A Knowledge Translation Programme to Increase the Utilization of Thoracic Spine Mobilization and Manipulation for Patients with Neck Pain.
There is extensive evidence that mobilization and manipulation of the thoracic spine is associated with improved outcomes in patients with neck pain. However, these evidence-based techniques are not always utilized. Successful knowledge translation programmes are needed to move the best available evidence to clinical practice. The purpose of the present research was to evaluate the effects of a structured knowledge translation programme on the frequency of manual therapy techniques performed by physical therapists on patients with neck pain. Prior to our intervention, we assessed physical therapists' use of thoracic spine intervention for the treatment of neck pain and their knowledge of the evidence. We delivered a multimodal knowledge translation programme and then reassessed their use and knowledge of the interventions. The majority of our physical therapists increased the use of thoracic spine techniques for their patients with neck pain. The increase was greater in those who used the techniques infrequently. Overall knowledge of the evidence appeared unchanged. Knowledge translation programmes are essential in ensuring clinical use of evidence-based practice. Our programme results, although on a small scale and not statistically significant, showed a positive trend toward increased thoracic spine manual therapy use for neck pain. Copyright © 2015 John Wiley & Sons, Ltd.


Primary hyperparathyroidism during pregnancy: management by minimally invasive surgery based on ultrasound localization.
Primary hyperparathyroidism in pregnancy has the potential to seriously impact the mother and foetus. Management may be difficult because the condition is usually diagnosed during pregnancy necessitating a rapid decision to proceed with surgery. Minimally invasive surgery is appealing due to shorter operative times and lower risk of complications. We present a consecutive series of eight women diagnosed with hyperparathyroidism during pregnancy. All eight women were treated successfully by parathyroidectomy during pregnancy with no maternal or foetal complications. Seven of these 8 women were treated with minimally invasive parathyroidectomy based on ultrasound localization. Where ultrasound localization is performed by experienced endocrine surgeons, minimally invasive parathyroidectomy is a feasible and safe approach in the pregnant patient with primary hyperparathyroidism.


Evidence for the late formation of hydrous asteroids from young meteoritic carbonates.
The accretion of small bodies in the Solar System is a fundamental process that was followed by planet formation. Chronological information of meteorites can constrain when asteroids formed. Secondary carbonates show extremely old (53)Mn-(53)Cr radiometric ages, indicating that some hydrous asteroids accreted rapidly. However, previous studies have failed to define accurate Mn/Cr ratios; hence, these old ages could be artefacts. Here we develop a new method for accurate Mn/Cr determination, and report a reliable age of 4,563.4+0.4/-0.5 million years ago for carbonates in carbonaceous chondrites. We find that these carbonates have identical ages, which are younger than those previously estimated. This result suggests the late onset of aqueous activities in the Solar System. The young carbonate age cannot be explained if the parent asteroid accreted within 3 million years after the birth of the Solar System. Thus, we conclude that hydrous asteroids accreted later than differentiated and metamorphosed asteroids.


Interaction of HSP20 with a viral RdRp changes its sub-cellular localization and distribution pattern in plants.
Small heat shock proteins (sHSPs) perform a fundamental role in protecting cells against a wide array of stresses but their biological function during viral infection remains unknown. Rice stripe virus (RSV) causes a severe disease of rice in Eastern Asia. OsHSP20 and its homologue (NbHSP20) were used as baits in yeast two-hybrid (YTH) assays to screen an RSV cDNA library and were found to interact with the viral RNA-dependent RNA polymerase (RdRp) of RSV. Interactions were confirmed by pull-down and BiFC assays. Further analysis showed that the N-terminus (residues 1-296) of the RdRp was crucial for the interaction between the HSP20s and viral RdRp and responsible for the alteration of the sub-cellular localization and distribution pattern of HSP20s in protoplasts of rice and epidermal cells of Nicotiana benthamiana. This is the first report that a plant virus or a viral protein alters the expression pattern or sub-cellular distribution of sHSPs.


Milk of calcium cyst mimicking renal calculi: a case report.
A milk of calcium cyst mimicking renal stone in a 51-year-old man was presented to remind the possibility of milk of calcium when a well-defined round density was observed on the renal shadow of the plain abdomen film and the importance of graphics or CT scans taken in different positions to see the changes in the calcium gravidation to prevent unnecessary surgical interventions due to misdiagnosis.


How important is seed predation to recruitment in stable populations of long-lived perennials?
The many evolutionary modifications to seed biology in response to seed predation do not necessarily imply that seed predators have an important impact on population recruitment. This is because competition between individual plants for rare safe sites can cause an 'oversupply' of seeds so far as a population is concerned. The importance of seed losses to population recruitment at any point in time is related to the abundance of safe sites (Fig. 1): it is zero when safe sites are absent, negligible when safe sites are rare, and greatest when safe sites are numerous enough for recruitment to be limited by seed supply. Here I interpret the impact of severe seed losses on population recruitment in four species of long-lived perennials (Eucalyptus baxteri, Leptospermum juniperinum, Casuarina pusilla and L. myrsinoides) by considering these losses in terms of the overall seed dynamics of the populations. I focus on seed supply and seedling survival, as a measure of the current abundance of safe sites, and the maintenance of seed banks, as a measure of the ability of populations to exploit any future changes in safe site abundance. Insect seed predators destroyed about 95% of total seeds in each case. However, these losses do not necessarily have an important impact on population recruitment, because: (i) in most years recruitment appears to be limited by a rarity of safe sites, and not by seed supply (which was as high as 43 germinable seeds/m2/yr); and (ii) the losses did not prevent the establishment of large seed banks (ranging from >30 to >1000 viable seeds/m2) potentially capable of exploiting temporary conditions favourable for recruitment. In contrast to the situation with many annual plants, patterns of recruitment in stable populations of long-lived perennials are often extremely complex, and the significance of seed losses therefore difficult to determine.


Structures of [M(Ura-H)(H2 O)n ](+) (M = Mg, Ca, Sr, Ba; n = 1-3) complexes in the gas phase by IRMPD spectroscopy and theoretical studies.
The structures of singly and doubly (and for Mg, triply) hydrated group 2 metal dications bound to deprotonated uracil were explored in the gas phase using infrared multiple photon dissociation spectroscopy in the mid-infrared region (1000-1900 cm(-1) ) and the O-H/N-H stretching region (2700-3800 cm(-1) ) in a Fourier transform ion cyclotron resonance mass spectrometer. The infrared multiple photon dissociation spectra were then compared with the computed IR spectra for various isomers. Calculations were performed using B3LYP with the 6-31 + G(d,p) basis set for all atoms except Ba(2+) and Sr(2+) , for which the LANL2DZ or the def2-TZVPP basis sets with relativistic core potentials were used. Atoms-in-molecules analysis was conducted for all lowest energy structures. The lowest energy isomers in all cases are those in which the one uracil is deprotonated at the N3 position, and the metal is coordinated to the N3 and O4 of uracil. Regardless of the degree of solvation, all water molecules are bound to the metal ion and participate in a hydrogen bond with a carbonyl of the uracil moiety.


Effects of high-pressure argon and nitrogen treatments on respiration, browning and antioxidant potential of minimally processed pineapples during shelf life.
High-pressure (HP) inert gas processing causes inert gas and water molecules to form clathrate hydrates that restrict intracellular water activity and enzymatic reactions. This technique can be used to preserve fruits and vegetables. In this study, minimally processed (MP) pineapples were treated with HP (∼10 MPa) argon (Ar) and nitrogen (N) for 20 min. The effects of these treatments on respiration, browning and antioxidant potential of MP pineapples were investigated after cutting and during 20 days of storage at 4 °C. Lower respiration rate and ethylene production were found in HP Ar- and HP N-treated samples compared with control samples. HP Ar and HP N treatments effectively reduced browning and loss of total phenols and ascorbic acid and maintained antioxidant capacity of MP pineapples. They did not cause a significant decline in tissue firmness or increase in juice leakage. HP Ar treatments had greater effects than HP N treatments on reduction of respiration rate and ethylene production and maintenance of phenolic compounds and DPPH(•) and ABTS(•+) radical-scavenging activities. Both HP Ar and HP N processing had beneficial effects on MP pineapples throughout 20 days of storage at 4 °C.


Bacteriological sterility of washed deglycerolized red blood cells after 72 hours storage.
Samples of reconstituted frozen red blood cells, maintained at 4 C for 72 hours prior to culture, revealed a bacterial contamination rate of less than 0.2 per cent, suggesting that the present shelf life of 24 hours may be safely extended to 72 hours.


Genome sequence of the thermophilic fresh-water bacterium Spirochaeta caldaria type strain (H1(T)), reclassification of Spirochaeta caldaria, Spirochaeta stenostrepta, and Spirochaeta zuelzerae in the genus Treponema as Treponema caldaria comb. nov., Treponema stenostrepta comb. nov., and Treponema zuelzerae comb. nov., and emendation of the genus Treponema.
Spirochaeta caldaria Pohlschroeder et al. 1995 is an obligately anaerobic, spiral-shaped bacterium that is motile via periplasmic flagella. The type strain, H1(T), was isolated in 1990 from cyanobacterial mat samples collected at a freshwater hot spring in Oregon, USA, and is of interest because it enhances the degradation of cellulose when grown in co-culture with Clostridium thermocellum. Here we provide a taxonomic re-evaluation for S. caldaria based on phylogenetic analyses of 16S rRNA sequences and whole genomes, and propose the reclassification of S. caldaria and two other Spirochaeta species as members of the emended genus Treponema. Whereas genera such as Borrelia and Sphaerochaeta possess well-distinguished genomic features related to their divergent lifestyles, the physiological and functional genomic characteristics of Spirochaeta and Treponema appear to be intermixed and are of little taxonomic value. The 3,239,340 bp long genome of strain H1(T) with its 2,869 protein-coding and 59 RNA genes is a part of the G enomic E ncyclopedia of Bacteria and Archaea project.


Synthesis and antimicrobial evaluation of new chalcones containing piperazine or 2,5-dichlorothiophene moiety.
Two new series of chalcones have been synthesized by reacting 1-(4-piperazin-1-yl-phenyl)ethanone and 1-(2,5-dichloro-3-thienyl)-1-ethanone with different substituted benzaldehydes in turn by Claisen-Schmidt condensation. The compounds have been characterized by IR, (1)H NMR spectral and microanalysis data. All the synthesized compounds have been evaluated for antimicrobial activity. Some of these derivatives are potentially active against Gram-positive bacteria, Staphylococcus aureus and Escherichia coli while the most potent compound (1) in this study showed MIC(50) value of 2.22 microg/mL against Candida albicans.


Evidence that the recA441 (tif-1) mutant of Escherichia coli K-12 contains a thermosensitive intragenic suppressor of RecA constitutive protease activity.
The recA441 mutant of Escherichia coli, which has been thought to have thermoinducible constitutive RecA protease activity, is known to have two mutations within recA. We show here that the mutation that alters codon 38 actually confers temperature-independent constitutive protease activity; the second mutation in recA441, which is at codon 298, appears to be acting as a temperature-sensitive suppressor of the protease activity.


