Compact high-pulse-energy ultraviolet laser source for ozone lidar measurements.
An all solid-state Ti:sapphire laser differential absorption lidar transmitter was developed. This all-solid-state laser provides a compact, robust, and highly reliable laser transmitter for potential application in differential absorption lidar measurements of atmospheric ozone. Two compact, high-energy-pulsed, and injection-seeded Ti:sapphire lasers operating at a pulse repetition frequency of 30 Hz and wavelengths of 867 and 900 nm, with M2 of 1.3, have been experimentally demonstrated and their properties compared with model results. The output pulse energy was 115 mJ at 867 nm and 105 mJ at 900 nm, with a slope efficiency of 40% and 32%, respectively. At these energies, the beam quality was good enough so that we were able to achieve 30 mJ of ultraviolet laser output at 289 and 300 nm after frequency tripling with two lithium triborate nonlinear crystals.


Trapped in the extinction vortex? Strong genetic effects in a declining vertebrate population.
Inbreeding and loss of genetic diversity are expected to increase the extinction risk of small populations, but detailed tests in natural populations are scarce. We combine long-term population and fitness data with those from two types of molecular markers to examine the role of genetic effects in a declining metapopulation of southern dunlins Calidris alpina schinzii, an endangered shorebird. The decline is associated with increased pairings between related individuals, including close inbreeding (as revealed by both field observations of parentage and molecular markers). Furthermore, reduced genetic diversity seems to affect individual fitness at several life stages. Higher genetic similarity between mates correlates negatively with the pair's hatching success. Moreover, offspring produced by related parents are more homozygous and suffer from increased mortality during embryonic development and possibly also after hatching. Our results demonstrate strong genetic effects in a rapidly declining population, emphasizing the importance of genetic factors for the persistence of small populations.


Retrospective analysis of equestrian-related injuries presenting to a level 1 trauma center.
Report the incidence, pattern, and severity of equestrian-related injuries presenting to a rural level 1 trauma center and detail the total radiation dose, imaging, and hospital charges related to those injuries. An IRB-approved retrospective review of patients presenting to our facility following equine-related trauma was conducted. Demographics, mechanism of injury, types and number of imaging exams, approximate radiation dose administered, imaging findings, Injury Severity Score (ISS), rate/length of hospitalization, and approximate cost of care were recorded. A total of 222 patients (161 F:61 M; mean age 38.5 years (range 4-79)) presented to our emergency department following horse-related injury. Mechanisms of injury included the following: fall (n = 186), kick (n = 18), stepped on (n = 9), and other (n = 9). Body part injured included extremity (26.1%), torso (26.6%), spine (25.7%), and head/neck (18.5%). Longer hospital admission, higher expenditure, increased CT/MR imaging, higher ISS, and radiation dose were noted in older patients and those injured by a fall or kick. Head injuries were more frequent following a horse kick (p = 0.006). Spinal and torso injuries were more common in patients older than 54 years (p = < 0.001) and those with falls (p < 0.04). Extremity injuries were more common in older patients (p < 0.001). Patient age greater than 54 years and mechanism of injury are strong predictors of the ISS, injury localization, healthcare expenditure, and mean hospital stay. With the exception of obvious minor wounds, full trauma work-ups (CT chest/abdomen/pelvis and cervical spine) are encouraged for equestrian-related injuries in older patients and those injured by a fall.


Estimation of computed tomography dose index in cone beam computed tomography: MOSFET measurements and Monte Carlo simulations.
To address the lack of accurate dose estimation method in cone beam computed tomography (CBCT), we performed point dose metal oxide semiconductor field-effect transistor (MOSFET) measurements and Monte Carlo (MC) simulations. A Varian On-Board Imager (OBI) was employed to measure point doses in the polymethyl methacrylate (PMMA) CT phantoms with MOSFETs for standard and low dose modes. A MC model of the OBI x-ray tube was developed using BEAMnrc/EGSnrc MC system and validated by the half value layer, x-ray spectrum and lateral and depth dose profiles. We compared the weighted computed tomography dose index (CTDIw) between MOSFET measurements and MC simulations. The CTDIw was found to be 8.39 cGy for the head scan and 4.58 cGy for the body scan from the MOSFET measurements in standard dose mode, and 1.89 cGy for the head and 1.11 cGy for the body in low dose mode, respectively. The CTDIw from MC compared well to the MOSFET measurements within 5% differences. In conclusion, a MC model for Varian CBCT has been established and this approach may be easily extended from the CBCT geometry to multi-detector CT geometry.


The Potential Role of Dietary Antioxidant Capacity in Preventing Age-Related Macular Degeneration.
Objectives: Age-related macular degeneration (AMD) is a progressive disorder among people aged ≥50 years. Some dietary factors associated with the susceptibility to AMD include dietary glycemic index and glycemic load, as well as intake of antioxidants and other nutrients, such as vitamins, minerals, and dietary fatty acids. Methods: This case-control study was conducted between July 2015 and February 2016 on 100 case subjects with AMD and 100 healthy controls without AMD. The participants were recruited from the Department of Ophthalmology of Hacettepe University Hospitals in Ankara, Turkey. Dietary intake was estimated from a 3-day food intake record and food frequency questionnaire, and anthropometric measurements were recorded. The relationship between nutritional factors and AMD was assessed using logistic regression. Results: Dietary total antioxidant intake of AMD group was found to be lower (p < 0.05) than that of healthy individuals. In a multivariate analysis, smoking, daily red meat intake, omega-6 intake, and higher glycemic index were identified as risk factors for AMD development. Meanwhile, daily fruit intake, daily fish intake, omega-3 intake, and zinc intake were associated with a protective effect. However, no difference was found in dietary total antioxidant capacity. Conclusions: In this study, a high dietary intake of carotenoids, vitamins C and E, zinc, and omega-3, as well as maintaining optimal waist circumference, were found to substantially reduce the risk of developing AMD in people aged >50 years. By contrast, in addition to smoking and old age, obesity, high red meat intake, and omega-6 intake might increase the risk of developing AMD. Therefore, a better understanding of nutritional risk factors is necessary for preventing AMD.


Effect of Tamarillo Fortification and Fermentation Process on Physicochemical Properties and Nutrient and Volatiles Content of Yoghurt.
Bright-red Laird's Large tamarillo is a unique and under-utilised fruit that is a dietary source of carotenoids, vitamins C and E, and dietary fibre. The effects of the addition of freeze-dried tamarillo powder (5-15%) to milk and yoghurt starter either before (PRE) or after (POS) fermentation on physicochemical properties were examined. Using LC-MS and GG-MS, nutrient and volatile contents of tamarillo yoghurt were also examined. The addition of tamarillo prior to fermentation was associated with a more yellow colour and higher concentrations of tocopherol compared to when tamarillo was added after fermentation. Higher elastic modulus, PUFAs, pro-vitamin A content, and vitamin C retention were observed for POS than PRE. All tamarillo yoghurts showed improvement in syneresis, lower lactose content, and higher concentrations of antioxidant vitamins than the commercial premium-assorted fruits yoghurt from New Zealand Food Composition Data. Yoghurt fortified with tamarillo powder offers the potential for the development of a high-value nutritional product that could be a good source of vitamin C and a source of vitamin E and β-carotene, and maintain the volatiles that give tamarillo its distinctive flavour.


The role of demographic surveillance systems (DSS) in assessing the health of communities: an example from rural Ethiopia.
Longitudinal demographic surveillance systems (DSSs) in selected populations can provide important information in situations where routine health information is incomplete or absent, particularly in developing countries. The Butajira Rural Health Project is one such example, initiated in rural Ethiopia in 1987. DSSs rely on regular community-based surveillance as a means of vital event registration, among a sufficient population base to draw meaningful conclusions about rates and trends in relatively rare events such as maternal death. Enquiries into specific health problems can also then use this framework to quantify particular issues or evaluate interventions. Demographic characteristics and trends for a rural Ethiopian population over a 10-y period are presented as an illustration of the DSS approach, based on 336 000 person-years observed. Overall life expectancy at birth was 50 y. Demographic parameters generally showed modest trends towards improvement over the 10-y period. The DSS approach is useful in characterising populations at the community level over a period of time, providing important information for health planning and intervention. Methodological issues underlying this approach need further exploration and development.


Structure of homoserine O-acetyltransferase from Staphylococcus aureus: the first Gram-positive ortholog structure.
Homoserine O-acetyltransferase (HTA) catalyzes the formation of L-O-acetyl-homoserine from L-homoserine through the transfer of an acetyl group from acetyl-CoA. This is the first committed step required for the biosynthesis of methionine in many fungi, Gram-positive bacteria and some Gram-negative bacteria. The structure of HTA from Staphylococcus aureus (SaHTA) has been determined to a resolution of 2.45 Å. The structure belongs to the α/β-hydrolase superfamily, consisting of two distinct domains: a core α/β-domain containing the catalytic site and a lid domain assembled into a helical bundle. The active site consists of a classical catalytic triad located at the end of a deep tunnel. Structure analysis revealed some important differences for SaHTA compared with the few known structures of HTA.


Oral, but not transdermal, administration of estrogens lowers tissue-type plasminogen activator levels in humans without affecting endothelial synthesis.
Oral estrogen administration decreases plasma levels of tissue-type plasminogen activator (tPA), which may be explained by a decrease in endothelial tPA synthesis, an increase in its hepatic clearance, or both. In the present study, we determined (1) differences between oral (ie, via the liver) ethinyl estradiol and transdermal (ie, systemic) 17beta-estradiol administration on plasma antigen levels of tPA and plasminogen activator inhibitor type-1 before and after 4 months of hormone administration and (2) effects on endothelial tPA synthesis, by measuring the local increase in plasma tPA during venous occlusion of the upper extremity. Thirty transsexual males (median age 32 years, range 20 to 44 years ) were randomly assigned to either oral ethinyl estradiol (n=15) or transdermal 17beta-estradiol (n=15); both treatments included the antiandrogen cyproterone acetate (CA). Ten males were treated with CA alone. Seventeen transsexual females (median age 27 years, range 18 to 37 years) were treated with intramuscular testosterone esters. Only oral ethinyl estradiol plus CA but neither transdermal 17beta-estradiol plus CA, nor oral CA, nor parenteral testosterone lowered plasma tPA and plasminogen activator inhibitor-1 (P<0.001 for both). tPA release during venous occlusion was not affected by oral ethinyl estradiol plus CA in males (P=0.52) or by parenteral testosterone in females (P=0.89). These data are consistent with a previous observation, in rodents, that the decrease in tPA after oral estrogen administration can be explained by an increase in hepatic tPA clearance, leaving endothelial tPA synthesis unchanged, and suggest that these mechanisms also explain the decrease in tPA in humans.


