractory to direct cortical stimulation. [K+]o in hypothermic animals returned to preischemic levels on reperfusion and continued to respond to direct cortical stimulation. Mild hypothermia prevented extensive infarction 24 hours after transient MCAO. The data suggest that transient focal ischemia is accompanied by early disturbances of potassium ion homeostasis during reperfusion, which are accompanied by loss of excitability and which may contribute ultimately to cortical infarction.


Search for clues to the evolutionary meaning of ciliate phylogeny.
Progress in ciliatology and in allied fields may demystify ciliate phylogenetics. Concentration on hymenostomes (mainly Tetrahymena and Paramecium) may have obscured directional features of ciliate physiology in phylogenetic problems. Therefore, means are suggested for "domesticating" the presumptively primitive, predominantly marine, sand-dwelling gymnostomes having nondividing macronuclei. The prize quarry is the marine psammophile Stephanopogon whose homokaryotic condition may mark it as a living fossil. Eventual axenic cultivation of these "primitive" ciliates may be aided by use as food of easily grown photosynthetic prokaryotes, some isolated from the marine sulfuretum or adjacent aerobic muds and sands where "karyorelictid" ciliates flourish.


Terrestrial or marine species distribution model: Why not both? A case study with seabirds.
Species reliant on both the terrestrial and marine realms present a challenge for conventional species distribution models (SDMs). For such species, standard single-realm SDMs may omit key information that could result in decreased model accuracy and performance. Existing approaches to habitat suitability modeling typically do not effectively combine information from multiple realms; this methodological gap can ultimately hamper management efforts for groups such as seabirds, seals, and turtles. This study, for the first time, jointly incorporates both terrestrial information and marine information into a single species distribution model framework. We do this by sampling nearby marine conditions for a given terrestrial point and vice versa using parameters set by each species' mean maximum foraging distance and then use standard SDM methods to generate habitat suitability predictions; therefore, our method does not rely on post hoc combination of several different models. Using three seabird species with very different ecologies, we investigate whether this new multi-realm approach can improve our ability to identify suitable habitats for these species. Results show that incorporating terrestrial information into marine SDMs, or vice versa, generally improves model performance, sometimes drastically. However, there is considerable variability between species in the level of improvement as well as in the particular method that produces the most improvement. Our approach provides a repeatable and transparent method to combine information from multiple ecological realms in a single SDM framework. Important advantages over existing solutions include the opportunity to, firstly, easily combine terrestrial and marine information for species that forage large distances inland or out to sea and, secondly, consider interactions between terrestrial and marine variables.


Size constancy following long-term visual deprivation.
We can estimate the veridical size of nearby objects reasonably well irrespective of their viewing distance. This perceptual capability, termed size constancy, is accomplished by combining information about retinal image size together with the viewing distance, or using the relational information available in the scene, via direct perception [1]. A previous study [2] showed that children typically underestimate the size of a distant object. This underestimation is reduced with time, suggesting that years of visual experience may be essential for attaining true size constancy. But what if you have had very limited vision during the early years of life? We studied 23 Ethiopian children suffering from bilateral, early-onset cataract, who were surgically treated only years after birth. Surprisingly, most children were able to estimate object size reasonably well irrespective of distance; in fact, they usually tended to overestimate the far-object size. Closer examination indicated that, although before surgery the patients were diagnosed as having a full, mature bilateral cataract, they nevertheless had some residual form of vision, typically limited to very close range. Gandhi et al.[3] earlier reported immediate susceptibility to geometric visual illusions in a similar group of newly-sighted children, concluding that size constancy was probably innate. We suggest that their immediate ability to judge physical size irrespective of distance is more likely to result from their previous visual experience.


Activity of quinupristin/dalfopristin against gram-positive bacteria: clinical applications and therapeutic potential.
In recent years there has been a dramatic worldwide increase in the prevalence of multiple drug-resistant strains of common Gram-positive bacteria. This highlights the need for a new class of antibiotic with activity against these organisms. Quinupristin/dalfopristin, the first injectable streptogramin antibiotic, has a unique spectrum of activity, encompassing most Gram-positive cocci (including multi-drug-resistant strains), respiratory pathogens and anaerobes, Gram-positive, and a prolonged post-antibiotic effect. Quinupristin/ dalfopristin is active in vitro against multi-drug-resistant isolates of Staphylococcus aureus, coagulase-negative staphylococci, penicillin-resistant pneumococci and vancomycin-resistant Enterococcus faecium. Clinical case reports have shown that the combination is active against intra-abdominal, aortic graft, bacteraemia and hydrocephalus shunt infections caused by multi-drug-resistant enterococci, particularly E. faecium. In almost all of these clinical situations the enterococcal infection had displayed resistance to all other antimicrobial therapies. Preliminary clinical data have demonstrated the activity of quinupristin/ dalfopristin against S. aureus bacteraemia, and quinupristin/dalfopristin may also prove useful in the treatment of pneumococcal infections. Thus, possible future applications of the combination include the treatment of multi-drug-resistant strains of staphylococci, streptococci and enterococci. Quinupristin/dalfopristin may prove useful in the treatment of staphylococcal infections in children, invasive systemic pneumococcal infections, and nosocomial and community-acquired Gram-positive infections in patients unable to tolerate beta-lactam antimicrobial agents or glycopeptide antibiotics.


Genome modification leads to phenotype reversal in human myotonic dystrophy type 1 induced pluripotent stem cell-derived neural stem cells.
Myotonic dystrophy type 1 (DM1) is caused by expanded CTG repeats in the 3'-untranslated region (3' UTR) of the DMPK gene. Correcting the mutation in DM1 stem cells would be an important step toward autologous stem cell therapy. The objective of this study is to demonstrate in vitro genome editing to prevent production of toxic mutant transcripts and reverse phenotypes in DM1 stem cells. Genome editing was performed in DM1 neural stem cells (NSCs) derived from human DM1 induced pluripotent stem (iPS) cells. An editing cassette containing SV40/bGH polyA signals was integrated upstream of the CTG repeats by TALEN-mediated homologous recombination (HR). The expression of mutant CUG repeats transcript was monitored by nuclear RNA foci, the molecular hallmarks of DM1, using RNA fluorescence in situ hybridization. Alternative splicing of microtubule-associated protein tau (MAPT) and muscleblind-like (MBNL) proteins were analyzed to further monitor the phenotype reversal after genome modification. The cassette was successfully inserted into DMPK intron 9 and this genomic modification led to complete disappearance of nuclear RNA foci. MAPT and MBNL 1, 2 aberrant splicing in DM1 NSCs were reversed to normal pattern in genome-modified NSCs. Genome modification by integration of exogenous polyA signals upstream of the DMPK CTG repeat expansion prevents the production of toxic RNA and leads to phenotype reversal in human DM1 iPS-cells derived stem cells. Our data provide proof-of-principle evidence that genome modification may be used to generate genetically modified progenitor cells as a first step toward autologous cell transfer therapy for DM1.