The changing distribution of neurons in the inner nuclear layer from metamorphosis to adult: a morphometric analysis of the anuran retina.
The generation and changing distribution of neurons of the inner nuclear layer (INL) in the retina of two anuran species, Bufo marinus and Xenopus laevis, were studied from metamorphosis to adult. Morphometric studies were undertaken at six developmental stages in Bufo and four in Xenopus. The number and thickness of neurons in the INL were established in 29 predetermined retinal locations from serial sections of the eyes cut vertically or horizontally. The total number of neurons in the INL increased from metamorphosis to adult from 826,000 +/- 185 to 18,760,000 +/- 562 (mean +/- SD) in Bufo and from 308,000 +/- 25 to 877,000 +/- 31 in Xenopus. Over the same period the surface area of the INL increased about 50-fold from 2 mm2 to 96 mm2 in Bufo and 5-fold from 2.5 mm2 to 13 mm2 in Xenopus. In Bufo the difference between the highest cell number (central-temporal retina) and the lowest cell number in a sample area (dorsal and ventral peripheral retina) was 2.1:1 at metamorphosis. This ratio increased to 3.4:1 in the adult. Both the cell number and cell density per sample area in the INL was found to be higher along the nasotemporal meridian of the eye overlying the visual streak of the ganglion cell layer (GCL) of the retina. The retinal distribution of neurons in the INL did not change significantly during postmetamorphic growth in Xenopus. At metamorphosis a 1.7:1 difference was found between the highest neuron number (retinal ciliary margin) and lowest neuron number (retinal centre) decreasing to 1.5:1 in the adult. Retinae were labelled with 3H-thymidine in 15 mm Bufos and examined 2, 6, 12 and 18 weeks later. Higher rates of cell addition to the nasal and temporal poles of the INL were found compared with that at the dorsal and ventral poles. The retinal radial growth at the ciliary margin of the dorsal, ventral, nasal and temporal poles between the time of isotope injection and 18 weeks survival was found to be uneven; more radial elongation occurred at the nasal, dorsal and ventral poles and less at the temporal pole. These observations suggest that (a) the neuron distribution of the INL in adult animals approximates that of the GCL and (b) the visual streak-like area of the INL in Bufo develops by a sustained differential cell addition at the temporal and nasal poles of the retina.


Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation.
Human skin immune homeostasis, and its regulation by specialized subsets of tissue-residing immune sentinels, is poorly understood. In this study, we identify an immunoregulatory tissue-resident dendritic cell (DC) in the dermis of human skin that is characterized by surface expression of CD141, CD14, and constitutive IL-10 secretion (CD141(+) DDCs). CD141(+) DDCs possess lymph node migratory capacity, induce T cell hyporesponsiveness, cross-present self-antigens to autoreactive T cells, and induce potent regulatory T cells that inhibit skin inflammation. Vitamin D(3) (VitD3) promotes certain phenotypic and functional properties of tissue-resident CD141(+) DDCs from human blood DCs. These CD141(+) DDC-like cells can be generated in vitro and, once transferred in vivo, have the capacity to inhibit xeno-graft versus host disease and tumor alloimmunity. These findings suggest that CD141(+) DDCs play an essential role in the maintenance of skin homeostasis and in the regulation of both systemic and tumor alloimmunity. Finally, VitD3-induced CD141(+) DDC-like cells have potential clinical use for their capacity to induce immune tolerance.


Selectivity of the excision of alkylation products in a xeroderma pigmentosum-derived lymphoblastoid line.
Lymphoblastoid cell derived from a complementation group C xeroderma patient were unable to remove 06-methyl guanine residues formed in DNA by treatment of cells with low concentration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The xeroderma cells were competent in their ability to excise 3-methyl adenine adducts. MNNG treatment induced excision repair in the xeroderma line and in addition the treatment resulted in the presence of numerous single-strand breaks in the DNA. The single gene, UV-excision-defective mutants of Escherichia coli, uvrA and uvrB, are able to excise MNNG-induced 06-methyl guanine adducts indicating that excision of this compound is not due to operation of UV endonuclease system.


Conservation cobenefits from air pollution regulation: Evidence from birds.
Massive wildlife losses over the past 50 y have brought new urgency to identifying both the drivers of population decline and potential solutions. We provide large-scale evidence that air pollution, specifically ozone, is associated with declines in bird abundance in the United States. We show that an air pollution regulation limiting ozone precursors emissions has delivered substantial benefits to bird conservation. Our estimates imply that air quality improvements over the past 4 decades have stemmed the decline in bird populations, averting the loss of 1.5 billion birds, ∼20% of current totals. Our results highlight that in addition to protecting human health, air pollution regulations have previously unrecognized and unquantified conservation cobenefits.


Cerebrospinal fluid Aβ42, phosphorylated Tau181, and resting-state functional connectivity.
Resting-state functional connectivity magnetic resonance imaging has great potential for characterizing pathophysiological changes during the preclinical phase of Alzheimer disease. To assess the relationship between default mode network integrity and cerebrospinal fluid biomarkers of Alzheimer disease pathology in cognitively normal older individuals. Cross-sectional cohort study at The Charles F. and Joanne Knight Alzheimer's Disease Research Center at Washington University in St Louis, St Louis, Missouri, among 207 older adults with normal cognition (Clinical Dementia Rating, 0). Resting-state functional connectivity magnetic resonance imaging measures of default mode network integrity. Decreased cerebrospinal fluid Aβ42 and increased cerebrospinal fluid phosphorylated tau181 were independently associated with reduced default mode network integrity, with the most prominent decreases in functional connectivity observed between the posterior cingulate and medial temporal regions. Observed reductions in functional connectivity were unattributable to age or structural atrophy in the posterior cingulate and medial temporal areas. Similar resting-state functional connectivity magnetic resonance imaging findings in relation to cerebrospinal fluid biomarkers were obtained using region-of-interest analyses and voxelwise correlation mapping. Both Aβ and tau pathology affect default mode network integrity before clinical onset of Alzheimer disease.


Serotonin uptake and imipramine binding in blood platelets and brain of Fawn-hooded and Sprague Dawley rats.
The kinetic parameters of serotonin (5-HT) uptake and imipramine binding of the synaptosomes and blood platelets of male Fawn-hooded rats, which have a 5-HT storage abnormality, and normal Sprague-Dawley rats were compared. The Vmax for 5-HT uptake of synaptosomes from Fawn-hooded rats was significantly greater than that of Sprague-Dawley rats whereas that of the platelets did not differ. The Km values of both the synaptosomes and platelets of the two rat strains were not significantly different. The Bmax values for 3H-imipramine binding in both platelets and brain of Fawn-hooded rats were significantly lower than those of the Sprague-Dawley rats. The Kd of imipramine binding to platelet membranes from Fawn-hooded rats was significantly less than that of the Sprague-Dawley rats but the Kd of the synaptosomes was not significantly different. These results indicate that 5-HT uptake and imipramine binding sites may be independently regulated and that platelets do not always manifest abnormalities present in brain 5-HT neurons and vice versa.


Irisin reduces inflammatory signaling pathways in inflammation-mediated metabolic syndrome.
Irisin is an exercise induced myokine first shown to induce the browning of white adipose tissue (WAT) which increases energy expenditure, improves glucose tolerance, and reduces insulin resistance. Among irisin's involvement in lipid homeostasis, osteoblast proliferation, and muscle growth, it also acts as a mediator of many inflammatory pathways throughout the body. This review aims to describe the role of irisin in inflammatory processes and understand how targeting irisin can alter the inflammatory response in metabolic syndrome (MetS). The mechanisms involved in irisin's anti-inflammatory functions include reducing production of pro-inflammatory cytokines while increasing production of anti-inflammatory cytokines, reducing macrophage proliferation, inducing alternatively activated (M2-type) macrophage polarization, inhibiting pathways of increased vascular permeability, and preventing the formation of inflammasomes. While there are some contradictory results, most studies found reduced levels of irisin in MetS and type II diabetes mellitus (T2DM). Irisin treatment of cells exposed to inflammatory stimuli ameliorates the inflammatory response and promotes cellular viability. Numerous methods have been studied to increase plasma irisin levels including dietary, behavioral, and pharmaceutical. Further investigation is necessary to understand how irisin can be targeted for disease modification.


Hypoglycaemic and anti-diabetic activity of stem bark extracts Erythrina indica in normal and alloxan-induced diabetic rats.
The objective of the study is to investigate the alcoholic (AlcE) and aqueous (AqsE) extracts of stem bark of Erythrina indica (Papilionaceae) for hypoglycaemic effects in normal and diabetic rats. Diabetes was induced in rats by a single dose administration of alloxan (120 mg/kg, i.p.) or by injecting dexamethasone (10 mg/kg, i.p.) for 10 days. In normal rats, AlcE and AqsE had significantly decreased the blood glucose level (BGL) in a dose dependent manner after repeated administration for 7 days. In alloxan-induced diabetic rats, both the extracts decreased blood sugar levels with significant improvement in glucose tolerance and body weight at the end of 1st, 2nd and 3rd week after test extract treatment. In case of dexamethasone induced insulin resistant diabetic rats, repeated administration of AlcE and AqsE inhibited the increase in blood glucose level and improved glucose tolerance induced by dexamethasone as compared to dexamethasone induced diabetic rats. These results suggest that both extracts possess hypoglycaemic activity in normal as well as in diabetic rats. Among AlcE and AqsE, AqsE possesses better hypoglycaemic activity than AlcE in all the models. Preliminary phytochemical investigations revealed that alcoholic extracts contain carbohydrates, alkaloids, flavonoids, saponins, phytosterols, phenolics and tannins. Aqueous extract contains carbohydrates, alkaloids, flavonoids, glycosides, phytosterols and triterpenoids. These phytoconstituents may be responsible for the hypoglycaemic activity of the plant.


Lifestyle Modification in Blood Pressure Study II (LIMBS): study protocol of a randomized controlled trial assessing the efficacy of a 24 week structured yoga program versus lifestyle modification on blood pressure reduction.
Hypertension is a major public health issue affecting 68 million adults in the United States. Lifestyle modifications including complementary therapies such as the movement based mind body practice of yoga have become increasingly popular in the United States and have been considered as a potential alternative to medication in blood pressure reduction. We completed a pilot study in 2009 which showed meaningful decreases in 24-hour ambulatory blood pressure readings after a 12 week period of yoga participation. Based on data from our pilot study we are now completing The Lifestyle Modification and Blood Pressure Study (LIMBS II) which is a phase 2 randomized controlled trial designed to determine the effects of yoga therapy and enhanced lifestyle modification on lowering blood pressure in pre-hypertensive and stage 1 hypertensive subjects. Using 24-hour ambulatory blood pressure monitoring, LIMBS II aims to compare the effects on blood pressure reduction in subjects randomized for 24 weeks to one of the three following groups: yoga therapy versus blood pressure education program (sodium restriction and walking program) versus a combination program that involves components of both groups. LIMBS II will also examine the impact that changes in blood pressure have on cerebral blood flow. If successful, the LIMBS study will determine if yoga therapy combined with enhanced lifestyle modification will result in clinically meaningful decreases in blood pressure and thus can be implemented as an alternative to drug therapy for patients with prehypertension and stage 1 hypertension.