Micro-miniature autonomous optical sensor array for monitoring ions and metabolites 2: color responses to pH, K+ and glucose.
In Part 1 of this series (Anal. Sci., 2006, 22, 383), design, fabrication, and optical data acquisition of an array of tiny color changing capsules embedded in a cellulose acetate bar, called the "sliver sensor", have been described. Capsule colors are read by a CCD camera and translated into blue, red and green Kubelka-Munk variables for quantitative analysis. The respective concentrations are determined using prior calibration. The approach may be adapted to different non-biological analytical problems, as well as in vitro and in vivo applications. To demonstrate this adaptability to potential in vivo use as an example, sensitivity for each target ion was tuned to cover the respective interstitial levels by varying the relative amount of ionophore used in the corresponding microscopic beads. After optimizing the ratio of glucose oxidase (GOX)-containing beads relative to the coupled pH sensing beads and their composition, reversible color response to glucose was obtained in the entire clinically relevant glucose concentration range (10 to 600 mg/dL, 0.55 to 33 mM). Decoupling of pH and glucose sensing from possible variations in interstitial sodium level and buffer capacity is currently being optimized for future in vivo use. In vitro and non-biological applications are also being explored.


Nonlinear layered lattice model and generalized solitary waves in imperfectly bonded structures.
We study nonlinear waves in a two-layered imperfectly bonded structure using a nonlinear lattice model. The key element of the model is an anharmonic chain of oscillating dipoles, which can be viewed as a basic lattice analog of a one-dimensional macroscopic waveguide. Long nonlinear longitudinal waves in a layered lattice with a soft middle (or bonding) layer are governed by a system of coupled Boussinesq-type equations. For this system we find conservation laws and show that pure solitary waves, which exist in a single equation and can exist in the coupled system in the symmetric case, are structurally unstable and are replaced with generalized solitary waves.


The value of incidence for the assessment of schistosomiasis control; a study in Southern Rhodesia.
Rapid assessment of the rate of transmission of schistosomiasis is essential in any control programme. It has been demonstrated that, by following the pattern of infection developing during a longitudinal study in a cohort of children under 6 years of age, it is possible to calculate the incidence of schistosomiasis in the community represented by that cohort. Children who were found by survey to be free from active infection with schistosomes were examined at intervals of 1, 3, or 4 months to determine the rate at which infections of either Schistosoma mansoni or S. haematobium occurred. This gave an immediate measure of the rate of transmission during the period under study. The rate can be calculated for unit time- in this study figures were extrapolated to 120 days. Data are presented to show how the incidence measured reflects the efficiency of snail control procedures carried out in the different farming areas.


Selective and rapid nuclear translocation of a c-Myc-containing complex after fertilization of Xenopus laevis eggs.
We report here unusual features of c-Myc specific to early embryonic development in Xenopus laevis, a period characterized by generalized transcriptional quiescence and rapid biphasic cell cycles. Two c-Myc protein forms, p61 and p64, are present in large amounts in the oocyte as well as during early development. In contrast, only p64 c-Myc is present in Xenopus somatic cells. p61 c-Myc is the direct translation product from both endogenous c-myc mRNAs and c-myc recombinant DNA. It is converted to the p64 c-Myc form after introduction into an egg extract, in the presence of phosphatase inhibitors. p61 and p64 belong to two distinct complexes localized in the cytoplasm of the oocyte. A 15S complex contains p64 c-Myc, and a 17.4S complex contains p61 c-Myc. Fertilization triggers the selective and total entry of only p64 c-Myc into the nucleus. This translocation occurs in a nonprogressive manner and is completed during the first cell cycles. This phenomenon results in an exceptionally high level of c-Myc in the nucleus, which returns to a somatic cell-like level only at the end of the blastulation period. During early development, when the entire embryonic genome is transcriptionally inactive, c-Myc does not exhibit a DNA binding activity with Max. Moreover, embryonic nuclei not only prevent the formation of c-Myc/Max complexes but also dissociate such preformed complexes. These peculiar aspects of c-Myc behavior suggest a function that could be linked to the rapid DNA replication cycles occurring during the early cell cycles rather than a function involving transcriptional activity.


Cardioprotective effects of calorie restriction against inflammation and apoptosis in ovariectomized obese rats: Role of classical estrogen receptors and SIRT1.
Obesity is a metabolic complication linked with bad eating habits and a sedentary lifestyle, and the heart is one of the target organs damaged by it. Estrogen deficiency during menopause worsens the situation. Calorie restriction (CR) can contribute to reducing cardiovascular disease (CVD) in postmenopausal conditions. Thus, the effects of CR on inflammation and apoptosis in ovariectomized rats' hearts with obesity were studied. Female Wistar rats were categorized into Sham and OVX (ovariectomized) groups and received a standard diet (SD) or high-fat diet (60%HFD) or calorie restriction (30% CR) for 16 weeks. The real-time PCR method was used to evaluate the inflammatory markers and estrogen receptors gene expression. Western-blot and ELISA methods were respectively used for the measurement of apoptosis and SIRT1 protein expression. HFD led to the elevation of body weight, IL-6 (interleukin-6) and TNF-α (tumor necrosis factor-α) and reduction of IL-10 (interleukin-10) gene expressions, and also an increment in protein levels of cleaved caspase-3, Bax and Bax/Bcl2 ratio and decrement in Bcl-2 in OVX rats (P < 0.001). Additionally, HFD reduced SIRT1 (sirtuin1) protein levels, ERα (estrogen receptor α), and ERβ (estrogen receptor β) gene expressions (P < 0.001). In contrast, CR declined body weight, IL-6 and TNF-α (P < 0.001), increased IL-10 expressions (P < 0.05), decreased cleaved caspase-3 (P < 0.001), Bax (P < 0.01), and Bax/Bcl2 ratio (P < 0.05), enhanced Bcl-2 (P < 0.001), increased SIRT1 (P < 0.05) and ERα (P < 0.001) and ERβ (P < 0.01) expressions. CR through the SIRT1 regulation and estrogen receptors attenuate obesity-induced-cardiac inflammation and apoptosis. CR can be a cardioprotective candidate in postmenopausal conditions.


Common and dysplastic naevi as risk factors for cutaneous malignant melanoma in a Swedish population.
Common naevi, dysplastic naevi (DN) and other phenotypic features were evaluated as melanoma risk factors in a Swedish case-control study. One-hundred and twenty-one prevalent melanoma cases and 378 randomly selected controls participated. The mean total body naevus count was 115 in the cases and 67 in the controls. Fifty-six per cent of the cases and 18% of the controls had clinical DN. The corresponding figures for histologically diagnosed DN were 40% and 8% respectively. Clinical DN was as good as histologically diagnosed DN in identifying individuals at risk for melanoma. Subjects with sun-sensitive skin, greater than or equal to 150 naevi and presence of DN have 50 times higher melanoma risk than those without these characteristics.


Comparison of longitudinal trends in self-reported symptoms and COVID-19 case activity in Ontario, Canada.
Limitations in laboratory diagnostic capacity impact population surveillance of COVID-19. It is currently unknown whether participatory surveillance tools for COVID-19 correspond to government-reported case trends longitudinally and if it can be used as an adjunct to laboratory testing. The primary objective of this study was to determine whether self-reported COVID-19-like illness reflected laboratory-confirmed COVID-19 case trends in Ontario Canada. We retrospectively analyzed longitudinal self-reported symptoms data collected using an online tool-Outbreaks Near Me (ONM)-from April 20th, 2020, to March 7th, 2021 in Ontario, Canada. We measured the correlation between COVID-like illness among respondents and the weekly number of PCR-confirmed COVID-19 cases and provincial test positivity. We explored contemporaneous changes in other respiratory viruses, as well as the demographic characteristics of respondents to provide context for our findings. Between 3,849-11,185 individuals responded to the symptom survey each week. No correlations were seen been self-reported CLI and either cases or test positivity. Strong positive correlations were seen between CLI and both cases and test positivity before a previously documented rise in rhinovirus/enterovirus in fall 2020. Compared to participatory surveillance respondents, a higher proportion of COVID-19 cases in Ontario consistently came from low-income, racialized and immigrant areas of the province- these groups were less well represented among survey respondents. Although digital surveillance systems are low-cost tools that have been useful to signal the onset of viral outbreaks, in this longitudinal comparison of self-reported COVID-like illness to Ontario COVID-19 case data we did not find this to be the case. Seasonal respiratory virus transmission and population coverage may explain this discrepancy.


Relationship between corneal sensitivity, corneal thickness, corneal diameter, and intraocular pressure in normal cats and cats with congenital glaucoma.
To determine the effect of feline congenital glaucoma (FCG) on corneal sensitivity, and relationships between corneal sensitivity, central corneal thickness (CT), and corneal diameter (CD). Corneal sensitivity (estimated by corneal touch threshold [CTT] using Cochet-Bonnet esthesiometry); CT using ultrasonic pachymetry; intraocular pressure (IOP) using rebound tonometry; and maximal horizontal CD were measured in 16 normal and 14 FCG cats, both males and females, aged 7 months-3.5 years. All procedures complied with an Institutional Animal Care and Use Committee-approved protocol. Data were analyzed by linear regression: paired Student's t tests for between-eye comparisons, and unpaired Student's t tests for comparisons between groups. Relationships between parameters were evaluated by Pearson correlation coefficients and linear mixed effects modeling. For statistical tests, with the exception of values that were Benjamini-Hochberg adjusted for multiple comparisons, P-values < 0.05 were considered significant. Mean CTT and CT values were lower in FCG eyes relative to normal eyes, but differences were not statistically significant. Mean CD was significantly larger in FCG eyes relative to normal eyes, and there was a significant negative correlation between CD and CTT in FCG (r = -0.8564, corrected P = 0.005). These associations were confirmed in linear mixed effects models. Eyes with FCG have significantly larger CDs when compared with normal eyes, and larger CDs correlated with decreased corneal sensitivity in this group. Further studies are warranted to explore the effect of buphthalmos and corneal enlargement on corneal sensitivity and innervation in feline subjects with chronic glaucoma.


