Decreased activity of the red blood cell ATPase-dependent Na+ pump in patients with cardiac syndrome X.
Marked Na(+)/Li(+) countertransport hyperactivity and post-load hyperinsulinaemia have been described in 93% of patients with cardiac syndrome X. We hypothesized that more complex abnormalities in Na(+) traffic across the cell membrane are present in these patients. The aim of the present study was to evaluate the activities of the two main transporters responsible for transmembrane Na(+) transport, i.e. the ATPase-dependent Na(+) pump and the Na(+)-K(+)-2Cl(-) co-transporter, in a selected group of patients with cardiac syndrome X. We evaluated 19 patients with cardiac syndrome X and 14 control subjects. The ATPase-dependent Na(+) pump and Na(+)-K(+)-2Cl(-) co-transport activities were assessed from Na(+)-loaded red blood cells by using nystatine, in the presence of furosemide and ouabain, as appropriate. Erythrocyte Na(+)/Li(+) countertransport activity, serum lipid and post-load (75 g of oral glucose) insulin levels were also evaluated. The V(max) of Na(+)/Li(+) countertransport (P=0.0001) and post-load insulin levels (120 min; P=0.001) were confirmed to be higher in patients with syndrome X than in controls. The V(max) of Na(+)-K(+)-2Cl(-) co-transport was similar in patients and controls. By contrast, the V(max) of the ATPase-dependent Na(+) pump was significantly lower (P=0.002) in syndrome X patients (3.13+/-0.87 mmol.h(-1).l(-1)) than in controls (4.28+/-1.10 mmol.h(-1).l(-1)). Serum total cholesterol and triacylglycerol concentrations were also higher in patients with syndrome X than in control subjects (P<0.0001). Thus decreased activity of the ATPase-dependent Na(+) pump was present in patients with cardiac syndrome X. Such an abnormality has the biological potential to augment microvascular tone and the response to constrictor stimuli via increased intracellular free Ca(2+). Of note, syndrome X patients also manifested Na(+)/Li(+) countertransport hyperactivity which, in turn, is known to induce peripheral insulin resistance and consequent abnormalities in insulin secretion and lipid turnover. Thus cardiac syndrome X appears as a multifaceted syndrome presenting with either metabolic or cardiovascular symptoms, or both, based on the expression of complex abnormalities in Na(+) traffic across the cell membrane.


Mechanical Stimulation via Muscle Activity Is Necessary for the Maturation of Tendon Multiscale Mechanics During Embryonic Development.
During embryonic development, tendons transform into a hypocellular tissue with robust tensile load-bearing capabilities. Previous work suggests that this mechanical transformation is due to increases in collagen fibril length and is dependent on mechanical stimulation via muscle activity. However, the relationship between changes in the microscale tissue structure and changes in macroscale tendon mechanics is still unclear. Additionally, the specific effect of mechanical stimulation on the multiscale structure-function relationships of developing tendons is also unknown. Therefore, the objective of this study was to measure the changes in tendon mechanics and structure at multiple length scales during embryonic development with and without skeletal muscle paralysis. Tensile testing of tendons from chick embryos was performed to determine the macroscale tensile modulus as well as the magnitude of the fibril strains and interfibrillar sliding with applied tissue strain. Embryos were also treated with either decamethonium bromide or pancuronium bromide to produce rigid or flaccid paralysis. Histology was performed to assess changes in tendon size, spacing between tendon subunits, and collagen fiber diameter. We found that the increase in the macroscale modulus observed with development is accompanied by an increase in the fibril:tissue strain ratio, which is consistent with an increase in collagen fibril length. Additionally, we found that flaccid paralysis reduced the macroscale tendon modulus and the fibril:tissue strain ratio, whereas less pronounced effects that were not statistically significant were observed with rigid paralysis. Finally, skeletal paralysis also reduced the size of collagen fibril bundles (i.e., fibers). Together, these data suggest that more of the applied tissue strain is transmitted to the collagen fibrils at later embryonic ages, which leads to an increase in the tendon macroscale tensile mechanics. Furthermore, our data suggest that mechanical stimulation during development is necessary to induce structural and mechanical changes at multiple physical length scales. This information provides valuable insight into the multiscale structure-function relationships of developing tendons and the importance of mechanical stimulation in producing a robust tensile load-bearing soft tissue.


Control of tobacco-related disease.
As ways of discouraging tobacco consumption, the effects of increases in price and in quantitative information may have been under-emphasized. To decrease the hazards of tobacco, switches from cigarettes to pipes, cigars or 'smokeless' tobacco may be useful, as may a reduction in cigarette tar delivery. Indeed, the spread of existing tar level reductions from capitalist to socialist countries might prevent tens of thousands of lung cancer deaths each year in the early decades of the next century, and (perhaps by attempts to engineer cigarettes so that smokers of lower tar cigarettes are less likely to 'compensate' by taking more smoke) it should eventually also be possible to change cigarettes so as also to reduce their effects on heart and lung disease. Changes in consumption and in composition of tobacco products are complementary, not competing, strategies. If both are pursued effectively, then although the life expectancy of old people may not be much improved, the proportion of adults who die before reaching old age will decrease substantially.


Preoperative radiation theration therapy in rectal cancer.
This paper outlines progress being made in the use of preoperative irradiation as an adjunct to surgery in the management of cancer of the rectum and rectosigmoid. Studies have shown that the normal rectal mucosa has a marked capacity for repair during fractionated radiation treatments. There is evidence that the use of preoperative irradiation reduces the number of involved lymph nodes found at operation. No marked interference with the ability of the surgeon to perform an abdominal perineal resection has been observed. In patients who subsequently undergo such a procedure, there are some data indicating that longevity may be increased when surgery is supplemented with preoperative irradiation, although further comparative studies are needed. Two studies are now under way by national clinical investigative groups.


Utility of Diffusion Modeling of Cogstate Brief Battery Test Performance in Detecting Mild Cognitive Impairment.
Cognitive testing data are essential to the diagnosis of mild cognitive impairment (MCI), and computerized cognitive testing, such as the Cogstate Brief Battery, has proven helpful in efficiently identifying harbingers of dementia. This study provides a side-by-side comparison of traditional Cogstate outcomes and diffusion modeling of these outcomes in predicting MCI diagnosis. Participants included 257 older adults (160 = normal cognition; 97 = MCI). Results showed that both traditional Cogstate and diffusion modeling analyses predicted MCI diagnosis with acceptable accuracy. Cogstate measures of recognition learning and working memory accuracy and diffusion modeling variable of decision-making efficiency (drift rate) and nondecisional time were most predictive of MCI. While participants with normal cognition demonstrated a change in response caution (boundary separation) when transitioning tasks, participants with MCI did not evidence this change.


Private dental health expenditure in Greece by region and income: comparison between the years 1987 and 1998.
The purpose of this study was to describe the evolution of private dental health expenditure in Greece, between the years 1987 and 1998, and to investigate whether there is evidence of variation by region and income. The primary data were derived from the Household Budget Survey of the National Statistical Service of Greece from which private dental expenditure was estimated using the Consumer Price Index (CPI). 1. In both years the greatest annual dental health expenditure per capita was observed in urban areas and in 1998 it had increased by 9.4% while in semi-urban and rural areas it decreased (by 33.33% and 11.25% respectively). 2. The annual expenditure per capita was distributed according to the monthly income of the population, but in 1998 the differences were more pronounced and higher income groups showed an increase of 67.2%. 3. Statistical analysis showed no significant differences in the distribution of expenditure between geographic areas over the decade (p>0.05). Private dental health expenditure in Greece is differentiated by income level and geographic region and these variations became more pronounced over the decade. Similar percentages in the distribution of dental expenditure between the geographic areas suggest that during the decade no changes have been made towards increasing the amount of dental care for members of populations in semi-urban and rural areas.


Skin dose estimation for various beam modifiers and source-to-surface distances for 6MV photons.
The purpose of this study was to learn the skin dose estimation for various beam modifiers at various source-to-surface distances (SSDs) for a 6 MV photon. Surface and buildup region doses were measured with an acrylic slab phantom and Markus 0.055 cc parallel plate (PP) ionization chamber. Measurements were carried out for open fields, motorized wedge fields, acrylic block tray fields ranging from 3 x 3 cm(2) to 30 x 30 cm(2). Twenty-five percent of the field was blocked with a cerrobend block and a Multileaf collimator (MLC). The effect of the blocks on the skin dose was measured for a 20 x 20 cm(2) field size, at 80 cm, 100 cm and 120 cm SSD. During the use of isocentric treatments, whereby the tumor is positioned at 100 cm from the source, depending on the depth of the tumor and size of the patient, the SSD can vary from 80 cm to 100 cm. To achieve a larger field size, the SSD can also be extended up to 120 cm at times. The skin dose increased as field size increased. The skin dose for the open 10 x10 cm(2) field was 15.5%, 14.8% and 15.5% at 80 cm, 100 cm and 120 cm SSDs, respectively. The skin dose due to a motorized 60 degrees wedge for the 10 x 10 cm(2) field was 9.9%, 9.5%, and 9.5% at 80 cm, 100 cm and 120 cm SSDs. The skin dose due to acrylic block tray, of thickness 1.0 cm for a 10 x 10 cm(2) field was 27.0%, 17.2% and 16.1% at 80, 100 and 120 cm SSD respectively. Due to the use of an acrylic block tray, the surface dose was increased for all field sizes at the above three SSDs and the percentage skin dose was more dominant at the lower SSD and larger field size. The skin dose for a 30 x 30 cm(2) field size at 80 cm SSD was 38.3% and it was 70.4% for the open and acrylic block tray fields, respectively. The skin doses for motorized wedge fields were lower than for open fields. The effect of SSDs on the surface dose for motorized 60 degrees wedge fields was not significant for a small field size (difference was less than 1% up to a 15 x 15 cm(2) field size), but for a larger field (field size more than 15 x 15 cm(2)), the difference in a percentage skin dose was significant. The skin dose for the open field was more than that for the MLC blocked field and lower than that for the acrylic blocked tray field. The block was 25% of the 20 x 20 cm(2) open field. Skin doses were increased as the SSD decreased and were dominant for larger field sizes. The surface dose was weakly dependent on the MLC block.