[Comments and the diagnosis of vitality of early pregnancy in threatening abortion].
In a series of 79 consecutive patients examined by sonar and assays of human chorionic gonadotrophin in the first half of pregnancy 41 ultimately aborted. On analysis of the sonar and post abortion findings it was found, that the aborted pregnancies fell into 3 clearly defined groups: blighted ova, missed abortions and hydatidiform moles. Strict diagnostic sonar criteria of abnormality were established for these groups. Assays of human chorionic gonadotrophin have shown to be useful guides. But the overlap between their normal and abnormal ranges does not permit their use as sole arbitors of which pregnancies should be terminated.


Changes after major resection of experimental cirrhotic liver.
Liver cirrhosis was induced experimentally in dogs--hemodynamically, by constriction of the hepatic vein and pharmacologically, by administration of dimethylinitrosamine (DMNA)--after which approximately 45 per cent of the liver was resected. Results indicate that death after major resection of a cirrhotic liver was caused not only by too extensive a resection but also by the rapid progression of cirrhotic changes in the remnant liver during the postoperative course.


Hypoxia enhances the angiogenic potential of human dental pulp cells.
Trauma can result in the severing of the dental pulp vessels, leading to hypoxia and ultimately to pulp necrosis. Improved understanding of mechanisms underlying the response of dental pulp cells to hypoxic conditions might lead to better therapeutic alternatives for patients with dental trauma. The purpose of this study was to evaluate the effect of hypoxia on the angiogenic response mediated by human dental pulp stem cells (DPSCs) and human dental pulp fibroblasts (HDPFs). DPSCs and HDPFs were exposed to experimental hypoxic conditions. Hypoxia-inducible transcription factor-1alpha (HIF-1alpha) was evaluated by Western blot and immunocytochemistry, whereas vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression was evaluated by enzyme-linked immunosorbent assay. YC-1, an inhibitor of HIF-1alpha, was used to evaluate the functional effect of this transcriptional factor on hypoxia-induced VEGF expression. Conditioned medium from hypoxic and normoxic pulp cells was used to stimulate human dermal microvascular endothelial cells (HDMECs). HDMEC proliferation was measured by WST-1 assay, and angiogenic potential was evaluated by a capillary sprouting assay in 3-dimensional collagen matrices. Hypoxia enhanced HIF-1alpha and VEGF expression in DPSCs and HDPFs. In contrast, hypoxia did not induce bFGF expression in pulp cells. YC-1 partially inhibited hypoxia-induced HIF-1alpha and VEGF in these cells. The growth factor milieu of hypoxic HDPFs (but not hypoxic DPSCs) induced endothelial cell proliferation and sprouting as compared with medium from normoxic cells. Collectively, these data demonstrate that hypoxia induces complex and cell type-specific pro-angiogenic responses and suggest that VEGF (but not bFGF) participates in the revascularization of hypoxic dental pulps.


Asymmetrical cross-modal influence on neural encoding of auditory and visual features in natural scenes.
Natural scenes contain multi-modal information, which is integrated to form a coherent perception. Previous studies have demonstrated that cross-modal information can modulate neural encoding of low-level sensory features. These studies, however, mostly focus on the processing of single sensory events or rhythmic sensory sequences. Here, we investigate how the neural encoding of basic auditory and visual features is modulated by cross-modal information when the participants watch movie clips primarily composed of non-rhythmic events. We presented audiovisual congruent and audiovisual incongruent movie clips, and since attention can modulate cross-modal interactions, we separately analyzed high- and low-arousal movie clips. We recorded neural responses using electroencephalography (EEG), and employed the temporal response function (TRF) to quantify the neural encoding of auditory and visual features. The neural encoding of sound envelope is enhanced in the audiovisual congruent condition than the incongruent condition, but this effect is only significant for high-arousal movie clips. In contrast, audiovisual congruency does not significantly modulate the neural encoding of visual features, e.g., luminance or visual motion. In summary, our findings demonstrate asymmetrical cross-modal interactions during the processing of natural scenes that lack rhythmicity: Congruent visual information enhances low-level auditory processing, while congruent auditory information does not significantly modulate low-level visual processing.


Parallel progressive multiple sequence alignment on reconfigurable meshes.
One of the most fundamental and challenging tasks in bio-informatics is to identify related sequences and their hidden biological significance. The most popular and proven best practice method to accomplish this task is aligning multiple sequences together. However, multiple sequence alignment is a computing extensive task. In addition, the advancement in DNA/RNA and Protein sequencing techniques has created a vast amount of sequences to be analyzed that exceeding the capability of traditional computing models. Therefore, an effective parallel multiple sequence alignment model capable of resolving these issues is in a great demand. We design O(1) run-time solutions for both local and global dynamic programming pair-wise alignment algorithms on reconfigurable mesh computing model. To align m sequences with max length n, we combining the parallel pair-wise dynamic programming solutions with newly designed parallel components. We successfully reduce the progressive multiple sequence alignment algorithm's run-time complexity from O(m × n4) to O(m) using O(m × n3) processing units for scoring schemes that use three distinct values for match/mismatch/gap-extension. The general solution to multiple sequence alignment algorithm takes O(m × n4) processing units and completes in O(m) time. To our knowledge, this is the first time the progressive multiple sequence alignment algorithm is completely parallelized with O(m) run-time. We also provide a new parallel algorithm for the Longest Common Subsequence (LCS) with O(1) run-time using O(n3) processing units. This is a big improvement over the current best constant-time algorithm that uses O(n4) processing units.


Selenium supplementation, soluble tumor necrosis factor-alpha receptor type 1, and C-reactive protein during psoriasis therapy with narrowband ultraviolet B.
We examined the influence of supplementation with selenomethionine on soluble tumor necrosis factor-alpha receptor type 1 (sTNF-R1) and C-reactive protein (CRP) concentrations in patients with psoriasis who were treated with narrowband ultraviolet B. Thirty-seven patients had narrowband ultraviolet B therapy five times a week and received 200 mug of selenium daily as selenomethionine (group 1, n = 19) or placebo (group 2, n = 18) for 4 wk. Assessment, performed at baseline, after 2 and 4 wk, and 4 wk after the end of treatment included measurement of the Psoriasis Area and Severity Index (PASI) and serum concentrations of selenium (micrograms per liter), sTNF-R1 (nanograms per milliliter), and CRP (milligrams per liter). Control sera were obtained from 20 healthy volunteers. Baseline PASI was 12.70 +/- 5.48 (13.02 +/- 6.25 in group 1 and 12.37 +/- 4.71 in group 2), selenium concentration was 50.55 +/- 9.54 (49.05 +/- 10.38 and 52.13 +/- 8.61, respectively), sTNF-R1 concentration was 1.91 +/- 0.38 (1.96 +/- 0.37 and 1.87 +/- 0.40, respectively), and CRP concentration was 25.34 +/- 8.27 (26.12 +/- 8.42 and 24.57 +/- 7.72). In controls, selenium concentration was 48.71 +/- 9.39 (P > 0.05 versus patients), sTNF-R1 concentration was 1.48 +/- 0.30 (P < 0.05), CRP concentration was <6. The baseline sTNF-R1 level correlated to PASI value (r = 0.40, P < 0.05) and CRP concentration (r = 0.36, P > 0.05). The treatment resulted in an almost parallel decrease in PASI in both groups. At 4 wk after the end of treatment, selenium concentrations were 83.77 +/- 5.13 in group 1 and 52.12 +/- 7.54 in group 2 (P < 0.05), sTNF-R1 concentrations were 1.72 +/- 0.27 and 1.47 +/- 0.26 (P < 0.05), and CRP concentrations were 7.72 +/- 4.23 and 8.15 +/- 3.32, respectively (P > 0.05). Selenium concentration correlated inversely with CRP in group 1. The results confirm that sTNF-R1 and CRP concentrations are increated in active psoriasis and that supplementation with selenomethionine for 4 wk in safe doses is ineffacious as adjuvant therapy in patients with psoriasis.


Modeling Crevicular Fluid Flow and Host-Oral Microbiome Interactions in a Gingival Crevice-on-Chip.
Gingival crevice and gingival crevicular fluid (GCF) flow play a crucial role at the gingiva-oral microbiome interface which contributes toward maintaining the balance between gingival health and periodontal disease. Interstitial flow of GCF strongly impacts the host-microbiome interactions and tissue responses. However, currently available in vitro preclinical models largely disregard the dynamic nature of gingival crevicular microenvironment, thus limiting the progress in the development of periodontal therapeutics. Here, a proof-of-principle "gingival crevice-on-chip" microfluidic platform to culture gingival connective tissue equivalent (CTE) under dynamic interstitial fluid flow mimicking the GCF is described. On-chip co-culture using oral symbiont (Streptococcus oralis) shows the potential to recapitulate microbial colonization, formation of biofilm-like structures at the tissue-microbiome interface, long-term co-culture, and bacterial clearance secondary to simulated GCF (s-GCF) flow. Further, on-chip exposure of the gingival CTEs to the toll-like receptor-2 (TLR-2) agonist or periodontal pathogen Fusobacterium nucleatum demonstrates the potential to mimic early gingival inflammation. In contrast to direct exposure, the induction of s-GCF flow toward the bacterial front attenuates the secretion of inflammatory mediators demonstrating the protective effect of GCF flow. This proposed in vitro platform offers the potential to study complex host-microbe interactions in periodontal disease and the development of periodontal therapeutics under near-microphysiological conditions.


Training children in road crossing skills using a roadside simulation.
Five-year-old children were trained in road-crossing skill using a new method which allows them to act safely in relation to vehicles on a normal road. The children learned to time their crossings of a "pretend road" as if the vehicles were on this, rather than on the adjacent road. A previous study, using a single lane of traffic, showed that many children performed well in this simulation with minimal instruction, but that five-year-olds were generally less proficient than older children. In the present study, the method was extended to the more realistic case of two-way traffic, and training programmes for five-year-olds were assessed. (In addition, the performances of adults in the two-way pretend task and in actually crossing the road were compared; the results confirmed the validity of the simulation. After a few sessions of guided practice, the children's efficiency in making use of gaps by setting off promptly after a vehicle had passed improved markedly; in single-lane crossing they reached almost adult standard. In both single-lane and two-way crossing they became as successful as adults in completing their crossings before a second vehicle passed and they took account of the duration of the gap by crossing more quickly when time was short. They remained very cautious, rejecting many adequate gaps. The standard of performance after a few sessions of two-way crossing was maintained over a three week break in training. Practice with one-way traffic did not help them with two-way crossing. In sum, after practice in the simulation, five year olds develop a degree of competence normally shown by older children, whose experience on the roads puts them at lower risk. This suggests that the simulation, which allows children to safely explore and develop their capabilities more fully than when actually crossing the road, would be a valuable addition to road safety programmes.


