Development of the Good Health Research Practice course: ensuring quality across all health research in humans.
Quality and ethics need to be embedded into all areas of research with human participants. Good Clinical Practice (GCP) guidelines are international ethical and scientific quality standards for designing, conducting, recording and reporting trials involving human participants. Compliance with GCP is expected to provide public assurance that the rights, safety and wellbeing of participants are protected and that the clinical research data are credible. However, whilst GCP guidelines, particularly their principles, are recommended across all research types, it is difficult for non-clinical trial research to fit in with the exacting requirements of GCP. There is therefore a need for guidance that allows health researchers to adhere to the principles of GCP, which will improve the quality and ethical conduct of all research involving human participants. These concerns have led to the development of the Good Health Research Practice (GHRP) course. Its goal is to ensure that research is conducted to the highest possible standards, similar to the conduct of trials to GCP. The GHRP course provides training and guidance to ensure quality and ethical conduct across all health-related research. The GHRP course has been run so far on eight occasions. Feedback from delegates has been overwhelmingly positive, with most delegates stating that the course was useful in developing their research protocols and documents. Whilst most training in research starts with a guideline, GHRP has started with a course and the experience gained over running the courses will be used to write a standardised guideline for the conduct of health-related research outside the realm of clinical trials, so that researchers, funders and ethics committees do not try to fit non-trials into clinical trials standards.


Physical performance evaluation of a 256-slice CT-scanner for four-dimensional imaging.
We have developed a prototype 256-slice CT-scanner for four-dimensional (4D) imaging that employs continuous rotations of a cone-beam. Since a cone-beam scan along a circular orbit does not collect a complete set of data to make an exact reconstruction of a volume [three-dimensional (3D) image], it might cause disadvantages or artifacts. To examine effects of the cone-beam data collection on image quality, we have evaluated physical performance of the prototype 256-slice CT-scanner with 0.5 mm slices and compared it to that of a 16-slice CT-scanner with 0.75 mm slices. As a result, we found that image noise, uniformity, and high contrast detectability were independent of z coordinate. A Feldkamp artifact was observed in distortion measurements. Full width at half maximum (FWHM) of slice sensitivity profiles (SSP) increased with z coordinate though it seemed to be caused by other reasons than incompleteness of data. With regard to low contrast detectability, smaller objects were detected more clearly at the midplane (z = 0 mm) than at z = 40 mm, though circular-band like artifacts affected detection. The comparison between the 16-slice and the 256-slice scanners showed better performance for the 16-slice scanner regarding the SSP, low contrast detectability, and distortion. The inferiorities of the 256-slice scanner in other than distortion measurement (Feldkamp artifact) seemed to be partly caused by the prototype nature of the scanner and should be improved in the future scanner. The image noise, uniformity, and high contrast detectability were almost identical for both CTs. The 256-slice scanner was superior to the 16-slice scanner regarding the PSF, though it was caused by the smaller transverse beam width of the 256-slice scanner. In order to compare both scanners comprehensively in terms of exposure dose, noise, slice thickness, and transverse spatial resolution, K=Dsigma2ha3 was calculated, where D was exposure dose (CT dose index), sigma was magnitude of noise, h was slice thickness (FWHM of SSP), and a was transverse spatial resolution (FWHM of PSF). The results showed that the K value was 25% larger for the 16-slice scanner, and that the 256-slice scanner was 1.25 times more effective than the 16-slice scanner at the midplane. The superiority in K value for the 256-slice scanner might be partly caused by decrease of wasted exposure with a wide-angle cone-beam scan. In spite of the several problems of the 256-slice scanner, it took a volume data approximately 1.0 mm (transverse) x 1.3 mm (longitudinal) resolution for a wide field of view (approximately 100 mm long) along the zeta axis in a 1 s scan if resolution was defined by the FWHM of the PSF or the SSP, which should be very useful to take dynamic 3D (4D) images of moving organs.


Evolution of allantoinase and allantoicase involved in urate degradation in liver peroxisomes. A rapid purification of amphibian allantoinase and allantoicase complex, its subunit locations of the two enzymes, and its comparison with fish allantoinase and allantoicase.
Allantoinase and allantoicase are located in the same protein molecule in amphibian liver, whereas the two enzymes are different proteins in marine fish and invertebrate liver (Takada, Y., and Noguchi, T. (1983) J. Biol. Chem. 258, 4762-4764). The amphibian enzyme was rapidly purified from frog liver by using its following characteristics. 1) The enzyme binds to the intracellular membranes in the hypotonic solution. 2) The membrane-bound enzyme is not solubilized by the detergent. 3) The membrane-bound enzyme is solubilized by oxaloacetate. The electrophoresis of the purified enzyme gave a single protein band in the absence of sodium dodecyl sulfate, and gave two protein bands with molecular weights of 48,000 and 54,000, respectively, in the presence of sodium dodecyl sulfate. With a specific antibody raised against each subunit, allantoinase activity was found to be from the large subunit, and allantoicase activity to be from the small subunit. This amphibian allantoinase and allantoicase complex was compared with allantoinase and allantoicase purified from fish liver. Fish allantoinase was a single peptide and fish allantoicase was composed of two identical subunits. Fish allantoinase had an identical molecular weight with amphibian large (allantoinase) subunit and the subunit of fish allantoicase with amphibian small (allantoicase) subunit. These results suggest that the evolution of fish to amphibian resulted in the dissociation of allantoicase into subunits and in the association of allantoinase with allantoicase. The two enzymes are lost by further evolution.


Platelet beta-secretase activity is increased in Alzheimer's disease.
beta-Secretase activity is the rate-limiting step in Abeta peptide production from amyloid precursor protein. Abeta is a major component of Alzheimer's disease (AD) cortical amyloid plaques. beta-Secretase activity is elevated in post mortem brain tissue in AD. The current study investigated whether beta-secretase activity was also elevated in peripheral blood platelets. We developed a novel fluorimetric beta-secretase activity assay to investigate platelets isolated from individuals with AD (n=86), and age-matched controls (n=115). Platelet membrane beta-secretase activity (expressed as initial rate) varied over fourfold between individuals, raising important questions about in vivo regulation of this proteolytic activity. Nonetheless, we identified a significant 17% increase in platelet membrane beta-secretase activity in individuals with AD compared to controls (p=0.0003, unpaired t-test). Platelet membrane beta-secretase activity did not correlate with mini-mental state examination (MMSE) score in the AD group (mean MMSE=17.7, range 1-23), indicating that the increase did not occur as a secondary result of the disease process, and may even have preceded symptom onset.


Palliative care models: international perspective.
The delivery of palliative care can vary greatly between countries depending on socioeconomic conditions and cultural issues. The evolution and development of palliative care varies greatly and influences the development of palliative care models. Models of palliative care in three different countries are discussed and suggestions are made for the future development of palliative care in developing and developed countries.


New insights into steroid resistant asthma.
The term "steroid resistant (SR) asthma" refers to a group of asthmatics who have persistent airway obstruction and immune activation despite treatment with high doses of systemic glucocorticoids. There are at least two forms of SR asthma, i.e. primary and acquired types. Type I SR asthma is acquired and is associated with abnormally reduced glucocorticoid receptor (GCR) ligand and DNA binding affinity. Type II SR asthma appears to be due to a constitutive defect and is associated with low numbers of GCRs. An important distinction between these two types of SR asthma is that the GCR defect in Type I, but not Type II, SR asthma is reversible in culture and is sustained by incubation with combination IL-2 and IL-4. Recent studies suggest that the abnormal GCR binding in Type I SR asthma may be due to cytokine-driven alternative splicing of the GCR pre-mRNA to a novel isoform called GCRbeta which does not bind glucocorticoids but antagonizes the transactivating activity of the classic GCR. These GCR changes along with recent evidence for increased transcription factor activation in SR asthma which may inhibit GCR/DNA interactions as well as the selective recruitment of neutrophils into the airways of certain patients with severe asthma contribute to the heterogeneity of mechanisms underlying steroid resistance.


[Relationships between occupational exposure and cancer of the testis].
Prevalence of cancer of the testis has been increasing in recent decades. We studied risk of testicular cancer in relation to occupations and occupational exposures. A significantly increased risk of testicular cancer is associated with occupations in the agricultural, tannery and mechanical industries. Consistent associations with painting, mining, plastic and metal working, and occupational use of hand-held radar have been observed. Because of the small number of exposed subjects in some studies, results have been spurious in many cases and require further analysis.


Three-year results of visual outcome with disease activity-guided ranibizumab algorithm for the treatment of exudative age-related macular degeneration.
To evaluate 3-year follow-up treatment outcomes with ranibizumab (Lucentis(®)) 0.5 mg administered either monthly or quarterly on a pro re nata (PRN) basis according to a disease activity-guided monitoring and treatment algorithm. A total of 316 treatment-naive eyes of 316 patients with exudative age-related macular degeneration met the criteria for inclusion in this retrospective, interventional case series. Patients were treated with ranibizumab 0.5 mg according to a disease activity-guided algorithm with monthly monitoring. Optical coherence tomography and fluorescein angiography were routinely used to assess disease activity: active lesions were treated with a series of three monthly injections, whereas inactive lesions were treated with quarterly injections. Mean Early Treatment Diabetic Retinopathy Study best-corrected visual acuity improved from 52 letters at baseline to 59 letters at 12 months, achieved with a mean of 7.1 injections, 61 letters at 24 months with a mean of 5.0 injections administered in the second year and 60 letters at 36 months with a mean number of 5.2 injections. Monthly visits and a morphology-driven PRN regimen with 3 injections in case of recurrence plus quarterly injections in case of inactive CNV resulted in an average VA gain of 7-9 letters that could be maintained over 3 years.


Inflammatory pseudotumor of the spleen: US and MRI findings.
The ultrasound and color Doppler sonography characteristics of inflammatory pseudotumor (IPT) of the spleen are nonspecific, and thus preoperative diagnosis of the tumor is difficult. We describe a case of IPT of the spleen studied with ultrasound, color Doppler sonography, CT, and MRI, and we report the usefulness of US and MRI findings of the tumor.