Stretch-induced growth in chicken wing muscles: effects on hereditary muscular dystrophy.
Skeletal muscle growth induced by passive stretch was characterized in the Patigialis muscle of chicks with hereditary muscular dystrophy. When the muscle of 6-wk-old chicks was stretched for 1 wk, the effects on muscle growth and on muscle pathology were variable, but in general few differences between stretched and unstretched muscles were observed. However, when the muscle of 1-wk-old chicks was stretched for 6 wk, the effects on muscle growth and on prevention of pathology were dramatic. Similar to results obtained previously when normal chick muscles were stretched [Holly et al., Am. J. Physiol. 238 (Cell Physiol. 7): C62-C71, 1980; Barnett et al., Am. J. Physiol. 239 (Cell Physiol. 8): C39-C46, 1980], stretched dystrophic muscle increased in weight (200%), cross-sectional area (107%), and fiber cross-sectional area (82%). DNA concentration, which is severalfold higher in unstretched dystrophic muscle compared with unstretched normal muscle, fell to values not different from normal values after being stretched. Nuclei per square millimeter also were the same for stretched dystrophic and stretched normal muscle. Histograms indicated that stretching induced a fiber distribution in dystrophic muscle qualitatively similar to that found in stretched normal muscle. Cytochemical observations revealed a dramatic protective effect of stretch against the progressive pathology of dystrophy. It is concluded that stretch of muscle applied to newly hatched dystrophic chicks is a powerful deterrent of symptoms characteristic of hereditary muscular dystrophy. Stretch imposed after the symptoms of dystrophy are apparent provides little, if any, protection.


In vitro expansion of mammalian telomere repeats by DNA polymerase alpha-primase.
Among the polymerases, DNA polymerase alpha-primase is involved in lagging strand DNA synthesis. A previous report indicated that DNA polymerase alpha-primase initiates primer RNA synthesis with purine bases on a single-stranded G-rich telomere repeat. In this study, we found that DNA polymerase alpha-primase precisely initiated with adenosine opposite the 3'-side thymidine in the G-rich telomere repeat 5'-(TTAGGG)(n)-3' under rATP-rich conditions. Then, DNA polymerase alpha-primase synthesized the nascent DNA fragments by extending the primer. It was remarkable that DNA polymerase alpha-primase further expanded the product DNA far beyond the length of the template DNA, as ladders of multiple hexanucleotides on polyacrylamide gel electrophoresis. Using an oligomer duplex 5'-A(GGGTTA)(5)-3'/5'-(TAACCC)(5)T-3' as a template-primer, we show that both the Klenow fragment of Escherichia coli DNA polymerase I and HIV reverse transcriptase could expand telomere DNA sequences as well, giving products greater than the size of the template DNA. The maximum product lengths with these polymerases were approximately 40-90 nt longer than the template length. Our data imply that DNA polymerases have an intrinsic activity to expand the hexanucleotide repeats of the telomere sequence by a slippage mechanism and that DNA polymerase alpha uses both the repeat DNA primers and the de novo RNA primers for expansion. On the other hand, a plasmid harboring a eukaryotic telomere repeat showed remarkable genetic instability in E.coli. The telomere repeats exhibited either expansions or deletions by multiple hexanucleotide repeats during culture for a number of generations, suggesting involvement of the slippage mechanism in the instability of telomeric DNA in vivo.


[Construction and expression of replication-deficient recombinant adenovirus vector with hNET gene by adeasy-1 system].
To construct and identify the recombinant replication deficient adenovirus vector which codes for human Norepinephrine Transporter (hNET) gene by using the method of homogenous recombination in bacteria. hNET gene was obtained from the recombinant plasmid pCMV5 via Kpn I + Xba I digestion, and subcloned into E1 deleted expression plasmid pAdtrack-CMV shuttle vector, forming transfer vector pAdtrack-CMV-hNET. Then it was linearized with Pme I followed by homologous recombination with bone plasmid pAdEasy-1 in BJ5183 cells to generate recombinant plasmid Ad-hNET. The DNA of identified Ad-hNET was digested with Pac I and transfected to HEK293 cells by liposome-mediated method to package recombinant adenovirus. The PCR technique was applied to detect the target gene and Western Blotting to verify the expression of hNET. The titre of the Ad-hNET was measured with the aid of green fluorescence protein (GFP) expression after multiplication and purification. By sequencing, it was confirmed that the product was the gene of hNET. PCR test, restriction endonuclease digestion and Western Blotting confirmed the successful construction of the recombinants Ad-hNET. The titre of purified recombinant adenovirus Ad-hNET was 1.2 X 10(10) pfu/mL. The recombinant adenovirus with the hNET gene was constructed successfully. It will be helpful for the further investigation of its potentiality to be applied in the tumors targeted therapeutic strategy.


Genes required for completion of import of proteins into the endoplasmic reticulum in yeast.
Yeast secretory mutants sec53 and sec59 define a posttranslational stage in the penetration of glycoprotein precursors into the endoplasmic reticulum (ER). In the previous report we showed that at the restrictive temperature (37 degrees C) these mutants accumulate enzymatically inactive and incompletely glycosylated forms of the secretory enzyme invertase and the vacuolar enzyme carboxypeptidase Y. Cell fractionation experiments reveal that these precursor forms remain firmly bound to the ER membrane. However, upon return to the permissive temperature (24 degrees C), the invertase precursors are glycosylated, become partially active, and are secreted. Thermoreversible conversion does not require protein synthesis, but does require energy. In contrast to the effect of these mutations, inhibition of oligosaccharide synthesis with tunicamycin at 37 degrees C causes irreversible accumulation of unglycosylated invertase. The effect of the drug is exaggerated by high temperature since unglycosylated invertase synthesized in the presence of tunicamycin at 25 degrees C is secreted. A portion of the invertase polypeptide accumulated at 37 degrees C is preserved when membranes from sec53 and sec59 are treated with trypsin. In the presence of Triton X-100 or saponin, the invertase is degraded completely. The protected fragment appears to represent a portion of the invertase polypeptide that is embedded in or firmly associated with the ER membrane. This association may develop early during the synthesis of invertase, so that in the absence of translocation, some of the completed polypeptide chain remains exposed on the cytoplasmic surface of the ER.


HUE-WAVELENGTH RELATION MEASURED BY COLOR-NAMING METHOD FOR THREE RETINAL LOCATIONS.
A method of hue measurement, in which an absolute color-naming procedure is utilized, has been applied to spectral stimuli delivered as flashes at 0 degrees, 20 degrees, and 40 degrees eccentricity in an otherwise dark field. The method yields very reliable measures, especially at 0 degrees. Color-naming at 0 degrees differs little from that at 20 degrees, but a marked deterioration of performance occurs between 20 and 40 degrees. This is reflected by a reduction in red and especially green responses, and a lower reliability of the measurements. Additional estimates were also obtained which showed a decrease in measured saturation but increasing reliability of the saturation measurements with increasing eccentricity.


Demonstration of safety of probiotics -- a review.
Probiotics are commonly defined as viable microorganisms (bacteria or yeasts) that exhibit a beneficial effect on the health of the host when they are ingested. They are used in foods, especially in fermented dairy products, but also in pharmaceutical preparations. The development of new probiotic strains aims at more active beneficial organisms. In the case of novel microorganisms and modified organisms the question of their safety and the risk to benefit ratio have to be assessed. Lactic acid bacteria (LAB) in foods have a long history of safe use. Members of the genera Lactococcus and Lactobacillus are most commonly given generally-recognised-as-safe (GRAS) status whilst members of the genera Streptococcus and Enterococcus and some other genera of LAB contain some opportunistic pathogens. Lactic acid bacteria are intrinsically resistant to many antibiotics. In many cases resistances are not, however, transmissible, and the species are also sensitive to many clinically used antibiotics even in the case of a lactic acid bacteria- associated opportunistic infection. Therefore no particular safety concern is associated with intrinsic type of resistance. Plasmid-associated antibiotic resistance, which occasionally occurs, is another matter because of the possibility of the resistance spreading to other, more harmful species and genera. The transmissible enterococcal resistance against glycopeptide antibiotics (vancomycin and teicoplanin) is particularly noteworthy, as vancomycin is one of the last effective antibiotics left in the treatment of certain multidrug-resistant pathogens. New species and more specific strains of probiotic bacteria are constantly identified. Prior to incorporating new strains into products their efficacy should be carefully assessed, and a case by case evaluation as to whether they share the safety status of traditional food-grade organisms should be made. The current documentation of adverse effects in the literature is reviewed. Future recommendations for the safety of already existing and new probiotics will be given.


Histamine H1 receptor blockade predominantly impairs sensory processes in human sensorimotor performance.
Centrally active antihistamines impair cognitive performance, particularly sensorimotor performance. The aim of the present study was to further elucidate the scarcely studied subprocesses involved in sensorimotor performance, which may be affected by H1 receptor blockade. Better knowledge about the cognitive deficits associated with histamine dysfunction can contribute to better treatment of clinical disorders in which histamine hypofunction may be a contributing factor, such as in schizophrenia. Interactions of dexchlorpheniramine with specific task manipulations in a choice reaction time task were studied. Task demands were increased at the level of sensory subprocesses by decreasing stimulus quality, and at the level of motor subprocesses by increasing response complexity. A total of 18 healthy volunteers (9 female) aged between 18 and 45 years participated in a three-way, double-blind, crossover design. Treatments were single oral doses of 4 mg dexchlorpheniramine, 1 mg lorazepam and placebo. Behavioural effects were assessed by measuring reaction times and effects on brain activity by event-related potentials. Dexchlorpheniramine significantly slowed reaction times, but did not significantly interact with task manipulations. However, it did significantly interact with stimulus quality, as measured by event-related potentials. Lorazepam slowed reaction times and interacted with perceptual manipulations, as shown by effects on reaction times. The results confirm that the histamine system is involved in sensory information processing and show that H1 blockade does not affect motoric information processing. Histamine hypofunction in clinical disorders may cause impaired sensory processing, which may be a drug target.


