Safety and effect of Neuroform Atlas stent in the treatment of symptomatic intracranial stenosis: A single-center experience.
Vascular intracranial stenosis (IS) is a significant cause of acute ischemic stroke (AIS). This single-center study aims to show that symptomatic IS treatment by using the Neuroform Atlas stent (Stryker neurovascular, Kalamazoo, MI, USA) could be effective in reducing vessel stenosis. Ten patients affected by AIS or TIA, in the vascular territory of high-grade intracranial atherosclerotic lesions (>70% of vessel stenosis), older than 18-year-old, were treated by implanting a Neuroform Atlas stent (diameter of 4.5mm in 80% and 4mm in 20%). 70% of the patients underwent pre-stenting intracranial angioplasty. Patients were between 54.8 and 83 years old (mean 68.46y ± 8.44y), 70% males and 30% females. At admission, 50% of all patients had an AIS and 50% a TIA. Restoration of the stenotic lumen was obtained after the endovascular procedure. The percentage mean of vascular stenosis was 83.7% ± 6.09% before treatment (t0), 52.2% ± 10.42% at the end of treatment (t1) and 46.2% ± 8.28% at the follow-up (t2). The IS percentage mean reduction between t0 and t1 was 31.5% ± 7.31%, and between t1 and t2 was 6% ± 5.47%, t0 and t2 of 37.5% ± 7.38%. Percentage reduction of IS was highly significant between time t0 and t1 (p = 0.005), and t0 and t2 (p = 0.005), also with a significant reduction between t1 and t2 (p = 0.012). No patient had experienced an increase of the ischemic area in the vascular territory of the target vessel at 3 months from the initial assessment. 10% of patients experienced a 3-months negative outcome (mRS = 5), 90% experienced a favorable outcome (mRS ≤2). Intracranial stenosis endovascular treatment with Neuroform Atlas stent provides encouraging results, with a statistically significant association between the vascular caliber improvement and the endovascular treatment.


A clinical biochemist's view of the investigation of suspected inherited metabolic disease.
The necessity for a multi-disciplinary approach to the study of genetic disease is discussed. The progress of laboratory investigation programmes made it not feasible and inefficient to run a full metabolic investigation programme in every new patient suspected of inherited metabolic disease. An application form for metabolic investigation is described, which can be used to collect clinical information relevant to metabolic disease. On the basis of the patient's clinical information, selection criteria are given to decide which laboratory investigation programme has to be performed in the individual patient. A full metabolic laboratory investigation programme is described and illustrated with some examples of abnormal metabolite patterns. Diagnostic results over a 2-year period are presented.


Eel calcitonin binding site distribution and antinociceptive activity in rats.
The distribution of binding site for [125I]-eel-calcitonin (ECT) to rat central nervous system, studied by an autoradiographic technique, showed concentrations of binding in the diencephalon, the brain stem and the spinal cord. Large accumulations of grains were seen in the hypothalamus, the amygdala, in the fasciculus medialis prosencephali, in the fasciculus longitudinalis medialis, in the ventrolateral part of the periventricular gray matter, in the lemniscus medialis and in the raphe nuclei. The density of grains in the reticular formation and in the nucleus tractus spinalis nervi trigemini was more moderate. In the spinal cord, grains were scattered throughout the dorsal horns. Binding of the ligand was displaced equally by cold ECT and by salmon CT(sCT), indicating that both peptides bind to the same receptors. Human CT was much weaker than sCT in displacing [125I]-ECT binding. The administration of ECT into the brain ventricles of rats dose-dependently induced a significant and long-lasting enhancement of hot-plate latencies comparable with that obtained with sCT. The antinociceptive activity induced by ECT is compatible with the topographical distribution of binding sites for the peptide and is a further indication that fish CTs are active in the mammalian brain.


How carnivorous fungi use three-celled constricting rings to trap nematodes.
Predacious fungi form specialized hyphae structures to trap nematodes and other microscopic animals. Among the six kinds of trapping devices, the constricting ring is the only one that actively captures nematodes. When a nematode enters the aperture of the ring, which is formed by three cells, the cells rapidly triple their volume, close the aperture and hold the nematode in place. Hyphae then penetrate and consume the nematode. This paper reviews the data and hypotheses on conserving the evolution of constricting rings and their cytological and molecular mechanisms.


Delayed postnatal adaptation of pulmonary hemodynamics in infants of diabetic mothers.
To test the hypothesis with Doppler ultrasound method that the postnatal adaptation of the pulmonary and ductal hemodynamics in infants of diabetic mothers is disturbed. Infants of diabetic mothers are prone to respiratory distress caused by characteristic fetal metabolic abnormalities such as hyperglycemia and hyperinsulinemia with subsequent excess fetal growth. However, the postnatal course of the pulmonary and ductal hemodynamics is poorly known in these neonates. The presence of ductal shunting and the mean aortopulmonary pressure difference across the ductus arteriosus reflecting pulmonary artery pressure, as well as the left ventricular output, were serially evaluated with Doppler ultrasound method at 2, 12, 24, 48, and 72 hours of age in 47 infants of diabetic mothers and 37 control neonates of nondiabetic mothers. The infants of diabetic mothers had a higher incidence of patent ductus arteriosus at 12 (p = 0.03) and 48 hours (p = 0.006) of life than control infants, but none of the infants of diabetic mothers needed ductal closure. Bidirectional ductal shunting was found more frequently in infants of diabetic mothers than control infants during the first day of life. The mean ductal aortopulmonary pressure difference was significantly higher in the control infants than in infants of diabetic mothers during the first 24 hours of life (p = 0.002). The mean systemic pressure values were higher in the infants of diabetic mothers than control infants (p = 0.002), but no significant differences in the left ventricular output were seen between the study groups during the first 3 days of life. The closure of the ductus arteriosus and postnatal decrease in pulmonary artery pressure are delayed in infants of diabetic mothers when compared with control infants during the first days of life. Left ventricular output values in infants of diabetic mothers do not differ from those of the control infants.


Estimation of the optimum density of the Selk'nam from Tierra del Fuego: Inferences about human dynamics in extreme environments.
The Selk'nam, a hunter-gatherer group that inhabited Isla Grande (Tierra del Fuego), became extinct soon after coming into contact with Europeans (XIX century). The population of this tribe was estimated from mission archives and the application of a hunter-gatherer ecological model. Both approaches suggest that the widely accepted number of 3,500-4,000 individuals for this human group is an overestimation, and that 1,500 may be more accurate. This yields a population density of 0.04 persons/km2 , a very low value, but which is in accordance with the extremely harsh environment. The low population density was an essential adaptive strategy to the complex ecological equilibrium of Tierra del Fuego. Indirectly, this factor may have contributed to the rapid disappearance of this population with the breakdown of the traditional way of life. In addition, the missionary registers show that most of the aborigines died of infectious diseases, a situation exacerbated by the high population density in the missions. The reconstruction of the decline of the Selk'nam population may be used to evaluate the impact of European contact on other American hunter-gatherer groups and also to elucidate the adaptive patterns of human groups in adverse environments. Am. J. Hum. Biol. 9:699-708, 1997. © 1997 Wiley-Liss, Inc.


Assessment of Health Risk and Presence of Metals in Water and Fish Samples from Doce River, Brazil, After Fundão Dam Collapse.
The rupture of the Fundão dam released about 50 million m3 of mining tailings in the Doce river basin. To assess the potential for environmental contamination and the risks of residual exposure of the human population generated by these tailings, water and fish samples from the Doce river were collected 25 days after the accident and analyzed the physicochemical parameters of the water and levels of metals by ICP-MS, in addition to the temporal variability of the concentration of these elements through other studies. This was the first study to carry out an assessment of the health risk associated with the consumption of fish contaminated by metals from the areas affected by the disaster. The values of turbidity (5460 NTU), electrical conductivity (74.8 μS cm-1), total dissolved solids (892 mg L-1) and total suspended solids (772 mg L-1) were above the maximum limit allowed by Brazilian legislation, due to the presence of large amounts of solid materials released after the dam rupture. The analysis of metals in water samples indicated high concentrations of Al (1,906.71 μg L-1), Mn (370.32 μg L-1), Fe (8,503.50 μg L-1) and Hg (34.25 μg L-1), while for the fish samples, only As (1,033.98 μg kg-1) and Hg (herbivorous: 505.32 μg kg-1; predatory: 1,184.09 μg kg-1) presented levels above those established by Brazilian legislation. The health risk assessment showed that the estimated daily intake for Hg was higher than the reference dose, reinforcing the need for monitoring the area affected by the disaster.


NADH oxidase of liver plasma membrane stimulated by diferric transferrin and neoplastic transformation induced by the carcinogen 2-acetylaminofluorene.
NADH oxidase of purified plasma membranes (electron transfer from NADH to oxygen) was stimulated by the growth factor diferric transferrin. This stimulation was of an activity not inhibited by cyanide and was not seen in plasma membranes prepared from hyperplastic nodules from liver of animals fed the hepatocarcinogen, 2-acetylaminofluorene, nor was it due to reduction of iron associated with diferric transferrin. With plasma membranes from nodules, the activity was already elevated and the added transferrin was without effect. The stimulation by diferric transferrin did not correlate with the absence of transferrin receptors which were increased at the nodule plasma membranes. With liver plasma membranes, the stimulation by diferric transferrin raised the plasma membrane NADH oxidase specific activity to approximately that of the nodule plasma membranes. In contrast to NADH oxidase, which was markedly stimulated by the diferric transferrin, NADH ferricyanide oxidoreductase or reduction of ferric ammonium citrate by liver plasma membranes was approximately equal to or slightly greater than that of the nodule plasma membrane and unaffected by diferric transferrin. The results suggest the possibility of coupling of NADH oxidase activity to a growth factor response in mammalian cells as observed previously for this enzyme in another system.


