Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study.
High-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population. This study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group. Of 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade ≥ IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included ≥ 4 lymph nodes retrieved, estimated intraoperative blood loss ≤ 350 mL, perioperative blood transfusion rate ≤ 13%, operative time ≤ 332 min, length of hospital stay ≤ 8 days, R1 margin rate ≤ 7%, complication rate ≤ 22%, and rate of grade ≥ IIIa complications ≤ 11%. Surgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery.


Impacts of household vulnerability on hurricane logistics evacuation under COVID-19: The case of U.S. Hampton Roads.
Historical data suggest that when a severe tropical storm or hurricane impacts a community, the vulnerable segment of the population suffers the most severe consequences. With an increased aging population, it is crucial to understand how vulnerability alters evacuation behavior. Emergent variables such as fear of COVID-19 require additional exploration. People afraid of COVID-19 exposure may refuse to evacuate, exposing themselves unnecessarily. Differentiation is critical to evacuation logistics since it is needed to determine what proportion would stay in a local shelter, public or other, rather than evacuating or staying in their home and guide the logistics resource allocation process. This research uses data from a web and phone survey conducted in the Hampton Roads area of U.S. Virginia, with 2,200 valid responses to analyze the influence of social and demographic vulnerability factors and risk perception on evacuation decisions. This research contributes to the existing literature by developing a multinomial order logit model based on vulnerability factors and intended evacuation decisions, including staying at home, looking for a shelter, or leaving the Hampton Roads area. Findings show that race and risk perception are the variables that influence the decision-making process the most. Fear of COVID-19 transmission is also associated with an increased likelihood of leaving homes during evacuation. The variations in findings from previous studies are discussed regarding their implications for logistics emergency managers.


Characteristics of success in mentoring and research productivity - a case-control study of academic centers.
While mentoring has been associated with research productivity, the specific characteristics of successful mentoring have not been well studied. Thus, we performed a case-control study to identify characteristics of successful mentoring programs. Institutions were divided based on number of plenary research presentations at an annual society meeting over 6years. Case institutions (Group A) had more presentations vs. controls (Group B). A survey of professors and research fellows assessed characteristics of their mentoring program. Chi-square and logistic regression analyses were performed. Of 159 surveyed, response rates were 46% for professors and 51% for fellows. Compared to Group B, Group A was more likely to have: an additional year of protected fellowship research training (62% vs. 24%; p=0.003), an established program to connect a mentor and mentee with similar research interests (52% vs. 27%; p=0.049), methods to provide feedback to mentors (62% vs. 29%; p=0.01), require mentee research progress reports (45% vs. 21%; p=0.047), and report ease of identifying a mentor (90% vs. 69%; p=0.046). On multivariate analyses, the additional year of research training (OR=7.53, 95% CI: 2.10-27.09; p=0.002) and ease at identifying a research mentor (OR=7.45, 95% CI: 1.44-38.6; p=0.017) remained as independent factors associated with higher research productivity. Our data suggest that programs can enhance research productivity with the incorporation of accountability features including formalized reports of progress and mentorship feedback in fellowship training. Facilitating the identification of a mentor and providing an additional year of research may be independent factors associated with research productivity.


Humanin peptides block calcium influx of rat hippocampal neurons by altering fibrogenesis of Abeta(1-40).
Humanin peptides (including HN, HNG and other mutants) were reported previously that antagonize neurotoxicity caused by various familial Alzheimer's disease (FAD) genes and Abeta derivatives. Herein, we describe the aggregation dynamics and the representative morphological characteristics of Abeta(1-40) after different time of addition humanin peptides, which revealed that (a) the interactions of both HN and HNG with Abeta(1-40) induced quick and significant increase of light-scattering intensity, and (b) HNG also caused obvious morphological alteration from fibrillary to amorphous. In the meantime, the experiments also revealed that the interaction of HNG with Abeta(1-40) could decrease Abeta(1-40)-induced calcium rise, an initial event accompanying Abeta(1-40)-induced apoptosis of cultured neurons. Our results indicate that HNG can protect neurons by altering Abeta(1-40) morphology.


Devoid of dentistry.
Dental curricula in UK dental schools are seemingly excising ever more skills as each generation of students is trained. This has implications for the quality of education held by the latest dental graduates, and furthermore potentially for the standard of care that their patients may receive. This leaves us today somewhat nostalgic for a bygone era when dental undergraduate education was replete with a fuller repertoire.


Statistical approaches to analyse patient-reported outcomes as response variables: an application to health-related quality of life.
Patient-reported outcomes (PRO) are used as primary endpoints in medical research and their statistical analysis is an important methodological issue. Theoretical assumptions of the selected methodology and interpretation of its results are issues to take into account when selecting an appropriate statistical technique to analyse data. We present eight methods of analysis of a popular PRO tool under different assumptions that lead to different interpretations of the results. All methods were applied to responses obtained from two of the health dimensions of the SF-36 Health Survey. The proposed methods are: multiple linear regression (MLR), with least square and bootstrap estimations, tobit regression, ordinal logistic and probit regressions, beta-binomial regression (BBR), binomial-logit-normal regression (BLNR) and coarsening. Selection of an appropriate model depends not only on its distributional assumptions but also on the continuous or ordinal features of the response and the fact that they are constrained to a bounded interval. The BBR approach renders satisfactory results in a broad number of situations. MLR is not recommended, especially with skewed outcomes. Ordinal methods are only appropriate for outcomes with a few number of categories. Tobit regression is an acceptable option under normality assumptions and in the presence of moderate ceiling or floor effect. The BLNR and coarsening proposals are also acceptable, but only under certain distributional assumptions that are difficult to test a priori. Interpretation of the results is more convenient when using the BBR, BLNR and ordinal logistic regression approaches.


Nonvisualization of suppressed thyroid tissue on Tl-201 scintigraphy.
Tl-201 scintigraphy has been used to visualize thyroid tissue that is suppressed by an autonomously functioning thyroid nodule. Reports have indicated that the sensitivity of this technique rivals that obtained by I-123 scanning after thyroid-stimulating hormone stimulation. We report a case of triiodothyronine toxicosis caused by an autonomously functioning thyroid nodule in which the suppressed thyroid tissue was not visualized on Tl-201 scintigraphy. The suppressed tissue was readily identified with ultrasound imaging, which demonstrates the utility of this technique in differentiating between thyroid suppression and agenesis.


[Long-term steroid therapy in children: is adjunct therapy relevant in nephrotic syndrome?].
The impact of glucocorticoids on bone is specifically relevant in children exposed to a long course of treatment. Corticosteroids lead to a decrease in bone formation, mainly by osteoblastic inhibition in trabecular bone. They also play an indirect role in bone metabolism through systemic actions, such as bone maturation delay, hypogonadism, pubertal delay, and IGF1 inhibition. A systematic review of the literature was conducted. We found 12 clinical trials of interventions including calcium, vitamin D, growth hormone, calcitonin, and bisphosphonates for preventing bone disease in children receiving steroid therapy. There were few randomized controlled trials (n=7), with a limited number of patients, so that a meta-analysis could not be performed. Calcium and vitamin D supplementation may, however, have a beneficial effect on bone in children with nephrotic syndrome receiving long-term steroid therapy. We, therefore, recommend routine vitamin D supplementation, use of steroid-sparing protocols, and global prevention of risk to bone (adequate calcium intake, sun exposure, and physical activity).


Distinct but Concerted Roles of ATR, DNA-PK, and Chk1 in Countering Replication Stress during S Phase.
The ATR-Chk1 pathway is critical for DNA damage responses and cell-cycle progression. Chk1 inhibition is more deleterious to cycling cells than ATR inhibition, raising questions about ATR and Chk1 functions in the absence of extrinsic replication stress. Here we show that a key role of ATR in S phase is to coordinate RRM2 accumulation and origin firing. ATR inhibitor (ATRi) induces massive ssDNA accumulation and replication catastrophe in a fraction of early S-phase cells. In other S-phase cells, however, ATRi induces moderate ssDNA and triggers a DNA-PK and Chk1-mediated backup pathway to suppress origin firing. The backup pathway creates a threshold such that ATRi selectively kills cells under high replication stress, whereas Chk1 inhibitor induces cell death at a lower threshold. The levels of ATRi-induced ssDNA correlate with ATRi sensitivity in a panel of cell lines, suggesting that ATRi-induced ssDNA could be predictive of ATRi sensitivity in cancer cells.


Influence of water activity on the production of T-2 Toxin byFusarium sporotrichioides.
The production of T-2 Toxin by two strains ofFusarium sporotrichioides at high (0.995), medium (0.970) and low (0.945) water activity (aw) was investigated. The organisms were incubated in an optimal liquid base medium (Wort broth) adjusted to the different aw values. With decreasing aw the amount of T-2 Toxin in the culture supernatants fell drastically. Comparing cultures that had reached almost equal mycelial dry weights, those of low aw had T-2 Toxin levels 10 to 100 times lower than those of high aw. This effect was observed using both glycerol or sodium chloride as humectants.


Sex steroids modulate motor-correlated increases in cerebellar discharge.
Adult female rats implanted with a microelectrode drive unit were trained to walk on a computer-controlled treadmill apparatus (10 s on every 20 s for 2 h) during recording of single Purkinje neurons in the paravermal area of the anterior cerebellum. Vigorous increases in the firing rate of individual units were found to be correlated with movement of specific limbs in particular stages of the step cycle during treadmill locomotion. Both spontaneous and motor-evoked discharge of individual Purkinje neurons were monitored before and after s.c. injection of either 17 beta estradiol (E2, 100 ng/kg) or progesterone (P, 50 micrograms). The percent increase in firing rate during locomotion versus rest was determined as a measure of the evoked:spontaneous discharge ratio. Drug-induced changes in this ratio indicate differential effects on the individual parameters, rather than simple excitatory or inhibitory effects. For all neurons tested, E2 augmented the movement-evoked discharge over pre-E2 control levels. The onset for this effect occurred at 15 min post-steroid, with a peak response noted at 30-35 min post-steroid. By 60-90 min, a partial recovery of the evoked:spontaneous ratio was noted, although absolute increases in both parameters were still observed, indicating long-term effects on neuronal activity. These effects were independent of the stage of the estrous cycle. In contrast, P decreased absolute firing rates of Purkinje cells during stationary and locomotor phases. However, the evoked:spontaneous ratio was decreased to an even greater degree. The latency for this effect was 9-12 min, with recovery to control levels of response seen at 30 min post-steroid. This response was typical of cells tested on estrus and diestrus 1. Cells tested on proestrus or diestrus 2, when E2 levels are increasing, were not modulated by P using the above paradigm.