Barriers to accrual and enrollment in brain tumor trials.
Many factors contribute to the poor survival of malignant brain tumor patients, some of which are not easily remedied. However, one contributor to the lack of progress that may be modifiable is poor clinical trial accrual. Surveys of brain tumor patients and neuro-oncology providers suggest that clinicians do a poor job of discussing clinical trials with patients and referring patients for clinical trials. Yet, data from the Cancer Action Network of the American Cancer Society suggest that most eligible oncology patients asked to enroll on a clinical trial will agree to do so. To this end, the Society for Neuro-Oncology (SNO) in collaboration with the Response Assessment in Neuro-Oncology (RANO) Working Group, patient advocacy groups, clinical trial cooperative groups, including the Adult Brain Tumor Consortium (ABTC), and other partners are working together with the intent to double clinical trial accrual over the next 5 years. Here we describe the factors contributing to poor clinical trial accrual in neuro-oncology and offer possible solutions.


Rapid development of drug-resistant mutants of poliovirus.
Guanidine hydrochloride is a potent inhibitor of poliovirus synthesis in cell culture. However, the viral progeny which do grow in the presence of guani-dine may become approximately 10,000 times more resistant to the drug. The phenomenon of drug resistance poses yet another problem in the search for a satisfactory viral chemotherapeutic agent.


Sensorimotor factors affecting gait variability in older people--a population-based study.
Intra-individual gait variability predicts falls and disability in older people. Knowledge of factors that contribute to gait variability may lead to interventions aimed at reducing decline in mobility and falls risk. The aim of this population-based study was to examine whether poorer performance on a range of sensorimotor measures was associated with greater gait variability. Individuals aged 60-86 years (n = 412) were randomly selected from the Southern Tasmanian electoral roll. Spatial (step length and step width) and temporal (step time and double support time [DST]) gait measures were recorded with a GAITRite walkway. Variability for each gait measure was the standard deviation of measurements recorded during six walks. Sensorimotor measures included visual contrast sensitivity, lower limb proprioception, quadriceps strength, reaction time, and body sway (eyes open and closed). Regression analysis was used to determine the relationships between sensorimotor measures and gait variability. Greater sway on a foam mat (eyes closed) was associated with greater variability in all gait measures (p < .05). Slower reaction time was associated with greater variability in both temporal gait measures (p < .05), whereas poorer proprioception was only associated with greater DST variability (p = .01) and weaker quadriceps strength with greater step time variability. Other sensorimotor factors were not independently associated with gait variability. Body sway, reaction time, quadriceps strength, and proprioception are likely factors that may explain gait variability in the general older population. Further research is warranted to determine causality of these associations and whether intervention programs addressing these factors may reduce gait variability in older people.


Geographic patterns of the climate sensitivity of lakes.
Climate change is a well-recognized threat to lake ecosystems and, although there likely exists geographic variation in the sensitivity of lakes to climate, broad-scale, long-term studies are needed to understand this variation. Further, the potential mediating role of local to regional ecological context on these responses is not well documented. In this study, we examined relationships between climate and water clarity in 365 lakes from 1981 to 2010 in two distinct regions in the northeastern and midwestern United States. We asked (1) How do climate-water-clarity relationships vary across watersheds and between two geographic regions? and (2) Do certain characteristics make some lakes more climate sensitive than others? We found strong differences in climate-water-clarity relationships both within and across the two regions. For example, in the northeastern region, water clarity was often negatively correlated with summer precipitation (median correlation = -0.32, n = 160 lakes), but was not correlated with summer average maximum temperature (median correlation = 0.09, n = 205 lakes). In the midwestern region, water clarity was not related to summer precipitation (median correlation = -0.04), but was often negatively correlated with summer average maximum temperature (median correlation = -0.18). There were few strong relationships between local and sub-regional ecological context and a lake's sensitivity to climate. For example, ecological context variables explained just 16-18% of variation in summer precipitation sensitivity, which was most related to total phosphorus, chlorophyll a, lake depth, and hydrology in both regions. Sensitivity to summer maximum temperature was even less predictable in both regions, with 4% or less of variation explained using all ecological context variables. Overall, we identified differences in the climate sensitivity of lakes across regions and found that local and sub-regional ecological context weakly influences the sensitivity of lakes to climate. Our findings suggest that local to regional drivers may combine to influence the sensitivity of lake ecosystems to climate change, and that sensitivities among lakes are highly variable within and across regions. This variability suggests that lakes are sensitive to different aspects of climate change (temperature vs. precipitation) and that responses of lakes to climate are heterogeneous and complex.


[Anorgasmy prevalence in women attended at Familiar Medicine Unit no. 1 in Obregon, Sonora, Mexico].
To estimate the prevalence of anorgasmy in women. An observational, descriptive and transversal study was done from August 2002 to January 2003 surveying women with sexual activity in a clinic of the Mexican Institute of Social Security in Obregon, Sonora. The questionnaire was validated by the UNAM. The analyzed variables were: age, scholar degree, the age in which women started sexual activity, number of children, marital status, the number of sexual partners, pleasure to sex for the women, satisfaction and feeling like doing sex, who decides and begins to do sex, frequency of sexual intercourse, knowledge about orgasm and one's own experience, as well as psychosomatic symptoms. Data were analyzed by descriptive statistics, chi square test and Likert's scale. Seventy-three women were surveyed, with ages between 16 and 46 years. Anorgasmy frequency was of 6.8%; 53.4% of the women had secondary education and 37% superior education. Time of active sexual life varied between 1 and 30 years; the knowledge about orgasm was of 74%. The orgasmic dysfunction is lower in this region than that reported in the bibliography, this could be due to the greater scholar degree of women, social and cultural issues, and the women's independence. Nevertheless, the health team must be qualified to detect and treat it, in order to avoid complications.


Clustering patients on the basis of their individual course of low back pain over a six month period.
Several researchers have searched for subgroups in the heterogeneous population of patients with non-specific low back pain (LBP). To date, subgroups have been identified based on psychological profiles and the variation of pain. This multicentre prospective observational study explored the 6- month clinical course with measurements of bothersomeness that were collected from weekly text messages that were sent by 176 patients with LBP. A hierarchical cluster analysis, Ward's method, was used to cluster patients according to the development of their pain. Four clusters with distinctly different clinical courses were described and further validated against clinical baseline variables and outcomes. Cluster 1, a "stable" cluster, where the course was relatively unchanged over time, contained young patients with good self- rated health. Cluster 2, a group of "fast improvers" who were very bothered initially but rapidly improved, consisted of patients who rated their health as relatively poor but experienced the fewest number of days with bothersome pain of all the clusters. Cluster 3 was the "typical patient" group, with medium bothersomeness at baseline and an average improvement over the first 4-5 weeks. Finally, cluster 4 contained the "slow improvers", a group of patients who improved over 12 weeks. This group contained older individuals who had more LBP the previous year and who also experienced most days with bothersome pain of all the clusters. It is possible to define clinically meaningful clusters of patients based on their individual course of LBP over time. Future research should aim to reproduce these clusters in different populations, add further clinical variables to distinguish the clusters and test different treatment strategies for them.


Nutritional status of iodine in pregnant women in Catalonia (Spain): study on hygiene-dietetic habits and iodine in urine.
It is a priority to achieve an adequate nutritional status of iodine during pregnancy since iodine deficiency in this population may have repercussions on the mother during both gestation and post partum as well as on the foetus, the neonate and the child at different ages. According to the WHO, iodine deficiency is the most frequent cause of mental retardation and irrreversible cerebral lesions around the world. However, few studies have been published on the nutritional status of iodine in the pregnant population within the Primary Care setting, a health care level which plays an essential role in the education and control of pregnant women. Therefore, the aim of the present study is: 1.- To know the hygiene-dietetic habits related to the intake of foods rich in iodine and smoking during pregnancy. 2.- To determine the prevalence of iodine deficiency and the factors associated with its appearance during pregnancy. We will perform a cluster randomised, controlled, multicentre trial. Randomisation unit: Primary Care Team. 898 pregnant women over the age of 17 years attending consultation to a midwife during the first trimester of pregnancy in the participating primary care centres. consumption of iodine-rich foods and iodine deficiency. Points of assessment: each trimester of the gestation. group education during the first trimester of gestation on healthy hygiene-dietetic habits and the importance of an adequate iodine nutritional status. descriptive analysis of all variables will be performed as well as multilevel logistic regression. All analyses will be done carried out on an intention to treat basis and will be fitted for potential confounding factors and variables of clinical importance. Evidence of generalised iodine deficiency during pregnancy could lead to the promotion of interventions of prevention such as how to improve and intensify health care educational programmes for pregnant women. ClinicalTrials.gov: NCT01301768.


Genetic counseling graduate program faculty perspectives on sharing education materials among programs.
Rapid advancements in genetics care requires responsive genetic counseling (GC) training capable of integrating new discoveries and practice into their curricula. The utilization of shared or standardized educational resources may address this need. Recognizing the potential of shared resources, the Pharmacogenetics (PGx) Working Group of the NSGC Precision Medicine Special Interest Group (SIG) launched a standardized education module using a flipped-classroom format to provide all GC programs equal access to PGx expertise and alleviate the burden of curriculum development. Following the initial success of the program, we aimed to explore the utilization of shared and standardized education resources more broadly, and better understand the perspectives of GC program faculty regarding their use. Twenty-nine program faculty representing at least 14 programs responded to an online survey. The majority (n = 21) reported sharing educational materials with another GC program, and 90% of those reported the shared materials to be beneficial as they promote collaboration, efficiency, address a gap in content, and provide access to experts. Similar benefits were described when using a standardized curriculum, which was defined as standardized lectures and activities created about a particular topic and made available to all genetic counseling programs; 16 participants indicated they would be very likely or likely to use a standardized curriculum. A secondary aim of the survey was to assess the existing PGx module that utilizes a flipped-classroom format. Overall, the PGx module was well received, indicating that a standardized shared module is well-suited for instruction on emerging and specialty topics. All participants believed the flipped-classroom format to be very or somewhat beneficial. In summary, results indicate that shared educational materials, including standardized education modules, are a potential solution to challenges related to efficiency and access to content experts in GC education, and program leadership is receptive to using them.