Domains regulating transcriptional activity of the inducible orphan receptor NGFI-B.
NGFI-B is an early response gene which encodes a protein that has strong homology with nuclear receptors in the DNA binding domain and in carboxyl-terminal domains responsible for ligand binding and regulation of transcriptional activity. Previously, we have demonstrated that NGFI-B is transcriptionally active in cells grown in vitro in the absence of exogenously added ligand. However, the ligand for NGFI-B does not appear to be a component of cell culture medium, as NGFI-B remained active when expressed in cells grown in medium lacking phenol red, serum, essential vitamins, or essential amino acids. To define the transactivation domains, a mutational analysis was conducted which revealed that a serine/threonine-rich area of 18 amino acids within the amino terminus, termed TAB-1, is an important transcriptional activation domain. The mutation of two adjacent serine and threonine residues within TAB-1 significantly decreased transactivation by NGFI-B. An examination of the role of the carboxyl terminus in regulating NGFI-B transcriptional activity revealed that, in accordance with other nuclear receptors, mutants lacking portions of the carboxyl terminus had greatly decreased activity. The similarity with other receptors was further supported by studies with the mutant B delta 414-597 which encodes a fully active, truncated receptor analogous to a hormone-independent, constitutively active glucocorticoid receptor truncation mutant. This NGFI-B truncation mutant had activity similar to wild type NGFI-B in a number of mammalian cell lines; however, in contrast, it was 8-fold more active than the wild type receptor in the Drosophila S2 cell line, suggesting that insect cells either lack the NGFI-B ligand or obligatory accessory factors.


Self-averaging stochastic Kohn-Sham density-functional theory.
We formulate the Kohn-Sham density functional theory (KS-DFT) as a statistical theory in which the electron density is determined from an average of correlated stochastic densities in a trace formula. The key idea is that it is sufficient to converge the total energy per electron to within a predefined statistical error in order to obtain reliable estimates of the electronic band structure, the forces on nuclei, the density and its moments, etc. The fluctuations in the total energy per electron are guaranteed to decay to zero as the system size increases. This facilitates "self-averaging" which leads to the first ever report of sublinear scaling KS-DFT electronic structure. The approach sidesteps calculation of the density matrix and thus, is insensitive to its evasive sparseness, as demonstrated here for silicon nanocrystals. The formalism is not only appealing in terms of its promise to far push the limits of application of KS-DFT, but also represents a cognitive change in the way we think of electronic structure calculations as this stochastic theory seamlessly converges to the thermodynamic limit.


Temperature variation in caves and its significance for subterranean ecosystems.
Climate change affects all ecosystems, but subterranean ecosystems are repeatedly neglected from political and public agendas. Cave habitats are home to unknown and endangered species, with low trait variability and intrinsic vulnerability to recover from human-induced disturbances. We studied the annual variability and cyclicity of temperatures in caves vis-à-vis surface in different climatic areas. We hypothesize that cave temperatures follow the average temperature pattern at the surface for each location with a slight delay in the signal, but we found three different thermal patterns occurring in caves: (1) high positive correlation and a similar thermal pattern to the surface, (2) low correlation and a slight thermal delay of the signal from the surface, and (3) high negative correlation with an extreme delay from the surface. We found daily thermal cycles in some caves, which may potentially control the circadian rhythms of cave organisms. Our results show that caves had lower thermal amplitude than the surface, and that thermal averages within caves approximately correspond to the to the annual average of surface temperature. Caves buffer external temperature and act as refugia for biota in extreme climatic events. Likewise, temperature increases at surface will lead to increment in caves, threatening subterranean biota and ecosystem services.


Prognostic implications of morphology and karyotype in primary myelodysplastic syndromes.
Forty-nine patients with primary myelodysplastic syndromes (MDS) were subclassified according to French-American-British (FAB) Cooperative Group criteria. Eight patients had acquired idiopathic sideroblastic anemia (AISA), ten had chronic myelomonocytic leukemia (CMMoL), 14 had refractory anemia (RA), nine had refractory anemia with excess blasts (RAEB), and five had refractory anemia with excess blasts in transformation (RAEB-T); three patients could not be subclassified. The actuarial median survival for patients with AISA or with RA had not been reached at 60 months of follow-up. The median survival times for patients with CMMoL, RAEB, and RAEB-T were 25, 21, and 16 months, respectively. The percentages of patients with each subtype who developed ANLL were none in AISA, 20% in CMMoL, 7% in RA, 56% in RAEB, and 40% in RAEB-T. Patients with CMMoL had a poor prognosis independent of transformation to acute nonlymphocytic leukemia (ANLL), whereas patients with RAEB and RAEB-T had a high incidence of transformation and short survival times. Clonal chromosomal abnormalities were present in bone marrow cells from 19 patients at the time of diagnosis, and two others developed an abnormal karyotype at the time of leukemic transformation. The most frequent abnormalities, including initial and evolutionary changes, were trisomy 8 (9 patients), deletion of 5q (4 patients), and deletion of 20q (4 patients). The median survival times were 32 months for patients with an abnormal karyotype, and 48 months for those with a normal karyotype (P = 0.2). Specific chromosomal abnormalities were not associated with particular histologic subtypes; however, a high percentage of patients with RAEB and RAEB-T had an abnormal clone (89% and 80%, respectively). The percentages of patients with clonal abnormalities were 13% for AISA, 20% for CMMoL, and 29% for RA. The MDS transformed to ANLL in 42% of patients with an abnormal karyotype, compared to 10% of those with an initially normal karyotype (P less than .01). Among patients with RA, RAEB, and RAEB-T, the risk of leukemic transformation was confined to those with an abnormal karyotype (P less than .01). Thus, in the present study, morphology and karyotype combined were the best indicators of outcome in patients with MDS.


Value of x ray examinations of the cervical spine.
The value of x ray examination of the cervical spine was studied. In one district general hospital it has been estimated that such examinations occupy one radiographer and one room for four hours a week. Eighty-five per cent of patients aged 60 or more who had been referred for an x ray examination of the neck in one year were reported as having cervical spondylosis, and there were no unexpected findings of infection or malignancy at any age. The reports of patients referred for x ray examination of the cervical spine were compared with those of control patients who had originally attended for barium studies. There was no significant difference in the prevalence of cervical spondylosis between the two groups, although the severity of the disc changes was greater among cases than controls. There were no consistent relations between symptoms and changes seen on x ray films. It is suggested that x ray examinations should be performed only when there is a clinical suspicion of malignancy or infection, after trauma, or when surgery may be indicated. There is little point in taking x ray films of the neck to diagnose cervical spondylosis.


Inflammatory and Apoptotic Regulatory Activity of Tanshinone IIA in Helicobacter pylori-Infected Cells.
Helicobacter pylori infections induce host cell inflammation and apoptosis, however, they are conflicting. Tanshinone IIA is an active compound of Salvia miltiorrhiza Bge. In this study, we investigated the regulatory effects of tanshinone IIA on H. pylori-induced inflammation and apoptosis in vitro. Tanshinone IIA treatments (13.6-54.4[Formula: see text][Formula: see text]M) significantly decreased nuclear factor kappa B (NF-kB) and mitogen-activated protein kinase (MAPK) [p-38 and C-terminal Jun-kinase 1/2 (JNK1/2)] protein expressions and inflammatory substance [cyclooxygenase-2 (COX-2), 5-lipooxygenase (5-LOX), intercellular adhesion molecule-1 (ICAM-1), reactive oxygen species (ROS), nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1[Formula: see text] (IL-1[Formula: see text], IL-6, and IL-8] production in the H. pylori-infected cells. In contrast, tanshinone IIA treatments significantly increased apoptotic relevant protein [Bcl-2-associated X protein (Bax) and caspase 9] expressions and increased mitochondrial transmembrane potential ([Formula: see text] disruption, mitochondrial cytochrome [Formula: see text] (cyt [Formula: see text] release, and caspase cascades. Tanshinone IIA treatments effectively decreased H. pylori-induced inflammation and significantly promoted H. pylori-induced intrinsic apoptosis through NF-kB and MAPK (p-38 and JNK) pathways. Tanshinone IIA has great potential as a candidate to protect host cells from H. pylori-induced severe inflammation and gastric cancer.


The complete DNA sequence of minute virus of mice, an autonomous parvovirus.
We have determined the complete nucleotide sequence of the genome of Minute Virus of Mice, an autonomous parvovirus. This single-stranded DNA is 5081 nucleotides long. The 3'-and 5'-ends of the viral strand contain imperfect palindromic sequences which consist, respectively, of 115 and 206 nucleotides. The 3'-terminal palindrome is composed of a unique sequence, whereas the 5'-terminal palindrome contains two sequences in equimolar amounts; these are related in that one is the inverted complement of the other. The DNA strand complementary to that which is encapsidated into virions contains two large open reading frames which together span almost the entire genome. Transcriptional and translational signals within the sequence have been identified and related to the known map coordinates of the viral transcripts. In this report we summarize some of the salient structural and organizational features of the MVM genome.


Crystallization Regulation by Self-Assembling Liquid Crystal Template Enables Efficient and Stable Perovskite Solar Cells.
It is found that the disordered growth of bottom perovskite film deteriorates the buried interface of perovskite solar cells (PSCs), so developing a new material to modify the buried interface for regulating the crystal growth and defect passivation is an effective approach for improving the photovoltaic performance of PSCs. Here, we developed a new ionic liquid crystal (ILC, 1-Dodecyl-3-methylimidazolium tetrafluoroborate) as both crystal regulator and defect passivator to modify the buried interface of PSCs. The high lattice matching between this ILC and perovskite promotes preferential growth of perovskite film along [001] direction, while the oriented ILC with mesomorphic phase has a strong chemical interaction with perovskite to passivate the interface defect, as a result, the modified buried interface exhibits suppressed defects, improved band alignment, reduced nonradiative recombination losses, and enhanced charge extraction. The ILC-modified PSC delivers a power conversion efficiency of 24.92 % and maintains 94 % of the original value after storage in ambient for 3000 h.