Antifibrotic mechanism of deferoxamine in concanavalin A induced-liver fibrosis: Impact on interferon therapy.
Iron-overload is a well-known factor of hepatotoxicity and liver fibrosis, which found to be a common finding among hepatitis C virus patients and related to interferon resistance. We aimed to elucidate the potential antifibrotic effect of deferoxamine; the main iron chelator, and its additional usefulness to interferon-based therapy in concanavalin A-induced immunological model of liver fibrosis. Rats were treated with deferoxamine and/or pegylated interferon-α for 6 weeks. Hepatotoxicity indices, oxidative stress, inflammatory and liver fibrosis markers were assessed. Concanavalin A induced a significant increase in hepatotoxicity indices and lipid peroxidation accompanied with a significant depletion of total antioxidant capacity, glutathione level and superoxide dismutase activity. Besides, it increased CD4(+) T-cells content and the downstream inflammatory cascades, including NF-κB, TNF-α, iNOS, COX-2, IL-6 and IFN-γ. Furthermore, α-SMA, TGF-β1 and hydroxyproline were increased markedly, which confirmed by histopathology. Treatment with either deferoxamine or pegylated interferon-α alone reduced liver fibrosis markers significantly and improved liver histology. However, some of the hepatotoxicity indices and oxidative stress markers did not improve upon pegylated interferon-α treatment alone, besides the remarkable increase in IL-6. Combination therapy of deferoxamine with pegylated interferon-α further improved all previous markers, ameliorated IL-6 elevation, as well as increased hepcidin expression. In conclusion, our study provides evidences for the potent antifibrotic effects of deferoxamine and the underlying mechanisms that involved attenuating oxidative stress and subsequent inflammatory cascade, as well as the production of profibrogenic factors. Addition of deferoxamine to interferon regimen for HCV patients may offer a promising adjuvant modality to enhance therapeutic response.


Dual-response fluorescence sensing of H2PO4- and CO32- using AJP filter paper based on a pH-stable CdII-based luminescent metal-organic framework.
A new CdII-based luminescent metal-organic framework (LMOF) with the formula {[Cd(BIBT)(NDC)]·solvents}n (JXUST-32, BIBT = 4,7-bi(1H-imidazol-1-yl)benzo-[2,1,3]thiadiazole and H2NDC = 2,6-naphthalenedicarboxylic acid) was successfully synthesized by a solvothermal method. JXUST-32 shows a two-dimensional (4,4)-connected network and exhibits significant fluorescence red shift and slight enhancement for H2PO4- and CO32- sensing with detection limits of 0.11 and 0.12 μM, respectively. In addition, JXUST-32 has good thermal stability, chemical stability and recyclability. Significantly, JXUST-32 represents a fluorescence red-shift dual response MOF sensor for H2PO4- and CO32- detection and the analytes can be identified by the naked eye, aerosol jet printing filter paper, light-emitting diode beads and luminescent films.


Arthroscopic lateral retinacular release of the alar ligament. Indications and long-term results.
The indications for and results of arthroscopic release of the lateral alar ligament are evaluated. This technique was used exclusively in cases of anterior patellar pain due to lateral hypertension resulting from disalignment of the extensor apparatus. It was used on 21 knees with a follow-up of 15-36 months. Excellent or good results were obtained in 85% of the cases, according to both subjective and objective evaluation.


Predicting the Prognosis of Fuchs Endothelial Corneal Dystrophy by Using Scheimpflug Tomography.
To determine if Scheimpflug tomography pachymetry map and posterior elevation map patterns, central corneal thickness (CCT), and corneal backscatter can predict the prognosis of Fuchs endothelial corneal dystrophy (FECD). Cross-sectional study with follow-up of outcomes. Ninety-six eyes (56 subjects) with a range of severity of FECD. Corneas were graded by cornea specialists according to the area and confluence of guttae and the presence of clinically definite edema. Masked and randomized Scheimpflug imaging pachymetry map and posterior elevation map patterns were assessed by 1 observer for loss of regular isopachs, displacement of the thinnest point of the cornea, and the presence of posterior surface depression. The prognosis of eyes over a 5-year (median) follow-up period was determined based on FECD progression (new onset of clinically definite edema or ≥5% increase in CCT) or intervention by endothelial keratoplasty. Cumulative probabilities of progression and intervention were estimated from survival analyses, with risk factors determined by using Cox proportional hazards models. Pachymetry map and posterior elevation map patterns, corneal backscatter, and CCT (ultrasonic pachymetry). In univariate analyses, loss of regular isopachs (hazard ratio [HR], 18.00) displacement of the thinnest point (HR, 11.53), focal posterior surface depression (HR, 10.21), and anterior corneal backscatter (HR, 1.22, per 1-grayscale unit increment), were risk factors for progression or intervention (P < 0.001), whereas CCT (HR, 1.30, per 25-μm increment) was not (P = 0.15). In multivariate analyses, loss of regular isopachs (HR, 11.57; P < 0.001) and displacement of the thinnest point (HR, 5.61; P = 0.02) were independent and clinically important risk factors for progression and intervention. The 5-year cumulative risk of disease progression and intervention was 7%, 48%, and 89% when none, 1 or 2, and all 3 pachymetry map and posterior elevation map parameters were present, respectively (P <0.001). The 4-year cumulative risk of disease progression and intervention after uncomplicated cataract surgery was 0%, 50%, and 75% when none, 1 or 2, and all 3 pachymetry map and posterior elevation map parameters were present, respectively (P < 0.001). Three Scheimpflug tomography pachymetry map and posterior elevation map patterns can predict FECD prognosis independent of CCT. The risk of FECD progression and intervention, including after uncomplicated cataract surgery, increases according to the number of parameters present.


The use of normothermic liver preservation in combined liver and lung transplantation: A single-center experience.
Combined liver and lung transplantation (CLLT) is indicated in patients with both end-stage liver and lung disease. Ex-situ normothermic machine perfusion (NMP) has been previously used for extended normothermic lung preservation in CLLT. We aim to describe our single-center experience using ex-situ NMP for extended normothermic liver preservation in CLLT. Four CLLTs were performed from 2019 to 2020 with the lung transplanted first for all patients. Median ex-situ pump time for the liver was 413 min (IQR 400-424). Over a median follow-up of 15 months (IQR 14-19), all patients were alive and doing well. Normothermic extended liver preservation is a safe method to allow prolonged cold ischemia using normothermic perfusion of the liver during CLLT.


[Antibodies to the structural and nonstructural gag-coded proteins of type-D retroviruses in patients with lymphadenopathy].
Screening of antibodies to structural and nonstructural gag gene-coded proteins in humans with lymphadenopathy and AIDS was performed by means of radioimmunoprecipitation (RIP) and western blotting. Pr78gag precursor of gag-coded proteins of type-D retrovirus from Hep-2 cells served as an antigen in RIP tests. Total number of sera (of humans with lymphoadenopathy) under RIP analysis was 18 and one sera of AIDS patient. Six of them reacted with Pr78gag and one out of one AIDS serum. Over 80 sera samples of humans with lymphadenopathy have been tested by means of western blotting with proteins of Mason-Pfizer monkey virus as antigens. Antibodies to p27 (major internal protein of Mason-Pfizer monkey virus) were detected in 12 sera samples of those with lymphadenopathy (dilution 1:100) and in 9 out of 12 sera of AIDS patients (dilution 1:100-1:400). Results obtained make it possible to predict that type-D retroviruses are associated with acquired immunodeficiency syndrome and generalized lymphadenopathy and could play some role in development of this illness in humans.


Trace element status of children with PKU and normal children.
The trace mineral (chromium, copper, iron, selenium, and zinc) status of 10 children (4 to 13.8 years) with phenylketonuria (PKU) and 9 normal children (6.5 to 15.9 years) was assessed. The children with PKU were treated with a phenylalanine-free L-amino acid mix that supplied the following percentages (mean +/- standard deviation) of total daily intake: energy, 45 +/- 13; protein, 75 +/- 11; copper (Cu), 62 +/- 10; iron (Fe), 82 +/- 7; selenium (Se), 40 +/- 20; and zinc (Zn) 87 +/- 8. Diet records and blood samples were collected from each subject. Children with PKU had significantly greater mean intakes of Cu, Fe, and Zn than normal children. Mean serum Cu, Fe, and Zn concentrations of the children with PKU and normal children were not different despite significantly greater intakes by the children with PKU. Normal children had a significantly greater mean serum Se concentration and a mean blood chromium concentration 1.6 times that of children with PKU. Individuals whose primary source of protein is an elemental diet are especially at risk for multiple trace mineral deficiencies. Manufacturers of chemically defined medical foods should evaluate composition, specifically molar ratios between minerals, as a basis for product formulation.


PEG-PLA nanoparticles decorated with small-molecule PSMA ligand for targeted delivery of galbanic acid and docetaxel to prostate cancer cells.
Prostate cancer (PCa) is one of the most prevalent non-drug delivery system cutaneous malignancies. Undoubtedly, introducing novel treatment options to achieve higher therapeutic index will be worthwhile. In this study, we report for the first time, a novel targeted self-assembled based on PEG-PLA nanoparticles (PEG-PLA NPs) containing galbanic acid (GBA) and docetaxel, which was targeted using ((S)-2-(3-((S)-5-amino-1-carboxypentyl) ureido) pentanedioic acid (ACUPA), a small molecule inhibitor targeting prostate-specific membrane antigen (PSMA), in prostate cancer cell line. The prepared NPs were characterized by different analytical methods. The MTT assay was used to compare the anti-proliferation of drugs-loaded PEG-PLA NPs and ACUPA-PEG-PLA against LNCaP (PSMA+ ) and PC3 (PSMA- ) cells. PEG-PLA NPs with an average size of 130-140 nm had an enhanced release of GBA and docetaxel at pH 5.5 compared with pH 7.5. Spectrofluorometric analysis suggested that ACUPA-modified PEG-PLA could effectively enhance the drug uptake in PSMA+ prostate cancer cells. Cytotoxicity studies showed that the targeted NPs loaded with different concentrations of GBA and fixed concentration of docetaxel (4 nM) have shown higher toxicity (IC50 30 ± 3 µM) than both free GBA (80 ± 4.5 µM) and nontargeted NPs (IC50 40 ± 4.6 µM) in LNCaP cells. Collectively, these findings suggest that ACUPA-conjugated PEG-PLA nanosystem containing GBA and docetaxel is a viable delivery carrier for various cancer-targeting PSMA that suffer from short circulation half-life and limited therapeutic efficacy.