Thermodynamic impact of abasic sites on simulated translesion DNA synthesis.
Loss of a base in DNA and the creation of an abasic (apurinic/apyrimidinic, AP) site is a frequent lesion that may occur spontaneously, or as a consequence of the action of DNA-damaging agents. The AP lesion is mutagenic or lethal if not repaired. We report a systematic thermodynamic investigation by differential scanning calorimetry on the evolution, during primer extension, of a model AP site in chemically simulated DNA translesion synthesis. Incorporation of dAMP (deoxyadenosine monophosphate), as well as dTMP (deoxythymidine monophosphate), opposite an AP site is enthalpically unfavorable, although incorporation of dTMP is more enthalpically unfavorable than that of dAMP. This finding is in a good agreement with experimental data showing that AP sites block various DNA polymerases of eukaryotic and prokaryotic origin and that, if bypassed, dAMP is preferentially inserted, whereas insertion of dTMP is less likely. The results emphasize the importance of thermodynamic contributions to the insertion of nucleotides opposite an AP site by DNA polymerases.


Articulation rate in childhood and adolescence: Hebrew speakers.
This study aimed to quantify articulation rate among Hebrew speaking children and adolescents across a wide age range, and to assess whether age-related differences vary according to metric. One hundred and forty children, in seven age groups, participated in this cross-sectional study. All children were recorded during conversation and a picture description task, and articulation rate was measured using three metrics: word per minute (WPM), syllable per second (SPS) and phone per second (PPS). A significant increase in articulation rate was observed with age. Rate measurements during conversation were significantly faster than in picture description, and no gender differences were found. In general, the SPS and PPS metrics yielded equivalent results, which were different from those obtained with the WPM metric. Articulation rate among normally fluent children and adolescents increased with age. Furthermore, an increase in rate was evident after the age of 13 years.


Description of antibiotic use variability among US nursing homes using electronic health record data.
Antibiotics are frequently prescribed in nursing homes; national data describing facility-level antibiotic use are lacking. The objective of this analysis was to describe variability in antibiotic use in nursing homes across the United States using electronic health record orders. A retrospective cohort study of antibiotic orders for 309,884 residents in 1,664 US nursing homes in 2016 were included in the analysis. Antibiotic use rates were calculated as antibiotic days of therapy (DOT) per 1,000 resident days and were compared by type of stay (short stay ≤100 days vs long stay >100 days). Prescribing indications and the duration of nursing home-initiated antibiotic orders were described. Facility-level correlations of antibiotic use, adjusting for resident health and facility characteristics, were assessed using multivariate linear regression models. In 2016, 54% of residents received at least 1 systemic antibiotic. The overall rate of antibiotic use was 88 DOT per 1,000 resident days. The 3 most common antibiotic classes prescribed were fluoroquinolones (18%), cephalosporins (18%), and urinary anti-infectives (9%). Antibiotics were most frequently prescribed for urinary tract infections, and the median duration of an antibiotic course was 7 days (interquartile range, 5-10). Higher facility antibiotic use rates correlated positively with higher proportions of short-stay residents, for-profit ownership, residents with low cognitive performance, and having at least 1 resident on a ventilator. Available facility-level characteristics only predicted a small proportion of variability observed (Model R2 version 0.24 software). Using electronic health record orders, variability was found among US nursing-home antibiotic prescribing practices, highlighting potential opportunities for targeted improvement of prescribing practices.


Late solitary cerebral metastasis from renal cell carcinoma: a case report and review of the literature.
Metastatic disease to the brain occurs in 5%-10% of cases of renal cell carcinoma (RCC). Solitary involvement of the brain is less common with a reported incidence of 0.6%-2.5% in large autopsy series. In a review of the literature, only five cases of solitary brain metastasis from RCC with a latency period greater than 10 years have been documented. In this article, we report the case of an 86-year-old white female who developed a brain metastasis 15 years after nephrectomy. As a result of our experience with this patient and a review of the literature, we conclude that in patients with a history of RCC, metastatic lesions from the primary tumor must remain in the differential when evaluating any subsequent brain lesion, as metastases may appear well over a decade after nephrectomy.


Stability of phase-contrast tomography.
Phase-contrast tomography (PCT) allows three-dimensional imaging of objects that display insufficient contrast for conventional absorption-based tomography. We prove that PCT is stable with respect to high-frequency noise in experimental phase-contrast data, unlike conventional tomography, which is known to be mildly unstable. We use known properties of the three-dimensional x-ray transform and transport-of-intensity equation to construct a matrix representation of the forward PCT operator. We then invert this formula to show that, under natural boundary conditions, the PCT reconstruction operator exists and leads to a unique solution. We show that the singular values s(n) of the reconstruction operator have asymptotic behavior s(n)=O(n(-3/2)), guaranteeing the mathematical stability of the reconstruction process.


Genetic transformation of Drosophila melanogaster with an autonomous P element: phenotypic and molecular analyses of long-established transformed lines.
Following transformation of a Drosophila melanogaster true M strain with an autonomous P element, six lines were established and monitored for their molecular and phenotypic properties during a 4-yr period. The number of P elements increased with time in all the lines but the rate of increase differed among lines. Furthermore, degenerate elements arose in each of the lines during propagation. By the end of the 4th yr, the total number of elements in every line was similar to that of a very strong P strain.--At the phenotypic level, all of the transformed lines evolved high P activity, but only three developed complete or nearly complete regulatory ability. The other three lines attained only intermediate levels of regulation over the 4-yr period. One of these lines was particularly noteworthy. Although it contained as many as 55 P elements per genome (20 of which were potentially complete) and had extremely high P activity potential, it continued to exhibit limited regulatory ability. In addition, when females of this line were maintained at high temperatures, the ability to suppress P activity was even further diminished. A strain with this combination of molecular and phenotypic properties, in an apparently stable configuration, has not been previously described.--The results are discussed in the context of the possible role of degenerate elements in regulating P element expression.


Characterization of long-term elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate beads in vitro by two distinct sample collection methods.
OBJECTIVE To characterize long-term elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CI-CSH) beads in vitro by comparing 2 distinct sample collection methods designed to mimic 2 in vivo environments. SAMPLES 162 CI-CSH beads containing 4.6 mg of carboplatin (2.4 mg of platinum/bead). PROCEDURES For method 1, which mimicked an in vivo environment with rapid and complete fluid exchange, each of 3 plastic 10-mL conical tubes contained 3 CI-CSH beads and 5 mL of PBS solution. Eluent samples were obtained by evacuation of all fluid at 1, 2, 3, 6, 9, and 12 hours and 1, 2, 3, 6, 9, 12, 15, 18, 22, 26, and 30 days. Five milliliters of fresh PBS solution was then added to each tube. For method 2, which mimicked an in vivo environment with no fluid exchange, each of 51 tubes (ie, 3 tubes/17 sample collection times) contained 3 CI-CSH beads and 5 mL of PBS solution. Eluent samples were obtained from the assigned tubes for each time point. All samples were analyzed for platinum content by inductively coupled plasma-mass spectrometry. RESULTS Platinum was released from CI-CSH beads for 22 to 30 days. Significant differences were found in platinum concentration and percentage of platinum eluted from CI-CSH beads over time for each method. Platinum concentrations and elution percentages in method 2 samples were significantly higher than those of method 1 samples, except for the first hour measurements. CONCLUSIONS AND CLINICAL RELEVANCE Sample collection methods 1 and 2 may provide estimates of the minimum and maximum platinum release, respectively, from CI-CSH beads in vivo.


Beneficial actions of superoxide dismutase and catalase in stunned myocardium of dogs.
Recent evidence suggests that oxygen free radicals may partially mediate irreversible ischemia-reperfusion injury in the myocardium. In the present study, the effect of a combination of two oxygen free radical scavengers, superoxide dismutase plus catalase (SOD + CAT), on the recovery of subendocardial segment function following 15 min of coronary artery occlusion followed by 3 h of reperfusion ("stunned" myocardium) was compared with a control group in barbital-anesthetized dogs. Myocardial segment shortening (%SS) in the subendocardium of nonischemic and ischemic areas was measured by sonomicrometry and regional blood flow by radioactive microspheres. SOD and CAT were infused into the left atrium 30 min before and throughout the occlusion period. Compared with the control group, %SS in the subendocardium of the ischemic region was significantly (P less than 0.05) greater in the SOD plus CAT-treated group during occlusion and throughout reperfusion. Since there were no significant differences in hemodynamics or regional myocardial blood flow between the SOD plus CAT and the control groups, these results suggest that toxic oxygen free radicals may be partially involved in the reversible ischemic injury that occurs during short periods of coronary occlusion followed by reperfusion.


Viral transmission by blood products: a perspective of events covered by the recent tribunal of enquiry into the Irish Blood Transfusion Board.
The recent Tribunal of Enquiry into the Irish Blood Transfusion Board considered the transmission of the Hepatitis C virus (HCV) from the Irish perspective, considering particularly the medico-legal aspects of the specific transmission of HCV by anti-Rhesus D immunoglobulin (anti-D) manufactured by the Irish Blood Transfusion Service Board. However, there have been many other transmission episodes of HCV by intravenous immunoglobulin (IVIG) preparations and this brief review on the viral safety of immunoglobulin preparations considers the wider aspects of HCV transmission by immunoglobulin preparations.


A Fluorescence Resonance Energy Transfer Aptasensor for Aflatoxin B1 Based on Ligand-Induced ssDNA Displacement.
In this study, a fluorescence resonance energy transfer (FRET)-based aptasensor for the detection of aflatoxin B1 (AFB1) was designed using a carboxyfluorescein (FAM)-labeled aptamer and short complementary DNA (cDNA) labeled with low molecular quencher RTQ1. The sensing principle was based on the detection of restored FAM-aptamer fluorescence due to the ligand-induced displacement of cDNA in the presence of AFB1, leading to the destruction of the aptamer/cDNA duplex and preventing the convergence of FAM and RTQ1 at the effective FRET distance. Under optimal sensing conditions, a linear correlation was obtained between the fluorescence intensity of the FAM-aptamer and the AFB1 concentration in the range of 2.5-208.3 ng/mL with the detection limit of the assay equal to 0.2 ng/mL. The assay time was 30 min. The proposed FRET aptasensor has been successfully validated by analyzing white wine and corn flour samples, with recovery ranging from 76.7% to 91.9% and 84.0% to 86.5%, respectively. This work demonstrates the possibilities of labeled cDNA as an effective and easily accessible tool for sensitive AFB1 detection. The homogeneous FRET aptasensor is an appropriate choice for contaminant screening in complex matrices.