Systematic Review and Network Meta-Analysis of Treatments for Chemotherapy-Naive Patients with Asymptomatic/Mildly Symptomatic Metastatic Castration-Resistant Prostate Cancer.
To estimate the relative effectiveness of enzalutamide in chemotherapy-naive metastatic castration-resistant prostate cancer by conducting a systematic literature review and a network meta-analysis (NMA). A systematic literature review identified randomized controlled trials comparing enzalutamide, abiraterone/prednisone, radium-223, sipuleucel-T, or docetaxel with each other or placebo in chemotherapy-naive or mixed populations (with and without prior chemotherapy) with asymptomatic/mildly symptomatic metastatic castration-resistant prostate cancer. Feasibility assessment evaluated the trials' suitability for NMA inclusion. The main outcomes were hazard ratios (HRs) for overall survival (OS) and radiographic progression-free survival (rPFS). Searches of relevant bibliographic databases, trial registers, Web sites, and conference abstracts conducted in October 2014 identified 25,712 records. Ten randomized controlled trials were eligible for the NMA. Enzalutamide was superior to placebo for OS and rPFS (fixed-effects model). NMA results (fixed-effects model) showed no evidence of a difference between enzalutamide and abiraterone/prednisone (HR 0.95 [95% CrI 0.77-1.16]), sipuleucel-T (HR 1.07 [95% CrI 0.84-1.37]), or radium-223 (HR 1.10 [95% CrI 0.87-1.37]) for OS. HRs were similar for the random-effects model. Nevertheless, results (fixed-effects model) suggested that enzalutamide was superior to abiraterone/prednisone (HR 0.59 [95% CrI 0.48-0.72]) and sipuleucel-T (HR 0.32 [95% CrI 0.25-0.42]) for rPFS. Results also suggested superiority of enzalutamide versus placebo, abiraterone/prednisone, or sipuleucel-T for time to chemotherapy. For rPFS, the NMA suggests that enzalutamide is superior to abiraterone/prednisone and sipuleucel-T. There is no evidence of a statistically significant difference in OS between enzalutamide and abiraterone/prednisone, sipuleucel-T, or radium-223. Given the limitations in network construction and underlying assumptions made to complete these analyses, results should be interpreted with caution.


Histotypic reaggregation of dissociated imaginal disc cells ofDrosophila melanogaster culturedin vivo.
Cell dissociates of wing and leg imaginal discs perform, culturedin vivo, disc specific morphogenetic movements leading to their aggregation into layers and vesicles. These histological patterns correspond directly with the final cuticular patterns which appear after metamorphosis of the same implants.The reaggregation into layers is achieved before the entry of the blastems into metamorphosis, and reflects the existence of traits of differentiation in the isolated imaginal disc cells.The bearing of selective affinity and reaggregation on cell differentiation of imaginal discs cells is discussed.


Real-world progression in the survival of de novo Metastatic prostate cancer over the past decade.
The impact of evolving treatment strategies for metastatic prostate cancer (mPCa) on real-world survival is not well understood. We analyzed changes in mPCa survival over the past decade and discussed the potential driving factors behind these changes. Our study involved 43,228 mPCa patients (2004-2020) from the SEER database, divided into 4 diagnostic periods. We used a multivariate Cox proportional hazards model to evaluate diagnostic periods' influence on overall mortality (OM) and prostate cancer-specific mortality (PSM), and calculated relative median survival improvements between adjacent periods. Subgroup analyses based on age and distant metastasis sites were conducted. Patients diagnosed in 2016 to 2020 experienced significantly reduced mortality risk compared to those in 2004 to 2007 (HR 0.64 for OM, HR 0.62 for CSM, both P < 0.001). The study period witnessed an absolute improvement in median overall survival (OS) and prostate cancer-specific survival (PCSS), 17 months (54.8%) and 25 months (67.6%) respectively. The most rapid relative survival improvement occurred post-2016, with a 29.7% increase in median OS and a 37.8% increase in PCSS compared to 2012 to 2015. There was a significant reduction in mortality risk throughout the study period in both age groups (age <75 and ≥75), but absolute survival gains were smaller in the older group (24 months [68.6%] vs. 8 months [32%] for OS, 36 months [90.0%] vs. 11 months [33.3%] for PCSS), with lower relative survival improvements after 2016 (37.2% vs. 17.9% for OS, 49% vs. 22.2% for PCSS). All metastasis site subgroups (except M1a) exhibited a significant reduction in mortality risk (all P < 0.001). Absolute survival improvements were 58 months (134.9%) for M1a, 16 months (50.0%) for M1b, and 17 months (54.8%) for M1c. The survival of mPCa have significantly improved over the past decade, although the progress is slower in elderly patients. Investigating the underlying reasons for survival differences among various patient profiles can further refine mPCa treatment strategies.


Engineering 3D bio-artificial heart muscle: the acellular ventricular extracellular matrix model.
Current therapies in left ventricular systolic dysfunction and end-stage heart failure include mechanical assist devices or transplant. The development of a tissue-engineered integrative platform would present a therapeutic option that overcomes the limitations associated with current treatment modalities. This study provides a foundation for the fabrication and preliminary viability of the acellular ventricular extracellular matrix (AVEM) model. Acellular ventricular extracellular matrix was fabricated by culturing 4 million rat neonatal cardiac cells around an excised acellular ventricular segment. Acellular ventricular extracellular matrix generated a maximum spontaneous contractile force of 388.3 μN and demonstrated a Frank-Starling relationship at varying pretensions. Histologic assessment displayed cell cohesion and adhesion within the AVEM as a result of passive cell seeding.


Dietary restriction reduces hippocampal neurogenesis and granule cell neuron density without affecting the density of mossy fibers.
The hippocampal formation undergoes significant morphological and functional changes after prolonged caloric and dietary restriction (DR). In this study we tested whether prolonged DR results in deleterious alterations in hippocampal neurogenesis, density of granule cell neurons and mossy fibers, all of which support plasticity in the dentate gyrus. Young adult animals either experienced free access to food (control condition), or every-other-day feeding regimen (DR condition) for 3months. The number of Ki-67 cells and 28-day old 5-bromo-2'-deoxyuridine (BrdU) cells were quantified in the dorsal and ventral dentate gyrus to determine the effect of DR on cellular proliferation and survival of neural progenitor cells in the anatomically defined regions of the dentate gyrus. The density of granule cell neurons and synaptoporin were also quantified to determine the effect of DR on granule cell neurons and mossy fiber projections in the dentate gyrus. Our results show that DR increases cellular proliferation and concurrently reduces survival of newly born neurons in the ventral dentate gyrus without effecting the number of cells in the dorsal dentate gyrus. DR reduced density of granule cell neurons in the dorsal dentate gyrus. These alterations in the number of granule cell neurons did not affect mossy fiber density in DR animals, which was visualized as no differences in synaptoporin expression. Our findings demonstrate that granule cell neurons in the dentate gyrus are vulnerable to chronic DR and that the reorganization of granule cells in the dentate gyrus subregions is not producing concomitant alterations in dentate gyrus neuronal circuitry with this type of DR.


Predicting fetal weight. Are Leopold's maneuvers still worth teaching to medical students and house staff?
To assess the value of teaching Leopold's maneuvers to medical students and house staff physicians for the purpose of estimating term fetal weight. Forty-four patients between 37 and 42 weeks of gestation were asked to estimate their fetus's weight upon presentation for delivery. A medical student or house staff physician then performed Leopold's maneuvers to assess fetal weight manually. For comparison, a previously published birth weight prediction equation was used to calculate fetal weight based upon maternal and pregnancy-specific characteristics alone, and obstetric ultrasonography was performed to measure fetal biometric parameters for use with standard ultrasonic fetal weight prediction equations. House staff physicians performed significantly better than medical students in making fetal weight predictions to within +/- 10% of actual birth weight using Leopold's maneuvers (71% vs. 38%, P < .05). House staff who made tactile assessments of fetal weight were able to predict birth weight to within 15% of actual weight more often than mothers making estimations (P < .05), but medical students could not (P = .53). The correlation between predicted and actual birth weights was .60 for Leopold's maneuvers, .45 for maternal estimates of fetal weight, .55 for the birth weight prediction equation and .63 for the best of eight ultrasonic prediction equations tested. House staff physicians make more accurate predictions of term fetal weight using Leopold's maneuvers than do medical students. This is presumably due to the increased experience of house staff in using such tactile techniques. Leopold's maneuvers are a useful method of estimating fetal weight and should continue to be taught to both medical students and house staff.


Leaving no stone unturned: Role of profibrotic genes in oral submucous fibrosis - A systematic review.
Understanding the molecular pathogenesis of an entity helps in devising the mode of progression as well as mode of therapy. Even with years of research to claim the understanding of the molecular pathogenesis of oral submucous fibrosis (OSMF) is limited. More deeper knowledge of the genes responsible for this will help in understanding and managing this disease better. The articles published during a time period of 1990-2020 were chosen in accordance with the inclusion and exclusion criteria according to the PRISMA guidelines. From a total of 80 articles obtained from both electronic search of PUBMED, EMBASE, MEDLINE and Cochrane registry as well as the manual search only 21 articles were selected and analyzed. Careful analysis of the samples revealed that transforming growth factor-beta may be a potential biomarker or a candidate for targeted therapy in OSMF.


Stimulus Control Research and Practice: Considerations of Stimulus Disparity and Salience for Discrimination Training.
Stimulus control plays a prominent role in behavior-analytic service delivery, as many discrimination skills are necessary for daily interactions. Clarification and standardization of terminology are necessary for the advancement of research and practice on stimulus control. The purpose of the present article is to provide an overview of stimulus control and discrimination training as they relate to the disparity and salience of stimuli. An overview and examples of stimulus disparity and stimulus salience are provided, followed by recommendations for efficacious service delivery.


Is preventable sight loss truly preventable? An exploration of a public health indicator for sight loss due to age-related macular degeneration in England.
Age-related macular degeneration accounts for the majority of severe sight impairment and sight impairment registration and certifications in adults in the UK [1, 2]. Whilst these treatments are effective in arresting nAMD progression, there is currently no treatment for GA [1, 3, 4]. This paper provides an update to the data collected by Bunce et al. [3] and details the number of people certified together with incidence rates for the various types of AMD by: sex, sight impairment status, and for all ages using the 2016/2017 and 2017/2018 CVI due to AMD data for England from the Moorfields Eye Hospital, supplemented with 2017-2018 PHOF indicator 4.12i/E12a data. The study population includes individuals of all ages in England who were newly certified with visual impairment due to AMD. Between 2016 and 2017, CVIs due to AMD totalled to 11,215; between 2017 and 2018, CVIs due to AMD totalled to 10,914. The PHOF indicator 4.12i/E12a assessed showed that overall rates of AMD certifications have steadily declined in England from 131.5 per 100,000 in 2010/2011 to 106.7 per 100,000 in 2017/2018. As treatment is available for nAMD, a reduction in nAMD certifications could be expected; however, growth of the elderly population in England combined with there currently being no treatment available for GA means AMD certification rates should be increasing. Therefore, it is postulated that not all cases of AMD are being certified and registered with some likely going undiagnosed.


