[Biobanks European infrastructure].
Biobanks are structured repositories of human tissue samples connected with specific information. They became an integral part of personalized medicine in the new millennium. At the European research area biobanks are isolated not well coordinated and connected to the network. European commission supports European infrastructure BBMRI-ERIC (Biobanks and Biomolecular Resources Research Infrastructure European Research Infrastructure Consortium), consortium of 54 members with more than 225 associated organizations, largely biobanks from over 30 countries. The aim is to support biomedical research using stored samples. Czech Republic is a member of the consortium as a national node BBMRI_CZ, consisting of five partners.


Targeted disruption of the pemphigus vulgaris antigen (desmoglein 3) gene in mice causes loss of keratinocyte cell adhesion with a phenotype similar to pemphigus vulgaris.
In patients with pemphigus vulgaris (PV), autoantibodies against desmoglein 3 (Dsg3) cause loss of cell-cell adhesion of keratinocytes in the basal and immediate suprabasal layers of stratified squamous epithelia. The pathology, at least partially, may depend on protease release from keratinocytes, but might also result from antibodies interfering with an adhesion function of Dsg3. However, a direct role of desmogleins in cell adhesion has not been shown. To test whether Dsg3 mediates adhesion, we genetically engineered mice with a targeted disruption of the DSG3 gene. DSG3 -/- mice had no DSG3 mRNA by RNase protection assay and no Dsg3 protein by immunofluorescence (IF) and immunoblots. These mice were normal at birth, but by 8-10 d weighed less than DSG3 +/- or +/+ littermates, and at around day 18 were grossly runted. We speculated that oral lesions (typical in PV patients) might be inhibiting food intake, causing this runting. Indeed, oropharyngeal biopsies showed erosions with histology typical of PV, including suprabasilar acantholysis and "tombstoning" of basal cells. EM showed separation of desmosomes. Traumatized skin also had crusting and suprabasilar acantholysis. Runted mice showed hair loss at weaning. The runting and hair loss phenotype of DSG3 -/- mice is identical to that of a previously reported mouse mutant, balding (bal). Breeding indicated that bal is coallelic with the targeted mutation. We also showed that bal mice lack Dsg3 by IF, have typical PV oral lesions, and have a DSG3 gene mutation. These results demonstrate the critical importance of Dsg3 for adhesion in deep stratified squamous epithelia and suggest that pemphigus autoantibodies might interfere directly with such a function.


Complete genome sequence of a human enterovirus 71 strain isolated in brunei in 2006.
The complete genome sequence of a human enterovirus 71 strain isolated in Brunei in 2006 was determined. Phylogenetic analysis based on the complete genome sequence classified this strain into subgenogroup B5.


Psychoanalytic psychotherapy with men with intellectual disabilities: a preliminary outcome study.
Psychotherapy has been demonstrated to be an effective form of treatment for people with psychological problems. However, there is considerable resistance to attempts to generalize these findings to people with intellectual disabilities. Such therapeutic disdain has a long history without any empirical foundation. Recently it has been argued on philosophical grounds that people with intellectual disabilities should have access to the same services as everyone else. Furthermore, that people with intellectual disabilities should be actively targeted as they are more likely to have psychological difficulties than non-handicapped people. The therapeutic literature concerning people with intellectual disabilities is overwhelmingly behavioural. More recently various psychotherapeutic approaches have been explored as alternatives to behavioural interventions. Publication of several case studies in the late 1980s and early 1990s has provided some evidence for the benefit of various psychotherapeutic approaches with people with intellectual disabilities. However, there are no outcome studies. This paper reports an outcome study of individual psychoanalytic psychotherapy provided in normal clinical practice for 25 men with intellectual disabilities who were referred for behaviour problems. Of the 25 participants in the study, 20 completed treatment. In most cases the problem behaviour was eliminated and this was maintained at six months follow-up.


Synchronous RCC with NHL: a case report.
A 55 year old man presented with cervical adenopathy of two months duration.Biopsy of the node showed T-cell lymphoma, which was confirmed by immunohistochemistry. An abdominal CT done for the staging work-up of the lymphoma, revealed a left renal mass which histologically proved to be renal cell carcinoma [RCC], grade II, stage I. An association between RCC and lymphoma is rare and this case is documented for the synchronous and concurrent occurrence of non-Hodgkin's lymphoma [NHL] of T-cell type and RCC.


Mechanisms of pathogenesis in drug hepatotoxicity putting the stress on mitochondria.
Mitochondria play key roles in aerobic life and in cell death. Thus, interference of normal mitochondrial function impairs cellular energy and lipid metabolism and leads to the unleashing of mediators of cell death. The role of mitochondria in cell death due to drug hepatotoxicity has been receiving renewed attention and it is therefore timely to assess the current status of this area.


A hip disarticulation prostheses test system to simulate gait for prostheses evaluation.
The limited number of hip prostheses users makes it less feasible to conduct amputee tests for prosthesis development in the clinic, which restricts the development efficiency of the intelligent prostheses. This study proposes a hip disarticulation prostheses test system (HDPTS) to supplement the amputee tests for hip disarticulation prosthesis (HDP) evaluation, which would potentially facilitate the prosthesis evaluation safety and development efficiency. The hip trajectory of an individual with normal gait was acquired and reproduced by calculating the corresponding movement joint angle of a manipulator. Then, an HDP was fit on an amputee and on the HDPTS respectively to obtain the hip and knee joint angles of the HDP during walking. Comparing the root mean square error (RMSE) of the expected and planned trajectory, the joint angles between the amputee test and HDPTS test, to verify the feasibility and accuracy of the HDPTS for prosthesis evaluation. The RMSE between the expected and planned trajectory value was less than 1.20 mm (< 0.19%). The RMSE of the joint angles between the amputee test and HDPTS test were 2.18∘ (1.8%) and 3.13∘ (5.92%) for hip and knee joint respectively. The HDPTS was found accurate in hip trajectory reproduction and feasible in gait simulation for the prosthesis evaluation, which could potentially supplement the amputee test for prosthesis design thus improving prosthesis test safety and development efficiency.


Family structure as recalled by borderline patients.
Research on the family of the borderline patient has been largely descriptive or anecdotal. This work was designed to provide data on the families of 26 patients fulfilling stringent criteria for borderline personality disorder. A standardized scoring instrument recorded the impressions of the adult borderline of his family experience during childhood and adolescence. The male parental figure was perceived as dominant significantly more often than the female figure. Female figures manifested significantly more affection toward the borderline child. Family relations tended to be perceived as deteriorating and to be more conflictual as the borderline patient aged. Results were discussed in terms of the developmental psychology, genetics, and existent family research on the borderline patient.


Limbic Encephalitis With Dual Positivity.
Limbic encephalitis is a well-defined clinical disorder among paraneoplastic neurological syndromes. Although it is not always possible to identify specific autoantibodies in limbic encephalitis, the presence of anti-neuronal nuclear antibody type 1 (ANNA1 or anti-Hu), anti-Ma2, collapsin response mediator protein 5 (CRMP-5-IgG or anti-CV2), anti-GABAB receptors and anti-amphiphysin antibodies are often detected. A 66-year-old male patient with complaints of forgetfulness was evaluated in our clinic after having seizures. In the neurological examination, the patient was found to be confused. In cranial MR fluid-attenuated inversion recovery (FLAIR) and T2-weighted images, the right hippocampal and parahippocampal structures showed hyperintense areas complying with limbic encephalitis. He had improvement with a course of 2 g/kg intravenous immunoglobulin (IVIG) followed by high-dose methylprednisolone therapy. Following the high-dose methylprednisolone therapy, anti-PCA1 (Yo) and anti-amphiphysin antibodies were positive and the tissue pathology report confirmed combined small-cell carcinoma and large-cell neuroendocrine carcinoma of the lung. In recent years, paraneoplastic neurological syndromes are better recognized with the identification of specific antibodies and the ubiquitous information on pathogenesis. This is the first known report in the literature that a case with both positive anti-PCA1 (Yo) and anti-amphiphysin antibodies together and underlying small-cell and large-cell neuroendocrine carcinomas.


