Oral administration of visceral adipose tissue antigens ameliorates metabolic disorders in mice and elevates visceral adipose tissue-resident CD4+CD25+Foxp3+ regulatory T cells.
Obesity and type 2 diabetes are linked with chronic, low-grade inflammation in visceral adipose tissue (VAT). A unique population of VAT-resident CD4+Foxp3+ Tregs plays a crucial role in regulating VAT inflammation and metabolic homeostasis. VAT-resident Tregs display a highly restricted TCR repertoire, suggesting they recognize certain autoantigen(s) in VAT. A dramatic reduction of VAT-resident Tregs has been shown to closely correlate with obesity-related VAT chronic inflammation and metabolic disorders. Oral tolerance strategy may modulate inflammatory response to autoantigens by several mechanisms including induction of autoantigen-specific Tregs. Here, we explored the effects and cellular mechanism of oral administration of VAT pooled antigens on high-fat diet (HFD)-induced metabolic disorders in mice. Indeed, we found that oral treatment of VAT mixture antigens effectively inhibited gain in body weight and fat mass, ameliorated serum lipid parameters, and improved insulin sensitivity in HFD mice. This strategy was shown to significantly restore HFD-induced decrease of VAT-resident Tregs, accompanied by a hampered M2-type to M1-type macrophages phenotypic switch as well as decreased CD8+ T cells infiltration in VAT. Thus, oral administration of VAT antigens may be a novel and safe strategy against obesity and its related metabolic disorders.


[Technique of thulium laser in managing bladder cuff in nephroureterectomy for upper urinary tract urothelium carcinoma].
To explore the application of thulium laser (2 µm laser) in managing bladder cuff in nephroureterectomy for upper urinary tract urothelium carcinoma (UUT-UC). The medical records of 56 patients undergoing nephroureterectomy at our hospital were reviewed retrospectively. The operative indicators, oncologic outcomes and clinicopathologic data were compared among the groups of open surgery (Group A), electric coagulation (Group B) and thulium laser technique (Group C). Furthermore a model of burst pressure measurement was built to measure the different burst pressures of sealing distal ureter. The follow-up results: when the indicators of operative duration, intraoperative blood loss volume, removal time of drainage tube, removal time of catheter and hospital stays were compared among three groups, Group A had no statistical differences with Group B/C in terms of removal time of drainage tube and removal time of catheter. But significant statistical differences existed in terms of operative duration, intraoperative blood loss volume and hospital stays ((232 ± 52) vs (148 ± 47) and (130 ± 49) min, (358 ± 81) vs (136 ± 74) and (145 ± 70) ml, (13 ± 3) vs (11 ± 4) and (10 ± 3) d, all P < 0.05). No statistical differences existed between Groups B and C in terms of all the above indicators. Burst pressure measurement results: no statistical differences existed between Group C and B ((116 ± 21) vs (139 ± 32) cm H2O, P > 0.05). For the surgical treatment of UUT-UC, thulium laser technique has no difference in operation indicators and oncologic outcomes compared to open surgery. Besides, it has the advantages of improved spatial beam quality and more precise tissue incision.


[Quality assurance of rehabilitation by the German pension insurance: an overview].
The German pension insurance has in recent years developed a comprehensive programme for quality assurance in rehabilitation, and has implemented the programme into routine practice. Different aspects of rehabilitation are evaluated with differentiated instruments. Issues dealt with inter alia include the quality of rehabilitative care in a narrower sense, the structure and organisation of the rehabilitation centres, as well as quality from the patients' perspective. On the whole, positive results predominate. Big differences in quality however have been found between the rehabilitation centres. The data collections and data evaluations carried out make a continuous process of quality assurance reporting possible for use by rehabilitation centres and pension insurance agencies. This will enable targeted initiatives for quality improvement. The methods and procedures of quality assurance are enhanced at regular intervals, and the scope of quality assurance is extended. Thus, rehab quality assurance is also expanded to cover ambulant rehabilitation or rehabilitation of children and young people.


Vitamin C intake and the risk of preterm delivery.
Ascorbic acid deficiency may lead to premature rupture of the membranes. The study included a prospective cohort of pregnant women, aged >/=16 years, with singleton gestations who received care at one of four prenatal clinics in central North Carolina from 1995 through 1998. Vitamin C intake preconceptionally and during the second trimester was examined for its association with preterm delivery and subsets of preterm labor, premature rupture of the membranes, and medical induction in 2064 women. Women who had total vitamin C intakes of <10th percentile preconceptionally had twice the risk of preterm delivery because of premature rupture of the membranes (relative risk, 2.2; 95% CI, 1.1, 4.5). This risk was attenuated slightly for second-trimester intake (relative risk, 1.7; 95% CI, 0.8, 3.5). The elevated risk of preterm premature rupture of the membranes was greatest for women with a low vitamin C intake during both time periods. Because diet and supplement use are modifiable behaviors, corroboration of these findings would suggest a possible intervention strategy.


Minimally Invasive Surgery for the Removal of Posterior Intraocular Foreign Bodies.
This is a prospective clinical assay that included six patients who were diagnosed with penetrating corneal injury, traumatic cataract, and posterior segment intraocular foreign body (IOFB). Following anterior segment repair and extraction of traumatic cataract by clear cornea phacoemulsification, a standard 25-gauge transconjunctival pars plana vitrectomy was performed to find and release the IOFB. With active suction using a 25-gauge silicone tipped cannula, the foreign body was retrieved and safely placed in the anterior chamber. After stabilization of the anterior chamber with viscoelastic injection, IOFB extraction through the main phaco incision was easily performed, followed by placement of an intraocular lens. Of the six patients, 66.6% showed a significant improvement of visual acuity. No complications associated directly with the surgical procedure occurred. Our surgical technique is a safe alternative for handling and removing a posterior IOFB. There was no need for a scleral incision.


OsYSL2 is a rice metal-nicotianamine transporter that is regulated by iron and expressed in the phloem.
We identified 18 putative yellow stripe 1 (YS1)-like genes (OsYSLs) in the rice genome that exhibited 36-76% sequence similarity to maize iron(III)-phytosiderophore transporter YS1. Of particular interest was OsYSL2, the transcripts of which were not detected in the roots of either iron-sufficient or iron-deficient plants, but dramatic expression was induced in the leaves by iron deficiency. Based on the nucleotide sequence, OsYSL2 was predicted to encode a polypeptide of 674 amino acids containing 14 putative transmembrane domains. OsYSL2:green fluorescent protein (GFP) was localized in the plasma membrane of onion epidermal cells. Promoter:beta-glucuronidase (GUS) analysis revealed that OsYSL2 was expressed in companion cells in iron-sufficient roots. GUS activity was increased in companion cells, but no GUS staining was observed in epidermal or cortex cells, even in iron-deficient roots. In the leaves and leaf sheaths of iron-sufficient rice, GUS staining was observed in phloem cells of the vascular bundles. In iron-deficient leaves, the OsYSL2 promoter was active in all tissues with particularly strong GUS activity evident in companion cells. The phloem-specific expression of the OsYSL2 promoter suggests that OsYSL2 is involved in the phloem transport of iron. Strong OsYSL2 promoter activity was also detected in developing seeds. Electrophysiological measurements using Xenopus laevis oocytes showed that OsYSL2 transported iron(II)-nicotianamine (NA) and manganese(II)-NA, but did not transport iron(III)-phyosiderophore. These results suggest that OsYSL2 is a rice metal-NA transporter that is responsible for the phloem transport of iron and manganese, including the translocation of iron and manganese into the grain.


Occupancy of the sodalite cages in the blue ultramarine pigments.
A quantitative EPR study of blue ultramarine pigments has been performed in order to determine the concentration of the S(3)(-) chromophore. Copper sulfate CuSO(4) x 5H(2)O has been used as a standard, while a ruby crystal was used as an inner standard to take into account the changes of the quality factor of the cavity. These experiments show that, in the most-colored pigments, less than half of the sodalite cages are occupied by a S(3)(-) radical. In other experiments, it has been shown that the blue ultramarine pigments can be significantly modified by heating under a dynamic vacuum. The concentrations of S(3)(-) and S(2)(-), as deduced from EPR and Raman experiments, are increased after this type of treatment. These changes imply that sulfur species are transformed into S(3)(-) or S(2)(-) during this treatment. It is discussed that these sulfur species could be S(2)(-).


Coronary artery bypass surgery prior to resection of abdominal aortic aneurysm in patients with unstable coronary artery disease.
Coronary artery disease (CAD) is associated with abdominal aortic aneurysm in greater than 60% of cases. CAD continues to affect postoperative complication rates. Half of the deaths that follow resection of abdominal aortic aneurysms are due to perioperative myocardial infarctions. On evaluation for surgical resection of an abdominal aortic aneurysm, six patients were found to have significant CAD. Each underwent coronary artery bypass surgery prior to elective resection of the aneurysm. No deaths or myocardial infarctions occurred following any of the procedures. We restrict our indications for coronary angiography to the evaluation of patients with unstable angina (pain at rest or after minimal exertion) in whom noninvasive studies reveal evidence of CAD, and for patients who are unresponsive to medical management.


A survey of technology literacy and use in cancer survivors from the Alberta Cancer Exercise program.
Supervised physical activity interventions can improve cancer survivor quality of life. However, they are resource intensive and may not support physical activity maintenance. Therefore, most cancer survivors remain inactive. Electronic health is a promising tool to support physical activity maintenance, yet technology-based physical activity interventions in oncology have shown mixed effectiveness. We surveyed cancer participants in the Alberta Cancer Exercise program to better understand their experience with technology. Alberta Cancer Exercise participants were invited to complete a survey on technology literacy, usage, and perceived usefulness. Summary statistics were calculated for all variables. Multiple regression examined demographic prediction of technology usage and literacy. The response rate was 52.6% (n = 627/1191), with 93.3% survey completion (n = 585/627). Respondents were 60.6 ± 11.0 years old, 96.2% Caucasian, and of high socioeconomic status (83.3% with post-secondary education, 65.5% with income >$60,000). While electronic health literacy was low (mean 1.73 ± 0.73/4), computer (87.6%) and smartphone (87.5%) use was widespread, with 94.6% of smartphone users reporting daily use. One in two respondents used mobile applications or wearable trackers for physical activity, which were perceived as useful by >80% of users. Age and income were significant predictors of technology use and literacy. Technology is part of the lives of cancer survivors who engaged in a physical activity program, with mobile devices perceived as useful to support physical activity. However, the present findings highlight a need to increase electronic health literacy via education and tailoring of digital tools. These survey findings are being used to build our patient-centered, technology-supported physical activity interventions.