Theories of serial flow in intergenerational transfers.
Recent improvements in the economic position of the elderly population necessitate a more thorough understanding of the serial flow of economic supports from preceding to succeeding generations. Five theories which might extend our understanding of the decision rules employed in intergenerational transfers are discussed. They are: social exchange theory, the kin selection theory of altruism, human capital theory, social constructivist theory, and rational transfers theory. The underlying assumptions of these theories are presented and compared, and models of intergenerational transactions are developed. Comparative studies are recommended in order to gain deeper insights into the relative strengths and weaknesses of these different views of relationships between the generations.


Achieving Procedural Competence during Nephrology Fellowship Training: Current Requirements and Educational Research.
Concerns have previously been raised as to whether training programs are ensuring that nephrology fellows achieve competence in the procedural skills required for independent practice. We sought to review the current requirements for procedural training as well as educational research pertaining to achieving competence in the core nephrology procedures of nontunneled (temporary) hemodialysis catheter insertion and percutaneous kidney biopsy. At this time, there is no universal approach to procedural training and assessment during nephrology fellowship. Nonetheless, simulation-based mastery learning programs have been shown to be effective in improving fellows' skills in nontunneled (temporary) hemodialysis catheter insertion and should be provided by all nephrology training programs. For percutaneous kidney biopsy, the development and evaluation of inexpensive simulators are a promising starting point for future study. Current practice with respect to procedural training during nephrology fellowship remains imperfect; however, the ongoing shift toward competency-based evaluation provides opportunities to refocus on improvement.


Highly Fluorescent Pyridinium Betaines for Light Harvesting.
We report the findings of our experimental and theoretical investigations into the properties of pyridinium enolates and their potential utility in light-harvesting applications, such as in luminescent solar concentrators (LSCs). We present the synthesis, structures, photophysical characterization, and wavefunction-based quantum-chemical studies of five cyclobetaines. The performance of an LSC device incorporating one of these cyclobetaines is shown to be comparable to state-of-the-art devices.


Computed tomography-guided transforaminal lumbar puncture using local anesthesia and a straight 22-gauge spinal needle for intrathecal nusinersen in adults: Findings in 77 procedures.
Intrathecal nusinersen is the first Food and Drug Administration-approved treatment for spinal muscular atrophy. Reliable intrathecal access is critical for initial and maintenance therapy; however, this can be challenging in older patients with spinal muscular atrophy many of whom have had prior lumbar instrumentation and osseous fusion. Transforaminal lumbar punctures have emerged as a technique for intrathecal access that avoids the hazards of cervical punctures. We describe our technique for transforaminal lumbar punctures under computed tomography guidance using local anesthesia and a straight 22-gauge needle. Following local institutional review board approval, medical records of all patients undergoing computed tomography-guided transforaminal lumbar puncture for intrathecal nusinersen injection were obtained and analyzed. The rate of technical success and immediate complications were recorded. Any delayed complications noted in a 3-day follow-up phone call and future office visit were also recorded. Data collation and analysis were performed using Excel. A total of 77 transforaminal lumbar punctures were performed with intrathecal administration of nusinersen, for a 100% technical success rate. Local anesthesia was used in 76 cases, with conscious sedation used in one case. General anesthesia was not used in any case. There were no major complications. One patient had a postdural puncture headache that resolved completely after a transforaminal epidural blood patch performed 4 days later. Intrathecal administration of nusinersen is critical for treatment of patients with spinal muscular atrophy. Our described technique allows for reliable access to the intrathecal space using local anesthesia and a straight 22-gauge spinal needle under computed tomography guidance, and is easily reproducible.


Clinical segmental pancreas transplantation without duct anastomosis in diabetic renal allograft recipients.
Segmental pancreatic allografts with unligated ducts were transplanted intraperitoneally to five diabetic patients who had received renal allografts more than 2 yr earlier. One patient is alive with a functioning graft 10.5 mo later. Two patients rejected their grafts at approximately 2 and 3 mo but are alive 8--9 mo later after resumption of exogenous insulin therapy. In both patients, carbohydrate metabolism was nearly normal during the period of graft function. Two patients died of infectious complications between 1 and 2 mo after transplantation. The main hazard of pancreas transplantation relates to the immunosuppression necessary to prevent rejection, setting the stage for infectious complications. Technically, pancreas transplantation is a feasible and efficient procedure, and, if better methods are developed for preventing rejection, it should be applicable to patients prone to develop secondary complications of diabetes.


Effects of gamma irradiation on collagen damage and remodeling.
To evaluate the dose-time dependences of structural changes occurring in collagen within 24 hours to three months after gamma-irradiation at doses from 2-40 Gy in vivo. Rat's tail tendon was chosen as in vivo model, with its highly ordered collagen structure allowing the changes to be interpreted unambiguously. Macromolecular level (I) was investigated by differential scanning calorimetry (DSC); fibers and bundles level (II) by laser scanning microscopy (LSM), and bulk tissue microstructural level (III) by cross-polarization optical coherence tomography (CP-OCT). For (I), the formation of molecular cross-links and breaks appeared to be a principal mechanism of collagen remodeling, with the cross-links number dependent on radiation dose. Changes on level (II) involved primary, secondary and tertiary bundles splitting in a day and a week after irradiation. Bulk collagen microstructure (III) demonstrated early widening of the interference fringes on CP-OCT images observed to occur in the tendon as result of this splitting. At all three levels, the observed collagen changes demonstrated complete remodeling within ∼ a month following irradiation. The time course and dose dependencies of the observed collagen changes at different levels of its hierarchy further contribute to elucidating the role of connective tissue in the radiotherapy process.


Gonad-related factors promote muscle performance gain during postnatal development in male and female mice.
To better define the role of male and female gonad-related factors (MGRF, presumably testosterone, and FGRF, presumably estradiol, respectively) on mouse hindlimb skeletal muscle contractile performance/function gain during postnatal development, we analyzed the effect of castration initiated before puberty in male and female mice. We found that muscle absolute and specific (normalized to muscle weight) maximal forces were decreased in 6-mo-old male and female castrated mice compared with age- and sex-matched intact mice, without alteration in neuromuscular transmission. Moreover, castration decreased absolute and specific maximal powers, another important aspect of muscle performance, in 6-mo-old males, but not in females. Absolute maximal force was similarly reduced by castration in 3-mo-old muscle fiber androgen receptor (AR)-deficient and wild-type male mice, indicating that the effect of MGRF was muscle fiber AR independent. Castration reduced the muscle weight gain in 3-mo mice of both sexes and in 6-mo females but not in males. We also found that bone morphogenetic protein signaling through Smad1/5/9 was not altered by castration in atrophic muscle of 3-mo-old mice of both sexes. Moreover, castration decreased the sexual dimorphism regarding muscle performance. Together, these results demonstrated that in the long term, MGRF and FGRF promote muscle performance gain in mice during postnatal development, independently of muscle growth in males, largely via improving muscle contractile quality (force and power normalized), and that MGFR and FGRF also contribute to sexual dimorphism. However, the mechanisms underlying MGFR and FGRF actions remain to be determined.


[Occurrence of Escherichia coli in urinary tract infection].
Regarding P-fimbriae, K1 antigen, sero O-type and factors on the host (age, sex and morbidity) with are the pathogenic factors in E. coli, an assessment has been made as to what relations these factors have in urinary tract infection. By age, cases of P-fimbriae is seen in large numbers among pregnant women and infants but less among the people aged 16-30. A similar trend was observed regarding K1 antigen. An assessment made by sex show a trend that E. coli which carries P-fimbriae tends to emerge frequently in males. By morbidity, P-fimbriated strain was seen in many severe cases among pregnant women and infants. The fact has become evident further as a result of making an investigation with K1 antigen added. However, the result of an assessment made in adult cases showed that P-fimbriae was seen frequently in simple cystitis conversely. As the reason for P-fimbriae being observed more in males, participations of immunological stage and anatomical factors on the host side in the pathogenicity was resumed, and the main cause that P-fimbriae is seen more in severe pregnant and infantile cases was presumed to be vesicoureteral reflux. Regarding group sero O-type and morbidity, the types reported so far were detected also at our hospital, but a very interesting finding we have obtained was that the stains P-fimbriae and K1 antigen were observed in types 2, 12, 18 and 75.


Intracerebral Hemorrhage due to Thrombosis with Thrombocytopenia Syndrome after Vaccination against COVID-19: the First Fatal Case in Korea.
Vaccination with an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in the rare development of thrombosis with thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4). This is a life-threating condition that may be accompanied by bleeding due to thrombocytopenia with thrombosis of the cerebral venous sinus or splanchnic vein. Herein, we describe the first fatal case of thrombosis with thrombocytopenia syndrome in Korea, presenting with intracranial hemorrhage caused by cerebral venous sinus thrombosis. A 33-year-old Korean man received the first dose of the ChAdOx1 nCoV-19 vaccination. He developed severe headache with vomiting 9 days after the vaccination. Twelve days after vaccination, he was admitted to the hospital with neurological symptoms and was diagnosed with cerebral venous sinus thrombosis, which was accompanied by intracranial hemorrhage. Thrombocytopenia and D-dimer elevation were observed, and the result of the PF4 enzyme-linked immunosorbent assay antibody test was reported to be strongly positive. Despite intensive treatment, including intravenous immunoglobulin injection and endovascular mechanical thrombectomy, the patient died 19 days after vaccination. Physicians need to be aware of thrombosis with thrombocytopenia syndrome (TTS) in adenoviral vector-vaccinated patients. Endovascular mechanical thrombectomy might be a useful therapeutic option for the treatment of TTS with cerebral venous sinus thrombosis.


The geographical distribution and socioeconomic risk factors of COVID-19, tuberculosis and leprosy in Fortaleza, Brazil.
Fortaleza (Brazil) is high endemic for coronavirus disease 2019 (COVID-19), tuberculosis (TB) and leprosy. These three diseases share respiratory droplets through coughing or sneezing as the main mode of transmission but differ in incubation time, with COVID-19 having a short and leprosy a long incubation time. Consequently, contacts of a patient are at higher risk of infection and developing these diseases. There might be scope for combined preventive measures, but a better understanding of the geographical distribution and relevant socioeconomic risk factors of the three diseases is needed first. This study aims to describe the geographic distribution of COVID-19, TB and leprosy incidence and to identify common socioeconomic risk factors. The total number of new cases of COVID-19, TB and leprosy, as well as socioeconomic and demographic variables, were retrieved from official registers. The geographical distribution of COVID-19, TB and leprosy rates per neighbourhood was visualised in Quantum GIS, and spatial autocorrelation was measured with Moran's I in GeoDa. A spatial regression model was applied to understand the association between COVID-19, TB, leprosy rates, and socioeconomic factors. COVID-19 and TB showed a more homogenous distribution, whereas leprosy is located more in the south and west of Fortaleza. One neighbourhood (Pedras) in the southeast was identified as high endemic for all three diseases. Literacy was a socioeconomic risk factor for all three diseases: a high literacy rate increases the risk of COVID-19, and a low literacy rate (i.e., illiteracy) increases the risk of TB and leprosy. In addition, high income was associated with COVID-19, while low income with TB. Despite the similar mode of transmission, COVID-19, TB and leprosy show a different distribution of cases in Fortaleza. In addition, associated risk factors are related to wealth in COVID-19 and to poverty in TB and leprosy. These findings may support policymakers in developing (partially combined) primary and secondary prevention considering the efficient use of resources.