Causal association between heart failure and bone mineral density: Insights from a two-sample bidirectional Mendelian randomization study.
In recent times, the association between HF and BMD has attracted enormous interest in the scientific community. However, published epidemiological observational studies on the relationship between HF and BMD remain inconclusive. Herein, we evaluated from the analytical perspective a two-sample bidirectional MR study to analyze the causal association between HF and BMD using a summary-level GWAS Catalog. To select instrumental SNPs strongly associated with exposure, we took a series of rigorous quality control steps at the time of analysis. The causal MR assessment of HF on the risk of BMD was performed first and then in the opposite direction. To make the conclusions more reliable and robust, the fixed-effects IVW, weighted median-based method, MR-Egger, simple mode and weighted mode were utilized. A maximum likelihood model was also used if necessary. MR-Egger regression, IVW "leave-one-out" sensitivity analysis, MR-PRESSO, MR-Egger intercept test and Cochran's Q statistic methods were used to assess heterogeneity and pleiotropy. Our MR studies supported a meaningful causal association between HF and TB-BMD (IVW: OR = 0.78, 95% CI: 0.68-0.87, p = 0.00588). At the same time, we did not find a significant causal relationship between HF and FA-BMD, FN-BMD or LS-BMD. No significant causal relationships between BMD and HF were observed. This bidirectional MR analysis suggested a causal association of HF with only low TB-BMD, while the reverse causality hypothesis was not found. Studies of the prevention and treatment of total bone mineral density decline in patients with heart failure need to be performed.


Tissue kallikrein deficiency aggravates cardiac remodelling and decreases survival after myocardial infarction in mice.
Tissue kallikrein (TK) is a major kinin-releasing enzyme present in arteries. TK is involved in cardioprotection in the setting of acute myocardial ischaemia but its role in post-ischaemic heart failure (HF), a major cause of delayed mortality after myocardial infarction (MI), is unknown. To determine whether TK deficiency in the mouse influences survival and cardiac remodelling after MI. MI was induced in 10 week-old male TK-deficient mice and wild-type littermates. Survival was assessed up to 14 months. Cardiac morphological and functional parameters were serially measured by echocardiography. In another experiment, myocardial capillary density and NOS content were evaluated at 3 months. Infarct size was similar in both genotypes. MI resulted in severe cardiac dysfunction. Up to 12 months after MI, TK(-/-) mice displayed an increased mortality rate (P<0.05, relative risk of death=3.41) and aggravation of left ventricular hypertrophy and dilatation by comparison with TK(+/+) (+18% and +27% respectively, both P<0.05). NOS1 and NOS3 were abnormally regulated in the heart of TK(-/-) mice after MI. TK exerts a protective role in HF in mice. Coronary effects are probably involved. As partial genetic deficiency in TK activity occurs in humans, TK-deficient subjects may be at increased risk of mortality in HF.


The role of the iminium bond in the inhibition of reverse transcriptase by quaternary benzophenanthridines.
The quaternary benzo[c]phenanthridines fagaronine, nitidine and O-methylfagaronine have been reviewed as potential antitumour and antiviral agents. Their mode of action has not been established, but their ability to bind with DNA by intercalation is believed to be involved. Of the three synthetic analogues of O-methylfagaronine which we have synthesized, methoxidine and ethoxidine are active against HIV-1 reverse transcriptase (IC50 values 2.8 microM and 2.4 microM respectively) whereas hydroxidine is inactive. One of the prerequisites for the enzyme inhibitory activity of this class of molecule is the presence of an iminium group--it is well known that a positive charge on a polyaromatic nucleus facilitates intercalative binding with DNA. Through UV spectrophotometric and modelling studies, we have shown that the iminium bond plays a more fundamental role in enzyme inhibition through its susceptibility to nucleophilic attack--the inactive analogue hydroxidine has a non-electrophilic iminium bond. Consequently, we have demonstrated that iminium bond electrophilicity is a parameter which needs to be considered in ternary complex formation with reverse transcriptase.


Diagnosing Transthyretin Cardiac Amyloidosis by Technetium Tc 99m Pyrophosphate: A Test in Evolution.
This study aimed to characterize trends in technetium Tc 99m pyrophosphate (99mTc-PYP) scanning for amyloid transthyretin cardiac amyloidosis (ATTR-CA) diagnosis, to determine whether patients underwent appropriate assessment with monoclonal protein and genetic testing, to evaluate use of single-photon emission computed tomography (SPECT) in addition to planar imaging, and to identify predictive factors for ATTR-CA. 99mTc-PYP scintigraphy has been repurposed for noninvasive diagnosis of ATTR-CA. Increasing use of 99mTc-PYP can facilitate identification of ATTR-CA, but appropriate use is critical for accurate diagnosis in an era of high-cost targeted therapeutics. Patients undergoing 99mTc-PYP scanning 1 h after injection at a quaternary care center from 2010 to 2019 were analyzed; clinical information was abstracted; and SPECT results were analyzed. Over the decade, endomyocardial biopsy rates remained stable with scanning rates peaking at 132 in 2019 (p < 0.001). Among 753 patients (516 men, mean age 77 years), 307 (41%) had a visual score of 0, 177 (23%) of 1, and 269 (36%) of 2 or 3. Of 751 patients with analyzable heart to contralateral chest ratios, 249 (33%) had a ratio ≥1.5. Monoclonal protein testing status was assessed in 550 patients, of these, 174 (32%) did not undergo both serum immunofixation and serum free light chain analysis tests, and 331 (60%) did not undergo all 3 tests-serum immunofixation, serum free light chain analysis, and urine protein electrophoresis. Of 196 patients with confirmed ATTR-CA, 143 (73%) had genetic testing for transthyretin mutations. In 103 patients undergoing cardiac biopsy, grades 2 and 3 99mTc-PYP had sensitivity of 94% and specificity of 89% for ATTR-CA with 100% specificity for grade 3 scans. With respect to SPECT as a reference standard, planar imaging had false positive results in 16 of 25 (64%) grade 2 scans. Use of noninvasive testing with 99mTc-PYP scanning for evaluation of ATTR-CA is increasing, and the inclusion of monoclonal protein testing and SPECT imaging is crucial to rule out amyloid light chain amyloidosis and distinguish myocardial retention from blood pooling.


Diagnostic accuracy of upper gastrointestinal series in children with suspected intestinal malrotation.
Intestinal malrotation (IM) results from an altered or incomplete rotation of the fetal midgut around the superior mesenteric artery axis. The abnormal anatomy of IM is associated with risk of acute midgut volvulus which can lead to catastrophic clinical consequences. The upper gastro-intestinal series (UGI) is addressed as the gold standard diagnosis procedure, but a variable failure degree has been described in literature. The aim of the study was to analyze the UGI exam and describe which features are the most reproducible and reliable in diagnosing IM. Medical records of patients surgically treated for suspected IM between 2007 and 2020 at a single pediatric tertiary care center were retrospectively reviewed. UGI inter-observer agreement and diagnostic accuracy were statistically calculated. Images obtained with antero-posterior (AP) projections were the most significant in terms of IM diagnosis. Duodenal-Jejunal Junction (DJJ) abnormal position resulted to be the most reliable parameter (Se = 0.88; Sp = 0.54) as well as the most readable, with an inter-reader agreement of 83% (k = 0.70, CI 0.49-0.90). The First Jejunal Loops (FJL), caecum altered position and duodenal dilatation could be considered additional data. Lateral projections demonstrated an overall low sensitivity (Se = 0.80) and specificity (Sp = 0.33) with a PPV of 0.85 and a NPV of 0.25. UGI on the sole AP projections ensures a good diagnostic accuracy. The position of the third portion of the duodenum on lateral views showed an overall low reliability, therefore it was not helpful but rather deceiving in diagnosing IM.


Cardiac function by magnetic resonance imaging.
Gated magnetic resonance imaging of the heart displays cardiac structures with excellent resolution. This ability should be useful for assessment of cardiac physiology where acquisition of systolic and diastolic images is required. In this study, left ventricular ejection fraction was determined in 50 patients from oblique long axis views of the left ventricle using the area length formula. Angulated views were obtained by electronic gradient angulation. For comparison, all patients had monoplane angiocardiography in the RAO position. Forty-five patients were also studied by radionuclide ventriculography. Ejection fractions determined by MRI and angiocardiography were closely correlated (r = 0.90). Correlation between MRI and radionuclide ventriculography was also acceptable (r = 0.79). In addition to global left ventricular function, MR images provide information about regional wall motion. In order to acquire a three-dimensional set of images at various phases of the cardiac cycle, shorter imaging times are mandatory. A new imaging technique with potential for functional studies uses low flip angles, short repetition times and gradient refocused echoes. Up to 40 images can be obtained within one cardiac cycle. When displayed in a looped fashion, visual assessment of cardiac motion, intracardiac blood flow, and systolic wall thickening is possible. Potential advantages of functional studies by MRI are the concomitant acquisition of anatomical information and the three dimensional frame of reference.


Space-mapped auditory projections from the inferior colliculus to the optic tectum in the barn owl (Tyto alba).
The optic tectum of the owl contains a topographic representation of auditory space. We have investigated the source of this space-mapped auditory activity by using retrograde tracing with horseradish peroxidase. The major source of auditory input to the optic tectum is the ipsilateral external nucleus of the inferior colliculus (ICX), which is known to contain a map of auditory space also. Additional minor projections originate in the superficial nucleus of the inferior colliculus and the nucleus isthmi parvocellularis. There is no apparent projection to the optic tectum from the contralateral ICX or any other brainstem auditory nucleus. The projection from the ICX to the optic tectum is point-to-point: rostral ICX projects to rostral tectum, caudal ICX to caudal tectum, dorsal ICX to dorsomedial tectum, and ventral ICX to ventral tectum. Thus, the space-mapped organization that exists in the ICX is passed on by topographic projections to the optic tectum.


Genome-wide analyses of circadian systems.
Circadian gene expression is a pervasive feature of tissue physiology, regulating approx. 10% of transcript and protein abundance in tissues such as the liver. Technological developments have accelerated our ability to probe circadian variation of gene expression, in particular by using microarrays. Recent advances in high-throughput sequencing have similarly led to novel insights into the regulation of genes at the DNA and chromatin levels. Furthermore, tools such as RNA interference are being used to perturb gene function at a truly systems level, allowing dissection of the clockwork in increasing depth. This chapter will highlight progress in these areas, focusing on key techniques that have helped, and will continue to help, with the investigation of circadian physiology.


