Colorectal cancer screening with faecal immunochemical test: Patterns of participation.
To evaluate participation and participation patterns in a population-based screening programme for colorectal cancer (CRC) using the faecal immunochemical test (FIT). All individuals invited to three consecutive screening rounds in the population-based CRC screening between October 2015 and December 2020 in the Stockholm-Gotland Region, Sweden were included. Patterns of participation were assessed. The study included 26 541 individuals which resulted in 79 623 screening events. The overall uptake rate was 71.5% and women had a significantly higher participation rate. The participation rate increased significantly between the first and third screening round for both men and women, and the increase was larger among men than women (66.1 to 70.7% vs. 73.1 to 75.4%). In total, 80.9% participated at least once. Consistent participation was the most common participation pattern (61.0%). The probability of attending all three consecutive rounds after initial participation was 87.7%. Over the three rounds, 17.4% participated after a reminder letter. Screening individuals attending after a reminder letter had a higher proportion of drop-outs in the following screening round compared to initial participants (15.4% vs 6.2%). A constant and high participation rate was observed in population-based FIT-screening for CRC. Initial participation was a strong predictor for continuous participation. The need for a reminder letter before participation was a risk factor for subsequent drop-out.


Nuclear localization and transforming activity of human papillomavirus type 16 E7-beta-galactosidase fusion protein: characterization of the nuclear localization sequence.
A MAb 9F6 was capable of staining HPV16 E7 in a human cervical carcinoma line, CaSki, and rat 3Y1 cells stably expressing HPV16 E7 gene. Contrary to the current understanding of E7 as a nuclear protein, the site of staining was clearly cytoplasmic. The subcellular localization of E7 was further studied by using the beta-galactosidase (beta-gal) receptor method. A fusion protein composed of E7 and beta-gal was stably expressed in rat 3Y1 cells. The beta-gal activity in these cells was detected mostly in the nucleus, even though 9F6 still stained the cytoplasm of these cells. The fusion protein was also found to be oncogenic since transfected 3Y1 cells acquired transformed phenotypes such as increased saturation density and anchorage-independent growth. These results indicate that biologically active E7 exists mostly in the nucleus, but nuclear E7 is masked from 9F6. A series of deletion mutants of E7 further demonstrated that the amino acid sequence from 16 to 41 was enough to transport beta-gal into the nucleus. A mutation either at amino acid 24 or 26 which is known to disrupt the binding of E7 to RB, the retinoblastoma gene product, did not strongly affect the nuclear localization of the fusion protein, suggesting that the nuclear transportation of E7 is mostly independent of RB binding.


Preliminary report on household contact studies of the prevention of pertussis in Japanese children by Takeda diphtheria and tetanus toxoids and acellular pertussis vaccine combined.
Acellular pertussis vaccines combined with diphtheria and tetanus toxoids and adsorbed onto an aluminum salt (AcPDT) have been used exclusively in Japan for the immunization of children since 1981. (Interagency Report 2), 1987; Kimura et al. 1), 1985) Immunization of children is initiated at two years of age with a booster dose one year later. Morbidity and mortality rates from pertussis, which had steadily increased since 1975 because of poor acceptance of the whole cell preparation, have declined since widespread use of AcPDT (Kimura, 1985). The apparent efficacy of AcPDT has also been demonstrated by several household contact studies in which rates of pertussis in immunized and unimmunized children exposed to the disease in their own homes were determined. In these studies vaccine efficacy ranged between 78 and 93 percent (Interagency Report). However, there are six different manufacturers of AcPDT in Japan, and their products vary in antigenic constituents. One manufacturer produces AcPDT that contains about 50 percent pertussis toxoid and 50 percent filamentous hemagglutinin (B-type AcPDT). Four manufacturers market vaccines that contain predominantly FHA, approximately 10 percent pertussis toxoid, and approximately one percent agglutinogens (T-type AcPDT). The sixth product comprises pertussis toxoid and FHA in amounts that are intermediate between the B- and T-types. With the exception of one small study (Aoyama, 1988) all of the Japanese studies have considered these AcPDT products as a group, and accordingly product-specific information concerning efficacy is not available.(ABSTRACT TRUNCATED AT 250 WORDS)


Childhood Otitis Media: A Cohort Study With 30-Year Follow-Up of Hearing (The HUNT Study).
To study the extent to which otitis media (OM) in childhood is associated with adult hearing thresholds. Furthermore, to study whether the effects of OM on adult hearing thresholds are moderated by age or noise exposure. Population-based cohort study of 32,786 participants who had their hearing tested by pure-tone audiometry in primary school and again at ages ranging from 20 to 56 years. Three thousand sixty-six children were diagnosed with hearing loss; the remaining sample had normal childhood hearing. Compared with participants with normal childhood hearing, those diagnosed with childhood hearing loss caused by otitis media with effusion (n = 1255), chronic suppurative otitis media (CSOM; n = 108), or hearing loss after recurrent acute otitis media (rAOM; n = 613) had significantly increased adult hearing thresholds in the whole frequency range (2 dB/17-20 dB/7-10 dB, respectively). The effects were adjusted for age, sex, and noise exposure. Children diagnosed with hearing loss after rAOM had somewhat improved hearing thresholds as adults. The effects of CSOM and hearing loss after rAOM on adult hearing thresholds were larger in participants tested in middle adulthood (ages 40 to 56 years) than in those tested in young adulthood (ages 20 to 40 years). Eardrum pathology added a marginally increased risk of adult hearing loss (1-3 dB) in children with otitis media with effusion or hearing loss after rAOM. The study could not reveal significant differences in the effect of self-reported noise exposure on adult hearing thresholds between the groups with OM and the group with normal childhood hearing. This cohort study indicates that CSOM and rAOM in childhood are associated with adult hearing loss, underlining the importance of optimal treatment in these conditions. It appears that ears with a subsequent hearing loss after OM in childhood age at a faster rate than those without; however this should be confirmed by studies with several follow-up tests through adulthood.


Coronary endothelial dysfunction demonstrated by means of (15)O-labeled water PET/CT in hypothyroid cardiomyopathy.
Hypothyroidism is a rare cause of dilated cardiomyopathy. Triiodothyronine was found to target endothelial nitric oxide synthase, which serves to enhance peripheral vascular relaxation by acting on vascular smooth muscle cells. In patients with subclinical hypothyroidism, adenosine-induced coronary flow reserve is significantly reduced. We report the case of a 46-year-old woman with hypothyroid cardiomyopathy manifested as reversible severe left ventricular dysfunction (LVEF = 32%). O-labeled water PET at rest and during cold pressor test showed a severe coronary endothelial dysfunction. In patients with severe hypothyroidism, endothelial function is impaired and may be an important mechanism of heart failure.


Peptidomics in Drosophila melanogaster.
In analogy with proteomics technology, where all proteins expressed in a cell or tissue are analysed, the peptidomic approach aims at the simultaneous visualisation and identification of the whole peptidome of a cell or tissue, ie all expressed peptides with their post-translational modifications. With nanoscale liquid chromatography (nanoLC), combined with mass spectrometry and subsequent database searching, the peptidome of the Drosophila larval brain has been identified at the amino acid sequence level. In a single experiment involving only 50 Drosophila larval brains, one can obtain a display of the expressed peptides. In this paper, current peptidomics technology will be explained, using Drosophila as an example. Compared with the 400,000 Drosophila whole bodies that were required as a starting material for traditional biochemical peptide purification rounds, the authors are convinced that peptidomics technology, which in the future will certainly be applied to the analysis of different physiological states, has the inherent potential to bring about a true revolution in the study of the molecular physiology of Drosophila.


Nanoparticle-rich diesel exhaust-induced liver damage via inhibited transactivation of peroxisome proliferator-activated receptor alpha.
Diesel exhaust emission contains a high amount of nano-sized particles and is considered to be systemically distributed in the body. However, few studies about the effects of nanoparticle rich-diesel exhaust (NR-DE) on liver have been reported. The present investigation focuses on the effects of NR-DE on livers in rats, especially concerning inflammation and lipid metabolism. Male F344 rats were exposed to fresh air or low (24 ± 7 µg/m3 ), medium (39 ± 4 µg/m3 ) and high (138 ± 20 µg/m3 ) concentrations of NR-DE for 1, 2, or 3 months (5 hours/day, 5 days/week). Exposure to both medium and high concentrations of NR-DE for one month increased plasma asparate aminotransferase and alanine aminotransferase activities, while only high concentrations increased plasma interleukin-6 and hepatic nuclear factor kappa B (NFκB), suggesting that activation of hepatic inflammatory signaling took place. Although these exposures elevated peroxisome proliferator-activated receptor (PPAR) α levels or its binding activity to the response element, neither activated PPARα-target genes such as β-oxidative enzymes nor inhibited NFκB elevation. Thus, NR-DE may contain some materials that inhibit PPARα activation in relation to lipid metabolism and inflammation. Taken together, NR-DE exposure at one month may cause inflammation; however, this finding may not be observed after a longer exposure period. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1985-1995, 2016.


Single-molecule sequence detection via microfluidic planar extensional flow at a stagnation point.
We demonstrate the use of a microfluidic stagnation point flow to trap and extend single molecules of double-stranded (ds) genomic DNA for detection of target sequences along the DNA backbone. Mutant EcoRI-based fluorescent markers are bound sequence-specifically to fluorescently labeled ds lambda-DNA. The marker-DNA complexes are introduced into a microfluidic cross slot consisting of flow channels that intersect at ninety degrees. Buffered solution containing the marker-DNA complexes flows in one channel of the cross slot, pure buffer flows in the opposing channel at the same flow rate, and fluid exits the two channels at ninety degrees from the inlet channels. This creates a stagnation point at the center of a planar extensional flow, where marker-DNA complexes may be trapped and elongated along the outflow axis. The degree of elongation can be controlled using the flow strength (i.e., a non-dimensional flow rate) in the device. Both the DNA backbone and the markers bound along the stretched DNA are observed directly using fluorescence microscopy, and the location of the markers along the DNA backbone is measured. We find that our method permits detection of each of the five expected target site positions to within 1.5 kb with standard deviations of <1.5 kb. We compare the method's precision and accuracy at molecular extensions of 68% and 88% of the contour length to binding distributions from similar data obtained via molecular combing. We also provide evidence that increased mixing of the sample during binding of the marker to the DNA improves binding to internal target sequences of dsDNA, presumably by extending the DNA and making the internal binding sites more accessible.