Evaluation of the transcutaneous oxygen method used at 37 degrees C for measurement of reactive hyperaemia in the skin.
The transcutaneous oxygen electrode used at an electrode temperature of 35-37 degrees C measures changes in PO2 at the skin surface that are mainly determined by changes in skin blood flow. Simultaneously, information about tissue PO2 in a defined skin area can be obtained by calculation. The reproducibility of this new application of the transcutaneous PO2 technique and factors influencing the recordings were analysed. Reactive hyperaemia was best recorded at 37 degrees C, where the coefficient of variation (CV) was 14% and the correlation coefficient was 0.90 between duplicate measurements within 15 min (n = 57). The day-to-day variation was greater (CV 19-28%). No significant spatial differences in reactive hyperaemia were noted when the distance between the electrodes was no more than 3 cm on the same forearm. A slightly lower reactive hyperaemia was noted when the arm with the electrode was elevated above the level of the heart, as compared with a lower position. Age and sex had significant influence, children (n = 34) exhibiting a greater postocclusive peak tcPO2 response than adults (n = 67). In adults, females (n = 30) showed significantly higher peak tcPO2 values during reactive hyperaemia than males. This method is a new application of the tcPO2 technique and can be used as a noninvasive tool for simultaneous blood flow and tissue PO2 studies in microcirculatory research.


Multiple internal sorting determinants can contribute to the trafficking of cruciferin to protein storage vacuoles.
Trafficking of seed storage proteins to protein storage vacuoles is mediated by carboxy terminal and internal sorting determinants (ISDs). Protein modelling was used to identify candidate ISDs residing near surface-exposed regions in Arabidopsis thaliana cruciferin A (AtCruA). These were verified by AtCruA fusion to yellow fluorescent protein (YFP) and expression in developing embryos of A. thaliana. As the presence of endogenous cruciferin was found to mask the effects of weaker ISDs, experiments were conducted in a line that was devoid of cruciferin. In total, nine ISDs were discovered and a core determinant defined using a series of alanine scanning and deletion mutant variants. Coupling of functional data from AtCruA ISD-YFP fusions with statistical analysis of the physiochemical properties of analogous regions from several 11/12S globulins revealed that cruciferin ISDs likely adhere to the following rules: (1) ISDs are adjacent to or within hydrophilic, surface-exposed regions that serve to present them on the protein's surface; (2) ISDs generally have a hydrophobic character; (3) ISDs tend to have Leu or Ile residues at their core; (4) ISDs are approximately eight amino acids long with the physiochemical consensus [hydrophobic][preferably charged][small or hydrophobic, but not tiny][IL][polar, preferably charged][small, but not charged][hydrophobic, not charged, preferably not polar][hydrophobic, not tiny, preferably not polar]. Microscopic evidence is also presented for the presence of an interconnected protein storage vacuolar network in embryo cells, rather than discreet, individual vacuoles.


Microtubule-Targeting Agents Eribulin and Paclitaxel Differentially Affect Neuronal Cell Bodies in Chemotherapy-Induced Peripheral Neuropathy.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anticancer treatment with microtubule-targeted agents (MTAs). The frequency of severe CIPN, which can be dose limiting and even life threatening, varies widely among different MTAs. For example, paclitaxel induces a higher frequency of severe CIPN than does eribulin. Different MTAs also possess distinct mechanisms of microtubule-targeted action. Recently, we demonstrated that paclitaxel and eribulin differentially affect sciatic nerve axons, with paclitaxel inducing more pronounced neurodegenerative effects and eribulin inducing greater microtubule stabilizing biochemical effects. Here, we complement and extend these axonal studies by assessing the effects of paclitaxel and eribulin in the cell bodies of sciatic nerve axons, housed in the dorsal root ganglia (DRG). Importantly, the microtubule network in cell bodies is known to be significantly more dynamic than in axons. Paclitaxel induced activating transcription factor 3 expression, a marker of neuronal stress/injury. Paclitaxel also increased expression levels of acetylated tubulin and end binding protein 1, markers of microtubule stability and growth, respectively. These effects are hypothesized to be detrimental to the dynamic microtubule network within the cell bodies. In contrast, eribulin had no significant effect on any of these parameters in the cell bodies. Taken together, DRG cell bodies and their axons, two distinct neuronal cell compartments, contain functionally distinct microtubule networks that exhibit unique biochemical responses to different MTA treatments. We hypothesize that these distinct mechanistic actions may underlie the variability seen in the initiation, progression, persistence, and recovery from CIPN.


Genetic variation of SCNN1A influences lung diffusing capacity in cystic fibrosis.
Epithelial Na channels (ENaCs) play a crucial role in ion and fluid regulation in the lung. In cystic fibrosis (CF), Na hyperabsorption results from ENaC overactivity, leading to airway dehydration. Previous work has demonstrated functional genetic variation of SCNN1A (the gene encoding the ENaC α-subunit), manifesting as an alanine (A) to threonine (T) substitution at amino acid 663, with the αT663 variant resulting in a more active channel. We assessed the influence of genetic variation of SCNN1A on the diffusing capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO), together with alveolar-capillary membrane conductance (DM), pulmonary capillary blood volume, and alveolar volume (VA) at rest and during peak exercise in 18 patients with CF (10 homozygous for αA663 (AA group) and 8 with at least one T663 allele (AT/TT group)). Because of the more active channel, we hypothesized that the AT/TT group would show a greater increase in DLCO, DLNO, and DM with exercise because of exercise-mediated ENaC inhibition and subsequent attenuation of Na hyperabsorption. The AT/TT group had significantly lower pulmonary function, weight, and body mass index than the AA group. Both groups had similar peak workloads, relative peak oxygen consumptions, and cardiopulmonary responses to exercise. The AT/TT group demonstrated a greater increase in DLNO, DLNO/VA, and DM in response to exercise (% increases: DLNO = 18 ± 11 vs 41 ± 38; DLNO/VA = 14 ± 21 vs 40 ± 37; DM = 15 ± 11 vs 41 ± 38, AA vs AT/TT, respectively). There were no differences between groups in absolute diffusing capacity measures at peak exercise. These results suggest that genetic variation of the α-subunit of ENaC differentially affects the diffusing capacity response to exercise in patients with CF.


Infection of mice lacking the common cytokine receptor gamma-chain (gamma(c)) reveals an unexpected role for CD4+ T lymphocytes in early IFN-gamma-dependent resistance to Toxoplasma gondii.
Mice lacking the common cytokine receptor gamma-chain (gamma(c)) gene exhibit defective development of NK cells and CD8+ T cells and greatly diminished production of IFN-gamma. Because resistance of SCID mice to Toxoplasma gondii requires IL-12-dependent IFN-gamma production by NK cells, we expected that gamma(c)-deficient mice would succumb rapidly to the parasite. Surprisingly, however, most gamma(c)-deficient mice survived the acute phase of T. gondii infection. As in wild-type mice, this resistance required IL-12 and IFN-gamma; nevertheless, whereas wild-type mice depleted of CD4+ T cells survived, anti-CD4+ treated gamma(c)-deficient mice displayed diminished production of IFN-gamma and all succumbed to acute infection. These data not only reveal a role for CD4+ T lymphocytes in IFN-gamma-dependent host defense but also establish SCID and gamma(c)-deficient mice as powerful complementary tools for assessing the function of NK vs CD4+ T cells in immunopathophysiologic responses.


The restricted cellular host range of human herpesvirus 8.
A selection of primary and transformed cell types were evaluated for their susceptibility to infection with human herpesvirus 8 (HHV-8)/Kaposi's sarcoma-associated herpesvirus. Sources of HHV-8 included Kaposi's sarcoma lesion punch biopsies that were either cocultured directly with target cells or that were first cocultured with human lymphocytes to derive HHV-8-containing fluids that were inoculated onto target cells. HHV-8 was also obtained from primary effusion lymphoma-derived cell lines. Techniques to detect infection included the PCR, immunofluorescence assays and in situ hybridization. Susceptible cells included human umbilical cord blood mononuclear cells (UCMC), adult CD19 B cells, macrophages and certain endothelial cells of human and animal origin, including some that are transformed with human papilloma virus type 16 E6 and E7 genes. The infection of lymphocytes did not yield established lymphoblastoid cell lines (LCL) and virus infection persisted for only 4-7 days. However, long-term HHV-8 infection of UCMC could be achieved by coinfection with Epstein-Barr virus. HHV-8 could also infect UCMC LCL recently derived by Epstein-Barr virus transformation, but long-established LCL could not be infected with HHV-8. These data provide further biological evidence in cell culture for the limited cellular host range of HHV-8 to CD19 B cells, macrophages, and certain endothelial cells.


Sclerotherapy of esophageal varices.
Sclerotherapy of esophageal varices is being reevaluated by many surgeons because of increasing dissatisfaction with shunting procedures. A new technique of sclerotherapy using the flexible fiberoptic endoscope with balloon tamponade of variceal channels is being evaluated. To date, 18 patients have been treated by us with this method. Nine patients with active bleeding had control of their hemorrhage. Two patients experienced three episodes of rebleeding. Of patients not actively bleeding at the time of injection, one patient experienced rebleeding and subsequently died. Four other deaths not related to varices have occurred in this series. All surviving patients underwent repeated sclerotherapy until eradication of varices was achieved. This report demonstrates the feasibility of sclerotherapy of esophageal varices using the flexible fiberoptic endoscope.