The PaleoJump database for abrupt transitions in past climates.
Tipping points (TPs) in Earth's climate system have been the subject of increasing interest and concern in recent years, given the risk that anthropogenic forcing could cause abrupt, potentially irreversible, climate transitions. Paleoclimate records are essential for identifying past TPs and for gaining a thorough understanding of the underlying nonlinearities and bifurcation mechanisms. However, the quality, resolution, and reliability of these records can vary, making it important to carefully select the ones that provide the most accurate representation of past climates. Moreover, as paleoclimate time series vary in their origin, time spans, and periodicities, an objective, automated methodology is crucial for identifying and comparing TPs. To address these challenges, we introduce the open-source PaleoJump database, which contains a collection of carefully selected, high-resolution records originating in ice cores, marine sediments, speleothems, terrestrial records, and lake sediments. These records describe climate variability on centennial, millennial and longer time scales and cover all the continents and ocean basins. We provide an overview of their spatial distribution and discuss the gaps in coverage. Our statistical methodology includes an augmented Kolmogorov-Smirnov test and Recurrence Quantification Analysis; it is applied here, for illustration purposes, to selected records in which abrupt transitions are automatically detected and the presence of potential tipping elements is investigated. These transitions are shown in the PaleoJump database along with other essential information about the records, including location, temporal scale and resolution, as well as temporal plots. This open-source database represents, therefore, a valuable resource for researchers investigating TPs in past climates.


Small bowel obstruction due to herniation into an extra-anatomical arterial bypass tunnel: a first case report.
We highlight the importance of considering rarer causes of small bowel obstruction in patients presenting after extra-anatomical arterial bypass. Our patient underwent a left common iliac-to-bifemoral bypass extra-anatomical graft for critical limb ischaemia. The patient developed mechanical small bowel obstruction on the 20th postoperative day. Emergency laparotomy revealed incarcerated, obstructed small bowel trapped in the graft tunnel. Recovery was satisfactory following small bowel resection. To the best of our knowledge, small bowel herniation into an arterial bypass graft tunnel, with successful treatment outcome, has not been reported to date.


Longitudinal microstructural changes of cerebral white matter and their association with mobility performance in older persons.
Mobility impairment in older persons is associated with brain white matter hyperintensities (WMH), a common finding in magnetic resonance images and one established imaging biomarker of small vessel disease. The contribution of possible microstructural abnormalities within normal-appearing white matter (NAWM) to mobility, however, remains unclear. We used diffusion tensor imaging (DTI) measures, i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), to assess microstructural changes within supratentorial NAWM and WMH sub-compartments, and to investigate their association with changes in mobility performance, i.e. Tinetti assessment and the 2.5-meters walk time test. We analyzed baseline (N = 86, age ≥75 years) and 4-year (N = 41) follow-up data. Results from cross-sectional analysis on baseline data showed significant correlation between WMH volume and NAWM-FA (r = -0.33, p = 0.002), NAWM-AD (r = 0.32, p = 0.003) and NAWM-RD (r = 0.39, p = 0.0002). Our longitudinal analysis showed that after 4-years, FA and AD decreased and RD increased within NAWM. In regional tract-based analysis decrease in NAWM-FA and increase in NAWM-RD within the genu of the corpus callosum correlated with slower walk time independent of age, gender and WMH burden. In conclusion, global DTI indices of microstructural integrity indicate that significant changes occur in the supratentorial NAWM over four years. The observed changes likely reflect white matter deterioration resulting from aging as well as accrual of cerebrovascular injury associated with small vessel disease. The observed association between mobility scores and regional measures of NAWM microstructural integrity within the corpus callosum suggests that subtle changes within this structure may contribute to mobility impairment.


Dual X-ray absorptiometry quality control: comparison of visual examination and process-control charts.
Dual X-ray absorptiometry (DXA) is widely used to monitor treatment efficacy in reducing the rate of bone mineral loss. In order to assure the validity of these measurements, instrument quality control of the DXA scanners becomes very important. This paper compares five quality control procedures (visual inspection, Shewhart chart with sensitizing rules, Shewhart chart with sensitizing rules and a filter for clinically insignificant mean changes, moving average chart and standard deviation, and cumulative sum chart [CUSUM]) in their ability to identify scanner malfunction by means of (1) an analysis of five longitudinal phantom data sets that had been collected during a clinical trial and (2) an analysis of simulated data sets. The visual inspection method is relatively subjective and depends on the operator's experience and attention. The regular Shewhart chart with sensitizing rules has a high false alarm rate. The Shewhart chart with sensitizing rules and an additional filter for clinically insignificant mean changes has the lowest false alarm rate but a relatively low sensitivity. The CUSUM method has good sensitivity and a low false alarm rate. In addition, this method provides an estimate of the date a change in the DXA scanner performance might have occurred. The method combining a moving average chart and a moving standard deviation chart came closest to the performance of the CUSUM method. Comparing the advantages and disadvantages of all methods, we propose the use of the CUSUM method as a quality control procedure for monitoring DXA scanner performance. For clinical trials use of the more intuitive Shewhart charts may be acceptable at the individual sites provided their scanner performance is followed up by CUSUM analysis at a central quality assurance center.


Microwave accelerated selective Soxhlet extraction for the determination of organophosphorus and carbamate pesticides in ginseng with gas chromatography/mass spectrometry.
Microwave accelerated selective Soxhlet extraction (MA-SSE), a novel selective extraction technique, was investigated in this study. A Soxhlet extraction system containing a glass filter was designed as an extractor. During the procedure of MA-SSE, both the target analytes and the interfering components were extracted from the sample into the extraction solvent enhanced by microwave irradiation. After the solvent flowed though the sorbent, the interfering components were adsorbed by the sorbent, and the target analytes remaining in the solvent were collected in the extraction bottle. No cleanup or filtration was required after extraction. The efficiency of the MA-SSE approach was demonstrated in the determination of organophosphorus and carbamate pesticide residues in ginseng by gas chromatography/mass spectrometry (GC/MS). Under the optimized conditions, low limits of detection (0.050-0.50 μg/kg) were obtained. The recoveries were in the range of 72.0-110.1% with relative standard deviations less than 7.1%. Because of the effect of microwave irradiation, MA-SSE showed significant advantage compared with other extraction techniques. The sorbent used in this study showed good cleanup ability. The mechanism of MA-SSE was demonstrated to be based on the rupture of the cell walls according to the structural changes of ginseng samples. On the basis of the results, MA-SSE as a simple and effective sample preparation technique for the analysis of pesticide residues in complex matrixes shows great promise.


Contraction-mediating alpha 2-adrenoceptors in the mouse vas deferens.
The question of the existence of postjunctional, contraction-mediating alpha 2-adrenoceptors, in addition to the known alpha 1-adrenoceptors, was studied in the mouse isolated vas deferens. Both the alpha 1-selective agonist phenylephrine and the alpha 2-selective agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) caused contraction of the vas deferens. In the presence of the alpha 1-selective antagonist prazosin (added in order to prevent an alpha 1 component in the effect of high concentrations of UK 14,304), the alpha 2-selective antagonist yohimbine and idazoxan shifted the concentration-response curve of UK 14,304 to the right in a manner compatible with competitive antagonism and with dissociation constants KB indicating the involvement of alpha 2-adrenoceptors. The maximal contraction elicited by UK 14,304 (in the presence of prazosin) was much lower than the maximal contraction elicited by phenylephrine. The effect of UK 14,304 was not changed by the P2-purinoceptor agonist alpha,beta-methylene-ATP and was reduced by neuropeptide Y, but was markedly enhanced by relatively low concentrations of phenylephrine. When the sympathetic fibres of the vas deferens were stimulated by trains of ten widely spaced (0.5 Hz) electric pulses, the tissue responded with ten separate twitches in which purinergic and adrenergic components were isolated by prazosin and suramin, respectively. Prazosin reduced the first adrenergic twitch in these trains at concentrations close to its KB value at alpha 1-adrenoceptors, whereas yohimbine and idazoxan reduced the first adrenergic twitch at concentrations far lower than their KB values at alpha 1-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)


Cell type dependence of herpes simplex virus gene expression and of processing of viral protein.
R325, a recombinant virus constructed from the wild type herpes simplex virus 1 strain F [HSV-1(F)] carries a 500 bp deletion in the alpha 22 gene. Both viruses are temperature sensitive for growth and late gene expression in HEp-2 cells. To determine the properties of alpha 22 protein and to identify the product of the non deleted 5' portion of the alpha 22 gene in R325, infected BHK and HEp-2 cells incubated at permissive and non-permissive temperatures were electrophoretically separated in denaturing polyacrylamide gels, electrically transferred to a nitrocellulose sheet and reacted with rabbit polyclonal antibody to an oligopeptide synthesized according to the predicted aminoacid sequence of the 5' terminus of alpha 22. The results were as follows: the authentic alpha 22 protein was detected in infected BHK and HEp-2 cells maintained at either 34 degrees C (permissive) or 39 degrees C (non-permissive) temperatures, the truncated protein specified by R325 accumulated at 39 degrees C but not at 34 degrees C. Furthermore, the proteins made in BHK cells were processed to higher apparent molecular weights and formed several bands in contrast to the single band formed by the protein made in HEp-2 cells; the temporal pattern of expression of HSV-1(F) and R325 at the 39 degrees C was more advanced in BHK cells than in HEp-2 cells. Specifically, in BHK cells at the non-permissive temperature alpha protein synthesis was shut off earlier and gamma proteins not made in infected HEp-2 cells were detected. These studies suggest that folding of viral proteins may be in part cell dependent and either compensate or exacerbate the effects of mutations in specific genes.