Music training is associated with cortical synchronization reflected in EEG coherence during verbal memory encoding.
Music training can improve cognitive functions. Previous studies have shown that children and adults with music training demonstrate better verbal learning and memory performance than those without such training. Although prior studies have shown an association between music training and changes in the structural and functional organization of the brain, there is no concrete evidence of the underlying neural correlates of the verbal memory encoding phase involved in such enhanced memory performance. Therefore, we carried out an electroencephalography (EEG) study to investigate how music training was associated with brain activity during the verbal memory encoding phase. Sixty participants were recruited, 30 of whom had received music training for at least one year (the MT group) and 30 of whom had never received music training (the NMT group). The participants in the two groups were matched for age, education, gender distribution, and cognitive capability. Their verbal and visual memory functions were assessed using standardized neuropsychological tests and EEG was used to record their brain activity during the verbal memory encoding phase. Consistent with previous studies, the MT group demonstrated better verbal memory than the NMT group during both the learning and the delayed recall trials in the paper-and-pencil tests. The MT group also exhibited greater learning capacity during the learning trials. Compared with the NMT group, the MT group showed an increase in long-range left and right intrahemispheric EEG coherence in the theta frequency band during the verbal memory encoding phase. In addition, their event-related left intrahemispheric theta coherence was positively associated with subsequent verbal memory performance as measured by discrimination scores. These results suggest that music training may modulate the cortical synchronization of the neural networks involved in verbal memory formation.


Hospital Surge Capacity: A Web-Based Simulation Tool for Emergency Planners.
The National Center for the Study of Preparedness and Catastrophic Event Response (PACER) has created a publicly available simulation tool called Surge (accessible at http://www.pacerapps.org) to estimate surge capacity for user-defined hospitals. Based on user input, a Monte Carlo simulation algorithm forecasts available hospital bed capacity over a 7-day period and iteratively assesses the ability to accommodate disaster patients. Currently, the tool can simulate bed capacity for acute mass casualty events (such as explosions) only and does not specifically simulate staff and supply inventory. Strategies to expand hospital capacity, such as (1) opening unlicensed beds, (2) canceling elective admissions, and (3) implementing reverse triage, can be interactively evaluated. In the present application of the tool, various response strategies were systematically investigated for 3 nationally representative hospital settings (large urban, midsize community, small rural). The simulation experiments estimated baseline surge capacity between 7% (large hospitals) and 22% (small hospitals) of staffed beds. Combining all response strategies simulated surge capacity between 30% and 40% of staffed beds. Response strategies were more impactful in the large urban hospital simulation owing to higher baseline occupancy and greater proportion of elective admissions. The publicly available Surge tool enables proactive assessment of hospital surge capacity to support improved decision-making for disaster response. (Disaster Med Public Health Preparedness. 2018;12:513-522).


Prospective associations of poor diet quality with long-term incidence of protein-energy malnutrition in community-dwelling older adults: the Health, Aging, and Body Composition (Health ABC) Study.
Protein-energy malnutrition (PEM) is a major problem in older adults. Whether poor diet quality is an indicator for the long-term development of PEM is unknown. The aim was to determine whether poor diet quality is associated with the incidence of PEM in community-dwelling older adults. We used data on 2234 US community-dwelling older adults aged 70-79 y of the Health, Aging, and Body Composition (Health ABC) Study. In 1998-1999, dietary intake over the preceding year was measured by using a Block food-frequency questionnaire. Indicators of diet quality include the Healthy Eating Index (HEI), energy intake, and protein intake. Outcomes were determined annually by using measured weight and height and included the following: 1) incident PEM [body mass index (in kg/m2) <20, involuntary weight loss of ≥5% in the preceding year at any follow-up examination, or both] and 2) incident persistent PEM (having PEM at 2 consecutive follow-up examinations). Associations of indicators of diet quality with 4-y and 3-y incidence of PEM and persistent PEM, respectively, were examined by multivariable Cox regression analyses. The quality of the diet, as assessed with the HEI, was rated as "poor" for 6.4% and as "needs improvement" for 73.0% of the participants. During follow-up, 24.9% of the participants developed PEM and 8.5% developed persistent PEM. A poor HEI score was not associated with incident PEM or persistent PEM. Lower baseline energy intake was associated with a lower incidence of PEM (HR per 100-kcal/d lower intake: 0.98; 95% CI: 0.97, 0.99) and persistent PEM (HR: 0.97; 95% CI: 0.95, 0.99), although lower baseline protein intake was observed to be associated with a higher incidence of persistent PEM (HR per 10-g/d lower intake: 1.15; 95% CI: 1.03, 1.29). These findings do not indicate that a poor diet quality is a risk factor for the long-term development of PEM in community-dwelling older adults, although there is an indication that lower protein intake is associated with higher PEM risk.


Modeling the indirect economic implications of musculoskeletal disorders and treatment.
Musculoskeletal disorders impose a substantial economic burden on American society, but few studies have examined the economic benefits associated with treating such disorders. The purpose of this research is to estimate the indirect economic implications of activity limitations associated with musculoskeletal disorders and to quantifying the potential economic gains from elective surgery to treat arthritis of the knee and hip. Using regression analysis with the National Health Interview Survey (2004-2010 data, n=185,829 adults) we quantify the relationship between severity of activity limitations (walking, sitting, standing, etc.) and employment, household income, missed work days, and receipt of supplemental security income for disability. Activity limitations are combined to create an index similar to the Functional Ability Index from the Short Form 36 Health Questionnaire (SF-36) often used in clinical trials to measure patient functional mobility. This index is included in the regression analyses. We use data from published, prospective clinical trials to establish the improvement in patient functional ability following surgery to treat arthritis of the knee and hip. Improved physical function is associated with higher likelihood of employment, higher household income and fewer missed work days for those who are employed, and reduced likelihood of receiving supplemental security income for disability. The magnitude of the impact and statistical significance vary by activity limitation and severity. Each percentage point increase in the index value is associated with a 2-percentage-point increase in the odds of being employed, a 3-percentage-point-day decline in work days missed and an additional $180 in annual household income if employed, and a 2-percentage-point decline in the odds of receiving supplemental security income for disability. All estimates are statistically significant at the 0.05 level. Using a large, representative sample of non-institutionalized adults in the U.S., we find that physical activity limitations are associated with worse economic outcomes across multiple economic metrics. Combined with estimates of improved functional ability following knee and hip surgery, we quantify some of the economic benefits of surgery for arthritis of the knee and hip. This information helps improve understanding of the societal benefits of medical treatment for musculoskeletal conditions.


Synergistically Enhanced Wound Healing of a Vapor-Constructed Porous Scaffold.
In this study, a porous, three-dimensional material of parylene (poly-p-xylylene) incorporating keratin was fabricated. As an FDA-approved material, parylene is highly stable and biocompatible. Keratin is an abundant natural material that can enhance cell adhesion and wound healing. A unique vapor deposition construction technique dispersed keratin homogenously in the parylene system. Instead of using a conventional template, a sublimating template was applied. This composite porous scaffold was investigated mechanically and biologically. In addition, human adipose stem cells were cultured on the scaffold. The synergistic functions, including biocompatibility, permeability, cell adhesion, and stem cell differentiation, were investigated. A mouse excisional wound-healing model further verified that using the porous composite scaffold with stem cells accelerated the wound healing process, supporting its in vivo efficacy. The positive results demonstrated that this material has the potential to serve as a wound repair platform.