Prediction of suitable habitat shifts and assessment of ecological niche overlaps for three Tridentiger species with intertidal and subtidal characteristics under future climate changes.
To show how dramatic global climate change affects marine ecosystem species in different habitats. We used a joint species distribution model (SDM) and an ecological niche model (ENM) to investigate the suitable habitat shifts and ecological niche overlaps of the Tridentiger fishes. In the present study, the SDM results showed that 5 hotspots were identified for T. trigonocephalus and T. barbatus, and 4 hotspots for T. bifasciatus. The study on center-of-mass transfer revealed notable reductions in the habitual range of the three Tridentiger species with future climate change and no significant bipolar shifts in the center of mass. The ENM results indicated that T. trigonocephalus and T. barbatus exhibited the greatest ecological niche overlap with Schoener's D (D) and Hellinger-based I (I) values of 0.4719 and 0.7690, respectively. Both SDM and ENM results have suggested that T. trigonocephalus occupied a wider distribution and greater adaptability to future climate change. This study sought to measure the variations in the effects of global climate change on marine species in different habitats. Our study first found that intertidal species with specific life histories may be more resilient to environmental change.


[Direct total body CT scan in multi-trauma patients].
Immediate total body computed tomography (CT) scanning has become important in the early diagnostic phase of trauma care because of its high diagnostic accuracy. However, literature provides limited evidence whether immediate total body CT leads to better clinical outcome then conventional radiographic imaging supplemented with selective CT scanning in trauma patients. The aim of the REACT-2 trial is to determine the value of immediate total body CT scanning in trauma patients. The REACT-2 trial is an international, multicenter randomized clinical trial. All participating trauma centers have a multi-slice CT scanner located in the trauma room or at the Emergency Department (ED). All adult, non-pregnant, severely injured trauma patients according to predefined criteria will be included. The intervention group will receive a contrast-enhanced total body CT scan (head to pelvis) during the primary survey. The control group will be evaluated according to local conventional trauma imaging protocols (based on ATLS guidelines) supplemented with selective CT scanning. Primary outcome will be in-hospital mortality. Secondary outcomes are differences in mortality and morbidity during the first year post trauma, several trauma work-up time intervals, radiation exposure, general health and quality of life at 6 and 12 months post trauma and cost-effectiveness. The REACT-2 trial is the first multicenter randomized clinical trial that will provide evidence on the value of immediate total body CT scanning during the primary survey of severely injured trauma patients.


Overcoming Barriers to Implementing New Therapies for Diabetic Kidney Disease: Lessons Learned.
As a result of the growing number of patients with type 2 diabetes mellitus, the prevalence of diabetic kidney disease (DKD) has proven to be one of the fastest growing health care challenges globally. Early detection and initiation of appropriate interventions to slow the progression of DKD are impeded by low awareness of the health consequences of DKD, high complexity of care that includes the need for lifestyle modifications, difficulties with adhering to increasingly complicated medication regimens, and low acceptance and application of guideline-directed management. After 2 decades of status quo in the care of patients with DKD, recently approved glucose-lowering agents are promising to transform care by demonstrating slowed DKD disease progression and improved survival. As has been learned over the last 2 decades, multiple barriers exist to the optimal integration and utilization of new therapies to improve kidney outcomes. The health care community, professional societies, and regulatory agencies must join efforts to develop implementation strategies for increasing DKD awareness, detection, and treatment.


Bacterial worth in genotoxicity assessment studies.
Bacterial-based genotoxicity test systems play a significant role in the detection and evaluation of genotoxicity in vitro and have gained importance due to attributes like wide applicability, speed, high sensitivity, good reproducibility, and simplicity. The Salmonella microsomal mutagenicity assay was created by Ames and colleagues at the beginning of the 1970s, and it was based on the fundamental notion that in auxotrophic bacterial strains with inhibited growth, a mutant gene would revert to its original state on exposure to genotoxicants. This is the most successful and widely used in vitro genotoxicity test. Later, a number of additional test systems that incorporated DNA repair mechanisms including the bacterial SOS response were created. Genetic engineering has further provided significant advancement in these test systems with the development of highly sophisticated bacterial tester strains with significantly increased sensitivity to evaluate the chemical nature of hazardous substances and pollutants. These bacterial bioassays render an opportunity to detect the defined effects of compounds at the molecular level. In this review, all the aspects related to the bacterial system in genotoxicity assessment have been summarized and their role is elaborated concerning real-time requirements and future perspectives.


Peroxisome proliferator-activated receptors (PPARs) are potential drug targets for cancer therapy.
Peroxisome-proliferator-activated receptors (PPARs) are nuclear hormone receptors including PPARα, PPARδ and PPARγ, which play an important role in regulating cancer cell proliferation, survival, apoptosis, and tumor growth. Activation of PPARs by endogenous or synthetic compounds regulates tumor progression in various tissues. Although each PPAR isotype suppresses or promotes tumor development depending on the specific tissues or ligands, the mechanism is still unclear. In this review, we summarized the regulative mechanism of PPARs on cancer progression.


Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status.
Research suggests that heredity and early fetal development play a causal role in autism. This case-control study explored the association between perinatal factors, parental psychiatric history, socioeconomic status, and risk of autism. The study was nested within a cohort of all children born in Denmark after 1972 and at risk of being diagnosed with autism until December 1999. Prospectively recorded data were obtained from nationwide registries in Denmark. Cases totaled 698 children with a diagnosis of autism; each case was individually matched by gender, birth year, and age to 25 controls. Analyses by conditional logistic regression produced risk ratios and 95% confidence intervals. Adjusted analyses showed that the risk of autism was associated with breech presentation (risk ratio (RR) = 1.63, 95% confidence interval (CI): 1.18, 2.26), low Apgar score at 5 minutes (RR = 1.89, 95% CI: 1.10, 3.27), gestational age at birth <35 weeks (RR = 2.45, 95% CI: 1.55, 3.86), and parental psychiatric history (schizophrenia-like psychosis: RR = 3.44, 95% CI: 1.48, 7.95; affective disorder: RR = 2.91, 95% CI: 1.65, 5.14). Analyses showed no statistically significant association between risk of autism and weight for gestational age, parity, number of antenatal visits, parental age, or socioeconomic status. Results suggest that prenatal environmental factors and parental psychopathology are associated with the risk of autism. These factors seem to act independently.


Bulging fontanelle in febrile infants: is lumbar puncture mandatory?
To determine the aetiologies and clinical characteristics of infants with fever and a bulging fontanelle. The medical records of all febrile infants with a bulging fontanelle who underwent a lumbar puncture from January 2000 to February 2008 in Assaf Harofeh Medical Center, a university affiliated hospital in central Israel, were identified. 153 patients met the inclusion criteria. The male to female ratio was 100:53; age range was 3-11 months with a mean age of 5.6 (SD 1.8) months and a median age of 5 months. Cerebrospinal fluid pleocytosis was found in 42 cases (27.3%), including one case of bacterial meningitis (0.6%). Other leading diagnoses were aseptic meningitis (26.7%), upper respiratory tract infection (18.3%), viral disease not otherwise specified (15.6%), roseola infantum (8.5%) and acute otitis media (6.5%). Appearance on admission was described as good to excellent in 113 (73.8%) infants, none of whom had bacterial meningitis. 32 had aseptic meningitis and 17 had other bacterial disease (pneumonia, acute otitis media, pyelonephritis, bacteraemia, shigella or salmonella gastroenteritis). All the latter had, upon admission, symptoms, signs, laboratory tests or imaging studies suggesting a bacterial aetiology. In this large cohort, all infants who appeared well on admission and had normal clinical, laboratory and imaging studies had benign (non-bacterial) disease. In an infant who appears well and has no evidence of bacterial disease, it is reasonable to observe the infant and withhold lumbar puncture. Prospective studies should be carried out to confirm this approach.


Nelfinavir induces adipocyte insulin resistance through the induction of oxidative stress: differential protective effect of antioxidant agents.
Antiretroviral therapy is frequently associated with adverse metabolic effects and lipodystrophy, but the role of HIV protease inhibitors and the mechanisms involved are poorly understood. The HIV protease inhibitor nelfinavir (NFV) impairs insulin signal propagation by inducing similar signalling defects to those induced by exposure to oxidative stress. We set out to determine if oxidative stress is involved in NFV-induced insulin resistance in 3T3-L1 adipocytes, and whether antioxidant agents with unique modes of action can prevent this effect. Cells exposed to NFV exhibited the following markers of increased oxidative stress: a decrease in both total and low molecular weight reduced thiols, a 20-fold increase in haem oxygenase 1 (HO-1) mRNA, an increase in intracellular reactive oxygen species production (determined by 2',7'-dichlorofluorescein fluorescence), and increased markers of apoptosis. Enhancing cellular thiols with N-acetylcystein prevented the NFV-induced drop in reduced thiols and partially protected against the induction in HO-1, but failed to prevent insulin resistance or cleavage of poly ADP ribose polymerase (PARP), a process indicative of activation of pro-apoptotic caspases. Conversely, the superoxide dismutase-mimetic antioxidant MnTBAP had no effect on cellular thiols in response to NFV, but protected against HO-1 induction and against the impairment in insulin-stimulated Akt/protein kinase B activation and PARP cleavage. Induction of oxidative stress plays a role in adipocyte insulin resistance and apoptosis induced by NFV through a radical-dependent but thiol-independent mechanism(s). The results may suggest a new mechanism for the adverse effects of NFV on fat cells, and offer potential new intervention approaches.


Complete discrimination of strain and temperature using Brillouin frequency shift and birefringence in a polarization-maintaining fiber.
This paper presents a novel method that realizes simultaneous and completely discriminative measurement of strain and temperature using one piece of Panda-type polarization-maintaining fibre. Two independent optical parameters in the fiber, the Brillouin frequency shift and the birefringence, are measured by evaluating the spectrum of stimulated Brillouin scattering (SBS) and that of the dynamic acoustic grating generated in SBS to get two independent responses to strain and temperature. We found that the Brillouin frequency shift and the birefringence have the same signs for strain-dependence but opposite signs for temperature-dependence. In experiment, the birefringence in the PMF is characterized with a precision of approximately 10(-8) by detecting the diffraction spectrum of the dynamic acoustic grating. A reproducible accuracy of discriminating strain and temperature as fine as 3 micro-strains and 0.08 degrees Celsius is demonstrated.