Long-lasting dyspnoea in patients otherwise clinically and radiologically recovered from COVID pneumonia: a probe for checking persisting disorders in capillary lung volume as a cause.
During SARS-CoV-2 infection, diffuse alveolar damage and pulmonary microvascular abnormalities are critical events that result in gas exchange disorders of varying severity and duration. The only measure of carbon monoxide (CO) diffusing capacity (DLCO) is unable to distinguish the alveolar from the vascular side of present and residual diffusive abnormalities, and measure of nitric oxide (NO) diffusing capacity (DLNO) is also recommended. Dyspnoea, despite being understudied, persists in a significant proportion of patients for several weeks after hospital discharge. The goal of this study was to look into the underlying cause of long-term dyspnoea in patients who were "clinically and radiologically recovered" from COVID pneumonia by assessing DLCO and DLNO at the same time. Patients of both genders, aged ≥18 years, who had a CT scan showing complete resolution of COVID-related parenchymal lesions were recruited consecutively. Spirometrical volumes, blood haemoglobin, SpO2, DLCO, DLNO and capillary blood volume (Vc) were measured. Data from patients without dyspnoea (group A) and from patients still claiming dyspnoea after 12-16 weeks from their hospital discharge (group B) were statistically compared. Forty patients were recruited: 19 in group A and 21 in group B. Groups were comparable for their general characteristics and spirometrical volumes, that were in the normal range. Mean values for DLCO, DLNO and Vc were significantly and substantially lower than predicted only in patients of group B (p<0.011; p<0.0036; p<0.02; p<0.001, respectively). The DLNO/ DLCO ratio was higher in group B (p<0.001) and inversely correlated to Vc values (-0.3636). The single-breath, simultaneous measurement of DLCO, DLNO, and Vc demonstrated that problems with blood gas exchange can persist even after parenchymal lesions have healed completely. Regardless of the normality of spirometric volumes, there was a significant reduction in lung capillary blood volume. In these patients, the cause of long-term dyspnoea may be related to hidden abnormalities in the vascular side of diffusive function. In the near future, novel therapeutic approaches against residual and symptomatic signs of long-COVID are possible.


Implications of the growing incidence of global colorectal cancer.
The expanding worldwide burden of colorectal cancer (CRC) is a significant public health issue. Understanding the shift in the geo-demographic, socioeconomic, environmental, and biogenetic distribution of CRC is paramount. The Human Development Index (HDI) measuring life expectancy, education, and gross national income is a composite index comparing health outcomes between countries. This has been shown to be a useful comparison tool in measuring the health dimension among high, middle, and low-income countries. CRC has a wide global distribution in incidence and mortality with majority of cases occurring in countries with a high or very high HDI. However, in developing countries and in those undergoing rapid socioeconomic growth, there has also been a marked rise in CRC rates as well. This pattern is noted globally and seems to correlate with increase in a country's specific HDI. Additionally, another unique pattern of CRC incidence has emerged with more cancers being diagnosed in adults younger than 50 years old. Further investigation is needed to determine CRC risks reduction and implementation of primary prevention and early detection strategies within different country specific healthcare systems. Globally, improvement in healthcare equality, access to medical care and screening for CRC particularly in resource-limited (low HDI) countries is essential.


Monoclonal antibody-based immunoassays for the specific quantitation of rat PAI-1 antigen and activity in biological samples.
Two enzyme-linked immunosorbent assays (ELISAs) for the quantitation of rat plasminogen activator inhibitor-1 (PAI-1) antigen and activity, respectively, in biological fluids were developed using monoclonal antibodies raised against recombinant rat PAI-1. These assays had a lower limit of sensitivity in plasma of 0.3 and 0.15 ng/ml, respectively. The intra-assay, inter-assay and inter-dilution coefficients of variation were 9, 14 and 9%, respectively, for the antigen assay and 8, 17 and 13%, respectively for the activity assay. Assay recoveries of recombinant rat PAI-1 (5 to 20 ng/ml) added to plasma were 73 to 88% and 89 to 93% for the antigen and the activity assay, respectively. The level of PAI-1 antigen in rat plasma was 1.8 +/- 0.9 ng/ml (mean +/- SD, n = 18), with a corresponding value of 1.0 +/- 0.5 ng/ml for PAI-1 activity. In lysed platelet-rich rat plasma PAI-1 antigen was 6.0 +/- 1.0 ng/ml (n = 8) and PAI-1 activity was 2.3 +/- 0.4 ng/ml (n = 8). Endotoxin injection (0.5 mg/kg) induced a time-dependent increase of both PAI-1 antigen and PAI-1 activity levels in rat plasma. eventually resulting in a 100- to 200-fold increase (p < 0.0001 vs. baseline). A linear correlation was found between PAI-1 antigen and activity levels in normal plasma (r = 0.63, n = 18, p < 0.01) and in plasma from endotoxin-treated rats (r = 0.90, n = 35, p < 0.001). Application of these assays for the analysis of gel filtration experiments of plasma from endotoxin-treated rats demonstrated that PAI-1 antigen eluted as two peaks (with corresponding Mr of approximately 430 kDa and 61 kDa) whereas PAI-1 activity eluted as a single peak corresponding with the high molecular weight antigen form. Thus, these unique assays allowing the specific determination of rat PAI-1 antigen and rat PAI-1 activity may constitute important tools for further investigations on the pathophysiological role of PAI-1 in a variety of experimental rat models.


Gradient Boosted Machine Learning Model to Predict H2, CH4, and CO2 Uptake in Metal-Organic Frameworks Using Experimental Data.
Predictive screening of metal-organic framework (MOF) materials for their gas uptake properties has been previously limited by using data from a range of simulated sources, meaning the final predictions are dependent on the performance of these original models. In this work, experimental gas uptake data has been used to create a Gradient Boosted Tree model for the prediction of H2, CH4, and CO2 uptake over a range of temperatures and pressures in MOF materials. The descriptors used in this database were obtained from the literature, with no computational modeling needed. This model was repeated 10 times, showing an average R2 of 0.86 and a mean absolute error (MAE) of ±2.88 wt % across the runs. This model will provide gas uptake predictions for a range of gases, temperatures, and pressures as a one-stop solution, with the data provided being based on previous experimental observations in the literature, rather than simulations, which may differ from their real-world results. The objective of this work is to create a machine learning model for the inference of gas uptake in MOFs. The basis of model development is experimental as opposed to simulated data to realize its applications by practitioners. The real-world nature of this research materializes in a focus on the application of algorithms as opposed to the detailed assessment of the algorithms.


Prognostic scales in advanced heart failure.
Heart transplantation (HT) is the treatment of choice for patients with advanced heart failure (HF) who remain symptomatic despite optimal medical therapy. Due to the shortage of organs for transplantation and constantly increasing number of patients placed on waiting lists, accurate risk stratification is a crucial element of management in this population. Prognostic scales allow one to evaluate the patient prognosis, estimate the potential benefits of therapy and identify those patients most likely to benefit from advanced methods of treatment. In this review, we describe prognostic scales in advanced HF, concentrating on commonly used tools - the Heart Failure Survival Score (HFSS) and Seattle Heart Failure Model (SHFM) - as well as on the new promising scales for evaluating waiting list mortality and post-transplant outcomes.


Primary intrauterine dysgerminoma in a pregnant woman: A rare case report.
Primary extraovarian dysgerminoma is very rare. Nearly all reported uterine germ cell tumors are nondysgerminoma. Herein, we reported a primary intrauterine dysgerminoma. A 21-year-old pregnant woman G2 L1 with a gestational age of 33 weeks referred to an obstetric ward with a chief complaint of labor pain and membrane rupture. Ultrasonography showed a large hypoechoic lobulated area adjacent to the lower part of her uterus. She underwent an operation and a huge mass was detected in her uterus, which was extended to her pelvic floor. Histopathological and immunohistochemical examinations were consistent with dysgerminoma.


Quantitative and functional differences between peripheral blood myeloid dendritic cells from patients with pleural and parenchymal lung tuberculosis.
Dendritic cells (DCs) play a pivotal role in generating protective host immunity to Mycobacterium tuberculosis. Few studies have addressed DC function in the context of active tuberculosis (TB), largely due to technical constraints in obtaining adequate numbers of DC from sick patients. We quantitated peripheral blood myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in the whole blood of patients with active TB and show that blood from patients with pleural TB was characterized by high circulating levels of mDCs. We also developed and optimized a novel whole-blood assay to study mDC production of the Th1-promoting cytokine interleukin 12 (IL-12) and upregulation of the maturation marker CCR7 after incubation with mycobacteria. We found that pleural TB was associated with increased IL-12 production and CCR7 expression compared to lung parenchymal disease. Our findings suggest important differences in innate immunity between patients with different forms of active TB, and this may contribute to the differences in natural history observed between the two groups.


Phase I implementation of an academic medical record for integrating information management competencies into a nursing curriculum.
This paper is the report of the first phase of a case study from the University of Utah to help students and faculty integrate electronic information management into the nursing curriculum. Cerner AES, a live-production clinical information system with an academic overlay, has been implemented into the first semester of an undergraduate nursing program. A consortium of schools that use Cerner AES collaborate in the design and implementation of forms used by students. The consortium also allows members to share strategies for using the system. By using the system students are developing needed informatics competencies for beginning level nurses. The paper discusses the implementation strategies used and initial results of this project. Plans for expanding the project throughout the nursing curriculum are also presented.


Testing the limits of structural thinking about gender.
When seeking to explain social regularities (such as gender differences in the labor market) people often rely on internal features of the targets, frequently neglecting structural and systemic factors external to the targets. For example, people might think women leave the job market after childbirth because they are less competent or are better suited for child-rearing than men, thereby eliding socio-cultural and economic factors that disadvantage women. Across two studies (total N = 192) we probe 4- and 5-year-olds and 7- and 8-year-olds' internal versus structural reasoning about gender. We explore the evaluative and behavioral implications of this reasoning process with both novel gendered behaviors that were experimentally created and familiar gendered behaviors that exist outside of a lab context. We show that children generate more structural explanations, evaluate the structural explanation more positively, expect behaviors to be more mutable, and evaluate gender non-conforming behaviors more positively when structural cues are provided. However, we also show that such information may be of limited effectiveness at reducing pre-existing group-based discriminatory behaviors: children continue to report less willingness to affiliate with peers who display non-conforming behaviors even in the presence of structural cues. Taken together, these results provide evidence concerning children's structural reasoning about gender categories and shed new light on how such reasoning might affect social evaluations and behavioral intentions.