Expanding the clinical spectrum of STIP1 homology and U-box containing protein 1-associated ataxia.
STUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1 are now considered a frequent cause of cerebellar ataxia. We aimed to improve the clinical, radiological, and molecular delineation of SCAR16 and SCA48. Retrospective collection of patients with SCAR16 or SCA48 diagnosed in three French genetic centers (Montpellier, Strasbourg and Nancy). Here, we report four SCAR16 and nine SCA48 patients from two SCAR16 and five SCA48 unrelated French families. All presented with slowly progressive cerebellar ataxia. Additional findings included cognitive decline, dystonia, parkinsonism and swallowing difficulties. The age at onset was highly variable, ranging from 14 to 76 years. Brain MRI showed marked cerebellar atrophy in all patients. Phenotypic findings associated with STUB1 pathogenic variations cover a broad spectrum, ranging from isolated slowly progressive ataxia to severe encephalopathy, and include extrapyramidal features. We described five new pathogenic variations, two previously reported pathogenic variations, and two rare variants of unknown significance in association with STUB1-related disorders. We also report the first pathogenic variation associated with both dominant and recessive forms of inheritance (SCAR16 and SCA48). Even though differences are observed between the recessive and dominant forms, it appears that a continuum exists between these two entities. While adding new symptoms associated with STUB1 pathogenic variations, we insist on the difficulty of genetic counselling in STUB1-related pathologies. Finally, we underscore the usefulness of DAT-scan as an additional clue for diagnosis.


Production of consonants by prelinguistically deaf children with cochlear implants.
Consonant production following the sensory restoration of audition was investigated in 22 prelinguistically deaf French children who received cochlear implants. Spontaneous speech productions were recorded at 6, 12, and 18 months post-surgery and consonant inventories were derived from both glossable and non-glossable phones using two acquisition criteria. The results showed that children initiated appropriate production of consonants after six months of implant use. Stops and labials were the most frequently produced speech sounds, whereas glides and palatals were still infrequent after 18 months. Speech accuracy also improved throughout the study. Consonant visibility appeared to influence the order of acquisition in the first months following the implantation and, as experience with auditory information increased, patterns of development tended to resemble those seen in children with normal hearing. Finally, a signed mode of communication and oral rehabilitation programs prior to implantation were better outcome predictors than age at implantation.


Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies.
N-Acetyl-aspartate is found in high concentrations in all areas of the brain, but is undetectable in non-neuronal tissue. In order to characterize the cellular localization of N-acetyl-aspartate in brain, highly specific monoclonal antibodies against N-acetyl-aspartate were produced by fusing spleen lymphocytes obtained from mice immunized with N-acetyl-aspartate conjugated to thyroglobulin by carbodiimide with P3/x63-Ag8.653 mouse myeloma cells. Clones were selected which secrete IgG2a(k) antibodies highly specific for conjugated N-acetyl-aspartate. Only 3-6% cross-reactivity with conjugated N-acetyl-aspartate-glutamate was observed at high antibody concentrations, whereas no cross-reactivity (less than 1%) was observed with conjugated N-acetyl-glutamate or aspartate. Preincubation of the antibodies with 0.5 mg/ml conjugated N-acetyl-aspartate blocked immunoreactivity more than 90%, while preincubation with conjugated N-acetyl-aspartate-glutamate and free N-acetyl-aspartate had no effect. Immunocytochemical staining has shown that N-acetyl-aspartate-like immunoreactivity is localized in neurons, which are widely distributed throughout the brain. The immunoreactive neurons exhibited intense staining of the perikarya, proximal dendrites and axons. No consistent pattern of distribution of immunoreactivity was observed with regard to primary neurotransmitter characteristics of stained neurons although neurons with long projections or extensive arbors, such as pyramidal cells in cortex, locus coeruleus, motor neurons and Purkinje cells, stained much more intensively than local circuit neurons.


Professional or Amateur? The Phonological Output Buffer as a Working Memory Operator.
The Phonological Output Buffer (POB) is thought to be the stage in language production where phonemes are held in working memory and assembled into words. The neural implementation of the POB remains unclear despite a wealth of phenomenological data. Individuals with POB impairment make phonological errors when they produce words and non-words, including phoneme omissions, insertions, transpositions, substitutions and perseverations. Errors can apply to different kinds and sizes of units, such as phonemes, number words, morphological affixes, and function words, and evidence from POB impairments suggests that units tend to substituted with units of the same kind-e.g., numbers with numbers and whole morphological affixes with other affixes. This suggests that different units are processed and stored in the POB in the same stage, but perhaps separately in different mini-stores. Further, similar impairments can affect the buffer used to produce Sign Language, which raises the question of whether it is instantiated in a distinct device with the same design. However, what appear as separate buffers may be distinct regions in the activity space of a single extended POB network, connected with a lexicon network. The self-consistency of this idea can be assessed by studying an autoassociative Potts network, as a model of memory storage distributed over several cortical areas, and testing whether the network can represent both units of word and signs, reflecting the types and patterns of errors made by individuals with POB impairment.


Transcatheter mitral valve replacement: factors associated with screening success and failure.
Transcatheter mitral valve replacement (TMVR) is a promising therapeutic solution to treat high-risk patients with severe mitral regurgitation (MR) contraindicated to surgery. Optimal selection of patients who will benefit from the procedure is of paramount importance. We aimed to investigate factors associated with TMVR screening. From November 2016 to July 2018, we examined conditions associated with TMVR screening success in patients referred to the two French heart valve clinics with the greatest TMVR experience. Among a total of 40 consecutively screened patients, 16 (40%) were selected for TMVR (8 Twelve Intrepid, 7 Tendyne and 1 HighLife), while 24 patients (60%) were refused for TMVR mainly because of a too large mitral annulus (MA) (n=15, 62% of those refused), or too small anatomy and risk of neo-left ventricular outflow tract (LVOT) obstruction (n=6, 25% of those refused). Patients with suitable anatomy for TMVR were more often male and more frequently suffered from secondary MR (p=0.01) associated with previous myocardial infarction and presented a commissure-to-commissure diameter less than 39 mm (AUC=0.72, p=0.0085) and LVESD greater than 32 mm (AUC=0.83, p<0.0001) on transthoracic echocardiography, and an MA area less than 17.6 cm² (AUC=0.95, p<0.0001) and anteroposterior diameter greater than 41.6 mm (AUC=0.87, p<0.001) on CT scan. Despite several prostheses being available, most patients referred to heart valve clinics who are good candidates with regard to their clinical profile cannot have TMVR because of mismatch between their anatomy and prosthesis characteristics. Our findings suggest the need to develop new prostheses adapted to larger mitral annuli but with a lower impact on the LVOT.


Hybridization of Zinc Oxide Tetrapods for Selective Gas Sensing Applications.
In this work, the exceptionally improved sensing capability of highly porous three-dimensional (3-D) hybrid ceramic networks toward reducing gases is demonstrated for the first time. The 3-D hybrid ceramic networks are based on doped metal oxides (MexOy and ZnxMe1-xOy, Me = Fe, Cu, Al) and alloyed zinc oxide tetrapods (ZnO-T) forming numerous junctions and heterojunctions. A change in morphology of the samples and formation of different complex microstructures is achieved by mixing the metallic (Fe, Cu, Al) microparticles with ZnO-T grown by the flame transport synthesis (FTS) in different weight ratios (ZnO-T:Me, e.g., 20:1) followed by subsequent thermal annealing in air. The gas sensing studies reveal the possibility to control and change/tune the selectivity of the materials, depending on the elemental content ratio and the type of added metal oxide in the 3-D ZnO-T hybrid networks. While pristine ZnO-T networks showed a good response to H2 gas, a change/tune in selectivity to ethanol vapor with a decrease in optimal operating temperature was observed in the networks hybridized with Fe-oxide and Cu-oxide. In the case of hybridization with ZnAl2O4, an improvement of H2 gas response (to ∼7.5) was reached at lower doping concentrations (20:1), whereas the increase in concentration of ZnAl2O4 (ZnO-T:Al, 10:1), the selectivity changes to methane CH4 gas (response is about 28). Selectivity tuning to different gases is attributed to the catalytic properties of the metal oxides after hybridization, while the gas sensitivity improvement is mainly associated with additional modulation of the electrical resistance by the built-in potential barriers between n-n and n-p heterojunctions, during adsorption and desorption of gaseous species. Density functional theory based calculations provided the mechanistic insights into the interactions between different hybrid networks and gas molecules to support the experimentally observed results. The studied networked materials and sensor structures performances would provide particular advantages in the field of fundamental research, applied physics studies, and industrial and ecological applications.


Prevention and treatment of murine experimental allergic encephalomyelitis with T cell receptor V beta-specific antibodies.
Experimental allergic encephalomyelitis (EAE) is a model system for T cell-mediated autoimmune disease. Symptoms of EAE are similar to those of multiple sclerosis (MS) in humans. EAE is induced in susceptible animal strains by immunization with myelin basic protein (MBP) and potent adjuvant. The major T cell response to MBP in B10.PL mice is directed towards an NH2-terminal epitope and involves T cells expressing either V beta 8.2 or V beta 13 gene segments. Animals treated with a TCR V beta 8-specific mAb have a reduced incidence of EAE. We report here that the in vivo administration of a combination of anti-V beta 8.2 and anti-V beta 13 mAbs results in a long-term elimination of T cells involved in the response to MBP. When given before MBP immunization, anti-TCR antibody treatment leads to nearly complete protection against EAE. Antibody treatment also results in a dramatic reversal of paralysis in diseased animals. Thus, treatment with a combination of V beta-specific antibodies is a very effective therapy for the prevention and treatment of EAE. It is hoped that the future characterization of TCR V gene usage in human autoimmune diseases may lead to similar strategies of immune intervention.