Investigating the crucial role of selected Bifidobacterium probiotic strains in preventing or reducing inflammation by affecting the autophagy pathway.
Several studies have shown that probiotics can prevent and reduce inflammation in inflammation-related diseases. However, few studies have focused on the interaction between host and probiotics in modulating the immune system through autophagy. Therefore, we aimed to investigate the preventive and/or therapeutic effects of native potential probiotic breast milk-isolated Bifidobacterium spp. (i.e. B. bifidum, B. longum, and B. infantis) on the inflammatory cascade by affecting autophagy gene expression 24 and 48 hours after treatment. Autophagy genes involved in different stages of the autophagy process were selected by qPCR. Gene expression investigation was accomplished by exposing the human colorectal adenocarcinoma cell line (HT-29) to sonicated pathogens (1.5 × 108 bacterial CFU ml-1) and adding Bifidobacterium spp. (MOI10) before, after, and simultaneously with induction of inflammation. An equal volume of RPMI medium was used as a control. Generally, our native potential probiotic Bifidobacterium spp. can increase the autophagy gene expression in comparison with pathogen. Moreover, the increase in gene expression was observed with our probiotic strains' consumption in all stages of autophagy. Totally, our selected Bifidobacterium spp. can increase autophagy gene expression before, simultaneously, and after the inflammation induction, so they can prevent and reduce inflammation in an in-vitro model of inflammation.


Tumour heterogeneity revealed by unsupervised decomposition of dynamic contrast-enhanced magnetic resonance imaging is associated with underlying gene expression patterns and poor survival in breast cancer patients.
Heterogeneity is a common finding within tumours. We evaluated the imaging features of tumours based on the decomposition of tumoural dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data to identify their prognostic value for breast cancer survival and to explore their biological importance. Imaging features (n = 14), such as texture, histogram distribution and morphological features, were extracted to determine their associations with recurrence-free survival (RFS) in patients in the training cohort (n = 61) from The Cancer Imaging Archive (TCIA). The prognostic value of the features was evaluated in an independent dataset of 173 patients (i.e. the reproducibility cohort) from the TCIA I-SPY 1 TRIAL dataset. Radiogenomic analysis was performed in an additional cohort, the radiogenomic cohort (n = 87), using DCE-MRI from TCGA-BRCA and corresponding gene expression data from The Cancer Genome Atlas (TCGA). The MRI tumour area was decomposed by convex analysis of mixtures (CAM), resulting in 3 components that represent plasma input, fast-flow kinetics and slow-flow kinetics. The prognostic MRI features were associated with the gene expression module in which the pathway was analysed. Furthermore, a multigene signature for each prognostic imaging feature was built, and the prognostic value for RFS and overall survival (OS) was confirmed in an additional cohort from TCGA. Three image features (i.e. the maximum probability from the precontrast MR series, the median value from the second postcontrast series and the overall tumour volume) were independently correlated with RFS (p values of 0.0018, 0.0036 and 0.0032, respectively). The maximum probability feature from the fast-flow kinetics subregion was also significantly associated with RFS and OS in the reproducibility cohort. Additionally, this feature had a high correlation with the gene expression module (r = 0.59), and the pathway analysis showed that Ras signalling, a breast cancer-related pathway, was significantly enriched (corrected p value = 0.0044). Gene signatures (n = 43) associated with the maximum probability feature were assessed for associations with RFS (p = 0.035) and OS (p = 0.027) in an independent dataset containing 1010 gene expression samples. Among the 43 gene signatures, Ras signalling was also significantly enriched. Dynamic pattern deconvolution revealed that tumour heterogeneity was associated with poor survival and cancer-related pathways in breast cancer.


Galactosyl derivatives of L-arginine and D-arginine: synthesis, stability, cell permeation, and nitric oxide production in pituitary GH3 cells.
Nitric oxide (NO) is critical for the normal physiological regulation of the nervous system and other tissues. L-Arginine, but not D-arginine, is the natural substrate for nitric oxide synthase (NOS), for it is enzymatically converted to NO and L-citrulline. However, recent evidence suggests that D-arginine can also produce NO and NO-derivatives via a different pathway. The aim of the present paper was to raise NO levels in the cells by increasing the cell permeation of its precursors. To this aim, two galactosyl prodrugs, L-arginine-D-galactos-6'-yl ester (L-ArgGal) and D-arginine-D-galactos-6'-yl ester (D-ArgGal) were synthesized. Remarkably, using the HPLC-ESI/MS technique, we found that L-ArgGal and D-ArgGal prodrugs both increased the concentration levels of L- and D-arginine and their derivatives in pituitary GH3 cells. Furthermore, we found that D-ArgGal (1) penetrated cell membranes more rapidly than its precursor D-arginine, (2) released arginine more slowly and in greater amounts than L-ArgGal, and (3) produced much higher levels of DAF-2 monitored NO and nitrite than did L-ArgGal under the same experimental conditions. In conclusion, these results indicate that an increase in the cell permeation of L- and D-arginine by L-ArgGal and D-ArgGal can lead to an increase in NO levels.


Acupoint Stimulation for Acne: A Systematic Review of Randomized Controlled Trials.
Acupoint stimulation-including acupuncture, moxibustion, cupping, acupoint injection, and acupoint catgut embedding-has shown a beneficial effect for treating acne. However, comprehensive evaluation of current clinical evidence is lacking. The aim of this review was to assess the effectiveness and safety of all acupoint stimulation techniques used to treat acne vulgaris. A systematic review was conducted. It included only randomized controlled trials on acupoint stimulation for acne. Six electronic databases were searched for English and Chinese language studies. All searches ended in May 2012. Studies were selected for eligibility and assessed for quality. RevMan 5.1 software was used for data analysis with an effect estimate presented as risk ratios (RR) or mean difference (MD) with a 95% confidence interval (CI). Studies with subjects who were diagnosed with acne vulgaris, or papulopustular, inflammatory, adolescent, or polymorphic acne-regardless of gender, age, and ethnicity-were included. Interventions included any acupoint stimulation technique-such as acupuncture, moxibustion, cupping, acupoint injection, and acupoint catgut embedding-compared with no treatment, placebo, or conventional pharmaceutical medication. Reduction of signs and symptoms and presence of adverse effects were examined. Forty-three trials involving 3453 patients with acne were included. The methodological quality of trials was generally poor in terms of randomization, blinding, and intention-to-treat analysis. Meta-analyses showed significant differences in increasing the number of cured patients between acupuncture plus herbal medicine and herbal medicine alone (RR: 1.60; 95% CI: 1.19-2.14; P=0.002), and between acupuncture plus herbal facial mask and herbal facial mask alone (RR: 2.14; 95% CI: 1.29-3.55; P=0.003). Cupping therapy was significantly better than pharmaceutical medications for increasing the number of cured patients (RR: 2.11; 95% CI: 1.45-3.07; P<0.0001). Serious adverse events were not reported in all included trials. Acupoint stimulation therapies combined with other treatments appears to be effective for acne. However, further large, rigorously designed trials are needed to confirm these findings.