Focal adhesion kinase PTK2 autophosphorylation is not required for the activation of sodium-hydrogen exchange by decreased cell volume in the preimplantation mouse embryo.
SummaryRecovery from decreased cell volume is accomplished by a regulated increase of intracellular osmolarity. The acute response is activation of inorganic ion transport into the cell, the main effector of which is the Na+/H+ exchanger NHE1. NHE1 is rapidly activated by a cell volume decrease in early embryos, but how this occurs is incompletely understood. Elucidating cell volume-regulatory mechanisms in early embryos is important, as it has been shown that their dysregulation results in preimplantation developmental arrest. The kinase JAK2 has a role in volume-mediated NHE1 activation in at least some cells, including 2-cell stage mouse embryos. However, while 2-cell embryos show partial inhibition of NHE1 when JAK2 activity is blocked, NHE1 activation in 1-cell embryos is JAK2-independent, implying a requirement for additional signalling mechanisms. As focal adhesion kinase (FAK aka PTK2) becomes phosphorylated and activated in some cell types in response to decreased cell volume, we sought to determine whether it was involved in NHE1 activation in the early mouse embryo. FAK activity requires initial autophosphorylation of a tyrosine residue, Y397. However, FAK Y397 phosphorylation levels were not increased in either 1- or 2-cell embryos after cell volume was decreased. Furthermore, the selective FAK inhibitor PF-562271 did not affect NHE1 activation at concentrations that essentially eliminated Y397 phosphorylation. Thus, autophosphorylation of FAK Y397 does not appear to be required for NHE1 activation induced by a decrease in cell volume in early mouse embryos.


Structure, function, and productivity from the National Dental Practice-Based Research Network.
Following inception in 2005 as a multiregional practice-based research network (PBRN), the "National Dental PBRN" expanded nationwide in 2012, and in 2019 implemented additional organizational changes. The objectives are to: (1) describe the new structure and function of the network; and (2) quantify its scientific productivity since 2005. A national Administrative and Resource Center is based in Alabama; regional and specialty nodes are based in Alabama, Florida, Illinois, Minnesota, Oregon, New York, and Texas. A Network Coordinating Center is based in Oregon. Studies are funded via investigator-initiated grants. Scientific productivity is assessed using specific metrics, including the Relative Citation Ratio. To date, 58 studies have been completed or are in data collection or development. These studies have investigated a broad range of topics using a wide variety of study designs. Of the studies that have completed enrollment, 70,665 patients were enrolled, as were 19,827 practitioners (some participated in multiple studies), plus electronic records for 790,493 patients in two data-only studies. To date, these studies have led to 193 peer-reviewed scientific publications in 62 different journals. The mean (1.40) Relative Citation Ratio of Network publications connotes a greater-than-average influence in their fields. These metrics demonstrate that the PBRN research context can successfully engage practitioners and patients from diverse settings nationally with a high and sustained level of scientific productivity. This infrastructure has enabled clinical scientists in oral health and nonoral health topics and provided additional recruitment venues outside of the typical academic health center research context.


ALS-associated TBK1 variant p.G175S is defective in phosphorylation of p62 and impacts TBK1-mediated signalling and TDP-43 autophagic degradation.
Mutations affecting SQSTM1 coding for p62 and TANK-Binding Kinase 1 (TBK1) have been implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TBK1 is a serine-threonine kinase that regulates p62's activity as an autophagy receptor via phosphorylation and also has roles in neuroinflammatory signalling pathways. The mechanisms underlying ALS and FTLD pathogenesis as a result of TBK1 mutations are incompletely understood, however, loss of TBK1 function can lead to dysregulated autophagy and mitophagy. Here, we report that an ALS-associated TBK1 variant affecting the kinase domain, p.G175S, is defective in phosphorylation of p62 at Ser-403, a modification critical for regulating its ubiquitin-binding function, as well as downstream phosphorylation at Ser-349. Consistent with these findings, expression of p.G175S TBK1 was associated with decreased induction of autophagy compared to wild type and reduced degradation of the ALS-linked protein TDP-43. Expression of wild type TBK1 increased NF-κB signalling ~300 fold in comparison to empty vector cells, whereas p.G175S TBK1 was unable to promote NF-κB signalling above levels observed in empty vector transfected cells. We also noted a hitherto unknown role for TBK1 as a suppressor of oxidative stress (Nrf2) signalling and show that p.G175S TBK1 expressing cells lose this inhibitory function. Our data suggest that TBK1 ALS mutations may broadly impair p62-mediated cell signalling, which ultimately may reduce neuronal survival, in addition TDP-43 was not efficiently degraded, together these effects may contribute to TBK1 mutation associated ALS and FTLD pathogenesis.


Ubiquitous Presence and Novel Diversity of Anaerobic Alkane Degraders in Cold Marine Sediments.
Alkanes are major constituents of crude oil and are released to the marine environment by natural seepage and from anthropogenic sources. Due to their chemical inertness, their removal from anoxic marine sediments is primarily controlled by the activity of anaerobic alkane-degrading microorganisms. To facilitate comprehensive cultivation-independent surveys of the diversity and distribution of anaerobic alkane degraders, we designed novel PCR primers that cover all known diversity of the 1-methylalkyl succinate synthase gene (masD/assA), which catalyzes the initial activation of alkanes. We studied masD/assA gene diversity in pristine and seepage-impacted Danish coastal sediments, as well as in sediments and alkane-degrading enrichment cultures from the Middle Valley (MV) hydrothermal vent system in the Pacific Northwest. MasD/assA genes were ubiquitously present, and the primers captured the diversity of both known and previously undiscovered masD/assA gene diversity. Seepage sediments were dominated by a single masD/assA gene cluster, which is presumably indicative of a substrate-adapted community, while pristine sediments harbored a diverse range of masD/assA phylotypes including those present in seepage sediments. This rare biosphere of anaerobic alkane degraders will likely increase in abundance in the event of seepage or accidental oil spillage. Nanomolar concentrations of short-chain alkanes (SCA) were detected in pristine and seepage sediments. Interestingly, anaerobic alkane degraders closely related to strain BuS5, the only SCA degrader in pure culture, were found in mesophilic MV enrichments, but not in cold sediments from Danish waters. We propose that the new masD/assA gene lineages in these sediments represent novel phylotypes that are either fueled by naturally occurring low levels of SCA or that metabolize medium- to long-chain alkanes. Our study highlights that masD/assA genes are a relevant diagnostic marker to identify seepage and microseepage, e.g., during prospecting for oil and gas, and may act as an indicator of anthropogenic oil spills in marine sediments.


Strengthening an academic nursing center through partnership.
Nurse-managed health centers offer holistic health care and patient-centered health promotion and disease prevention. These goals are particularly well suited to the needs of children and their families. Few reports in the literature, however, have described such practices. The purpose of this paper is to describe one practice, Valencia Health Services (VHS), a nurse-managed, academic health center providing primary care to pediatric and adolescent patients. Valencia Health Services offers interdisciplinary, comprehensive health services to ethnically diverse children and their families through an inter-university partnership and provides clinical experiences and research opportunities, under the supervision of expert faculty-clinicians, to students of nursing (advanced practice, public health, and case management), social work and psychology. Valencia Health Services is the rare nurse-managed academic health center that provides comprehensive health care to children and adolescents. The multifaceted demands of such a health center, however, present both unique opportunities for quality care and service and considerable ongoing challenges.


[Features of the postsynaptic potentials and ion currents in synapses of fast and slow rat muscle fibers].
The time course of spontaneous miniature end-plate potentials (MEPP) and currents (MEPC) was compared in fast and slow muscle fibres using extracellular focal recording or voltage-clamp technique. The mean values of the rise and decline half-time of MEPP and MEPC in slow fibres was 1.3-1.4 times as much as those in fast ones. A smaller difference was observed after AChE inhibition. Decay of the end-plate currents remained generally exponential and its rate depended on the membrane potential level. Distribution of different muscle fibres according to the time course of MEPP and MEPC in fast and slow muscles correlates with the content of the different fibre types identified on other properties. The possible factors controlling the time course of postsynaptic responses (AChE activity, the length of diffusional pathways, differences in the membrane passive electrical properties) and their significance in synapses of different types are discussed.


19th-century camouflaged mechanical hearing devices.
The aim of this review is to present 19th century mechanical hearing devices that were designed for concealment or camouflage. Extensive literature, past and current, along with museum catalogs, trade catalogs, and advertisements, were examined to identify mechanical devices designed for concealment. Several mechanical devices were selected for acoustic gain measurements. Measurements were made in an anechoic chamber using a Knowles Electronics Manikin for Acoustic Research fitted with a Zwislocki coupler and a pressure microphone in the right ear. One-third-octave bands of noise were presented via a KLH Model 6 loudspeaker placed at a distance of 2.23 m on-axis. The sound level at the ear of the Knowles Electronics Manikin for Acoustic Research was recorded with and without the device in place. A wide variety of 19th century hearing devices designed for concealment were identified. Some hearing devices, such as fans, parasols, lorgnettes, water canteens, walking sticks, chairs/thrones, hats, and books, were concealed within everyday items. Other hearing devices, such as artificial conchae, bouquet holders, and hair and beard receptors, wereconcealed on the person. The insertion gain of a representative concealed device, the Aurolese Phone, averaged approximately 3.5 dB in the range of frequencies most relevant for speech communication. The ingenuity behind the design of 19th century mechanical hearing devices created for concealment or camouflage is to be commended. For the Aurolese Phone, some acoustic benefit was possible despite design constraints imposed by its concealed nature.