Dynamic Modeling of Carnobacterium maltaromaticum CNCM I-3298 Growth and Metabolite Production and Model-Based Process Optimization.
Carnobacterium maltaromaticum is a species of lactic acid bacteria found in dairy, meat, and fish, with technological properties useful in food biopreservation and flavor development. In more recent years, it has also proven to be a key element of biological time-temperature integrators for tracking temperature variations experienced by perishable foods along the cold-chain. A dynamic model for the growth of C. maltaromaticum CNCM I-3298 and production of four metabolites (formic acid, acetic acid, lactic acid, and ethanol) from trehalose in batch culture was developed using the reaction scheme formalism. The dependence of the specific growth and production rates as well as the product inhibition parameters on the operating conditions were described by the response surface method. The parameters of the model were calibrated from eight experiments, covering a broad spectrum of culture conditions (temperatures between 20 and 37 °C; pH between 6.0 and 9.5). The model was validated against another set of eight independent experiments performed under different conditions selected in the same range. The model correctly predicted the growth kinetics of C. maltaromaticum CNCM I-3298 as well as the dynamics of the carbon source conversion, with a mean relative error of 10% for biomass and 14% for trehalose and the metabolites. The paper illustrates that the proposed model is a valuable tool for optimizing the culture of C. maltaromaticum CNCM I-3298 by determining operating conditions that favor the production of biomass or selected metabolites. Model-based optimization may thus reduce the number of experiments and substantially speed up the process development, with potential applications in food technology for producing starters and improving the yield and productivity of the fermentation of sugars into metabolites of industrial interest.


Reverse breech extraction in cases of second stage caesarean section.
Our objective was to examine the feasibility of reverse breech extraction to disengage fetal head from the pelvis at second stage caesarean section (CS). A total of 50 consecutive women with singleton term pregnancies undergoing urgent CS at second stage were retrospectively evaluated. A total of 29 were delivered by the reverse breech manoeuvre (study group) and 21 women were delivered by the conventional approach (control group). The reverse breech extraction was successful in all cases of the study group. The mean estimated blood loss during operation, haemoglobin drop, Apgar scores at 1 and 5 min as well as cord PH were similar between the groups. The mean newborn weights were similar, 3492 ± 426 and 3610 ± 392 g in the study and control group, respectively. One case of an inadvertent extension of the low transverse incision was encountered in each group. Also, in three cases of the study group the incision was intentionally extended to an inverted T-shape to facilitate the manoeuvre. None of the newborns in both groups had trauma related to the extraction or were admitted to the neonatal intensive care unit. All women following CS had a low rate complication rate in the postpartum period. We conclude that reverse breech extraction seems to be feasible to disengage fetal head from the pelvis at second stage CS. Maternal and newborn complications following this manoeuvre seem to be low.


Neuromuscular Junction Changes in a Mouse Model of Charcot-Marie-Tooth Disease Type 4C.
The neuromuscular junction (NMJ) appears to be a site of pathology in a number of peripheral nerve diseases. Charcot-Marie-Tooth (CMT) 4C is an autosomal recessive, early onset, demyelinating neuropathy. Numerous mutations in the SH3TC2 gene have been shown to underlie the condition often associated with scoliosis, foot deformities, and reduced nerve conduction velocities. Mice with exon 1 of the Sh3tc2 gene knocked out demonstrate many of the features seen in patients. To determine if NMJ pathology is contributory to the pathomechanisms of CMT4C we examined NMJs in the gastrocnemius muscle of SH3TC2-deficient mice. In addition, we performed proteomic assessment of the sciatic nerve to identify protein factors contributing to the NMJ alterations and the survival of demyelinated axons. Morphological and gene expression analysis of NMJs revealed a lack of continuity between the pre- and post-synaptic apparatus, increases in post-synaptic fragmentation and dispersal, and an increase in expression of the gamma subunit of the acetylcholine receptor. There were no changes in axonal width or the number of axonal inputs to the NMJ. Proteome investigations of the sciatic nerve revealed altered expression of extracellular matrix proteins important for NMJ integrity. Together these observations suggest that CMT4C pathology includes a compromised NMJ even in the absence of changes to the innervating axon.


Change of chloride ion channel conductance is an early event of slow-to-fast fibre type transition during unloading-induced muscle disuse.
Disuse of postural slow-twitch muscles, as it occurs in hypogravity, induces a slow-to-fast myofibre type transition. Nothing is known about the effects of weightlessness on the resting membrane chloride conductance (gCl), which controls sarcolemma excitability and influences fibre type transition during development and adult life. Using the current-clamp method, we observed that rat hindlimb unloading (HU) for 1-3 weeks increased gCl in fibres of the slow-twitch soleus (Sol) muscle toward values found in fast muscle. Northern blot analysis suggested that this effect resulted from an increased ClC-1 chloride channel mRNA level. In the meantime, a 4-fold increase in fibres expressing fast isoforms of the myosin heavy chain (MHC) was observed by immunostaining of muscle sections. Also, Sol muscle function evolved toward a fast phenotype during HU, as demonstrated by the positive shift of the threshold potential for contraction. After 3-days HU, Sol muscle immunostaining and RT-PCR experiments revealed no change in MHC protein and mRNA expression, whereas the gCl was already maximally increased, due to a pharmacologically probed, increased activity of ClC-1 channels. Thus the increase in gCl is an early event in Sol muscle experiencing unloading, suggesting that gCl may play a role in muscle adaptation to modified use. Pharmacological modulation of ClC-1 channels may help to prevent disuse-induced muscle impairment.


Microencapsulated krill and tuna oil blend raises plasma long-chain n-3 polyunsaturated fatty acid levels compared to tuna oil with similar increases in ileal contractility in rats.
Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) may be more bioavailable from krill oil compared to fish oil due to their phospholipid structure. We tested whether a microencapsulated krill and tuna oil blend (ME-TOKO) provided greater LC n-3 PUFA bioavailability, improved blood lipid profiles and increased intestinal contractility compared to microencapsulated tuna oil (ME-TO). Rats were divided into three groups to receive isocaloric diets containing ME-TO, ME-TOKO and microencapsulated olive oil (ME-OO) at 0.3 or 2 g/100 g for 4 weeks. Final body and organ weights, feed intake and waste output were similar. ME-TOKO rats had higher plasma total LC n-3 PUFA levels compared to ME-TO, but liver LC n-3 PUFA levels and plasma triglyceride and cholesterol levels were similar in non-fasted rats. Diets containing 2% ME-TO and ME-TOKO also showed similar increases in ileal contractility. In summary, ME-TO bioavailability of LC n-3 PUFA was similar to ME-TOKO.


Radiotracer Injection Into the Catheter Balloon: A Subtle Pitfall Which Can Be Overlooked in Direct Radionuclide Cystography.
We reported a 4-year-old girl with history of bilateral vesicoureteral reflux who underwent direct radionuclide cystography in our department. Radiotracer was mistakenly injected in the catheter balloon. The filling phase showed no change in the bladder volume, and the catheter balloon was apparent as an intense activity in the base of the bladder. The procedure was repeated with correct injection of the tracer into the catheter. Wrong injection of the radiotracer into the catheter balloon should always be borne in mind in similar cases.


Determination of piezo-optic coefficients of crystals by means of four-point bending.
A technique developed recently for determining piezo-optic coefficients (POCs) of isotropic optical media, which represents a combination of digital imaging laser interferometry and a classical four-point bending method, is generalized and applied to a single-crystalline anisotropic material. The peculiarities of measuring procedures and data processing for the case of optically uniaxial crystals are described in detail. The capabilities of the technique are tested on the example of canonical nonlinear optical crystal LiNbO3. The high precision achieved in determination of the POCs for isotropic and anisotropic materials testifies that the technique should be both versatile and reliable.


Collision-induced absorption in Ar-Kr gas mixtures: A molecular dynamics study with new potential and dipole data.
We have implemented a scheme for classical molecular dynamics simulations of collision-induced absorption. The program has been applied to a gas mixture of argon (Ar) and krypton (Kr). The simulations are compared with accurate quantum dynamical calculations. The comparisons of the absorption coefficients show that classical molecular dynamics is correct within 10% for photon wave numbers up to 220 cm-1 at a temperature of 200 K for this system. At higher temperatures, the agreement is even better. Molecular dynamics accounts for many-body interactions, which, for example, give rise to continuous dimer formation and destruction in the gas. In this way, the method has an advantage compared with bimolecular classical (trajectory) treatments. The calculations are carried out with a new empirical Ar-Kr pair potential. This has been obtained through extensive analysis of experimental thermophysical and transport properties. We also present a new high level ab initio Ar-Kr potential curve for comparison, as well as ab initio interaction-induced dipole curves computed with different methods. In addition, the Ar-Kr polarizability and hyperpolarizability are reported. A comparison of the computed absorption spectra with an experiment taken at 300 K shows satisfactory agreement although a difference in absolute magnitude of 10%-15% persists. This discrepancy we attribute mainly to experimental uncertainty.


Fast detection of de novo copy number variants from SNP arrays for case-parent trios.
In studies of case-parent trios, we define copy number variants (CNVs) in the offspring that differ from the parental copy numbers as de novo and of interest for their potential functional role in disease. Among the leading array-based methods for discovery of de novo CNVs in case-parent trios is the joint hidden Markov model (HMM) implemented in the PennCNV software. However, the computational demands of the joint HMM are substantial and the extent to which false positive identifications occur in case-parent trios has not been well described. We evaluate these issues in a study of oral cleft case-parent trios. Our analysis of the oral cleft trios reveals that genomic waves represent a substantial source of false positive identifications in the joint HMM, despite a wave-correction implementation in PennCNV. In addition, the noise of low-level summaries of relative copy number (log R ratios) is strongly associated with batch and correlated with the frequency of de novo CNV calls. Exploiting the trio design, we propose a univariate statistic for relative copy number referred to as the minimum distance that can reduce technical variation from probe effects and genomic waves. We use circular binary segmentation to segment the minimum distance and maximum a posteriori estimation to infer de novo CNVs from the segmented genome. Compared to PennCNV on simulated data, MinimumDistance identifies fewer false positives on average and is comparable to PennCNV with respect to false negatives. Genomic waves contribute to discordance of PennCNV and MinimumDistance for high coverage de novo calls, while highly concordant calls on chromosome 22 were validated by quantitative PCR. Computationally, MinimumDistance provides a nearly 8-fold increase in speed relative to the joint HMM in a study of oral cleft trios. Our results indicate that batch effects and genomic waves are important considerations for case-parent studies of de novo CNV, and that the minimum distance is an effective statistic for reducing technical variation contributing to false de novo discoveries. Coupled with segmentation and maximum a posteriori estimation, our algorithm compares favorably to the joint HMM with MinimumDistance being much faster.