Assessing the presence and spread of Renibacterium salmoninarum between farmed and wild fish in Sweden.
Bacterial kidney disease (BKD) can be a devastating bacterial infection in salmonids, and it is present in aquaculture throughout the world. BKD is caused by the Gram-positive facultative intracellular bacterium Renibacterium salmoninarum (R. salmoninarum) that is spread both horizontally and vertically. Disease signs include external ulcerations and blisters and internal signs such as organ swelling, granulomas, petechiae and ascites. In Sweden, BKD accounts for a significant income loss in aquacultures due to expensive decontamination of the facility and increased disease susceptibility for the immunocompromised fish leading to higher mortality rates. In addition, uncontrolled spread in aquaculture may threaten the survival of wild fish populations. The aim of our study was to investigate the prevalence of R. salmoninarum in wild salmonids caught in Swedish waters where net pen farms with a recent history of BKD are present. Four rivers with at least one BKD-positive or recently BKD-positive farm were selected. In addition, we evaluated the use of environmental DNA (eDNA) for surveillance and monitoring of ongoing infections at these locations. In total, 1058 fish were sampled from four different river systems, and of them 52 (4.9%) were positive for R. salmoninarum by antigen ELISA. Surprisingly, these fish were not evenly distributed between the four river systems, but 50 were caught in the same river (Ljungan). This accounts for an alarmingly high rate of 17% R. salmoninarum-positive samples in wild salmonids in this area. This number is far above what was expected and clearly shows the risk with an open farming system as well as the importance of effective health monitoring programmes to avoid an uncontrolled spread of the disease. The use of eDNA for monitoring BKD is somewhat difficult to evaluate. Few of the water samples analysed were PCR positive for R. salmoninarum (2 of 38) and those were collected where no ELISA positive fish were identified. In addition to water, sediment samples were collected under a net pen farm that had recently slaughtered all fish due to ongoing R. salmoninarum infections. Sediment samples are more promising than water as 4 of 5 samples at one farming facility where positive for R. salmoninarum. Thus, sediment samples may be valuable for monitoring potential ongoing BKD in farms, without the need to sacrifice valuable fish.


Efficacy and safety of rush immunotherapy with alum-precipitated allergens in canine atopic dermatitis.
Canine atopic dermatitis is a very common disease in small animal practice. Its only specific treatment is allergen immunotherapy. In rush-immunotherapy (RIT) increasing doses of allergen extract are injected subcutaneously in short intervals. Maintenance doses are achieved within one day compared to weeks or months with conventional immunotherapy. The aim of this study was to evaluate the safety and efficacy of RIT with alum-precipitated allergens. A series of 20 dogs with atopic dermatitis underwent RIT with alum-precipitated allergens. Pruritus and medications at the start of the immunotherapy and 12 months afterwards were compared and adverse effects were recorded. Significant improvement in pruritus (p = 0.0001) and medication scores (p = 0.0004) was noted after approximately 12 months of treatment. The observed clinical response was good to excellent in 70% of the dogs, consistent with other published reports. One dog vomited once during the induction day, with no other clinical problems and completion of the normal protocol. The other 19 dogs showed no adverse effects at all during or after RIT. RIT with alum-precipitated allergens seems to be a safe and efficacious method to treat dogs with atopic dermatitis.


The lysosomal GPCR-like protein GPR137B regulates Rag and mTORC1 localization and activity.
Cell growth is controlled by a lysosomal signalling complex containing Rag small GTPases and mammalian target of rapamycin complex 1 (mTORC1) kinase. Here, we carried out a microscopy-based genome-wide human short interfering RNA screen and discovered a lysosome-localized G protein-coupled receptor (GPCR)-like protein, GPR137B, that interacts with Rag GTPases, increases Rag localization and activity, and thereby regulates mTORC1 translocation and activity. High GPR137B expression can recruit and activate mTORC1 in the absence of amino acids. Furthermore, GPR137B also regulates the dissociation of activated Rag from lysosomes, suggesting that GPR137B controls a cycle of Rag activation and dissociation from lysosomes. GPR137B-knockout cells exhibited defective autophagy and an expanded lysosome compartment, similar to Rag-knockout cells. Like zebrafish RagA mutants, GPR137B-mutant zebrafish had upregulated TFEB target gene expression and an expanded lysosome compartment in microglia. Thus, GPR137B is a GPCR-like lysosomal regulatory protein that controls dynamic Rag and mTORC1 localization and activity as well as lysosome morphology.


Protein kinase C inhibits caveolae-mediated endocytosis of TRPV5.
Transient receptor potential vanilloid 5 (TRPV5) constitutes the apical entry pathway for transepithelial Ca(2+) reabsorption in kidney. Many hormones alter renal Ca(2+) reabsorption at least partly by regulating TRPV5. The mechanism for acute regulation of TRPV5 by phospholipase C-coupled hormones is largely unknown. Here, we found that protein kinase C (PKC) activator 1-oleoyl-acetyl-sn-glycerol (OAG) increased TRPV5 current density and surface abundance in cultured cells. The OAG-mediated increase of TRPV5 was prevented by preincubation with specific PKC inhibitors. Coexpression with a dominant-negative dynamin increased the basal TRPV5 current density and prevented the increase by OAG. Knockdown of caveolin-1 by small interference RNA (siRNA) prevented the increase of TRPV5 by OAG. In contrast, knockdown of clathrin heavy chain had no effects. OAG had no effect on TRPV5 expressed in caveolin-1 null cells derived from caveolin-1 knockout mice. Forced expression of recombinant caveolin-1 restored the regulation of TRPV5 by OAG in caveolin-1 knockout cells. Mutations of serine-299 and/or serine-654 of TRPV5 (consensus residues for phosphorylation by PKC) abolished the regulation by OAG. Parathyroid hormone (PTH) increased TRPV5 current density in cells coexpressing TRPV5 and type 1 PTH receptor. The increase caused by PTH was prevented by PKC inhibitor, mutation of serine-299/serine-654, or by knockdown of caveolin-1. Thus, TRPV5 undergoes constitutive caveolae-mediated endocytosis. Activation of PKC increases cell surface abundance of TRPV5 by inhibiting the endocytosis. This mechanism of regulation by PKC may contribute to the acute stimulation of TRPV5 and renal Ca(2+) reabsorption by PTH.


Xylem-specific and tension stress-responsive coexpression of KORRIGAN endoglucanase and three secondary wall-associated cellulose synthase genes in aspen trees.
In nature, angiosperm trees develop tension wood on the upper side of their leaning trunks and drooping branches. Development of tension wood is one of the straightening mechanisms by which trees counteract leaning or bending of stem and resume upward growth. Tension wood is characterized by the development of a highly crystalline cellulose-enriched gelatinous layer next to the lumen of the tension wood fibers. Thus experimental induction of tension wood provides a system to understand the process of cellulose biosynthesis in trees. Since KORRIGAN endoglucanases (KOR) appear to play an important role in cellulose biosynthesis in Arabidopsis, we cloned PtrKOR, a full-length KOR cDNA from aspen xylem. Using RT-PCR, in situ hybridization, and tissue-print assays, we show that PtrKOR gene expression is significantly elevated on the upper side of the bent aspen stem in response to tension stress while KOR expression is significantly suppressed on the opposite side experiencing compression stress. Moreover, three previously reported aspen cellulose synthase genes, namely, PtrCesA1, PtrCesA2, and PtrCesA3 that are closely associated with secondary cell wall development in the xylem cells exhibited similar tension stress-responsive behavior. Our results suggest that coexpression of these four proteins is important for the biosynthesis of highly crystalline cellulose typically present in tension wood fibers. Their simultaneous genetic manipulation may lead to industrially relevant improvement of cellulose in transgenic crops and trees.