Paradoxical effect of rapamycin on inflammatory stress-induced insulin resistance in vitro and in vivo.
Insulin resistance is closely related to inflammatory stress and the mammalian target of rapamycin/S6 kinase (mTOR/S6K) pathway. The present study investigated whether rapamycin, a specific inhibitor of mTOR, ameliorates inflammatory stress-induced insulin resistance in vitro and in vivo. We used tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) stimulation in HepG2 hepatocytes, C2C12 myoblasts and 3T3-L1 adipocytes and casein injection in C57BL/6J mice to induce inflammatory stress. Our results showed that inflammatory stress impairs insulin signaling by reducing the expression of total IRS-1, p-IRS-1 (tyr632), and p-AKT (ser473); it also activates the mTOR/S6K signaling pathway both in vitro and in vivo. In vitro, rapamycin treatment reversed inflammatory cytokine-stimulated IRS-1 serine phosphorylation, increased insulin signaling to AKT and enhanced glucose utilization. In vivo, rapamycin treatment also ameliorated the impaired insulin signaling induced by inflammatory stress, but it induced pancreatic β-cell apoptosis, reduced pancreatic β-cell function and enhanced hepatic gluconeogenesis, thereby resulting in hyperglycemia and glucose intolerance in casein-injected mice. Our results indicate a paradoxical effect of rapamycin on insulin resistance between the in vitro and in vivo environments under inflammatory stress and provide additional insight into the clinical application of rapamycin.


Age-specific and year of birth changes in hospital admissions during a period of unexplained higher deaths in England.
Policy makers have assumed that increase in medical demands and costs are attributable to the increasing age of the population and the inability of health and social care to limit demand. Analysis of data obtained from NHS and Office of National Statistics. Population-adjusted age-specific patterns in medical admissions and deaths have increased over the period 2012/13 to 2015/16 in the NHS in England. The growth is both age and year of birth specific, and the youngest appear to be worst affected. Overall there has been a growth of 30,870 admissions (15% increase) in 25-29year olds compared to 119,280 extra admissions (7% increase) for 70-74year olds. Admissions of younger medical patients have also increased more so than for pneumonia, and the increase in all-cause mortality appears to be influenced by the patients' year of birth. In England, medical admissions and deaths (all-cause mortality) have recently displayed very high unexplained growth. The fact that these are associated with patient year of birth suggests that the cause(s) may be related to infectious or other environmental factors encountered earlier in life.


Bilateral postpartum vulvar edema associated with maternal death.
Reported is a maternal death associated with bilateral postpartum vulvar edema. Data are reviewed for this patient and four other patients who were previously reported to have had a syndrome of unilateral postpartum vulvar edema associated with maternal death. Overall, an 80% mortality rate has been observed.


Basal forebrain neuronal inhibition enables rapid behavioral stopping.
Cognitive inhibitory control, the ability to rapidly suppress responses inappropriate for the context, is essential for flexible and adaptive behavior. Although most studies on inhibitory control have focused on the fronto-basal-ganglia circuit, we found that rapid behavioral stopping is enabled by neuronal inhibition in the basal forebrain (BF). In rats performing the stop signal task, putative noncholinergic BF neurons with phasic bursting responses to the go signal were nearly completely inhibited by the stop signal. The onset of BF neuronal inhibition was tightly coupled with and temporally preceded the latency to stop, the stop signal reaction time. Artificial inhibition of BF activity in the absence of the stop signal was sufficient to reproduce rapid behavioral stopping. These results reveal a previously unknown subcortical mechanism of rapid inhibitory control by the BF, which provides bidirectional control over the speed of response generation and inhibition.


A portrait of wellbore leakage in northeastern British Columbia, Canada.
Oil and gas well leakage is of public concern primarily due to the perceived risks of aquifer contamination and greenhouse gas (GHG) emissions. This study examined well leakage data from the British Columbia Oil and Gas Commission (BC OGC) to identify leakage pathways and initially quantify incident rates of leakage and GHG emissions from leaking wells. Three types of leakage are distinguished: "surface casing vent flow" (SCVF), "outside the surface casing leakage" (OSCL), and "cap leakage" (CL). In British Columbia (BC), the majority of reported incidents involve SCVF of gases, which does not pose a risk of aquifer contamination but does contribute to GHG emissions. Reported liquid leakage of brines and hydrocarbons is rarer. OSCL and CL of gas are more serious problems due to the risk of long-term leakage from abandoned wells; some were reported to be leaking gas several decades after they were permanently abandoned. According to the requirements of provincial regulation, 21,525 have been tested for leakage. In total, 2,329 wells in BC have had reported leakage during the lifetime of the well. This represents 10.8% of all wells in the assumed test population. However, it seems likely that wells drilled and/or abandoned before 2010 have unreported leakage. In BC, the total GHG emission from gas SCVF is estimated to reach about 75,000 t/y based on the existing inventory calculation; however, this number is likely higher due to underreporting.


Influence of the natural radon radiation on the spread of the COVID 19 pandemic.
The statistics of COVID-19 accumulated in Ukraine show areas with a significantly lower incidence of diseases. The purpose of the study was to identify factors that could influence the pattern of the pandemic in a particular area. Within the study it was assumed that the level of health care is approximately the same throughout the country. Population density was considered the main factor influencing the dynamics of the spread of infection. To reduce the impact of changes in population density across regions, it was normalized by the average population density in the country. The normalization of statistics for the country resulted in a model in the form of a linear relationship between the normalized values of the number of COVID-19 cases in the region and the size of the region. Subsequent analysis of the graphical data made it possible to identify four regions with the lowest incidence of COVID-19. The geographical proximity of these regions Dnipro, Kherson, Vinnytsia and Kirovograd, indicates the presence of a common factor for them, not typical for the rest of Ukraine. Such a factor may be the location of 83% of Ukraine's uranium deposits in the territories around Kirovohrad. Radon is one of the decay products of uranium, so the population of these areas may experience increased exposure to radon. This noble gas has more than a century of medical use, in particular for pulmonary diseases, although there is still no consensus about its effectiveness and side effects. Considering that COVID-19 was often complicated by pulmonary diseases, it can be assumed that the geological specificity of these four regions of Ukraine had an impact on the course of the COVID-19 pandemic in their territories. The study findings are important in terms of further COVID-19 research and prevention strategies.


Simple biological systems for assessing the activity of superoxide dismutase mimics.
Half a century of research provided unambiguous proof that superoxide and species derived from it-reactive oxygen species (ROS)-play a central role in many diseases and degenerative processes. This stimulated the search for pharmaceutical agents that are capable of preventing oxidative damage, and methods of assessing their therapeutic potential. The limitations of superoxide dismutase (SOD) as a therapeutic tool directed attention to small molecules, SOD mimics, that are capable of catalytically scavenging superoxide. Several groups of compounds, based on either metal complexes, including metalloporphyrins, metallocorroles, Mn(II) cyclic polyamines, and Mn(III) salen derivatives, or non-metal based compounds, such as fullerenes, nitrones, and nitroxides, have been developed and studied in vitro and in vivo. Very few entered clinical trials. Development of SOD mimics requires in-depth understanding of their mechanisms of biological action. Elucidation of both molecular features, essential for efficient ROS-scavenging in vivo, and factors limiting the potential side effects requires biologically relevant and, at the same time, relatively simple testing systems. This review discuses the advantages and limitations of genetically engineered SOD-deficient unicellular organisms, Escherichia coli and Saccharomyces cerevisiae as tools for investigating the efficacy and mechanisms of biological actions of SOD mimics. These simple systems allow the scrutiny of the minimal requirements for a functional SOD mimic: the association of a high catalytic activity for superoxide dismutation, low toxicity, and an efficient cellular uptake/biodistribution.


A case series of de novo inflammatory bowel disease after kidney transplantation.
Diarrhea, which is common after transplantation, may be due to infections and immunosuppressive therapy. Inflammatory bowel disease (IBD) de novo or as an exacerbation of pre-existent disease is a rare complication after kidney transplantation with pre-existing disease having a less aggressive clinical course than the de novo disease. Cytomegalovirus mismatch, prescription of tacrolimus instead of cyclosporine or mycophenolate mofetil rather than azathioprine as well as low-dose corticosteroid treatments have been linked to an increased incidence of IBD. This series of renal transplant recipients with de novo IBD showed a higher incidence and more aggressive course than that previously described, possibly related to increased use of tacrolimus with minimization of steroids.


Influence of Parenting Quality and Neuroticism on Perceived Job Stressors and Psychological and Physical Stress Response in Adult Workers from the Community.
The complex interaction between parenting styles, job stressors, and the stress response has not been clarified to date. We hypothesized that neuroticism acts as a mediator in the effects of parenting quality on perceived job stressors and the psychological and physical stress response (PPSR), and tested this hypothesis using covariance structure analysis. We conducted research between April 2017 and April 2018 on 597 adult from the community, and 69 subjects were excluded owing to missing data or nonworkers. Finally, a total of 528 participants were analyzed using the following self-administered questionnaires: the Parental Bonding Instrument, the shortened Eysenck Personality Questionnaire-Revised, and the Brief Job Stress Questionnaire (BJSQ). The data were analyzed by single regression analyses and covariance structure analyses. Job stress was assessed by the BJSQ and 2 subscales, ie, perceived job stressors and the PPSR. This study was approved by the Ethics Committee of Tokyo Medical University. On covariance structure analysis, high parental overprotection was associated with high neuroticism and high PPSR directly, but had no significant effect on perceived job stressors. High parental overprotection was associated with high-perceived job stressors and the high PPSR indirectly through enhanced neuroticism. High parental overprotection was also associated with the high PPSR indirectly through 2 combined paths of neuroticism and perceived job stressors. This model accounted for 40% of the variability of the PPSR. On the other hand, parental care had opposite effects to parental overprotection, and this model of parental care accounted for 39% of the variability of PPSR. The model fits of the 2 models were good. Our results suggest that the quality of parenting in childhood is associated with perceived job stressors and the PPSR indirectly through neuroticism.