Epidermal growth factor receptor gene mutation in non-small cell lung cancer using highly sensitive and fast TaqMan PCR assay.
Epidermal growth factor receptor (EGFR) gene mutations have been found in a subset of non-small cell lung cancer (NSCLC) with good clinical response to gefitinib therapy. A quick and sensitive method with large throughput is required to utilize the information to determine whether the molecular targeted therapy should be applied for the particular NSCLC patients. Using probes for the 13 different mutations including 11 that have already been reported, we have genotyped the EGFR mutation status in 94 NSCLC patients using the TaqMan PCR assay. We have also genotyped the EGFR mutations status in additional 182 NSCLC patients, as well as 63 gastric, 95 esophagus and 70 colon carcinoma patients. In 94 NSCLC samples, the result of the TaqMan PCR assay perfectly matched with that of the sequencing excluding one patient. In one sample in which no EGFR mutation was detected by direct sequencing, the TaqMan PCR assay detected a mutation. This patient was a gefitinib responder. In a serial dilution study, the assay could detect a mutant sample diluted in 1/10 with a wild-type sample. Of 182 NSCLC samples, 46 mutations were detected. EGFR mutation was significantly correlated with gender, smoking status, pathological subtypes, and differentiation of lung cancers. There was no mutation detected by the TaqMan PCR assay in gastric, esophagus and colon carcinomas. TaqMan PCR assay is a rapid and sensitive method of detection of EGFR mutations with high throughput, and may be useful to determine whether gefitinib should be offered for the treatment of NSCLC patients. The TaqMan PCR assay can offer us a complementary and confirmative test.


The "Cocoon," first alongside midwifery-led unit within a Belgian hospital: Comparison of the maternal and neonatal outcomes with the standard obstetric unit over 2 years.
Our aim was to compare maternal and neonatal outcomes of women with a low-risk pregnancy attending the "Cocoon," an alongside midwifery-led birth center and care pathway, with women with a low-risk pregnancy attending the traditional care pathway in a tertiary care hospital in Belgium. We performed a retrospective cohort study of maternal and neonatal outcomes of women with a low-risk pregnancy who chose to adhere to the Cocoon pathway of care (n = 590) and women with a low-risk pregnancy who chose the traditional pathway of care (n = 394) from March 1, 2014, to February 29, 2016. We performed all analyses using an intention-to-treat approach. In this setting, the cesarean birth rate was 10.3% compared with 16.0% in the traditional care pathway (adjusted odds ratios [aOR] 0.42 [95% CI 0.25-0.69]), the induction rate was 16.3% compared with 30.5% (0.46 [0.30-0.69]), the epidural analgesia rate was 24.9% compared with 59.1% (0.15 [0.09-0.22]), and the episiotomy rate was 6.8% compared with 14.5% (0.31 [0.17-0.56]). There was no increase in adverse neonatal outcomes. Intrapartum and postpartum transfer rates to the traditional pathway of care were 21.1% and 7.1%, respectively. Women planning their births in the midwifery-led unit, the Cocoon, experienced fewer interventions with no increase in adverse neonatal outcomes. Our study gives initial support for the introduction of similar midwifery-led care pathways in other hospitals in Belgium.


Surgical treatment of Ebstein's anomaly. Early and late results in twenty patients subjected to valve replacement.
Twenty patients with Ebstein's anomaly underwent corrective operations between 1965 and 1978. Sixteen were in Functional Class III or IV (N.Y.H.A.) and four were in Class II but were having episodes of anoxia, syncope, or a rapid increase in cardiac size. In the first 10 cases (1965 to 1972) the tricuspid valve was replaced with a Starr-Edwards prosthesis, and in the second group (1972 to 1978) a dura mater valve was used. Five patients also underwent plication of a very large atrialized right ventricular segment. The atrial septal defect was closed totally in four cases, partially in eleven cases, and left open in five cases; one patient also underwent closure of the ventricular septal defect. Four patients died in the immediate postoperative period, three of whom were in the first group. There were three late postoperative deaths in the remaining 16 patients, all of them in the first group. All 13 of the surviving patients are in Functional Class I, except for one patient who is in Class II.


Somatic embryogenesis and plant regeneration of cassava (Manihot esculenta Crantz) landraces from Cameroon.
A procedure to regenerate cassava (Manihot esculenta Crantz) cultivars from Cameroon via somatic embryogenesis (SE) was developed. Shoot apical meristems and immature leaf lobes were used as explants on Murashige and Skoog (MS) basal medium containing 33 or 50 µM of the auxins Picloram (Pic), 2,4-Dichlorophenoxyacetic acid (2,4-D), Dicamba (Dic), and α-Naphthalene acetic acid. Cultivar performance was assessed using SE and number of somatic embryos produced. Overall, the frequency of primary somatic embryogenesis (PSE) and the mean number of somatic embryos produced varied considerably with genotype, type of auxin and concentration tested. For example, cultivar (cv.) Ngan Mbada showed the best performance on MS medium supplemented with 50 µM Pic with a SE frequency of 40 % and an average number of somatic embryos of 90. The second best performance was recorded in cv. Local Red on MS medium supplemented with 33 µM 2,4-D, where the SE frequency was 40 % and an average number of somatic embryos of 60.5. Cultivar Ekona Red recorded the best performance on medium supplemented with 50 µM Pic showing a SE frequency of 47 % and an average number of somatic embryos of 45. We further examined secondary and cyclic somatic embryogenesis (SSE, CSE) and both were also observed to vary with genotype, however, both exhibited significantly higher frequencies of SE compared with PSE. SE started to decline at the fourth cycle of embryogenesis. Examination of organogenesis showed that shoot bud induction from green cotyledons varied across cultivars and benzylaminopurine was shown to outperform Thidiazuron in the ability to induce organogenesis. Furthermore, the frequencies of bud induction were identical under light and dark conditions. Finally, regenerated plants grew easily in the greenhouse with 90-100 % survival rate and did not display detectable variation in morphology.


Fidelity levels of DNA polymerases in tumorigenic state cells and serially transplantable tumor cells.
It is well known that point mutations exist in oncogenes and tumor suppressor genes of tumor cells, and one of the causes of these mutations may be misincorporation by error-prone DNA polymerases. This hypothesis is supported by the observation of decreased fidelity levels of DNA polymerases in mouse spleen containing tumorigenic cells after infection with Friend virus, and in aged animals that suffer high rates of tumorigenesis. However, this decrease in fidelity is disadvantageous for tumor cells maintained by serial transplantation. Therefore, we measured the fidelity levels of DNA polymerases in tumor cells transplanted through many passages. The fidelity levels of DNA polymerases from Yoshida ascites hepatoma, Rhodamine sarcoma, mouse ascites hepatoma-134, and Ehrlich ascites carcinoma cells derived from rats and mice are very high for in-vitro DNA synthesis on synthetic polynucleotides. These results suggest that many kinds of mutant cells arise during tumorigenesis. Among these mutant cells, cells showing decreased DNA polymerase(s) fidelities are present and these cells may undergo cell death. On the other hand, cells with mutations in various oncogenes and tumor suppressor genes and without mutations in DNA polymerase genes may survive as serially transplantable tumor cells.


Data highlighting phenotypic diversity of urine-associated Escherichia coli isolates.
This article provides a reusable dataset describing detailed phenotypic and associated clinical parameters in n=303 clinical isolates of urinary Escherichia coli collected at Vanderbilt University Medical Center. De-identified clinical data collected with each isolate are detailed here and correlated to biofilm abundance and metabolomics data. Biofilm-abundance data were collected for each isolate under different in vitro conditions along with datasets quantifying biofilm abundance of each isolate under different conditions. Metabolomics data were collected from a subset of bacterial strains isolated from uncomplicated cases of cystitis or cases with no apparent symptoms accompanying colonization. For more insight, please see "Defining a Molecular Signature for Uropathogenic versus Urocolonizing Escherichia coli: The Status of the Field and New Clinical Opportunities" [1].


Antimicrobial evaluation of new metallic complexes with xylitol active against P. aeruginosa and C. albicans: MIC determination, post-agent effect and Zn-uptake.
Xylitol (xylH5) is metabolized via the pentose pathway in humans, but it is unsuitable as an energy source for many microorganisms where it produces a xylitol-induced growth inhibition and disturbance in protein synthesis. For this reason, xylitol is used in the prophylaxis of several infections. In the search of better antimicrobial agents, new copper and zinc complexes with xylitol were synthesized and characterized by analytical and spectrosco pic methods: Na2[Cu3(xylH−4)2]·NaCl·4.5H2O (Cu-xyl) and [Zn4(xylH−4)2(H2O)2]·NaCl·3H2O (Zn-xyl). Both copper and zinc complexes presented higher MIC against Pseudomona aeruginosa than the free xylitol while two different behaviors were found against Candida albicans depending on the complex. The growth curves showed that Cu-xyl presented lower activity than the free ligand during all the studied period. In the case of Znxyl the growth curves showed that the inhibition of the microorganism growth in the first stage was equivalent to that of xylitol but in the second stage (after 18 h) Zn-xyl inhibited more. Besides, the PAE (post agent effect)obtained for Zn-xyl and xyl showed that the recovery from the damage of microbial cells had a delay of 14 and 13 h respectively. This behavior could be useful in prophylaxis treatments for infectious diseases where it is important that the antimicrobial effect lasts longer. With the aim to understand the microbiological activities the analysis of the particle size, lipophilicity and Zn uptake was performed.


Restraint stress and adrenalectomy do not affect the level of rat cerebral enolase.
Gamma gamma (gamma gamma) enolase amount and enolase isozyme activities were measured in brain structures involved in stress response (hypothalamic paraventricular and supraoptic nuclei, locus coeruleus, hippocampus, A1 and A2 regions, hypophysis). Analyses were made in rats after immobilization or adrenalectomy, two experimental conditions that have been reported to increase brain glucose consumption and protein synthesis. In control rats enolase content was highest in the A1 region and hippocampus and lowest in hypophysis. A positive correlation was found between the enzyme level and its activity in the brain regions studied. However, in stressed or adrenalectomized rats, the level of glycolytic enzyme enolase was not significantly modified.


Uncovering novel loci for mesocotyl elongation and shoot length in indica rice through genome-wide association mapping.
Totally, 23 loci were detected, and 383 candidate genes were identified, and four of these candidate genes, Os01g0392100, Os04g0630000, Os01g0904700 and Os07g0615000, were regarded as promising targets. Direct-seeding cultivation is becoming popular in rice (Oryza sativa L.)-planting countries because it is labor- and time-efficient. However, low seedling establishment and slow seedling emergence have restricted the application and popularity of the technique. Mesocotyl elongation and shoot length are two important traits that can enhance rice seedling emergence. A single nucleotide polymorphism (SNP) is a genome sequence variation caused by a single base within a population, and SNPs evenly distributed throughout the genomes of plant species. In this study, a genome-wide association study (GWAS), based on 4136 SNPs, was performed using a compressed mixed linear model that accounted for population structure and relative kinship to detect novel loci for the two traits. Totally, 23 loci were identified, including five loci located known QTLs region. For the mesocotyl elongation, 17 major loci were identified, explaining ~19.31 % of the phenotypic variation. For the shoot length, six major loci were detected, explaining ~ 39.79 % of the phenotypic variation. In total, 383 candidate genes were included in a 200-kb genomic region (± 100 kb of each locus). Additionally, 32 SNPs were identified in 30 candidate genes. Relative expression level analyses indicated that four candidate genes containing SNP variations, Os01g0392100, Os04g0630000, Os01g0904700 and Os07g0615000, represented promising targets. Finally, eight elite accessions with long mesocotyl and shoot lengths were chosen as breeding donors for further rice direct-seeding variety modifications.