Usefulness of white blood cell count to mean platelet volume ratio in the prediction of SYNTAX score in patients with non-ST elevation myocardial infarction.
White blood cell (WBC) count to mean platelet volume (MPV) ratio (WMR) is associated with major adverse cardiovascular events in patients with non-ST elevation acute coronary syndrome (NSTEMI). We aimed to compare WMR between NSTEMI patients and matched-controls and to evaluate its predictive value on SYNTAX score. Total 175 patients with NSTEMI and 160 age and co-morbidity matched subjects were recruited in our study. WMR was compared between the patient and control groups. The patient group was further subdivided into 3 tertiles according to SYNTAX scores as follows: low SYNTAX score tertile (score ≤22, 141 patients); intermediate SYNTAX score tertile (score between 23 and 32, 20 patients); and, high SYNTAX score tertile (score ≥33, 14 patients). WMR was further assessed among the tertiles. WMR was significantly greater in the patient group compared to the control group (p<0,001). WMR among low, intermediate and high score tertiles were calculated to be 890±26, 1090±042 and 1500±65, respectively (p <0,001). In receiver operating characteristics (ROC) analysis, WMR >960 predicted a SYNTAX score ≥23 with 80.6% sensitivity and 67.6% specificity (AUC: 0.756; 95% CI: 0.685 - 0.818; p <0.0001) and a WMR >1360 predicted a SYNTAX score ≥33 with 71.4% sensitivity and 93% specificity (AUC: 0.840; 95%CI: 0.777 - 0.892; p <0.0001). WMR value was significantly elevated in NSTEMI patients, compared to controls. Higher WMR was associated with greater SYNTAX score in patients with NSTEMI. WMR may be used to predict severity of the CAD and to implement risk stratification in patients with NSTEMI.


A new secondary metabolite from the fermented mycelia of Streptomyces antibiotic H41-55.
An actinomycete strain, H41-55 from sea sediment was identified as Streptomyces antibiotic on the basis of its morphological, physiological and biochemical characteristics as well as 16S rDNA data. A new secondary metabolite, (2S,3R)-N-[3-(formylamino)-2-hydroxybenzoyl]-l-threonine propyl ester (1), together with five known compounds was isolated from fermentation product by use of silica gel and Sephadex LH-20 column chromatography, and preparative RP-C18 HPLC, and identified by HR-TOF-MS and NMR spectra. The cytotoxicities of these isolates against three cancer cell lines and their antifungal activities on Candida albicans were tested. Compounds 1, 3, 5, and 6 displayed moderate cytotoxicity. 5 and 6 showed inhibitory activity on C. albicans.


Comparison of Ferric Sulfate Combined Mineral Trioxide Aggregate Pulpotomy and Zinc Oxide Eugenol Pulpectomy of Primary Maxillary Incisors: An 18-month Randomized, Controlled Trial.
The purpose of this study was to compare outcomes and survival of ferric sulfate with mineral trioxide aggregate (FS+MTA) pulpotomy and root canal therapy (RCT) in carious vital primary maxillary incisors. In this parallel group noninferiority trial, asymptomatic carious vital primary incisors with pulp exposure in healthy 18- to 46-month-olds were allocated randomly to receive FS+MTA pulpotomy or RCT between September 2010 and September 2012. Each incisor was classified into one of the following radiographic outcomes: N (incisor without pathologic change); Po (pathologic change present, follow-up recommended); Px (pathologic change present, extract.) Clinical findings and incisor survival were secondary outcomes. Seventy subjects were enrolled with a total of 172 incisors. Twelve- and 18-month radiographic outcomes demonstrated no statistical difference between FS+MTA pulpotomy and RCT incisors for Px outcomes (P=0.38; odds ratio equals 0.60; 95 percent confidence interval equals 0.19 to 1.89; chi-square test). There was no statistical differences in clinical outcomes for FS+MTA pulpotomy and RCT at 12 and 18 months (P=0.51; Fisher's exact test) or survival for FS+MTA pulpotomy and RCT incisors (P=0.11; log-rank test). Ferric Sulfate with Mineral Trioxide Aggregate (FS+MTA) is an alternative to RCT for vital primary incisors.


Integrated Acoustic Separation, Enrichment, and Microchip Polymerase Chain Reaction Detection of Bacteria from Blood for Rapid Sepsis Diagnostics.
This paper describes an integrated microsystem for rapid separation, enrichment, and detection of bacteria from blood, addressing the unmet clinical need for rapid sepsis diagnostics. The blood sample is first processed in an acoustophoresis chip, where red blood cells are focused to the center of the channel by an acoustic standing wave and sequentially removed. The bacteria-containing plasma proceeds to a glass capillary with a localized acoustic standing wave field where the bacteria are trapped onto suspended polystyrene particles. The trapped bacteria are subsequently washed while held in the acoustic trap and released into a polymer microchip containing dried polymerase chain reaction (PCR) reagents, followed by thermocycling for target sequence amplification. The entire process is completed in less than 2 h. Testing with Pseudomonas putida spiked into whole blood revealed a detection limit of 1000 bacteria/mL for this first-generation analysis system. In samples from septic patients, the system was able to detect Escherichia coli in half of the cases identified by blood culture. This indicates that the current system detects bacteria in patient samples in the upper part of the of clinically relevant bacteria concentration range and that a further developed acoustic sample preparation system may open the door for a new and faster automated method to diagnose sepsis.


Effectiveness and Predictors of Response to 1-Hz Repetitive Transcranial Magnetic Stimulation in Patients With Obsessive-Compulsive Disorder.
The present study aimed to assess the effectiveness of repetitive transcranial magnetic stimulation (rTMS) treatment targeting either supplementary motor area (SMA) or orbitofrontal cortex (OFC) among patients with OCD in real-world clinical practice settings. Also, the present study explored for potential predictors of response to rTMS treatment. Retrospective review and analysis of records of 79 patients with medication-refractory OCD, all of whom had received 20 sessions of 1-Hz rTMS as part of routine clinical care. Of 79 patients, 46 received rTMS over the bilateral SMA and 33 over the left OFC. A reduction of 25% and 35% in Yale-Brown Obsessive Compulsive Scale (YBOCS) scores was used to classify outcome as partial and complete response, respectively. Statistical analysis was done using SPSS version 23.0. There was a significant decrease in mean YBOCS score from baseline to end of treatment (7.68 ± 5.62; t = 12.14, P < 0.001). Forty-five patients (57%) met criteria for partial response, of which 32 patients (40.5%) showed complete response. There was no significant difference in outcomes between patients receiving rTMS over SMA or OFC. Binary logistic regression analysis revealed presence of comorbid depression and higher baseline YBOCS score to be associated with lesser likelihood of response to rTMS. This study provided evidence for overall effectiveness of adjunctive 1-Hz rTMS treatment over either SMA or OFC in patients with medication-refractory OCD, and reported comorbid depression and higher pretreatment YBOCS scores as potential predictors of poor response to rTMS.


Deep Infection after Distal Radius Open-reduction Internal Fixation: A Case Series.
Given its low incidence, the management of deep infection following distal radius open-reduction internal fixation (ORIF) has not been well reported. In an effort to expand our current understanding, the purpose of this case series is to present the treatment strategies and functional outcomes associated with deep infection after distal radius ORIF. All patients with deep infections after distal radius ORIF over a ten-year period were identified and their treatment courses asessed. The cohort consisted of three women and one man with an average age of 55.5 ± 17.6 years. Mean time from infection presentation to irrigation and debridement (I&D) with removal of hardware (ROH) was 16 days (Range: 3 - 44 days). The identified bacterial species in all cases was Staphylococcus aureus (MRSA = 2, MSSA = 2). Three patients were treated with intravenous antibiotics, while one patient was treated with oral antibiotics. Mean time from infection presentation to final clinical follow-up was 11 months (Range: 3 - 20 months). Two patients required repeat I&D. A clinical determination of successful infection eradication was made in all cases. The reported rate of deep infection after distal radius ORIF is less than 1%. There is no well-defined treatment algorithm for patients with deep infection after distal radius ORIF. However, removal of hardware and post-operative oral or intravenous antibiotic therapy appears effective, and is consistent with the standard practices of treating infection after other orthopaedic surgeries.


Re-KALC for a Meaningful Beginning: The Practice of Being.
The new year is a time for goal setting, reflection, and new beginnings. Often, resolutions begin with self-improvements of the physical kind-losing weight, exercising, eating clean. These are important ideas and goals, although often difficult to sustain in part because sustaining is an implied element of each. Intentions are different than goals in the sense that an intention can be implemented in any moment in time simply through the process of mindful reflection. J Contin Educ Nurs. 2018;49(2):55-56.