Coordinate regulation of stromelysin and collagenase genes determined with cDNA probes.
Secreted proteinases are required for tumor metastasis, angiogenesis, and tissue remodeling during wound healing and embryonic growth. Thus, the regulation of the genes of secreted proteinases may serve as an interesting model for growth-controlled genes in general. We studied the genes of the secreted proteinases stromelysin and collagenase by using molecularly cloned cDNAs from each proteinase. Stromelysin cDNA was cloned by differential screening of a total cDNA library from rabbit synovial cells treated with phorbol 12-myristate 13-acetate, which yielded a clone of 1.2 kilobase pairs; collagenase cDNA was obtained by cloning reverse transcripts of anti-collagenase-immunoadsorbed polysomal mRNA, which yielded a clone of 0.8 kilobase pairs. Stromelysin and collagenase mRNA species of 2.2 and 2.4 kilobases, respectively, were detected on hybridization blots of RNA from phorbol 12-myristate 13-acetate-treated but not untreated rabbit synovial cells. Expression of stromelysin mRNA was also induced in rabbit alveolar macrophages and rabbit brain capillary endothelial cells treated with phorbol 12-myristate 13-acetate. Stromelysin and collagenase mRNA were both induced by phorbol 12-myristate 13-acetate and cytochalasin B at a constant ratio of the two gene products; this suggests coordinate regulation. The fact that induction was blocked after inhibition of protein synthesis by cycloheximide implicates an indirect signal transduction pathway that requires new protein synthesis.


Myofibromas with atypical features: expanding the morphologic spectrum of a benign entity.
Typical myofibromas are biphasic tumors composed of a central zone of immature spindled to rounded cells arranged in a pericytic pattern and a peripheral zone of myoid nodules. Central necrosis is occasionally seen. A small but undefined subset of myofibromas displays atypical features that may lead to a misdiagnosis of sarcoma. To more completely characterize these tumors and define their behavior, we analyzed our experience with myofibromas having 1 or more atypical features including hypercellularity, absent or inconspicuous, poorly demarcated myoid nodules, infiltrative growth pattern, and perineural invasion. Of 266 cases of myofibromas, 24 cases were retrieved on the basis of pathology reports in which atypical features were mentioned. The tumors presented in 16 male and 8 female individuals (mean age 17 y; range, 2 wk to 62 y) as masses of variable size (mean 3.0 cm; range, 1.5 to 6.5 cm). Fourteen cases arose on the head and neck and 10 cases on the limbs. The referring or suspected diagnosis was sarcoma in 8 cases. The tumors were typically more cellular than ordinary myofibroma with levels of cellularity similar to that expected in fibrosarcoma (22/24). In addition, they displayed inconspicuous, loosely cohesive (22/24) or absent myoid nodules (2/24), infiltrating borders (19/24), intravascular growth (5/24), and perineural invasion/nerve entrapment (6/24). The mean mitotic rate was 5 mitoses/10 high-power fields, but no tumor showed significant cytologic atypia. The tumors were positive for actins (11/11) and CD34 (2/8). Follow-up in 14 patients revealed no distant metastases. We conclude that a small subset of myofibromas shows atypical features that complicate the diagnosis but do not adversely affect outcome.


[Positive mutation as regards n-alkane oxidation in Pseudomonas denitrificans].
Differences in the overall protein composition were studied in the wild-type and mutant cells of Pseudomonas denitrificans. Pleiotropic mutation was established, which was characterized by quantitative and qualitative changes in at least 6 to 8 protein fractions and corresponded to the appearance of 2 to 3 steps of oxidation of higher n-alkanes, as had been found earlier in biochemical experiments. New enzymatic functions may appear on the basis of genetically determined proteins available, upon reorganization of the intracellular structure caused by propagating changes induced by mutation.


Bicultural stress and adolescent risk behaviors in a community sample of Latinos and non-Latino European Americans.
The study examined the relation between adolescent risk behaviors and bicultural stress due to discrimination, immigration, and acculturation factors. We hypothesized bicultural stress would be related to increased risk behavior and depressive symptoms independent of socioeconomic status, ethnic self-identification, and acculturation. Middle school student participants (n=519; median age 14) completed a self-report questionnaire on their risk behaviors, psychosocial antecedents, and socio-demographic factors. Latino (304) and non-Latino European American (215) students were surveyed through a large, urban, West Coast US school district. More bicultural stress was significantly related to reports of all risk behaviors (i.e. smoking, drinking, drug use, and violence) and depressive symptoms. Further, bicultural stress was a robust explanatory variable across sub-groups, and appears largely independent from depressive symptoms. The hypotheses were supported. Bicultural stress appears to be an important underlying factor for health disparities among US adolescents. Future research may consider promoting well-being in majority, as well as minority adolescents, through targeting sources of bicultural stressors or examining ways to moderate their effects on adolescent risk behaviors.


Solution of the Fokker-Planck Equation by Cross Approximation Method in the Tensor Train Format.
We propose the novel numerical scheme for solution of the multidimensional Fokker-Planck equation, which is based on the Chebyshev interpolation and the spectral differentiation techniques as well as low rank tensor approximations, namely, the tensor train decomposition and the multidimensional cross approximation method, which in combination makes it possible to drastically reduce the number of degrees of freedom required to maintain accuracy as dimensionality increases. We demonstrate the effectiveness of the proposed approach on a number of multidimensional problems, including Ornstein-Uhlenbeck process and the dumbbell model. The developed computationally efficient solver can be used in a wide range of practically significant problems, including density estimation in machine learning applications.


Association between eating behaviour and diet quality: eating alone vs. eating with others.
To discover the association between eating alone and diet quality among Korean adults who eat alone measured by the mean adequacy ratio (MAR), METHODS: The cross-sectional study in diet quality which was measured by nutrient intakes, indicated as MAR and nutrient adequacy ratio (NAR) with the Korean National Health and Nutrition Examination Survey (KNHANES) VI 2013-2015 data. Study population was 8523 Korean adults. Multiple linear regression was performed to identify the association between eating behaviour and MAR and further study analysed how socioeconomic factors influence the diet quality of those who eat alone. We found that the diet quality of people who eat alone was lower than that of people who eat together in both male (β: - 0.110, p = 0.002) and female participants (β: - 0.069, p = 0.005). Among who eats alone, the socioeconomic factors that negatively influenced MAR with the living arrangement, education level, income levels, and various occupation classifications. People who eat alone have nutrition intake below the recommended amount. This could lead to serious health problems not only to those who are socially disadvantaged but also those who are in a higher social stratum. Policy-makers should develop strategies to enhance diet quality to prevent potential risk factors.


Genetic determinants of blood pressure responses to caffeine drinking.
The widely observed between-subject variability in cardiovascular responses to coffee may have a genetic basis. We evaluated acute blood pressure (BP) responses to caffeine and explored whether they are influenced by candidate gene variants affecting caffeine metabolism (for cytochrome P450 1A2), adenosine metabolism (for adenosine receptor and AMP deaminase), or catecholamine receptors. We recruited 110 healthy male habitual moderate coffee drinkers who refrained from drinking coffee on the day preceding the study. Each subject underwent ambulatory BP monitoring at 6-min intervals for 2 h. Each participant was administered, in a double-blind design, 40 mL of either a decaffeinated coffee preparation plus 3 mg caffeine/kg (caf) or the corresponding vehicle (decaf). The protocol was repeated 24 h later with the alternative preparation. Blood samples were collected for genetic and plasma caffeine and catecholamine evaluations. Compared with decaf, caf was associated with a mean (± SD) significant increase in systolic BP of 4 ± 12 mm Hg and in diastolic BP of 3 ± 10 mm Hg (P < 0.001 for both). Plasma caffeine and adrenaline increased after caf, but not after decaf. Of 11 gene polymorphisms analyzed, a relation was observed between the ADORA2A TT variant and the change in SBP peak and between the ADRA2B I variant and the changes in both SBP mean and peak; mean peak change in SBP; these variants were associated with increased SBP responses to caf. Variability in the acute BP response to coffee may be partly explained by genetic polymorphisms of the adenosine A2A receptors and α(2)-adrenergic receptors. This trial is registered at clinicaltrials.gov as NCT01330680.