The vasculitis in IBD is associated with the degree of inflammation.
The role of vasculitis in the pathogenesis of IBD remains unclear. The aim of this study was to evaluate the detection rate of vasculitis in patients with IBD, its location in the intestinal wall layers and whether it occurs dependent of the degree of inflammation. Immunohistological staining with the endothelial cell marker CD31 and the pan-T cell marker CD3 was performed in 56 colonic specimens of Crohn's disease, in 43 of ulcerative colitis, and in 5 of colon cancer. Quantification of the degree of inflammation was done using a histological colitis score. There was no sign of vasculitis in the healthy intestinal wall layers. In Crohn's disease, specimens with minor inflammatory activity (score 0-2) disclosed no vasculitis. Vasculitis was observed in 82% of the specimens with an inflammatory degree of 3 and in 100% with an inflammatory degree of 4. Vasculitis was detected in all intestinal wall layers altered by inflammation. A direct association between vasculitis and granulomas was observed in only 5% of the specimens with an inflammatory degree of 4. All ulcerative colitis specimens evidenced an inflammatory degree between 2 and 4. No vasculitis was found in specimens with an inflammatory degree of 2, but in 57% with an inflammatory degree of 3 and in 100% with an inflammatory degree of 4. Vasculitis is only detectable in the mucous membrane changed by inflammation. Thus, the vasculitis in IBD is exclusively observed in the intestinal wall layers altered by inflammation. The extent of vasculitis depends on the degree of inflammation. An association between vasculitis and granuloma in Crohn's disease is seen in 5% of the cases.


Genome-wide Interrogation of Protein-DNA Interactions in Mammalian Cells Using ChIPmentation.
Mapping the genomic locations of chromatin-associated proteins, such as transcription factors and histone modifications, is key to understanding the mechanisms of transcriptional regulation. ChIPmentation offers a simple and robust way of investigating the genomic binding sites of a protein using relatively low-input material. Here, we present a detailed protocol for the key steps that lead to a successful ChIPmentation experiment, as well as a quick analysis pipeline to examine the data. For complete details on the use and execution of this protocol, please refer to Schmidl et al. (2015). For example data produced by this protocol, please refer to Henriksson et al. (2019) and Zhang et al. (2019).


Measuring the impact of forensic science in detecting burglary and autocrime offences.
As UK investment in forensic science has increased, the government has taken a fresh interest in how far this has led to dividends in terms of the detection of crime and its reduction. The Home Office funded 'Pathfinder Project' sought to monitor and document the complex relationships between the collection and use of forensic material (looking at a range of forensic science techniques) and its impact on crime detection. The project specifically targeted the 'volume' crimes of burglary and vehicle crime. Detailed data was gathered on all stages of the process between the collection and use of forensic material and crime detection. The model falls into two conceptual phases--scene attendance to suspect identification and identification to detection. From the analysis it was found that approximately one third of burglary and autocrime scenes are visited by SOCOs. While scientific identifications are only made in a minority of burglary and autocrime offences overall, it belies their importance. About one in ten of burglary and autocrime cases are cleared up by the police and it is estimated that fingerprints and SGMPlus were a contributory factor in achieving one third of these clear ups.


A Bayesian approach to real-time spatiotemporal prediction systems for bronchiolitis.
Respiratory Syncytial Virus (RSV) induced bronchiolitis is a common lung infection and a major cause of infant hospitalization and mortality. Unfortunately, there is no known cure for RSV but several vaccines are in various stages of clinical trials. Currently, immunoprophylaxis is a preventative measure consisting of a series of monthly shots that should be administered at the start, and throughout, peak RSV season. Thus, the successful implementation of immunoprophylaxis is contingent upon understanding when outbreak seasons will begin, peak, and end. In this research we estimate the seasonal epidemic curves of RSV induced bronchiolitis using a spatially varying change point model. Further, in a novel approach and using the fitted change point model, we develop a historical matching algorithm to generate real time predictions of seasonal curves for future years.


Cobalt exposure increases the risk of fibrosis of people living near E‑waste recycling area.
The toxicity of heavy metals is one of the major public health issues leading to hazardous effects on humans. Many studies focus on the adverse effects on people who were working in or living near E-waste recycling. However, little is known to the sustaining effects of E-waste exposure on human health after the recycling factories were shut down. In the present study, we collected the blood of people living near E‑waste recycling facilities after the recycling factories were closed for 2 years. Eight heavy metals were examined in all blood samples. The results revealed that the blood levels of lead (Pb), nickel (Ni), cobalt (Co), mercury (Hg) were significantly higher in the exposed group than in the reference group, and no difference was observed for copper (Cu), zinc (Zn), stannum (Sn), cadmium (Cd). Transforming growth factor-β (TGF-β) and alpha-smooth muscle actin (α-SMA) were analyzed as the important indicators of fibrosis, which were statistically significantly higher in the exposed group than in the reference group. 8-isoprostane (8-I) and malondialdehyde (MDA) as the biomarkers of oxidative stress (OS) were elevated in the exposed group. Furthermore, both Spearman correlation and multiple linear regression showed that Co was positively correlated with TGF-β, α-SMA and 8-I in the exposed group. Accordingly, we speculate that high concentrations of Co dissolved in the blood may increase the risk of tissue fibrosis through stimulating myofibroblast activation and OS involve in the process, which may provide some potential new hints for the intervention for tissue fibrosis in the future.


Identification and analysis of genes associated with the synthesis of bioactive constituents in Dendrobium officinale using RNA-Seq.
Dendrobium officinale L. is an important traditional herb with high commercial value in China. Several bioactive constituents, including polysaccharides and alkaloids, reportedly make major contributions toward the excellent medicinal effect of D. officinale. In this study, the contents of polysaccharides and alkaloids in various organs of D. officinale were measured and compared. We took advantage of transcriptomes from four organs to explore biological mechanisms in the organ-specific distribution of active ingredients in D. officinale. Based on Kyoto Encyclopedia of Genes and Genomes pathways, unigenes related to the enzymes involved in fructose and mannose metabolism and unigenes associated with putative upstream elements of the alkaloid biosynthetic pathway were identified. A large number of candidates, including 35 full-length glycosyltransferase genes and 49 full-length P450 genes, were also identified based on the transcriptome data, and the organ-specific expression pattern of these genes was determined. Furthermore, differential expression of all candidate genes was analyzed in two Dendrobium species, D. nobile L. and D. officinale. The data will supply important clues to exploit useful genes involved in polysaccharide and alkaloid synthesis.


Von Hippel-Lindau disease and erythrocytosis: radioimmunoassay of erythropoietin in cyst fluid from a brainstem hemangioblastoma.
A 59-year-old woman with von Hippel-Lindau disease developed erythrocytosis and a recurrent intracranial hemangioblastoma. Radioimmunoassay showed an elevated level of erythropoietin in her serum. Cyst fluid from the tumor also contained erythropoietin, concentrated a thousandfold relative to the serum level. Production of erythropoietin by hemangioblastomas may explain the erythrocytosis present in some patients with von Hippel-Lindau disease.


The taste of neuroinflammation: Molecular mechanisms linking taste sensing to neuroinflammatory responses.
Evidence indicates a critical role of neuroinflammatory response as an underlying pathophysiological process in several central nervous system disorders, including neurodegenerative diseases. However, the molecular mechanisms that trigger neuroinflammatory processes are not fully known. The discovery of bitter taste receptors in regions other than the oral cavity substantially increased research interests on their functional roles in extra-oral tissues. It is now widely accepted that bitter taste receptors, for instance, in the respiratory, intestinal, reproductive and urinary tracts, are crucial not only for sensing poisonous substances, but also, act as immune sentinels, mobilizing defense mechanisms against pathogenic aggression. The relatively recent discovery of bitter taste receptors in the brain has intensified research investigation on the functional implication of cerebral bitter taste receptor expression. Very recent data suggest that responses of bitter taste receptors to neurotoxins and microbial molecules, under normal condition, are necessary to prevent neuroinflammatory reactions. Furthermore, emerging data have revealed that downregulation of key components of the taste receptor signaling cascade leads to increased oxidative stress and inflammasome signaling in neurons that ultimately culminate in neuroinflammation. Nevertheless, the mechanisms that link taste receptor mediated surveillance of the extracellular milieu to neuroinflammatory responses are not completely understood. This review integrates new data on the molecular mechanisms that link bitter taste receptor sensing to neuroinflammatory responses. The role of bitter taste receptor-mediated sensing of toxigenic substances in brain disorders is also discussed. The therapeutic significance of targeting these receptors for potential treatment of neurodegenerative diseases is also highlighted.


Putative Local Adaptive SNPs in the Genus Avicennia.
The genus Avicennia with eight species grow in intertidal zones of tropical and temperate regions, ranging in distribution from West Asia, to Australia, and Latin America. These mangroves have several medicinal applications for mankind. Many genetic and phylogenetic studies have been carried out on mangroves, but none is concerned with geographical adaptation of SNPs. We therefore, used ITS sequences of about 120 Avicennia taxa growing in different parts of the world and undertook computational analyses to identify discriminating SNPs among these species and to study their association with geographical variables. A combination of multivariate and Bayesian approaches such as CCA, RDA, and LFMM were conducted to identify the SNPs with potential adaptation to geographical and ecological variables. Manhattan plot revealed that many of these SNPs are significantly associated with these variables. The genetic changes accompanied by local and geographical adaptation were illustrated by skyline plot. These genetic changes occurred not under a molecular clock model of evolution and probably under a positive selection pressure imposed in different geographical regions in which these plants grow.