Perception of Cosmetic Procedures among Saudis during COVID-19 Pandemic.
A novel coronavirus disease (COVID-19) was first reported in December 2019 in Wuhan, China. The fast spread of the virus has led to a significant reduction in the numbers of elective procedures especially cosmetic interventions. Although many measures have been carried out to offload the health care system, it is unclear whether these changes had an effect on general population perception toward undergoing cosmetic procedures. The aim of this study was to assess the perception of Saudis toward undergoing a cosmetic surgery during the COVID-19 pandemic. An online survey consisting of two parts was used, with a series of questions about cosmetic procedures, in general, and cosmetic procedures during the COVID-19 pandemic, in particular. The survey included Saudis (age 18 to 60 years) with access to social media. A total of 563 respondents participated in this survey. The vast majority were women (86.9%) and were between 18 and 24 years old (38.7%). Some 27.4% considered a cosmetic procedure during the COVID-19 pandemic; however, only 11.9% underwent any. In the majority of the participants (86%), the pandemic did not change their minds about having a cosmetic procedure. About 49.7% agreed that fear of contracting the virus would be a factor for not undergoing a cosmetic procedure during the pandemic. Clear differences in the engagement and perception of cosmetic procedures during the COVID-19 pandemic exist among Saudis. More studies are needed to explore the effects of pandemics on aesthetic practice and to find ways to perform elective procedures in a safe way.


Academic and school health issues among children exposed to maternal intimate partner abuse.
To determine the association between children's exposure to maternal intimate partner violence (IPV) and academic problems and school health concerns. The study population consisted of 153 children aged 5 to 16 years who attended public school and whose mothers experienced police- or court-reported IPV. The comparison group consisted of public school peers of the exposed children. Generalized linear modeling using a binomial distribution and log-link function served as the primary method of analysis. Urban public school district. The occurrence of academic problems and type-specific school nurse visits during the 1-year study period. Children whose mothers experienced IPV were more likely to be suspended from school (relative risk [RR], 1.8; 95% confidence interval [CI], 1.2-1.7) and to have had frequent non-suspension-related absences (RR, 1.6; 95% CI, 1.0-2.3) than comparison children after adjusting for relevant confounders. Intimate partner violence-exposed children were more likely to have a school nurse visit for social or emotional complaints (RR, 2.2; 95% CI, 1.3-3.9), a visit that resulted in being sent home from school (RR, 1.6; 95% CI, 1.1-2.3), or a visit that led to referral to the school speech pathologist (RR, 7.5; 95% CI, 1.9-29.6) relative to comparison schoolchildren after adjusting for relevant confounders. Children's exposure to maternal IPV is significantly associated with the occurrence of academic problems and school health concerns. Describing the increased risk of the academic and health problems exhibited by IPV-exposed children relative to nonexposed children offers the possibility of improving the likelihood that clinicians will identify the woman who experienced abuse and her children, and promote referral to appropriate resources.


Hormonal effects on prevention or regression of atheroma.
White Leghorn cockerels, fed either normal or cholesterol enriched food, were injected with saline, peanut oil, testosterone, oestradiol, progesterone, or oestradiol plus progesterone for 87 days. The ascending aortas, descending aortas and abdominal aortas were examined by light and electron microscopy and both qualitative and quantitative assessments made. The results were subjected to multivariate analysis. Cholesterol feeding increased lipid storage and round cell infiltration in the endothelium and intima, and both the degree of lipid storage and the amount of lumen obstruction was much greater in the abdominal aorta than in the ascending or descending aorta. Treatment with oestrogen plus progesterone, regardless of diet or site of action, caused a highly significant reduction in the percentage of normal cells of the endothelium. Those cockerels treated with oil, androgen and progesterone showed significantly less large foamy eosinophilic endothelial cells than those treated with oestrogen plus progesterone. The degree of round cell infiltration was increased by androgen and oestrogen, but not by oestrogen plus progesterone, when compared with both saline treated and oil treated controls. Cholesterol feeding caused a reduced percentage of normal endothelial cells. This was significantly enhanced by treatment with androgen, progesterone and saline. The effect of cholesterol feeding as a cause of a reduced percentage of normal, and an increased percentage of foamy eosinophilic endothelial cells, was significantly enhanced in the ascending aorta and the descending aorta but not in the abdominal aorta. The same site-dietary interaction was observed in the trend towards an excess of large clear cells over large eosinophilic cells in the intima. In spite of this the extent of plaque likely to cause obstruction as a result of this site-dietary interaction was increased only in the abdominal aorta. An unexpected treatment-site interaction was that progesterone had an enhanced effect, causing disruption of the internal elastic lamina of the ascending aorta but not of the descending or abdominal aortas. There was no evidence that diet or treatment increased the amount of acid esterase in the tissues, even though the chickens showed the expected species deficiency of this enzyme, but there was a significant relationship between the presence of lipid and the amount of acid esterase in the plaques of the abdominal aorta. Male albino Wistar rats were primed with peanut oil, oestrogen and triamcinolone before subcutaneous granulomas were induced by implanting cholesterol, and then treated with these substances for longer periods. Cryostat sections of the granulo


Learning disabilities and anxiety: a meta-analysis.
This article presents the results of a meta-analysis of the empirical literature on anxious symptomatology among school-aged students with learning disabilities (LD) in comparison to their non-LD peers. Fifty-eight studies met inclusion criteria. Results indicate that students with LD had higher mean scores on measures of anxiety than did non-LD students. The overall effect size was statistically significant and medium in magnitude (d=.61) although substantial heterogeneity of results was found. Moderator effects were examined for informant type, gender, grade, publication status, and identification source. Informant type (i.e., self-, parent, or teacher report) explained a significant amount of variability in the sample of studies, and identification source (i.e., school identified or special school and clinic/hospital identified) approached statistical significance. Implications for assessment and intervention are discussed.


Effect of emergency department fibrinogen testing on survival of trauma patients receiving blood transfusions.
: Fibrinogen is the first clotting factor to reach critically low levels during blood loss and its depletion is associated with coagulopathy, increased blood loss, transfusion requirements and mortality after trauma. However, direct measurements of fibrinogen concentration or function are not included in many Emergency Department (ED) trauma laboratory testing protocols. We hypothesized that including a test of fibrinogen concentration in the ED would be associated with increased survival for trauma patients requiring blood transfusions.To test this hypothesis, we performed a single-centre retrospective study of the effect of a resulted fibrinogen concentration measurement performed in the ED on survival of trauma patients receiving blood transfusions within the first 4 h of their hospital arrival. Multivariate logistic regression was used test the effect of a fibrinogen test on hospital survival after adjusting for the influence of INR, injury severity, lowest recorded blood pressure and blood transfusion intensity defined as the number of red blood cell units transfused in the first 4 h or care.Of 11 404 trauma registry individuals from 2016 to 2017, 843 (7.4%) received any blood transfusions within the first 4 h of ED care, of whom 635 (75.3%) had a documented fibrinogen concentration ordered and resulted. Multivariate logistic regression for hospital survival demonstrated a significant interaction effect between the presence of a fibrinogen test and transfusion intensity (Whole Model P < 0.0001, Interaction P = 0.035). Repeat analysis after stratifying for those individuals receiving more than 4 units of red blood cell units within 4 h of care found that the presence of a fibrinogen test was independently associated with survival only for those receiving more than 4 units [FIB test odds ratio for survival = 3.5 (1.0, 10.8), P = 0.03].Fibrinogen testing in the ED may be a valuable addition to resuscitation of the trauma patient receiving significant blood transfusions.


Evaluation and Optimization of in silico designed Sphingosine-1-Phosphate (S1P) Receptor Subtype 1 Modulators for the Management of Multiple Sclerosis.
Multiple Sclerosis (MS) is a chronic autoimmune disorder affecting the Central Nervous System (CNS) through inflammation, demyelination and neurodegeneration. Sphingosine-1-phosphate receptor (S1PR1) modulators have been approved for the management of MS. Phosphorylated fingolimod mimics endogenous sphingosine-1-phosphate (S1P), a bioactive lipid that regulates remyelination and cell injury. Amiselimod was developed as a successor of fingolimod, with more specificity for S1PR1, and showed promising results until phase 2 clinical trials. This study utilized the fingolimod and amiselimod scaffolds, together with their critical binding interactions for the S1PR1 Ligand Binding Pocket, as templates for the in silico de novo design of high efficiency binding Lipinski rule-compliant molecules. A rigorous selection process identified two molecules, Molecules 003 and 019, deriving from fingolimod and amiselimod, respectively, which were deemed most suitable for further optimization.


Performance of long-stay schizophrenics after drug withdrawal on matched immediate and delayed recall tasks.
Both anticholinergic and neuroleptic drugs were withdrawn from eight long-stay hospitalized chronic schizophrenics. These patients and normal controls were then tested on Calev, Venables & Monk's (1983) immediate and delayed matched recall tasks to evaluate their rate of forgetting of verbal well-encoded materials. The results showed rapid forgetting in schizophrenics. This finding suggests that a post-encoding deficit characterizes long-stay schizophrenics after drug withdrawal. Cognitive and brain pathologies that may explain these results are discussed.


Difference and similarity of dielectric relaxation processes among polyols.
Complex permittivity measurements were performed on sorbitol, xylitol, and sorbitol-xylitol mixture in the supercooled liquid state in an extremely wide frequency range from 10 microHz to 500 MHz at temperatures near and above the glass transition temperature. We determined detailed behavior of the relaxation parameters such as relaxation frequency and broadening against temperature not only for the alpha process but also for the beta process above the glass transition temperature, to the best of our knowledge, for the first time. Since supercooled liquids are in the quasi-equilibrium state, the behavior of all the relaxation parameters for the beta process can be compared among the polyols as well as those for the alpha process. The relaxation frequencies of the alpha processes follow the Vogel-Fulcher-Tammann manner and the loci in the Arrhenius diagram are different corresponding to the difference of the glass transition temperatures. On the other hand, the relaxation frequencies of the beta processes, which are often called as the Johari-Goldstein processes, follow the Arrhenius-type temperature dependence. The relaxation parameters for the beta process are quite similar among the polyols at temperatures below the alphabeta merging temperature, T(M). However, they show anomalous behavior near T(M), which depends on the molecular size of materials. These results suggest that the origin of the beta process is essentially the same among the polyols.