Difference in the alveolar bone remodeling between the adolescents and adults during upper incisor retraction: a retrospective study.
The purpose of this study was to compare the difference of alveolar bone remodeling between the adolescents and adults in the maxillary incisor area during retraction. This retrospective study included 72 female patients who needed moderate anchorage to correct the bimaxillary protrusion. Subjects were further divided into the minor group (n = 36, 11-16 years old) and adult group (n = 36, 18-35 years old). Digital lateral cephalography and cone beam CT scanning were taken in each patient before (T0) and after treatment (T1). Cephalometry was conducted to assess incisor retraction, while alveolar bone thickness (ABT), alveolar bone distance (ABD), and alveolar bone area (ABA) were detected to assess changes in the alveolar bone. No difference in the inclination of upper incisors was observed at both T0 and T1 between two groups. Changes in the alveolar bone showed a similar tendency with bone apposition on the labial side and bone resorption on the palatal side in both groups. Less increase in the labial ABT (T1-T0) and more decrease in the palatal ABT (T1-T0) was found in the adult group, leading to less total ABT in the adult group. Higher reduction in ABD (T1-T0) was found in the adult group. Moreover, more decrease in the ABA (T1-T0) was found in the adult group. Adult patients have less alveolar bone support after treatment when compared with young adolescents. Orthodontists should take the age into consideration to reduce the potential periodontal risks during the treatment planning.


Clinical significance of anti-Yt(b). Report of a case using a 51chromium red cell survival study.
Several published reports have documented the variable survival of Yt(a+) red cells (RBC) in patients with anti-Yt(a) as measured by 51Chromium (Cr)-labeled RBC survival studies. Similar studies with anti-Yt(b) have not been reported. A 51Cr-labeled RBC survival study was performed using Yt(b+) RBCs and a monocyte monolayer assay in a young hemodialysis patient who required chronic transfusion therapy and who had developed anti-Yt(b). The survival of the transfused RBCs was 100 and 93 percent at 1 and 24 hours, respectively, with a half life of 21 days at termination of the study (normal, 28 to 32 days). These results showed no evidence of rapid destruction of the Yt(b+) RBCs, indicating that this patient could be transfused safely with blood from Yt(b+) donors. Long-term survival of the 51Cr-labeled Yt(b+) RBCs was shortened moderately, however, a finding that correlated with a slightly abnormal monocyte monolayer assay test.


Detection of reaction time by an adaptive filter based on the least squares fit.
An adaptive filter based on the least squares fit between a template and individual records was developed. It has been applied to compute reaction times of a voluntary movement. Its performance was tested by comparing these reaction times with the latency of the EMG responses. Different properties of the least squares fit technique and Woody's filter technique (Woody 1967) are discussed.


IGF-I generation test in prepubertal children with Noonan syndrome due to mutations in the PTPN11 gene.
Short stature represents one of the main features of children with Noonan syndrome. The reason for impaired growth remains largely unknown. To assess GH and IGF1 secretion in children with Noonan syndrome. 12 prepubertal children with Noonan syndrome due to mutations in the PTPN11 gene [7 males, 6 females; median age, years: 8.6 (range 5.1-13.4)] were studied; 12 prepubertal children with short stature (SS) [7 males, 5 females; median age, years: 8.1 (range 4.8-13.1)] served as the control group. GH secretion after arginine stimulation test; IGF1 generation test by measurement of IGF1 levels before and after recombinant GH (rGH) administration (0.05 mg/kg/day for 4 days). Baseline and stimulated peak values of GH were not significantly different between the two groups. At +120 minutes, GH levels remained significantly higher (p = 0.0121) in comparison with baseline values in children with Noonan syndrome. Baseline IGFI levels in patients and in SS controls were not significantly different, in contrast to values after the rGH generation test [205 ng/mL (interquartiles 138.2-252.5 ng/mL) and 284.5 ng/mL (interquartiles 172-476 ng/mL), respectively; p = 0.0248]. IGF1 values were significantly related to height (baseline: r = 773, p = 0.0320; peak: r = 0.591, p = 0.0428) in children with Noonan syndrome. Blunted increase of IGF1 after the rGH generation test was present in children with Noonan syndrome due to mutations in the PTPN11 gene in comparison with SS children. This finding may be due to partial GH resistance in the former likely related to altered Ras-MAPK signaling pathway.


Shah-Waardenburg syndrome.
A case of Shah-Waardenburg syndrome, a rare variant of Waardenburg syndrome, is presented. Inherited as an autosomal recessive or dominant trait, the disorder presumably results from defective migration of neural crest cells. It clinically manifests with pigmentary anomalies and congenital megacolon.


Mechanism and amelioration of recombinant human interleukin-11 (rhIL-11)-induced anemia in healthy subjects.
Recombinant human interleukin-11 (rhIL-11), or Neumega rhIL-11 Growth Factor, is a recombinant cytokine that stimulates megakaryocytopoiesis, increases platelet production, and also has shown anti-inflammatory and immune-modulating activity. Mild, reversible anemia was the most common adverse event observed in clinical studies and was demonstrated to be related to hemodilution. The purpose of this study was to examine the renal mechanisms of the rhIL-11-induced volume retention and devise a possible therapeutic intervention to ameliorate this effect. Eighteen healthy volunteers (9 male and 9 female) on a controlled sodium (180 mEq/day) and potassium (120 mEq/day) diet were randomized to one of six treatment sequences in a three-period crossover design. Each subject received 25 micrograms/kg IL-11 s.c. once daily, 25 micrograms/kg IL-11 s.c. once daily + Maxzide-25 twice daily, or placebo for 7 days in a crossover design. There was a 14-day washout period between treatment periods. Renal clearance parameters indicated that mean sodium excretion was decreased compared to placebo within 8 hours after dosing with rhIL-11, with these results reaching statistical significance 8 to 16 hours postdose (p < 0.01). The cumulative sodium excretion (mEq +/- SD) over the 7-day treatment period for each respective treatment group was the following: rhIL-11 = 833 +/- 154, rhIL-11 + Maxzide-25 twice daily = 1114 +/- 178, and placebo = 982 +/- 193 (p < 0.01). Hemoglobin concentration and hematocrit values, used as indicators of hemodilution, decreased in the rhIL-11-treated group as compared to the baseline and placebo groups (p < 0.01). Concurrent dosing with Maxzide-25 twice daily reduced the rhIL-11-associated hemodilution by about 50%.


Associations between serum cholinesterase and incident hyper-LDL cholesterolemia, hypertriglyceridemia and hypo-HDL cholesterolemia as well as changes in lipid levels in a health screening population.
To investigate longitudinal associations between serum cholinesterase (ChE) and lipid status. Hazard ratios (HRs) of incident hyper-LDL cholesterolemia, hypertriglyceridemia and hypo-HDL cholesterolemia for baseline ChE and correlation coefficients between baseline ChE and changes in LDL cholesterol, log triglycerides and HDL cholesterol during 5 years were calculated in a health screening population. During the 5-year follow-up period, 337 men (22.9%) and 208 women (26.3%), 330 men (24.3%) and 114 women (12.4%) and 137 men (8.3%) and 117 women (12.7%) developed hyper-LDL cholesterolemia, hypertriglyceridemia and hypo-HDL cholesterolemia, respectively. The HRs of incident hyper-LDL cholesterolemia, hypertriglyceridemia and hypo-HDL cholesterolemia for each 1 SD increase in baseline ChE were 1.15 (p = 0.009) in men and 1.17 (p = 0.017) in women, 1.25 (p < 0.001) in men and 1.37 (p < 0.001) in women and 1.15 (p = 0.113) in men and 1.12 (p = 0.248) in women, respectively adjusted for BMI and other confounders, while the HRs were not significant after further adjusted for each baseline lipid level except for the HR of hypertriglyceridemia in women (HR, 1.22 (p = 0.047)). The baseline ChE was inversely correlated with the changes in LDL cholesterol (r = -0.117, p < 0.001) and log triglycerides (r = -0.114, p < 0.001) in men and the change in LDL cholesterol (r = -0.191, p < 0.001) in women. ChE was positively associated with incident hyper-LDL cholesterolemia and hypertriglyceridemia adjusted for BMI, while with only incident hypertriglyceridemia in women after further adjusted for the baseline lipid level.


A 1,4-dihydropyridine derivative reduces DNA damage and stimulates DNA repair in human cells in vitro.
Compounds of the 1,4-dihydropyridine (1,4-DHP) series have been shown to reduce spontaneous, alkylation- and radiation-induced mutation rates in animal test systems. Here we report studies using AV-153, the 1,4-DHP derivative that showed the highest antimutagenic activity in those tests, to examine if it modulates DNA repair in human peripheral blood lymphocytes and in two human lymphoblastoid cell lines, Raji and HL-60. AV-153 caused a 50% inhibition of growth (IC50) of Raji and HL-60 cells at 14.9+/-1.2 and 10.3+/-0.8mM, respectively, but did not show a cytotoxic effect at concentrations <100 microM. Alkaline single-cell gel electrophoresis (comet) assays showed that AV-153 reduced the number of DNA strand breaks in untreated cells and also in cells exposed to 2 Gy of gamma-radiation, 100 microM ethylmethane sulfonate (EMS), or 100 microM H2O2. DNA damage was reduced by up to 87% at AV-153 concentrations between 1 and 10nM, and a positive dose-effect relationship was seen between 0.01 and 1 nM. Comparison of the kinetics of DNA strand-break rejoining in the presence and absence of AV-153 revealed a considerable influence on the rate of repair. In view of the resemblance of this compound's structure to that of dihydronicotinamide, a substrate for poly(ADP-rybose)polymerase, the modulation of DNA repair by AV-153 could involve an influence on poly(ADP)ribosylation.