Chickpea protein isolates obtained by wet extraction as emulsifying agents.
Wet extraction of protein from defatted chickpea (variety Thiva (T), Greece) flour, at alkaline or slightly acidic pH, followed by isoelectric precipitation (pI) or ultrafiltration (UF) to recover the protein, was employed to obtain a number of chickpea protein isolates, enriched either in protein constituents belonging to the globulin (TpI, TUF, TUFG) or to the albumin fraction (TUFA). The interfacial activity and film-forming ability of the isolate protein constituents as well as their emulsifying properties were evaluated. The method applied for chickpea protein isolate preparation influenced to an appreciable extent their composition, adsorption behaviour to oil-water interfaces and emulsion formation and stabilization characteristics, especially with respect to oil droplet flocculation and coalescence. The isolates also differed in their ability to stabilize emulsions subjected to thermal processing or following storage under freezing conditions. The results are discussed in terms of compositional and, possibly, structural differences existing between the protein constituents of the chickpea isolates that may influence their functional behaviour in emulsion systems. The method applied for isolate preparation influenced to an appreciable extent the ability of proteins to adsorb to the oil-water interface and stabilize emulsions during long-time ageing or following heat treatment or freezing.


Interpretations and pitfalls in modelling vector-transmitted infections.
In this paper we propose a debate on the role of mathematical models in evaluating control strategies for vector-borne infections. Mathematical models must have their complexity adjusted to their goals, and we have basically two classes of models. At one extreme we have models that are intended to check if our intuition about why a certain phenomenon occurs is correct. At the other extreme, we have models whose goals are to predict future outcomes. These models are necessarily very complex. There are models in between these classes. Here we examine two models, one of each class and study the possible pitfalls that may be incurred. We begin by showing how to simplify the description of a complicated model for a vector-borne infection. Next, we examine one example found in a recent paper that illustrates the dangers of basing control strategies on models without considering their limitations. The model in this paper is of the second class. Following this, we review an interesting paper (a model of the first class) that contains some biological assumptions that are inappropriate for dengue but may apply to other vector-borne infections. In conclusion, we list some misgivings about modelling presented in this paper for debate.


Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT).
Obesity represents the most important single risk factor in the pathogenesis of type 2 diabetes, a disease which is characterized by a resistance to insulin-stimulated glucose uptake and a gross decompensation of systemic glucose metabolism. Despite considerable progress in the understanding of glucose metabolism, the molecular mechanisms of its regulation in health and disease remain under-investigated, while novel approaches to prevent and treat diabetes are urgently needed. Diet derived glucose stimulates the pancreatic secretion of insulin, which serves as the principal regulator of cellular anabolic processes during the fed-state and thus balances blood glucose levels to maintain systemic energy status. Chronic overfeeding triggers meta-inflammation, which leads to alterations in peripheral insulin receptor-associated signaling and thus reduces the sensitivity to insulin-mediated glucose disposal. These events ultimately result in elevated fasting glucose and insulin levels as well as a reduction in glucose tolerance, which in turn serve as important indicators of insulin resistance. Here, we present a protocol for the generation and metabolic characterization of high-fat diet (HFD)-fed mice as a frequently used model of diet-induced insulin resistance. We illustrate in detail the oral glucose tolerance test (OGTT), which monitors the peripheral disposal of an orally administered glucose load and insulin secretion over time. Additionally, we present a protocol for the insulin tolerance test (ITT) to monitor whole-body insulin action. Together, these methods and their downstream applications represent powerful tools to characterize the general metabolic phenotype of mice as well as to specifically assess alterations in glucose metabolism. They may be especially useful in the broad research field of insulin resistance, diabetes and obesity to provide a better understanding of pathogenesis as well as to test the effects of therapeutic interventions.


Early life stress triggers persistent colonic barrier dysfunction and exacerbates colitis in adult IL-10-/- mice.
It has become increasingly evident that disease flares in the human inflammatory bowel diseases are influenced by life stress. It is known that life stress can trigger disturbances in intestinal barrier function and activate proinflammatory signaling pathways, which are important contributors to intestinal inflammation and clinical disease; however, the exact mechanisms of stress-induced inflammatory bowel disease exacerbations remain to be elucidated. Here, we presented a model of early life stress-induced exacerbation of colitis in interleukin (IL)-10 mice. C57Bl/6 wild-type and IL-10 mice were exposed to neonatal maternal separation (NMS) stress on postnatal days 1 to 18 and reared under normal conditions until 10 to 12 weeks of age. At this time, histopathology, colitis scores, intestinal barrier function, proinflammatory cytokine expression, and mast cell activity were evaluated. NMS increased the severity of colitis IL-10 mice indicated by greater colitis scores and colonic proinflammatory cytokine concentrations. NMS and IL-10 increased colonic permeability; however, NMS alone did not induce colitis. Increased mast cell activation and colonic tryptase release were observed in IL-10 mice exposed to NMS, indicating mast cell activation. This study demonstrates that colitis in IL-10 mice can be exacerbated by NMS stress. The precise mechanisms of enhanced colitis severity in NMS IL10 mice are unclear but persistent defects in intestinal barrier function likely play a contributing role. NMS serves as a novel model to investigate the mechanisms by which early life stress influences the development and course of inflammatory bowel disease in adulthood.


[Macdonald Critchley].
In this paper, I review some of the writings of Macdonald Critchley with an accompanying biographical sketch. The contents of his first book, "Mirror-Writing" (1928) as well as those of "Aphasiology and other aspects of language" (1970), and his views on aphasia are presented. The book "Mirror-Writing" consists of a major review of mirror writing and related reversal phenomena. This monograph provides great insight on these symptoms, which are rare today. The ideas of Critchley on cerebral function and dysfunction (evolution and dissolution) substantially succeeded those of John Hughlings Jackson. Critchley's holistic view of aphasia is also briefly reviewed in this paper. The principal of Critchley's thoughts on neurological symptomatology is an interest in the origins of the brain, behavior, and language.


Interprofessional collaboration in the renal care settings: Experiences in the COVID-19 era.
The role of interprofessional collaboration (IPC) in healthcare is increasingly emphasized. Due to significant comorbidity in renal patients who require highly specialized procedures, proper IPC is an essential component in renal care. During the coronavirus disease 2019 (COVID-19) pandemic, the existing and proven collaboration mechanisms were put to the test. To assess IPC in the renal care settings in the era of COVID-19 pandemic. The survey consisted of the Assessment of Interprofessional Team Collaboration Scale II (AITCS-II) (3 subscales - partnership, cooperation and coordination, maximum of 5 points), questions about work conditions and factors influencing work during the pandemic, as well as demographic data. The survey was distributed in 8 renal care settings (4 hospital wards with dialysis units and 4 individual dialysis units); 127 participants filled out the survey; 26.8% of participants were physicians, 68.5% nurses and 4.7% other staff members, i.e., administrative assistants. Mean work experience in their current team was 16.8 ±11.7 years among nurses and 11.6 ±9.7 years among physicians. Interprofessional collaboration was assessed by physicians and nurses, respectively, as follows: partnership 4.03 ±0.79 compared to 3.58 ±0.73 (p = 0.003), cooperation 4.28 ±0.59 compared to 3.71 ±0.72 (p = 0.0002), and coordination 3.83 ±0.87 compared to 3.48 ±0.82 (p = 0.04). The specific workplace did not influence the IPC rates; 49.9% of physicians and 40.1% of nurses agreed or strongly agreed that the collaboration worsened during the pandemic; 47% of physicians and 42.4% of nurses admitted that the communication has significantly deteriorated. An increased level of stress, new procedures and fear of getting infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were, according to the participants, the most significant factors for the worsening of IPC. The exceptional circumstances faced during the pandemic have a significant impact on IPC, which may influence patients' satisfaction and safety. An active support for healthcare teams in the field of IPC is especially important in this challenging reality.


Positive Information of COVID-19 and Anxiety: A Moderated Mediation Model of Risk Perception and Intolerance of Uncertainty.
Although COVID-19 information has been shown to play an important role in anxiety, little is known about the mediating and moderating mechanisms underlying this relationship. In the present study, we examined whether risk perception mediated the relationship between positive information of COVID-19 and anxiety and whether this mediating process was moderated by intolerance of uncertainty. A sample of 3,341 college students participated in this study and completed questionnaires regarding positive information of COVID-19, risk perception, intolerance of uncertainty, and anxiety. The results indicated that positive information of COVID-19 was significantly and negatively associated with anxiety and that risk perception partially mediated this relationship. Intolerance of uncertainty further moderated the relationship between positive information of COVID-19 and risk perception. Specifically, the relationship between positive information of COVID-19 and risk perception was significant for college students with low intolerance of uncertainty, while it became weaker for those with high intolerance of uncertainty.


Comparison of the in vitro sperm penetration test using human cervical mucus and bovine estrus cervical mucus with the postcoital test.
The objective of this study was to determine how well bovine estrus cervical mucus could be substituted for human cervical mucus in the in vitro sperm penetration test (SPT) and how well the SPT compares with the postcoital test (PCT). The subjects were couples chosen at random from our infertility clinic population. The complete infertility evaluation of these couples included a PCT performed at the time of anticipated ovulation. Human cervical mucus quality was assessed using a scoring system which evaluated amount, spinnbarkeit, ferning, viscosity, and cellularity. SPT's were performed in flat capillary tubes filled with cervical mucus and exposed to semen samples for 90 minutes. Thirty-five couples had SPT's performed with wife's mucus and bovine mucus. Test results showed that PCT results correlated significantly with the SPT (P 0.02) but r was low (r = 0.37). The cervical mucus score correlated well with the SPT (P 0.001, r = 0.52) but less well with the PCT (P 0.03, r = .30). It is concluded that the SPT performed with either wife's mucus or bovine mucus is not an adequate substitute for the PCT but provides complementary information.