Three-dimensional scapular kinematics and scapulohumeral rhythm in patients with glenohumeral osteoarthritis or frozen shoulder.
We aimed to describe 3D scapular kinematics and scapulohumeral rhythm (SHR) in glenohumeral (GH) osteoarthritis shoulders compared to unaffected shoulders and to compare the abnormal scapular kinematic schema for GH osteoarthritis with that for frozen shoulder. Thirty-two patients with stiff shoulder (16 with GH osteoarthritis and 16 with frozen shoulder) performed maximal arm elevation in two planes, sagittal and frontal. Scapular rotations and humeral elevation of the affected and unaffected shoulders were measured by the Polhemus Fastrak electromagnetic system. Patients with GH osteoarthritis were older, had longer disease duration (p<0.001) and less restricted humeral elevation in the frontal plane (p=0.01). Protraction was significantly lower for the affected shoulders except for arm elevation in the frontal plane in the GH osteoarthritis group. Furthermore, protraction was lower with frozen shoulder than GH osteoarthritis during arm elevation in the frontal plane. Scapular lateral rotation and SHR were significantly higher for the affected shoulders in both groups whatever the plane of elevation. SHR showed a fair to moderate negative correlation with maximal humeral elevation in both groups and appears to be higher with frozen shoulder than GH osteoarthritis. In addition, SHR of the affected shoulder showed a fair to moderate correlation with disease duration only with GH osteoarthritis. Scapular tilt did not differ between affected and unaffected sides and was not influenced by type of disease. In conclusion, the increased scapular lateral rotation described in frozen shoulder is also observed in GH osteoarthritis. SHR of the affected shoulder is inversely related to severity of limitation of shoulder range of motion, which suggests a compensatory pattern.


Acral pseudolymphomatous angiokeratoma of children (APACHE): a case report and immunohistological study.
Acral pseudolymphomatous angiokeratoma of children (APACHE) is a new clinical entity that is characterized by angiomatous papules on the extremities. We report a case APACHE in a 14-year-old Japanese girl with asymptomatic red and violaceous papules and nodules on the ring finger of the left hand. Histological and immunohistochemical studies of our patient indicated that APACHE is a pseudolymphoma rather than an angiokeratoma.


Factors that Affect Depression and Anxiety in Service and Sales Workers Who Interact With Angry Clients.
We evaluated depression and anxiety in service and sales workers from Korea who interacted with angry clients to identify factors that mediated and moderated depression and anxiety in these workers. This was a secondary analysis of data from the fifth Korean Working Conditions Survey conducted in 2017. A structural equation model was used for mediation and moderation analysis. Service and sales workers who had more interactions with angry clients had increased risk for depression and anxiety. Experiencing clients' adverse behaviors (acute episodes) mediated the relationship between interacting with angry clients (a chronic situation) on depression and anxiety. Job satisfaction and managers' support moderated the relationship between interacting with angry clients and mental health problems. We suggest that employers of service and sales workers should recruit staff based on their aptitude for such work, thus ensuring job satisfaction, and train them to deal with angry clients in such a way that they experience less emotional burden. Employers should also make bylaws requiring managers to directly take care of adverse social behavior by clients. Furthermore, a sociocultural campaign to prevent adverse social behavior by clients is also needed.


Ultrasmall iron oxide nanoparticles cisplatin (IV) prodrug nanoconjugate: ICP-MS based strategies to evaluate the formation and drug delivery capabilities in single cells.
Ultrasmall iron oxide nanoparticles (<10 nm) were explored here as nanotransporters of cis-diamminetetrachloroplatinum (IV) (a cisplatin prodrug) in cellular models. The coating of the particles containing reactive carboxylic acid groups enabled the formation of a stable conjugate between the prodrug and the nanoparticles using one pot reaction. The nanoconjugate was characterized by different techniques exhibiting diameters of about 6.6 ± 1.0 nm. The use of a hyphenated strategy based on high performance liquid chromatography (HPLC) coupled to inductively coupled plasma mass spectrometry (ICP-MS) permitted the quantitative evaluation of Fe and Pt in the nanoconjugate. Furthermore, the cellular uptake of the synthetic nanoconjugate was explored by single cell-ICP-MS (SC-ICP) which was used for the first time in this type of studies. The experiments in A2780 and A2780cis, sensitive and resistant ovarian cancer cell models respectively, revealed intracellular platinum concentrations of 12 fg/cell and 4 fg/cell, respectively which were 4-fold higher with respect to the uptake of cisplatin in both models. Intracellular drug release from the nanoconjugate was proved by measuring DNA platination in the same cells. In this case, levels of about 250 ng Pt/mg DNA were observed, about 5-fold higher when the nanoconjugate was used in comparison to cisplatin. Furthermore, the differences between the two lines turned to be significantly smaller than in the case of using cisplatin. The quantitative analytical tools developed here provided essential information required to fully characterize the developed nanoplatforms particularly important to overcome drug resistance.


Hormonal control of vitellogenin synthesis in avian liver.
Estradiol induces the synthesis of vitellogenin in the avian liver. We describe the precursor-product relationship between vitellogenin and the yolk proteins phosvitin and lipovitellin. The high rate of vitellogenin synthesis is a consequence of the accumulation of a stable messenger RNA. We suggest that estradiol acts at the level of the genome by opening a hitherto non-transcribed gene.


Vasculogenic conditioning of peripheral blood mononuclear cells promotes endothelial progenitor cell expansion and phenotype transition of anti-inflammatory macrophage and T lymphocyte to cells with regenerative potential.
Cell-based therapies involving mononuclear cells (MNCs) have been developed for vascular regeneration to treat ischemic diseases; however, quality control of therapeutic MNCs has not been evaluated. We investigated the therapeutic potential of peripheral blood (PB) MNCs, operated by recently developed quality and quantity (QQ) culture of endothelial progenitor cells (EPCs). PBs were collected from healthy volunteers; peripheral blood mononuclear cells (PBMNCs) isolated from these PBs were subjected to QQ culture for 7 days with medium containing stem cell factor, thrombopoietin, Flt-3 ligand, vascular endothelial growth factor, and interleukin-6. The resulting cells (QQMNCs) in EPC colony-forming assay generated significantly more definitive EPC colonies than PBMNCs. In flow cytometry, macrophages and helper T lymphocytes of QQMNCs became phenotypically polarized into angiogenic, anti-inflammatory, and regenerative subsets: classical M1 to alternative M2; T helper (Th)1 to Th2; angiogenic or regulatory T-cell expansion. Quantitative real-time polymerase chain reaction (qRT-PCR) assay revealed the predominant proangiogenic gene expressions in QQMNCs versus PBMNCs. Using murine ischemic hindlimb models, the efficacy of QQMNC intramuscular transplantation (Tx) was compared to that of PBMNCTx, cultured "early EPC" Tx (eEPCTx), and granulocyte colony-stimulating factor mobilized CD34(+) cell Tx (GmCD34Tx). Laser Doppler imaging revealed the blood perfusion recovery in ischemic hindlimbs after QQMNCTx superior to after PBMNCTx and eEPCTx, but also earlier than after GmCD34Tx. Histological evaluations and qRT-PCR assays in ischemic hindlimbs demonstrated that QQMNCTx, similarly to GmCD34Tx, enhanced angiovasculogenesis and myogenesis, whereas it preponderantly inhibited inflammation and fibrosis versus PBMNCTx and eEPCTx. QQ culture potentiates the ability of PBMNCs to promote regeneration of injured tissue; considering the feasible cell preparation, QQ culture-treated PBMNCs may provide a promising therapeutic option for ischemic diseases. irb.med.u-tokai.ac.jp/d/2/monthly/2010.html; IRB No.: 10R-020.URL: irb.med.u-tokai.ac.jp/d/2/monthly/201312.html; IRB No.: 13R228.


Follistatin improves skeletal muscle healing after injury and disease through an interaction with muscle regeneration, angiogenesis, and fibrosis.
Recovery from skeletal muscle injury is often incomplete because of the formation of fibrosis and inadequate myofiber regeneration; therefore, injured muscle could benefit significantly from therapies that both stimulate muscle regeneration and inhibit fibrosis. To this end, we focused on blocking myostatin, a member of the transforming growth factor-β superfamily and a negative regulator of muscle regeneration, with the myostatin antagonist follistatin. In vivo, follistatin-overexpressing transgenic mice underwent significantly greater myofiber regeneration and had less fibrosis formation compared with wild-type mice after skeletal muscle injury. Follistatin's mode of action is likely due to its ability to block myostatin and enhance neovacularization. Furthermore, muscle progenitor cells isolated from follistatin-overexpressing mice were significantly superior to muscle progenitors isolated from wild-type mice at regenerating dystrophin-positive myofibers when transplanted into the skeletal muscle of dystrophic mdx/severe combined immunodeficiency mice. In vitro, follistatin stimulated myoblasts to express MyoD, Myf5, and myogenin, which are myogenic transcription factors that promote myogenic differentiation. Moreover, follistatin's ability to enhance muscle differentiation is at least partially due to its ability to block myostatin, activin A, and transforming growth factor-β1, all of which are negative regulators of muscle cell differentiation. The findings of this study suggest that follistatin is a promising agent for improving skeletal muscle healing after injury and muscle diseases, such as the muscular dystrophies.


An ethnobotanical survey of medicinal plants used by the Didayi tribe of Malkangiri district of Orissa, India.
An ethnobotanical survey was carried out among the ethnic community (Didayi) in Malkangiri district, Orissa. A total of 53 medicinal plant species belonging to 34 families and 52 different species are described under this study.


Comparative analysis between tuberculous meningitis and other forms of extrapulmonary tuberculosis.
Tuberculosis is a multisystem disease that may affect any organ or tissue. Tuberculous meningitis (TBM) is the most severe form of tuberculosis and commonly affects the brain. We aimed to study the epidemiological, clinical, therapeutic and evolutionary features of TBM among adults and to compare them with other forms of extrapulmonary tuberculosis. We conducted a retrospective study including all patients hospitalized for extrapulmonary tuberculosis in the infectious disease department in Sfax, Tunisia between 1993 and 2018. We specified the particularities of TBM cases, and we compared them with other extrapulmonary tuberculosis cases. We encountered 78 patients diagnosed with TBM, among 519 patients with extrapulmonary tuberculosis (15%). The median age was 36 years (23-50) years. There were 44 females (56.4%). In comparison with other forms of extrapulmonary tuberculosis, fever [odds ratio (OR)=4.4; p<0.001], asthenia (OR=3.4; p<0.001) and anorexia (OR=2.3; p=0.001) were significantly more frequent in TBM patients. Adverse effects of antitubercular therapy were more frequent among TBM patients (OR=3.1; p<0.001). The mean duration of antitubercular therapy was 15 (12-20) months. Recovery occurred in 66 cases (84.6%), complications in 44 cases (56.4%) and death in 7 cases (9%). Comparison of the disease evolution showed that complications (OR=7.4; p<0.001) and mortality rates (OR=10.7; p<0.001) were significantly more frequent in TBM patients, while recovery was significantly more frequent in other sites of extrapulmonary tuberculosis patients (OR=0.5; p=0.02). In our country, TBM remains a disabling disease. Despite antitubercular therapy, the prognosis was more severe with the occurrence of not only complications but also a high mortality rate in comparison with other forms of extrapulmonary tuberculosis. When clinical and laboratory features suggest the diagnosis of TBM, clinicians should look for tuberculosis elsewhere in the body.