A systematic review of human-to-human transmission of measles vaccine virus.
Measles is one of the most contagious human diseases. Administration of the live attenuated measles vaccine has substantially reduced childhood mortality and morbidity since its licensure in 1963. The live but attenuated form of the vaccine describes a virus poorly adapted to replicating in human tissue, but with a replication yield sufficient to elicit an immune response for long-term protection. Given the high transmissibility of the wild-type virus and that transmission of other live vaccine viruses has been documented, we conducted a systematic review to establish if there is any evidence of human-to-human transmission of the live attenuated measles vaccine virus. We reviewed 773 articles for genotypic confirmation of a vaccine virus transmitted from a recently vaccinated individual to a susceptible close contact. No evidence of human-to-human transmission of the measles vaccine virus has been reported amongst the thousands of clinical samples genotyped during outbreaks or endemic transmission and individual case studies worldwide.


Platelet shape change evoked by selective activation of P2X1 purinoceptors with alpha,beta-methylene ATP.
Simultaneous measurements of [Ca2+]i and light transmission were used to examine the relationship between P2X1 receptor activation and functional platelet responses. The P2X1 agonist alpha,beta-MeATP evoked a transient [Ca2+]i increase and a reversible decrease in light transmission; both responses required external Ca2+ and the nucleotidase apyrase. The transmission response was due to shape change only, verified by scanning electron microscopy and insensitivity to Reopro, a GPIIbIIIa antagonist. Alpha,beta-MeATP stimulated smaller shape changes than ADP, however P2X1 responses had a lifespan of <2 h following resuspension in saline and may be considerably larger in vivo. A peak [Ca2+]i increase of >50 nM was required for detectable shape change. Overlap of concentration-response relationships for alpha,beta-MeATP-evoked [Ca2+]i and shape change suggests that other second messengers are not involved. Therefore, the physiological P2X1 agonist ATP can contribute to platelet activation, in contrast to its previously described inhibitory action at metabotropic platelet purinoceptors.


Social capital, collective efficacy and the provision of social support services and amenities by municipalities in the Netherlands.
Differential provision of local services and amenities has been proposed as a mechanism behind the relationship between social capital and health. The aim of this study was to investigate whether social capital and collective efficacy are related to the provision of social support services and amenities in Dutch municipalities, against a background of decentralisation of long-term care to municipalities. We used data on neighbourhood social capital, collective efficacy (the extent to which people are willing to work for the common good), and the provision of services and amenities in 2012. We included the services municipalities provide to support informal caregivers (e.g. respite care), individual services and support (e.g. domiciliary help), and general and collective services and amenities (e.g. lending point for wheelchairs). Data for social capital were collected between May 2011 and September 2012. Social capital was measured by focusing on contacts between neighbours. A social capital measure was estimated for 414 municipalities with ecometric measurements. A measure of collective efficacy was constructed based on information about the experienced responsibility for the liveability of the neighbourhood by residents in 2012, average charity collection returns in municipalities in 2012, voter turnout at the municipal elections in 2010 and the percentage of blood donors in 2012. We conducted Poisson regression and negative binomial regression to test our hypotheses. We found no relationship between social capital and the provision of services and amenities in municipalities. We found an interaction effect (coefficient = 3.11, 95% CI = 0.72-5.51, P = 0.011) of social capital and collective efficacy on the provision of support services for informal caregivers in rural municipalities. To gain more insight in the relationship between social capital and health, it will be important to study the relationship between social capital and differential provision of services and amenities more extensively and in different contexts.


The well-man visit: addressing a man's health to optimize pregnancy outcomes.
Male health and health care before conception has received little attention by many physicians. Only recently has the importance of the health of men before conception been explored. The benefits of preconception care are important, including ensuring that all pregnancies are planned and wanted, improving the man's genetic and biologic contributions to the pregnancy, improving reproductive health and outcomes for female partners, improving the man's capacity for and understanding of parenthood, and enhancing the man's overall health through access to primary care.


Study on the interaction of Se and erythrocyte membrane--protective effect of Se on the erythrocyte membranes.
During the ageing of erythrocyte membrane, the spectrin content, Na,K-ATPase activity as well as the lipid fluidity are obviously decreased. However, supplementation of a trace amount of Na2SeO3 in the medium could prevent the dissociation of spectrin from membrane and delay the changes of Na,K-ATPase activity and lipid fluidity. The effectiveness is proportional to Se concentration within the range of 0.1-1.0 ppm. Similar effect of supplementation of Se on the intact erythrocytes during ageing has been also observed. The protective action of Se on biomembranes is generally interpreted in terms of the activity of Se-containing glutathione peroxidase (GSHPx). However, GSHPx mainly distributes in the cytoplasma of erythrocytes, therefore it seems that the protective action of supplemented Se on the isolated erythrocyte membrane might not be related to the activity of GSHPx.


Water decoction of coptidis rhizoma prevents oxidative damage in erythrocytes of mice.
Coptidis Rhizoma (Coptis chinensis) has been reported to have antioxidative effect on hemolysis of erythrocytes induced by acetylphenylhydrazine in mice and rats. However, the ability of Coptidis Rhizoma to protect structure and function of erythrocytes membrane and morphology of erythrocytes against oxidative damage remains unknown. In this study, we undertook a characterization of antioxidative activity in erythrocytes membrane of Coptidis Rhizoma using an in vivo model of acetylphenylhydrazine-induced mice together with in vitro studies with 2,2-azo-bis (2-amidinopropane) dihydrochloride-induced erythrocytes for further morphology characterization. Acetylphenylhydrazine-induced mice were treated intragastrically with Coptidis Rhizoma at doses of 0.3, 0.6, and 1.2 g/kg per day for 3 days and at the dose of 0.6 and 1.2 g/kg it showed that there was an increasing trend in membranes cytoskeletal proteins of band I-IV, especially a significant upregulation in band II. Significant increase in phosphatidylserine and phosphatidylcholine content at the dose of 1.2 g/kg Coptidis Rhizoma was obsereved. At all doses of Coptidis Rhizoma, the declined membrane fluidity of acetylphenylhydrazine-induced mice was significantly increased. In addition, at the dose of 1.2 g/kg Coptidis Rhizoma treatment showed a significant increase in Ca(2+)/Mg(2+)-ATPase activity and there was an increasing trend in the activity of Na(+)/K(+)-ATPase. In vitro, Coptidis Rhizoma protected erythrocytes from 2,2-azo-bis (2-amidinopropane) dihydrochloride-induced hemolysis in a dose-dependent manner at concentrations of 0.25-1.5 mg/ml, and also significantly inhibited the 2,2-azo-bis (2-amidinopropane) dihydrochloride-induced morphological alterations in mice erythrocytes. These results demonstrate that Coptidis Rhizoma is capable of protecting erythrocytes against oxidative damage probably by acting as an antioxidant and maintaining membrane integrity.


Treelink: data integration, clustering and visualization of phylogenetic trees.
Phylogenetic trees are central to a wide range of biological studies. In many of these studies, tree nodes need to be associated with a variety of attributes. For example, in studies concerned with viral relationships, tree nodes are associated with epidemiological information, such as location, age and subtype. Gene trees used in comparative genomics are usually linked with taxonomic information, such as functional annotations and events. A wide variety of tree visualization and annotation tools have been developed in the past, however none of them are intended for an integrative and comparative analysis. Treelink is a platform-independent software for linking datasets and sequence files to phylogenetic trees. The application allows an automated integration of datasets to trees for operations such as classifying a tree based on a field or showing the distribution of selected data attributes in branches and leafs. Genomic and proteonomic sequences can also be linked to the tree and extracted from internal and external nodes. A novel clustering algorithm to simplify trees and display the most divergent clades was also developed, where validation can be achieved using the data integration and classification function. Integrated geographical information allows ancestral character reconstruction for phylogeographic plotting based on parsimony and likelihood algorithms. Our software can successfully integrate phylogenetic trees with different data sources, and perform operations to differentiate and visualize those differences within a tree. File support includes the most popular formats such as newick and csv. Exporting visualizations as images, cluster outputs and genomic sequences is supported. Treelink is available as a web and desktop application at http://www.treelinkapp.com .


Pairwise alignment of interaction networks by fast identification of maximal conserved patterns.
A number of tools for the alignment of protein-protein interaction (PPI) networks have laid the foundation for PPI network analysis. They typically find conserved interaction patterns by various local or global search algorithms, and then validate the results using genome annotation. The improvement of the speed, scalability and accuracy of network alignment is still the target of ongoing research. In view of this, we introduce a connected-components based algorithm, called HopeMap for pairwise network alignment with the focus on fast identification of maximal conserved patterns across species. Observing that the number of true homologs across species is relatively small compared to the total number of proteins in all species, we start with highly homologous groups across species, find maximal conserved interaction patterns globally with a generic scoring system, and validate the results across multiple known functional annotations. The results are evaluated in terms of statistical enrichment of gene ontology (GO) terms and KEGG ortholog groups (KO) within conserved interaction patters. HopeMap is fast, with linear computational cost, accurate in terms of KO groups and GO terms specificity and sensitivity, and extensible to multiple network alignment.


Simultaneous Ribosome Profiling of Human Host Cells Infected with Toxoplasma gondii.
Toxoplasma gondii is a ubiquitous obligate intracellular parasite that infects the nucleated cells of warm-blooded animals. From within the parasitophorous vacuole in which they reside, Toxoplasma tachyzoites secrete an arsenal of effector proteins that can reprogram host gene expression to facilitate parasite survival and replication. Gaining a better understanding of how host gene expression is altered upon infection is central for understanding parasite strategies for host invasion and for developing new parasite therapies. Here, we applied ribosome profiling coupled with mRNA measurements to concurrently study gene expression in the parasite and in host human foreskin fibroblasts. By examining the parasite transcriptome and translatome, we identified potential upstream open reading frames that may permit the stress-induced preferential translation of parasite mRNAs. We also determined that tachyzoites reduce host death-associated pathways and increase survival, proliferation, and motility in both quiescent and proliferative host cell models of infection. Additionally, proliferative cells alter their gene expression in ways that are consistent with massive transcriptional rewiring, while quiescent cells were best characterized by reentry into the cell cycle. We also identified a translational control regimen consistent with mechanistic target of rapamycin (mTOR) activation in quiescent cells and, to a lesser degree, in proliferative cells. This study illustrates the utility of the method for dissection of gene expression programs simultaneously in the parasite and host.IMPORTANCEToxoplasma gondii is a single-celled parasite that has infected up to one-third of the world's population. Significant overhauls in gene expression in both the parasite and the host cell accompany parasite invasion, and a better understanding of these changes may lead to the development of new therapeutic agents. In this study, we employed ribosome profiling to determine the changes that occur at the levels of transcription and translation in both the parasite and the infected host cell at the same time. We discovered features of Toxoplasma mRNAs that suggest a means for controlling parasite gene expression under stressful conditions. We also show that differences in host gene expression occur depending on whether they are confluent or not. Our findings demonstrate the feasibility of using ribosomal profiling to interrogate the host-parasite dynamic under a variety of conditions.