The follicle-stimulating hormone receptor Asn680Ser polymorphism is associated with preterm birth in Hispanic women.
Recently, a study based on the analysis of accelerated evolution of related genes at birth identified the follicle-stimulating hormone receptor (FSHR) as a possible candidate for the development of preterm delivery. Additionally, FSHR expression has been described in extragonadal tissue including the placenta. Therefore, the aim of the present study was to determine the association between the N680S polymorphism of the follicle-stimulating hormone receptor and preterm birth in a population of Hispanic women. Placenta samples were obtained from 64 women who had preterm births and 54 control cases. DNA was extracted and genotyped for the N680S FSHR gene polymorphism by polymerase chain reaction-restriction fragment length polymorphism. The χ2 test and t-test were used to calculate statistical significance. Statistically significant differences in genotype frequencies for the N680S polymorphism were observed between preterm and term groups (p = .04). Based on the Akaike information criterion values, the dominant model showed that the NN genotype had a significantly increased risk of preterm birth compared with the SS + NS genotype (OR 2.52, 95% CI 1.20-5.33, p = .02). The results herein suggest that the FSHR polymorphism N680S is significantly associated with preterm birth in the Hispanic population.


Effects of sodium benzoate, a widely used food preservative, on glucose homeostasis and metabolic profiles in humans.
Sodium benzoate is a widely used preservative found in many foods and soft drinks. It is metabolized within mitochondria to produce hippurate, which is then cleared by the kidneys. We previously reported that ingestion of sodium benzoate at the generally regarded as safe (GRAS) dose leads to a robust excursion in the plasma hippurate level [1]. Since previous reports demonstrated adverse effects of benzoate and hippurate on glucose homeostasis in cells and in animal models, we hypothesized that benzoate might represent a widespread and underappreciated diabetogenic dietary exposure in humans. Here, we evaluated whether acute exposure to GRAS levels of sodium benzoate alters insulin and glucose homeostasis through a randomized, controlled, cross-over study of 14 overweight subjects. Serial blood samples were collected following an oral glucose challenge, in the presence or absence of sodium benzoate. Outcome measurements included glucose, insulin, glucagon, as well as temporal mass spectrometry-based metabolic profiles. We did not find a statistically significant effect of an acute oral exposure to sodium benzoate on glucose homeostasis. Of the 146 metabolites targeted, four changed significantly in response to benzoate, including the expected rise in benzoate and hippurate. In addition, anthranilic acid, a tryptophan metabolite, exhibited a robust rise, while acetylglycine dropped. Although our study shows that GRAS doses of benzoate do not have an acute, adverse effect on glucose homeostasis, future studies will be necessary to explore the metabolic impact of chronic benzoate exposure.


Gallbladder torsion. Case report.
Gallbladder torsion is a rare surgical emergency occurring primarily in elderly women. The anatomical background is a variation in the attachment of the gallbladder to the inferior margin of the liver. Increasing life span will probably lead to an increasing number of cases, and gallbladder torsion must be kept in mind in patients with sudden onset of pain in the upper right quadrant, nausea, vomiting, and a palpable mass. None of the laboratory routines or non-invasive examinations enables one to make the right preoperative diagnosis. Treatment is cholecystectomy. Promptly treated, the prognosis is good.


[Almost complete regression of cerebral arteriovenous malformation--report of a case (author's transl)].
Spontaneous regression or disappearance of cerebral arteriovenous malformation (AVM) had been rarely reported in the literatures. Regression after carotid ligation or radiation therapy are not spontaneous one, because these treatments may have some influences on morphological changes of AVM by CBF dynamic change or by some radiobiological effects on AVM. The reported case is 57 aged male. He had an episode of sudden onset of left hemiparesis 7 years ago and was treated conservatively at a private doctor. Afterward he enjoyed his life, for 4 years, he consulted our clinic on account of left hemiconvulsion. Right CAG revealed right parietal AVM (3.5 X 4.0 X 5.O) with dilated feeding and draining vessels. Patient denyed operation at that time, but again consulted our clinic on account of severe left hemiconvulsion. Right CAG was performed again, but right parietal AVM was almost not visualized and feeding and draining vessels were diminished in diameter. Inspite of repeated 4 vessel angiographies AVM was remarkably regressed, and also no angiospastic vessels and intracerebral hematoma were absent in these angiographies. Though spontaneous regression of cerebral AVM is rare course, we report the importance of morphological follow up, when cerebral AVM is nondefinitively treated.


Temperature-Dependent Raman Spectroscopy of Titanium Trisulfide (TiS3) Nanoribbons and Nanosheets.
Titanium trisulfide (TiS3) has recently attracted the interest of the 2D community because it presents a direct bandgap of ∼1.0 eV, shows remarkable photoresponse, and has a predicted carrier mobility up to 10000 cm(2) V(-1) s(-1). However, a study of the vibrational properties of TiS3, relevant to understanding the electron-phonon interaction that can be the main mechanism limiting the charge carrier mobility, is still lacking. In this work, we take the first steps to study the vibrational properties of TiS3 through temperature-dependent Raman spectroscopy measurements of TiS3 nanoribbons and nanosheets. Our investigation shows that all the Raman modes linearly soften (red shift) as the temperature increases from 88 to 570 K due to anharmonic vibrations of the lattice, which also includes contributions from the lattice thermal expansion. This softening with the temperature of the TiS3 modes is more pronounced than that observed in other 2D semiconductors, such as MoS2, MoSe2, WSe2, and black phosphorus (BP). This marked temperature dependence of the Raman spectra could be exploited to determine the temperature of TiS3 nanodevices by using Raman spectroscopy as a noninvasive and local thermal probe. Interestingly, the TiS3 nanosheets show a stronger temperature dependence of the Raman modes than the nanoribbons, which we attribute to lower interlayer coupling in the nanosheets.


Depth acquisition in single-pixel imaging with multiplexed illumination.
Single-pixel imaging (SPI) has drawn wide attentions due to its high signal-to-noise ratio and wide working spectrum, providing a feasible solution when array sensors are expensive or not available. In the conventional SPI, the target's depth information is lost in the acquisition process due to the 3D-to-1D projection. In this work, we report an efficient depth acquisition method that enables the existing SPI systems to obtain reflectance and depth information without any additional hardware. The technique employs a multiplexed illumination strategy that contains both random and sinusoidal codes, which simultaneously encode the target's spatial and depth information into the single measurement sequence. In the reconstruction phase, we build a convolutional neural network to decode both spatial and depth information from the 1D measurements. Compared to the conventional scene acquisition method, the end-to-end deep-learning reconstruction reduces both sampling ratio (30%) and computational complexity (two orders of magnitude). Both simulations and experiments validate the method's effectiveness and high efficiency for additional depth acquisition in single-pixel imaging without additional hardware.


Targeting dental sealants in school-based programs: evaluation of an approach.
Several guidelines have been published in the United States to promote the appropriate use of sealants in both individual care and public health programs. Targeting sealants to children and teeth at high risk for dental caries has been accepted as a desirable strategy in school-based programs. However, there is little evidence to show that programs are complying with these guidelines. This report examined the extent to which sealants were targeted to high-risk children at 11 different school-based programs in New York State. Data on 3357 children ages seven to nine were analyzed. The percent of children receiving sealants ranged from 41% to 88%. While in two sites (St. Lawrence & Onondaga) fewer than 52% of the children received sealants; more than 73% received sealants in the remaining nine sites (P < 0.05). The results suggest that there was a wide variation in the implementation of the guidelines for sealant use. Some reasons for not adhering to the guidelines were: difficulty in assuring parents and local dentists that some children were not at risk for caries; lack of confidence in the risk-assessment method; uncertainty regarding what constitutes deep pits and fissures; fear of misclassifying children and requests by school administrators, parents and local dentists that all children should benefit from preventive measures.


Quantitative-profiling of neurotransmitter abnormalities in the disease progression of experimental diabetic encephalopathy rat.
Diabetic encephalopathy (DE) is one of the most prevalent chronic complications of diabetes mellitus (DM), with neither effective prevention nor proven therapeutic regimen. This study aims to uncover the potential dysregulation pattern of the neurotransmitters in a rat model of streptozotocin (STZ)-induced experimental DE. For that purpose, male Sprague-Dawley (SD) rats were treated with a single intraperitoneal injection of STZ. Cognitive performance was detected with the Morris water maze (MWM) test. Serum, cerebrospinal fluid (CSF), and brain tissues were collected to measure the levels of neurotransmitters. Compared with the control rats, the acetylcholine (ACh) levels in serum, CSF, hippocampus, and cortex were all significantly down-regulated as early as 6 weeks in the STZ treatment group. In contrast, the glutamate (Glu) levels were decreased in CSF and the hippocampus, but unaffected in the serum and cortex of STZ-treated rats. As for γ-aminobutyric acid (GABA), it was down-regulated in serum, but up-regulated in CSF, hippocampus, and the cortex in the STZ-treated group. The mRNA expressions of neurotransmitter-related rate limiting enzymes (including AChE, GAD1, and GAD2) and pro-inflammatory cytokines (including IL-1β and TNF-α) were all increased in the DE rats. Our data suggest that DM induces isoform-dependent and tissue-specific neurotransmitter abnormalities, and that neuroinflammation may underlay the nervous system dysfunction observed in the progression of DE.


Differences in Stability, Cytotoxicity, and Mechanism of Action of Ru(II) and Pt(II) Complexes of a Bidentate N,O Donor Ligand.
We report [RuII(L)(η6-p-cym)Cl] (1 and 2) and [PtII(L)(DMSO)Cl] (3 and 4) complexes, where L is a chelate imine ligand derived from chloroethylamine and salicylaldehyde (HL1) or o-vanillin (HL2). The complexes were characterized by single-crystal X-ray diffraction and other analytical techniques. The 1H nuclear magnetic resonance data show that both the Ru(II) and Pt(II) complexes start forming the aquated complex within an hour. The aquated complexes are stable at least up to 24 h. The complexes bind to the N7 of the model nucleobase 9-ethylguanine (9-EtG). Interaction with calf thymus (CT) DNA shows moderate binding interactions with binding constants, Kb (3.7 ± 1.2) × 103 M-1 and (4.3 ± 1.9) × 103 M-1 for 1 and 3, respectively. The complexes exhibit significant antiproliferative activity against human pancreas ductal adenocarcinoma (Mia PaCa-2), triple negative metastatic breast adenocarcinoma (MDA-MB-231), hepatocellular carcinoma (Hep G2), and colorectal adenocarcinoma (HT-29) cell lines. The studies show that with the same ligand the Pt(II) complexes are more potent than the Ru(II) complexes. The in vitro potencies of all the complexes toward pancreatic cancer cell line MIA PaCa-2 are more than cisplatin (CDDP). The Pt(II) and Ru(II) complexes show similar binding constants with CT-DNA, but the reactivity of the Pt(II) complex 3 with 9-EtG is faster and their overall cell killing pathways are different. This is evident from the arrest of the cell cycle by the Ru(II) complex 1 in the G2/M phase in contrast to the SubG1 phase arrest by the Pt(II) complex 3. The immunoblot study shows that 3 increases cyclin D and Bcl-2 expression in MDA-MB-231 due to the SubG1 phase arrest where these proteins express in greater quantities. However, both 1 and 3 kill in the apoptotic pathway via dose-dependent activation of caspase 3. Complex 3 depolarizes the mitochondria more efficiently than 1, suggesting its higher preference for the intrinsic pathway of apoptosis. Our work reveals that the same bidentate ligand with a change of the metal center, viz, Pt(II) or Ru(II), imparts significant variation in cytotoxic dosage and pathway of action due to specific intrinsic properties of a metal center (viz, coordination geometry, solution stability) manifested in a complex.