Long-term effects of n-3 fatty acids on serum lipids and glycaemic control.
The long-term influence of n-3 polyunsaturated fatty acids (n-3 PUFAs) on serum lipids and glucose homeostasis was studied in a group of non-diabetic, moderately hypertriglyceridaemic patients undergoing coronary artery bypass grafting. They were investigated according to the same procedure before and 6 months after the operation. Following randomization postoperatively, 28 patients received 3.4 g eicosapentaenoic and docosahexaenoic acid per day, whereas 29 patients comprised the control group. The decline in serum triglycerides after 6 months was significantly greater in the n-3 PUFA group than in the control group (median decline, -33.2% vs. -11.1%, p = 0.002), while no group difference was noted in serum total, HDL, or LDL cholesterol levels. Fasting plasma glucose levels decreased less in the n-3 PUFA group compared with the control group (median change, -0.2 mmol l-1 vs. -0.5 mmol l-1, p = 0.054). The corresponding changes in fasting insulin levels were -2 mIU ml-1 in the n-3 PUFA group and no change in the control group (p = 0.039). In both groups combined, the recorded changes in serum triglyceride and serum insulin levels were negatively correlated with the change in serum phospholipid n-3 fatty acids (r = -0.35, p = 0.008 and r = -0.32, p = 0.016, respectively). An oral glucose tolerance test revealed no significant group differences after 6 months, neither in the peak levels, nor in the areas under the curves between 0 and 3h after the glucose load for glucose, insulin, and C-peptide.(ABSTRACT TRUNCATED AT 250 WORDS)


Highly sensitive and multiplexed analysis of CpG methylation at single-base resolution with ligation-based exponential amplification.
DNA methylation is a primary epigenetic mechanism for transcriptional regulation during normal development and the occurrence of diseases, including cancers. DNA methylation has been increasingly utilized as a biomarker for cancer detection and differential diagnosis. Generally, one type of cancer is associated with several CpG methylation sites and detection of multiplexed CpG methylation can greatly improve the accuracy of cancer diagnosis. In this paper, we have developed a novel ligase chain reaction (LCR)-based method for multiplexed detection of CpG methylation in genomic DNA at single-base resolution. By rationally designing the two pairs of DNA probes for LCR, the bisulfite-treated methylated DNA target can be exponentially amplified by thermal cycling of the ligation reaction, in which one-base mismatch can be discriminated against, and thus high sensitivity and specificity for the detection of DNA methylation can be achieved. The LCR-based method can accurately determine as low as 10 aM methylated DNA fragment and 10 ng methylated genomic DNA. 0.1% methylated DNA can be detected in the presence of a large excess of unmethylated DNA. Moreover, by simply encoding one of the DNA probes in the LCR with a different length of poly(A) for detection of methylation at different CpG sites, the CpG methylation at different sites can produce LCR products with different lengths, and thus, can be simultaneously detected with one-tube LCR amplification and separation by capillary electrophoresis.


Contractility of single cardiomyocytes differentiated from pluripotent stem cells depends on physiological shape and substrate stiffness.
Single cardiomyocytes contain myofibrils that harbor the sarcomere-based contractile machinery of the myocardium. Cardiomyocytes differentiated from human pluripotent stem cells (hPSC-CMs) have potential as an in vitro model of heart activity. However, their fetal-like misalignment of myofibrils limits their usefulness for modeling contractile activity. We analyzed the effects of cell shape and substrate stiffness on the shortening and movement of labeled sarcomeres and the translation of sarcomere activity to mechanical output (contractility) in live engineered hPSC-CMs. Single hPSC-CMs were cultured on polyacrylamide substrates of physiological stiffness (10 kPa), and Matrigel micropatterns were used to generate physiological shapes (2,000-µm(2) rectangles with length:width aspect ratios of 5:1-7:1) and a mature alignment of myofibrils. Translation of sarcomere shortening to mechanical output was highest in 7:1 hPSC-CMs. Increased substrate stiffness and applied overstretch induced myofibril defects in 7:1 hPSC-CMs and decreased mechanical output. Inhibitors of nonmuscle myosin activity repressed the assembly of myofibrils, showing that subcellular tension drives the improved contractile activity in these engineered hPSC-CMs. Other factors associated with improved contractility were axially directed calcium flow, systematic mitochondrial distribution, more mature electrophysiology, and evidence of transverse-tubule formation. These findings support the potential of these engineered hPSC-CMs as powerful models for studying myocardial contractility at the cellular level.


Human dendritic cells respond to Helicobacter pylori, promoting NK cell and Th1-effector responses in vitro.
Helicobacter pylori infection leads to chronic gastric inflammation. The current study determined the response of human APCs, NK cells, and T cells toward the bacteria in vitro. Human monocyte-derived dendritic cells (DC) were incubated with bacteria for 48 h. Intact H. pylori at a multitude of infection 5 stimulated the expression of MHC class II (4- to 7-fold), CD80, and CD86 B7 molecules (10- to 12-fold) and the CD83 costimulatory molecule (>30-fold) as well as IL-12 secretion (>50-fold) in DCs, and thereby, strongly induced their maturation and activation. CD56(+)/CD4(-) NK cells, as well as CD4(+)/CD45RA(+) naive T cells, were isolated and incubated with DCs pulsed with intact bacteria or different cellular fractions. Coculture of H. pylori-pulsed DCs with NK cells strongly potentiated the secretion of TNF-alpha and IFN-gamma. Coculture of naive T cells with H. pylori-pulsed DCs significantly enhanced TNF-alpha, IFN-gamma, and IL-2 secretion as well as T-bet mRNA levels, while GATA-3 mRNA was lowered. However, the effect appeared attenuated compared with coculture with Escherichia coli. A greater stimulation was seen with naive T cells and DCs pulsed with H. pylori membrane preparations. Intact H. pylori potently induced the maturation and activation of human monocyte-derived DC and thereby promote NK and Th1 effector responses. The strong activation of NK cells may be important for the innate immune response. Th1-polarized T cells were induced especially by incubation with membrane preparations of H. pylori, suggesting that membrane proteins may account for the specific adaptive immune response.


Prevalence and Mortality of Moose (Alces alces) Infected with Elaeophora schneideri in Montana, USA.
Elaeophora schneideri is a filarial nematode of North America that occasionally infects aberrant ruminant hosts such as moose (Alces alces). The role E. schneideri plays in clinical morbidity or mortality of moose remains uncertain. We sampled predominantly hunter-killed adult moose (n=127) to characterize the spatial patterns of prevalence and intensity of worms in carotid arteries of moose in Montana. We compared prevalence and intensity of E. schneideri within these moose to a separate sample of adult moose that died of health-related causes (n=34). We found lower prevalence in northwest Montana (0.06) than in the remainder of the state (0.42). We also found both higher prevalence of E. schneideri and higher intensity to be correlated with increased probability of health-related mortality. Our results suggest presence and intensity of E. schneideri correlate with mortality of moose, although the mechanisms of mortality remain uncertain.


Time to Long-Acting Reversible Contraceptive Uptake Over Twelve Months Postpartum: Findings of the Yam Daabo Cluster Randomized-Controlled Trial in Burkina Faso and the Democratic Republic of the Congo.
An earlier adoption of contraceptive methods during the postpartum period could help women to extend the inter-pregnancy interval. This article aimed to determine and compare the timing of long-acting reversible contraceptives (LARC) use (ie, intrauterine device and implant) in Burkina Faso (BF) and DR Congo (DRC) between the intervention and control groups. A total of 1120 postpartum women were enrolled and followed up to 12 months postpartum. We used Yam-Daabo trial data which was a multi-intervention, single-blinded, cluster-randomised controlled trial done in primary health-care centres (clusters) in both countries. Centres were randomly allocated to receive the six-component intervention or standard antenatal and postnatal care in matched pairs (1:1). We did a secondary analysis using Royston-Parmar's semi-parametric model to estimate the effect of the interventions on the median time of LARC uptake. Our analysis included 567 postpartum women in BF (284 in the intervention group and 283 in the control group) and 553 in the DRC (274 in the intervention group and 279 in the control group). After showing an increase in family planning use in these two African countries, Yam Daabo's interventions showed a reduction of the median time of LARCs adoption in the intervention group compared to the control group in both countries (difference of 39 days in Burkina Faso; difference of 86 days in the DR Congo). The Yam Daabo intervention package resulted in increased and earlier adoption of LARC in rural settings in Burkina Faso and urban settings in DR Congo. Such an intervention could be relevant in similar contexts in Sub-Saharan Africa with very high fertility rates and high unmet needs for contraception.


Production of BP178, a derivative of the synthetic antibacterial peptide BP100, in the rice seed endosperm.
BP178 peptide is a synthetic BP100-magainin derivative possessing strong inhibitory activity against plant pathogenic bacteria, offering a great potential for future applications in plant protection and other fields. Here we report the production and recovery of a bioactive BP178 peptide using rice seeds as biofactories. A synthetic gene encoding the BP178 peptide was prepared and introduced in rice plants. The gene was efficiently expressed in transgenic rice under the control of an endosperm-specific promoter. Among the three endosperm-specific rice promoters (Glutelin B1, Glutelin B4 or Globulin 1), best results were obtained when using the Globulin 1 promoter. The BP178 peptide accumulated in the seed endosperm and was easily recovered from rice seeds using a simple procedure with a yield of 21 μg/g. The transgene was stably inherited for at least three generations, and peptide accumulation remained stable during long term storage of transgenic seeds. The purified peptide showed in vitro activity against the bacterial plant pathogen Dickeya sp., the causal agent of the dark brown sheath rot of rice. Seedlings of transgenic events showed enhanced resistance to the fungal pathogen Fusarium verticillioides, supporting that the in planta produced peptide was biologically active. The strategy developed in this work for the sustainable production of BP178 peptide using rice seeds as biofactories represents a promising system for future production of peptides for plant protection and possibly in other fields.


Staff members' beliefs about seclusion and restraint in child psychiatric hospitals.
Staff members beliefs about seclusion and restraint are influential in determining how and when these interventions are employed. Yet there are few studies of staff beliefs in individual hospitals and no comparative studies across hospitals. To measure staff members' beliefs about the rationale for and efficacy of the use of seclusion and restraint with children and adolescents. A survey of staff members (N = 320) from 13 public and private child psychiatric hospitals. Results indicate a low to moderate level of confidence among all staff groups regarding the efficacy of seclusion and restraint. Staff members from private hospitals were significantly more positive in their assessment of these interventions than were staff members from the public sector. We hypothesize that the persistent use of coercive interventions in which staff have a low level of confidence reflect both the influence of tradition in the management of aggressive behavior and unacknowledged avoidant/coercive staff responses to patents labeled as deviant. Differences between the public and private sectors and between hospitals within each sector imply that the practice of seclusion and restraint may be idiosyncratic to each institution, and suggest the need for a generally accepted standard for their use.