Integration of genome-scale modeling and transcript profiling reveals metabolic pathways underlying light and temperature acclimation in Arabidopsis.
Understanding metabolic acclimation of plants to challenging environmental conditions is essential for dissecting the role of metabolic pathways in growth and survival. As stresses involve simultaneous physiological alterations across all levels of cellular organization, a comprehensive characterization of the role of metabolic pathways in acclimation necessitates integration of genome-scale models with high-throughput data. Here, we present an integrative optimization-based approach, which, by coupling a plant metabolic network model and transcriptomics data, can predict the metabolic pathways affected in a single, carefully controlled experiment. Moreover, we propose three optimization-based indices that characterize different aspects of metabolic pathway behavior in the context of the entire metabolic network. We demonstrate that the proposed approach and indices facilitate quantitative comparisons and characterization of the plant metabolic response under eight different light and/or temperature conditions. The predictions of the metabolic functions involved in metabolic acclimation of Arabidopsis thaliana to the changing conditions are in line with experimental evidence and result in a hypothesis about the role of homocysteine-to-Cys interconversion and Asn biosynthesis. The approach can also be used to reveal the role of particular metabolic pathways in other scenarios, while taking into consideration the entirety of characterized plant metabolism.


Perceptual speed does not cause intelligence, and intelligence does not cause perceptual speed.
There is ongoing debate whether the efficiency of local cognitive processes leads to global cognitive ability or whether global ability feeds the efficiency of basic processes. A prominent example is the well-replicated association between inspection time (IT), a measure of perceptual discrimination speed, and intelligence (IQ), where it is not known whether increased speed is a cause or consequence of high IQ. We investigated the direction of causation between IT and IQ in 2012 genetically related subjects from Australia and The Netherlands. Models in which the reliable variance of each observed variable was specified as a latent trait showed IT correlations of -0.44 and -0.33 with respective Performance and Verbal IQ; heritabilities were 57% (IT), 83% (PIQ) and 77% (VIQ). Directional causation models provided poor fits to the data, with covariation best explained by pleiotropic genes (influencing variation in both IT and IQ). This finding of a common genetic factor provides a better target for identifying genes involved in cognition than genes which are unique to specific traits.


Contrast-Enhanced Ultrasound for Monitoring Non-surgical Treatments of Uterine Fibroids: A Systematic Review.
Non-surgical treatment options for uterine fibroids are uterine artery embolization (UAE), high-intensity focused ultrasound ablation (HIFUA), and percutaneous microwave ablation (PMWA). Magnetic resonance imaging (MRI) is the reference standard imaging method before and after these procedures. Contrast-enhanced ultrasound (CEUS) has been studied as an alternative to MRI for evaluating the fibroids' characteristics and responses to non-surgical treatments. PubMed, Ovid MEDLINE and Scopus databases were searched for literature published from January 2000 through June 7, 2020, that investigated the application of CEUS as an adjunct to monitor UAE, HIFUA or PMWA in human uterine fibroid treatments. Two independent reviewers analyzed 128 publications, out of which 17 were included. Based on this systematic review, CEUS provides detailed data about fibroid volume and vascularization prior, during and post UAE, and it helps determine the endpoint of the procedure. HIFUA with intra-procedural CEUS has faster volume shrinkage over a shorter time period with less needed energy and provides early detection of residual tissue after HIFUA. CEUS and contrast-enhanced MRI have sufficient agreement to be used interchangeably in the clinic to evaluate the therapeutic effect of PMWA and HIFUA on fibroids.


Carcinoid tumors of the rectum.
Carcinoid tumors of the rectum are not uncommon. However, multiple rectal carcinoids are very rare but can occur. The behavior of the rectal carcinoids is different than that of carcinoid tumors in other areas of the gastrointestinal tract. All carcinoids are malignant, and management is based on size and depth of invasion.


Carcinoma of the nasopharynx in Northern Israel: epidemiology and treatment results.
Between 1968 and 1984, 49 patients with carcinoma of the nasopharynx were treated at the Northern Israel Oncology Center. There were 6 stage I-II patients (12%) and 43 stage III-IV patients (88%). According to ethnic origin, there were 27 (55%) non-Ashkenazi Jews, 9 (18%) Ashkenazi Jews, and 13 (27%) Arabs. This distribution is different from the percentages of these ethnic groups in Northern Israel. All patients received combined cobalt 60 and 8-10 MeV electron beam radiotherapy to the primary tumor and the entire neck. Twelve stage III-IV patients received three courses of chemotherapy using bleomycin, methotrexate, and cisplatin (BMP) prior to definitive radiotherapy. The following 5-yr actuarial survival figures were achieved: all patients, 42%; stage I-II, 63%; stage III-IV, 37%; Arabs, 53%, non-Ashkenazi Jews, 47%; Ashkenazi Jews, 22%; BMP+radiotherapy, 54%; radiotherapy alone, 42%. It is concluded that there is an ethnic-related pattern of nasopharyngeal carcinoma in Northern Israel. Prognosis is better in non-Ashkenazi Jews and Arabs with early-stage lymphoepithelioma or anaplastic carcinoma, younger than 45 yr old, and receiving more than 5,500 cGy. Chemotherapy by BMP improves initial control rates with questionable benefit to long-term survival.


Surveillance of diphtheria in the Netherlands between 2000-2021: cutaneous diphtheria supersedes the respiratory form.
Diphtheria is a severe respiratory or cutaneous infectious disease, caused by exotoxin producing Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis. Diphtheria is once again prevalent due to breakdown of immunisation programmes, social disruption and unrest. This study describes the notified diphtheria cases in the Netherlands between 2000-2021 and isolates that were sent to the National Institute for Public Health and the Environment (RIVM). File investigation was performed including all notified cases and isolates of C. diphtheriae, C. ulcerans and C. pseudotuberculosis that were tested for toxin production using a toxin-PCR and Elek test. An exploratory review was performed to understand transmission in populations with a high vaccination uptake. Eighteen diphtheria notifications were made with confirmed toxigenic C. diphtheriae (n = 9) or ulcerans (n = 9) between 2000 and 2021. Seventeen (94.4%) presented with a cutaneous infection. All cases with a suspected source abroad (n = 8) concerned infection with C. diphtheriae. In contrast, 9/10 cases infected in the Netherlands were caused by C. ulcerans, a zoonosis. Secondary transmission was not reported. Isolates of C. ulcerans sent to the RIVM produced more often the diphtheria exotoxin (11/31; 35%) than C. diphtheriae (7/89; 7.9%). Both human-to-human transmission of C. diphtheriae and animal-to-human transmission of C. ulcerans rarely occurs in the Netherlands. Cases mainly present with a cutaneous infection. Travel-related cases remain a risk for transmission to populations with low vaccination coverage, highlighting the importance of immunization and diphtheria control measures.


Posterior urethral valves managed by cutaneous ureterostomy with subsequent ureteral reconstruction.
Six boys, 2 weeks to 5 years old, underwent cutaneous ureterostomy for massively dilated upper urinary tracts secondary to obstruction by posterior urethral valves. Cutaneous ureterostomies had been performed elsewhere in 2 patients. Two patients underwent transurethral fulguration of the valves initially with no improvement. Blood urea nitrogen, creatinine and serum electrolyte values continued to increase and, therefore, cutaneous ureterostomies were performed with dramatic improvement. Two patients presented with sepsis, one of whom had a positive blood culture. Both children had severe pyonephrosis and after the conditions improved with medical treatment cutaneous ureterostomies were done. The total number of surgical procedures required for all patients was 59, including renal biopsies, nephrostomies and cystoscopies. No kidneys, except for the severely dysplastic ones, were lost and all patients resumed normal growth rates and have had no urinary tract infections. All laboratory values are within normal limits.


Hunger Potentiates the Habenular Winner Pathway for Social Conflict by Orexin-Promoted Biased Alternative Splicing of the AMPA Receptor Gene.
Many animals fight for dominance between conspecifics. Because winners could obtain more resources than losers, fighting outcomes are important for the animal's survival, especially in a situation with insufficient resources, such as hunger. However, it remains unclear whether and how hunger affects fighting outcomes. Herein, we investigate the effects of food deprivation on brain activity and fighting behaviors in zebrafish. We report that starvation induces winning in social conflicts. Before the fights, starved fish show potentiation of the lateral subregion of the dorsal habenula (dHbL)-dorsal/intermediate interpeduncular nucleus (d/iIPN) pathway, which is known to be essential for and potentiated after winning fights. Circuit potentiation is mediated by hypothalamic orexin/hypocretin neuropeptides, which prolong AMPA-type glutamate receptor (AMPAR) activity by increasing the expression of a flip type of alternative splicing variant of the AMPAR subunit. This mechanism may underlie how hungry vertebrates win fights and may be commonly shared across animal phylogeny.


Immunocytochemical investigations of murine leukodystrophies. A study of the mutants 'jimpy' (jp) and 'myelin deficient' (mld).
Sections of the central nervous system of the leukodystrophic mouse mutants 'jimpy' (jp) and 'myelin deficient' (mld), as well as of healthy littermates, were immunostained for glial fibrillary acidic protein (GFA), myelin basic protein (MBP) and myelin-associated glycoprotein (MAG). Adjacent sections were stained conventionally for myelin. In jp, GFA-stained astrocytes were abnormally prominent already at the age of 12 days. A considerable amount of MBP and MAG was present in the vicinity of axons, although no myelin was visible in the conventional stains for myelin. In mld, GFA-staining astrocytes were present in normal numbers. MAG could be demonstrated in its normal localization along axons, but MBP was visible only in the comparatively old animal (85 days). Here, it was demonstrated in an abnormal site--the perikarya and the proximal parts of the processes of oligodendrocytes. Thin myelin sheaths present in this animal could not be stained for MBP.


Three-Dimensional Image Fusion of 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography and Contrast-Enhanced Computed Tomography for Computer-Assisted Planning of Maxillectomy of Recurrent Maxillary Squamous Cell Carcinoma and Defect Reconstruction.
The purpose of this study was to describe new technology assisted by 3-dimensional (3D) image fusion of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT (CECT) for computer planning of a maxillectomy of recurrent maxillary squamous cell carcinoma and defect reconstruction. Treatment of recurrent maxillary squamous cell carcinoma usually includes tumor resection and free flap reconstruction. FDG-PET/CT provided images of regions of abnormal glucose uptake and thus showed metabolic tumor volume to guide tumor resection. CECT data were used to create 3D reconstructed images of vessels to show the vascular diameters and locations, so that the most suitable vein and artery could be selected during anastomosis of the free flap. The data from preoperative maxillofacial CECT scans and FDG-PET/CT imaging were imported into the navigation system (iPlan 3.0; Brainlab, Feldkirchen, Germany). Three-dimensional image fusion between FDG-PET/CT and CECT was accomplished using Brainlab software according to the position of the 2 skulls simulated in the CECT image and PET/CT image, respectively. After verification of the image fusion accuracy, the 3D reconstruction images of the metabolic tumor, vessels, and other critical structures could be visualized within the same coordinate system. These sagittal, coronal, axial, and 3D reconstruction images were used to determine the virtual osteotomy sites and reconstruction plan, which was provided to the surgeon and used for surgical navigation. The average shift of the 3D image fusion between FDG-PET/CT and CECT was less than 1 mm. This technique, by clearly showing the metabolic tumor volume and the most suitable vessels for anastomosis, facilitated resection and reconstruction of recurrent maxillary squamous cell carcinoma. We used 3D image fusion of FDG-PET/CT and CECT to successfully accomplish resection and reconstruction of recurrent maxillary squamous cell carcinoma. This method has the potential to improve the clinical outcomes of these challenging procedures.