[Ibrutinib inhibits mesenchymal stem cells-mediated drug resistance in diffuse large B-cell lymphoma].
Objective: To explore the mechanism of ibrutinib on drug resistance diffuse large B-cell lymphoma (DLBCL) cells. Methods: DLBCL cell line was cultured with mesenchymal stem cells (MSC) , and DLBCL cells which migrated and adhered to MSC under microscope was counted. The secretion of CXCL12 by MSC were measured by ELISA. The expression of CXCR4 on DLBCL cells were measured by flow cytometry, HBL-1 cells were transfected with a CXCR4-lentivector. An Annexin Ⅴ-binding assay was used to detect the induction of apoptosis. Clonogenic growth of DLBCL cells was evaluated on MethoCult media. Ibrutinib was injected into NOD/SCID mice, tumor growth was assessed via caliper measurements every 3 days. Results: MSC promoted migration and adhesion of DLBCL cells to MSC. Ibrutinib inhibited migration and adhesion of DLBCL cells to MSC in a dose-dependent manner (P<0.05) . CXCL12 secreted by MSC and CXCR4 expressed on DLBCL cells could induce each other, which upgraded the levels of secretion and expression. Ibrutinib could inhibit the secretion of CXCL12 (SUDHL10: 660 pg/ml vs 1 400 pg/ml, P=0.004; HBL-1: 720 pg/ml vs 1 490 pg/ml, P=0.018; DLBCL:850 pg/ml vs 1 450 pg/ml, P=0.004) and expression of CXCR4 (P<0.05) . When co-cultured with MSC, the ratio of HBL-1 cells apoptosis in the group of control, mitoxantrone, ibrutinib, mitoxantrone+ibrutinib were respectively 15.1%, 17.5%, 23.5%, 58.7%. After transfected with a CXCR4-lentivector and overexpressed CXCR4, the ratios of HBL-1 cells apoptosis were 14.2%, 16.1%, 22.5%, 38.3% respectively. The ratio of DLBCL cells apoptosis induced by mitoxantrone was lower when co-cultured with MSC (P<0.05) . But with the addition of ibrutinib, the ratio of apoptosis was increaed and it was similar to cultivation without MSC, which suggested ibrutinib could inhibit drug-resistance induced by MSC. But after transfected with a CXCR4-lentivector, the overexpression of CXCR4 was detected and the ratio of apoptosis was significantly lower when co-cultured with MSC which demonstrated that ibrutinib inhibited drug-resistance by inhibiting the expression of CXCR4. MSC enhanced lymphoma clonogenicity in vitro and lymphoma cell growth in vivo. The number of colonies of control, MSC, Ibrutinib, MSC+Ibrutinib were 113±5, 205±4, 62±9, 123±3 (2.5×10(3)/well, x±s) , respectively. The tumor volume of NOD/SCID mice were respectively 6 500, 17 000, 4 000, 10 000 mm(3). Ibrutinib inhibited lymphoma clonogenicity in vitro and lymphoma cell growth in vitro. Conclusion: Ibrutinib targeted the CXCL12/CXCR4 axis, inhibited the expression of CXCR4 and inhibited MSC-mediated drug resistance. Ibrutinib also inhibited lymphoma clonogenicity in vitro and lymphoma cell growth in vivo. These results provided a scientific rationality for relapsed/refractory DLBCL treatment with ibrutinib.


IL-6 variant is associated with metastasis in breast cancer patients.
Although tumor metastases remain significant drivers of mortality, the genetic factors that increase the risks of metastases are not fully identified. Interleukin 6 (IL-6) has emerged as an important factor in breast cancer progression with IL-6 single nucleotide polymorphism (SNP) variants shown to affect survival. We hypothesized that SNPs of the IL-6 promoter at rs1800795 in breast cancer patients are associated with distant metastases. We performed an initial case-control study using Vanderbilt University Medical Center's BioVU, a genomic biobank linked to de-identified electronic medical records in the Synthetic Derivative database, to identify germline SNPs that may predict the development of metastatic disease to any site from any solid tumor including breast cancer. We identified a SNP in IL-6: rs1800795 to be of significance and evaluated this finding using a separate, matched-pair cohort of breast cancer patients with and without metastases from The Ohio State University Wexner Medical Center. The initial study suggested that GG relative to CG at rs1800795 (OR 1.52; 95% CI 1.14-2.02; p = 0.004) was significantly associated with the development of metastases. This association was also observed in the Ohio State University cohort (OR 2.23; 95% CI 1.06-4.71; p = 0.001). There were no significant relationships between rs1800795 status and any patient or tumor characteristics, including estrogen receptor status. These findings suggest that GG SNP at IL-6: rs1800795 may indicate an increased risk of metastasis of primary breast cancer. Further studies in larger population sets are warranted as advanced screening and prophylactic intervention might be employed in GG carriers.


IRFR-Net: Interactive Recursive Feature-Reshaping Network for Detecting Salient Objects in RGB-D Images.
Using attention mechanisms in saliency detection networks enables effective feature extraction, and using linear methods can promote proper feature fusion, as verified in numerous existing models. Current networks usually combine depth maps with red-green-blue (RGB) images for salient object detection (SOD). However, fully leveraging depth information complementary to RGB information by accurately highlighting salient objects deserves further study. We combine a gated attention mechanism and a linear fusion method to construct a dual-stream interactive recursive feature-reshaping network (IRFR-Net). The streams for RGB and depth data communicate through a backbone encoder to thoroughly extract complementary information. First, we design a context extraction module (CEM) to obtain low-level depth foreground information. Subsequently, the gated attention fusion module (GAFM) is applied to the RGB depth (RGB-D) information to obtain advantageous structural and spatial fusion features. Then, adjacent depth information is globally integrated to obtain complementary context features. We also introduce a weighted atrous spatial pyramid pooling (WASPP) module to extract the multiscale local information of depth features. Finally, global and local features are fused in a bottom-up scheme to effectively highlight salient objects. Comprehensive experiments on eight representative datasets demonstrate that the proposed IRFR-Net outperforms 11 state-of-the-art (SOTA) RGB-D approaches in various evaluation indicators.


Aging is associated with resistance to effects of leptin on fat distribution and insulin action.
Leptin has been shown to modulate total body fat and visceral fat distribution and to enhance insulin action in young rats. We hypothesize that failure of leptin action may contribute to the increase in visceral fat and insulin resistance in aging. By chronic subcutaneous infusion of leptin over 7 days, we increased leptin levels in young rats to match the levels in aging ad libitum fed rats. Leptin induced an approximately 50% decrease in food intake compared with saline controls, an approximately 50% decrease in visceral fat, and improved hepatic (fourfold) and peripheral (30%) insulin action (euglycemic hyperinsulinemic clamp technique) compared with the pair-fed group (p <.001). Although the plasma leptin level was doubled in aging rats, leptin failed to produce a significant change in food intake, in fat mass and its distribution, and in hepatic and peripheral insulin action. Increasing plasma leptin levels failed to suppress leptin gene expression in aging rats as compared with the approximately 50% suppression seen in young rats (p <.01). We propose that leptin resistance may play a causative role in the metabolic decline seen with aging.


Sustained Immunoparalysis in Endotoxin-Tolerized Monocytic Cells.
Sepsis is associated with a strong inflammatory reaction triggering a complex and prolonged immune response. Septic patients have been shown to develop sustained immunosuppression due to a reduced responsiveness of leukocytes to pathogens. Changes in cellular metabolism of leukocytes have been linked to this phenomenon and contribute to the ongoing immunological derangement. However, the underlying mechanisms of these phenomena are incompletely understood. In cell culture models, we mimicked LPS tolerance conditions to provide evidence that epigenetic modifications account for monocyte metabolic changes which cause immune paralysis in restimulated septic monocytes. In detail, we observed differential methylation of CpG sites related to metabolic activity in human PBMCs 18 h after septic challenge. The examination of changes in immune function and metabolic pathways was performed in LPS-tolerized monocytic THP-1 cells. Passaged THP-1 cells, inheriting initial LPS challenge, presented with dysregulation of cytokine expression and oxygen consumption for up to 7 days after the initial LPS treatment. Proinflammatory cytokine concentrations of TNFα and IL1β were significantly suppressed following a second LPS challenge (p < 0.001) on day 7 after first LPS stimulation. However, the analysis of cellular metabolism did not reveal any noteworthy alterations between tolerant and nontolerant THP-1 monocytes. No quantitative differences in ATP and NADH synthesis or participating enzymes of energy metabolism occurred. Our data demonstrate that the function and epigenetic modifications of septic and tolerized monocytes can be examined in vitro with the help of our LPS model. Changes in CpG site methylation and monocyte function point to a correlation between epigenetic modification in metabolic pathways and reduced monocyte function under postseptic conditions.


Community psychology: individuals and interventions in community context.
Community psychology has historically focused on understanding individual behavior in sociocultural context, assessing high-impact contexts, and working in and with communities to improve their resources and influence over their futures. This review adopts an ecological perspective on recent developments in the field, beginning with philosophy of science and progressing through a series of substantive research and intervention domains that characterize current work. These domains include research on the ecology of lives, the assessment of social settings and their impact on behavior, culture and diversity as expressed in the community research process, and community intervention.


Pearls in the Wrong Pockets: Idiopathic Scrotal Calcinosis.
Idiopathic scrotal calcinosis, also called dystrophic scrotal calcinosis, is a rare benign condition that causes superficial intradermal scrotal calcifications. We present one such case of a 40-year-old married man who underwent PET/CT scan for staging workup of lymphoma and revealed this rare entity incidentally without any other testicular pathology.