Experiences of Using a Self-management Mobile App Among Individuals With Heart Failure: Qualitative Study.
Interventions that focus on the self-management of heart failure are vital to promoting health in patients with heart failure. Mobile health (mHealth) apps are becoming more integrated into practice to promote self-management strategies for chronic diseases, optimize care delivery, and reduce health disparities. The purpose of this study was to explore the experience of using a self-management mHealth intervention in individuals with heart failure to inform a future mHealth intervention study. This study used a qualitative descriptive design. Participants were enrolled in the intervention groups of a larger parent study using a mobile app related to self-management of heart failure. The purposive, convenient, criterion-based sample for this qualitative analysis comprised 10 patients who responded to phone calls and were willing to be interviewed. Inclusion criteria for the parent study were adults who were hospitalized at Nebraska Medical Center with a primary diagnosis and an episode of acute decompensated heart failure; discharged to home without services such as home health care; had access to a mobile phone; and were able to speak, hear, and understand English. Study participants were middle-aged (mean age 55.8, SD 12 years; range 36-73 years). They had completed a mean of 13.5 (SD 2.2) years (range 11-17 years) of education. Of the 10 participants, 6 (60%) were male. Half of them (5/10, 50%) were New York Heart Association Classification Class III patients and the other half were Class IV patients. The intervention revealed four self-management themes, including (1) I didn't realize, and now I know; (2) It feels good to focus on my health; (3) I am the leader of my health care team; and (4) My health is improving. Participants who used a self-management mHealth app intervention for heart failure reported an overall positive experience. Their statements were organized into four major themes. The education provided during the study increased self-awareness and promoted self-management of their heart failure. The mHealth app supported patient empowerment, resulting in better heart failure management and improved quality of life. Participants advocated for themselves by becoming the leader of their health, especially when communicating with their health care team. Finally, the mHealth app was used by the participants as a self-management tool to assist in symptom management and improve their overall health. Future research should study symptom evaluation, medication tracking, and possibly serve as a health provider communication platform to empower individuals to be leaders in their chronic disease management.


[Fluorescence guided resection of malignant brain tumors - breakthrough in the surgery of brain tumors].
Malignant gliomas, among others the glioblastoma multiforme, are the most frequent brain tumors. The glioblastoma itself represents the most unfavorable tumor. In Switzerland, about 450 humans contract a glioblastoma each year. The median survival time is under 12 months, thus the prognosis is dismal despite a combination of surgery, radiotherapy and chemotherapy. Surgical resection presents the major constituent in the management of patients with a glioblastoma. Postoperative radio- and chemotherapy have beneficial effects on the survival time and quality of life. Surgical removal of glioblastomas is challenging due to their infiltrative growth pattern. Therefore, the target extent of resection can only be achieved partially. For some time now, a new in Germany developed method is used in the Neurosurgical Clinic of the Cantonal Hospital in St. Gallen: The 5-ALA-guided microsurgical resection method allows a targeted and secure surgical resection of the tumor. A preoperative administered substance colors the tumor and makes it better visible for the neurosurgeon. Consequently, the healthy brain tissue can be better distinguished from the tumor. This permits not only a larger complete surgical resection of the tumor but also minimizes the resection of healthy tissue.


Treatment outcome and predictors of poor clinical response in extensively drug-resistant gram-negative urinary tract infection among children: A single-institution experience.
Extensively drug-resistant (XDR) is defined as isolates sensitive only to two or fewer antimicrobial categories. This paper aims to present the treatment outcome and identify factors associated with poor clinical response among children with XDR gram-negative urinary tract infection (UTI). This is a retrospective cohort conducted at a tertiary pediatric hospital from January 2014 to June 2017. All patients diagnosed with culture-proven XDR gram-negative UTI were identified and analyzed. Descriptive statistics were used to summarize demographic and clinical characteristics. Patients were categorized according to treatment outcomes: success vs. failure. Univariate analysis and multivariate logistic regression were used to assess statistical differences between the groups and determined patient variables that are predictive of poor response. Odds ratio (OR) and corresponding 95% confidence interval (CI) were generated. A total of 29 (19.2%) XDR gram-negative pediatric UTIs were identified within the 42-month study period. No significant differences were noted in demographic characteristics between the groups. Treatment outcome of XDR gram-negative UTI patients showed that combination therapy with colistin had the highest success rate (40.9%), followed by non-colistin (36.4%) and combination therapy without colistin (22.7%). However, univariate analysis showed no significant difference among the different treatment groups (p=0.65). On multivariate logistic regression, receiving immunosuppressant and the presence of indwelling urinary catheters were independent predictors of poor clinical response among pediatric patients with XDR gram-negative UTI (OR 19.44, 95% CI 1.50-251.4, p=0.023 and OR 20.78, 95% CI 1.16-371.28, p=0.039; respectively). The treatment success rate of XDR gram-negative pediatric UTI ranged from 22.7-36.4%. This finding emphasizes the need to advocate antibiotic stewardship to prevent further increase in XDR UTIs. Indwelling urinary catheters and receipt of immunosuppressants are associated with poor clinical outcome.


A finite element model for performing intravascular ultrasound elastography of human atherosclerotic coronary arteries.
Intravascular ultrasound (US) elastography measures in an artery the arterial radial strain and displays it in an elastogram. An elastogram adds diagnostic information, such as the proneness of a plaque to rupture and its material composition. However, radial strain depends upon the material properties of an artery, including geometry and used catheter position. Therefore, there is not always a one-to-one correspondence between radial strain and rupture-proneness or material composition. Both the dependence and the correspondence can be quantified after a proper finite element model (FEM) is available. Therefore, this paper proposes a FEM and shows that it can model the arterial strain behavior. Its modelling capability was evaluated by comparing simulated with measured elastograms. Measured elastograms were processed from radiofrequency (RF) data obtained in vitro from six objects: a vessel-mimicking phantom and five excised human atherosclerotic coronary arteries. A FEM was created for each object and used to simulate an elastogram; the material properties and geometry of the FEM were obtained from the histology of the object. Comparison was performed upon high strain regions (HStR), because these regions have proven to contain plaques that show the hallmarks of vulnerable plaques. Eight HStR were automatically identified from the five arteries. Statistical tests showed that there was no significant difference between simulated and corresponding measured elastograms in location, surface area or mean strain value of a HStR. The results demonstrate that the FEM can simulate elastograms measured from arteries. As such, the FEM may help in quantifying strain-dependencies and assist in tissue characterization by reconstructing a Young's modulus image from a measured elastogram.


Brain imaging in myotonic dystrophy type 1: A systematic review.
To systematically review brain imaging studies in myotonic dystrophy type 1 (DM1). We searched Embase (index period 1974-2016) and MEDLINE (index period 1946-2016) for studies in patients with DM1 using MRI, magnetic resonance spectroscopy (MRS), functional MRI (fMRI), CT, ultrasound, PET, or SPECT. From 81 studies, we extracted clinical characteristics, primary outcomes, clinical-genetic correlations, and information on potential risk of bias. Results were summarized and pooled prevalence of imaging abnormalities was calculated, where possible. In DM1, various imaging changes are widely dispersed throughout the brain, with apparently little anatomical specificity. We found general atrophy and widespread gray matter volume reductions in all 4 cortical lobes, the basal ganglia, and cerebellum. The pooled prevalence of white matter hyperintensities is 70% (95% CI 64-77), compared with 6% (95% CI 3-12) in unaffected controls. DTI shows increased mean diffusivity in all 4 lobes and reduced fractional anisotropy in virtually all major association, projection, and commissural white matter tracts. Functional studies demonstrate reduced glucose uptake and cerebral perfusion in frontal, parietal, and temporal lobes, and abnormal fMRI connectivity patterns that correlate with personality traits. There is significant between-study heterogeneity in terms of imaging methods, which together with the established clinical variability of DM1 may explain divergent results. Longitudinal studies are remarkably scarce. DM1 brains show widespread white and gray matter involvement throughout the brain, which is supported by abnormal resting-state network, PET/SPECT, and MRS parameters. Longitudinal studies evaluating spatiotemporal imaging changes are essential.


Outer membrane vesicles of Pasteurella multocida contain virulence factors.
Pasteurella multocida (Pm) is a gram-negative bacterium able to infect different animal species, including human beings. This bacterium causes economic losses to the livestock industry because of its high morbidity and mortality in animals. In this work, we report the characterization of outer membrane vesicles (OMVs) released into the culture medium by different Pm serogroups. Purified OMVs in the range of 50-300 nm were observed by electron microscopy. Serum obtained from chickens infected with Pm recognized several proteins from Pm OMVs. Additionally, rabbit antiserum directed against a secreted protease from Actinobacillus pleuropneumoniae recognized a similar protein in the Pm OVMs, suggesting that OMVs from these bacterial species contain common immunogenic proteins. OmpA, a multifunctional protein, was identified in OMVs from different Pm serogroups, and its concentration was twofold higher in OMVs from Pm serogroups B and D than in OMVs from other serogroups. Three outer membrane proteins were also identified: OmpH, OmpW, and transferrin-binding protein. Three bands of 65, 110, and 250 kDa with proteolytic activity were detected in Pm OMVs of serogroups A and E. Additionally, β-lactamase activity was detected only in OMVs from Pm 12945 Amp(r) (serogroup A). Pm OMVs may be involved in different aspects of disease pathogenesis.


Determinants of early weaning and use of unmodified cow's milk in infants: a systematic review.
Introduction of complementary foods (weaning) before 4 to 6 months of age and unmodified cow's milk before age 12 months are associated with several health risks. To develop effective interventions to discourage these practices, evidence of their determinants is needed. This systematic review identified documents from seven electronic databases (database inception 2008) and reference lists, and by contacting authors. Seventy-eight studies in developed countries, published between 1976 and 2008, quantifying the association between either feeding practice and its potential determinants were included. Study quality was systematically assessed in terms of representativeness, sample size, method of outcome ascertainment, and approach to statistical analysis. The distribution of evidence for each determinant was visualized in a harvest plot showing the strength and direction of associations found and the quality of relevant studies. The strength of evidence for each determinant was summarized as strong, moderate, limited, or inconclusive, using an algorithm based on the consistency of the results of studies of the highest available quality. Strong evidence denoted that the determinant was examined in three or more high-quality studies and >/=75% of results were consistent. Strong evidence was found for six determinants of early weaning (ie, young maternal age, low maternal education, low socioeconomic status, absence or short duration of breastfeeding, maternal smoking, and lack of information or advice from health care providers) and for two determinants of early introduction of unmodified cow's milk (ie, low maternal education and low socioeconomic status). Of these determinants, improving advice given by health care providers appears the most tractable area for intervention in the short term.