The diagnostic accuracy of lung auscultation in adult patients with acute pulmonary pathologies: a meta-analysis.
The stethoscope is used as first line diagnostic tool in assessment of patients with pulmonary symptoms. However, there is much debate about the diagnostic accuracy of this instrument. This meta-analysis aims to evaluate the diagnostic accuracy of lung auscultation for the most common respiratory pathologies. Studies concerning adult patients with respiratory symptoms are included. Main outcomes are pooled estimates of sensitivity and specificity with 95% confidence intervals, likelihood ratios (LRs), area under the curve (AUC) of lung auscultation for different pulmonary pathologies and breath sounds. A meta-regression analysis is performed to reduce observed heterogeneity. For 34 studies the overall pooled sensitivity for lung auscultation is 37% and specificity 89%. LRs and AUC of auscultation for congestive heart failure, pneumonia and obstructive lung diseases are low, LR- and specificity are acceptable. Abnormal breath sounds are highly specific for (hemato)pneumothorax in patients with trauma. Results are limited by significant heterogeneity. Lung auscultation has a low sensitivity in different clinical settings and patient populations, thereby hampering its clinical utility. When better diagnostic modalities are available, they should replace lung auscultation. Only in resource limited settings, with a high prevalence of disease and in experienced hands, lung auscultation has still a role.


Rotavirus as an aetiological organism in acute watery diarrhoea in Delhi children: reappraisal of clinical and epidemiological characteristics.
Four-hundred children below 3 years of age with acute watery diarrhoea were studied over a 12-month period for detection of rotavirus (RV) antigen in the stool samples. Detection of RV antigen in the cases has been compared with 175 age-matched non-diarrhoea controls. Overall positivity for detection of RV antigen was 6 per cent which is much lower than earlier studies. Even during the peak season the RV antigen detection was positive only in 13 per cent cases. However, RV antigen detection was significantly higher in cases than in the controls (P < 0.05). No significant correlation was noticed between the detection of RV antigen in the stool and environmental temperature, rainfall, and relative humidity except for higher percentage of RV antigen detection between February and April. Clinical profile of cases with RV antigen-positive stools has been compared with RV antigen-negative controls. Preceding history of vomiting and respiratory symptoms were noticed in higher percentage of RV antigen-positive cases, but no reliable 'clinical predictor' could be identified to differentiate RV diarrhoea from non-RV diarrhoea. Presence or absence of fecal polymorphonuclear leucocytes do not seem to rule out or suggest RV diarrhoea.


A new norsesquiterpene from Hainan soft coral Sinularia sp.
A new norsesquiterpene, sinunorcaryophyllenol (1), together with four known related terpenoids (2-5) have been isolated from Hainan soft coral Sinularia sp. The structure of the new compound was elucidated on the basis of detailed spectroscopic data analysis and by comparison with related model compounds.


Subcostal loculated pleural effusion in congestive heart failure: an unusual case of vanishing tumor.
Localized collection of fluid in an interlobar fissure as a consequence of congestive heart failure is a well-known entity. It has been termed vanishing tumor because of its appearance as a mass lesion in the lung and its propensity to resolve with diuretic therapy. We report a case of loculated pleural effusion in the subcostal pleural space without interlobar fluid collection. This was initially thought to represent an occult metastatic malignancy; however, the cause of the density became obvious when it disappeared with therapy of heart failure and recurred concurrent with cardiac decompensation. Loculated pleural effusion must be included in the differential diagnosis of roentgenographic densities in the chest when seen in subcostal as well as in interlobar locations.


Testosterone and 5 alpha-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines.
Androgens are of biological and clinical importance for the growth and development of breast cancer in women, and the androgen receptor (AR) has been shown to be a predictor of tumor differentiation. In the present study, we investigated the relationship between AR status and testosterone and 5 alpha-dihydrotestosterone (DHT)-dependent proliferation of the human breast carcinoma cell lines MCF-7, T47-D, MDA-MB 435S and BT-20. AR status was studied by means of immunocytochemistry and Western blot analysis. All four cell lines stained positively for AR. Western blot analysis revealed a strong expression of AR in MCF-7, in contrast to BT-20 cells. According to proliferation kinetics, we observed a significant (p < or = 0.05) dose-dependent inhibition of cell growth by testosterone and DHT treatment in all four cell lines. In the estrogen receptor (ER)-negative cell lines BT-20 and MDA-MB 435S, testosterone was a more potent inhibitor of cell proliferation than DHT (p < or = 0.05), in contrast to the ER-positive cells lines MCF-7 and T47-D, in which a stronger inhibition of proliferation was achieved by DHT. A partial transformation of testosterone to estrogen in ER-positive cells might be an explanation for this effect. Our data favor a possible role of androgens in growth regulation of breast cancer. Clinical studies are needed to analyze the importance of AR as a possible predictor in response to endocrine therapy of breast cancer.


Polycystic disease of the kidney. Evaluation and classification based on nephron segment and cell-type specific markers.
The usefulness of various segment and cell-type specific antibody, lectin and functional markers in the study of cystic renal lesions was evaluated. For this purpose, kidneys from recessive polycystic kidney disease (RPKD), thought to involve mainly the collecting ducts, and cystic kidneys of Meckel's syndrome (MS), which show dilation randomly along the nephron, were studied. The segment (and differentiation-stage)-specific anti-brush-border (specific for proximal tubules) antibodies stained morphologically normal proximal tubules, failed to react with cyst wall epithelium in RPKD, but readily stained some cysts in MS. Immunostaining for Tamm-Horsfall glycoprotein (distal tubules) similarly revealed normal tubular profiles, and also stained moderately dilated tubules, but not the large cysts in either disease type. Lectin markers of the distal tubules and collecting ducts (peanut agglutinin, Helix pomatia agglutinin and Dolichos biflorus agglutinin) reacted with both dilated tubules and with the cyst walls in RPKD and Meckel kidneys, suggesting that in RPKD, the dilations also occur in the distal nephron in addition to the collecting duct, and in MS in any part of the renal tubule. The cell type-specific functional marker of the collecting duct, anti-NaK-ATPase reactivity (found in principal cells) could be seen in RPKD but not in Meckel kidney cysts, suggesting a minor involvement of principal cells in MS. Consistent with this, only occasional carbonic anhydrase (found in intercalated cells) or band 3 (bicarbonate-chloride exchanger molecule of intercalated cells) of collecting ducts positive cells in the cysts could be seen, suggesting that intercalated cells are only sparsely seen in these lesions. The results show the usefulness of a panel of independent markers in studying the segment, cell-type and function-specific features of renal cystic lesions as a basis for their classification.


Dynamic confirmation of fixation techniques of the tibial tubercle osteotomy.
The tibial tubercle osteotomy is gaining popularity for revision total knee arthroplasty; however, the potential for tubercle displacement has been a concern. This study compared the mechanical behavior of the tibial tubercle osteotomy after screw and cerclage wire fixation. Tibial tubercle osteotomy was done on 40 tibias from cadavers with equal numbers fixed by either screws or wires. Specimens were loaded cyclically to simulate straight leg raises and then loaded to failure with the patellar tendon oriented 0 degrees or 25 degrees from the tibial axis. Tibial tubercle osteotomy cyclic displacement was greater for wire constructs at 25 degrees than all other constructs. Failure loads were greater for screw constructs at 25 degrees than both wire constructs. Screw constructs failed at 1429 +/- 348 N (0 degrees) and at 1925 +/- 982 N (25 degrees). Wire constructs failed at 1072 +/- 260 N (0 degrees) and at 893 +/- 293 N (25 degrees). Bone mineral density correlated positively with failure loads. Straight leg raise (400 N) and knee extension (250 N) against gravity during rehabilitation should be feasible with either screw or wire fixation after tibial tubercle osteotomy. Special care should be taken for the large patient and patients with decreased bone density.


[Fibrinolytic peptidases of Bacillus].
The fibrinolytic enzymes are peptidases, which belong to the class of hydrolytic enzymes. They are able to dissolve the insoluble fibrin. This review presents the fibrinolytic peptidases of Bacillus. The methods of increasing biosynthesis of these enzymes, determination of their activity, isolation and purification have been observed. The fibrinolytic peptidases of Bacillus are serine- and metallopeptidases. Its can hydrolyze both the natural substrates (fibrin, fibrinogen and hemoglobin) and synthetic substrates. The high stability of these enzymes in a wide range of pH (5-12) and temperature (10-75 degrees C) permits using them in pharmacology, medicine for the prevention and treatment of cardiovascular diseases.


Exome array analysis identifies CAV1/CAV2 as a susceptibility locus for intraocular pressure.
Intraocular pressure (IOP) is an important clinical parameter in the evaluation of ocular health. Elevated IOP is a major risk factor for primary open-angle glaucoma (POAG). The goal of this study was to identify rare and less common variants that influence IOP. We performed an exome array analysis in a subset of 1660 individuals from a population-based cohort, the Beaver Dam Eye Study. Associations with IOP were tested on 45,849 single nucleotide variants and 12,390 autosomal genes across the genome. Intraocular pressure was suggestively associated with novel variants located in FAR2 at 12p11.22 (rs4931170, P = 1.2 × 10(-5)), in GGA3 at 17q25.1 (rs52809447, P = 6.7 × 10(-5)), and in PKDREJ at 22q13.31 (rs7291444, P = 7.4 × 10(-5)). Gene-based analysis found suggestive associations between IOP and the genes HAP1, MTBP, FREM3, and PHF12. We successfully replicated the associations with GAS7 (P = 7.4 × 10(-3)) for IOP, and also identified a previously reported POAG locus in the CAV1/CAV2 region to be associated with IOP (P = 3.3 × 10(-3)). This association was confirmed in a meta-analysis with three published genome-wide association studies (Pcombined = 4.0 × 10(-11)). Our results suggest that novel genetic variants and genes with multiple, less common variants may play a role in the control of IOP. The implication of the caveolin genes, CAV1/CAV2, as a common genetic factor influencing both IOP variations and POAG may provide new insights of the underlying mechanism leading to glaucoma and glaucomatous visual field loss.