Results of the treatment of rectal prolapse operated according to Ripstein.
59 patients have been submitted to abdominal rectopexi according to Ripstein. The operative mortality was 5%, which was, however, not wholly due to the operation. The mortality-rate shows, however, that patients older than 60 years of age must be carefully evaluated preoperatively. The recurrence-rate was 5,4% with a mean observation period of 5 years. The method appears to be satisfactory for treatment of rectal prolapse.


Down-regulation of microRNA-216b inhibits IL-1β-induced chondrocyte injury by up-regulation of Smad3.
Osteoarthritis (OA) is the most common type of joint disease, leading to a major cause of pain and disability. OA is characterized by the continuous degradation of articular cartilage, mainly resulting in an imbalance between synthesis and degradation of articular chondrocyte extracellular matrix (ECM). Aberrant miR-216b expression has been found in multiple cancers. However, the level of miR-216b in OA cartilage and its role in progression of this disease are still unknown. In the present study, the functional roles of miR-216b and its expression in OA tissues and interleukin-1β (IL-1β)-induced chondrocytes were examined. We found that the level of miR-216b was significantly higher and Smad3 expression was obviously lower in OA cartilage and IL-1β-induced chondrocytes than in normal tissues and cells. Furthermore, a bioinformatics analysis and luciferase reporter assay identified Smad3 as a direct target gene of miR-216b, and Smad3 expression was reduced by miR-216b overexpression at both the mRNA and protein levels. A functional analysis demonstrated that miR-216b down-regulation obviously alleviated the IL-1β-induced inhibition in cell proliferation, type II collagen, and aggrecan down-regulation and matrix metalloproteinase-13 (MMP-13) up-regulation, while miR-216b overexpression had the opposite effects. Knockdown of Smad3 by siRNA reversed the effects of the miR-216b inhibitor on cell proliferation, the expressions of type II collagen, aggrecan, and MMP-13. Our results suggested that miR-216b contributes to progression of OA by directly targeting Smad3, providing a potential therapeutic target for treatment of OA.


Germinal center-independent affinity maturation in tumor necrosis factor receptor 1-deficient mice.
Germinal centers (GCs) have been identified as site at which the somatic mutation of immunoglobulins occurs.However, somatic mutations in immunoglobulins have also been observed in animals that normally do not harbor germinal centers. This clearly indicates that somatic mutations can occur in the absence of germinal centers. We therefore attempted to determine whether or not GCs exist in TNFR1-deficient mice, and are essential for the somatic mutation of immunoglobulins, using (4-hydroxy-3-nitropheny)acetyl-ovalbumin (NP-OVA). Both wild-type and TNFR1-deficient mice were immunized with NPOVA, and then examined with regard to the existence of GCs. No typical B-cell follicles were detected in the TNFR1-deficient mice. Cell proliferation was detected throughout all splenic tissue types, and no in vivo immunecomplex retention was observed in the TNFR1-deficient mice. All of these data strongly suggest that no GCs were formed in the TNFR1-deficient mice. Although TNFR1-deficient mice are unable to form GCs, serological analyses indicated that affinity maturation had been achieved in both the wild-type and TNFR1-deficient mice. We therefore isolated and sequenced several DNA clones from wild-type and the TNFR1-deficient mice. Eight out of 12 wild-type clones, and 11 out of 14 clones of the TNFR-1-deficient mice contained mutations at the CDR1 site. Thus, the wild-type and TNFR1-deficient mice were not extremely different with regard to types and rates of somatic mutation. Also, high-affinity antibodies were detected in both types of mice. Collectively, our data appear to show that affinity maturation may occur in TNFR1-deficient mice, which completely lack GCs.


DHX32 expression is an indicator of poor breast cancer prognosis.
Emerging evidence suggests that DEAH-box polypeptide 32 (DHX32) serves an important role in the progression and metastasis of cancer. However, the role of DHX32 in breast cancer remains to be completely elucidated. The aim of the present study was to evaluate the expression and clinical significance of DHX32 in breast cancer. The reverse transcription-quantitative polymerase chain reaction was performed to analyze DHX32 messenger (m)RNA expression, and western blotting and immunohistochemistry were performed to examine DHX32 protein expression in breast cancer and adjacent non-cancerous tissues. The association in breast cancer between DHX32 expression, clinicopathological features and prognosis was analyzed using 193 breast cancer tissue samples. The results of the present study demonstrated that breast cancer tissues exhibited increased DHX32 mRNA and protein expression compared with adjacent non-cancerous tissues (P<0.001). In addition, DHX32 expression was significantly associated with breast cancer clinical stage (P=0.006), histological grade (P=0.029), lymph node metastasis (P<0.001) and expression of the proliferation marker Ki-67 (P=0.004). Kaplan-Meier estimator analysis indicated that increased DHX32 expression is associated with poor prognosis in patients with breast cancer. Furthermore, the Cox proportional hazards model indicated that DHX32 expression is an independent prognostic factor for decreased overall survival and disease-free survival in patients with breast cancer. In conclusion, the results of the present study suggest that DHX32 overexpression is an unfavorable prognostic biomarker in breast cancer and a potential therapeutic target of future breast cancer treatments.


Immunoregulatory Effects of Tolerogenic Probiotics in Multiple Sclerosis.
Gut microbiota has essential roles in the prevention and progression of multiple sclerosis (MS). The association between the gut microbiota and the central nervous system (CNS) or immune system response of MS patients has been documented in many studies. The composition of the gut microbiota could lead to sensitization or resistance against promotion and development of MS disease. Probiotics are the major part of gut microflorapopulation and could be substituted with tolerogenic probiotics that protect the CNS against autoimmune responses. Tolerogenic probiotics with anti-inflammatory and immuno-modulatory properties have effects on intestinal flora and can reestablish regulatory mucosal and systemic immune responses. Probiotics are able to prevent and restore excessive activation of inflammatory responses, especially autoreactive T cells and inflammatory cytokines. Tolerogenic probiotics, through induction of regulatory T cells and increase of anti-inflammatory cytokines, play a crucial role in controlling inflammation and maintaining tolerance and hemostasis. Therefore, probiotics can be considered as a preventive or therapeutic tool in MS. In the present review, we focus on the immunoregulatory effects of tolerogenic probiotics on the severity of disease, as well as Th1, Th2, and Treg populations in different experimental and human studies of MS.


[Preclinical and clinical treatment of instable pelvic injuries : Results of an online survey].
Instable pelvic injuries are often associated with a high blood loss, which can effectively be curtailed by rapid external stabilization of the pelvis. The S3 guidelines on the treatment of multiple trauma and the severely injured recommend an initial stability testing in cases of an instable pelvis and hemodynamic instability even though the sensitivity is very low, with subsequent external stabilization. Radiological diagnostic procedures are also becoming more important for early diagnostics. An online survey of the current management of instable pelvic injuries was carried out with 266 participants via the e-mail distribution list of the German Society of Trauma Surgery (DGU).Most answers in the survey were received from very experienced senior and chief physicians at level 1 trauma centers. The vast majority of the participants recommended carrying out mechanical stabilization testing and most wanted to do the testing themselves independent of any previous findings. Most participants would only carry out a pelvic stabilization if they themselves had recognized instability during the stability testing and many of them even in cases of hemodynamic instability alone, although several studies have reported a very low sensitivity of 26-44 % for stability testing. The preferred procedure for emergency stabilization in the emergency room was the pelvic sling, which in contrast to invasive tools was often implemented before radiological imaging was completed. In preclinical treatment the vacuum mattress was used more often for stabilization than the pelvic sling. In radiological examinations a whole body computed tomography (CT) scan was mostly used, sometimes combined with an anteroposterior pelvic x-ray. In cases of persisting hemorrhage in spite of external stabilization, most participants preferred a pelvic tamponade but angioembolization was also highly rated.Because many of the participants relied on their own findings from stability testing for a decision on external emergency stabilization despite the very low sensitivity, in cases of false negative testing there is a risk of insufficient treatment resulting in life-threatening hemorrhage. From our viewpoint, it therefore makes sense to treat patients with a suspicion of instable pelvic fractures based on the trauma mechanism and clinical examination (without mechanical stability testing) with non-invasive external pelvic stabilization as early as possible.


Antihypertensive role of tissue kallikrein in hyperaldosteronism in the mouse.
Tissue kallikrein (TK) is synthesized in arteries and distal renal tubule, the main target of aldosterone. Urinary kallikrein excretion increases in hyperaldosteronism. We tested the hypothesis that TK is involved in the cardiovascular and renal effects of high aldosterone. Kallikrein-deficient mice (TK-/-), and wild-type (WT) littermates, studied on two different genetic backgrounds, were treated with aldosterone and high-NaCl diet for 1 month. Control mice received vehicle and standard NaCl diet. Treatment induced 5- to 7-fold increase in plasma aldosterone, suppressed renin secretion, and increased urinary TK activity. In 129SvJ-C57BL/6J mice, blood pressure monitored by radiotelemetry was not different between control TK-/- and WT mice. In TK-/- mice, aldosterone induced larger increases in blood pressure than in WT mice (+47 vs. +27 mm Hg; genotype-treatment interaction, P < 0.05). Night-day difference was also exacerbated in treated TK-/- mice (P < 0.01). Moderate cardiac septal hypertrophy was observed in hypertensive animals without major change in heart function. Aldosterone-salt increased kidney weight similarly in both genotypes but induced a 2-fold increase in renal mRNA abundance of epithelial sodium channel subunits only in TK-/- mice. The hypertensive effect of TK deficiency was also documented in treated C57BL/6J mice. In this strain, aldosterone-induced hypertension was only observed in TK-/- mice (+16 mm Hg, P < 0.01). These findings show that TK deficiency exacerbates aldosterone-salt-induced hypertension. This effect may be due at least in part to enhanced sodium reabsorption in the distal nephron aggravating sodium retention. The study suggests that kallikrein plays an antihypertensive role in hyperaldosteronism.