Hybrid gold atomic cluster-cobalt oxide scaffolds for dual tandem electrocatalytic sensing of cysteine.
Innovations in nanoelectrochemistry have opened a plethora of techniques for the preparation of nanometer sized electrochemical probes with tunable properties. Atomic clusters emerged at the crossroad of physics and chemistry has immense potential as novel "electron antennaes" in electrocatalysis. Herein, we report the electrochemical synthesis and the synergistic electrocatalytic effect of metal oxide supported gold atomic clusters for subnanomolar level sensing of cysteine. The developed gold atomic clusters and the hybrid materials were characterized by spectral, morphological and electrochemical methods. Comparative evaluation of the critical role of surfactants in stabilizing the hybrid material and the mechanistic aspects of support scaffolds has been discussed. Different complexing agents were sequentially screened in order to get the optimum electrolyte composition for developing a uniform, reproducible sensing film. The developed modified electrode exhibits highly reproducible wider calibration range of 10(-10) to 10(-6) M with lower detection limits of 1.6×10(-11) M for cysteine. To gain a greater understanding of such advantageous behavior achieved with this electrode, studies on electrode kinetics of charge-transfer processes were also done.


Changes in fetal brain aromatase activity following in utero 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure in rats.
Aromatase catalyzes intraneuronal conversion of androgens to estrogens in the hypothalamus-preoptic area at a specific time during development. This local estrogen formation has a central role in sexual differentiation. To investigate the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on sexual differentiation, TCDD (800 and 1600 ng/kg) was orally administered to pregnant Holtzman rats on gestation day (GD) 15, and the change in brain aromatase activity of fetuses (GD20) and pups (postnatal day 2) was examined. Litter means of brain aromatase activity in the hypo-preoptic area of control fetuses were higher in males than in females (female/male ratio was 0.7). This ratio of aromatase activity increased in a TCDD-concentration dependent manner, reaching 1 at the higher dose. There was a similar change in aromatase activity in brains of pups (PND 2). These results suggest that in utero TCDD exposure induces demasculinization in male offspring by inhibiting the aromatase activity in the brain during central nervous system development.


Methyl 4-(3-chloro-prop-oxy)benzoate.
In the crystal structure of the title compound, C(11)H(13)ClO(3), inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into zigzag chains along the c axis.


Giant electron tails and passing electron pinch effects in tokamak-core turbulence.
The anomalous particle transport in a tokamak core is believed to be linked to the advection of magnetically trapped electrons alone, owing to the passing electrons maintaining a thermal equilibrium along the field lines. Surprisingly, in nonlinear numerical studies, the radial flux of passing electrons rivals that of the trapped ones. The strong interaction of passing electrons and electric fluctuations is mediated by long tails of the modes along the magnetic field, which are generated by the passing electrons in the first place.


Research development in the pathogenesis of neuropathic diabetic foot ulceration.
Neuropathic ulceration is the most prevalent type of chronic lesion of the diabetic foot. Its pathogenesis is mainly related to the abnormally increased pressure on the sole of the foot, secondary to lack of sensation and deformities induced by peripheral sensory-motor neuropathy, which are associated with an abnormal gait. The incidence of the ulcerative state is brought on by repetitive postural trauma, which causes a chronic inflammatory state, characterized by hypertrophy of skin layers and diffuse, intense inflammatory infiltrate throughout the ulcer. The off-loading of the ulcer will restore the healing process, leading to a reparative phase that will be histologically and biochemically evident.


Editorial for the Special Issue "New Drugs for Breast Cancer Treatment".
Breast cancer (BC) is the deadliest neoplastic disease for women worldwide [...].


Super resolution reconstruction of CT images based on multi-scale attention mechanism.
CT diagnosis has been widely used in clinic because of its special diagnostic value. The image resolution of CT imaging system is constrained by X-ray focus size, detector element spacing, reconstruction algorithm and other factors, which makes the generated CT image have some problems, such as low contrast, insufficient high-frequency information, poor perceptual quality and so on. To solve the above problems, a super-resolution reconstruction method of CT image based on multi-scale attention mechanism is proposed. First, use a 3 × 3 and a 1 × 1 convolution layer extracting shallow features. In order to better extract the high-frequency features of CT images and improve the image contrast, a multi-scale attention module is designed to adaptively detect the information of different scales, improve the expression ability of features, integrate the channel attention mechanism and spatial attention mechanism, and pay more attention to important information, retain more valuable information. Finally, sub-pixel convolution is used to improve the resolution of CT image and reconstruct high-resolution CT image. The experimental results show that this method can effectively improve the CT image contrast and suppress the noise. The peak signal-to-noise ratio and structural similarity of the reconstructed CT image are better than the comparison method, and has a good subjective visual effect.


Effects of removing a highly conserved disulfide bond in ubiquitin-associated domain of human HOIP on biochemical characteristics.
Disulfide bond formed between the cysteine pairs plays a key role in maintaining the integrity of the protein structure and function. The ubiquitin-associated (UBA) domain of human HOIP contains three cysteine residues, Cys504, Cys551, and Cys572. Disulfide bonds formed by Cys504 and Cys551 residues are highly conserved, but the effect of disulfide bonds on the biochemical characteristics of UBA has not been elucidated. In addition, due to the presence of isolated Cys572, inactive inclusion bodies may be formed during protein expression or trigger protein aggregation during protein purification. In this study, the co-expression of SUMO fusion protein combined with SUMO protease (ULP enzyme) in Escherichia coli was successfully applied to improve the soluble expression of UBA domain. Introduced three mutants (UBAC551A, UBAC572A and UBAC551,572A) determined the effects of disulfide bonds on the biochemical characteristics of UBA. Circular dichroism and analytical size exclusion chromatography results showed that the target proteins obtained by co-expression could be folded correctly and had biological activity. Both thermal-induced and urea-induced results demonstrated that the elimination of disulfide bonds would significantly reduce the stability of UBA. Fluorescence spectroscopy result showed that the elimination of disulfide bonds slightly increases the binding affinity of UBA to ligands. In summary, soluble, stable and active UBA domain and its mutants were prepared by co-expression system, which will further contribute to the structural and functional research of UBA.


Diarrhoea and garbage disposal in Salvador, Brazil.
The association of infantile diarrhoea with the presence of garbage in the environment was investigated in Canabrava, a peripheral neighbourhood of Salvador, northeast of Brazil. A cross-sectional study was conducted with all the 184 children aged less than two years residing in Canabrava, which is located close to the city garbage dump. Variables selected for study included the method used for the disposal of excrement, type of floor, mother's education, unemployment of the head of the family, regularity of the water supply, presence of toilet, storage of garbage inside the house, age, gender, duration of breastfeeding, and the number of people per room. The estimated prevalence of diarrhoea was 21.2%. Exposure to garbage in the environment was found to be the most important factor associated with diarrhoea (adjusted odds ratio [AOR] = 3.98, 95% CI 1.56-10.13). Other important variables were the mother's education (AOR = 2.79, 95% CI 1.09-7.13), maternal breastfeeding (AOR = 2.30, 95% CI 1.05-5.04), and unemployment of the head of the family (AOR = 2.09, 95% CI 0.93-4.69). These findings indicate the necessity of adopting solutions in the public domain and of intersectorial policies for the reduction of diarrhoea.


A new formula for estimating metabolic rate.
A formula for estimating metaoblic rate using inlet volume flow and oxygen fractionation of outlet air is derived. The formula is simplified and the error induced is evaluated and compared with that of Weir's formula.


The Transradial Approach and Antithrombotic Therapy: Rationale and Outcomes.
This article reviews antithrombotic strategies for percutaneous coronary interventions according to the access site and the current evidence with the aim of limiting ischemic complications and preventing radial artery occlusion (RAO). Prevention of RAO should be part of the quality control of any radial program. The incidence of RAO postcatheterization and interventions should be determined initially using the echo-duplex and then frequently assessed using the more cost-effective pulse oximetry technique. Any evidence of higher risk of RAO should prompt internal analysis and multidisciplinary mechanisms to be put in place.