Spinal cord fusion with PEG-GNRs (TexasPEG): Neurophysiological recovery in 24 hours in rats.
The GEMINI spinal cord fusion protocol has been developed to achieve a successful cephalosomatic anastomosis. Here, for the first time, we report the effects of locally applied water-soluble, conductive PEG(polyethylene glycol)ylated graphene nanoribbons (PEG-GNRs) on neurophysiologic conduction after sharp cervical cord transection in rats. PEG-GNRs were produced by the polymerization of ethylene oxide from anion-edged graphene nanoribbons. These combine the fusogenic potential of PEG with the electrical conducting properties of the graphene nanoribbons. Laminectomy and transection of cervical spinal cord (C5) was performed on Female Sprague-Dawley (SD) rats. After applying PEG-GNR on the severed part, electrophysiological recovery of the reconstructed cervical spinal cord was confirmed by somatosensory evoked potentials (SSEPs) at 24 h after surgery. While no SSEPs were detected in the control group, PEG-GNR treated group showed fast recovery of SSEPs at 24 h after the surgery. In this preliminary dataset, for the first time, we report the effect of a novel form of PEG with the goal of rapid reconstruction of a sharply severed spinal cord.


Improvement of Blood-Brain Barrier Integrity in Traumatic Brain Injury and Hemorrhagic Shock Following Treatment With Valproic Acid and Fresh Frozen Plasma.
Combined traumatic brain injury and hemorrhagic shock are highly lethal. Following injuries, the integrity of the blood-brain barrier can be impaired, contributing to secondary brain insults. The status of the blood-brain barrier represents a potential factor impacting long-term neurologic outcomes in combined injuries. Treatment strategies involving plasma-based resuscitation and valproic acid therapy have shown efficacy in this setting. We hypothesize that a component of this beneficial effect is related to blood-brain barrier preservation. Following controlled traumatic brain injury, hemorrhagic shock, various resuscitation and treatment strategies were evaluated for their association with blood-brain barrier integrity. Analysis of gene expression profiles was performed using Porcine Gene ST 1.1 microarray. Pathway analysis was completed using network analysis tools (Gene Ontology, Ingenuity Pathway Analysis, and Parametric Gene Set Enrichment Analysis). Female Yorkshire swine were subjected to controlled traumatic brain injury and 2 hours of hemorrhagic shock (40% blood volume, mean arterial pressure 30-35 mmHg). Subjects were resuscitated with 1) normal saline, 2) fresh frozen plasma, 3) hetastarch, 4) fresh frozen plasma + valproic acid, or 5) hetastarch + valproic acid (n = 5 per group). After 6 hours of observation, brains were harvested for evaluation. Immunofluoroscopic evaluation of the traumatic brain injury site revealed significantly increased expression of tight-junction associated proteins (zona occludin-1, claudin-5) following combination therapy (fresh frozen plasma + valproic acid and hetastarch + valproic acid). The extracellular matrix protein laminin was found to have significantly improved expression with combination therapies. Pathway analysis indicated that valproic acid significantly modulated pathways involved in endothelial barrier function and cell signaling. Resuscitation with fresh frozen plasma results in improved expression of proteins essential for blood-brain barrier integrity. The addition of valproic acid provides significant improvement to these protein expression profiles. This is likely secondary to activation of key pathways related to endothelial functions.


Do Hispanic children need to know about stroke prevention?
When compared to Hispanics in their native countries, the frequency of stroke in the Hispanic American population is higher. This has been linked to an increase in smoking, inactivity, and obesity. Initially these health issues were thought to affect only Hispanic adults, but research confirms that first- and second-generation adolescents and young adults continue to demonstrate these habits. Education has been shown to be an effective method of stroke prevention by increasing an individual's knowledge base. As demonstrated in a previous study performed in the Hispanic community, when educational material is presented in a familiar environment and offers lifestyle options that are culturally realistic, there is an increase in knowledge and compliance with lifestyle changes. The focus of education for stroke prevention has always been placed on older adults, but little has been done to alter the cultural risk factors found in the young adult and adolescent population in order to prevent stroke in the future.


Creatine transporter-deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy.
Creatine (Cr) is a nitrogenous organic acid and plays roles such as fast phosphate energy buffer to replenish ATP, osmolyte, antioxidant, neuromodulator, and as a compound with anabolic and ergogenic properties in muscle. Cr is taken from the diet or endogenously synthetized by the enzymes arginine:glycine amidinotransferase and guanidinoacetate methyltransferase, and specifically taken up by the transporter SLC6A8. Loss-of-function mutations in the genes encoding for the enzymes or the transporter cause creatine deficiency syndromes (CDS). CDS are characterized by brain Cr deficiency, intellectual disability with severe speech delay, behavioral troubles, epilepsy, and motor dysfunction. Among CDS, the X-linked Cr transporter deficiency (CTD) is the most prevalent with no efficient treatment so far. Different animal models of CTD show reduced brain Cr levels, cognitive deficiencies, and together they cover other traits similar to those of patients. However, motor function was poorly explored in CTD models, and some controversies in the phenotype exist in comparison with CTD patients. Our recently described Slc6a8Y389C knock-in rat model of CTD showed mild impaired motor function, morphological alterations in cerebellum, reduced muscular mass, Cr deficiency, and increased guanidinoacetate content in muscle, although no consistent signs of muscle atrophy. Our results indicate that such motor dysfunction co-occurred with both nervous and muscle dysfunctions, suggesting that muscle strength and performance as well as neuronal connectivity might be affected by this Cr deficiency in muscle and brain.


Ribonucleic acid synthesis by chromatin isolated from Phaseolus aureus Roxb. : The effect of endogenous ribonuclease.
Chromatin was isolated from the hypocotyls of Phaseolus aureus Roxb. and assayed for endogenous RNA polymerase (EC 22.214.171.124) activity in vitro. The molecular size of the RNA product, measured by polyacrylamide gel electrophoresis, was found to be much smaller than that known to be synthesised in vivo and was affected by the assay temperature. Although conventional enzyme assays provided no evidence for the presence of ribonuclease in chromatin, a more sensitive technique revealed sufficient ribonuclease activity to degrade high-molecular weight RNA to smaller fragments. The inclusion of unlabelled exogenous RNA in the media for chromatin preparation and RNA polymerase assay substantially increased the molecular-weight of the RNA products synthesised in vitro.


Attenuated NOx responses and myocardial ischemia, a possible risk for structural vascular disease in African men: the SABPA study.
Chronically elevated blood pressure has been associated with impaired NO-mediated vasodilation and structural vascular disease risk. This study aimed to determine whether significant associations exist regarding NO metabolite (NOx) responses, cardiovascular function and structural vascular disease in a cohort of African and Caucasian men. The study included 81 African and 94 Caucasian male teachers stratified via median splits into low and high NOx ethnic groups. Ambulatory blood pressure, electrocardiogram monitoring and ultrasound carotid intima-media thickness (CIMT) images were obtained. Cardiovascular measurements and fasting blood for NOx responses were measured during rest and on challenging the cardiovascular system with the Stroop colour-word conflict test. African men displayed significantly higher resting NOx as well as higher number of 24 h silent ischemic events than their Caucasian counterparts. Low NOx African men displayed enhanced α-adrenergic and ECG ST segment depression acute mental stress responses as well as 24 h silent ischemic events associated with CIMT (adjusted R(2) = 0.47; β = 0.25; confidence interval (CI) = 0.13, 0.41). African men demonstrated a vulnerable cardiovascular profile. Novel findings revealed α-adrenergic-driven blood pressure responses and less NO bioavailability during acute stress. The association between myocardial ischemia and CIMT in this group emphasized their risk for future coronary artery disease and cerebrovascular events.


Genome-wide identification and characterization of gene family for RWP-RK transcription factors in wheat (Triticum aestivum L.).
RWP-RKs represent a small family of transcription factors (TFs) that are unique to plants and function particularly under conditions of nitrogen starvation. These RWP-RKs have been classified in two sub-families, NLPs (NIN-like proteins) and RKDs (RWP-RK domain proteins). NLPs regulate tissue-specific expression of genes involved in nitrogen use efficiency (NUE) and RKDs regulate expression of genes involved in gametogenesis/embryogenesis. During the present study, using in silico approach, 37 wheat RWP-RK genes were identified, which included 18 TaNLPs (2865 to 7340 bp with 4/5 exons), distributed on 15 chromosomes from 5 homoeologous groups (with two genes each on 4B,4D and 5A) and 19 TaRKDs (1064 to 5768 bp with 1 to 6 exons) distributed on 12 chromosomes from 4 homoeologous groups (except groups 1, 4 and 5); 2-3 splice variants were also available in 9 of the 37 genes. Sixteen (16) of these genes also carried 24 SSRs (simple sequence repeats), while 11 genes had targets for 13 different miRNAs. At the protein level, MD simulation analysis suggested their interaction with nitrate-ions. Significant differences were observed in the expression of only two (TaNLP1 and TaNLP2) of the nine representative genes that were used for in silico expression analysis under varying levels of N at post-anthesis stage (data for other genes was not available for in silico expression analysis). Differences in expression were also observed during qRT-PCR, when expression of four representative genes (TaNLP2, TaNLP7, TaRKD6 and TaRKD9) was examined in roots and shoots of seedlings (under different conditions of N supply) in two contrasting genotypes which differed in NUE (C306 with low NUE and HUW468 with high NUE). These four genes for qRT-PCR were selected on the basis of previous literature, level of homology and the level of expression (in silico study). In particular, the TaNLP7 gene showed significant up-regulation in the roots and shoots of HUW468 (with higher NUE) during N-starvation; this gene has already been characterized in Arabidopsis and tobacco, and is known to be involved in nitrate-signal transduction pathway.