Radiologic assessment of response to therapy: comparison of RECIST Versions 1.1 and 1.0.
Improvements in radiologic imaging technology and therapeutic options available for management of tumors have necessitated the revision of guidelines for the imaging-based assessment of tumor response to therapy. The purpose of this article is to familiarize radiologists with the modifications to the Response Evaluation Criteria in Solid Tumors (RECIST) that have been incorporated in the latest version of the guidelines, RECIST 1.1. The most important differences between this version and the previous one, RECIST 1.0, include reductions in the maximum number of lesions per patient and per organ that may be targeted for measurement, augmentation of the criteria defining progressive disease, additional guidelines for reporting findings of lesions that are too small to measure and for measuring lesions that appear to have fragmented or coalesced at follow-up imaging, new criteria for characterizing lymphadenopathy, new criteria for selecting bone lesions and cystic lesions as targets for measurement, and the inclusion of findings at positron emission tomography among the indicators of disease response.


Development of an Internet-Based Cognitive Behavioral Therapy Self-Help Program for Arabic-Speaking Immigrants: Mixed-Methods Study.
Recent years have seen an increase in Arabic-speaking immigrants in Sweden and other European countries, with research showing this group to suffer from elevated levels of various forms of psychological disorders. There is a lack of treatment options for immigrants with mild to moderate mental health problems, with barriers including lack of accessible services and concerns that problems will not be understood by health care providers. This study aims to describe the process of developing a transdiagnostic internet-based cognitive behavioral therapy self-help program in Arabic for mild to moderate symptoms of common psychological problems such as anxiety, depression, and insomnia. The iterative development process, including feedback from 105 pilot users as well as 2 focus groups, is described. Overall, the modules were rated as acceptable by the pilot users, with overall ratings ranging from 3 to 4 points on average for the respective modules on a 5-point Likert scale. Feedback from the 2 focus groups was overall positive with regard to the content and structure of the program but also included suggestions for improving the Arabic translation as well as the usability of the material. An internet-based self-help program that is deemed acceptable by an Arabic-speaking audience can be successfully developed, thus providing increased access to psychological help for an at-risk population. However, further research regarding the efficacy of this type of intervention is warranted.


Dietary vitamin D and calcium intake and mammographic density in postmenopausal women.
Dietary intake of vitamin D and calcium may be related to risk of breast cancer, possibly by affecting mammographic density. However, the few studies that have evaluated the association between these nutrients and mammographic density in postmenopausal women have had inconsistent results. We conducted a cross-sectional analysis in 808 participants of the Mammogram Density Ancillary Study of the Women's Health Initiative. Mammographic percent density was measured using baseline mammograms taken before randomization of participants in the intervention trials. Vitamin D and calcium intake was assessed with a validated food frequency questionnaire and an inventory of current supplement use, both completed at baseline. After adjustment for age, body mass index, regional solar irradiance, and other factors, we did not find a relationship between vitamin D or calcium intake and mammographic density. Mean mammographic percent densities in women reporting total vitamin D intakes of less than 100, 100 to 199, 200 to 399, 400 to 599, and 600 or greater IU/day were 5.8%, 10.4%, 6.2%, 3.8%, and 5.1%, respectively (P trend = 0.67). Results in women reporting a total calcium intake of less than 500, 500 to 749, 750 to 999, 1,000 to 1,199, and 1,200 or greater mg/day were 7.3%, 4.9%, 7.3%, 6.9%, and 7.11%, respectively (P trend = 0.51). We did not observe any effect modification by overall level of mammographic density or solar irradiance, but supplemental vitamin D use was associated with lower density in younger women (P interaction = 0.009). These findings do not support a relationship between dietary vitamin D or calcium intake and mammographic density in postmenopausal women. Additional studies should explore these associations in women of different ages and in relation to serum vitamin D levels.


Efficacy and tolerability of quetiapine in the treatment of borderline personality disorder: A pilot study.
Second-generation antipsychotics with a favorable tolerability profile have offered new treatment options for patients with borderline personality disorder. Sparse data are available on the use of quetia-pine in treating this disorder. The aim of the present study is to investigate efficacy and tolerability of quetia-pine in a group of patients with borderline personality disorder. Fourteen consecutive outpatients with a DSM-IV diagnosis of borderline personality disorder were treated for 12 weeks with open-label quetiapine at the dose of 200-400 mg/day. Patients were assessed at baseline, week 4, and week 12 with the Clinical Global Impressions (CGI) severity item, the Brief Psychiatric Rating Scale (BPRS), the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Social and Occupational Functioning Assessment Scale (SOFAS), the Borderline Personality Disorder Severity Index (BPDSI), and the Barratt Impulsiveness Scale-version 11 (BIS-11). Adverse effects were evaluated using the Dosage Record and Treatment Emergent Symptom Scale. Statistical analysis was performed with the ANOVA for repeated measures. Significant p values were < or = .05. Eleven patients completed the study. Three patients (21.4%) dropped out due to excessive somnolence or noncompliance. The mean +/- SD dose of quetia-pine was 309.09 +/- 83.12 mg/day. A significant change was found for the scores of the following scales: CGI severity item, BPRS, HAM-A, SOFAS, BPDSI total score, BPDSI items "impulsivity" and "outbursts of anger," and BIS-11. Common adverse effects were mild-to-moderate somnolence, dry mouth, and dizziness. Initial data suggest that quetiapine is efficacious and well tolerated in treating patients who have borderline personality disorder, particularly when impulsiveness/aggressiveness-related symptoms are prominent. At the moment, no reliable comparison is available in the literature. Double-blind controlled trials are needed to verify these findings.


Kinetically Controlled Linker Binding in Rare Earth-2,5-Dihydroxyterepthalic Acid Metal-Organic Frameworks and Its Predicted Effects on Acid Gas Adsorption.
In the pursuit of highly stable and selective metal-organic frameworks (MOFs) for the adsorption of caustic acid gas species, an entire series of rare earth MOFs have been explored. Each of the MOFs in this series (RE-DOBDC; RE = La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu; DOBDC = 2,5-dihydroxyterepthalic acid) was synthesized in the tetragonal space group I4/m. Crystallized MOF samples, specifically Eu-DOBDC, were seen to have a combination of monodentate and bidentate binding when synthesized under typical reaction conditions, resulting in a contortion of the structure. However, extended crystallization times determined that this binding is kinetically controlled and that the monodentate binding option was crystallographically eliminated by extended reaction times at higher temperatures. Furthermore, this series allows for the direct study of the effect of the metal center on the structure of the of the MOF; herein, the lanthanide metal ionic radii contraction across the periodic table results in a reduction of the MOF pore size and lattice parameters. Scanning electron microscopy-energy-dispersive spectroscopy was used to investigate the stages of crystal growth for these RE-DOBDC MOFs. All MOFs, except Er-DOBDC had a minimum of two stages of growth. These analogues were demonstrated by analysis of neutron diffraction (PND) to exhibit a cooperative rotational distortion of the secondary building unit, resulting in two crystallographically distinct linker sublattices. Computational modeling efforts were used to show distinct differences on acid gas (NO2 and SO2) binding energies for RE-DOBDC MOFs when comparing the monodentate/bidentate combined linker with the bidentate-only linker crystal structures.