Ca2+ Dynamics of Gap Junction Coupled and Uncoupled Deiters' Cells in the Organ of Corti in Hearing BALB/c Mice.
ATP, as a paracrine signalling molecule, induces intracellular Ca2+ elevation via the activation of purinergic receptors on the surface of glia-like cochlear supporting cells. These cells, including the Deiters' cells (DCs), are also coupled by gap junctions that allow the propagation of intercellular Ca2+ waves via diffusion of Ca2+ mobilising second messenger IP3 between neighbouring cells. We have compared the ATP-evoked Ca2+ transients and the effect of two different gap junction (GJ) blockers (octanol and carbenoxolone, CBX) on the Ca2+ transients in DCs located in the apical and middle turns of the hemicochlea preparation of BALB/c mice (P14-19). Octanol had no effect on Ca2+ signalling, while CBX inhibited the ATP response, more prominently in the middle turn. Based on astrocyte models and using our experimental results, we successfully simulated the Ca2+ dynamics in DCs in different cochlear regions. The mathematical model reliably described the Ca2+ transients in the DCs and suggested that the tonotopical differences could originate from differences in purinoceptor and Ca2+ pump expressions and in IP3-Ca2+ release mechanisms. The cochlear turn-dependent effect of CBX might be the result of the differing connexin isoform composition of GJs along the tonotopic axis. The contribution of IP3-mediated Ca2+ signalling inhibition by CBX cannot be excluded.


Association of Mycoplasma pneumoniae infection with increased risk of asthma in children.
The present study was conducted to investigate the relationship between Mycoplasma pneumoniae (MP) infection and the risk of asthma among children by detecting the rate of MP immunoglobulin M (MP-IgM) and the eosinophil (EOS) count. A total of 139 asthmatic children were enrolled as the case group and assigned into three groups: Group A (aged <3 years, n=42), group B (aged 3-8 years, n=45) and group C (aged >8 years, n=52). Additionally, 115 healthy children were enrolled in the control group. Enzyme-linked immunosorbent assay was used to measure the MP-IgM-positive rate. EOS count was detected in the experimental and control groups by using a hemocytometer analyzer. A meta-analysis was performed by using the Comprehensive Meta-Analysis version 2.0 software. The positive rates of the MP-IgM and EOS count in the experimental group were significantly higher than those in control group (both P<0.001). Furthermore, the asthmatic children in group C had a higher MP-IgM-positive rate and EOS count as compared to those in groups A and B, respectively (all P<0.05). Results from groups A and B were not statistically significant (all P>0.05). The meta-analysis further confirmed that asthmatic children had a higher MP-IgM-positive rate as compared to the healthy controls (P<0.001). Age-stratified analysis revealed that the MP-IgM-positive rate in asthmatic children aged ≥8 and <8 years was significantly higher than that in the healthy controls (P=0.003 and P<0.001). Asthmatic children had a higher MP-IgM-positive rate and EOS count as compared with controls, suggesting that the MP infection may be closely associated with the risk of asthma. Additionally, the positive rate of MP-IgM may indicate an important biological marker in predicting the development of asthma.


Fetal scapular length in the ultrasonographic assessment of gestational age.
A prospective cross-sectional study of 515 singleton fetuses of ages between 15 and 42 weeks' gestation was performed. At gestational ages greater than 26 weeks, only fetuses with a sonographic estimated fetal weight between the 10th and 90th percentiles for growth were included. Scapular length (cm) as a function of gestational age (weeks) was expressed by the regression equation: SL = 0.3289 + 0.9553 (GA) with a Pearson correlation coefficient of R2 = 0.942. This study defines the normal limits of scapular length, demonstrates a high correlation between scapular length, gestational age, and other standard measurements of fetal growth, and indicates that scapular length can predict gestational age in fetuses with normal growth.


Tissue factor expression by myeloid cells contributes to protective immune response against Mycobacterium tuberculosis infection.
Tissue factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium tuberculosis (M. tb) infection by using mice lacking the TF gene in myeloid cells (TF(Δ) ) and human monocyte derived macrophages (MDMs). We found that during M. tb infection, a deficiency of TF in myeloid cells was associated with reduced inducible nitric oxide synthase (iNOS) expression, enhanced arginase 1 (Arg1) expression, enhanced IL-10 production and reduced apoptosis in infected macrophages, which augmented M. tb growth. Our results demonstrate that a deficiency of TF in myeloid cells promotes M2-like phenotype in M .tb infected macrophages. A deficiency in TF expression by myeloid cells was also associated with reduced fibrin deposition and increased matrix metalloproteases (MMP)-2 and MMP-9 mediated inflammation in M. tb infected lungs. Our studies demonstrate that TF expressed by myeloid cells has newly recognized abilities to polarize macrophages and to regulate M. tb growth.


Retrospective age-of-onset and projected lifetime prevalence of psychiatric disorders among U.S. Army National Guard soldiers.
The study of military-related mental health has been disproportionately focused on current symptomology rather than potentially more informative life course mental health. Indeed, no study has assessed age-of-onset and projected lifetime prevalence of disorders among reservists. Age-of-onset and projected lifetime DSM-IV anxiety, mood, and substance use disorders were assessed in 671 Ohio Army National Guard soldiers aged 17-60 years. Between 2008 and 2012, face-to-face clinical assessments and surveys were conducted using the Structured Clinical Interview for DSM-IV and Clinician-Administered PTSD Scale. Lifetime prevalence of psychiatric disorders was 61%. Alcohol abuse/dependence (44%) and major depressive disorder (23%) were the most common disorders. The majority (64%) of participants reported disorders antedating enlistment. Median age-of-onset varied with anxiety disorders - particularly phobias and OCD - having the earliest (median=15 years) and mood disorders the latest median age-of-onset (median=21 years). The study was limited by both the retrospective investigation of age-of-onset and the location of our sample. As our sample may not represent the general military population, our findings need to be confirmed in additional samples. Each psychiatric disorder exhibited a distinct age-of-onset pattern, such that phobias and OCD onset earliest, substance use disorders onset during a short interval from late-adolescence to early-adulthood, and mood disorders onset the latest. Our finding that the majority of participants reported disorders antedating enlistment suggests that an assessment of lifetime psychopathology is essential to understanding the mental health burden of both current and former military personnel.


Therapeutic effect of parenteral magnesium on noise-induced hearing loss in the guinea pig.
We have recently demonstrated in the guinea pig that preventive dietary magnesium supplement can significantly reduce impulse noise induced hearing loss by on average 18 dB. The purpose of the present study was to examine whether magnesium might also have a therapeutic effect on noise trauma. Anesthetized guinea pigs were exposed to an impulse noise series (1/s) of L(peak) 167 dB (L(eq,ls) 127 dB) for 38 min. The permanent hearing threshold shift (PTS) was determined one week post-exposure, using auditory brainstem response audiometry at a frequency range of 0.5-32 kHz. The total magnesium concentrations of perilymph (PL), cerebrospinal fluid and blood were analysed by atomic absorption spectrometry at different times of treatment. In a first set of experiments, animals on a low initial magnesium status were injected either of 4 different dose levels of magnesium (1.14-3.42 mmol MgSO4 s.c./kg per day) for 3 days or saline as a placebo. The treatment was started immediately after the exposure. The magnesium groups received drinking water with an additive of 39 mmol MgCl2/l for one week and the placebo group tap water (0.43 mmol Mg/l) alone. A dose level of 2.85 mmol Mg has proved to be most effective and reduced the PTS by 13-20 dB compared to the placebo group. The magnesium concentrations increased to above 4 mmol/l in serum and to 1.2 mmol/l in PL during the first 3 days of this treatment. In a second set of experiments, we tested the dependence of the therapeutic efficacy on the post-exposure time of onset of the optimal treatment (1 min, 2 h and 4 h), using guinea pigs on normal initial magnesium status. In the 1 min-group, the reduction of hearing loss was similar to that found in the first series. The therapeutic effect decreases with the length of time elapsed between the end of exposure and the beginning of treatment. In a few animals, hair cell stereocilia were examined using scanning electron microscopy. The results also revealed a magnesium related reduced susceptibility of hair cell stereocilia to impulse noise exposure.


The optimal exercise intensity for the unbiased comparison of thermoregulatory responses between groups unmatched for body size during uncompensable heat stress.
We sought to identify the appropriate exercise intensity for unbiased comparisons of changes in rectal temperature (ΔTre) and local sweat rates (LSR) between groups unmatched for body size during uncompensable heat stress. Sixteen males vastly different in body morphology were separated into two equal groups [small (SM): 65.8 ± 6.2 kg, 1.8 ± 0.1 m2; large (LG): 100.0 ± 13.1 kg, 2.3 ± 0.1 m2], but matched for sudomotor thermosensitivity (SM: 1.3 ± 0.6; LG: 1.1 ± 0.4 mg·cm-2·min-1·°C-1). The maximum potential for evaporation (Emax) for each participant was assessed using an incremental humidity protocol. On separate occasions, participants then completed 60 min of cycling in a 35°C and 70% RH environment at (1) 50% of VO2max, (2) a heat production (Hprod) of 520 W, (3) Hprod relative to mass (6 W·kg-1), and (4) Hprod relative to mass above Emax (3 W·kg-1>Emax). Emax was similar between LG (347 ± 39 W, 154 ± 15 W·m-2) and SM (313 ± 63 W, 176 ± 34 W·m-2, P > 0.12). ΔTre was greater in SM compared to LG at 520 W (SM: 1.5 ± 0.5; LG 0.8 ± 0.3°C, P < 0.001) and at 50% of VO2max (SM: 1.4 ± 0.5; LG 0.9 ± 0.3°C, P < 0.001). However, ΔTre was similar between groups when Hprod was either 6 W·kg-1 (SM: 0.9 ± 0.3; LG 0.9 ± 0.2°C, P = 0.98) and 3 W·kg-1>Emax (SM: 1.4 ± 0.5; LG 1.3 ± 0.4°C, P = 0.99). LSR was similar between LG and SM irrespective of condition, suggesting maximum LSR was attained (SM: 1.10 ± 0.23; LG: 1.07 ± 0.35 mg·cm-2·min-1, P = 0.50). In conclusion, systematic differences in ΔTre and LSR between groups unmatched for body size during uncompensable heat stress can be avoided by a fixed Hprod in W·kg-1 or W·kg-1>Emax.