Do gestational age and weight for gestational age predict concordance in parental perceptions of infant temperament?
To study whether infant weight for gestational age, and gestational age predict mother- and father-rated infant temperament (IBQ) at 6 months. The sample comprised of family units with both biological parents and infants born at term (n = 152). Data on weight and gestational age were collected form obstetric database. Infants born small for gestational age (SGA) (weight < 10th percentile for gestational age) were rated by both parents as significantly more fearful and negatively reactive compared to infants born appropriate for gestational age (AGA). Infants born SGA defined by using the lowest 15th or 20th percentile groups did not differ from AGA group in temperament. The weekly continuum of gestational age predicted differences in parental ratings of infant temperamental attentiveness. The predictive significance of infant weight for gestational age and gestational age for behavioral outcomes appear true also for infants born at term. Concordance in parental perceptions of an infant born SGA emphasizes the clinical significance of the findings.


Sustained Swimming Training Is Associated With Reversible Filet Texture Changes of European Sea Bass (Dicentrarchus labrax L.).
This present study aimed to investigate the effect of training and detraining on the growth, chemical composition, white muscle fibers, and filet texture of the European sea bass (Dicentrarchus labrax L.). Fish were divided into control and training groups, which were subjected to water velocities of 0.2 and 1.0 body length per second (bl s-1), respectively, for 32 days (phase I). Half of the fish in the training group were then randomly selected and detrained at a velocity of 0.2 bl s-1 for another 32 days (detraining group), while the velocity of the remaining fish in the training group (1 bl s-1), and control group (0.2 bl s-1) remained unchanged (phase II). The results showed that the growth, body composition, and white muscle fiber densities of the control and trained fish were not significantly different in either phase. Training significantly altered the muscle fiber distribution (P < 0.05), with the training group having fewer 80-90 μm fibers than the control and detraining group at the end of the experiment (P < 0.05). The training group also had significantly higher values for white fiber muscle textural parameters (hardness, adhesiveness, cohesiveness, springiness, gumminess, and chewiness) in phase I (P < 0.05), and these parameters correlated significantly with pH (P < 0.05). However, these differences in texture and the pH correlation weakened when the fish were detrained in phase II. These results indicated that an increase in muscle pH after training may alter the flesh texture characteristics of sea bass. In addition, sustained swimming could induce a reversible change in the filet texture of sea bass.


Effects of viewing distance on accommodative and pupillary responses following a three-dimensional task.
We have investigated accommodation and pupil responses after viewing stereoscopic images related to the resting position of accommodation. After a 10-min visual task viewing stereoscopic three-dimensional images, measurements of dynamic accommodation and pupil response were made using an infrared optometer and a pupil analyser. Four conditions were given for the viewing distance: 0.4 m (closer than the subjects' resting position), 1 m (approximating to their resting state), and 1.5 and 3 m (farther than the resting position). For the 0.4- and 1-m groups, a delay in the accommodation response for near-to-far movement was shown after the task, from 817 to 1120 ms and from 830 to 898 ms, respectively, but there was no change in the pupillary response. In the 1.5- and 3-m groups, on the other hand, a significant delay in the accommodation response for far-to-near movement was shown, from 827 to 912 ms and from 857 to 1150 ms, respectively, and greater miosis was found, from 7.2 to 9.2 mm2 and from 8.0 to 10.4 mm2. The data reveal that there are different after-effects on accommodation and pupillary functions when subjects perform the task within their accommodative resting position, than when the task is performed outside the resting position.


Translucency and masking properties of two ceramic materials for heat-press technology.
To assess the translucency of two pressable ceramics and to analyze their masking property when placed on different tooth-shaded backgrounds. Thirty discs (1-mm thickness) were fabricated using two pressable ceramics (shade/translucency): 1M1T/HT, 1M2T/HT, 2M2T (VITA PM9), and A1LT/HT, B1LT/HT, A2LT (e.max Press). Color measurements of discs were performed with a dental spectrophotometer on tooth-colored backgrounds (A1/A2/A3/A3.5/A4), and black and white backings. The masking property was calculated as the color difference (CIEDE2000) between parameters of discs on control (A1, A2) and test backgrounds (A3, A3.5, A4). One-way ANOVA was used for assessing differences in translucency parameter (TP) between ceramics. Two-way ANOVA was used for detecting differences among groups when measured over tooth-shaded backgrounds (α = 0.05, Bonferroni correction). TP ranged between 14.96 (B1LT) and 25.18 (1M1HT). A significant difference in TP was found between tested ceramics (F = 949.949, P < .001). However, TP did not vary significantly between 1M1HT and 1M2HT (P > .05), 1M1T, A1HT and B1HT (P > .05), 1M2T, 2M2T, and A2HT (P > .05). A significant interaction effect of underlying background on color of ceramic discs was found (F = 107.994, P < .001). VITA PM9 demonstrated higher translucency than e.max Press ceramics. Except A1LT, all ceramic materials evaluated showed poor masking properties on A4 background. Highly translucent ceramics should be wisely used for restoring the appearance of dental structures since background color has a large effect upon these materials. The more recently introduced pressable ceramics showed high levels of translucency.


[Metabolism of fibrinogen in the cirrhotic patient. Dynamic study by isotope method].
The authors studied the metabolism of fibrinogen labelled with iodine 125 in 57 cirrhotic patients and 25 controls. Their results show that if the 82 subjects are grouped according to biological period values (T) and plasma pool (N.I.) of each of them, 4 distinct populations emerge. In each of these 4 groups a physiopathological interpretation of fibrinogen metabolism may be proposed. In the context of consumption coagulopathies in cirrhosis, the examination is of real value and offers an objective criterion of therapeutic effectiveness.


Slavery, smallpox, and revolution: 1792 in Ile de France (Mauritius).
In 1792 a slave-ship arrived on the french Indian Ocean island of Ile de France (Mauritius) from South India, bringing with it smallpox. As the epidemic spread, a heated debate ensued over the practice of inoculation. The island was in the throes of revolutionary politics and the community of French colonists were acutely aware of their new rights as 'citizens'. In the course of the smallpox epidemic, many of the political tenisons of the period came to focus on the question of inoculation, and were played out on the bodies of slaves. Whilst some citizens asserted their right, as property owners, to inoculate their slaves, others, equally vehemently, objected to the practice and asserted their right to protect their slaves from infection. Eighteenth-century colonial medicine was largely geared to keeping the bodies of slaves and workers productive and useful, but formal medicine never had a monopoly. Slaves on Ile de France brought with them a rich array of medical beliefs and practices from Africa, India, and Madagascar. We have little direct historical evidence for these, but we do know that many slaves came from areas in which forces of smallpox inoculation were known and practised.


Barrett's Esophagus: A Review of Biology and Therapeutic Approaches.
Despite advances in diagnosis and therapy, esophageal cancer remains a highly lethal disease. The incidence of esophageal adenocarcinoma (EAC) has risen faster than that of any other cancer in the western world, and Barrett's esophagus (BE) may be a significant contributing factor. In-depth knowledge of biology of cancer progression and cancer could lead to the identification of biomarkers that are the hallmark of BE's progression. By integrating validated biomarkers of progression into clinical practice, there is a possibility of identifying high-risk patient population for targeted surveillance, and such biomarkers may serve as novel therapeutic targets for chemoprevention and therapy. Clinical management of BE has improved considerably due to the improvements in endoscopic resection and ablation techniques. We discuss the current status of biology and therapeutic approaches to BE.


Reinvestigation of carrier transport properties in liquid crystalline 2-phenylbenzothiazole derivatives.
We have reinvestigated the charge carrier transport properties in a liquid crystal of 2-(4'-heptyloxyphenyl)-6-dodecylthiobenzothiazole (7O-PBT-S12), for which the electronic conduction was first established in rodlike liquid crystals and for which the highest hole mobility in the smectic A (SmA) phase ever achieved was reported. We found that 7O-PBT-S12 exhibited three crystal phases, one of which appeared in a limited temperature range of 10 degrees just below the phase transition temperature from the SmA phase. In this crystal phase, nondispersive transient photohole currents were observed in time-of-flight experiments, and its hole mobility was determined to be 8 x 10(-3) cm(2)/Vs, slightly higher than that reported previously in the SmA phase. For the SmA phase, however, the hole mobility was 1 x 10(-4) cm(2)/Vs. Furthermore, we established the electron transport in the SmA phase of purified 7O-PBT-S12, whose mobility was the same as the hole mobility in that phase. In order to confirm generality of the new findings in 7O-PBT-S12, we investigated the carrier transport properties of its derivative having a short hydrocarbon chain, 2-(4'-heptyloxyphenyl)-6-butylthiobenzothiazole (7O-PBT-S4), and obtained comparable results. The present results correct a mistake in the previous report and give an idea of what a typical mobility in the SmA phase is. On the basis of these results, we discuss what determines the charge carrier mobility in smectic mesophases.


A UK-wide survey of follow-up practices for patients with high-grade glioma treated with radical intent.
High-grade glioma profoundly affects patients and their families. The best ongoing care for patients completing radical treatment is uncertain. To address this issue a UK-wide audit surveying the follow-up practices of multidisciplinary cancer teams was conducted. An online survey package was used with a paper version available. Of 102 clinicians approached 86 replied, a response rate of 84%. Three-monthly outpatient department appointments led by an oncologist and a specialist nurse were the norm, but more controversially, some centres conduct joint clinics with the whole neurosurgical/oncology team present or available. Nurse-led telephone follow-up in place of hospital visits is uncommon. Regular scanning is conducted despite the clinical benefits being contentious. Access to a range of allied services providing supportive care is considered, but the actual levels of need and the efficiency with which they are delivered require further investigation. The picture of UK follow-up practices revealed by this survey demonstrates that research is now needed to determine what preferences patients and families have for follow-up and their satisfaction with these.


Chromosome 18q deletion syndrome with autoimmune diabetes mellitus: putative genomic loci for autoimmunity and immunodeficiency.
A girl with 18q deletion syndrome was diagnosed with autoimmune diabetes mellitus and Hashimoto's thyroiditis at the age of 3 yr. In addition, the girl suffered from recurrent infections due to immunoglobulin A and IgG4 deficiency. She was also found to have CD3+CD4+FoxP3+, CD3+CD4+FoxP3+CD25+, and CD3+CD4+CD25+CD127 regulatory T cells deficiency. The exceptional coincidence of the two autoimmune disorders occurring at an early age, and associated with immune deficiency, implies that genes located on deleted 19.4 Mbp region at 18q21.32-q23 (chr18:58,660,699-78,012,870) might play a role in the pathogenesis of autoimmunity leading to β cell destruction and diabetes.