Surgical results of double-orifice left atrioventricular valve associated with atrioventricular septal defects.
Double-orifice left atrioventricular valve (LAVV) is a rare but surgically important anomaly, which is regarded as a risk factor for surgical correction of atrioventricular septal defects (AVSDs). Of 209 consecutive patients with AVSDs, double-orifice LAVV was identified in 19 patients (9.1%, including 7 infants). Preoperative LAVV function, surgical procedures and results, incidence of postoperative LAVV dysfunction and reoperations were reviewed and compared between patients with this valve malformation (group I, n = 19) and those without it (group II, n = 190). There were no operative or late deaths in group I. Preoperative LAVV function was similar in both groups. The cleft was totally closed in 77.2% of group II and 47.1% of group I (p < 0.01). In partial AVSDs, freedom from postoperative LAVV insufficiency was 77.0% in group II versus 30.5% in group I at 5 years (p = 0.009) and freedom from reoperation was 89.9% in group II versus 58.3% in group I at 5 years (p = 0.012); however, there was no difference in complete AVSDs. None of the infants in group I underwent total cleft closure and 4 of them showed more than moderate LAVV insufficiency postoperatively. Double-orifice LAVV is a significant predictor for postoperative LAVV incompetence and reoperation in partial AVSDs, but not in complete AVSDs. Surgical procedures for the cleft should be individualized with careful intraoperative evaluation of the structure and function of this abnormal valve, especially in partial AVSDs and infants.


Lifting a familiar object: visual size analysis, not memory for object weight, scales lift force.
The brain can accurately predict the forces needed to efficiently manipulate familiar objects in relation to mechanical properties such as weight. These predictions involve memory or some type of central representation, but visual analysis of size also yields accurate predictions of the needed fingertip forces. This raises the issue of which process (weight memory or visual size analysis) is used during everyday life when handling familiar objects. Our aim was to determine if subjects use a sensorimotor memory of weight, or a visual size analysis, to predictively set their vertical lift force when lifting a recently handled object. Two groups of subjects lifted an opaque brown bottle filled with water (470 g) during the first experimental session, and then rested for 15 min in a different room. Both groups were told that they would lift the same bottle in their next session. However, the experimental group returned to lift a slightly smaller bottle filled with water (360 g) that otherwise was identical in appearance to the first bottle. The control group returned to lift the same bottle from the first session, which was only partially filled with water so that it also weighed 360 g. At the end of the second session subjects were asked if they observed any changes between sessions, but no subject indicated awareness of a specific change. An acceleration ratio was computed by dividing the peak vertical acceleration during the first lift of the second session by the average peak acceleration of the last five lifts during the first session. This ratio was >1 for the control subjects 1.30 (SEM 0.08), indicating that they scaled their lift force for the first lift of the second session based on a memory of the (heavier) bottle from the first session. In contrast, the acceleration ratio was 0.94 (0.10) for the experimental group (P < 0.011). We conclude that the experimental group processed visual cues concerning the size of the bottle. These findings raise the possibility that even with familiar objects we predict fingertip forces using an on-line visual analysis of size (along with memory of density), rather than accessing memory related to object weight.


Dissociation of suppression of tumorigenicity and differentiation in vitro effected by transfer of single human chromosomes into human neuroblastoma cells.
The development of human neuroblastoma is associated with abnormalities of the short arm of chromosome 1 (1p). To determine the importance of sequences on that part of chromosome 1, we transferred translocated chromosomes containing normal portions of chromosome 1p or 1q into the neuroblastoma cell line NGP.1A.TR1 and also normal intact chromosomes 11 and 17 as putative controls. Transfer of chromosome t(X;1q) had no effect on any property we studied of the neuroblastoma cells. It was found that the transfer of chromosome t(X;1p) induced neuronal differentiation, but most of those cells died. The cell lines that grew out from the survivors lacked the t(X;1p) chromosome and were still tumorigenic. Transfer of chromosome 11 induced differentiation but did not affect cell proliferation or the tumorigenic phenotype. We have also demonstrated the existence of a new tumor suppressor gene on chromosome 17 that does not induce differentiation in vitro but completely suppresses the tumor-forming ability of the neuroblastoma cells. Differentiation of neuroblastoma cells in vitro and suppression of tumorigenicity are therefore controlled by multiple genes on different chromosomes and are not necessarily correlated.


Detection of xerostomia, Sicca, and Sjogren's syndromes in a national sample of adults.
To assess the prevalence and determinants of xerostomia among adults and identify how many of the ones experiencing xerostomia have Sicca and Sjogren's syndromes. This cross-sectional study included 1405 35-74-year-old Lithuanians (51.7% response rate) from the five largest Lithuanian cities and 10 peri-urban and rural areas that were randomly selected from each of the 10 Lithuanian counties. Xerostomia was determined by the self-reported experience of dry mouth as "often" or "always". A dentist diagnosed Sicca syndrome by unstimulated whole sialometry and the Schirmer's test, and all cases were referred to a rheumatologist to confirm Sjogren's syndrome. Self-reported questionnaires collected data about the determinants. The prevalence of xerostomia was 8.0% (n = 112), Sicca syndrome was diagnosed for 8 participants (0.60%), and Sjogren's syndrome for 2 participants (0.14%), with this being the first time it was diagnosed. Experiencing xerostomia was associated with older age (OR 1.7, 95% CI 1.1-2.6), urban residence (OR 3.3, 95% CI 1.6-5.0), presence of systemic diseases (OR 2.5, 95% CI 1.4-3.3), and the use of alcohol (OR 0.6, 95% CI 0.4-0.9). The higher proportion of participants with Sicca syndrome involved females, of older age, having systemic diseases, and using medications. The prevalence of xerostomia was 8.0% and the determinants of xerostomia were older age, urban residence, systemic diseases, and absence of using alcohol. In total, 0.6% of participants had Sicca syndrome, which was more prevalent among females, older subjects, those with systematic diseases, and those using medications. Sjogren's syndrome was diagnosed in 0.14% of participants. Clinical relevance Dental clinicians need to be trained to identify potential Sjogren's syndrome cases.


[Lecithinase activity of Vibrio cholerae and of vibrios not agglutinated by O-cholera serum].
The lecithinase activities of 187 V. cholerae strains differing in their virulence and 70 cultures of NAG vibrios of different origin varied in all experimental groups. The level of lecithinase activity in the groups of V. cholerae strains having low virulence, or no virulence at all, was considerably higher than in virulent strains. NAG vibrios isolated from diarrhea patients and from samples of lake and pond water did not differ in the activity of this enzyme.


Rev-erbα modulates the hypothalamic orexinergic system to influence pleasurable feeding behaviour in mice.
The drive to eat is regulated by two compensatory brain pathways termed as homeostatic and hedonic. Hypothalamic orexinergic (ORX) neurons regulate metabolism, feeding and reward, thus controlling physiological and hedonic appetite. Circadian regulation of feeding, metabolism and rhythmic activity of ORX cells are driven by the brain suprachiasmatic clock. How the circadian clock impacts on ORX signalling and feeding-reward rhythms is, however, unknown. Here we used mice lacking the nuclear receptor REV-ERBα, a transcription repressor and a key component of the molecular clockwork, to study food-reward behaviour. Rev-Erbα mutant mice showed highly motivated behaviours to obtain palatable food, an increase in the intake and preference for tasty diets, and in the expression of the ORX protein in the hypothalamus. Palatable food intake was inhibited in animals treated with the ORX1R antagonist. Analyzing the Orx promoter, we found Retinoic acid-related Orphan receptor Response Element binding sites for Rev-Erbα. Furthermore, Rev-Erbα dampened the activation of Orx in vitro and in vivo. Our data provide evidence for a possible repressive role of Rev-Erbα in the regulation of ORX signalling, highlighting an implication of the circadian clockwork in modulating food-reward behaviours with an important impact for the central regulation of overeating.


Nurse IOM members' contributions to the Institute of Medicine.
Nursing is the largest health care profession, and Institute of Medicine (IOM) nurse members have the potential to contribute to health policy through IOM activities. We studied reported activities of IOM nurse members. To describe activities of IOM nurse members within the IOM. An e-mail survey was conducted that asked nurse IOM members to assess self-reported IOM activities. Of 57 members, 47 had functioning e-mail addresses, and 33 usable responses were received. The survey consisted of 9 questions dealing with roles and responsibilities undertaken in the previous 5 years. Data analyses were descriptive. The data suggest that nurses have made considerable contributions to the IOM and their participation seems to be as high, or higher, than other disciplines. In an era of health care reform, there is additional opportunity for nurse IOM members to enhance their work in the IOM.


[Chronic unilateral distal juvenile muscular atrophy localized to the upper extremity (Hirayama type). A European case].
A 40 year-old Frenchman had had for 12 years, an amyotrophy of one upper limb. Clinical features were similar to those previously reported in Japan and India i.e. atrophy limited to one hand and forearm, with mild functional discomfort, and slow progression for 2 years after which the disorder did not progress. Electromyography showed disturbances of anterior horn cell type. The cause of this syndrome is unknown, no pathological case has yet been reported. The prognosis appears to be good.


"Age could not wither her…" because of her cytotoxic CD4+ T cells?
Cytotoxic CD4+ T cells specific for CMV cull senescent skin fibroblasts.