An exaggerated blood pressure response to exercise is associated with the dietary sodium, potassium, and antioxidant vitamin intake in normotensive subjects.
This study was designed to examine the associations between an exaggerated systolic blood pressure (SBP) response to exercise and the nutrient intake in normotensive subjects. The subjects consisted of 302 normotensive subjects (64 males and 238 females; age, 48.4 ± 11.3 years) without a history of cardiovascular disease or stroke who were not taking any medications. Each subject performed a multistage graded submaximal exercise stress test using an electric bicycle ergometer, and their blood pressure was measured at rest and during the last minute of each stage. The nutrient intake was assessed using a self-administered food frequency questionnaire. An exaggerated SBP response to exercise was defined according to the criteria of the Framingham Study (peak SBP ≥210 mmHg in males, or ≥190 mmHg in females). An exaggerated SBP response to exercise was observed in 85 subjects. A multiple logistic regression analysis revealed that the dietary sodium-to-potassium (Na/K) ratio (odds ratio [OR]: 5.75, 95% confidence interval [CI]: 2.37-13.75, p = 0.001) and vitamin E intake (OR: 0.67, 95% CI: 0.51-0.93, p = 0.012) were significantly associated with an exaggerated SBP response to exercise. Furthermore, the percent change in SBP during exercise was found to be significantly associated with an increase in the dietary Na/K ratio (p for trend = 0.0005) and a decrease in the vitamin E intake (p for trend = 0.018). These results suggest that an exaggerated SBP response to exercise was associated with the dietary sodium, potassium, and antioxidant vitamin intake in normotensive subjects.


Multidisciplinary approaches to understanding collective cell migration in developmental biology.
Mathematical models are becoming increasingly integrated with experimental efforts in the study of biological systems. Collective cell migration in developmental biology is a particularly fruitful application area for the development of theoretical models to predict the behaviour of complex multicellular systems with many interacting parts. In this context, mathematical models provide a tool to assess the consistency of experimental observations with testable mechanistic hypotheses. In this review, we showcase examples from recent years of multidisciplinary investigations of neural crest cell migration. The neural crest model system has been used to study how collective migration of cell populations is shaped by cell-cell interactions, cell-environmental interactions and heterogeneity between cells. The wide range of emergent behaviours exhibited by neural crest cells in different embryonal locations and in different organisms helps us chart out the spectrum of collective cell migration. At the same time, this diversity in migratory characteristics highlights the need to reconcile or unify the array of currently hypothesized mechanisms through the next generation of experimental data and generalized theoretical descriptions.


Advantages and limitations of endoscopic endonasal approaches to the skull base.
The anatomy of the skull base is extremely complex with an abundance of critical neurovascular bundles and their corresponding foramina as well as the insertions and origins of multiple masticatory and craniocervical muscles. These anatomic intricacies increase the difficulty of surgery within this area. Advantages and disadvantages of endoscopic endonasal approaches (EEAs) based on the authors' sequential learning and experience are described. EEAs offer the advantages of using preexistent air spaces that enable accessing various areas of the skull base, while avoiding external incisions or scars and obviating the need for the translocation of the maxillofacial skeleton. In addition, EEAs are well suited to preserve neurologic, visual, and masticatory functions as well as cosmesis. However, the sinonasal corridor must be expanded and optimized to access the skull base adequately, facilitate the reconstruction of the surgical defect, avoid sinonasal complications, and minimize sequelae. Important considerations can limit or indicate the approach, such as the nature of the pathology, including location, diagnosis, and vascularity; patient characteristics, including age and medical comorbidities; surgeon attributes, including training, experience, and expertise; the resultant need to reconstruct large skull base defects and feasible alternatives to do so; and institutional resources, including adjunctive services, an intensive care unit, and operating room equipment. EEAs are important techniques in contemporary skull base surgery. Understanding the indications for and limitations of these approaches help to maximize outcomes.


Increasing availability of benzodiazepines among people who inject drugs in a Canadian setting.
Benzodiazepine misuse is associated with mortality and is common among people who inject drugs (PWID). This study aimed to examine the temporal trends in the availability of benzodiazepines among PWID in a Canadian setting, and to identify factors associated with more immediate access to benzodiazepines. Data were derived from 3 prospective cohorts of PWID in Vancouver, Canada, between June 2012 and May 2015. The primary outcome was the perceived availability of benzodiazepines, measured in 3 levels: not available, delayed availability (available in ≥10 minutes), and immediate availability (available in <10 minutes). The authors used multivariable generalized estimating equations to identify factors associated with availability of benzodiazepines. In total, 1641 individuals were included in these analyses. In multivariable analyses, factors associated with immediate benzodiazepine availability included incarceration (adjusted odds ratio [AOR]: 1.42, 95% confidence interval [CI]: 1.06, 1.89) and participation in methadone maintenance therapy (MMT) (AOR: 1.35, 95% CI: 1.14, 1.60). Factors associated with delayed benzodiazepine availability included incarceration (AOR: 1.45, 95% CI: 1.02, 2.07) and participation in MMT (AOR: 1.77, 95% CI: 1.48, 2.12). Benzodiazepine availability increased throughout the study period for both immediate (AOR: 1.14, 95% CI: 1.10, 1.18 per 6-month follow-up period) and delayed (AOR: 1.17, 95% CI: 1.12, 1.22 per 6-month follow-up period) availability. Among our sample of PWID, benzodiazepine availability is increasing and was associated with health and criminal justice system characteristics. Our findings indicate a need to examine prescribing practices and educate both PWID and health care providers about the risks associated with benzodiazepine use.


Cross-species analysis and comparison of the inner ear between chickens and mice.
The inner ear of mammals includes the cochlea and vestibule, which house specialized hair cells that are responsible for hearing and balance, respectively. While cochlear hair cells fail to regenerate following damage, those of the utricle, which is part of the vestibular apparatus, show partial regeneration. In birds, the macula lagena, a unique ear structure in this clade, has the ability to regenerate hair cells similarly to the utricle. Many studies have sought to explain regeneration in terms of evolution and species differences. However, it remains unclear what the cellular and molecular basis is behind the differences in inner ear structures and between avians and mammals. In the present study, we first investigated the anatomical structures of the inner ear of both chickens and rodents. We then performed RNA sequencing (RNA-Seq) and made cross-species analyses of the expression of homologous genes obtained from the inner ear tissue from both chickens and mice. Finally, we focused on the lagena, the basilar papilla, and the utricle in chickens and identified differentially expressed genes between tissues and determined the expression patterns of genes involved in inner ear structure formation by single-cell RNA sequencing and bulk RNA-Seq. We concluded that the cellular and molecular composition of the lagena is more similar to that of the utricle than the cochlea. Taken together, our study provides a valuable resource for the study of inner ear evolution and development.


Plaunotol stimulates endogenous secretin release and exocrine pancreatic secretion in rats.
The effect of the new antiulcer agent plaunotol on the release of endogenous secretin and the pancreatic exocrine secretion was investigated in anesthetized rats. In 48 rats with pancreatic and biliary diversion, continuous intraduodenal infusion of plaunotol in 3 graded doses (5, 20 and 80 mg/h/rat) resulted in significant increases in both circulating plasma secretin concentration and pancreatic exocrine secretion, including volume and bicarbonate output, in a dose-dependent manner (r = 0.655, p less than 0.001; r = 0.598, p less than 0.001; r = 0.436, p less than 0.01, respectively). The pancreatic bicarbonate output was closely correlated to plasma secretin concentrations (r = 0.631, p less than 0.001). Amylase output also increased after plaunotol administration, but not in a dose-dependent manner (r = 0.092, n.s.). These findings suggest strongly that the increase in pancreatic secretion of fluid and bicarbonate output was mainly due to increased endogenous secretin release resulting from plaunotol administration.


Trust in haptic assistance: weighting visual and haptic cues based on error history.
To effectively interpret and interact with the world, humans weight redundant estimates from different sensory cues to form one coherent, integrated estimate. Recent advancements in physical assistance systems, where guiding forces are computed by an intelligent agent, enable the presentation of augmented cues. It is unknown, however, if cue weighting can be extended to augmented cues. Previous research has shown that cue weighting is determined by the reliability (inversely related to uncertainty) of cues within a trial, yet augmented cues may also be affected by errors that vary over trials. In this study, we investigate whether people can learn to appropriately weight a haptic cue from an intelligent assistance system based on its error history. Subjects held a haptic device and reached to a hidden target using a visual (Gaussian distributed dots) and haptic (force channel) cue. The error of the augmented haptic cue varied from trial to trial based on a Gaussian distribution. Subjects learned to estimate the target location by weighting the visual and augmented haptic cues based on their perceptual uncertainty and experienced errors. With both cues available, subjects were able to find the target with an improved or equal performance compared to what was possible with one cue alone. Our results show that the brain can learn to reweight augmented cues from intelligent agents, akin to previous observations of the reweighting of naturally occurring cues. In addition, these results suggest that the weighting of a cue is not only affected by its within-trial reliability but also the history of errors.