Intralesional laser treatment of voluminous vascular lesions in the oral cavity.
In laser treatment of voluminous vascular lesions, there are many cases in which submucosally located angioma remnants cannot be reached by noncontact superficial laser application. To diminish these remnants we used intralesional photocoagulation (ILP) in treatment of oral vascular lesions, because this approach is effective in treatment of voluminous vascular lesions of the skin. Four cases of voluminous vascular malformation in the oral cavity were treated by ILP using a potassium-titanyl-phosphate (KTP) laser. In 1 case, treatment was carried out under ultrasound and manual control. All lesions showed more than 70% regression after the first ILP session, and the treatment outcome was satisfactory. There were no serious complications, such as bleeding or invasive infection. Ultrasonography was useful for guiding laser treatment in the oral cavity. Intralesional photocoagulation treatment with a KTP laser is effective and safe for treatment of a vascular lesion in the oral cavity.


Temperature-mediated flower size plasticity in Arabidopsis.
Organisms can rapidly mitigate the effects of environmental changes by changing their phenotypes, known as phenotypic plasticity. Yet, little is known about the temperature-mediated plasticity of traits that are directly linked to plant fitness such as flower size. We discovered substantial genetic variation in flower size plasticity to temperature both among selfing Arabidopsis thaliana and outcrossing A. arenosa individuals collected from a natural growth habitat. Genetic analysis using a panel of 290 A. thaliana accession and mutant lines revealed that MADS AFFECTING FLOWERING (MAF) 2-5 gene cluster, previously shown to regulate temperature-mediated flowering time, was associated to the flower size plasticity to temperature. Furthermore, our findings pointed that the control of plasticity differs from control of the trait itself. Altogether, our study advances the understanding of genetic and molecular factors underlying plasticity on fundamental fitness traits, such as flower size, in response to future climate scenarios.


New insight in the neuropharmacological activity of Humulus lupulus L.
The purpose of the present study was to investigate the effects of Humulus lupulus CO2 extract and its fraction containing alpha-acids on the central nervous system of rats. Both tested substances were able to prolong pentobarbital sleeping time, without affecting the latency to the loss of the righting reflex. This effect was dose-dependent, starting from a minimal dose of 10 mg/kg. Neither the extract nor its alpha-acid fraction affected the locomotor activity in the open field test or exerted an anxiolytic effect in rats submitted to the elevated plus-maze test. Interestingly both compounds reduced the immobility time during the behavioral despair test when administered three times (24, 5 and 1 h) before the test. In conclusion this report shows that Humulus lupulus CO2 extract exerts: (a) a pentobarbital sleep-enhancing property without influencing the motor behavior of rats; (b) an antidepressant activity. The same effects were elicited by the administration of the Humulus lupulus fraction containing alpha-acids, which can be considered as the major responsible for the enhanced pentobarbital effect and for the antidepressant property.


The medical humanities - a brief introduction.
The medical humanities is a broad area of study and practice encompassing all nontechnical or 'human' aspects of medicine. This article introduces a series in the medical humanities in Australian Family Physician. The medical humanities serve three main goals: the study of the human aspects of medicine from within traditional arts disciplines of history, philosophy, sociology and literature; the intersection of medicine and the creative arts; and the training of more insightful and compassionate doctors. This article briefly explores these three goals and discusses their value for the medical community.


Cytophysiological Changes in the Follicular Epithelium of the Thyroid Gland after Long-Term Exposure to Low Doses of Dichlorodiphenyltrichloroethane (DDT).
Exposure to endocrine disruptors is considered as a risk factor thyroid gland diseases. We analyzed cytophysiological changes in rat thyroid follicular epithelium after long-term exposure to low doses of the most widespread disruptor DDT. Analysis of thyroid hormone production and light and electron microscopy of thyroid gland samples revealed cytophysiological changes in thyroid epithelium related to impaired transport through the apical membrane, suppressed Golgi complex activity, and impaired thyrotrophic hormone regulation of the secretory functions of thyroid cells, which led to compensatory transition from merocrine to microapocrine secret release.


Branched chain amino/keto acid supplementation following severe burn injury: a preliminary report.
14 severely burned patients were randomly assigned to receive one of three nasogastric feeds commencing after the resuscitation period and continuing for 15 days. Group A received a feed with a high leucine content (31% of protein as branched chain amino-acids, BCAA). Group B received a similar feed to Group A but 65% of the leucine was replaced by alpha-ketoisocaproate (KIC). Group C received a whole protein feed (16% of the protein content as BCAA), and acted as a control group. Targeted energy intake was twice the calculated Basal Metabolic Rate (BMR). Group A had significantly reduced urinary 3-methylhistidine (3-MEH) and serum urea, compared with the control group. Serum total protein, albumin and transferrin and apparent nitrogen balance were not significantly different. Group B's results did not vary significantly from controls. Leucine enrichment reduces muscle protein breakdown benefiting burn patients fed enterally when compared to a standard feed, whereas KIC enrichment does not.


The Effect of Doxycycline on PMA-Induced MUC5B Expression via MMP-9 and p38 in NCI-H292 Cells.
Doxycycline is commonly used in medicine for its bacteriostatic antimicrobial properties. Recent studies have reported that doxycycline also has anti-inflammatory effects. Matrix metalloproteinase (MMP)-9 has been found to be involved in the physiological and pathological process of inflammatory airway disease. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, is known to stimulate the expression of MMP and mucin genes in the airway and intestinal epithelial cells. Therefore, the effects and signal pathways of doxycycline on PMA-induced MUC5B expression dependent MMP-9 in human airway epithelial cells were investigated. In human NCI-H292 airway epithelial cells, MUC5B and MMP-9 mRNA expression, MUC5B protein expression, and MMP-9 protein activity after the treatment with PMA, MMP-9 or doxycycline were determined by reverse transcriptase-polymerase chain reaction, enzyme immunoassay, gelatin zymography, and Western blot analysis. PMA increased MMP-9 and MUC5B expression. MMP-9 increased MUC5B expression. Doxycycline inhibited PMA-induced MUC5B expression, and PMA-induced MMP-9 mRNA expression and protein activity. Doxycycline inhibited phosphorylation of p38 induced by PMA and MMP-9. The results of this study suggest that doxycycline inhibited PMA-induced MUC5B mRNA expression and protein production through the MMP-9 and p38 pathways in human NCI-H292 airway epithelial cells.


Ulnar neuropathies in rheumatoid arthritis.
A loss of functional motor axons in the median and ulnar nerves occurred in half of thirty-three patients with rheumatoid arthritis. Weakness of small hand muscles may predispose to the development of ulnar deviation of the fingers in patients with joint disease at the radio-ulnar and metacarpophalangeal joints. There is no evidence that spasm of small hand muscles is a significant cause of ulnar deviation of the fingers in rheumatoid arthritis. Ulnar deviation of the fingers in rheumatoid arthritis is not due to selective impairment of the ulnar nerve or the deep palmar branch of the ulnar nerve even though ulnar deviation of the fingers can occur in association with such lesions and in the absence of joint disease.


Identifying the High-Risk Fetus in the Low-Risk Mother Using Fetal Doppler Screening.
Identifying the high-risk fetus in the low-risk pregnant mother (LRM) is a neglected area of research. Fetal growth restriction (FGR) is a major cause of stillbirths, especially in low- and middle-income countries (LMICs). FGR is very poorly detected particularly in healthy pregnant women classified as low risk. Umbiflow is an inexpensive continuous-wave Doppler ultrasound (CWDU) apparatus that is suitable for use by low-level health care providers for screening low-risk pregnant populations. It can easily detect umbilical artery blood flow in the cord, which correlates well with placental function, and poor placental function correlates well with FGR.Use of CWDU to screen an LMIC population of more than 7,000 LRMs has demonstrated a high prevalence of abnormal umbilical artery flow of 13%, and absent end-diastolic flow, which is associated with end-stage placental disease, was found in 1.2%. This is 10 times higher than previously reported in high-income countries. Screening with CWDU together with a standard protocol managing those pregnancies with abnormal placental blood flow resulted in a 43% reduction in stillbirths (risk ratio: 0.57; 95% confidence interval=0.29, 0.85) in this LRM population. Further, follow-up of infants who had abnormal umbilical artery blood flow showed that these infants had significantly less fat-free mass at ages 6 weeks, 10 weeks, 14 weeks, and 6 months, than those with normal umbilical artery blood flow (P<.015), confirming that CWDU was able to detect true FGR.Thus, screening with CWDU can detect the fetus at risk of stillbirth, and infants likely to have suboptimal growth and development postnatally. Screening with CWDU in LRMs opens the door to a step change in preventing stillbirths in LMICs.


Quantitative biofouling diagnosis in full scale nanofiltration and reverse osmosis installations.
Biofilm accumulation in nanofiltration and reverse osmosis membrane elements results in a relative increase of normalised pressure drop (DeltaNPD). However, an increase in DeltaNPD is not exclusively linked to biofouling. In order to quantify biofouling, the biomass parameters adenosine triphosphate (ATP), total cell count and heterotrophic plate count in membrane elements were investigated during membrane autopsies and compared with DeltaNPD in test rigs and 15 full scale investigations with different types of feed water. The combination of biomass related parameters ATP and total cell count in membrane elements seem to be suitable parameters for diagnosis of biofouling, whereas plate counts were not appropriate to assess biofouling. The applied DeltaNPD measurement was too insensitive for early detection of fouling. Measurements of biological parameters in the water were shown to be not appropriate in quantifying biofouling. Evidently, there is a need for a practical tool, sensitive pressure drop data and systematic research.