Checking for voice disorders without clinical intervention: The Greek and global VHI thresholds for voice disordered patients.
Voice disorders often remain undiagnosed. Many self-perceived questionnaires exist for various medical conditions. Here, we used the Greek Voice Handicap Index (VHI) to address the aforementioned problem. Everyone can fill in the VHI questionnaire and rate their symptoms easily. The innovative feature of this research is the global cut-off score calculated for the VHI. Therefore, the VHI is now capable of helping clinicians establish a more customizable treatment plan with the cut-off point identifying patients without normal phonation. For the purpose of finding the global cut-off point, a group of 180 participants was recruited in Greece (90 non-dysphonic participants and 90 with different types of dysphonia). The voice disordered group had higher VHI scores than those of the control group. In contrast to previous studies, we provided and validated for the first time the cut-off points for all VHI domains and, finally, a global cut-off point through ROC and precision-recall analysis in a voice disordered population. In practice, a score higher than the well-estimated global score indicates (without intervention) a possible voice disorder. Nevertheless, if the score is near the threshold, then the patient should definitely follow preventive measures.


Humoral immune system and ulcerative colitis activity. III. Immune complexes.
Serum immune complexes (IMC) were examined by means of 4.166% polyethylene glycol precipitation. IMC were found in 33.3% of all examined patients (12.8% of inactive and 51.1% of active colitis). Polyethylene glycol serum precipitation was correlated with the activity of the disease, and was found to be increased in patients with extensive morbid process and with duration of the disease. In the patients with extraintestinal manifestations IMC increased particularly in those with skin lesions. Our study confirmed suggestion of other authors on the possible role of the pathogenesis of UC and in extraintestinal complications. Their secondary role however, cannot be excluded.


The Eurasian Elk's (Alces alces) Brain Base Arteries in View of Vascular Variation.
This article presents the results of analysis of the arterial vascular region of the Eurasian elk, which is a representative of the Cervidae family. The study was conducted on 39 Eurasian elks. The head arteries of 25 animals were filled with LBS 3040 synthetic latex. The head arteries of the other 14 Eurasian elks were filled with an acetone solution of stained chlorinated polyvinyl chloride and macerated. The arterial circle of the Eurasian elk's brain is composed of bilateral rostral cerebral arteries and caudal communicating arteries. The basilar artery closes the arterial circle caudally. The rostral cerebral artery first ramifies into the rostral choroidal artery, then, the middle cerebral artery and the rostral communicating artery. The caudal cerebral artery and the rostral cerebellar artery branch off the caudal communicating artery. The arterial pattern of the Eurasian elk's brain base is similar to the arteries found in other deer. Like in other Ruminantia, the rostral epidural rete mirabile is a unique structure in the Eurasian elk's arterial system. Anat Rec, 302:339-345, 2019. © 2018 Wiley Periodicals, Inc.


Rare case of single coronary artery in a patient with liver cirrhosis.
We report here the case of a 58-year-old male presented with atypical chest pain, dyspnea and fatigue, with a medical history of liver cirrhosis and undergoing treatment with beta-blocker. The clinical exam was normal. The 12-lead electrocardiogram (ECG) showed normal heart rate, without repolarization changes. Transthoracic echocardiography revealed no wall motion abnormalities of the left ventricle, moderate tricuspid regurgitation with mild pulmonary hypertension and left ventricular hypertrophy. The biochemical markers for myocardial infarction were negative. He underwent coronary angiography that revealed a single coronary artery originating from the right coronary sinus of Valsalva.


Marital Status and Sex-Based Differences in Outcomes After Transcatheter Aortic Valve Implantation.
Studies have shown improved outcomes among married patients who underwent cardiovascular surgery; however, this has not been well studied in transcatheter aortic valve implantation (TAVi). We examined the impact of marital status and patient sex on outcomes after TAVi. Patients who underwent TAVi from January 2015 to June 2018 were reviewed and stratified into 3 groups: single, married, and widowed. The impact of marital status and sex on 30-day outcomes was assessed using a stepwise logistic regression analysis. Cumulative survival was estimated using Kaplan-Meier analysis and adjusted survival with multivariable Cox proportional hazards modeling. A total of 785 patients were included: 149 single, 413 married, and 223 widowed. Widowed patients were older (84 vs 79 years) with higher Society of Thoracic Surgeons risk scores (6.79% vs 5.51%, both p ≤0.001) than married patients. Neither marital status nor sex was associated with 30-day mortality or home discharge. However, 1-year survival revealed a differential survival penalty, with married females (p = 0.041) having lower survival and married males (p = 0.007) having higher survival than their single counterparts. This survival penalty persisted in the adjusted analyses (married females hazard ratio [HR] 2.24, p = 0.009; widowed males HR 2.42, p = 0.057). For patients who were readmitted in the first year, adjusted analysis showed widowed status was associated with higher 30-day readmissions (HR 1.91, p = 0.012) in both sexes. In conclusion, these findings suggest that marital status does not impact both sexes equally after TAVi; identifying at-risk patients and targeted interventions, such as adjusting discharge planning to ensure adequate home social support, may help improve outcomes.


Clinical phenotype and the lack of mutations in the CHRNG, CHRND, and CHRNA1 genes in two Indian families with Escobar syndrome.
The objective of this study was to report the clinical phenotype and genetic analysis of two Indian families with Escobar syndrome (ES). The diagnosis of ES in both families was made on the basis of published clinical features. Blood samples were collected from members of both families and used in genomic DNA isolation. The entire coding regions and intron-exon junctions of the ES gene CHRNG (cholinergic receptor, nicotinic, gamma), and two other related genes, CHRND and CHRNA1, were amplified and sequenced to search for mutations in both families. Both families show a typical form of ES. Sequencing of the entire coding regions including the intron-exon junctions of the three genes did not yield any mutations in these families. In conclusion, it is possible that the mutations in these genes are located in the promoter or deep intronic regions that we failed to identify or the ES in these families is caused by mutations in a different gene. The lack of mutations in CHRNG has also been reported in several families, suggesting the possibility of at least one more gene for this syndrome.


α-Acetoxyarone synthesis via iodine-catalyzed and tert-butyl hydroperoxide-mediateded self-intermolecular oxidative coupling of aryl ketones.
We present a metal-free method for α-acetoxyarone synthesis by self-intermolecular oxidative coupling of aryl ketones using I2-tert-butyl hydroperoxide (TBHP). Under the optimum conditions, various aryl ketones gave the corresponding products in moderate to excellent yields. A series of control experiments were performed; the results suggest the involvement of radical pathways. Multiple radical intermediates were generated in situ and the overall process involved several different reactions, which proceeded self-sequentially in a single reactor. A labeling experiment using 18O-labeled H2O confirmed that the oxygen in the product was derived from TBHP, not from H2O in the TBHP solvent.


Effect of Sacroiliac Joint Mobilization on the Level of Soft Tissue Pain Threshold in Asymptomatic Women.
This study aimed to evaluate the effect of sacroiliac joint (SIJ) mobilization and/or self-mobilization on the level of soft tissue pain threshold in 21- to 23-year-old asymptomatic women (n = 20). The FPIX Wagner Algometer was applied to compute the pressure pain threshold (PPT) over the right and left side of the iliolumbar ligament and lumbar erector spinae (L3). Measurements were taken of the right SIJ before and after a randomized protocol of oscillating mobilization, self-mobilization, and placebo treatment. A main effect of intervention (mobilization, self-mobilization, placebo) was confirmed by analysis of variance, with increases in PPT over the iliolumbar ligament (F = 13.04, P < .05) and erector spinae (F = 12.28, P < .05) on the mobilized side. The Wilcoxon test indicated that SIJ mobilization increased PPT over the iliolumbar ligament (P < .05) and erector spinae (P < .05) on both sides. Self-mobilization increased erector spinae PPT on the exercised side (P < .05), whereas the placebo did not cause any changes in PPT (P > .05). The study provides evidence of local and global pain modulation resulting from oscillatory mobilization of the SIJ in women without pain symptoms. Self-mobilization of the SIJ has limited analgesic application.


Integrated research into the nanoparticle-protein corona: a new focus for safe, sustainable and equitable development of nanomedicines.
Much contemporary nanotoxicology, nanotherapeutic and nanoregulatory research has been characterized by a focus on investigating how delivery of engineered nanoparticles (ENPs) to cells is dictated primarily by components of the ENP surface. An alternative model, some implications of which are discussed here, begins with fundamental physicochemical research into the interaction of a dynamic nanoparticle-protein corona (NPC) with biological systems. The proposed new model also requires, however, that any such fresh NPC physicochemical research approach should involve integration and targeted collaboration from the earliest stages with nanotoxicology, nanotherapeutics and nanoregulatory expertise. The justification for this integrated approach, we argue, relates not just to efficiency and promotion of innovation but to an acknowledgement that public-funded basic physicochemical research in particular should now be accepted to incorporate strong higher order public-goods elements from its inception, not merely after product development at the technology-transfer stage. Issues, such as university-research cooperation, commercialization and intellectual property protection, safety and cost-effectiveness regulatory assessment, as well as technology transfer should not be viewed as second tier considerations, even in a 'blue sky' NPC basic research agenda.