Influence of race, gender, and socioeconomic status on binge eating frequency in a population-based sample.
This study investigates race and gender differences in the demographic and socioeconomic determinants of frequency of binge eating using a population-based sample. An analysis of self-reported data on 573 women and 360 men (range, 18-97 years) from a cross-sectional, multistage area probability sample of individuals aged 18 years and older residing in the Detroit metropolitan area conducted in 1995. For women, the frequency of binge eating is negatively associated with age and family income, and positively associated with being married, depression, and time residing in polluted neighborhoods. For men, the frequency of binge eating is negatively associated with age. The frequency of binge eating was not affected by education, race, obesity, or current dieting. The frequency of binge eating is highest among adults younger than 40 years. It follows an income gradient for women, but not for men. After controls for individual disadvantage, there is no residual Black/White difference in binge eating.


Temperature dependence of the viscoelastic properties of a natural gastropod mucus by Brillouin light scattering spectroscopy.
Brillouin spectroscopy was used to probe the viscoelastic properties of a natural gastropod mucus at GHz frequencies over the range -11 °C ≤ T ≤ 52 °C. Anomalies in the temperature dependence of mucus longitudinal acoustic mode peak parameters and associated viscoelastic properties at T = -2.5 °C, together with the appearance of a peak due to ice at this temperature, suggest that the mucus undergoes a phase transition from a viscous liquid state to one in which liquid mucus and solid ice phases coexist. Failure of this transition to proceed to completion even at -11 °C is attributed to glycoprotein-water interaction. The temperature dependence of the viscoelastic properties and the phase behaviour suggest that water molecules bind to glycoprotein at a temperature above the onset of freezing and that the reduced ability of this bound water to take on a configuration that facilitates freezing is responsible for the observed freezing point depression and gradual nature of the liquid-solid transition.


Unusual gastric foreign body: a case report.
Ingestion of foreign bodies, either intentionally or accidentally, is quite common. The authors report an unusual case in which a 32-year-old man deliberately assembled a large metallic aggregate in his stomach by swallowing magnets and coins in order to relieve epigastric discomfort. The collection was retrieved by laparotomy and gastrotomy; a gastric ulcer was also found and it was oversewn. Management of this patient is discussed and the principles of treatment for ingested foreign bodies are reviewed.


Navigated versus conventional pediatric spinal deformity surgery: Navigation independently predicts reoperation and infectious complications.
Literature on treating pediatric spinal deformity with navigation is limited, particularly using large nationally represented cohorts. Further, the comparison of single-institution data to national-level database outcomes is also lacking. (1) To compare navigated versus conventional posterior pediatric deformity surgery based on 30-day outcomes and perioperative factors using the National Surgical Quality Improvement Program (NSQIP) database and (2) to compare the outcomes of the NSQIP navigated group to those of fluoroscopy-only and navigated cases from a single-institution. Retrospective cohort study. Pediatric patients who underwent posterior deformity surgery with and without navigation were included. Primary outcomes were 30-day readmission, reoperation, morbidity, and complications. The second part of this study included AIS patients < 18 years old at a single institution between 2015 and 2019. Operative time, length of stay, transfusion rate, and complication rate were compared between single-institution and NSQIP groups. Univariate analyses with independent t-test and Chi-square or Fisher's exact test was used. Multivariate analyses through the application of binary logistic regression models. Part I of the study included 16,950 patients, with navigation utilized in 356 patients (2.1%). In multivariate analysis, navigation predicted reoperation, deep wound infection, and sepsis. After controlling for operative year, navigation no longer predicted reoperation. In Part II of the study, 288 single institution AIS patients were matched to 326 navigation patients from the NSQIP database. Operative time and transfusion rate were significantly higher for the NSQIP group. On a national scale, navigation predicted increased odds of reoperation and infectious-related events and yielded greater median relative value units (RVUs) per case but had longer operating room (OR) time and fewer RVUs-per-minute. After controlling for operative year, RVUs-per-minute and reoperation rates were similar between groups. The NSQIP navigated surgery group was associated with significantly higher operative time and transfusion rates compared to the single-institution groups.


That person is now with or without a mask: how encoding context modulates identity recognition.
Previous research has mostly approached face recognition and target identification by focusing on face perception mechanisms, but memory mechanisms also appear to play a role. Here, we examined how the presence of a mask interferes with the memory mechanisms involved in face recognition, focusing on the dynamic interplay between encoding and recognition processes. We approach two known memory effects: (a) matching study and test conditions effects (i.e., by presenting masked and/or unmasked faces) and (b) testing expectation effects (i.e., knowing in advance that a mask could be put on or taken off). Across three experiments using a yes/no recognition paradigm, the presence of a mask was orthogonally manipulated at the study and the test phases. All data showed no evidence of matching effects. In Experiment 1, the presence of masks either at study or test impaired the correct identification of a target. But in Experiments 2 and 3, in which the presence of masks at study or test was manipulated within participants, only masks presented at test-only impaired face identification. In these conditions, test expectations led participants to use similar encoding strategies to process masked and unmasked faces. Across all studies, participants were more liberal (i.e., used a more lenient criterion) when identifying masked faces presented at the test. We discuss these results and propose that to better understand how people may identify a face wearing a mask, researchers should take into account that memory is an active process of discrimination, in which expectations regarding test conditions may induce an encoding strategy that enables overcoming perceptual deficits.


[Effects of acupoint specificity on claustrophobia].
To observe the effectiveness of acupuncture on claustrophobia, and to explore the effects of acupoint specificity on claustrophobia. This was an evaluator-blinded randomized controlled trial. One hundred and sixty patients who presented with claustrophobia during magnetic resonance imaging examination were randomized into an acupoint group, a non-acupoint group, a sham-acupoint group and a blank group, 40 cases in each one. The patients in the acupoint group were treated with acupuncture at Zhaohai (KI 6), Taichong (LR 3), Lingdao (HT 4), Neiguan (PC 6), Shenmen (HT 7), Danzhong (CV 17), Baihui (GV 20) and Fengchi (GB 20). The patients in the non-acupoint group were treated with acupuncture at points 0.5 cun next to the acupoints above. The patients in the sham-acupoint group were treated with acupuncture at acupoints not closely correlated to claustrophobia in corresponding segment. All the acupuncture was given once. No treatment was used in the blank group. The state anxiety questionnaire (S-AI) was observed in all the patients at the end of MRI examination before and after treatment. The clinical therapeutic effects were compared among four groups. Compared before treatment, the S-AI score was reduced in the acupoint group, non-acupoint group and sham-acupoint group after treatment (P<0.05, P<0.01); the differences of S-AI score before and after treatment in the blank group were not statistically significant (P>0.05). After treatment, the S-AI scores in the acupoint group, non-acupoint group and sham-acupoint group was lower than that in the blank group (P<0.05, P<0.01), and the differences of S-AI score were higher than that in the blank group (P<0.01). The S-AI score in the acupoint group was lower than that in the non-acupoint group and sham-acupoint group (P<0.05), and the difference of S-AI score was higher than those in the non-acupoint group and sham-acupoint group (P<0.05). The difference of S-AI score in the non-acupoint group was higher than that in sham-acupoint group (P<0.05). The total effective rate was 92.5% (37/40) in the acupoint group, which was significantly superior to 25.0% (10/40) in the non- acupoint group, 17.5% (7/40) in the sham-acupoint group and 5.0% (2/40) in the blank group (P<0.05, P<0.01). Acupuncture showes superior effect on claustrophobia, and its tranquilizing effect may be related with acupoint specificity.


A siamese network with adaptive gated feature fusion for individual knee OA features grades prediction.
Grading individual knee osteoarthritis (OA) features is a fine-grained knee OA severity assessment. Existing methods ignore following problems: (1) more accurately located knee joints benefit subsequent grades prediction; (2) they do not consider knee joints' symmetry and semantic information, which help to improve grades prediction performance. To this end, we propose a SE-ResNext50-32x4d-based Siamese network with adaptive gated feature fusion method to simultaneously assess eight tasks. In our method, two cascaded small convolution neural networks are designed to locate more accurate knee joints. Detected knee joints are further cropped and split into left and right patches via their symmetry, which are fed into SE-ResNext50-32x4d-based Siamese network with shared weights, extracting more detailed knee features. The adaptive gated feature fusion method is used to capture richer semantic information for better feature representation here. Meanwhile, knee OA/non-knee OA classification task is added, helping extract richer features. We specially introduce a new evaluation metric (top±1 accuracy) aiming to measure model performance with ambiguous data labels. Our model is evaluated on two public datasets: OAI and MOST datasets, achieving the state-of-the-art results comparing to competing approaches. It has the potential to be a tool to assist clinical decision making.


The differential protection by WR2721 of skin versus growing cartilage following irradiation in weanling rats.
The potential for radioprotection of growing cartilage by the thiophosphate WR2721 was evaluated in weanling rats using single fractions of irradiation. Protection of acute skin toxicity was monitored simultaneously. Single doses of 600, 1200, 1800, or 2400 cGy were administered to the left tibia of CrL:CD(SD)BR female rats in groups of 12. Identically treated groups were injected with 310 mg/kg WR2721 (2/3 the determined LD50/30) in a concentration of 26 mg/ml intraperitoneally 15 min prior to irradiation. Rats untreated or given WR2721 without radiation served as control groups. Radiographs of the irradiated and unirradiated tibiae for each animal were obtained weekly to the date of sacrifice at 80 days following the initial treatment. Skin toxicity was assessed weekly starting on the second week using Moulder's scale (J.E. Moulder, J.J. Fischer, and A. Casey, Radiology 115, 465-470 (1975]. No significant difference in bone growth as measured by tibial lengths for the WR2721-treated or untreated animals was observed. Skin toxicity including moist desquamation occurred in irradiated limbs and was substantially less in rats treated with WR2721. As opposed to previous work with cysteamine, WR2721 as administered had no significant radioprotective effect on tibial growth in weanling rats but substantially reduced the accompanying skin toxicity.


Dermoids of the posterior fossa. Case reports and review.
Three children are presented with dermoid cysts of the posterior fossa, one of the most common locations of dermoid. They were initially diagnosed as having abscesses. Clinical presentations included hydrocephalus and recurrent meningitis. A helpful clue for identification is a bony defect of the skull on plain film or on a bone-window at Computed Tomography (CT).