Level of incongruence during cardiac rehabilitation and prediction of future CVD-related hospitalizations plus all-cause mortality.
Independent of traditional risk factors, psychosocial risk factors increase the risk of cardiovascular disease (CVD). Studies in the field of psychotherapy have shown that the construct of incongruence (meaning a discrepancy between desired and achieved goals) affects the outcome of therapy. We prospectively measured the impact of incongruence in patients after undergoing a cardiac rehabilitation program. We examined 198 CVD patients enrolled in a 8-12 week comprehensive cardiac rehabilitation program. Patients completed the German short version of the Incongruence Questionnaire and the SF-36 Health Questionnaire to measure quality of life (QoL) at discharge of rehabilitation. Endpoints at follow-up were CVD-related hospitalizations plus all-cause mortality. During a mean follow-up period of 54.3 months, 29 patients experienced a CVD-related hospitalization and 3 patients died. Incongruence at discharge of rehabilitation was independent of traditional risk factors a significant predictor for CVD-related hospitalizations plus all-cause mortality (HR 2.03, 95% CI 1.29-3.20, p = .002). We also found a significant interaction of incongruence with mental QoL (HR .96, 95% CI .92-.99, p = .027), i.e. incongruence predicted poor prognosis if QoL was low (p = .017), but not if QoL was high (p = .74). Incongruence at discharge predicted future CVD-related hospitalizations plus all-cause mortality and mental QoL moderated this relationship. Therefore, incongruence should be considered for effective treatment planning and outcome measurement.


Higher ratio of serum uric acid to serum creatinine (SUA/SCr) increases the risk of metabolic unhealthy phenotype.
It is very important to understand which factors play roles in switching from a healthy to an unhealthy metabolism. It is unclear if SUA/SCr is an independent risk factor for metabolic unhealthy phenotype. We examined whether SUA/SCr is associated with an increased risk for metabolic unhealthy phenotype in the Chinese population. As many as 3158 subjects aged 25-75 years who had a metabolic healthy phenotype at baseline were included in the retrospective cohort study. They were assigned to four groups based on the quartile of SUA/SCr. We compared the demographic and clinical characteristics among the four groups. The correlation between SUA/SCr and the risk of metabolic unhealthy phenotype in the overall population and stratified by subgroups was examined by logistic regression analyses. Greater SUA/SCr values were correlated with greater BMI, systolic and diastolic BP, TC, TG, RBC, WBC, HB, ALT, SUA and eGFR. During the two-year follow-up, 632 of the study subjects (20.01%) developed new-onset metabolic unhealthy phenotype from the total of 3158 study subjects. A statistically significant increase in the rates of metabolic unhealthy phenotype was observed with increasing SUA/SCr levels within each group. After multivariate adjustment, the adjusted ORs and 95% CIs were 1.44 (1.03-2.00) and 2.11 (1.52-2.94) in the Q3 group and Q4 group, respectively. SUA/SCr was positively related to the risk of metabolic unhealthy phenotype in the Chinese subjects, suggesting the potential of SUA/SCr to serve as an independent risk predictor in the development of metabolic unhealthy phenotype.


Toxins from cone snails: properties, applications and biotechnological production.
Cone snails are marine predators that use venoms to immobilize their prey. The venoms of these mollusks contain a cocktail of peptides that mainly target different voltage- and ligand-gated ion channels. Typically, conopeptides consist of ten to 30 amino acids but conopeptides with more than 60 amino acids have also been described. Due to their extraordinary pharmacological properties, conopeptides gained increasing interest in recent years. There are several conopeptides used in clinical trials and one peptide has received approval for the treatment of pain. Accordingly, there is an increasing need for the production of these peptides. So far, most individual conopeptides are synthesized using solid phase peptide synthesis. Here, we describe that at least some of these peptides can be obtained using prokaryotic or eukaryotic expression systems. This opens the possibility for biotechnological production of also larger amounts of long chain conopeptides for the use of these peptides in research and medical applications.


Acenaphtho[1,2-d][1,2,3]triazole and Its Kuratowski Complex: A π-Extended Tecton for Supramolecular and Coordinative Self-Assembly.
π-Extended acenaphtho[1,2-d][1,2,3]triazoles, the unsubstituted Anta-H and its di-tert-butyl derivative Dibanta-H, as well as 5,6,7,8-tetrahydro-1H-naphtho[2,3-d][1,2,3]triazole Cybta-H were obtained in concise syntheses. In the solid state, Dibanta-H forms an unprecedented hydrogen-bonded cyclic tetrad, stabilized by dispersion interactions of the bulky tBu substituents, whereas a cyclic triad was found in the crystal structure of Anta-H. These cyclic assemblies form infinite slipped stacks in the crystals. Evidence for analogous hydrogen-bonded self-assembly in solution was provided by low-temperature NMR spectroscopy and computational analyses. Kuratowski-type pentanuclear complexes [Zn5 Cl4 (Dibanta)6 ] and [Zn5 Cl4 (Cybta)6 ] were prepared from the respective triazoles. In the Dibanta complexes, the π-aromatic surfaces of the ligands extend from the edges of the tetrahedral Zn5 core, yielding an enlarged structure with significant internal molecular free volume and red-shifted fluorescence.


Effect of experimentally induced low back pain on postural sway with breathing.
Although breathing perturbs balance, in healthy individuals little sway is detected in ground reaction forces because small movements of the spine and lower limbs compensate for the postural disturbance. When people have chronic low back pain (LBP), sway at the ground is increased, possibly as a result of reduced compensatory motion of the trunk. The aim of this study was to determine whether postural compensation for breathing is reduced during experimentally induced pain. Subjects stood on a force plate with eyes open, eyes closed, and while breathing with hypercapnoea before and after injection of hypertonic saline into the right lumbar longissimus muscle to induce LBP. Motion of the lumbar spine, pelvis, and lower limbs was measured with four inclinometers fixed over bony landmarks. During experimental pain, motion of the trunk in association with breathing was reduced. However, despite this reduction in motion, there was no increase in postural sway with breathing. These data suggest that increased body sway with breathing in people with chronic LBP is not simply because of reduced trunk movement, but instead, indicates changes in coordination by the central nervous system that are not replicated by experimental nociceptor stimulation.


Synthesis and structure of distanna and tristanna ansa half-sandwich complexes of ruthenium and nickel.
The synthesis and structural characterization of the first tin-bridged ansa half-sandwich complexes via a two-step protocol from Na[η(5)-C(5)H(5)Ru(CO)(2)] and in situ generated Na[η(5)-C(5)H(5)Ni(CO)] are presented. Both compounds are characterized by multinuclear NMR spectroscopy and single-crystal diffraction.


Evaluation of head injury in a pediatric emergency department: pretrauma and posttrauma system.
To determine if trauma center protocols affect the number of tests and consultations performed and the length of time spent in the emergency department or hospital. A retrospective review and comparison of treatment for children with isolated head injury admitted to the emergency department before trauma center designation (group 1, 1985), and 5 years after implementation of trauma center protocols (group 2, 1991). Urban children's hospital, level I trauma center. One hundred sixty-five children met the enrollment criteria in 1985 and 162 met the criteria in 1991. Falls were the predominant mechanism of injury (55%) for both years. For patients with moderate injury (Glasgow Coma Scale score, 9-12) or severe injury (Glasgow Coma Scale score, <9), there was no difference in radiographic or laboratory evaluation. For patients with minimal head injury (Glasgow Coma Scale score, 15, no loss of consciousness, amnesia, seizure, focal neurologic findings, or persistent symptoms) and minor head injury (Glasgow Coma Scale score, >12, and loss of consciousness or amnesia), more radiologic and laboratory studies were done in 1991 that showed no clinically significant abnormalities. Patients with minimal head injury in group 2 were 14 times more likely to have cranial computed tomographic scans performed (95% confidence interval [CI], 3.4-67); 11 times more likely to have cervical spine radiographs (95% CI, 2.2-76.6); and 23 times more likely to have hepatic enzymes obtained (95% CI, 3-491). These differences persisted when analyzed by both the age of the patient and mechanism of injury. Application of trauma system protocols to isolated head injury patient evaluation results in increased use of laboratory and radiologic services. These practices have the potential to increase the cost of medical care without significantly improving outcome.


A Dual-Locked Tandem Fluorescent Probe for Imaging of Pyroptosis in Cancer Chemo-Immunotherapy.
Real-time imaging of programmed cancer cell death (PCD) is imperative to monitor cancer therapeutic efficacy and tailor therapeutic regimens; however, specific in vivo detection of intratumoral pyroptosis remains challenging. Herein, a dual-locked and tandem activatable probe (DTAP) is reported for near-infrared fluorescence (NIRF) imaging of intratumoral pyroptosis during cancer chemo-immunotherapy in living mice. The probe comprises a hemicyanine dye dual-locked with an enzyme-responsive moiety that can be tandemly cleaved by pyroptosis-related biomarker (Caspase-1) and cancer biomarker (GGT) to turn on its NIRF signal. As pyroptosis plays a vital role in triggering anti-tumor immune responses, the activated signal of DTAP correlates well with the population of tumor-infiltrating cytotoxic T lymphocytes and tumor growth inhibition, consequently permitting the prediction of cancer therapeutic efficacy. This study also provides a non-invasive technique to study the regulatory mechanism of pyroptosis in cancer therapy and to optimize cancer chemo-immunotherapies for precision medicine.


Caries removal in primary teeth--a systematic review.
This systematic review addressed what the ideal limit is for removing carious tissue to address a caries lesion. The Medline, Cochrane, and PubMed databases were searched for abstracts of English-language articles published between 2000 and 2010 as well as randomized clinical trials about the total, partial, and/or nonmechanical removal of carious tissue in primary teeth. The analysis of the abstracts was performed individually by two reviewers. The full text of potentially relevant studies was obtained, analyzed based on criteria for quality assessment of a randomized clinical trial, and placed in an evidence-based table. After reading the abstracts, 151 articles were excluded. Six references met the inclusion criteria and were selected for full reading. After the reviewers consulted with one another, three papers were considered potentially relevant to this review. This analysis suggests that minimally invasive procedures for dental tissue are viable choices for stopping caries lesions. Partial or nonmechanical removal of carious tissue favors the arrest of dental caries lesions.