Corticotropin-releasing hormone- and adrenocorticotropin-producing pituitary carcinoma with metastases to the liver and lung in a patient with Cushing's disease.
A 53-yr-old man with Cushing's disease was found to have a pituitary carcinoma with metastases to the liver and lung which produced both CRH and ACTH simultaneously. Despite removal of the pituitary tumor, his Cushing's disease worsened. Endocrinological examination then demonstrated elevated plasma CRH and markedly elevated plasma ACTH, beta-lipotropin, and cortisol concentrations, increased urinary 17-hydroxycorticosteroid and 17-ketosteroid excretion, and no suppression of serum cortisol after low or high dose dexamethasone administration. Urinary 17-hydroxycorticosteroid excretion increased in response to metyrapone, and lysine vasopressin elicited a striking increase in plasma ACTH. A computed tomographic scan of abdomen revealed multiple hypodense areas in the liver and bilateral adrenal hyperplasia. Postmortem histological examination revealed a necrotic hemorrhagic pituitary carcinoma with metastases to the liver, lung, and olfactory bulb. Immunohistochemical staining, gel filtration, and Northern blot analysis of liver and lung metastases revealed evidence of the production of both CRH and ACTH in these metastases. We concluded that the patient's pituitary carcinoma produced both CRH and ACTH.


Depression as a Manifestation of Obstructive Sleep Apnea.
Obstructive sleep apnea (OSA) often results in a wide range of comorbid conditions, predominantly of the cardiovascular/respiratory, endocrine/metabolic, and neuropsychiatric symptoms. In view of the ambiguity of literature regarding the association between OSA and depression, we conducted this study to show any association between the two disorders. The aim of the study was to see the association between OSA and depression and to study the prevalence of OSA in patients suffering from depression. We performed polysomnography (PSG) studies of patients that were referred from various subspecialty clinics from July 2011 to August 2013. Psychiatric diagnosis was done using mini international neuropsychiatric interview plus scale. This was followed by application of Hamilton Depression Rating Scale (HAM-D). Standard methods of statistical analysis were used for data analysis. Out of 182 patients who underwent PSG, 47 were suffering from depression with a mean age significantly more (P < 0.001) than that of other population (58.60 years vs. 53.60 years). In our 47 depressed patients, 44 (93.6%) had abnormal PSG. Based on apnea-hypopnea index score, 3 (6.8%) patients had mild, 18 (40.9%) had moderate, and 23 (52.3%) had severe OSA. The mean HAM-D score was significantly more in depression patients, (17. 35 ± 5.45) as compared to non depressive patents (8.64 ± 6.24) (P = 0.0001). This study demonstrates significant overlap between the sleep apnea and depression. Health specialists need more information about screening for patients with OSA to ensure proper diagnosis and treatment of those with the condition. Most of the clinicians do not suspect this important comorbidity of depression in the beginning resulting in delayed diagnosis.


Modeling measurement error in tumor characterization studies.
Etiologic studies of cancer increasingly use molecular features such as gene expression, DNA methylation and sequence mutation to subclassify the cancer type. In large population-based studies, the tumor tissues available for study are archival specimens that provide variable amounts of amplifiable DNA for molecular analysis. As molecular features measured from small amounts of tumor DNA are inherently noisy, we propose a novel approach to improve statistical efficiency when comparing groups of samples. We illustrate the phenomenon using the MethyLight technology, applying our proposed analysis to compare MLH1 DNA methylation levels in males and females studied in the Colon Cancer Family Registry. We introduce two methods for computing empirical weights to model heteroscedasticity that is caused by sampling variable quantities of DNA for molecular analysis. In a simulation study, we show that using these weights in a linear regression model is more powerful for identifying differentially methylated loci than standard regression analysis. The increase in power depends on the underlying relationship between variation in outcome measure and input DNA quantity in the study samples. Tumor characteristics measured from small amounts of tumor DNA are inherently noisy. We propose a statistical analysis that accounts for the measurement error due to sampling variation of the molecular feature and show how it can improve the power to detect differential characteristics between patient groups.


Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas.
The functional unit of the endocrine pancreas is the islet of Langerhans. Islets are nested within the exocrine tissue of the pancreas and are composed of alpha-, beta-, delta- and gamma-cells. beta-Cells produce insulin and form the core of the islet, whereas alpha-, delta- and gamma-cells are arranged at the periphery of the islet and secrete glucagon, somatostatin and a pancreatic polypeptide, respectively. Little is known about the molecular and genetic factors regulating the lineage of the different endocrine cells. Pancreas development is known to be abolished in Pdx1-mutant mice and Pax4 mutants lack insulin-producing beta-cells. Here we show that the paired-box gene Pax6 is expressed during the early stages of pancreatic development and in mature endocrine cells. The pancreas of Pax6 homozygous mutant mice lack glucagon-producing cells, suggesting that Pax6 is essential for the differentiation of alpha-cells. As mice lacking Pax4 and Pax6 fail to develop any mature endocrine cells, we conclude that both Pax genes are required for endocrine fate in the pancreas.


Fertility results after ovarian transposition for pelvic malignancies treated by external irradiation or brachytherapy.
The aim of this study was to assess the fertility outcome after ovarian transposition with uterine conservation and pelvic irradiation therapy for pelvic cancer. A total of 37 consecutive cases were reviewed. Of these, 27 patients were treated for a clear cell adenocarcinoma of the vagina and/or the cervix (group 1), nine for an ovarian pure dysgerminoma and one for a para-uterine soft tissue sarcoma (group 2). The pregnancy rate was 15% (4/27) in group 1 and 80% (8/10) in group 2 (P=0.01). A total of 18 pregnancies was observed in 12 patients. Of these, 16 pregnancies were obtained spontaneously and two after in-vitro fertilization. Of the spontaneous pregnancies, 12 (75%) were observed with ovaries still in the abdominal cavity (not repositioned). These results show that the prognosis for fertility is excellent after ovarian transposition and irradiation in patients with morphologically normal genital tracts (group 2). The prognosis is not as good for patients treated for a clear cell adenocarcinoma of the vagina and/or the cervix who may have morphological and/ or functional anomalies of the genital tract, following exposure to diethylstilboestrol and brachytherapy (group 1). Furthermore, these results show that repositioning of the ovary is not essential to achieve pregnancy.


Exploring the social and neighbourhood predictors of diabetes: a comparison between Toronto and Chicago.
This report examined the impact and extent that spatial access to primary care physicians (PCPs) and social neighbourhood-/community-level factors have on diabetes prevalence for Toronto and Chicago. The two-step floating catchment area method was used to compute spatial access scores. Bivariate correlation and multivariate linear regression identified the factors that were associated with, and/or predicted, diabetes prevalence. Potential spatial access to PCPs had no strong associations with diabetes prevalence. Low socio-economic status factors and certain ethnic groups were strongly associated with diabetes prevalence for both cities. For Toronto, South American place of birth, households below poverty and high school-level education predicted diabetes prevalence. African ethnicity and households below poverty predicted diabetes prevalence for Chicago. Although this report found no strong association between diabetes prevalence and access to PCPs, contextual factors significant in past individual-level diabetes studies were associated with diabetes prevalence at the neighbourhood/community level for Toronto and Chicago.


State of the union between cognitive neuroscience and emotion.
The 15th Annual Meeting of the Cognitive Neuroscience Society brought together researchers and exhibitors to discuss and present data relevant to the study of the mind using neuroscience methods, especially neuroimaging. A history of interdisciplinary communication, which was the basis of the creation of this society, continues to expand the scope of work presented at the meeting to include research on emotional and social processes as well as various forms of psychopathology. Neurotherapeutics and individual differences in treatment responsivity may be on the horizon.