[Pregnancy and overweight: underestimated consequences?].
As the prevalence of obesity grows in western countries, maternal obesity is becoming an increasingly frequent high-risk obstetrical situation. Obese women have a higher incidence of pregnancy complications (gestational diabetes, hypertension, toxaemia, etc.) and of adverse fetal outcomes (macrosomia, neural tube defects, perinatal mortality). Cesarean section is more frequent in obese women, resulting in a higher risk of anaesthetic and post-operative complications. Maternofetal complications are proportional to the degree of obesity, and even moderate overweight amplifies the risk. Long-term complications include worsening of maternal obesity, maternal type 2 diabetes, and childhood obesity and metabolic disorders. Before conception, these patients should receive tailored weight-loss advice and be screened for obesity complications. Food intake during pregnancy should be tailored to achieve the minimum maternal weight gain required for normal fetal growth. Long-term follow-up is required to prevent worsening of maternal obesity after delivery, and the child's growth curve should be closely watched


Complete spontaneous remission of small cell lung cancer in the absence of specific treatment: A case report.
Small cell lung cancer (SCLC) is a unique tumor that has a distinct clinical behavior and dismal prognosis. If untreated, it can become aggressively malignant, and life expectancy could be limited to weeks. Spontaneous regression of lung cancer has rarely been reported, and among them SCLC is even rarer. The underlying mechanisms of spontaneous regression are poorly understood. Here, we report a case of complete spontaneous SCLC remission in an elderly patient.


Development of a Bioreactor-Coupled Flow-Cell Setup for 3D In Situ Nanotomography of Mg Alloy Biodegradation.
Functional materials feature hierarchical microstructures that define their unique set of properties. The prediction and tailoring of these require a multiscale knowledge of the mechanistic interaction of microstructure and property. An important material in this respect is biodegradable magnesium alloys used for implant applications. To correlate the relationship between the microstructure and the nonlinear degradation process, high-resolution in situ three-dimensional (3D) imaging experiments must be performed. For this purpose, a novel experimental flow cell is presented which allows for the in situ 3D-nano imaging of the biodegradation process of materials with nominal resolutions below 100 nm using nanofocused hard X-ray radiation from a synchrotron source. The flow cell setup can operate under adjustable physiological and hydrodynamic conditions. As a model material, the biodegradation of thin Mg-4Ag wires in simulated body fluid under physiological conditions and a flow rate of 1 mL/min is studied. The use of two full-field nanotomographic imaging techniques, namely transmission X-ray microscopy and near-field holotomography, is compared, revealing holotomography as the superior imaging technique for this purpose. Additionally, the importance of maintaining physiological conditions is highlighted by the preliminary results. Supporting measurements using electron microscopy to investigate the chemical composition of the samples after degradation are performed.


[Effects of CeA lesions on the initiation and expression of sodium appetite in sodium-deficient rats].
To investigate the effects of central nucleus of amygdala (CeA) lesion on the initiation and expression of sodium appetite in sodium-deficient rats. Three groups of SD rats (n=6 in each group) were treated with bilateral CeA lesion, sham lesion or no lesion. After the recovery, the rats were fed with low-sodium diets for 14 days to establish a sodium-deficient rat model. The double-bottle selection in single cage test was used to observe the intake of 0.3 mol/L NaCl and DW in 5 timepoint with 24 hours in sodium-deficient rats. Immunofluorescence staining of aldosterone-sensitive neurons in the nucleus tractus solitarii (NTS)was used to investigate the effect of CeA lesion or not on the activity of aldosterone-sensitive neurons in rats with or without sodium deficiency. After fed with low-sodium diet for14 days, the volume and preference rate of 0.3 mol/L NaCl intake of the rats within 24 h were significantly increased compared with those before low-sodium diet (P<0.01). The intake volume and the preference rate of 0.3 mol/L NaCl in CeA lesion rats were significantly decreased than those in CeA sham lesion rats and normal rats in the sodium-deficient condition (P<0.01). The CeA lesion had no effects on the activity of aldosterone-sensitive neurons in NTS in rats with low-sodium diet. Low-sodium diet induces an increase in the expression of sodium appetite in rats. CeA lesions inhibit the behavioral expression of sodium appetite in sodium-deficient rats but have no effects on the initiation of sodium appetite in rats with sodium-deficient rats.


Contextual factors influence work outcomes in employed patients with ankylosing spondylitis starting etanercept: 2-year results from AS@Work.
The aim was to determine changes over time in work outcomes and investigate the predictive value of baseline personal and work-related factors on the evolution of work outcomes among employed patients with AS initiating etanercept. Employment status, absenteeism and presenteeism were assessed using the Work Productivity and Activity Impairment for AS questionnaire in a 24-month open-label, observational study (NCT01421303). The potential effect of baseline factors on work outcomes was analysed using predictive modelling (Cox regression and linear mixed models). After 24 months, 11/75 (14.7%) patients had permanently withdrawn from employment (seven because of AS). Absenteeism and presenteeism decreased significantly within 6 months of etanercept treatment and remained stable thereafter. Predictive modelling indicated that male sex (hazard ratio = 0.18; 95% CI: 0.04, 0.85), (log) number of working hours per week (hazard ratio = 0.13; 95% CI: 0.03, 0.51) and the possibility of developing skills (hazard ratio = 0.42; 95% CI: 0.19, 0.91) positively influenced time in employment. Over time, lower absenteeism was significantly associated with the quality of contact with colleagues [coefficient (s.e.): -0.35 (0.10)] and importance of the job for quality of life [-0.49 (0.17)], and higher absenteeism with current smoking [1.66 (0.44)] and change in job because of illness [1.51 (0.66)]. Over time, lower presenteeism was associated with male sex [-14.5 (2.64)], the possibility of postponing work [-6.60 (2.73)], quality of contact with colleagues [-2.04 (0.96)] and >50 workers in the company [-7.65 (2.76)], and higher presenteeism with manual profession [8.41 (2.72)]. Contextual factors influence work outcomes over time and should not be ignored when aiming to improve work outcomes in patients with AS. ClinicalTrials.gov, http://clinicaltrials.gov, NCT01421303.


[Serum cytokine levels in children with newly diagnosed active systemic juvenile idiopathic arthritis].
To study the changes in serum cytokines levels in children with newly diagnosed active systemic juvenile idiopathic arthritis (SJIA) and to explore the role of cytokines in the development and progression of SJIA. Seventy-four pediatric patients with active SJIA between January 2010 and December 2013 were included in the study. Serum levels of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukine-10 (IL-10), tumor necrosis factor (TNF), and interferon gamma (IFN-γ) were measured by flow cytometry in these patients. The levels of cytokines were also determined in 202 healthy children as the control group. Routine laboratory parameters including white blood cell (WBC) count, percentage of neutrophils, hemoglobin level, platelet count, hypersensitive C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR) were monitored in the patient group. The WBC count, percentage of neutrophils, hs-CRP, and ESR in 74 cases of SJIA were significantly above the normal range, their platelet counts were within the normal range, whereas hemoglobin levels were below the normal range. Compared with the control group, the patient group showed a significantly increased level of IL-6 (P<0.01) and significantly reduced levels of IL-4, IL-10, and TNF (P<0.01). However, there were no significant changes in serum levels of IL-2 and IFN-γ in the patient group (P>0.05). In SJIA children, IL-6 level, which was significantly elevated, was negatively correlated with hemoglobin level, which was significantly reduced (r=-0.244, P<0.05). Serum level of IL-6 is significantly increased in children with SJIA, and it has a negative correlation with anemia.


P-type calcium channels are blocked by the alkaloid daurisoline.
IN looking for a structurally defined non-peptide P-channel blocker we have tested the alkaloid daurisoline which has been isolated from traditional Chinese medicinal herb (Menispermum dauricum) used for the treatment of epilepsy, hypertension and asthma. We have found that daurisoline is an inhibitor of omega-Aga-IVA sensitive barium currents in cerebellar Purkinje cells and of excitatory postsynaptic potentials evoked in Purkinje cells by stimulating parallel fibres in acutely prepared cerebellar slices. Daurisoline did not significantly affect omega-Aga-IVA-insensitive barium currents recorded from granule cells freshly isolated from rat cerebellum. Daurisoline passes the blood-brain barrier and will, therefore, facilitate the functional characterization of brain calcium channels as well as the exploration of P-type calcium channels as possible drug targets.


Bioisosteres and Scaffold Hopping in Medicinal Chemistry.
The twin concepts of bioisosteric replacement and scaffold hopping are increasingly becoming important in modern drug design. The concepts of isosterism stretch back over a century, but only recently have systematic and data-intensive methods been used to explore appropriate replacements. Here, a summary of the history of bioisosterism is presented to provide context to the methods applied. Molecular similarity and data mining methods are introduced as approaches to introduce these replacements to rationalise the space of synthetic targets to consider in a medicinal chemistry project. Lastly, an outlook of the field is given of potential future improvements and areas of focus that should be considered to anyone interested in the field.


Motor root conduction in neuralgic amyotrophy: evidence of proximal conduction block.
To determine the presence and role of proximal conduction block in neuralgic amyotrophy. Percutaneous electrical stimulation of cervical roots and brachial plexus was employed in eight patients with neuralgic amyotrophy. Root to Erb's point compound muscle action potential amplitude ratios for abductor digiti minimi, extensor digitorum communis, biceps, and deltoid muscles were compared with results obtained from 10 healthy controls. Conduction block in the nerve to one muscle was found in three of eight patients (38%) suggesting focal proximal demyelination. Repeat studies showed axonal degeneration, resolution, and persistence of conduction block in these three patients respectively. Focal conduction block plays a significant part in the pathogenesis of neuralgic amyotrophy, which is generally regarded as an axon loss process. Therapeutic intervention should be directed to patients with persistent conduction block, with the aim of eradicating the block and possibly minimising subsequent axon loss.