3.0 T prostate MRI: Visual assessment of 2D and 3D T2-weighted imaging sequences using PI-QUAL score.
Comparing 2D and 3D T2 weighted sequences in terms of image quality in 3.0 T MRI with readers of varied experiences, using PI-QUAL inspired criteria. 91 male patients with suspected prostate cancer (PCa) underwent diagnostic prostate MRI on a 3.0 T MR system using a 32-channel phased-array torso coil before prostate biopsy. MRI protocol included 3D T2w images, axial 2D T2w images, axial diffusion-weighted images (DWI) with the corresponding ADC apparent diffusion coefficient maps, and axial dynamic contrast enhanced images. 3D T2w and 2D T2w imaging were compared by 4 radiologists using a Likert scale for image quality (overall anatomy, delineation of capsule, seminal vesicles, ejaculatory ducts, sphincter muscle, artifacts), tumor delimitation and conspicuity. No significant differences in terms of overall quality between 3D and 2D T2w images were found. However 2D T2w demonstrated higher rating than 3D T2w images as for the image quality of the external capsule, sphincter muscle and ejaculatory ducts delineation (p < 0.05). 3D T2w sequence can't replace 2D T2w sequence, despite good quality images but it remains more prone to artifacts. Quality of 2D T2w sequences was substantially superior to 3D sequences for delineation of key structures as external capsule, sphincter muscle. The use of PI-QUAL criteria allows reproducible analysis of the quality of T2 weighted images.


Quantitative interstitial lung disease scores in idiopathic inflammatory myopathies: longitudinal changes and clinical implications.
To investigate computer-aided quantitative scores from high-resolution CT (HRCT) images and determine their longitudinal changes and clinical significance in patients with idiopathic inflammatory myopathies (IIMs)-related interstitial lung disease (IIMs-ILD). The clinical data and HRCT images of 80 patients with IIMs who underwent serial HRCT scans at least twice were retrospectively analysed. Quantitative ILD (QILD) scores (%) were calculated as the sum of the extent of lung fibrosis, ground-glass opacity, and honeycombing. The individual time-estimated ΔQILD between two consecutive scans was derived using a linear approximation of yearly changes. The baseline median QILD (interquartile range) scores in the whole lung were 28.1% (19.1-43.8). The QILD was significantly correlated with forced vital capacity (r = -0.349, P = 0.002) and diffusing capacity for carbon monoxide (r = -0.381, P = 0.001). For ΔQILD between the first two scans, according to the visual ILD subtype, QILD aggravation was more frequent in patients with usual interstitial pneumonia (UIP) than non-UIP (80.0% vs 44.4%, P = 0.013). Multivariable logistic regression analyses identified UIP was significantly related to radiographic ILD progression (ΔQILD >2%, P = 0.015). Patients with higher baseline QILD scores (>28.1%) had a higher risk of lung transplantation or death (P = 0.015). In the analysis of three serial HRCT scans (n = 41), dynamic ΔQILD with four distinct patterns (improving, worsening, convex and concave) was observed. QILD changes in IIMs-ILD were dynamic, and baseline UIP patterns seemed to be related to a longitudinal progression in QILD. These may be potential imaging biomarkers for lung function, changes in ILD severity and prognosis in IIMs-ILD.


Detection of telomerase activity in biopsy samples of colorectal cancer.
Telomerase is a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends. The expression of telomerase is thought to be required for cellular immortality and oncogenesis. To investigate the role of telomerase in the pathogenesis of colorectal cancer, we analysed telomerase activity in biopsy samples of colorectal cancer and colonic adenomas. Using a polymerase chain reaction-based assay, we examined telomerase activity in 52 samples of colorectal cancer, 12 colonic adenomas and 30 normal colonic mucosa samples obtained by endoscopic biopsy. Telomerase activity was detectable in 88.5% (46/52) of colorectal carcinomas, in 50% (6/12) of colonic adenomas but not in normal colorectal mucosa. There was no correlation between telomerase activity and tumour location, type, size and differentiation (P > 0.05). It was concluded that telomerase activation plays a role in the evolution of colorectal cancer, and that measurement of telomerase activity in biopsied colorectal mucosa samples may provide information both as a diagnostic marker to detect small numbers of cancer cells, and as a screening method for patients at high risk for colorectal carcinoma.


The image quality and diagnostic performance of CT perfusion-derived CT angiography versus that of conventional CT angiography.
The combination of computed tomography angiography (CTA) and computed tomography perfusion (CTP) evaluation of cerebral perfusion status and vascular conditions can improve the diagnostic accuracy of infarction, ischemia, and vascular occlusion in stroke patients, as well as a comprehensive assessment of cerebral edema, collateral circulation, and blood perfusion in the lesion area. However, the consequent radiation safety and contrast agent nephropathy have aroused increasing concern. The purpose of this study was to assess the image quality and diagnostic accuracy of CTA images derived from CTP data, and to explore the feasibility of replacing conventional CTA. A total of 31 consecutive patients with suspected acute ischemic stroke were retrospectively analyzed. All patients underwent head and neck CTA and brain CTP examinations. All the CTP images were transmitted to the ShuKun artificial intelligence system, which reconstructs CTA derived from CTP (CTA-DF-CTP). The images were divided into 2 groups, including CTA-DF-CTP (Group A) and conventional CTA (Group B). The CT attenuation values, subjective image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), image quality, CT volume dose index (CTDIvol), dose length product (DLP), and effective radiation dose (ED) were compared between the 2 groups. Moreover, the consistency of vascular stenosis and stenosis degree between the 2 groups were measured and evaluated. There were no significant differences in image noise, SNR, or CNR between Groups A and B (P>0.05). The CT attenuation values of the arteries were higher in Group A than in B [internal carotid artery (ICA) =548±112 vs. 454±85 Hounsfield units (HU), middle cerebral artery (MCA) =453±118 vs. 388±70 HU, and basilar artery (BA) =431±99 vs. 360±83 HU] (P<0.01). The image quality of the 2 groups met the requirement of clinical diagnosis (4.97±0.18 vs. 4.94±0.25). No significant difference was found in subjective evaluation (P>0.05). In Group A compared with Group B, the following reductions were observed: CTDIvol (10.7%; 100.8 vs. 112.9 mGy), DLP (23.0%; 1,613±0 vs. 2,093±88 mGy·cm), and ED (23.0%; 5.00±0.00 vs. 6.49±0.27 mSv). CTA-DF-CTP data provide diagnostic accuracy and image quality similar to those of conventional CTA of head and neck CTA.


Genetic alterations of differentiated thyroid carcinoma in iodine-rich and iodine-deficient countries.
BRAF V600E mutation, RET rearrangements, and RAS mutations are the common genetic alterations in differentiated thyroid carcinomas derived from follicular thyroid cells. However, the relationship between these alterations and iodine intake is still controversial. To clarify the influence of iodine intake on the occurrence of differentiated thyroid carcinomas, we performed molecular analyses for two differentiated carcinomas, papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs), from an iodine-rich country (Japan) and an iodine-deficient country (Vietnam). We examined 120 PTCs (67 Japanese and 53 Vietnamese) and 74 FTCs (51 Japanese and 23 Vietnamese). We carried out allele-specific polymerase chain reaction (AS-PCR) for BRAF V600E, PCR and direct sequencing for RAS mutations (codon 12, 13, and 61 in NRAS, HRAS, and KRAS), and RT-PCR for RET/PTC1 and RET/PTC3. BRAF V600E was present in 55/67 (82.1%) Japanese PTCs and 44/53 (83%) Vietnamese PTCs. RET/PTC1 was identified in only one PTC from each country, and no samples had RET/PTC3. NRAS mutation was found in 17/51 (33.3%) Japanese FTCs and 4/23 (17.4%) Vietnamese FTCs. NRAS mutation was cited in codon 61 (20 cases) and codon 12 (one case). None of FTCs had KRAS or HRAS mutations. There were no significant differences in the prevalence of BRAF V600E, RET/PTC, or RAS mutations between the two countries. Our study showed no differences in genetic alterations of thyroid cancers from iodine-rich and iodine-deficient countries, possibly suggesting that iodine intake might not affect the genetic alterations of differentiated thyroid cancer.


Our experience with Solcoseryl Eye-Gel in the treatment of corneal lesions. A randomised double-blind study (with 1 color plate).
A comparative study of Solcoseryl Eye-Gel versus a 2.4% cysteine eye-gel was carried out under controlled conditions (randomised and double-blind) on a total of 61 patients with corneal lesions (52 foreign body injuries, 9 corneal erosions). The results showed a marked superiority of Solcoseryl Eye-Gel with respect to more rapid healing and also with respect to the possible subsequent development of a corneal macula.


Long-term impact of positive surgical margins on biochemical recurrence after radical prostatectomy: ten years of follow-up.
Positive surgical margins (PSMs) in men undergoing radical prostatectomy (RP) for prostate cancer are associated with an increased risk of biochemical recurrence. This study evaluated the long-term (>10 year) impact of PSMs on biochemical recurrence after RP in adjuvant treatment-naïve pT2-pT4 N0 men and determined predictors of prostate-specific antigen (PSA) failure. The institutional registry of 1276 patients who underwent RP at Henri Mondor Hospital from 1988 to 2001 was reviewed, identifying 403 patients with regular follow-up at the time of analysis. The study included 108 patients with PSMs who did not receive neoadjuvant or adjuvant therapy before PSA relapse. Median follow-up was 12.2 years. PSA failure was defined by a PSA rising by more than 0.2 ng/ml and biochemical recurrence-free survival (RFS) was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to analyse clinicopathological variables associated with biochemical recurrence. Biochemical recurrence 10 years after RP was 33.5% for patients regardless of the margin status. The 10-year biochemical RFS was 73% in men with negative margins compared to 49% in the case of PSM (p < 0.001). In multivariate analysis, margin status was a significantly predictive for PSA failure (hazard ratio 1.46, p = 0.04). After stratification by pathological stage, margin status was significantly predictive for biochemical RFS in pT2 (p < 0.001) and pT3a (p < 0.001), whereas the impact of PSM did not reach significance in pT3b (p = 0.16). After 10-year follow-up, PSMs remain an independent risk factor of biochemical RFS after RP with less relevant impact in pT3b disease. Randomized prospective trials are needed to determine the place of adjuvant versus delayed radiotherapy.