Skeletal histomorphometry in subjects on teriparatide or zoledronic acid therapy (SHOTZ) study: a randomized controlled trial.
Recent studies on the mechanism of action (MOA) of bone-active drugs have rekindled interest in how to present and interpret dynamic histomorphometric parameters of bone remodeling. We compared the effects of an established anabolic agent, teriparatide (TPTD), with those of a prototypical antiresorptive agent, zoledronic acid (ZOL). This was a 12-month, randomized, double-blind, active-comparator controlled, cross-sectional biopsy study. The study was conducted at 12 U.S. and Canadian centers. Healthy postmenopausal women with osteoporosis participated in the study. Subjects received TPTD 20 μg once daily by sc injection (n = 34) or ZOL 5 mg by iv infusion at baseline (n = 35). The primary end point was mineralizing surface/bone surface (MS/BS), a dynamic measure of bone formation, at month 6. A standard panel of dynamic and static histomorphometric indices was also assessed. When specimens with missing labels were encountered, several methods were used to calculate mineral apposition rate (MAR). Serum markers of bone turnover were also measured. Among 58 subjects with evaluable biopsies (TPTD = 28; ZOL = 30), MS/BS was significantly higher in the TPTD group (median: 5.60 vs. 0.16%, P < 0.001). Other bone formation indices, including MAR, were also higher in the TPTD group (P < 0.05). TPTD significantly increased procollagen type 1 N-terminal propeptide (PINP) at months 1, 3, 6, and 12 and carboxyterminal cross-linking telopeptide of collagen type 1 (CTX) from months 3 to 12. ZOL significantly decreased PINP and CTX below baseline at all time points. TPTD and ZOL possess fundamentally different mechanisms of action with opposite effects on bone formation based on this analysis of both histomorphometric data and serum markers of bone formation and resorption. An important mechanistic difference was a substantially higher MS/BS in the TPTD group. Overall, these results define the dynamic histomorphometric characteristics of anabolic activity relative to antiresorptive activity after treatment with these two drugs.


Algorithmic cooling of nuclear spins using long-lived singlet order.
Algorithmic cooling methods manipulate an open quantum system in order to lower its temperature below that of the environment. We achieve significant cooling of an ensemble of nuclear spin-pair systems by exploiting the long-lived nuclear singlet state, which is an antisymmetric quantum superposition of the "up" and "down" Zeeman states. The effect is demonstrated by nuclear magnetic resonance experiments on a molecular system containing a coupled pair of near-equivalent 13C nuclei. The populations of the system are subjected to a repeating sequence of cyclic permutations separated by relaxation intervals. The long-lived nuclear singlet order is pumped well beyond the unitary limit. The pumped singlet order is converted into nuclear magnetization which is enhanced by 21% relative to its thermal equilibrium value.


[Solid Tumors With Cold Agglutinins:Report of Two Cases and Literature Review].
Cold agglutinins(CA),autoantibodies against the antigen I or i on the surface of red blood cells,are mainly of IgM class,and the majority have κ light chains.They can lead to red blood cell agglutination at decreased body temperature and are usually associated with infections,drug reactions,autoimmune diseases,and hematological malignancies.However,solid tumors with CA are rare.We reported two cases of CA in the peripheral blood of patients with solid tumors.Peripheral complete blood cell count of the patients at admission showed reduced erythrocyte count and hematocrit,mismatching between erythrocyte count and hemoglobin,abnormally elevated levels of mean corpuscular hemoglobin and mean cell hemoglobin concentration.Peripheral blood smear showed erythrocyte aggregation.After the sample was preheated at 37 ℃ for 30 min,the reversibility of red blood cell aggregation was observed,and the erythrocyte parameters were corrected.


Quality of life and comorbidity among older home care clients: role of positive attitudes toward aging.
Comorbidity has a negative impact on quality of life (QoL). This study aimed to investigate whether the impact of comorbidity on QoL is lower in older home care clients with positive attitudes toward aging. Totally, 361 older adults aged 50-91 years who were clients of 14 home care agencies in two regions in the Czech Republic gave an in-person interview to research nurses and completed the WHOQOL-BREF, the WHOQOL-OLD, and the Attitudes to Aging Questionnaire. The Charlson comorbidity index was calculated using ICD-10 codes. To address possible interaction between comorbidity and attitudes toward aging for QoL, the presence of additive interaction between comorbidity and attitudes toward aging on QoL was examined by synergy index. All analyses were adjusted by age, gender, education, and living arrangement. A higher comorbidity index was significantly associated with lower scores of both QoL measures; one index increase was associated with 3.7 [95 % confidence interval (CI) 1.5: 5.9] decreases in generic QoL and 3.6 (95 % CI 1.3: 5.9) decreases in older-specific QoL. In stratified analyses by attitudes toward aging, comorbidity showed no association with QoL among those with positive attitudes, while it was significantly associated with low QoL in those without positive attitudes. The presence of additive interactions between comorbidity and less than positive attitudes on falling in low QoL was clearly suggested. The negative impact of comorbidity on QoL might be mitigated by promoting a positive self-perception of aging in older people.


Influence of a Neighboring Charged Group on Hydrophobic Hydration Shell Structure.
Raman multivariate curve resolution (Raman-MCR), as well as quantum and classical calculations, are used to probe water structural changes in the hydration shells of carboxylic acids and tetraalkyl ammonium ions with various aliphatic chain lengths. The results reveal that water molecules in the hydration shell around the hydrophobic chains undergo a temperature and chain length dependent structural transformation resembling that previously observed in aqueous solutions of n-alcohols. Deprotonation of the carboxylic acid headgroup (at pH ∼ 7) is found to suppress the onset of the hydration-shell structural transformation around the nearest aliphatic methylene group. Tetraalkyl ammonium cations are found to more strongly suppress the water structural transformation, perhaps reflecting the greater intramolecular charge delocalization and suppression of dangling OH defects in water's tetrahedral H-bond network. The observed coupling between ionic and hydrophobic groups, as well as the associated charge asymmetry, may influence the hydrophobicity of proteins and other materials.


[Phagocytosis in patients with splenectomy].
Phagocytosis was evaluated in nine patients with splenctomy undergoing renal transplant, eight renal transplanted patients without splenectomy, three immunodepressed patients with terminal renal failure, four patients with splenectomy and six healthy volunteers. For phagocytosis evaluation, neutrophils adhered to glass were used. They were cover with 4% latex and albumin containing culture medium with or without phagocytosis stimulating tetrapeptide extracted from IgG in each case. Phagocytosis was decreased in all groups studied. Immunodepressed patients showed the highest diminishment of phagocytosis and patients with splenectomy and immunodepression the lesser. It was speculated that such a finding is due to a decrease of tetrapeptide in serum.


Laser photocoagulation for choroidal neovascularisation in pathologic myopia.
Pathologic myopia is usually defined as the need for a spectacle correction of -6 diopters or higher. Choroidal neovascularisation (CNV) is the most commonly occurring cause of visual loss in people with pathologic myopia. In myopic macular degeneration the occurrence of newly formed vessels in the macula often leads to a fibrotic pigmented scar causing a blind spot in the centre of the visual field. The primary objective of this review was to examine the effects of laser photocoagulation for CNV associated with pathologic myopia. A secondary objective was to compare the effects of different photocoagulation techniques. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 2, 2005), MEDLINE (1966 to July 2005), EMBASE (1980 to July 2005, week 28), LILACS (July 2005) and the reference lists of included studies. We included randomised controlled trials comparing photocoagulation with observation or comparing different photocoagulation techniques in people with CNV associated with myopia of -6 diopters or higher. Two authors independently assessed the search results for eligibility. Two studies were included that enrolled people with CNV located at 100 microns or more from the foveal centre. One study compared photocoagulation with observation. At the final examination, 16/35 participants randomised to photocoagulation versus 31/35 randomised to observation had visual acuity of 20/100 or worse after 6 to 48 months. The second study randomised 27 eyes (26 patients) to photocoagulation with three laser wavelengths (9 eyes per group). The number of eyes losing two or more lines was 2 (577 nm), 3 (590 nm) and 3 (620 nm) after 3 to 17 months. In both studies comparisons were made using outcomes assessed at the final examination. As the final examination took place at different follow-up times it was difficult to interpret the findings and it was impossible to extract data for further analyses. Despite its use over several years the effectiveness of laser photocoagulation for myopic CNV has not been established. Although there was a suggestion of short-term effectiveness in one small study on non-subfoveal CNV the results were potentially biased. Observational studies suggest that the enlargement of the atrophic laser scar after laser treatment of non-subfoveal CNV could be a potentially vision-threatening long-term complication, even in eyes free of CNV recurrence.