Pain and function in patients with chronic low back pain and leg pain after Zhineng Qigong - a quasi-experimental feasibility study.
Qigong includes training for body and mind, one method is Zhineng Qigong. Scientific literature on qigong for chronic low back pain (LBP) is sparse. This study aimed to investigate feasibility including evaluation of a Zhineng Qigong intervention for pain and other lumbar spine-related symptoms, disability, and health-related quality of life in patients with chronic LBP and/or leg pain. Prospective interventional feasibility study without control group. Fifty-two chronic pain patients (18-75 years) with LBP and/or leg pain (Visual Analogue Scale ≥ 30) were recruited from orthopaedic clinics (spinal stenosis, spondylolisthesis, or segmental pain) and primary healthcare (chronic LBP). Patients from orthopaedic clinics were 1-6 years postoperative after lumbar spine surgery or on lumbar surgery waiting list. Patients received a 12-week training intervention with European Zhineng Qigong. The intervention consisted of face-to-face group activities in non-healthcare setting (4 weekends and 2 evenings per week), and individual Zhineng Qigong training. Main health outcomes were self-reported in a 14-day pain diary, Oswestry Disability Index (ODI), Short Form 36 version 2 (SF-36v2), and EuroQol 5 Dimensions 5 Levels (EQ-5D-5L), once directly before and once directly after the intervention. Recruitment rate was 11% and retention rate was 58%. Dropouts did not report higher pain (baseline), only 3 dropped out because of lumbar spine-related pain. Adherence was median 78 h group attendance (maximum 94 h) and 14 min daily individual training. Ability to collect outcomes was 100%. Thirty patients completed (mean 15 years symptom duration). Twenty-five had degenerative lumbar disorder, and 17 history of lumbar surgery. Results showed statistically significant (within-group) improvements in pain, ODI, all SF-36v2 scales, and EQ-5D-5L. Despite low recruitment rate, recruitment was sufficient. A multicentre randomized controlled trial is proposed, with efforts to increase recruitment and retention rate. After this Zhineng Qigong intervention patients with chronic LBP and/or leg pain, also patients with considerable remaining LBP/sciatica after lumbar surgery, had significantly improved in pain and function. Results support involvement of postoperative patients in a future study. The results are promising, and this intervention needs to be further evaluated to provide the most reliable evidence. NCT04520334. Retrospectively registered 20/08/2020.


TAL effector driven induction of a SWEET gene confers susceptibility to bacterial blight of cotton.
Transcription activator-like (TAL) effectors from Xanthomonas citri subsp. malvacearum (Xcm) are essential for bacterial blight of cotton (BBC). Here, by combining transcriptome profiling with TAL effector-binding element (EBE) prediction, we show that GhSWEET10, encoding a functional sucrose transporter, is induced by Avrb6, a TAL effector determining Xcm pathogenicity. Activation of GhSWEET10 by designer TAL effectors (dTALEs) restores virulence of Xcm avrb6 deletion strains, whereas silencing of GhSWEET10 compromises cotton susceptibility to infections. A BBC-resistant line carrying an unknown recessive b6 gene bears the same EBE as the susceptible line, but Avrb6-mediated induction of GhSWEET10 is reduced, suggesting a unique mechanism underlying b6-mediated resistance. We show via an extensive survey of GhSWEET transcriptional responsiveness to different Xcm field isolates that additional GhSWEETs may also be involved in BBC. These findings advance our understanding of the disease and resistance in cotton and may facilitate the development cotton with improved resistance to BBC.


A mechanical analysis of myomere shape in fish.
An architectural analysis is offered of the trunk muscles in fish, which are arranged in a longitudinal series of geometrically complex myomeres. The myomeres are separated by myosepta, collagenous sheets with complex fibre patterns. The muscle fibres in the myomeres are also arranged in complex three-dimensional patterns. Previously, it has been proposed that the muscle fibre arrangement allows for a uniform strain distribution within the muscle. Physical constraints limit the range of shapes that fibre-reinforced materials such as muscles can adopt, irrespective of their genetic profile. The three-dimensional shapes of myosepta are predicted by mechanical modelling from the requirements for mechanical stability and prescribed muscle fibre arrangements. The model can also be used to study the force transmission and likely locations of ligaments and bones in the myosepta. The model shows that the dorsal and ventral fins are located such that unfavourable mechanical interactions with the trunk muscles are avoided. In bony fish, extensive muscular deformations (notably in the region of the horizontal septum) that would not contribute to bending are avoided by the mechanical support of the skin, intramuscular bones and ribs. In sharks, the skin plays a more prominent role in avoiding such deformations because of the absence of bony elements.


Feedback regulation of thyrotropin by thyroxine under physiological conditions.
We have studied the contribution of thyroxine (T4) itself to the feedback regulation of thyrotropin (TSH) secretion. Thyroidectomized rats received T4 replacement by one of two methods: 1) 5 or 10 micrograms T4 . 100 g-1 . day-1 in drinking water or 2) continuous subcutaneous infusion of 0.5, 1.0, or 2.0 micrograms T4 . 100 g-1 . day-1. Replacement of 5 micrograms T4 . 100 g-1 . day-1 resulted in elevated plasma T4 and TSH while triiodothyronine (T3) was decreased. Replacement of 10 micrograms T4 . 100 g-1 . day-1 resulted in greater elevation of plasma T4, a transient decrease in T3, and no change in plasma TSH. Continuous replacement of T4 resulted in a dose-dependent elevation of plasma T4, little plasma T3 generation, and inhibition of the postthyroidectomy rise in plasma TSH. The pituitary responsiveness to thyrotropin-releasing hormone (TRH) was increased in groups receiving 1.0 or 2.0 micrograms T4 . 100 g-1 . day-1. It was concluded that 1) the plasma T4 exerts a negative feedback on basal TSH secretion in addition to that due to plasma T3 and 2) small amounts of T4 replacement enhance the TSH response to exogenous TRH in short-term hypothyroid rats.


Dynamics of glycolytic regulation during adaptation of Saccharomyces cerevisiae to fermentative metabolism.
The ability of baker's yeast (Saccharomyces cerevisiae) to rapidly increase its glycolytic flux upon a switch from respiratory to fermentative sugar metabolism is an important characteristic for many of its multiple industrial applications. An increased glycolytic flux can be achieved by an increase in the glycolytic enzyme capacities (V(max)) and/or by changes in the concentrations of low-molecular-weight substrates, products, and effectors. The goal of the present study was to understand the time-dependent, multilevel regulation of glycolytic enzymes during a switch from fully respiratory conditions to fully fermentative conditions. The switch from glucose-limited aerobic chemostat growth to full anaerobiosis and glucose excess resulted in rapid acceleration of fermentative metabolism. Although the capacities (V(max)) of the glycolytic enzymes did not change until 45 min after the switch, the intracellular levels of several substrates, products, and effectors involved in the regulation of glycolysis did change substantially during the initial 45 min (e.g., there was a buildup of the phosphofructokinase activator fructose-2,6-bisphosphate). This study revealed two distinct phases in the upregulation of glycolysis upon a switch to fermentative conditions: (i) an initial phase, in which regulation occurs completely through changes in metabolite levels; and (ii) a second phase, in which regulation is achieved through a combination of changes in V(max) and metabolite concentrations. This multilevel regulation study qualitatively explains the increase in flux through the glycolytic enzymes upon a switch of S. cerevisiae to fermentative conditions and provides a better understanding of the roles of different regulatory mechanisms that influence the dynamics of yeast glycolysis.


Barriers to the use of personal health records by patients: a structured review.
An increasing focus on personal electronic health records (PHRs) offers healthcare benefits for patients, particularly those in undeserved and marginalised populations, who are at risk of receiving less effective healthcare, and may have worse health outcomes. However, PHRs are likely to favour text, technical and health literate users, and be less suitable for disadvantaged patients. These concerns have prompted this review of the literature, which seeks evidence about barriers to the adoption and continued use of PHRs, the nature of the evidence for those barriers, and the stage of PHR implementation where particular barriers apply. Searches in PubMed, Embase, CINAHL and ProQuest databases were used to retrieve articles published in English after 2003 in a refereed journal, or presented in a refereed conference or scientific meeting. After screening to remove items which were out of scope, the phase of the PHR implementation, the type of investigation, and PHR barriers were categorised using thematic coding. The search retrieved 395 items; screening identified 34 in-scope publications, which provided evidence of 21 identified barriers to patient adoption and continued use of PHRs, categorised here as Individual, Demographic, Capability, Health-related, PHR or Attitudinal factors. Barriers were identified in most phases of PHR implementation, and in most types of study. A secondary outcome identified that eleven of the publications may have introduced a bias by excluding participants who were less affluent, less capable, or marginalised. PHR barriers can interfere with the decision to start using a PHR, with the adoption process, and with continued use, and the impact of particular barriers may vary at different phases of PHR adoption. The complex interrelationships which exist between many of the barriers is suggested in some publications, and emerges more clearly from this review. Many PHR barriers appear to be related to low socioeconomic status. A better understanding is needed of how the effect of barriers is manifested, how that effect can be countered, and how planning and implementation of PHR initiatives can make allowance for patient level barriers to PHR adoption and use, with appropriate actions to mitigate the effect of those barriers for more disadvantaged patients.


Management of axillo-subclavian arterial injuries and predictors of outcome.
Although incidence of subclavian and axillary artery injury account for less than 9% of all vascular injuries, trauma to these vessels presents a surgical challenge particularly with high mortality and morbidity rates. The aim of the study was to review our experience on subclavian and axillary vessels injury and to analyze factors that may influence results of reconstructive surgery. Data of 35 patients have been recorded between January 2000 and June 2010. Mean age was 24.86 ± 8.99 years and most were males (88.57%). Regression analysis was performed to find out factors affecting outcome. The mean follow-up time was 60 months. The artery was injured in 32 of the 35 cases (91.43%) and the vein was injured in nine cases (25.71%). Seven of 24 reconstructions with saphenous graft failed as a result of thrombosis, whereas all of seven prosthetic grafts were patent during the long-term follow-up period. Except one, all surgical interventions followed by warfarin administration were patent while seven repair failures occurred among the anticoagulation-free interventions. Autologous vein graft must be the first choice; however, in case of size discrepancy, prosthetic graft usage may be an alternative approach and postoperative administration of anticoagulants may be considered at least in the presence of certain risk factors such as native artery-graft diameter discrepancy, thrombus history and prosthetic graft.