First trimester prediction models for small-for- gestational age and fetal growth restricted fetuses without the presence of preeclampsia.
We established efficient first trimester prediction models for small-for-gestational age (SGA) and fetal growth restriction (FGR) without the presence of preeclampsia (PE) regardless of the gestational age of the onset of the disease [early FGR occurring before 32 gestational week or late FGR occurring after 32 gestational week]. The retrospective study was performed on singleton Caucasian pregnancies (n = 6440) during the period 11/2012-3/2020. Finally, 4469 out of 6440 pregnancies had complete medical records since they delivered in the Institute for the Care of Mother and Child, Prague, Czech Republic. The study included all cases diagnosed with SGA (n = 37) or FGR (n = 82) without PE, and 80 selected normal pregnancies. Four microRNAs (miR-1-3p, miR-20a-5p, miR-146a-5p, and miR-181a-5p) identified 75.68 % SGA cases at 10.0 % false positive rate (FPR). Eight microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-126-3p, miR-130b-3p, miR-146a-5p, miR-181a-5p, and miR-499a-5p) identified 83.80 % SGA cases at 10.0 % FPR. The prediction model for SGA based on microRNAs was further improved via implementation of maternal clinical characteristics [maternal age and BMI, an infertility treatment by assisted reproductive technology (ART), first trimester screening for PE and/or FGR and for spontaneous preterm, both by FMF algorithm]. Then 81.08 % and 89.19 % pregnancies developing SGA were identified at 10.0 % FPR in case of utilization of 4 microRNA and 8 microRNA biomarkers. Simplified prediction model for SGA based on limited number of maternal clinical characteristics (maternal age and BMI, an infertility treatment by ART, and 4 microRNAs) does not improve the detection rate of SGA (70.27 % SGA cases at 10.0 % FPR) when compared with prediction model for SGA based just on the expression profile of 4 or 8 microRNAs biomarkers. Seven microRNAs only (miR-16-5p, miR-20a-5p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-342-3p, and miR-574-3p) identified 42.68 % FGR cases at 10.0 % FPR (AUC 0.725). However, the combination of 10 microRNAs only (miR-16-5p, miR-20a-5p, miR-100-5p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-342-3p, and miR-574-3p) reached a higher discrimination power (AUC 0.774). It identified 40.24 % FGR cases at 10.0 % FPR. The prediction model for any subtype of FGR based on microRNAs was further improved via implementation of maternal clinical characteristics [maternal age and BMI, an infertility treatment by ART, the parity (nulliparity), the occurrence of SGA or FGR in previous gestation, and the occurrence of any autoimmune disorder, and the presence of chronic hypertension]. Then 64.63 % and 65.85 % pregnancies destinated to develop FGR were identified at 10.0 % FPR in case of utilization of 7 microRNA biomarkers or 10 microRNA biomarkers. When other clinical variables next to those ones mentioned above such as first trimester screening for PE and/or FGR and for spontaneous preterm, both by FMF algorithm, were added to the prediction model for FGR, the detection power was even increased to 74.39 % cases and 78.05 % cases at 10.0 % FPR.


Mortality Trends in Young People Aged 1-24 Years: Argentina, 1947-2012.
Global mortality trends highlight changing patterns in young people, especially young men, yet little evidence of long-term trends is available in Argentina. Given the lack of published evidenced within the country, this work seeks to construct long-term mortality trends for young people in Argentina. A descriptive mortality time series was developed for ages 1-24 years by sex and cause of death in Argentina during 1947-2012. Diverse international and domestic public data sources were used to calculate the specific mortality rates. Causes of death were classified into the 3 Global Burden of Disease groups to ensure comparability. The greatest decline in mortality was found in the 1-4 year age group. Women and girls of all ages had large decreases in mortality. Mortality in boys and men aged 15-24 years declined, but much less than in all other groups; mortality in this group was twice that of women and girls by 2012. Mortality as a result of communicable, nutritional, and maternal causes declined in all groups, but in young men injury mortality increased. In all groups, reductions were greater during the first half of the period. Long-term trends offer a broader view of health phenomena-like injury mortality, disproportionately affecting young men-so as to better inform actions and policy that could change ways of living and dying in Argentina.


In search of a surrogate: engineering human beta cell lines for therapy.
Replacement of insulin-producing cells is a promising therapy for the restoration of the beta cell mass that is destroyed in patients with type 1 diabetes (T1D). However, the use of large amounts of islets per transplant, coupled with the scarcity of donor tissue, diminishes its feasibility. Here we briefly discuss current progress in developing ideal functional beta cells as well as the rationale for developing renewable sources of insulin-producing cells that can be transplanted.


[Surgical consequences of anomalous arterial blood supply and aneurysms in the epigastric region (authors' translation)].
Abdominal angiography was performed in patients with occlusive disease of the iliofemoral arteries. In 85 of 389 patients, the anomalous arterial blood supply of the upper abdomen was detected accidentally: 81% of the variations were related to the hepatic artery, 19% to the celiac artery. The possible surgical consequences are discussed if these variations are disregarded. Four patients with aneurysms of the visceral arteries (three aneurysms of the hepatic artery, one aneurysm of the superior mesenteric artery) and one patient with a celiac artery compression syndrome were also detected. The latter diseases represent clear indication for operation with high chances of success if treated in time.


The contractile mechanism in cilia.
A detailed analysis is made of the motion and the forces in the cilium of Sabellaria over the complete cycle. The results indicate that the stiffness of the cilium is directly related to the moments produced by the internal contractile elements. A sliding filament model is developed to generate the complete cycle of motion. The activation of the force-producing elements, the peripheral fibers, occurs over their entire length at once during the effective stroke. In the recovery stroke the sliding of peripheral fibers relative to each other produces activation. The peripheral fibers contribute to the stiffness of the cilium in the sliding filament model only when they are not free to slide because of cross-linkage. The model describes successfully the motion of a variety of types of cilia.


Segregated precuneus network and default mode network in naturalistic imaging.
A resting-state network centered at the precuneus has been recently proposed as a precuneus network (PCUN) or "parietal memory network". Due to its spatial adjacency and overlapping with the default mode network (DMN), it is still not consensus to consider PCUN and DMN separately. Whether considering PCUN and DMN as different networks is a critical question that influences our understanding of brain functions and impairments. Previous resting-state studies using multiple methodologies have demonstrated a robust separation of the two networks. However, since there is no gold standard in justifying the functional difference between the networks in resting-state, we still lack of biological evidence to directly support the separation of the two networks. This study compared the responses and functional couplings of PCUN and DMN when participants were watching a movie and examined how the continuity of the movie context modulated the response of the networks. We identified PCUN and DMN in resting-state fMRI of 48 healthy subjects. The networks' response to a context-rich video and its context-shuffled version was characterized using the variance of temporal fluctuations and functional connectivity metrics. The results showed that (1) scrambling the contextual information altered the fluctuation level of DMN and PCUN in reversed ways; (2) compared to DMN, the FC within PCUN showed significantly higher sensitivity to the contextual continuity; (3) PCUN exhibited a significantly stronger functional network connectivity with the primary visual regions than DMN. These findings provide evidence for the distinct functional roles of PCUN and DMN in processing context-rich information and call for separately considering the functions and impairments of these networks in resting-state studies.


Sensitivity of B16 melanoma sublines to lymphokine-activated killer cells as determined by 51Cr-release and clonogenic assays.
The aim of this study was to compare the differential sensitivities of B16 melanoma sublines to LAK cells by means of the standard 51Cr release assay and a clonogenic assay, which measures both cell survival and proliferation. LAK cells, generated after 4 days incubation with 150 international units (IU)/ml of interleukin-2 (IL-2), showed both cytolytic and anti-proliferative activities against B16 targets. Using an 18 h 51Cr release assay, murine LAK cells showed the highest cytolytic activity against B16 parental cells compared to B16-F1, B16-F10, B16-FLR and B16-BL6 sublines at effector/target (E/T) ratios ranging from 6/1 to 100/1. Purified adherent LAK (A-LAK) cells showed greater cytolytic activity against B16 parental cells and other B16 sublines compared to LAK cells, but otherwise the pattern of reactivity was similar. Using a clonogenic assay, the surviving fraction of B16 parental cells co-cultivated with LAK cells decreased to 0 at an E/T ratio of 50/1, while a 400/1 ratio was required to achieve a similar reduction of B16-F1, B16-F10, B16-FLR, and B16-BL6 sublines. No differences in subline sensitivity were seen with the 51Cr release assay, but these were observed using the clonogenic assay. An inverse linear relationship existed between % surviving fraction, as determined by the clonogenic assay, and cytolytic activity, as determined by the 51Cr release assay. Our data indicate that the clonogenic assay can detect differences in target cell sensitivity that otherwise are undetectable by the standard 51Cr release assay. The clonogenic assay may prove useful in delineating the long-term anti-adherent and anti-proliferative properties of effector cells from their cytolytic activity.


Large-scale preparation of two minor polar polyphenols from Phyllanthus emblica Linn. by macroporous resin column chromatography and high-temperature preparative high-speed counter-current chromatography.
In the present study, an efficient strategy for the large-scale preparation of two minor polar polyphenols from Phyllanthus emblica L. has been established by macroporous resin column chromatography and high-temperature preparative high-speed counter-current chromatography. Macroporous resin column chromatography was used for the enrichment of the target polyphenols. The target polyphenols could be well enriched in the 10% ethanol fraction and the peak area proportion increased from 2.2% in the crude extract to 85.3% in the 10% ethanol fraction. Then, the 10% ethanol fraction was introduced to preparative high-speed counter-current chromatography for separation using an n-butanol-ethyl acetate-water (17:3:20, v/v/v) solvent system. In order to improve the retention of the stationary phase, a high-temperature preparative high-speed counter-current chromatography had been developed by using a 316 L stainless steel pipe as a column. A 50°C of column temperature was used and the retention rate of the stationary phase could reach 75%. Finally, 871 mg of compound Ⅰ and 534 mg of compound Ⅱ with purities higher than 98% were obtained from 4 g of the sample. The chemical structures were identified as corilagin and 1, 6-di-O-galloyl-β-D-glucoside by 1 H-NMR and 13 C-NMR.


Exploring real-world evidence to uncover unknown drug benefits and support the discovery of new treatment targets for depressive and bipolar disorders.
Major depressive and bipolar disorders are associated with impaired quality of life and high economic burden. Although progress has been made in our understanding of the underlying pathophysiology and the development of novel pharmacological treatments, a large unmet need remains for finding effective treatment options. The purpose of this study was to identify potential new mechanisms of actions or treatment targets that could inform future research and development opportunities for major depressive and bipolar disorders. A self-controlled cohort study was conducted to examine associations between 1933 medications and incidence of major depressive and bipolar disorders across four US insurance claims databases. Presence of incident depressive or bipolar disorders were captured for each patient prior to or after drug exposure and incident rate ratios were calculated. Medications that demonstrated ≥50% reduction in risk for both depressive and bipolar disorders within two or more databases were evaluated as potential treatment targets. Eight medications met our inclusion criteria, which fell into three treatment groups: drugs used in substance use disorders; drugs that affect the cholinergic system; and drugs used for the management of cardiovascular-related conditions. This study was not designed to confirm a causal association nor inform current clinical practice. Instead, this research and the methods employed intended to be hypothesis generating and help uncover potential treatment pathways that could warrant further investigation. Several potential drug targets that could aid further research and discovery into novel treatments for depressive and bipolar disorders were identified.