Effects of ATP on the interaction of Ca++, Mg++, and K+ with fragmented sarcoplasmic reticulum isolated from rabbit skeletal muscle.
Fragmented sarcoplasmic reticulum isolated from skeletal muscle of the rabbit has a cation-binding capacity of about 350 microeq/g of protein at neutral pH. The same binding sites bind Ca, Mg, K, and H ions and, consequently, the selective binding of Ca induced by ATP releases an amount of the other cations equivalent to the Ca taken up. At pH values below 6.2, an increasing number of binding sites are associated with H(+), and ATP induces exchange of Ca mostly for H(+). At pH values above 6.2, the binding sites exist in the form of Mg and K, and Ca is bound in exchange for these cations. The total bound Ca + Mg + K, expressed in microequivalents of cations bound per gram of protein, is approximately constant at various pCa values, which indicates a stoichiometric exchange of Ca for the other cations. To accomplish the same degree of exchange of Ca for other cations bound, in the absence of ATP, concentrations of free Ca(++) of about 1000-fold higher than those needed in the presence of ATP are required in the medium. We cannot distinguish between a mechanism whereby Ca actively transported into a compartment of the microsomal vesicles containing also the binding sites is bound passively to these sites in exchange for Mg, K, and H and another in which ATP selectively increases the affinity of surface-binding sites for Ca. Irrespective of the mechanism of accumulation, the Ca retained does not contribute to the activity of the cation in the membrane fraction. Caffeine (10 mM) has no effect on the binding of Ca, but releases a more labile fraction of Ca, which presumably accumulates in excess of the bound Ca. Procaine (5 mM) antagonizes the effect of caffeine. Acetylcholine and epinephrine have no effect on the binding of Ca.


Effect of a cooling gel on pain sensitivity and healing of hot-iron cattle brands.
Hot-iron branding is painful for cattle, but little is known about how long this pain lasts or effective alleviation methods. Previous work with pigs indicated that cooling burns with a gel (active ingredient: tea tree oil) improved healing compared to untreated wounds. Steers (210±21 kg) were hot-iron branded and allocated to 1 of 3 treatments: control (n=24), 1 gel application immediately after branding (1X; n=12), or 2 gel applications, 1 immediately after branding and one 1 d later (2X; n=12). Pain sensitivity was assessed by applying a known and increasing force with a von Frey anesthesiometer in 5 locations (in the center, at the top of, and 5 and 10 cm above the brand and on the equivalent location on the nonbranded side of the body) until animals showed a behavioral response. Healing was measured with a 6-point scale (1=fresh brand and 6=no scabbing and fully repigmented). Both measures, along with weight gain and surface temperature of the wound, were recorded before and 1, 2, 3, 7, 14, 21, 28, 35, 56, and 70 d after branding. The gel cooled the brand, with the most obvious differences on the day it was applied (3.7 to 4.2°C cooler than control; day×gel interaction, P=0.004). All wounds were at least partially repigmented by 70 d, but only 46% of brands were fully healed at this time. The healing process was slowed when a gel was applied twice (e.g., at 21 d, healing score of 2.5±0.1 and 2.7±0.1 vs. 2.0±0.2 for control and 1X vs. 2X, respectively; P=0.001). Brands tended to remain painful throughout the 70 d (in the center of the brand; before vs. d 1-35, P≤0.001; d 56, P=0.058; and d 70, P=0.092). Overall, gel had little effect on pain sensitivity. Weight gain was reduced on d 1 after branding compared to all other time points (P<0.001) but was not affected by gel application (P=0.277). In conclusion, applying gel did not improve outcomes after branding. In addition, by 70 d after the procedure, hot-iron brands still tended to be more painful than nonbranded tissue and 54% were not fully healed. These results raise additional animal welfare concerns about hot-iron branding.


Pituitary follistatin gene expression in female rats: evidence that inhibin regulates transcription.
Follistatin (FS), along with the members of the transforming growth factor beta family activin and inhibin, are important regulators of FSH secretion and messenger RNA production. While activin and inhibin appear to function as tonic modulators of FSH (stimulatory and inhibitory, respectively), dynamic changes in FS are noted through the estrous cycle and under varying physiological experimental paradigms. This suggests that FS is a major contributor to the precisely coordinated secretion of FSH that maintains reproductive function. The aim of this study was to investigate changes in FS, in particular the early (<12 h) rise observed after ovariectomy (OVX), and to determine whether these changes were as a consequence of variations in gene transcription rates. FS primary transcript (PT) and mRNA were found to increase 3-fold 12 h post-OVX, indicating increased gene transcription during this time period. Replacement with estradiol and/or blockade of GnRH had only modest effects on FS PT concentration. Inhibin immunoneutralization of intact rats resulted in a 3-fold increase in FS PT 12 h after administration of inhibin alpha antisera. Significant increases in FS mRNA at both 2 and 12 h also suggested that inhibin also may have effects on message stability. After administration of recombinant human inhibin A, there was a prompt decline in both FS PT and mRNA. These results indicate that inhibin is a major regulator of FS, both by transcriptional and nontranscriptional mechanisms.


Measurement of Chemical Exchange Rate Constants with Solvent Protons Using Radiation Damping
When chemical exchange occurs between a concentrated and a diluted species like the proton exchange between water and proteins in biochemical systems, it is difficult to use the conventional methods for a quantitative dynamical study. In this paper, a new approach which utilizes radiation damping of the strong water magnetization exchanging with the weak resonance of the mobile protons in biomolecules is proposed. It is demonstrated with a dilute guanidine solution, using the simple inversion-recovery pulse sequence, that the exchange rate constants between water and guanidine protons are evaluated by solving the Bloch equations modified with both the radiation damping and the chemical exchange effects. Copyright 1998 Academic Press.


D-serine is the dominant endogenous coagonist for NMDA receptor neurotoxicity in organotypic hippocampal slices.
D-serine occurs at high levels in the brain, where it is an endogenous coagonist at the "glycine site" of NMDA receptors. However, D-serine action has not been previously compared with that of endogenous glycine, and the relative importance of the two coagonists remains unclear. We now investigated the efficiencies of the two coagonists in mediating NMDA receptor neurotoxicity in organotypic hippocampal slices. Removal of endogenous D-serine from slices was achieved by pretreating the tissue with recombinant D-serine deaminase enzyme. This enzyme is several orders of magnitude more efficient than previous methods to remove D-serine. We report that complete removal of D-serine virtually abolished NMDA-elicited neurotoxicity but did not protect against kainate. Although levels of glycine were 10-fold higher than D-serine, endogenous glycine was ineffective in mediating NMDA receptor neurotoxicity. The effect of endogenous glycine could be observed only after simultaneous removal of endogenous D-serine and blockage of the glycine transporter GlyT1. Our data indicate that D-serine is the dominant coagonist for NMDA receptor-elicited neurotoxicity, mediating all cell death elicited by NMDA in organotypic slices. The results suggest an essential role for this unusual D-amino acid, with implications for the mechanism of neuronal death in the nervous system.


Effects of camera switching on fine accuracy in a motion capture system.
When using optical motion capture systems, increasing the number of cameras improves the visibility. However, the software used to deal with the information fusion from multiple cameras may compromise the accuracy of the system due to camera dropout, which can vary with time. In cadaver studies of radial head motion, increasing the number of cameras used by the motion capture system seemed to decrease the accuracy of the measurements. This study investigates the cause. The hypothesis was that errors in position can be induced when markers are obscured from and then restored to a camera's viewable range, as can happen in biomechanical studies. Accuracy studies quantified the capabilities of the motion capture system with precision translation and rotation movements. To illustrate the effect that abrupt perceived changes in a marker's position can have on the calculation of radial head travel, simulated motion experiments were performed. In these studies, random noise was added to simulated data, which obscured the resultant path of motion. Finally, camera-blocking experiments were performed in which precise movements were measured with a six-camera Vicon system and the errors between the actual and perceived motion were computed. During measurement, cameras were selectively blocked and restored to view. The maximum errors in translation and rotation were 3.7 mm and 0.837 deg, respectively. Repeated measures analysis of variance (ANOVAs) (alpha=0.05) confirmed that the camera-blocking influenced the results. Taken together, these results indicate that camera-switching can affect the observation of fine movements using a motion analysis system with a large number of cameras. One solution is to offer opportunity for user interaction in the software to choose the cameras used for each instant of time.