Bone marrow-derived cells response in proximal regions of nerves after peripheral nerve injury.
In recent years, bone marrow-derived cells have been found to be crucial for peripheral nerve regeneration. After traumatic peripheral nerve injury, bone marrow-derived macrophages quickly infiltrate into the distal regions of nerves. To explore the changes caused by bone marrow-derived cells within the proximal regions of the nerves, sciatic nerves of chimeric mice carrying bone marrow cells expressing green fluorescent protein were crushed to observe the infiltration of invading bone marrow-derived cells. Seven days after surgery, abundant bone marrow-derived cells had infiltrated into the damaged proximal nerve segments. The numbers of these cells increased to a peak at 2 weeks and then gradually returned to normal levels within 30 weeks. Through immunofluorescence staining, many of these cells were identified as macrophages, and they showed a similar infiltration tendency toward distal nerve segments. However, fewer cells infiltrated proximal segments than distal nerve segments. In conclusion, these findings suggest that bone marrow-derived cells response not only occurs within the distal nerve segments but may also take place within the proximal segments of nerve tissues after nerve injury.


Bioequivalence of two tablet formulations of helicidum adminstered in single dose to healthy Chinese volunteers.
In this 2 x 2, randomized, crossover bioequivalence study, two tablet preparations of helicidum were compared in 20 healthy Chinese male subjects. The drug was given in a single dose of three tablets (75 mg) and blood samples were withdrawn during 12 h after drug administration. Helicidum was separated and analyzed using a validated liquid chromatography-mass spectrum method. The pharmacokinetic parameters were determined from the plasma concentration-time profiles of both formulations. The primary calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the two preparations, using various statistical methods. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals fell within the acceptable range (80-120%) for bioequivalence. Based on these statistical inferences it can be concluded that the two tablet preparations of helicidum are likely to be bioequivalent.


The corporate compromise: a Marxist view of health maintenance organizations and prospective payment.
Recent developments in health care are strikingly congruent with a Marxist paradigm. For many years small scale owner producers (physicians) dominated medicine, and the corporate class supported the expansion of services. As health care expanded, corporate involvement in the direct provision of services emerged. This involvement is reflected not only in the rise of for-profit providers, but also in the influence of hospital administrators, utilization review organizations, insurance bureaucrats, and other functionaries unfamiliar with the clinical encounter, but well versed on the bottom line. Corporate providers' quest for increasing revenues has brought them into conflict with corporate purchasers of care, whose employee benefit costs have skyrocketed. This intercorporate conflict powerfully shapes health policy and has caused the rapid proliferation of health maintenance organizations and other forms of prospective payment. Corporate purchasers of care favor the incentives under prospective payment for providers to curtail care and its costs. For corporate providers, prospective payment has allowed increased profits even in the face of constrained revenues, because reimbursement is disconnected from resource use. Unfortunately, this corporate compromise serves patients and physicians poorly. Alternative policy options that challenge corporate interests could save money while improving care.


Immunohistological localization of endogenous unlabeled stem cells in wounded skin.
Various types of endogenous stem cells (SCs) participate in wound healing in the skin at different anatomical locations. SCs need to be identified through multiple markers, and this is usually performed using flow cytometry. However, immunohistological identification of endogenous stem cells in the skin at different anatomical locations by co-staining multiple SC markers has been seldom explored. We examined the immunohistological localization of four major types of SCs in wounded skin by co-staining for their multiple markers. Hematopoietic SCs were co-stained for Sca1 and CD45; mesenchymal SCs for Sca1, CD29, and CD106; adipose SCs for CD34, CD90, and CD105; and endothelial progenitor cells and their differentiated counterparts were co-stained for CD34, Tie2, and von Willebrand factor. We found Sca1(+)CD45(+) SCs in the epidermis, dermis and hypodermis of wounded skin. Sca1(+)CD29(+) and Sca1(+)CD106(+) mesenchymal SCs, CD34(+)CD105(+), CD34(+)CD90(+), and CD90(+)CD105(+) adipose SCs, as well as CD34(+)Tie2(+) endothelial progenitor cells were also located in the epidermis, dermis, and hypodermis. This study demonstrates the feasibility of using immunohistological staining to determine the location of SCs in wounded skin and the intracellular distribution of their molecular markers.


Metabolic syndrome as a risk factor for high intraocular pressure: the Korea National Health and Nutrition Examination Survey 2008-2010.
High intraocular pressure (IOP) is well established as the most significant risk factor for both the development and progression of primary open-angle glaucoma. Elevated IOP is more frequently seen in the presence of metabolic disturbances that are associated with the components of metabolic syndrome (MetS). The aim of this study was to investigate the association between ocular hypertension and MetS. We examined the relationship between ocular hypertension and MetS in 17,160 Korean adults without glaucoma aged >19 years (7,368 men and 9,792 women) who participated in the 2008-2010 Korea National Health and Nutrition Examination Survey. Multivariate logistic regression analysis was used to assess the relationship between MetS and ocular hypertension, after adjusting for age, body mass index, smoking, alcohol consumption, and regular exercise. The prevalence of MetS was 35.1% among males and 30.1% among females. The prevalence of ocular hypertension was 1.3% among males with MetS and 0.7% among females with MetS. Participants with MetS had a significantly higher IOP than those without MetS (P≤0.001), and each component of MetS had a different effect on the IOP. Hypertension was the strongest predictor of an elevated IOP. In multivariate regression analysis, ocular hypertension was significantly associated with MetS (P=0.027 for men; P=0.015 for women). There is a statistically significant relationship between MetS and ocular hypertension.


PAHs, PAH-induced carcinogenic potency, and particle-extract-Induced cytotoxicity of traffic-related nano/ultrafine particles.
Polycyclic aromatic hydrocarbons (PAHs) bound in nano/ ultrafine particles from vehicle emissions may cause adverse health effects. However, little is known about the characteristics of the nanoparticle-bound PAHs and the PAH-associated carcinogenic potency/cytotoxicity; therefore, traffic-related nano/ultrafine particles were collected in this study using a microorifice uniform deposition impactor(MOUDI) and a nano-MOUDI. For PM0.056--18, the difference in size-distribution of particulate total-PAHs between non-after-rain and after-rain samples was statistically significant at alpha = 0.05; however, this difference was not significant for PM0.01--0.056. The PAH correlation between PM0.01--0.1 and PM0.1--1.8 was lower for the after-rain samples than forthe non-after-rain samples. The average particulate total-PAHs in five samplings displayed a trimodal distribution with a major peak in the Aitken mode (0.032--0.056 microm). About half of the particulate total-PAHs were in the ultrafine size range. The BaPeq sums of BaP, IND, and DBA (with toxic equivalence factors > or = 0.1) accounted for approximately 90% of the total-BaPeq in the nano/ultrafine particles, although these three compounds contributed little to the mass of the sampled particles. The mean content of the particle-bound total-PAHs/-BaPeqs and the PAH/BaPeq-derived carcinogenic potency followed the order nano > ultrafine > fine > coarse. For a sunny day sample, the cytotoxicity of particle extracts (using 1:1 (v/v) n-hexane/dichloromethane) was significantly higher (p < 0.05) for the nano (particularly the 10-18 nm)/ultrafine particles than for the coarser particles and bleomycin. Therefore, traffic-related nano and ultrafine particles are possibly cytotoxic.


Creating a Lactation-Friendly Learning Environment for Medical Students and Residents: A Northern Canadian Perspective.
Background: Lactation is a normal postpartum physiological process that can continue in excess of 3 years and is often the sole nutritional source for infants in the first 6 months of life. Breastfeeding not only provides infant nutrition, but also facilitates maternal-infantile bonding. Lactating mothers separated from their children face multiple challenges in finding and accessing appropriate spaces and time for milk expression. Maternal employment is a great barrier to breastfeeding and accordingly has led to multiple advancements in the area of breastfeeding policy. One example of a policy is the Baby-Friendly Initiative. This initiative focused on breastfeeding promotion, support, and protection. However, the impact of such campaigns on lactating medical students and residents is thought to be low. Furthermore, breastfeeding rates differ vastly according to geographic locations in North America. Trends indicate decreased rates of breastfeeding in northern rural areas in comparison with southern urban counterparts. This highlights the need for increased protection, support, and creation of safe-lactation spaces for all working mothers including medical students and residents, and especially those in rural areas. Goals: To review challenges of breastfeeding as a medical trainee and delineate the creation of a lactation policy for medical learners and residents. Methodology: We conducted a literature review of breastfeeding policy and experiences of breastfeeding while in the learning environment. Results: Challenges of breastfeeding in medical school and residency include the complex, high-paced medical working environment where taking breaks or time off is often difficult. Few medical schools across North America have any breastfeeding policy. Conclusion: The Northern Ontario School of Medicine's lactation policy serves as a possible solution to the barriers medical students and residents face when breastfeeding in the academic environment. This policy creates lactation-friendly medical learning spaces through the entitlement of dedicated space and time for milk expression.


The sustainability of stock price fluctuations: Explanation from a recursive dynamic model.
The sustainability of stock price fluctuations indicated by many empirical studies hardly reconciles with the existing models in standard financial theories. This paper proposes a recursive dynamic asset pricing model based on the comprehensive impact of the sentiment investor, the information trader and the noise trader. The dynamic process of the asset price is characterized and a numerical simulation of the model is provided. The model captures the features of the actual stock price that are consistent with the empirical evidence on the sustainability of stock price fluctuations. It also offers a partial explanation for other financial anomalies, for example, asset price's overreaction, asset bubble and the financial crisis. The major finding is that investor sentiment is the key factor to understand the sustainability of stock price fluctuations.


Neoadjuvant chemotherapy for breast cancer: an evaluation of its efficacy and research progress.
Neoadjuvant chemotherapy (NAC) for breast cancer is widely used in the clinical setting to improve the chance of surgery, breast conservation and quality of life for patients with advanced breast cancer. A more accurate efficacy evaluation system is important for the decision of surgery timing and chemotherapy regimen implementation. However, current methods, encompassing imaging techniques such as ultrasound and MRI, along with non-imaging approaches like pathological evaluations, often fall short in accurately depicting the therapeutic effects of NAC. Imaging techniques are subjective and only reflect macroscopic morphological changes, while pathological evaluation is the gold standard for efficacy assessment but has the disadvantage of delayed results. In an effort to identify assessment methods that align more closely with real-world clinical demands, this paper provides an in-depth exploration of the principles and clinical applications of various assessment approaches in the neoadjuvant chemotherapy process.


[Urodynamics of the upper urinary tracts after ureteroplasty (experimental data)].
An experimental study on 12 mongrel dogs was made for assessment of urodynamics of the upper urinary tracts after reconstructive surgery. Ureterohydronephrosis was modelled by cryodestruction, confirmed by x-ray and radionuclide examinations. Urodynamics of the upper urinary tracts was studied by measurements of the intraluminal pressure and at multichannel impedance ureterography under thiopental anesthesia. It was found that reestablishment of normal urine passage after ureteroplasty is not accompanied by urodynamic recovery. Preoperative hyperfunction of the upper urinary tracts and their postoperative hypofunction appeared unfavourable prognostic signs for ureteroplasty outcomes.