Conformation-selective resonant photoelectron imaging from dipole-bound states of cold 3-hydroxyphenoxide.
We report a photoelectron imaging and photodetachment study of cryogenically cooled 3-hydroxyphenoxide (3HOP) anions, m-HO(C6H4)O-. In a previous preliminary study, two conformations of the cold 3HOP anions with different dipole bound states were observed [D. L. Huang et al., J. Phys. Chem. Lett. 6, 2153 (2015)]. Five near-threshold vibrational resonances were revealed in the photodetachment spectrum from the dipole-bound excited states of the two conformations. Here, we report a more extensive investigation of the two conformers with observation of thirty above-threshold vibrational resonances in a wide spectral range between 18 850 and 19 920 cm-1 (∼1000 cm-1 above the detachment thresholds). By tuning the detachment laser to the vibrational resonances in the photodetachment spectrum, high-resolution conformation-selective resonant photoelectron images are obtained. Using information of the autodetachment channels and theoretical vibrational frequencies, we are able to assign the resonant peaks in the photodetachment spectrum: seventeen are assigned to vibrational levels of anti-3HOP, eight to syn-3HOP, and five to overlapping vibrational levels of both conformers. From the photodetachment spectrum and the conformation-selective resonant photoelectron spectra, we have obtained fourteen fundamental vibrational frequencies for the neutral syn- and anti-m-HO(C6H4)O⋅ radicals. The possibility to produce conformation-selected neutral beams using resonant photodetachment via dipole-bound excited states of anions is discussed.


Rapid evolution of a bacterial iron acquisition system.
Under iron limitation, bacteria scavenge ferric (Fe3+ ) iron bound to siderophores or other chelates from the environment to fulfill their nutritional requirement. In gram-negative bacteria, the siderophore uptake system prototype consists of an outer membrane transporter, a periplasmic binding protein and a cytoplasmic membrane transporter, each specific for a single ferric siderophore or siderophore family. Here, we show that spontaneous single gain-of-function missense mutations in outer membrane transporter genes of Bradyrhizobium japonicum were sufficient to confer on cells the ability to use synthetic or natural iron siderophores, suggesting that selectivity is limited primarily to the outer membrane and can be readily modified. Moreover, growth on natural or synthetic chelators required the cytoplasmic membrane ferrous (Fe2+ ) iron transporter FeoB, suggesting that iron is both dissociated from the chelate and reduced to the ferrous form within the periplasm prior to cytoplasmic entry. The data suggest rapid adaptation to environmental iron by facile mutation of selective outer membrane transporter genes and by non-selective uptake components that do not require mutation to accommodate new iron sources.


[Pyrexia during delivery (author's transl)].
Amnionitis with pyrexia during labor and delivery and the perinatal complications of this syndrome are described. In our series the incidence of pyrexia during delivery was 0.54%. In 70 of 83 cases (84%) an intra-uterine infection was assumed to be the cause of the pyrexia. In 13 of 83 cases (16%) an extra-genital infection was the presumed cause. Intra-uterine infections are a grave danger for the mother and the newborn and constitute a severe complication. The mortality in cases with pyrexia during labor and delivery was elevated to 7 of 83 newborns (9%). Rapid delivery and the timely administration of antibiotics in sufficiently high dosages can prevent the manifestations of severe infections. Recommendations for the obstetric management of cases with pyrexia during labor and delivery are given.


Changes in kinetics of acetylcholine receptor channels after initial expression in Xenopus myocyte culture.
1. Developmental changes in single acetylcholine (ACh) receptor channel properties were analysed in cultured Xenopus myocytes at low temperatures (11-16 degrees C) using the cell-attached patch clamp technique. Single-channel recordings were done at fourteen stages of development ranging from several hours (stage 21) to 5 days (stage 47) after ACh receptors first appear in the muscle membrane. 2. Two types of channels, low conductance and high conductance, which have been described previously, were observed at all stages. At low concentrations of ACh, channel events often occurred as bursts of openings separated by closures briefer than 1 ms. Such bursts were treated as one event. Many brief, isolated channel openings, which were described in the preceding paper, were also observed. Developmental changes in burst duration, brief openings and brief closures were assessed for the period studied in culture. 3. Throughout development, most of the burst duration histograms for the low-conductance channel were not well fitted by a single exponential, having an excess of brief openings. The brief component could be largely accounted for by singly liganded openings, as described in the preceding paper. The burst durations reported here represent the main component of the distribution. At 150 nM-ACh, high-conductance channel burst duration histograms were well fitted by single exponentials. 4. There was a developmental increase in the percentage of single-channel events belonging to the high-conductance class. The percentage of high-conductance events remained low (less than 10%) for the first day after ACh receptors appeared (stages 20-34), and increased to 60% at stage 47. 5. In addition to a shift in channel population, there was a decrease in both low- and high-conductance channel burst durations during early stages of development (mostly within the first day in culture). The effect was more dramatic for the low-conductance channel: overall, low-conductance channel burst duration at 50 mV hyperpolarization over the resting potential decreased from 24 ms at stage 24/25 to 6 ms at stage 47, a 4-fold decrease. During the same period, high-conductance burst duration decreased from 10.6 to 4 ms. a 2.5-fold decrease. In contrast to the burst duration, the mean open time of 60 microseconds for the brief isolated class of opening in the low-conductance channel did not change with development. 6. Neither the single-channel conductance nor the voltage dependence of burst duration changed with development.(ABSTRACT TRUNCATED AT 400 WORDS)


Myeloid-derived suppressor cells regulate growth of multiple myeloma by inhibiting T cells in bone marrow.
Myeloid-derived suppressor cells (MDSC) are one of the major factors limiting the immune response in cancer. However, their role in bone marrow (BM), the site of primary localization of multiple myeloma (MM), is poorly understood. In this study, we found a significant accumulation of CD11b(+)CD14(-)CD33(+) immunosuppressive MDSC in BM of patients with newly diagnosed MM. To assess the possible role of MDSC in MM, we used immunocompetent mouse models. Immunosuppressive MDSC accumulated in BM of mice as early as 1 wk after tumor inoculation. S100A9 knockout (KO) mice, which are deficient in their ability to accumulate MDSC in tumor-bearing hosts, demonstrated reduced MDSC accumulation in BM after injection of MM cells compared with wild-type mice. Growth of the immunogenic MM cells was significantly reduced in S100A9KO mice. This effect was associated with the accumulation of Ag-specific CD8(+) T cells in BM and spleens of S100A9KO mice, but not wild-type mice, and was abrogated by the administration of anti-CD8 Ab or adoptive transfer of MDSC. Thus, the accumulation of MDSC at early stages of MM plays a critical role in MM progression and suggests that MDSC can be considered a possible therapeutic target in this disease.


Enumeration of Chemoorganotrophic Carbonyl Sulfide (COS)-degrading Microorganisms by the Most Probable Number Method.
Carbonyl sulfide (COS) is the most abundant sulfur compound in the atmosphere, and, thus, is important in the global sulfur cycle. Soil is a major sink of atmospheric COS and the numerical distribution of soil microorganisms that degrade COS is indispensable for estimating the COS-degrading potential of soil. However, difficulties are associated with counting COS-degrading microorganisms using culture-dependent approaches, such as the most probable number (MPN) method, because of the chemical hydrolysis of COS by water. We herein developed a two-step MPN method for COS-degrading microorganisms: the first step for chemoorganotrophic growth that supported a sufficient number of cells for COS degradation in the second step. Our new MPN analysis of various environmental samples revealed that the cell density of COS-degrading microorganisms in forest soils ranged between 106 and 108 MPN (g dry soil)-1, which was markedly higher than those in volcanic deposit and water samples, and strongly correlated with the rate of COS degradation in environmental samples. Numerically dominant COS degraders that were isolated from the MPN-positive culture were related to bacteria in the orders Bacillales and Actinomycetales. The present results provide numerical evidence for the ubiquity of COS-degrading microbes in natural environments.


Design, Synthesis and Bioactivities of Novel 1,4-Pentadien-3-one Derivatives Containing a Substituted Pyrazolyl Moiety.
In this study, in order to find novel biologically active penta-1,4-dien-3-one derivatives, a series of penta-1,4-dien-3-one compounds containing a substituted pyrazole subunit were designed and synthesized. Their structures were characterized by ¹H-NMR, 13C-NMR and elemental analysis. The preliminary bioassays displayed that most of the title compounds showed significant antiproliferative activity against HepG2 cell lines. Especially, compounds 7a-m, o, r, s, u, w, y and z were active against HepG2 cells with IC50 values of 0.10-5.05 μM, which were superior to that of the contrast sorafenib (IC50 = 16.20 μM).


Case report of Acremonium intraocular infection after cataract extraction.
A 64-year-old woman was referred to our clinic for the treatment of chronic uveitis in her left eye, which had started two weeks after an uncomplicated cataract extraction. She was treated with topical steroids with an initially good response, yet she subsequently developed severe inflammation and plaque-like material around the intraocular lens, despite continuous steroid therapy. She underwent pars plana vitrectomy, smear and culture of the aqueous and vitreous fluids, and intravitreal antibiotic injection under the impression of Propionibacterium acne (P. acne) endophthalmitis. As a result of the smear and culture of the vitreous fluid identified as an Acremonium species, she was treated with intravenous amphotericin B injections for five days, followed by oral voriconazole administration. During the post-operative 18-month follow-up, she was stable without significant relapse of uveitis. In this case, the best correction of visual acuity was an improvement from 20/40 to 20/20.


A comparative study on the effect of the insole materials with subtalar strapping in patients with medial compartment osteoarthritis of the knee.
Abstract This study was conducted to assess the symptomatic effects of the insole with an elevation of 12 mm composed of urethane (urethane insole) or of sponge rubber (rubber insole) with subtalar strapping in patients with medial compartment osteoarthritis of the knee (knee OA). The setting was an outpatient clinic. Eighty-four patients with knee OA were prospectively randomized, and evaluated and treated with the urethane or rubber insole for 4 weeks. Randomization was performed according to birth date and each participant was categorized into the urethane group or the rubber group. The percentage of remission of Lequesne index of severity for knee OA was compared between urethane and rubber insole groups at the conclusion of the study. Participants were asked to report adverse effects of use of the respective insoles. The percentage of remission was significantly improved in the urethane insole group (n = 42) compared with the rubber insole group (n = 42) (P = 0.001). Adverse effects were more common in the rubber insole group (17 out of 42, 40.5%) than in the urethane insole group (8 out of 42, 19.0%), and this was statistically significant (P = 0.028). The inserted insole in combination with subtalar strapping had a more natural form-fit to the sole than the insole insert alone. In our study of the subtalar strapping insole, an insole composed of urethane, was more comfortable than that of rubber sponge.