Phosphatidylinositol 3-Kinase Inhibition by Copanlisib in Relapsed or Refractory Indolent Lymphoma.
Purpose Phosphatidylinositol 3-kinase (PI3K) signaling is critical for the proliferation and survival of malignant B cells. Copanlisib, a pan-class I PI3K inhibitor with predominant activity against PI3K-α and -δ isoforms, has demonstrated efficacy and a manageable safety profile in patients with indolent lymphoma. Patients and Methods In this phase II study, 142 patients with relapsed or refractory indolent lymphoma after two or more lines of therapy were enrolled to receive copanlisib 60 mg intravenously on days 1, 8, and 15 of a 28-day cycle. The primary end point was objective response rate; secondary end points included duration of response, progression-free survival, and overall survival. In addition, safety and gene expression were evaluated. Results Median age was 63 years (range, 25 to 82 years), and patients had received a median of three (range, two to nine) prior regimens. The objective response rate was 59% (84 of 142 patients); 12% of patients achieved a complete response. Median time to response was 53 days. Median duration of response was 22.6 months, median progression-free survival was 11.2 months, and median overall survival had not yet been reached. The most frequent treatment-emergent adverse events were transient hyperglycemia (all grades, 50%; grade 3 or 4, 41%) and transient hypertension (all grades, 30%; grade 3, 24%). Other grade ≥3 events included decreased neutrophil count (24%) and lung infection (15%). High response rates to copanlisib were associated with high expression of PI3K/B-cell receptor signaling pathway genes. Conclusion PI3K-α and -δ inhibition by copanlisib demonstrated significant efficacy and a manageable safety profile in heavily pretreated patients with relapsed or refractory indolent lymphoma.


Immediate breast reconstruction with definitive anatomical implants after skin-sparing mastectomy.
One-stage breast reconstruction with definitive implants was the original method of breast reconstruction. It gave a round breast with a fixed shape. Lack of skin after mastectomy was the main concern who led to the development of techniques to provide 'new' breast skin such as autogenous reconstruction and tissue expanders. This made the use of definitive implants almost obsolete. Since skin-sparing mastectomy (SSM) basically removes the mammary gland and the nipple-areolar complex preserving almost all mammary skin, it makes the use of definitive implants in immediate breast reconstruction possible again. Moreover, the advent of anatomically shaped implants overcomes the drawback of round shape: the anatomical implant with hyperprojected lower pole and short upper pole matches very well the profile of a real breast. The authors report their experience in 36 immediate breast reconstruction after SSM with short upper pole-hyperprojected silicone gel prostheses carried out between October 2001 and October 2003. In most cases SSM is performed through a circumareolar incision. Axillary dissection is preferably performed through the same incision. The anatomical implant is placed in a submuscular position superiorly and in a subfascial pocket inferiorly. Because of skin redundancy and easy distension of subfascial tissue in the inferior pole of the breast, the implant fills the skin of the inferior mammary pole without needing any skin expansion. Whenever possible, the skin incision is closed with a purse-string suture. The skin will look very wrinkled at the end of the surgery, but it will flatten out in a few weeks. The contralateral breast is simultaneously corrected, if needed. Outcome was assessed by evaluation of photographs performed by the authors, by the patients themselves and by a blinded group of surgeons who evaluated breast volume and shape, breast symmetry, and overall outcome. More than 90% of each of these parameters was scored as good or excellent. Complication rates was low with a 8.3% rate. The use of definitive implants in immediate breast reconstruction after SSM is a one-stage breast reconstruction with low morbidity and very good results, and it is associated with high level of patient and surgeon satisfaction.


Hemichorea-hemiballismus may respond to topiramate.
Topiramate is a broad-spectrum anticonvulsant that is now widely used for adult and pediatric epilepsy. In a singular case, topiramate was recently reported to benefit vascular hemichorea-hemiballismus. The authors describe three cases of hemichorea-hemiballismus, one of vascular etiology and two of metabolic etiology, effectively treated with topiramate.


PEA3 transactivates the Muc4/sialomucin complex promoter in mammary epithelial and tumor cells.
Sialomucin complex (SMC, rat Muc4) is a heterodimeric glycoprotein composed of two subunits, the mucin component ascites sialoglycoprotein ASGP-1 and the transmembrane subunit ASGP-2, which is aberrantly expressed on the surfaces of a variety of tumor cells. Up-regulation of the Muc4/SMC gene in the 13762 sublines of the rat mammary adenocarcinoma correlates with the overexpression of transcription factor PEA3 and the receptor tyrosine kinase ErbB2. Here we report that PEA3 is capable of transactivating the Muc4/SMC promoter in a dose-dependent manner via direct attachment to a PEA3 binding site. ERM and ER81, the other two members of the PEA3 subfamily of transcription factors, could not transactivate the Muc4/SMC promoter. Transcriptional activation of Muc4/SMC by PEA3 is potentiated by Ras and MEKK1 kinases. These data suggest that expression of PEA3 in mammary tumors leads to up-regulation of Muc4/SMC transcription, the gene product of which may contribute to the metastatic potential of mammary tumors.


Oleic Acid, Cholesterol, and Linoleic Acid as Angiogenesis Initiators.
The current study determined the natural angiogenic molecules using an unbiased metabolomics approach. A chick chorioallantoic membrane (CAM) model was used to examine pro- and antiangiogenic molecules, followed by gas chromatography-mass spectrometry (GCMS) analysis. Vessel formation was analyzed quantitatively using the angiogenic index (p < 0.05). At embryonic day one, a white streak or circle area was observed when vessel formation begins. GCMS analysis and database search demonstrated that angiogenesis may initiate when oleic, cholesterol, and linoleic acids increased in the area of angiogenic reactions. The gain of function study was conducted by the injection of cholesterol and oleic acid into a chick embryo to determine the role of each lipid in angiogenesis. We propose that oleic acid, cholesterol, and linoleic acid are natural molecules that set the platform for the initiation stage of angiogenesis before other proteins including the vascular endothelial growth factor, angiopoietin, angiotensin, and erythropoietin join as the angiome in sprout extension and vessel maturation.


Immunocytochemical localization of renin in the submandibular gland of the mouse.
Renin was localized in the submandibular gland of the adult mouse at light and electron microscopic levels by the unlabeled antibody enzyme method of Sternberger. At the light microscopic level, renin was confined to the granular convoluted tubule (GCT) segment of the gland with considerable variation among GCT cells in intensity of staining. Some GCT cells failed to stain for renin. The pattern of staining was the same in the gland of male and female mice, but in the glands of females GCT segments were smaller and less numerous. At the electron microscopic level, staining for renin was also confined to the GCT cells, and was localized exclusively to the secretory granules. The intensity of staining of the secretory granules within a given GCT cell varied; some cells contained only minimally reactive or negative secretory granules. All other organelles within the GCT cell, except condensing vacuoles, failed to stain.