Prognosis in hypoxic ischemic encephalopathy.
A retrospective review of survivors of cardiopulmonary arrest included 56 patients. Twenty two had a good outcome and thirty four were seriously impaired. Depth and duration of post arrest coma correlated significantly with poor neurologic outcome. Seventy percent of the seriously impaired patients never regained consciousness and non emerged from coma within five days; all of the patients with good outcome were alert within twenty hours after resuscitation. Coma, motor unresponsiveness, absent brainstem reflexes were closely associated with dismal prognosis for neurologic outcome. This study cannot provide a basis for discontinuation of life support at any specific time.


Gender Dsyphoria and Psychiatric Disorders in Children and Adolescents with Congenital Adrenal Hyperplasia.
Gender identity, psychosexual function, psychiatric adjustment and quality of life have been investigated in congenital adrenal hyperplasia(CAH) patients. We aimed to investigate gender identity problems and the psychiatric disorders and associated factors in children and adolescents with CAH patients. Forty-five children and adolescents with CAH were included in the study. Psychiatric comorbidity was assessed using the Schedule for Affective Disorders and Schizophrenia for School Age Children - Present and Lifetime Version. Gender identity problems were investigated using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. The mean age of the sample was 11.02 years (SD: 3.25, range: 6-18). 51.1% of the patients had at least one lifetime comorbid psychiatric disorder. The most common diagnoses were anxiety disorders, attention deficit hyperactivity disorder(ADHD), tic disorders and enuresis nocturna. Tic disorders and ADHD were higher in males but they were not statistically significant. Two female patients were diagnosed with gender dysphoria and 18.5% of females showed variably masculinized behaviors. The girls with gender identity problems expressed lower satisfaction with their sex than other girls and boys. Children and adolescents with CAH had many psychiatric disorders, especially neurodevelopmental disorders. ADHD and tic disorders should be kept in mind during assessment especially in male patients. Gender dysphoria and masculine behaviors seem to be common in female patients with CAH so they should be carefully investigated.


Blockade of transforming growth factor-beta-activated kinase 1 activity enhances TRAIL-induced apoptosis through activation of a caspase cascade.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) is a member of the TNF-alpha ligand family that selectively induces apoptosis in a variety of tumor cells. To clarify the molecular mechanism of TRAIL-induced apoptosis, we focused on transforming growth factor-beta-activated kinase 1 (TAK1) mitogen-activated protein kinase (MAPK) kinase kinase, a key regulator of the TNF-alpha-induced activation of p65/RelA and c-Jun NH2-terminal kinase/p38 MAPKs. In human cervical carcinoma HeLa cells, TRAIL induced the delayed phosphorylation of endogenous TAK1 and its activator protein TAB1 and TAB2, which contrasted to the rapid response to TNF-alpha. Specific knockdown of TAK1 using small interfering RNA (siRNA) abrogated the TRAIL-induced activation of p65 and c-Jun NH2-terminal kinase/p38 MAPKs. TRAIL-induced apoptotic signals, including caspase-8, caspase-3, caspase-7, and poly(ADP-ribose) polymerase, were enhanced by TAK1 siRNA. Flow cytometry showed that the binding of Annexin V to cell surface was also synergistically increased by TRAIL in combination with TAK1 siRNA. In addition, pretreatment of cells with 5Z-7-oxozeaenol, a selective TAK1 kinase inhibitor, enhanced the TRAIL-induced cleavage of caspases and binding of Annexin V. The TAK1-mediated antiapoptotic effects were also observed in human lung adenocarcinoma A549 cells. In contrast, TAK1-deficient mouse embryonic fibroblasts are resistant to TRAIL-induced apoptosis, and treatment of control mouse embryonic fibroblasts with 5Z-7-oxozeaenol did not drastically promote the TRAIL-induced activation of a caspase cascade. These results suggest that TAK1 plays a critical role for TRAIL-induced apoptosis, and the blockade of TAK1 kinase will improve the chances of overcoming cancer.


Insights into the cellular pharmacokinetics and pharmacodynamics of thiopurine antimetabolites in a model of human intestinal cells.
Thiopurines, immunomodulating drugs used in the management of different chronic autoimmune conditions and as anti-leukemic agents, may exert in some cases gastrointestinal toxicity. Moreover, since these agents are administered orally, they are absorbed across the gastrointestinal tract epithelium. On these premises, cellular and molecular events occurring in intestinal cells may be important to understand thiopurine effects. However, quantitative information on the biotransformation of thiopurines in intestinal tissues is still limited. To shed light on biotransformation processes specific of the intestinal tissue, in this study thiopurine metabolites concentrations were analyzed by an in vitro model of human healthy colon, the HCEC cell line, upon exposure to cytotoxic concentrations of azathioprine or mercaptopurine; the investigation was carried out using an innovative mass spectrometry method, that allowed the simultaneous quantification of 11 mono-, di-, and triphosphate thionucleotides. Among the 11 metabolites evaluated, TIMP, TGMP, TGDP, TGTP, MeTIMP, MeTIDP and MeTITP were detectable in HCEC cells treated with azathioprine or mercaptopurine, considering two different incubation times before the addition of the drugs (4 and 48 h). Different associations between metabolites concentrations and cytotoxicity were detected. In particular, the cytotoxicity was dependent on the TGMP, TGDP, TGTP and MeTITP concentrations after the 4 h incubation before the addition of thiopurines. This may be an indication that, to study the association between thiopurine metabolite concentrations and the cytotoxicity activity in vitro, short growth times before treatment should be used. Moreover, for the first time our findings highlight the strong correlation between cytotoxicity and thiopurine pharmacokinetics in HCEC intestinal cells in vitro suggesting that these cells could be a suitable in vitro model for studying thiopurine intestinal cytotoxicity.


William's Portrait and Community Narrative.
This article describes one collaborative arts-based research project. Portrait artist Mark Gilbert considers lessons for art and healing from one patient, William, whose cancer and portraiture experiences illuminate reflection as a critical component of both a sitter's and an artist's coassembly of visual narrative and community.


Auramine O, an incense smoke ingredient, promotes lung cancer malignancy.
Burning incense to worship deities is a popular religious ritual in large parts of Asia, and is a popular custom affecting more than 1.5 billion adherents. Due to incomplete combustion, burning incense has been well recognized to generate airborne hazards to human health. However, the correlation between burning incense and lung cancer in epidemiological studies remains controversy. Therefore, we speculated that some unknown materials in incense smoke are involved in the initiation or progression of lung cancer. Based on this hypothesis, we identified a major compound auramine O (AuO) from the water-soluble fraction of incense burned condensate using mass spectrometry. AuO is commonly used in incense manufacture as a colorant. Due to thermostable, AuO released from burned incenses becomes an unexpected air pollutant. AuO is classified as a Group 2B chemical by the International Agency of Research on Cancer (IARC), however, the damage of AuO to the respiratory system remains elusive. Our study revealed that AuO has no apparent effect on malignant transformation; but, it dramatically promotes lung cancer malignancy. AuO accumulates in the nucleus and induces the autophagy activity in lung tumor cells. AuO significantly enhances migration and invasive abilities and the in vitro and in vivo stemness features of lung tumor cells through activating the expression of aldehyde dehydrogenase family 1 member A1 (ALDH1A1), and ALDH1A1 knockdown attenuates AuO-induced autophagy activity and blocks AuO-induced lung tumor malignancy. In conclusion, we found that AuO, an ingredient of incense smoke, significantly increases the metastatic abilities and stemness characters of lung tumor cells through the activation of ALDH1A1, which is known to be associated with poor outcome and progression of lung cancer. For public health, reducing or avoiding the use of AuO in incense is recommended.


Ovariectomy eliminates sex differences in rat tail artery response to adrenergic nerve stimulation.
The influence of gonadal hormones on vasoconstrictor responses to adrenergic nerve stimulation was investigated by comparing tail arteries from intact and gonadectomized male and female Fisher 344 rats. Arterial ring segments from females were significantly less responsive to transmural nerve stimulation (1-8 Hz) than arteries from age-matched males. Significant male-female differences persisted after correcting the contractile responses for sex-related differences in arterial mass, optimal resting tension, and maximal contractile force. Arteries were taken from cycling, intact females in either proestrus, estrus, metestrus, or diestrus, but no significant differences were found among the four stages for vasoconstrictor responses to either adrenergic nerve stimulation or exogenous norepinephrine. These data suggest adrenergic function in the artery is not affected by hormonal variations during the estrous cycle. After bilateral ovariectomy, however, contractile responses of female arteries to adrenergic nerve stimulation were increased to levels similar to those observed in male arteries. Orchidectomy of males, in contrast, had no effect on neural-evoked contraction. Low concentrations of norepinephrine also produced greater contractile responses in male compared with female arteries; however, this sex-related difference was eliminated by orchidectomy but not ovariectomy. Taken together, the results indicate that circulating gonadal hormones contribute to gender differences observed in rat tail artery. Vasoconstrictor responses to exogenous norepinephrine appear to be enhanced by testicular hormones. In contrast, vasoconstriction induced by adrenergic nerve stimulation appears to be influenced by chronic exposure to circulating ovarian hormones, resulting in a smaller vascular response in female arteries.


Heavy Metal Contamination Alters the Co-Decomposition of Leaves of the Invasive Tree Rhus typhina L. and the Native Tree Koelreuteria paniculata Laxm.
Invasive and native plants can coexist in the same habitat; however, the decomposition process may be altered by the mixing of invasive and native leaves. Heavy metal contamination may further alter the co-decomposition of both leaf types. This study evaluated the effects of two concentrations (35 mg·L-1 and 70 mg·L-1) and three types (Pb, Cu, and combined Pb + Cu) of heavy metal contamination on the co-decomposition of leaves of the invasive tree Rhus typhina L. and the native tree Koelreuteria paniculata Laxm, as well as the mixed effect intensity of the co-decomposition of the mixed leaves. A polyethylene litterbag experiment was performed over six months. The decomposition coefficient of the two trees, mixed effect intensity of the co-decomposition, soil pH and enzymatic activities, soil bacterial alpha diversity, and soil bacterial community structure were determined. A high concentration of Pb and combined Pb + Cu significantly reduced the decomposition rate of R. typhina leaves. A high concentration of Pb or Cu significantly reduced the decomposition rate of the mixed leaves. In general, R. typhina leaves decomposed faster than K. paniculata leaves did. There were synergistic effects observed for the co-decomposition of the mixed leaves treated with combined Pb + Cu, regardless of concentration, but there were antagonistic effects observed for the co-decomposition of the mixed leaves treated with either Pb or Cu, regardless of concentration. A high concentration of Pb or Cu may increase antagonistic effects regarding the co-decomposition of mixed-leaf groups. Thus, heavy metal contamination can significantly affect the intensity of the mixed effect on the co-decomposition of heterogeneous groups of leaves.