Phase III study of palonosetron for prevention of chemotherapy-induced nausea and vomiting in pediatric patients.
Palonosetron has demonstrated non-inferiority to ondansetron for prevention of chemotherapy-induced nausea and vomiting in pediatric patients in the United States and Europe. We conducted a single-arm registration study to evaluate the efficacy, safety and pharmacokinetics of palonosetron in pediatric patients in Japan. Key inclusion criteria were age of 28 days to 18 years and malignant disease for which initial highly emetogenic chemotherapy or moderately emetogenic chemotherapy was planned. Patients received palonosetron at 20 μg/kg over at least 30 s intravenously before the start of highly emetogenic chemotherapy or moderately emetogenic chemotherapy and received dexamethasone on Days 1-3. The primary endpoint was the proportion of patients achieving a complete response in the overall phase (0-120 h) in Course 1, and its threshold was set at 30%. From December 2016 to June 2019, 60 patients were enrolled, and 58 received at least one dose of palonosetron. The proportion of patients achieving a complete response during the overall phase was 58.6% (95% confidence interval, 44.9%-71.4%), showing the primary endpoint was met (P < 0.0001). Treatment-related adverse events occurred in two patients (3.4%). Regarding the pharmacokinetics of palonosetron, neither the plasma concentration immediately after administration nor the area under the plasma concentration-time curve from time 0 to infinity differed significantly among the age groups. We demonstrated the efficacy of palonosetron in pediatric patients receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy and confirmed the appropriateness of the 20 μg/kg dose, regardless of age, considering the safety and pharmacokinetic profiles. JapicCTI-163305, registered 6 June 2016.


Impact of intravenous magnesium on post-cardiothoracic surgery atrial fibrillation and length of hospital stay: a meta-analysis.
Postoperative atrial fibrillation can occur in 25% to 40% of patients undergoing cardiothoracic surgery. Although the majority of postoperative atrial fibrillation is benign, it has been associated with prolonged hospital length of stay. Magnesium prophylaxis against postoperative atrial fibrillation has been evaluated in several clinical trials; however these trials were small in size and therefore conveyed mixed or inconclusive results. In an attempt to better understand magnesium's role in this setting, we conducted a meta-analysis. A systematic literature search was conducted from January 1999 through August 2004 to identify trials of prophylactic magnesium in the setting of cardiothoracic surgery. The primary outcome measure was the incidence of postoperative atrial fibrillation. Trials were further analyzed based on cumulative doses of magnesium and perioperative time of initiation of prophylaxis, as well as length of stay. Seven randomized trials were identified. Upon meta-analysis, magnesium was found to prevent postoperative atrial fibrillation with an odds ratio of 0.66 and 95% confidence interval of 0.51 to 0.87. The incidence of postoperative atrial fibrillation was also significantly reduced in the low dose with an odds ratio of 0.36 and 95% confidence interval of 0.23 to 0.56, and in the preoperative groups with an odds ratio of 0.46 and 95% confidence interval of 0.31 to 0.67. Prophylactic magnesium reduced length of stay (n = 6 studies) by a weighted mean difference of 0.29 days, with a 95% confidence interval 0.54 to 0.05. Prophylactic magnesium reduced cardiothoracic surgery patients' risk of postoperative atrial fibrillation and length of stay. Administering lower doses and initiating prophylaxis in the preoperative period achieved the greatest reduction in postoperative atrial fibrillation.


A machine-learning-based alloy design platform that enables both forward and inverse predictions for thermo-mechanically controlled processed (TMCP) steel alloys.
Predicting mechanical properties such as yield strength (YS) and ultimate tensile strength (UTS) is an intricate undertaking in practice, notwithstanding a plethora of well-established theoretical and empirical models. A data-driven approach should be a fundamental exercise when making YS/UTS predictions. For this study, we collected 16 descriptors (attributes) that implicate the compositional and processing information and the corresponding YS/UTS values for 5473 thermo-mechanically controlled processed (TMCP) steel alloys. We set up an integrated machine-learning (ML) platform consisting of 16 ML algorithms to predict the YS/UTS based on the descriptors. The integrated ML platform involved regularization-based linear regression algorithms, ensemble ML algorithms, and some non-linear ML algorithms. Despite the dirty nature of most real-world industry data, we obtained acceptable holdout dataset test results such as R2 > 0.6 and MSE < 0.01 for seven non-linear ML algorithms. The seven fully trained non-linear ML models were used for the ensuing 'inverse design (prediction)' based on an elitist-reinforced, non-dominated sorting genetic algorithm (NSGA-II). The NSGA-II enabled us to predict solutions that exhibit desirable YS/UTS values for each ML algorithm. In addition, the NSGA-II-driven solutions in the 16-dimensional input feature space were visualized using holographic research strategy (HRS) in order to systematically compare and analyze the inverse-predicted solutions for each ML algorithm.


Absence of the major sialoglycoprotein in the membrane of human En(a--) erythrocytes and increased glycosylation of band 3.
The human En(a-) blood group is a rare recessive trait. These erythrocytes lack the major membrane sialoglycoprotein (PAS1, MN protein, or glycophorin) and contain a decreased amount of PAS2 as demonstrated by radiolabeling of surface porteins and chemical techniques. A third glycoprotein, Band 3, contains two labeled oligosaccharide chains; the more complex oligosaccharide has a higher molecular weight in En(1-) cells than in normal cells. A fourth glycoprotein, PAS3, is present in usual amounts in En(a-) cells. Cells heterozygous for En(a) are intermediate in these respects. The sialic acid is decreased in En(a-) cells, but the total carbohydrate is similar in the different membranes. The glycolipids are present in normal amounts but are much more exposed to galactose oxidase in En(a-) cells than in normal cells.


Ipsilateral BDNF mRNA expression in the motor cortex positively correlates with motor function of the affected forelimb after intracerebral hemorrhage.
Intracerebral hemorrhage (ICH) is a subtype of stroke that causes major motor impairments. Brain-derived neurotrophic factor (BDNF) is known to have important roles in neuroplasticity and beneficially contributes to stroke recovery. This study aimed to characterize BDNF expression in the motor cortex after ICH and investigate the relationship between cortical BDNF expression and behavioral outcomes using an ICH rat model. Wistar rats were divided into two groups: a SHAM group (n = 7) and an ICH group (n = 8). ICH was induced by the injection of collagenase into the left striatum near the internal capsule. For behavioral assessments, the cylinder test and open field test were performed before surgery and 3 days, 1 week, 2 weeks, and 4 weeks after surgery. Following the behavioral assessments at 4 weeks, BDNF expression in the ipsilateral and contralateral motor cortex was assayed using RT-PCR and ELISA methods. There was no significant difference in either cortical BDNF mRNA or protein expression levels between the SHAM and ICH groups. However, the asymmetry index of BDNF mRNA expression between the ipsilateral and contralateral hemispheres shifted to the ipsilateral hemisphere after ICH. Furthermore, the ipsilateral cortical BDNF mRNA expression level positively correlated with motor function in the affected forelimb after ICH. This study describes for the first time that cortical BDNF mRNA expression is related to post-ICH motor impairment. These results highlight the importance of assessing the interhemispheric laterality of BDNF expression and could help develop novel treatment strategies for BDNF-dependent recovery after ICH.


Neutrophils in lung cancer patients: Activation potential and neutrophil extracellular trap formation.
Patients with cancer have an increased risk of developing venous thromboembolism. Neutrophils and neutrophil extracellular traps (NETs) reportedly influence the risk of cancer-associated thrombosis. Subpopulations of high and low-density neutrophils (HDN/LDN) are of specific interest, as they might have different functions in cancer patients. We aimed to investigate differences between HDNs and LDNs of patients with lung cancer and healthy controls, and their ability of activation and NET formation. Within the framework of the Vienna Cancer and Thrombosis Study, a prospective observational cohort study, HDNs and LDNs from 20 patients with lung cancer and 20 controls were isolated by density gradient centrifugation. The ability of neutrophil subpopulations for activation and NET formation was investigated by flow cytometry. Compared to controls, patients with cancer had higher numbers of total leukocytes, HDNs, and LDNs. LDNs of patients were more frequently in an activated state (CD62L↓/CD16↑) at baseline (median [IQR] 5.9% [3.4-8.8] vs 2.5% [1.6-6.7]). HDNs and LDNs from patients showed a significantly increased response to stimulation with ionomycin (CD11b HDN: 98.5 [95.4-99.4] vs 41.7 [13.4-91.6]; LDN: 82.9 [63-94] vs 39.6 [17.3-72.1]). In addition, HDNs from patients showed a higher capability of NET formation after ionomycin stimulation compared to HDNs from healthy controls (18509.5 [12242.5-29470.3] vs 10001 [6618.8-18384.3]). Protumorigenic LDNs were elevated, and neutrophil subpopulations showed an increased activation profile and ability for NET formation in patients with cancer. These mechanisms might be involved in tumor promotion and contribute to the prothrombotic phenotype of neutrophils in cancer.


Anthocyanins isolated from the purple-fleshed sweet potato attenuate the proliferation of hepatic stellate cells by blocking the PDGF receptor.
During the process of liver fibrosis, hepatic stellate cells (HSCs) play a critical role in the increased formation and reduced degradation of extracellular matrix in the liver. We investigated the anti-proliferative effects of an anthocyanin fraction (AF), isolated from the purple-fleshed sweet potato, on platelet-derived growth factor (PDGF)-BB-dependent signaling pathways in HSC-T6 cells. HSC proliferation plays a pivotal role in liver fibrogenesis. The AF suppressed HSC activation, including PDGF-induced proliferation and α-smooth muscle actin (α-SMA) expression. Additionally, AF inhibited PDGF-BB-induced Akt and ERK1/2 phosphorylation. AF inhibited the phosphorylation level of PDGF receptor-β (PDGFR-β) following PDGF-BB stimulation, providing a mechanism for the inhibition of AF-mediated kinase. These results suggest that AF suppresses HSC proliferation by blocking PDGFR-β signaling, inhibiting Akt and ERK1/2 activation and α-SMA expression.