Characterization of globin mRNA from Xenopus laevis.
A 9S polyadenylated mRNA was isolated from 'xenopus laevis reticulocytes and purified by sedimentation and oligo-dT-cellulose chromatography. The size of this RNA estimated in denaturing agarose gels was 2.2 x 10(5) daltons. 9S polyadenylated mRNA hydridized to total DNA with a Cot1/2 of 3.8 x 10(3).


Impedance screening for otitis media with effusion in Nigerian children.
Tympanometry and acoustic reflex tests performed on 431 school children aged five to six years showed that eight per cent of the ears screened had type B or type C tympanograms suggestive of otitis media with effusion (1.2 per cent type B, and 6.8 per cent type C). Preliminary otoscopy revealed tympanic membrane appearances consistent with middle ear effusion in a correspondingly low proportion of ears (7.6 per cent), whilst acoustic reflex screening at 105 dB for three frequencies (0.5, 1 and 2 kHz) showed absent reflexes at one or more frequencies in 8.1 per cent of the ears. The findings indicate a relatively low prevalence of otitis media with effusion in children in Nigeria. Possible contributory factors are discussed.


Vaginoscopic Resection for Vaginal Rhabdomyosarcoma during Early Infancy: A Case Report.
Embryonal rhabdomyosarcoma, a malignant soft tissue neoplasm, is 1 of the most common pediatric tumors of the vagina. Although radical surgery has been replaced with radiation therapy, chemotherapy, and conservative surgery, the use of vaginoscopy is still uncommon. We present the case of an infant who underwent vaginoscopic resection because of botryoid sarcoma at 9 months of age.


Unraveling biogeochemical phosphorus dynamics in hyperarid Mars-analogue soils using stable oxygen isotopes in phosphate.
With annual precipitation less than 20 mm and extreme UV intensity, the Atacama Desert in northern Chile has long been utilized as an analogue for recent Mars. In these hyperarid environments, water and biomass are extremely limited, and thus, it becomes difficult to generate a full picture of biogeochemical phosphate-water dynamics. To address this problem, we sampled soils from five Atacama study sites and conducted three main analyses-stable oxygen isotopes in phosphate, enzyme pathway predictions, and cell culture experiments. We found that high sedimentation rates decrease the relative size of the organic phosphorus pool, which appears to hinder extremophiles. Phosphoenzyme and pathway prediction analyses imply that inorganic pyrophosphatase is the most likely catalytic agent to cycle P in these environments, and this process will rapidly overtake other P utilization strategies. In these soils, the biogenic δ18 O signatures of the soil phosphate (δ18 OPO4 ) can slowly overprint lithogenic δ18 OPO4 values over a timescale of tens to hundreds of millions of years when annual precipitation is more than 10 mm. The δ18 OPO4 of calcium-bound phosphate minerals seems to preserve the δ18 O signature of the water used for biogeochemical P cycling, pointing toward sporadic rainfall and gypsum hydration water as key moisture sources. Where precipitation is less than 2 mm, biological cycling is restricted and bedrock δ18 OPO4 values are preserved. This study demonstrates the utility of δ18 OPO4 values as indicative of biogeochemical cycling and hydrodynamics in an extremely dry Mars-analogue environment.


The population metabolism and life history tactics of Neobisium muscorum (Leach) (Arachnida: Pseudoscorpiones).
The population metabolism of N. muscorum at a beechwood site in southern England was determined for two separate year periods by two methods; a detailed computer analysis and a 'best estimate'. These methods, which are based on data of biomass, population dynamics, field temperatures, and respiration rates of all life stages with temperature, are compared. The validity of extrapolating laboratory determined basal metabolic rates to field activity is discussed; and the population metabolism of N. muscorum is compared with that reported for other soil and litter invertebrate species, both predatory and non-predatory.The metabolic rates of the adults of a second species of pseudoscorpion found at the beechwood site (Chthonius orthodactylus (Leach)), were determined, and the life cycle and metabolism of this species is compared to N. muscorum. The influence of low environmental temperatures on poikilothermic predators, with reference to life cycle strategies, basal metabolism and geographic distribution, is discussed.


Performance and microbial community dynamics in bioaugmented aerated filter reactor treating with coking wastewater.
In this study, zeolite-biological aerated filters (Z-BAFs) bioaugmented by free and magnetically immobilized cells of Arthrobacter sp. W1 were designed to treat coking wastewater containing high concentrations of phenol and naphthalene along with carbazole (CA), dibenzofuran (DBF), and dibenzothiophene (DBT). All treatments were carried out for a period of 100days and the data indicated that bioaugmented Z-BAFs with magnetically immobilized cells was most efficient for treating coking wastewaters. Illumina high-throughput sequencing was used to reveal the microbial community structures of Z-BAFs. Both bioaugmentation treatments could accelerate the shift of the bacterial community structures. The introduced strain W1 remained dominant in the bioaugmented Z-BAFs with magnetically immobilized cells, indicating both strain W1 and the indigenous degrading bacteria played the most significant role in the treatment. Overall, bioaugmented Z-BAF with magnetically immobilized cells can be used to efficiently degrade phenol, naphthalene, CA, DBF, and DBT in coking wastewater.


Drugs of abuse in oral fluid collected by two different sample kits--stability testing and validation using ultra performance tandem mass spectrometry analysis.
Oral fluid (OF) is an alternative matrix for monitoring drugs of abuse in workplace, clinical toxicology, criminal justice, and driving under the influence of drugs (DUID). OF is suitable for detection of drugs that have been taken recently. It is unproblematic to observe the collection and hence avoid the possibility of the samples being tampered. OF often contains compounds in low concentrations, and small volumes are often collected. It is therefore necessary to have a sensitive, multi component method for drug detection. In this study an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method has been developed. The samples were prepared by liquid-liquid extraction (LLE) with ethyl acetate/heptane (4:1) and the separation was achieved by an Acquity HSS T3-column (2.1 mm × 100 mm, 1.8 μm particles). Mass detection was performed by positive ion mode electrospray MS-MS. 32 drugs of abuse were determined with a cycle time of 9 min. Stability of drugs in oral fluid before analysis is an important factor that must be evaluated for each sampling device. The collection devices Intercept(®) and StatSure Saliva Sampler™ were tested using pools of real samples containing various drugs. The testing showed that 6-MAM (6-acetylmorphine), cocaine and zopiclone were the least stable compounds. In the testing for short term stability, StatSure Saliva Sampler™ showed better results. The testing of 1 year of storage at -20°C showed that most of the compounds were stable for both sampling devices, except for 6-MAM, cocaine and zopiclone. Samples of OF should be analysed as soon as possible after collection, and they should be kept frozen if immediate analysis is not possible.


Boswellic acids extract attenuates pulmonary fibrosis induced by bleomycin and oxidative stress from gamma irradiation in rats.
Interstitial pulmonary fibrosis is characterized by an altered cellular composition of the alveolar region with excessive deposition of collagen. Lung inflammation is also common in pulmonary fibrosis. This study aims to test the inhibition of 5-lipooxygenase (5-LOX) by boswellic acid (BA) extract in an experimental model of pulmonary fibrosis using bleomycin (BL). Boswellic acid extract (1 g/kg) was force-fed to rats seven days prior to administration of BL or gamma irradiation or both. BL (0.15 U/rat) in 25 μl of 0.9% normal saline (NS) or 0.9% NS alone was administered intratracheally. Rats were exposed to two fractionated doses of gamma irradiation (0.5 Gy/dose/week) with a gamma cell-40 (Cesium-137 irradiation units, Canada) during the last two weeks of the experiment. BA was administered during BL or irradiation treatment or both. After the animals were sacrificed, bronchoalveolar lavage was performed; lungs were weighed and processed separately for biochemical and histological studies. In rats treated with BL, levels of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) were significantly elevated (P = 0.05 and P = 0.005). Hydroxyproline was highly and extensively expressed. Immunoreactive compounds were abundantly expressed, represented in the levels of macrophages infiltrate, accumulation of eosinophils and neutrophils in the lung as well as the aggregation of fibroblasts in the fibrotic area. The levels of lipoxygenase enzyme activity were significantly increased (P = 0.005). Antioxidant activities measured in BL-treated rats deteriorated, coupled with the elevation of both levels of plasma lipid peroxide (LP) content and bronchoalveolar lavage lactate dehydrogenase activity. BA-treated rats had reduced number of macrophages, (P = 0.01), neutrophils in bronchoalveolar lavage (P = 0.01) and protein (P = 0.0001). Moreover, the hydroxyproline content was significantly lowered in BA-treated rats (P = 0.005). BA extract inhibited the TGF-ß induced fibrosis (P = 0.01) and 5-LOX activity levels (P = 0.005).Histologically, BA reduced the number of infiltrating cells, ameliorated the destruction of lung architecture and attenuated lung fibrosis. BA attenuates the BL-induced injury response in rats, such as collagen accumulation, airway dysfunction and injury. This study suggests that the blocking of 5-LOX may prevent the progression of fibrosis.


The effects of identification with a support group on the mental health of people with multiple sclerosis.
Multiple sclerosis (MS) is associated with various psychological problems, including depression and anxiety. Whilst MS support groups are intended to improve mental health, this goal is not always achieved. Taking a social identity approach, we hypothesise that it is the level of subjective identification with a support group (rather than simply support group membership per se) that positively affects the mental health of people with MS. 152 individuals with MS were recruited via UK MS support groups and completed a questionnaire. This included measures of support group identification, depression, anxiety and satisfaction with life, as well as control variables (education level and age). Analyses revealed that, as hypothesised, support group identification was significantly linked to depression, anxiety and satisfaction with life. Moreover, group identification explained a significant amount of variance in addition to that explained by education and age on each health outcome. Repeating the analysis to compare each of the three main sub-types of MS revealed these effects to be present for individuals with relapsing-remitting (RR) and Primary Progressive (PP) MS, but not for those with secondary progressive (SP) MS. We suggest that identifying highly with an MS support group has important positive outcomes for MS patients' mental health. This has implications for practicing clinicians: people with MS (particularly RRMS and PPMS) should be encouraged to engage with support groups, but more must be done to ensure they subjectively identify with these groups, rather than merely attend them.