Ross procedure.
In 1967 Donald Ross introduced the subcoronary Ross procedure consisting of transplantation of the autologous pulmonary valve into aortic position. We describe our 15-year experience in Ross procedures. 576 subcoronary operations have been performed (436 male and 140 female patients); the mean age was 45±11.9 years. (range, 13 to 70 years). The mean follow-up was 7±4.2 years (range, 0 to 16 years). There were 4597 patient years at follow-up with a clinical completeness of 95% and echo completeness of 91%. There were two operative deaths (0.3%) and 31 patients with reoperation. The survival is similar to that of the normal population and the freedom from allo- and autograft reoperation is 87% at 15 years. Autograft regurgitation at last examination was grade 0 in 40%, trace in 54%, grade I in 19%, grade II in 4% and grade III in 0.4%; the pressure gradient was smaller than 5 mmHg in 57% and between 5 and 10 mmHg in 24%. Only 6% had a transvalvular pressure gradient of more than 10 mmHg. After 15 years of experience it can be concluded that the subcoronary technique provides near normal survival in adult patients, with excellent hemodynamics and acceptable rate of reoperations.


EVOLUTION OF DRIVING X CHROMOSOMES AND RESISTANCE FACTORS IN EXPERIMENTAL POPULATIONS OF DROSOPHILA SIMULANS.
Sex-ratio drive is a particular case of meiotic drive, described in several Drosophila species, that causes males bearing driving X chromosome to produce a large excess of females in their progeny. In Drosophila simulans, driving X chromosomes and resistance factors located on the Y chromosome and on the autosomes have been previously reported. In this paper, we report the study of the dynamics of sex-ratio factors in experimental populations. We followed the evolution in frequency of driving X chromosomes in the absence of resistance factors and the evolution of resistance factors in the presence of driving X chromosomes. The driving X chromosome was lost, contrarily to theoretical expectations that predict its rapid invasion. Autosomal resistances increased in frequency, and resistant Y chromosomes invaded the population very quickly, as predicted by theoretical models. Fitness measurements showed that the loss of the driving X chromosome was due to a strong deleterious effect that was expressed only when distorting males were in competition with standard males. However, the spread of autosomal resistances reduced this deleterious effect. Implications for the maintenance of polymorphism in natural populations are discussed.


Incidence and outcome of osteoporotic fractures in 2004 in Sado City, Niigata Prefecture, Japan.
Osteoporotic fracture in elderly populations is increasing worldwide, but there are few data on the incidence and outcome of osteoporotic fractures, including upper extremity and vertebral fracture, during a certain period in a defined geographic area. The purpose of this study was to determine the incidence of osteoporotic fractures in a particular area: Sado City, Niigata Prefecture, Japan. From January to December 2004, osteoporotic fractures of the vertebra, hip, distal radius, and proximal humerus in Sado City were recorded. The incidence, age, gender, type of fracture (for hip fracture), right or left side (for distal radius, proximal humerus, and hip fracture), place of injury, cause of injury, outcome, hospitalization period, and patient status regarding taking of drugs for osteoporosis treatment were checked for each fracture. The incidence was calculated based on the whole population of Sado City. The incidence per 100,000 population was 232.8, 121.4, 108.6, and 37.1 for fractures of the vertebra, hip, distal radius, and proximal humerus, respectively. The total incidence of these four kinds of fracture was 499.9 per 100,000 persons per year. The average age at the time of injury was 81.4, 77.7, 75.7, and 60.2 years old for fractures of the hip, vertebra, proximal humerus, and distal radius, respectively. As the average age increased, the percentage of fractures that occurred indoors also increased; that is, a higher percentage of hip fractures occurred indoors, followed by fractures of the vertebra, proximal humerus, and distal radius. Most patients were not taking anti-osteoporosis drugs before fractures of the hip or vertebra. We determined the incidence of major osteoporotic fractures in 1 year in a defined geographic area. Our data showed that 81% of hip fracture patients also had a vertebral fracture and that the average age at the time of injury was higher for hip fractures than for vertebral fractures. Therefore, these results suggest that vertebral fracture leads to hip fracture, indicating that early fracture prevention and continuous prevention strategies through positive treatment are of importance in osteoporotic elderly people.


Breast Cancer-Derived Exosomes Reflect the Cell-of-Origin Phenotype.
A manner in which cells can communicate with each other is via secreted nanoparticles termed exosomes. These vesicles contain lipids, nucleic acids, and proteins, and are said to reflect the cell-of-origin. However, for the exosomal protein content, there is limited evidence in the literature to verify this statement. Here, proteomic assessment combined with pathway-enrichment analysis is used to demonstrate that the protein cargo of exosomes reflects the epithelial/mesenchymal phenotype of secreting breast cancer cells. Given that epithelial-mesenchymal plasticity is known to implicate various stages of cancer progression, the results suggest that breast cancer subtypes with distinct epithelial and mesenchymal phenotypes may be distinguished by directly assessing the protein content of exosomes. Additionally, the work is a substantial step toward verifying the statement that cell-derived exosomes reflect the phenotype of the cells-of-origin.


MyKidneyCoach, Patient Activation, and Clinical Outcomes in Diverse Kidney Transplant Recipients: A Randomized Control Pilot Trial.
Kidney transplant (KT) recipients who are not actively engaged in their care and lack self-management skills have poor transplant outcomes, which are disproportionately observed among Black KT recipients. This pilot study aimed to determine whether the MyKidneyCoach app, an mHealth intervention that provides self-management monitoring and coaching, improved patient activation, engagement, and nutritional behaviors in a diverse KT population. This was a randomized, age-stratified, parallel-group, attention-control, pilot study in post-KT patients. Participants were randomized into the attention-control with access to MyKidneyCoach for education and self-management (n = 9) or the intervention with additional tailored nurse coaching (n = 7). Feasibility, acceptability, and clinical outcomes were assessed. The acceptability of MyKidneyCoach by System Usability Scale was 67.5 (95% confidence interval [CI], 59.1-75.9). Completion rates based on actively using MyKidneyCoach were 81% (95% CI, 57%-93%) and study retention rate of 73%. Patient activation measure significantly increased overall by a mean of 11 points (95% CI, 3.2-18.8). Additionally, Black patients (n = 7) had higher nutrition self-efficacy scores of 80.5 (95% CI, 74.4-86.7) compared with 75.6 (95% CI, 71.1-80.1) in non-Black patients (n = 9) but lower patient activation measure scores of 69.3 (95% CI, 56.3-82.3) compared with 71.8 (95% CI, 62.5-81) in non-Black patients after 3 mo. MyKidneyCoach was easy to use and readily accepted with low attrition, and improvements were demonstrated in patient-reported outcomes. Both Black and non-Black participants using MyKidneyCoach showed improvement in self-management competencies; thus, this intervention may help reduce healthcare inequities in KT.


Pneumopericardium as a rare complication after esophagopericardial fistula.
Pneumopericardium is a rare clinical entity which is often complicated by trauma. Pneumoperdicardium resulting after esophagopericardial fistula is much rarer. We present a case of pneumopericardium as the complication of esophagopericardial fistula in a 53-year-old man. After undergoing radiotherapy for 26 times, the patient got a fever and an unspecified thoracic pain. Echocardiography showed the rectilinear echoes in the pericardium. Chest computed tomography revealed pneumopericardium, pericardial effusion, recurrence of lung cancer, and pneumonia in right lower and left lung.


Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis.
Ankylosing spondylitis (AS) is a chronic rheumatic and autoimmune disease. Little is known about the potential role of DNA methylation in the pathogenesis of AS. This study was undertaken to explore the potential role of DNA methylation in the genetic mechanism of AS. In this study, we compared the genome-wide DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) between five AS patients and five healthy subjects, using the Illumina Infinium HumanMethylation450 BeadChip. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate the relevance of the identified differentially methylated genes for AS, using another independent sample of five AS patients and five healthy subjects. Compared with healthy controls, we detected 1915 differentially methylated CpG sites mapped to 1214 genes. The HLA-DQB1 gene achieved the most significant signal (cg14323910, adjusted P = 1.84 × 10-6, β difference = 0.5634) for AS. Additionally, the CpG site cg04777551 of HLA-DQB1 presented a suggestive association with AS (adjusted P = 1.46 × 10-3, β difference = 0.3594). qRT-PCR observed that the mRNA expression level of HLA-DQB1 in AS PBMCs was significantly lower than that in healthy control PBMCs (ratio = 0.48 ± 0.10, P < 0.001). Gene Ontology (GO) and KEGG pathway enrichment analysis of differentially methylated genes identified four GO terms and 10 pathways for AS, functionally related to antigen dynamics and function. Our results demonstrated the altered DNA methylation profile of AS and implicated HLA-DQB1 in the development of AS.


Diagnostic issues in cerebral malaria: a study of 112 adolescents and adults in Lagos, Nigeria.
To determine the accuracy of initial diagnosis of cerebral malaria in adolescents and adults presenting at our tertiary centre and identify the clinical and laboratory parameters helpful in distinguishing cerebral malaria from other differential diagnosis. A retrospective review of 112 adolescents and adults initially diagnosed as having cerebral malaria was carried out. Clinical features (risk factors, mode of presentation, clinical course and final diagnosis) and laboratory parameters (level of parasitaemia, haematologic and biochemical values) were documented. A correct diagnosis was made in 52 patients (46.4%), with septicaemia (20.5%) and meningitis (15.2%) accounting for most misdiagnosis. The majority of correctly diagnosed were aged 11-25 years (92.3%), and a predisposing factor was identifiable in 46.2%. Parasitaemia was predominantly moderate to heavy in correctly diagnosed cases, compared to those misdiagnosed in whom it was mild to moderate. Case fatality was higher for misdiagnosed cases (18.6%). The probability of an alternate diagnosis amenable to other treatment regimes should always be explored. This is particularly important in patients of middle age and those with either absent predisposing factors or mild parasitaemia, in order to reduce case fatality.