Synthesis of the matriglycan hexasaccharide, -3Xylα1-3GlcAβ1-trimer and its interaction with laminin.
Matriglycan, a polysaccharide that is a pivotal part of the core M3 O-mannosyl glycan composed of the repeating disaccharide -3Xylα1-3GlcAβ1-, interacts with laminin to stabilize muscle tissue. We herein report the synthesis of matriglycan-repeating hexasaccharides equipped with an alkyne linker to form glycoconjugates. The key step in the formation of an α-linked xylosyl glycoside was resolved by solvent-specific separation from an anomeric mixture. Successful glycan elongation was regio- and stereoselectively performed to obtain (-3Xylα1-3GlcAβ1)3-O(C2H4O)3CH2CCH and the biotin conjugate. We also investigated interactions between matriglycan hexasaccharides and laminin-G-like domains 4 and 5 of laminin-α2 using saturation transfer difference-NMR. The dissociation constant obtained from bio-layer interferometry was estimated to be 7.5 × 10-8 M. These results indicate that a chemical approach may be applied to the reconstruction of muscle tissue.


Human leukemia mutations corrupt but do not abrogate GATA-2 function.
By inducing the generation and function of hematopoietic stem and progenitor cells, the master regulator of hematopoiesis GATA-2 controls the production of all blood cell types. Heterozygous GATA2 mutations cause immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. GATA2 disease mutations commonly disrupt amino acid residues that mediate DNA binding or cis-elements within a vital GATA2 intronic enhancer, suggesting a haploinsufficiency mechanism of pathogenesis. Mutations also occur in GATA2 coding regions distinct from the DNA-binding carboxyl-terminal zinc finger (C-finger), including the amino-terminal zinc finger (N-finger), and N-finger function is not established. Whether distinct mutations differentially impact GATA-2 mechanisms is unknown. Here, we demonstrate that N-finger mutations decreased GATA-2 chromatin occupancy and attenuated target gene regulation. We developed a genetic complementation assay to quantify GATA-2 function in myeloid progenitor cells from Gata2 -77 enhancer-mutant mice. GATA-2 complementation increased erythroid and myeloid differentiation. While GATA-2 disease mutants were not competent to induce erythroid differentiation of Lin-Kit+ myeloid progenitors, unexpectedly, they promoted myeloid differentiation and proliferation. As the myelopoiesis-promoting activity of GATA-2 mutants exceeded that of GATA-2, GATA2 disease mutations are not strictly inhibitory. Thus, we propose that the haploinsufficiency paradigm does not fully explain GATA-2-linked pathogenesis, and an amalgamation of qualitative and quantitative defects instigated by GATA2 mutations underlies the complex phenotypes of GATA-2-dependent pathologies.


The effectiveness of school physical education on students' cognitive competence: a systematic review and meta-analysis.
School physical education plays an important role in improving the cognitive competencies of students. The theoretical background related to how school physical education positively influences students' cognitive domains has been consistently structured; however, there are few previous studies that have systematically analyzed how physical education interventions produce positive outcomes related to learners' cognitive competencies. The aim of the present study was to analyze the effectiveness of physical education interventions on students' cognitive competencies. The study involved searching for related quantitative research studies through electronic research databases including SPORTDiscus, ScienceDirect, and MEDLINE Patent Applications and conducting a screening process considering the purpose of the meta-analysis. The present study assessed for a risk of bias, extracted data, and conducted a meta-analysis to determine the effectiveness of physical education interventions. According to the results of the meta-analysis, school physical education has a significant impact on students' cognitive competencies such as intelligence and academic achievement. In terms of the characteristics of the interventions, the effectiveness of aerobic exercise rooted in physical education was more significant than that of model-based physical education or traditional physical education. Based on the results of the meta-analysis, the present study concluded that school physical education has a statistically significant impact on changing students' cognitive conditions; however, there is need for a follow-up study on how the contents of school physical education and the methods of teaching have distinct effects on students' cognitive competencies.


Expression of neurotransmitter receptors and myc protooncogenes in subclones of a human neuroblastoma cell line.
Phenotypic variability of the human neuroblastoma cell line SK-N-SH was studied with the use of three subclones that interconvert at a slower rate than the parent cell line, i.e., a neuroblast-type subclone (SH-SY5Y), a nonneuronal, strongly substrate adherent subclone (SH-EP), and an intermediate type subclone (SH-IN). Rhodamine-phalloidin staining of actin fibers revealed differences in the cytoskeleton morphology of the three subclones, while the clathrin subunit proteins (heavy and light chains), components of coated vesicles, were invariant. Dramatic differences were observed for the expression of neurotransmitter systems, i.e., the mu and delta opioid receptor, the muscarinic cholinergic receptor and its effect on phosphatidylinositol turnover, and the uptake1 transporter for catecholamines. While these systems were strongly expressed in the parent line and the neuroblast-like clones SH-SY5Y and SH-IN, they were absent or barely detectable in the nonneuronal EP clone. Furthermore, the protooncogenes N- and c-myc were only expressed in the neuroblast containing lines, consistent with their growth characteristics of fully transformed cells. The strong c-myc expression in the absence of c- or N-myc amplification in SK-N-SH, adds a new form of high protooncogene activity in neuroblastoma cell lines. The remarkable differences of neurotransmitter systems and myc expression among the various phenotypes of human neuroblastoma cells should be considered in the therapy of neuroblastoma.


Thrombin and histamine induce stiffening of alveolar epithelial cells.
The mechanical properties of alveolar epithelial cells play a central role in maintaining the physical integrity of the alveolar epithelium. We studied the viscoelastic properties of alveolar epithelial cells (A549) in response to thrombin and histamine with optical magnetic twisting cytometry. Ferrimagnetic beads coated with Arg-Gly-Asp (RGD)-peptide or acetylated low-density lipoprotein were bound to cell surface receptors and subsequently twisted in an oscillatory magnetic field (0.1-100 Hz). The cell storage (G') and loss (G'') moduli were computed from twisting torque and bead displacement. In measurements with RGD-coated beads, thrombin (0.5 U/ml) induced a rapid and sustained threefold increase in G' and G'' at approximately 100 s after challenge. Histamine (100 microM) induced a rapid but transient twofold increase in G' and G'' with maximum values 60 s after challenge. Posttreatment with cytochalasin D abolished thrombin-induced cell stiffening. G' increased with frequency following a power law with exponent 0.214. G'' increased proportionally to G' up to 10 Hz but showed a steeper rise at higher frequencies. Thrombin caused a fall in the power-law exponent (0.164). In measurements with acetylated low-density lipoprotein-coated beads, minor changes (<20%) were observed in G' and G'' after the addition of thrombin and histamine. F-actin staining revealed that thrombin and histamine induced a profound reorganization of the actin cytoskeleton at the cell periphery and formation of actin bundles. In the mechanically dynamic environment of the lung, cell stiffening induced by thrombin and histamine increases centripetal tension, which could contribute to alveolar barrier dysfunction.


2-14C-mevalonate oxidation during rat development.
In vivo oxidation of 2-14C-mevalonate is very low in 1- to 3-day-old rats and then rises to adult levels. Kidney slices oxidize mevalonate at an equal rate during development. However, at the time of weaning the rate is transiently increased in male rats only.


N-ethyl-N-nitrosourea mutagenesis: boarding the mouse mutant express.
In the mouse, random mutagenesis with N-ethyl-N-nitrosourea (ENU) has been used since the 1970s in forward mutagenesis screens. However, only in the last decade has ENU mutagenesis been harnessed to generate a myriad of new mouse mutations in large-scale genetic screens and focused, smaller efforts. The development of additional genetic tools, such as balancer chromosomes, refinements in genetic mapping strategies, and evolution of specialized assays, has allowed these screens to achieve new levels of sophistication. The impressive productivity of these screens has led to a deluge of mouse mutants that wait to be harnessed. Here the basic large- and small-scale strategies are described, as are the basics of screen design. Finally, and importantly, this review describes the mechanisms by which such mutants may be accessed now and in the future. Thus, this review should serve both as an overview of the power of forward mutagenesis in the mouse and as a resource for those interested in developing their own screens, adding onto existing efforts, or obtaining specific mouse mutants that have already been generated.