[Molecular DNA-DNA hybridization in Pseudomonas fluorescens and Pseudomonas putida].
Taxonomic analysis was carried out and DNA-DNA homology studied in cultures of subgroups formed by numerical classification of 124 Pseudomonas fluorescens and P. putida strains. The GC content in the DNA of strains belonging to P. fluorescens subgroups varied from 61.2 to 64.5%, and their DNA-DNA homology with the type strain P. fluorescens ATCC 13525 was 24 to 83%. The lowest genome relatedness with the type culture was found in biotype C of P. fluorescens and P. aureofaciens strains. The GC content in the DNA of strains belonging to two subgroups formed by numerical classification of P. putida varied from 63.8 to 65.0%, and the homology of their DNA with the DNA of the type strain of P. fluorescens was 0 to 10% (for strains of the first and second subgroups, respectively).


(Re)creating community: Experiences of Older Women Forcibly Relocated During Apartheid.
This article explores sense of community with a group of older African women, who were forcibly relocated during apartheid. The situation of a marginalised group, with a history of disconnection from younger generations and from place, provides an opportunity to consider the relevance of community in later life. The research was conducted at a day centre for older people in the North West Province of South Africa, more than 50 years after forced relocations took place. Eleven older women (70 years and older) participated. Qualitative data were obtained through visual research methods and group discussions and were thematically analysed. Findings were that place and sense of belonging as well as elements of community were relevant. Participants reported limited connections to place in either childhood or current communities. Post relocation, a sense of belonging was expressed only in relation to a shared-interest community of peers that addressed their needs for safety, emotional support and instrumental care. Also, generational relations were strained, giving rise to a sense of loss of a community where both young and old were responsible for each other. Constrained resource communities have a profound impact on opportunities to create a sense of belonging. © 2013 The Authors. Journal of Community & Applied Social Psychology published by John Wiley & Sons Ltd.


The use of indirect calorimetry in the intensive care unit.
This review evaluates whether improvements have occurred in the value of predictive equations for use in designing nutritional therapeutic regimens in the ICU. The report also seeks to determine whether emerging strategies for nutrition therapy in the ICU change the need for an accurate measurement of energy requirements by indirect calorimetry. Predictive equations remain problematic for use in the critically ill patient. Inaccuracy of predictive equations introduces error in the design of a nutritional therapy regimen. The epidemic of obesity renders the calculations of requirements by predictive equations increasingly inaccurate at extremes of BMI. Certain patient populations appear to be hypometabolic, contradicting the traditional notion that critical illness increases energy expenditure. More recent data indicates that determination of which patients benefit from nutritional therapy may be based both on assessment of nutrition risk and delivery of sufficient nutrition therapy. The role of indirect calorimetry in the ICU should be expected to increase in the near future, as predictive equations may be too inaccurate to identify the appropriate goals of nutrition therapy.


Rubinstein-Taybi syndrome in children with tethered spinal cord.
The authors identified eight patients with Rubinstein-Taybi syndrome (RTS) and examined how the underlying conditions of this syndrome can impede the detection of symptoms associated with a tethered spinal cord. They also reviewed the literature and did not find any published series describing such an association with this syndrome. In this retrospective review, the authors report the diagnosis, treatment, and outcome of tethered spinal cord in eight children (age range 2-14 years) with RTS. The patients presented between 1995 and 2003 with neurogenic bladder, decreased activity, gait disturbance, and low-back pain. The children were examined using whole-spine magnetic resonance (MR) imaging and, in recent years, their spinal cord movement was assessed using cine MR imaging. After undergoing lumbar laminectomy and spinal cord untethering procedures, six patients experienced improvement in symptoms associated with tethered spinal cord such as pain, urinary tract infection, incontinence, spasticity, and neurogenic bladder. Although some underlying conditions of RTS may mask the symptoms of a tethered spinal cord in children, careful attention to the patient's medical history as provided by his or her parents may aid in early diagnosis, evaluation, and treatment, thus preventing further neurological deterioration and leading to improved outcomes.


Basal Ganglia involvement in Wernicke encephalopathy: report of 2 cases.
We present the neuroimaging and clinical findings in 2 nonalcoholic adult patients with WE as assessed by MR imaging. The first patient presented with gait ataxia and changes in consciousness. MR imaging disclosed bilateral lesions in the dorsal striatum and cerebellum. None of the regions typically affected in WE were involved. The second patient showed symmetric lesions in the posterior putamen associated with the alterations frequently and infrequently found WE.


A correlative study of serum digoxin levels and electrocardiographic measurements.
The ST-segment appearance, PR interval, corrected QU time and T-wave amplitude from standard electrocardiograms of 70 patients were correlated with serum digoxin levels done on the same day. The absence of a digtalis effect on ST segments, upright T waves and PTQ scores (a combination function of PR, QT and T) of one or less, correlated well with the absence of "toxic" serum digoxin levels (greater than 1,8 ng/ml). PTQ scores showed a significant linear correlation with serum digoxin levels, and PTQ scores of more than 3,0 were in all instances associated with "toxic" serum digoxin levels. These observations merit futher investigation and could be useful in clinical situations.


Magnetic resonance imaging (MRI) and relaxation spectrum analysis as methods to investigate swelling in whey protein gels.
Effective means for controlled delivery of nutrients and nutraceuticals are needed. Whey protein-based gels, as a model system and as a potential delivery system, exhibit pH-dependent swelling when placed in aqueous solutions. Understanding the physics that govern gel swelling is thus important when designing gel-based delivery platforms. The extent of swelling over time was monitored gravimetrically. In addition to gravimetric measurements, magnetic resonance imaging (MRI) a real-time noninvasive imaging technique that quantified changes in geometry and water content of these gels was utilized. Heat-set whey protein gels were prepared at pH 7 and swelling was monitored in aqueous solutions with pH values of 2.5, 7, and 10. Changes in dimension over time, as characterized by the number of voxels in an image, were correlated to gravimetric measurements. Excellent correlations between mass uptake and volume change (R(2)= 0.99) were obtained for the gels in aqueous solutions at pH 7 and 10, but not for gels in the aqueous solution at pH 2.5. To provide insight into the mechanisms for water uptake, nuclear magnetic resonance (NMR) relaxation times were measured in independent experiments. The relaxation spectrum for the spin-spin relaxation time (T(2)) showed the presence of 3 proton pools for pH 7 and 10 trials and 4 proton pools for pH 2.5 trials. Results demonstrate that MRI and NMR relaxation measurements provided information about swelling in whey protein gels that can constitute a new means for investigating and developing effective delivery systems for foods.


Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells.
The ability to respond to differential levels of oxygen is important to all respiring cells. The response to oxygen deficiency, or hypoxia, takes many forms and ranges from systemic adaptations to those that are cell autonomous. Perhaps the most ancient of the cell-autonomous adaptations to hypoxia is a metabolic one: the Pasteur effect, which includes decreased oxidative phosphorylation and an increase in anaerobic fermentation. Because anaerobic fermentation produces far less ATP than oxidative phosphorylation per molecule of glucose, increased activity of the glycolytic pathway is necessary to maintain free ATP levels in the hypoxic cell. Here, we present genetic and biochemical evidence that, in mammalian cells, this metabolic switch is regulated by the transcription factor HIF-1. As a result, cells lacking HIF-1alpha exhibit decreased growth rates during hypoxia, as well as decreased levels of lactic acid production and decreased acidosis. We show that this decrease in glycolytic capacity results in dramatically lowered free ATP levels in HIF-1alpha-deficient hypoxic cells. Thus, HIF-1 activation is an essential control element of the metabolic state during hypoxia; this requirement has important implications for the regulation of cell growth during development, angiogenesis, and vascular injury.