Left ventricular strain-curve morphology to distinguish between constrictive pericarditis and restrictive cardiomyopathy.
To distinguish between constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM) using cardiac magnetic resonance feature tracking (CMR-FT) left ventricle (LV) diastolic time-strain curve patterns and myocardial strain. A total of 32 CP patients, 27 RCM patients, and 25 control subjects were examined by CMR-FT and analysed for global strain, segmental strain, and LV time-strain curve patterns in the longitudinal, circumferential, and radial directions. Speckle tracking echocardiography (STE) strain imaging was performed in some cases. The peak global longitudinal strain (GLS) and global circumferential strain (GCS) of the RCM group were lower than those of the CP group. GLS [median (interquartile range) CP vs. RCM: -11.15 (-12.85, -9.35) vs. -6.5 (-8.75, -4.85), P < 0.001] and GCS (CP vs. RCM: -16.89 ± 5.11 vs. -13.37 ± 5.79, P < 0.001). In circumferential and radial directions, the strain ratios of the LV lateral/septal wall (LW/SW) of the CP group were significantly lower than those of the RCM group at the basal and mid segments. The CS ratio of LW/SW at the basal segment [CP vs. RCM: 0.95 (0.85, 1.25) vs. 1.43 (1.18, 1.89), P < 0.001] and mid segment [CP vs. RCM: 1.05 (0.92, 1.15) vs. 1.18 (1.06, 1.49), P = 0.026]. The RS ratio of LW/SW at the basal segment [CP vs. RCM: 0.97 (0.76, 1.37) vs. 1.55 (1.08, 2.31), P = 0.006] and mid segment [CP vs. RCM: 0.95 (0.70, 1.28) vs. 1.79 (1.32, 2.92), P < 0.001]. In the longitudinal and circumferential directions, the characteristic 'plateau' pattern of time-strain curves could be seen in the CP but not in the RCM during the diastole. The GCS ratio of 0-50%/50-75% diastolic period of the CP was higher than that of the RCM [CP vs. RCM: 17.01 (8.67, 23.75) vs. 5.38 (1.93, 11.24), P = 0.001], while the GCS ratio of 50-75%/75-100% diastolic period was lower than that of the RCM [CP vs. RCM: 0.36 (0.15, 1.67) vs. 1.12 (0.70, 5.58), P < 0.001]. The peak GLS (sensitivity, 85%; specificity, 78%) and the GCS ratio of 0-50%/50-75% diastolic period (sensitivity, 88%; specificity, 73%) had higher differential diagnosis value. The CMR-FT could distinctly differentiate CP from RCM based on LV myocardial strain and LV time-strain curve patterns. The characteristic 'plateau' pattern of the time-strain curve is specific for CP and not RCM and this curve can also be duplicated by STE.


Monitoring cytotoxic tumour treatment response by diffusion magnetic resonance imaging and proton spectroscopy.
Exposure of tumours to anti-cancer drugs, gene or radiation therapy consistently leads to an increase in water diffusion in the cases expressing favourable treatment response. The diffusion change coincides cytotoxic cell eradication and precedes volume reduction in drug or gene therapy-treated experimental tumours. Interestingly, the recent studies from human brain tumour patients undergoing chemotherapy show similar behaviour of diffusion, suggesting important application for MRI in patient management. In this review observations from diffusion MRI and MRS in the tumours during cytotoxic treatment are summarized and the cellular mechanisms affecting molecular mobility are discussed in the light of tissue microenvironmental and microdynamic changes.


The septin family of GTPases: architecture and dynamics.
Septins comprise a conserved family of proteins that are found primarily in fungi and animals. These GTP-binding proteins have several roles during cell division, cytoskeletal organization and membrane-remodelling events. One factor that is crucial for their functions is the ordered assembly of individual septins into oligomeric core complexes that, in turn, form higher-order structures such as filaments, rings and gauzes. The molecular details of these interactions and the mechanism by which septin-complex assembly is regulated have remained elusive. Recently, the first detailed structural views of the septin core have emerged, and these, along with studies of septin dynamics in vivo, have provided new insight into septin-complex assembly and septin function in vivo.


Evaluation of the health-related quality of life of patients with type 2 diabetes in relation to macrovascular and microvascular complications.
The complications of type 2 diabetes (T2DM) have a negative impact on health-related quality of life (HRQoL) and could lead to increased healthcare costs. However, there is a lack of evidence regarding how and to what extent T2DM complications, particularly macrovascular and microvascular complications, affect the patients' HRQoL. This study aimed to evaluate the HRQoL in relation to diabetes complications and identify associated factors among patients with T2DM. A cross-sectional study was conducted over six months on T2DM patients at a National University Hospital, Malaysia. Since Malaysia is a multiethnic country with majority Malay-speaking and English widely used, the Malay and English versions of the revised version Diabetes Quality of life (DQoL) questionnaire was used to measure HRQoL. Multiple Linear Regression was applied to estimate association of individual DQoL domains with T2DM-related complications, sociodemographic and clinical characteristics. A total of 513 patients were recruited in the study. Sociodemographic (age, gender, ethnicity, employment, education) and body mass index affected satisfaction, impact and worry domains while complications affected the impact domain. Poorer HRQoL were demonstrated for severe stages heart failure (p = 0.001), nephropathy (p = 0.029), retinopathy (p < 0.001). The presence of neuropathy (p = 0.004) and foot ulcer (p = 0.039) showed poor HRQoL regardless of severity stage. Increase frequencies of hypoglycaemia (p < 0.001) showed poorer HRQoL compared to those with lesser frequencies. The complications, sociodemographic and clinical characteristics of patients with T2DM affect the HRQoL domains differently. Understanding the point of which complication types and stages impact HRQoL the most can provide insights to clinicians to prioritise on effective interventions. The study findings may assist researchers and policymakers in selecting appropriate health state values when conducting cost-effectiveness studies to aid decision making.


Synergistic effect of 24-epibrassinolide and salicylic acid on photosynthetic efficiency and gene expression in Brassica juncea L. under Pb stress.
Lead (Pb) has wide-ranging effects on various essential physiological processes in plants including seed germination, root/ shoot growth, photosynthetic efficiency, water status, and activities of enzymes. The effect of combined treatment of 24-epibrassinolide (10-7 M, EBL) and salicylic acid (1 mM, SA) on growth, photosynthetic attributes, and phenolic compounds in 30-, 60-, and 90-day-old plants of Brassica juncea L. under Pb stress (0.25 mM, 0.50 mM, and 0.75 mM) were studied. It was observed that Pb toxicity resulted in lowered growth and photosynthetic efficiency. The expressions of CHLASE, PSY, CHS, and PAL genes were altered. Presoaking treatment with the combination of EBL and SA for metal-stressed plants mitigated the adverse effects of metal stress by improving growth and levels of pigment and phenolic compounds.


[Obtaining homogenous preparations of succinate dehydrogenase isoforms from the D-507 strain of Sphaerotilus natans].
Enzymatic preparations of two isoforms of succinate dehydrogenase (SDG) with specific activity of 22.00 E/mg of protein were obtained from the colorless sulfur bacterium Sphaerotilus natans D-507 cultured organotrophically. Both SDG forms were shown to be heteromers with subunit molecular masses of 70.8, 35.0, 31.8, and 16.2 kDa. The K(m) values for the first and the second forms of SDG were evaluated as 0.615 and 0.531 mM, respectively, with an optimal pH value of 7.2. It was found that the Cl- ion has an activating effect on the SDG activity that can be explained by the specific chemical modification of the enzyme molecule. The results suggest that the isolated enzyme forms are included in different multienzyme complexes, which provide the functioning of the tricarboxylic acid cycle, and SDG preparations can be used for the investigation of other enzyme systems or in vitro modeling of supramolecular cellular structures.


Problems in determing A2B group specific properties in blood stains.
Blood stains belonging to various sub-group A combinations were examined by the absorption-elution method (in comparison with Holzer method and mixed agglutination). No difficulties were encountered in the identification of A1, A2, and A1B blood stains, while identification of A antigen in A2B stains was dubious (always negative with the others methods). This seems to be due to low anti-sera titer in relation to A antigen in this subgroup combination.


Biomass-derived carbon nano-onions for the effective elimination of organic pollutants and oils from water.
Oil spillage and leakage of organic solvents have caused severe environmental and ecological damages. It is of great significance to develop a cost-efficient and green adsorbent material with high uptake efficiency to separate the oil-water mixture. In this work, biomass-derived CNOs were first time explored in the adsorption of organic pollutants and oils from water. Carbon nano-onions (CNOs) with hydrophobicity and oleophilicity were cost-effectively synthesized in an energy efficient flame pyrolysis process using flaxseed oil as a carbon source. The as-synthesized CNOs without any further surface modification have shown high adsorption efficiency in removing organic solvents and oils from the oil-water mixture. The CNOs could adsorb diverse organic solvents such as pyridine (36.81 mg g-1), dichloromethane (90.95 mg mg-1), aniline (76 mg mg-1), toluene (64 mg mg-1), chloroform (36.25 mg mg-1), methanol (49.25 mg mg-1), and ethanol (42.25 mg mg-1). The uptake capacity for petrol and diesel over CNOs was observed at 36.68 mg mg-1 and 58.1 mg mg-1, respectively. The adsorption of pyridine followed pseudo-second-order kinetics and Langmuir's isotherm model. Moreover, the adsorption efficiency of CNOs towards the remediation of pyridine was almost similar in real-water samples when tested in tap water, dam water, groundwater, and lake water. Similarly, the practical applicability for the separation of petrol and diesel was also verified in the real sample (sea water) and has been proven to be excellent. By simple evaporation, the recovered CNOs can be reused for more than 5 cycles. CNOs exhibit the promising potential to be used in practical applications for oil-polluted water treatment.


Elevated S100B protein as an early indicator of intracranial haemorrhage in infants subjected to extracorporeal membrane oxygenation.
The aim of this investigation was to verify whether plasma S100B could be a useful tool in identifying which infants subjected to extracorporeal membrane oxygenation (ECMO) might develop intracranial haemorrhage (ICH). A case-control study of eight infants who developed ICH during ECMO was conducted. Plasma samples collected daily after ECMO insertion were assessed for S100B and compared with those obtained from eight infants supported by ECMO who did not develop ICH. Cerebral ultrasound and Doppler velocimetry waveform patterns in the middle cerebral artery (MCA PI) were also recorded at the same time as blood sampling. S100B blood concentrations were significantly higher in the group of infants with ICH 72 h before any signs of haemorrhage could be detected by ultrasound (ICH: 2.91 +/- 0.91 microg/L vs. control: 0.53 +/- 0.15 microg/L), reaching their peak at day 6, when cerebral ultrasound scan patterns were suggestive of intracranial haemorrhage (ICH: 3.50 +/- 1.03 microg/L vs. control: 0.66 +/- 0.27 microg/L) (p < 0.05, for both). The highest S100B levels were observed in the three ICH infants who expired during the ECMO procedure (3.43 microg/L, 4.0 microg/L, 4.12 microg/L, respectively). MCA PI values in the ICH group were also significantly higher, but only 24 h before any ultrasound pattern of bleeding was detected (ICH: 2.31 +/- 0.22 vs control: 1.81 +/- 0.24) (p < 0.05). This study suggests that blood S100B measurement could be a promising tool for the identification of infants at risk of ICH when imaging assessment and clinical symptoms of haemorrhage might still be silent.


Immunotherapy after hematopoietic stem cell transplantation using umbilical cord blood-derived products.
Umbilical cord blood (UCB) is being increasingly used as a source of hematopoietic stem cells (HSC) for transplantation. UCB transplantation (UCBT) has some advantages such as less stringent HLA-matching requirements, fast availability of the graft and reduced incidence and severity of graft-versus-host disease. However, UCBT is also associated with a higher incidence of infection, graft failure, slow engraftment and slow immune reconstitution. UCB is mainly used as a source of HSC; however, it is also rich in immune cells that could be used to treat some of the main complications post-UCBT as well as other diseases, thus implicating the use of UCB for immunotherapy. Here, we aim to describe some of the therapies currently developed that use UCB as a cell source, focusing in particular on regulatory T cells and natural killer cells.