Development of striated rootlets during ciliogenesis in the human oviduct epithelium.
Striated rootlets in ciliated cells are conical banded structures composed of longitudinally aligned filaments. The formation of striated rootlets during ciliognesis in the human oviduct epithelium was studied by electron microscopy. Primitive rootlets appeared at the proximal side of basal bodies before or at the same time as ciliary budding. After the formation of several striations, the tip of the rootlets extended deeply toward the interior of the cell and became differentiated into two distinct parts, viz., the proximal conical part connected to the basal body and the distal fibrillar part. The periodicity of the striations in the fibrillar part was 68. 5+/-2.95 nm, about 5 nm longer than that of the conical part (63. 9+/-2.25 nm). The dark band in the striation was thicker in the fibrillar part than in the conical part. Since the fibrillar part was not observed in the mature cilium, this part was considered as being either degraded or changed into the conical part during ciliogenesis.


COVID-19 vaccination attitudes, values, intentions: US parents for their children, September 2021.
To compare vaccine-related attitudes and values of parents of children 2-17 years old to other adults, examine intentions to vaccinate their children, and identify factors associated with intending to vaccinate children. A nationally representative survey was conducted in September 2021 (just before the EUA for children 5-11 years old) using Ipsos KnowledgePanel, a probability-based web panel. The survey measured COVID-19 vaccination status, intentions, attitudes, values, and trust in public health authorities among US adults. Scale response options to survey items were dichotomized, and cross-tabulations and logistic regressions were performed. Parents had lower odds of reporting being vaccinated against COVID-19 than other adults even after adjusting for associated sociodemographic characteristics such as age (aOR: 0.66; 95 %CI: 0.50-0.87). The most prevalent parental concerns about COVID-19 vaccines included the speed of their development (88 %), potential side effects (78 %), suspicion of government (77 %), and suspicion of pharmaceutical companies (72 %). Fewer than half (42 %) of parents intended to vaccinate their children 5-11 years old, while 38 % were uncertain and 20 % were unlikely to ever vaccinate their children. Vaccinated parents had higher odds than unvaccinated parents of intending to vaccinate their children (OR: 675.51; 95 %CI: 106.46-4286.12). Discussions with healthcare providers who encouraged COVID-19 vaccination were positively associated with intent to vaccinate children (OR: 11.29; 95 %CI: 2.60-49.02). We found parental vaccination and conversations with providers were positively associated with intent to vaccinate children. Decisions about childhood vaccination need to be supported by healthcare providers and a public health system that makes vaccine access and related information equitable and accessible. Vaccination-related decision making should be guided by healthcare providers and provide information about safety and risk to children.


ACR Appropriateness Criteria® Assessment of Gravid Cervix.
Preterm birth remains the leading cause of perinatal morbidity and mortality. Although the greatest risk factor for preterm birth is a history of prior preterm birth, a short cervical length (≤25 mm) before 24 weeks' gestational age is also associated with increased risk of spontaneous preterm delivery. As such, cervical length assessment has become of particular interest in predicting those patients at risk for preterm birth. Other clinical scenarios (eg, preterm labor, induction of labor, and active labor) may arise, in which assessment of the cervix may be of interest. Ultrasound is the mainstay imaging modality for assessing the gravid cervix, with transvaginal ultrasound recommended in patients at high risk for preterm birth or suspected preterm labor. Transperineal ultrasound is an alternate approach in those cases where transvaginal ultrasound in contraindicated. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Trends in long-stay hospitalization in Denmark: a descriptive register study, 1972-1987.
By means of 4 cross-sections at 5-year intervals from 1972 to 1987, information on long-stay inpatients and daypatients was extracted from the computerized, cumulative psychiatric case register in Denmark. Long-stay refers to continuous hospitalization of more than 1 year. The prevalence of long-stay patients declined from 101 per 100,000 general population in 1972 to 38 per 100 000 in 1987. As the prevalence of all diagnoses declined, regardless of age and sex, it is suggested that the major cause of the observed trends is altered political and administrative strategies, influenced by and influencing altered capabilities and methods of treatment. The trends are described in detail and their implications discussed.


A human polysialyltransferase directs in vitro synthesis of polysialic acid.
Polysialic acid (PSA) is a linear homopolymer of alpha-2,8-linked sialic acid residues whose expression is developmentally regulated and modulates the adhesive property of the neural adhesion molecule, N-CAM. Recently, hamster and human cDNAs encoding polysialyltransferase (PST-1 for the hamster enzyme and PST for the human enzyme) were cloned, and by using the human cDNA it was demonstrated that the expression of PSA in N-CAM facilitates neurite outgrowth (Nakayama, J., Fukuda, M.N., Fredette, B., Ranscht, B., and Fukuda, M. (1995) Proc. Natl. Acad. Sci. U.S.A., 92, 7031-7035; Eckhardt, M.A., Mühlenhoff, M., Bethe, A., Koopman, J., Frosch, M., and Gerardy-Schahn, R. (1995) Nature 373, 715-718.) Although these studies demonstrated that PST-1 and PST synthesize PSA in cultured cells, it was not shown that they could catalyze the polycondensation of alpha-2,8-linked sialic acid on a glycoconjugate template containing alpha-2,3-linked sialic acid. Here we demonstrate that PSA formation by PST is independent from the presence of N-CAM in vivo. We then develop an in vitro assay of PSA synthesis using glycoproteins other than N-CAM as acceptors and a soluble PST as an enzyme source. The soluble PST, produced as a chimeric protein fused with protein A, was incubated with rat alpha 1-acid glycoprotein, fetuin or human alpha 1-acid glycoprotein as acceptors together with the donor substrate CMP-[14C]NeuNAc. Incubation of fetuin with the soluble PST, in particular, resulted in a high molecular weight product that was susceptible to PSA-specific endoneuraminidase. Polysialylated products were not formed when alpha-2,3-linked sialic acid was removed from the acceptor fetuin before incubation. These results establish that a single enzyme, PST, alone can catalyze both the addition of the first alpha-2,8-linked sialic acid to alpha-2,3-linked sialic acid and the polycondensation of all alpha-2,8-linked sialic acids, yielding PSA.


Effects of implant and vocal fold stiffness on voice production after medialization laryngoplasty in an MRI-based vocal fold model.
Medialization laryngoplasty is one of the primary surgical interventions in the treatment of glottal insufficiency due to vocal fold paralysis, paresis, or atrophy. During the surgery, an implant is laterally inserted into the larynx to medialize the affected vocal fold toward glottal midline, with the goal of improving glottal closure during phonation and voice production efficiency. While implants of different materials and geometry designs have been used, the effect of implant design on the voice outcome remains unclear. In this simulation study, the effect of implant stiffness was investigated in an MRI-based model of the vocal folds after medialization laryngoplasty. The results showed that implant stiffness had a significant impact on the phonation threshold pressure, glottal area waveform, and fundamental frequency, but only small effect on the closed quotient and other acoustic measures of the produced voice. The effect of implant stiffness also exhibited variability, depending on the stiffness conditions of the vocal fold and paraglottic tissues, indicating that individual differences need to be considered during the planning of medialization laryngoplasty.


New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders.
Neurodegenerative disorders remain a major burden for our society, affecting millions of people worldwide [...].


Intimate relationships and patterns of drug and sexual risk behaviors among people who inject drugs in Kazakhstan: A latent class analysis.
Multiple drug and sexual risk behaviors among people who inject drugs (PWID) in intimate relationships increase the risk of HIV and HCV transmission. Using data on PWID in intimate partnerships in Almaty, Kazakhstan, this study performed latent class analysis (LCA) on drug and sexual risk behaviors and estimated associations between dyadic relationship factors and membership in latent classes. LCA was performed on a sample of 510 PWID (181-females/FWID, 321-males/MWID) to identify levels of drug and sexual risk behaviors. Generalized structural equation modeling with multinomial regressions estimated associations between relationship factors (length risk reduction communication, risk reduction self-efficacy) and class membership after adjusting for substance use severity, overdose, depression, binge drinking, intimate partner violence, structural factors, and sociodemographic characteristics. Models were sex-stratified to include FWID and PWID. A 3-class model best fit the data and consisted of low, medium, and high-risk classes. GSEM found that greater injection self-efficacy was associated with a lower likelihood of membership in the high-risk class for PWID and FWID. For MWID, greater length of the relationship was associated with a lower likelihood of membership in the medium-risk class. Greater relationship communication was associated with increased risk of membership in the high-risk latent class for MWID. Future research must investigate if increasing risk reduction and safe sex self-efficacy could reduce drug and sexual risk behaviors and HIV transmission among PWID and their intimate partners. Interventions are needed that reduce power inequities within relationships as a method of increasing self-efficacy, particularly among women.


Marijuana coping motives interact with marijuana use frequency to predict anxious arousal, panic related catastrophic thinking, and worry among current marijuana users.
The present investigation evaluated whether coping motives for marijuana use interacted with past 30-day frequency of marijuana use in relation to anxiety-relevant variables among community-recruited young adult marijuana users (n=149). As expected, after covarying cigarettes per day, alcohol use, and total years of marijuana use, the interaction between frequency of past 30-day marijuana use and coping motives predicted anxious arousal symptoms, agoraphobic cognitions, and worry. Marijuana users who demonstrated high use frequency and high coping motives demonstrated the highest levels of anxiety across these anxiety-relevant criterion variables. No such effects were evident, as expected, for depressive symptoms, offering explanatory specificity for anxiety relative to depressive factors. These results are discussed in relation to better understanding the role of marijuana use and coping motives in regard to anxiety vulnerability.


Effects of stimulus intensity on laryngeal long latency responses in awake humans.
Percutaneous electrical stimulation applied to the internal branch of the superior laryngeal nerve (ISLN) results in two long latency laryngeal adductor responses in awake humans: an ipsilateral thyroarytenoid (TA) R1 muscle response at 16 ms, and later bilateral TA R2 muscle responses at 60 ms. The purpose of this study was to determine whether a functional relationship existed between the R1 and R2 responses by gradually increasing the level of electrical stimulation from threshold to supramaximal levels. R1 amplitude increased linearly with stimulation intensity in 9 of the 11 subjects, whereas R2 only had a positive linear relationship in 3 subjects and a negative relationship with stimulation intensity in 1 subject. Significant negative relationships were found between response latency and stimulation intensity in 3 subjects for the R1 responses and 3 other subjects for the R2 responses. Overall, R1 amplitudes increased systematically, whereas R2 responses varied in latency and amplitude with increasing stimulus intensity. Neither the latencies nor the amplitudes of the two responses were related after adjusting for stimulation intensity within subjects by using partial correlation coefficients. The R1 and R2 responses were functionally unrelated and most likely have different neural components.