Structural modification and biological activities of carboxymethyl Pachymaran.
Polysaccharides are good chelating agents for metal ions, which are often used to synthesize polysaccharide metal ion complexes. With carboxymethyl pachymaran (CMP) as the substrate, carboxymethyl pachymaran iron (CMPF), carboxymethyl pachymaran selenium (CMPS), and carboxymethyl pachymaran zinc (CMPZ) were synthesized by response surface methodology, and their biological characteristics were studied. The results showed that the CMP was a β-polysaccharide, and the degree of carboxymethylation was 0.6352. The polysaccharide metal ion complexes were characterized by physicochemical methods, scanning electron microscopy, Fourier transform infrared spectroscopy, circular dichroism spectroscopy, and nuclear magnetic resonance spectroscopy. All the polysaccharides and complexes possessed antioxidant activity in vitro with scavenging activities to ABTS, superoxide anions, and ferrous ions. CMPF, CMPS, and CMPZ caused significant inhibition of A2780 cell proliferation, promoted the production of reactive oxygen species, and induced apoptosis in a human ovarian cancer cell line (A2780 cells). These results suggest that the CMP complex may be an effective candidate drug for cancer treatment in the field of functional food and pharmacology.


von Willebrand factor: increased levels are related to poor prognosis in systemic sclerosis and not to tissue autoantibodies.
von Willebrand factor, C-reactive protein, rheumatoid factor, major organ involvement, antibodies to extractable nuclear antigen, anti-cardiolipin antibodies, anti-centromere antibodies and anti-nuclear antibodies were measured in 33 patients with systemic sclerosis. After five years, the nine patients who had died had initial levels of von Willebrand factor significantly higher (median 288 IU/dL, range 150-1170) than levels in the 24 who were still alive (median 148 IU/dL, range 65-262, Mann Whitney P = 0.0002). Increased levels of von Willebrand factor correlated with the time interval from blood sampling until the patient's death (Spearman's r = 0.73, P = 0.02). Levels of C-reactive protein, rheumatoid factor, and tissue autoantibodies, and age or the number of organs involved were unable to predict this outcome. We suggest that endothelial perturbation, as indicated by increased levels of von Willebrand factor, is a strong indicator of a poor prognosis in systemic sclerosis.


Awareness of kidney disease in the US population: findings from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2000.
The prevalence of end-stage renal disease (ESRD) in the US population has been predicted to increase by 48% during the next decade and will pose a significant health cost burden. Early identification and treatment of chronic kidney disease (CKD) is necessary to delay progression from CKD to ESRD. CKD awareness among patients is crucial to early intervention programs, but its prevalence and characteristics in the noninstitutionalized US population are unknown. The National Health and Nutrition Examination Survey 1999 to 2000 was used to determine prevalence estimates of kidney disease awareness, as well as demographics, health care access, and comorbid characteristics, of participants with CKD. In participants with CKD, 40.5% of patients with stage 1, 29.3% of patients with stage 2, 22.0% of patients with stage 3, and 44.5% of patients with stage 4 CKD were aware of their kidney disease, respectively. The aware and unaware groups did not differ by health care access. In multivariate regression modeling, lack of awareness was significantly associated with sex, race-ethnicity distribution, and hypertension. Kidney disease awareness is low among a representative sample of the noninstitutionalized US population. Groups at greater risk for kidney disease, such as non-Hispanic blacks, patients with hypertension, and men, were more likely to be unaware of having kidney disease, even with health care access similar to that of the aware group. Increased efforts to promote kidney disease awareness are needed and probably should target primary care providers involved in the screening process.


Antiapoptotic and anti-inflammatory effects of Pparγ agonist, pioglitazone, reversed Dox-induced cardiotoxicity through mediating of miR-130a downregulation in C57BL/6 mice.
Doxorubicin (Dox) is an antitumor agent widely used in cancer therapy, with notable side effects of cardiac toxicity. Peroxisome proliferator-activated receptor γ (PPARγ), is a transcriptional factor with antiapoptotic and anti-inflammatory properties. Recently we indicated that cardiac toxicity of Dox was due to upregulation of miR-130a and further suppressive effect on cardiac Pparγ in vitro. In this study, we extended our proposed hypothesis in vivo. To achieve this, pioglitazone (Pio) and GW9662 were used as the specific agonist and antagonist of Pparγ to treat Dox-injected mice. Heart function, apoptosis, and inflammation in heart tissue were studied. Pretreatment of Dox-injected mice with Pio resulted in elevated expression of Pparγ and suppression of miR-130a. However, GW9662 pretreatment was unable to increase miR-130a expression. Pio pretreatment led to partially cardiac toxicity limitation of Dox whereas GW9662 caused heart damage. Finally, our observation determined that activation of Pparγ was not adequate to reverse the Dox-induced toxicity completely.


Arachidonate lipoxygenase metabolite formation in gestational tissues.
Products of arachidonic acid metabolism via the lipoxygenase pathways have a potential role in the onset of human labor. We have determined whether activation of protein kinase C can modulate the rate of biosynthesis within the uterus of five important arachidonate lipoxygenase metabolites, i.e., leukotriene B4 (LTB4), LTC4, 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE and 15-HETE. Amnion, chorion laeve and decidual cells were isolated, grown to confluence and incubated with phorbol 12-myristate 13-acetate (PMA). PMA caused concentration-related stimulation of 5-HETE, 12-HETE and 15-HETE (but not LTB4) production; there were some stimulatory actions on decidual and amnion (but not chorion) LTC4 production. We postulate that activation of protein kinase C can result in enhanced production of arachidonate lipoxygenase metabolites that may have actions on the parturient process.


Abnormal expression of period 1 (PER1) in endometrial carcinoma.
The development of endometrial carcinoma (EC) is a multiple-step process, which includes inactivation of tumour suppressor genes, activation of oncogenes, and disturbance of cancer-related genes. Recent studies have shown that the circadian cycle may influence cancer development and prognosis. In this study, the expression of a circadian gene, PER1, was examined in 35 ECs and paired non-tumour tissues by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Expression levels of PER1 were significantly decreased in EC, and mutational analysis of the coding regions, together with methylation analysis of cytosine-phosphate guanosine (CpG) sites in the promoter area, was performed to investigate the possible mechanisms. The analyses detected four single nucleotide polymorphisms in both tumour and non-tumour tissues, which had no relationship with the expression of PER1. In the promoter area of the PER1 gene, the CpG sites were methylated in 31.4% of ECs, but in 11.4% of paired non-tumour tissues (p < 0.05). These results suggest that the down-regulation of PER1 expression in EC was partly due to inactivation of the PER1 gene by DNA methylation of the promoter and partly due to other factors. Analysis of the relationships between the expression of PER1, P53, c-MYC, cyclin A, cyclin B, and cyclin D1 showed no definite relationship. These results suggest that down-regulation of the PER1 gene disrupts the circadian rhythm, which may favour the survival of endometrial cancer cells.


Absence of liver tumor-initiating activity of kojic acid in mice.
In order to evaluate the tumor-initiating activity of kojic acid (KA) in mouse liver, an in vivo initiation assay in liver was performed using partially hepatectomized mice. Male ICR mice were fed on a basal diet (BD) containing 0 or 3% KA for 4 weeks, followed by distilled water (DW) containing 0 or 500 ppm phenobarbital (PB) for 13 weeks. Two weeks after the treatment with PB, two-thirds partial hepatectomy was preformed in all mice in order to enhance the regeneration and proliferating activities of the hepatocytes. In microscopic examinations, no proliferative lesion was observed in any of the groups. There were no differences in the number of gamma-glutamyltransferase-positive cells, an expected marker for preneoplastic hepatocytes in mice, between the KA + DW and the KA + PB groups. In the immunohistochemical analyses of the proliferating activity of hepatocytes, significant increases in the labeling index of proliferating cell nuclear antigen (PCNA) were observed in the BD + PB and KA + PB groups as compared to the BD + DW group; however, no significant difference in the positivity of PCNA was observed between the BD + PB and the KA + PB groups. These results of the present study suggest the possibility that KA has no tumor-initiating activity in the liver of mice.


Towards a Heuristic Neuropsychological Model of Adjudicative Competency.
This study sought to delineate the neuropsychological processes that undergird the psycho-legal concept of competency to stand trial (CST). Accordingly, we retrospectively examined the relationship between clinical judgments of competence or incompetence of defendants committed to a maximum-security psychiatric facility and neuropsychological measures of cognitive and social intelligence and declarative memory. Results indicated that both groups (competent and incompetent) showed similar levels of depressed cognitive intelligence with Wechsler full-scale IQ levels falling in the upper end of the borderline range. Compared with defendants clinically judged as incompetent, defendants recommended as competent scored significantly higher on measures of social intelligence and episodic memory, with the most pronounced advantage occurring on tests of verbal memory that place heavy demands on encoding, consolidation, and retrieval of aurally presented narrative material. Cognitive capacities in areas of social intelligence and episodic memory may play critical roles in developing a heuristic neuropsychological model of CST. The evaluation of these domains offers implications for the assessment, restoration, and understanding of CST.


Resistance factors in anaerobic bacteria.
Resistance transfer factors have been described in both Bacteroides and clostridia. The clindamycin (Cln) resistance transfer factors from the Bacteroides fragilis group of organisms have been best studied, including our own plasmid pBFTM10. The clindamycin resistance determinant (Cln X) of pBFTM10 can be detected in 90% of Cln resistant Bacteroides isolated from dispersed geographical areas. This determinant can be located in the chromosome and on plasmids. Recent studies from our laboratory have shown that the Cln X genes of pBFTM 10 are carried on a compound transposon, Tn4400. Bacteroides plasmids have been cloned in Escherichia coli and shuttle vectors have been developed that allow transfers of DNA from E. coli back to B. fragilis, using the broad host range plasmid RK2 to supply essential conjugation functions. We have shown that shuttle vectors containing pBFTM 10 can be retransferred from B. fragilis back to E. coli. In addition, a tetracycline transfer element from B. fragilis strain TM230 is able to promote high frequency conjugation between B. fragilis and E. coli. The results of these investigations indicate that Bacteroides has efficient mechanisms to exchange genetic material and that genetic exchange can occur between Bacteroides and E. coli, which exist in intimate contact in the human colon.