Polychlorinated biphenyls and organochlorine pesticides in milk of Norwegian women during lactation.
Milk samples of 14 women were analyzed for PCBs (polychlorinated biphenyls), p,p'-DDE, and HCB (hexachlorobenzene) during 11 intervals of a 120 day-lactation period. A general downward trend in residue levels was evident, and a statistically significant decline was observed for residue levels of PCBs (P less than 0.01) and HCB (P = 0.02) on the milk fat basis. Primipara (n = 9) had from 1.5 to 2.1 times higher mean residue levels than mothers nursing their second or third child (n = 9). Significant declines in residue levels during lactation of the first child were found, while no pronounced changes in residue levels were observed during lactation of the second or third child. Overall, residue levels in this study were lower than corresponding levels found earlier in Norway, and within the range of the corresponding levels found in another Norwegian human milk survey done at the same time.


Toward better preparedness for the next pandemic.
New York City has been described as the epicenter of the COVID-19 pandemic in the United States. While health care workers are notably at increased risk for COVID-19 infection, the impact on resident physicians remains unclear. In this issue of the JCI, Breazzano et al. surveyed resident physicians for their exposure to COVID-19 during the exponential phase of the COVID-19 pandemic. The researchers also assessed how personal protective equipment and COVID-19 testing protected health care workers from infection. This study highlights resident physician experiences of the first COVID-19 wave that can inform and improve preparedness for upcoming COVID-19 surges and other future epidemics.


Uncovering the underlying physical mechanism for cancer-immunity of MHC class I diversity.
The cancer cells are heterogeneous populated, which can be classified as MHC class I positive and MHC I class negative. They influence the immune system differently. In this work, we build a core cancer-immune circuit of MHC class I diversity including MHC class I positive cancer type, MHC I class I negative cancer type and 4 immune cell types to uncover the underlying mechanism of the cancer immunity based on the underlying landscape topography. We quantify four steady state attractors, normal state, two low cancer states and a high cancer state. The landscape topography changes upon changes in cancer self-activation and the related killing rate of the killer cells are illustrated. It demonstrates that the competition between the two cancer cell types. We simulate the tumorigenesis and development of cancer according to its biological process and classify these into 7 stages. This landscape framework provides a quantitative way to understand characteristics of these two cancer cell types under immune microenvironment and the underlying physical mechanisms of cancer cell evolution along cancer development.


Microwave ablation vs. parathyroidectomy for secondary hyperparathyroidism in maintenance hemodialysis patients.
Secondary hyperparathyroidism (SHPT) is a serious and common problem in patients undergoing maintenance hemodialysis. Minimally invasive microwave ablation (MWA) has been used to treat SHPT and shows some advantages. However, its efficacy is still undefined. The primary purpose of this study was to determine the efficacy and safety of MWA compared to total parathyroidectomy plus forearm autotransplantation. The SHPT patients who were undergoing maintenance hemodialysis (follow-up for 6 to 24 months after treatments) were divided into a MWA group (n = 33) and a parathyroidectomy group (n = 48). The efficacy (serum intact parathyroid hormone [iPTH], calcium, and phosphorus levels) and safety (hoarseness, hypocalcaemia, and persistently low iPTH) were compared between the two groups. Additionally, the study explored potential predictors of response to MWA by a logistic regression analysis. There were no significant differences in baseline characteristics between the two groups. The rates of achieving the recommended goal for iPTH were significantly higher in the MWA group than that in the parathyroidectomy group at all follow-up times: 57.58% vs. 12.50% at one-day (P < 0.001), 45.45% vs. 16.67% at 1-week (P = 0.005), 57.58% vs. 16.67% at 2-week (P < 0.001), 57.58% vs. 22.92% at 1-month (P = 0.002), and 69.70% vs. 35.42% at 3-month (P = 0.002), 76.47% vs. 28.57% at 6-month (P = 0.005), 87.50% vs. 47.37% at 12-month (P = 0.008), and 81.82% vs. 52.63% at 24-month (P = 0.015), respectively. However, there were no significant differences for phosphorus or calcium at any of the follow-up times (P > 0.05). The persistently low iPTH was more in the parathyroidectomy group (64.6%) than that in the MWA group (0%) (P < 0.001), but there was no significant difference in hoarseness or hypocalcaemia (P > 0.05). Baseline levels of iPTH (P = 0.021) and patient age (P = 0.011) were determined as predictors by univariate logistic regression analysis. The MWA could be an alternative to parathyroidectomy for SHPT but its eventual superiority has to be demonstrated by a proper study.


Inferior endothelial function improved following optimisation of asthma control in children.
Association between asthma control and cardiovascular disease (CVD) remains highly plausible as the two are related to chronic systemic inflammation. Children with physician-diagnosed asthma and matched healthy controls underwent endothelial function assessment. Repeat measurements were performed in uncontrolled asthmatics after initiation or up-titration of inhaled corticosteroids (ICS), compared to those with well-controlled asthma without ICS therapy. We found that children with uncontrolled asthma had inferior endothelial function compared to matched healthy controls. Enhancement in endothelial function, lung function and symptom control was observed in uncontrolled asthmatics after initiation or up-titration of inhaled corticosteroids (ICS). These results provided further evidence of a likely relationship between asthma control and cardiovascular health.


Pharmacotherapy of epileptic seizures in glioma patients: who, when, why and how long?
The risk for patients with primary brain tumors of experiencing an epileptic seizure at least once in the course of disease probably exceeds 50%, depending on tumor location and tumor type. Several aspects regarding the role of anticonvulsants in the treatment of brain tumor patients have remained controversial. We reviewed the seizure history in 107 patients undergoing a surgical procedure for glioma at our institution. The overall seizure incidence was 68%. Pre-operative seizures did not predict the occurrence of post-operative seizures. After surgery, postoperative chemo- or radiotherapy and anticonvulsive therapy one third of patients was seizure-free whereas one third showed frequent seizures despite this treatment. Seizure frequency increased regardless of anticonvulsive treatment with progressive or recurrent tumor growth. Based on a literature review and our institutional experience, we delineate some recommendations for the management of seizures in patients with brain tumors.


Reconstitution of Na+/H(+)-antiporter of bovine renal brush-border membrane into proteoliposomes and detection of a 110 kDa protein cross-reactive with antibodies against a human Na+/H(+)-antiporter partial peptide in antiport-active fractions after partial fractionation.
Bovine renal brush-border membranes were solubilized by 1.6% sodium cholate. Na+/H(+)-antiporter was recovered in the supernatant after centrifugation at 160,000 x g for 1 h and was successfully reconstituted into proteoliposomes by a cholate-dialysis procedure. The reconstituted Na+/H(+)-antiporter showed a pH-gradient dependent and amiloride-sensitive 22Na+ uptake very similar to that of brush-border membrane vesicles. Factors affecting the efficiency of reconstitution as well as the stability of the solubilized antiporter at various temperatures were studied. Sodium cholate-solubilized brush-border membrane proteins were fractionated by Sephacryl S-400 and DEAE-Toyopearl chromatography, and fractions containing reconstitutively active Na+/H(+)-antiporter were identified. A 110 kDa peptide cross-reactive with a polyclonal antibody against a C-terminal peptide (22-amino acid residues) of human Na+/H(+)-antiporter was consistently found on the immunoblot of the active fractions. A closely similar peptide was also detected in human placental membranes by this antibody. These results strongly suggest that the 110 kDa protein is responsible for Na+/H(+)-antiporter activity.


Participation in preschool activities of children with autistic spectrum disorder and comparison to typically developing children.
Participation is essential to children's development and is a major focus of intervention. This study aimed to describe the participation patterns of children with ASD, in comparison to typically developing (TD) children. 70 preschoolers participated: 33 children with ASD, attending non-inclusive-education settings; and 37 TD children, attending mainstream educational settings. Two occupational therapists assessed their participation through structured observations in self-care activities, play, learning, and social participation areas; demographic and environmental questionnaires were also completed. In the ASD group, frequency of participation was found to be significantly higher in ADL and learning than in other areas; level of performance was found to be significantly lower in social participation than in other areas. The TD group scored significantly higher than did the ASD group in most areas and scales. Initial findings tentatively showed that a structured educational environment for children with ASD may increase participation frequency. The findings are consistent with recognized disabilities in play and social participation among children with ASD, and their limitations in participation, compared to their TD peers in most areas. Further studies are needed to evaluate additional psychometric properties of the different scales, and the impact of educational environments on participation.


Preliminary data on the diagnostic accuracy of rubidium-82 cardiac PET perfusion imaging for the evaluation of ischemia in a pediatric population.
Evaluation of myocardial perfusion is sometimes necessary in children with congenital heart disease or acquired coronary artery abnormalities. Limited information is available regarding the clinical utility of myocardial perfusion imaging in children. PET imaging with rubidium-82 may provide a convenient clinical means of assessing regional circulatory compromise in pediatric patients with small hearts, due to its improved spatial resolution. Clinically indicated cardiac PET studies obtained in 22 pediatric patients were reviewed by two blinded observers and assigned myocardial perfusion scores using a standard 17-segment model. PET results were correlated with coronary angiography, available in 15 cases, to determine the accuracy of PET scanning for evaluating compromise of the myocardial circulation. Reversible defects consistent with myocardial ischemia were present in 6 of 15 (40%) PET cases. The sensitivity and specificity of cardiac PET for the detection of significant coronary artery disease were 100% and 82%, respectively. The positive predictive value of cardiac PET was 67%, while the negative predictive value was 100%. Cardiac PET imaging with rubidium-82 appears promising for the noninvasive assessment of myocardial perfusion in the pediatric population. The findings from this small series suggest that prospective study in a larger patient cohort merits consideration.


Phenomenological and molecular-level Petri net modeling and simulation of long-term potentiation.
Petri net-based modeling methods have been used in many research projects to represent biological systems. Among these, the hybrid functional Petri net (HFPN) was developed especially for biological modeling in order to provide biologists with a more intuitive Petri net-based method. In the literature, HFPNs are used to represent kinetic models at the molecular level. We present two models of long-term potentiation previously represented by differential equations which we have transformed into HFPN models: a phenomenological synapse model and a molecular-level model of the CaMKII regulation pathway. Through simulation, we obtained results similar to those of previous studies using these models. Our results open the way to a new type of modeling for systems biology where HFPNs are used to combine different levels of abstraction within one model. This approach can be useful in fully modeling a system at the molecular level when kinetic data is missing or when a full study of a system at the molecular level it is not within the scope of the research.