In vivo anti-cancer efficacy of magnetite nanocrystal--based system using locoregional hyperthermia combined with 5-fluorouracil chemotherapy.
We present an approach for synchronizing hyperthermia and thermal-responsive local drug release. The targeting probe has a magnetite nanocrystal (Fe₃O₄@PSMA) core and a polynucleotide shell that carries 5-fluorouracil (5-FU) and anti-human epidermal growth factor receptor 2 (anti-HER2) antibody for cancer cell-specific targeting. The targeting nanocrystals play as an important role to relay the externally delivered radiofrequency energy for tumor hyperthermia. Locoregional heat then triggers a drug release from the oligonucleotide carrier as it directly damages tumor cells. Cell viability assays and pathological examinations show that this synchronization is significantly more efficacious in both in vitro and in vivo models than hyperthermia or chemotherapy alone. Prominent tumor remission in vivo was achieved through radiofrequency synchronization of hyperthermia and chemotherapy after the nanoparticle had been intravenously injected.


[Physiopathology of chronic arthritis following chikungunya infection in man].
Chronic arthritis following chikungunya infection has no specific treatment. Studies on mice have confirmed involvement of fibroblasts and myoblasts as target cells replicating the virus and shown that macrophages play a key role in the innate immune response involving multiple cytokines and chimiokines. Paradoxically, TH1 and TH2 cytokine levels do not increase significantly during the acute and chronic phases, with the exception of interferon-gamma and IL12 that rise dramatically during the acute phase. The level of IL12 returns to normal in patients who recover. In contrast, patients who develop chronic arthritis show persistently high IL12 levels along with IFN-alpha within PBMC. Histologic examination of synovia reveals joint inflammation due to macrophages containing viral material. Metallo-protease (MMP2) also contributes to tissue damage. Chikungunya virus leads to apoptosis by both the intrinsic and extrinsic pathways.


Assignment of side-chain conformation using adiabatic energy mapping, free energy perturbation, and molecular dynamic simulations.
NMR spectroscopic analysis of the C-terminal Kunitz domain fragment (alpha3(VI)) from the human alpha3-chain of type VI collagen has revealed that the side chain of Trp21 exists in two unequally populated conformations. The major conformation (M) is identical to the conformation observed in the X-ray crystallographic structure, while the minor conformation (m) cannot structurally be resolved in detail by NMR due to insufficient NOE data. In the present study, we have applied: (1) rigid and adiabatic mapping, (2) free energy simulations, and (3) molecular dynamic simulations to elucidate the structure of the m conformer and to provide a possible pathway of the Trp21 side chain between the two conformers. Adiabatic energy mapping of conformations of the Trp21 side chain obtained by energy minimization identified two energy minima: One corresponding to the conformation of Trp21 observed in the X-ray crystallographic structure and solution structure of alpha3(VI) (the M conformation) and the second corresponding to the m conformation predicted by NMR spectroscopy. A transition pathway between the M and m conformation is suggested. The free-energy difference between the two conformers obtained by the thermodynamic integration method is calculated to 1.77+/-0.7 kcal/mol in favor of the M form, which is in good agreement with NMR results. Structural and dynamic properties of the major and minor conformers of the alpha3(VI) molecule were investigated by molecular dynamic. Essential dynamics analysis of the two resulting 800 ps trajectories reveals that when going from the M to the m conformation only small, localized changes in the protein structure are induced. However, notable differences are observed in the mobility of the binding loop (residues Thr13-Ile18), which is more flexible in the m conformation than in the M conformation. This suggests that the reorientation of Trp2 might influence the inhibitory activity against trypsin, despite the relative large distance between the binding loop and Trp21.


Undifferentiated carcinoma with osteoclast-like multinucleated giant cells arising in an ovarian mature cystic teratoma.
Malignant transformation is an unusual complication of mature cystic teratomas. Squamous cell carcinomas and adenocarcinomas are predominant among these malignant tumors. We present a 70-year-old Japanese woman with a giant ovarian tumor (30 x 23 x 9 cm) and multiple peritoneal dissemination. The huge tumor was filled with necrotic and fatty tissue and coagula accompanied with hair balls histologically diagnosed as undifferentiated carcinoma with multinucleated giant cells arising in an ovarian mature cystic teratoma. The residual disseminated tumors grew very rapidly and occupied the whole abdominal cavity again 3 weeks after the surgery. The patient died 5 weeks after the operation.


Calculated parenteral initial therapy of bacterial infections: Antibiotic treatment in the elderly.
This is the fifteenth chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. Multimorbidity, an atypical symptomatology of infections in combination with multimedication, the associated interaction risks and serious consequences of synergistic side effects characterize the conditions when deciding on the use of antibiotics in old age. Strict decision regarding the indication itself, choice of the best antibiotic even considering rare side effects which may be dangerous in the elderly, determining the correct dose, dosing interval and the shortest possible duration according to the physiological status of the patient as well as monitoring effectiveness and toxicity detect expected and unexpected side effects early. Recommendations must reflect the peculiarities of antibiotic treatment in elderly patients.


Eosinophilic chronic rhinosinusitis in East Asians.
Chronic rhinosinusitis (CRS) is a common disease worldwide, with a prevalence rate of 5%-15% in the general population. CRS is currently classified into two types: CRS with and without nasal polyps. CRS may also be divided into eosinophilic CRS (ECRS) and non-ECRS subtypes based on the presence of tissue eosinophilic infiltration or not. There are significant geographic and ethnic differences in the tissue eosinophilic infiltration, which is predominant in Western white patients and less common in East Asians, despite an increasing tendency for its prevalence in East Asia countries. ECRS differs significantly from non-ECRS in clinical characteristics, treatment outcomes and strategies, and underlying pathogenic mechanisms. ECRS commonly demonstrates more severe symptoms, polyp diseases with a higher incidence of bilateral polyps and sinonasal diseases on computed tomography, and the increase in blood eosinophils. ECRS is considered a special and recalcitrant subtype of CRS, commonly with poor treatment outcomes compared to non-ECRS. The differentiation of specific subtypes and clinical features of CRS will be important for developing novel treatment strategies and improving treatment outcomes for individual phenotypes of CRS. This review discusses clinical features, diagnosis, treatment and prognosis of ECRS in East Asians.


Identification and characterization of transcriptional arrest sites in exon 1 of the human adenosine deaminase gene.
Analysis of human adenosine deaminase (ADA) gene transcription in four different cell lines indicated that a high density of RNA polymerase II complexes is present at the 5' end of the gene and that the extent of transcription elongation beyond the promoter-proximal region governs gene expression. To determine the sequence requirements for a potential transcription arrest site in the promoter-proximal region, genomic clones containing the ADA promoter, exon 1, and various lengths of intron 1 were injected into Xenopus laevis oocyte germinal vesicles. Transcription analysis indicated that nascent ADA transcripts were highly represented at the promoter-proximal region of the injected templates, suggesting that transcription arrest occurred in the oocyte transcription system. Analysis of the transcription products indicated that ADA transcription initiated at the authentic start site and that the most prominent, short ADA transcripts were 105 nucleotides in length. The 3' end of these transcripts mapped within exon 1, 10 nucleotides downstream of the translation initiation codon. Deletion analysis demonstrated that sequences within exon 1 were sufficient to specify the synthesis of the 105-nucleotide transcripts. Taken together, these data suggest that a transcription arrest mechanism operates in the promoter-proximal region of the human ADA gene and that regulation of elongation beyond this point plays a major role in regulating ADA gene expression.


Evaluation of transmission infrared spectroscopy and digital and optical refractometers to identify low immunoglobulin G concentrations in alpaca serum.
This study aimed to evaluate the digital Brix and optical serum total protein (STP) refractometers for measuring concentrations of serum immunoglobulin G (IgG) in alpacas and compare them to IgG concentrations measured by the reference method of radial immunodiffusion (RID) assay. The appropriate cutoff point for Brix and STP refractometers and the transmission infrared (TIR) spectroscopy method was determined for low IgG concentrations (< 10 g/L). Serum samples were collected from alpacas (N = 169) and tested by both refractometers. The correlation between Brix % and STP was high [correlation coefficient (r) = 0.99]. However, the correlation coefficients between Brix % and STP with serum RID-IgG concentrations were only 0.56 and 0.55, respectively. Twenty-one (12.4%) of 169 alpaca serum samples had IgG concentrations of < 10 g/L. Using receiver operator characteristic curve (ROC) analysis, the optimal cutoff points for the TIR assay, digital Brix, and optical STP refractometers for assessing low IgG (RID < 10 g/L) were 13 g/L, 8.8%, and 50 g/L, respectively. The TIR assay showed higher sensitivity (Se = 95.2%) and specificity (Sp = 96.8%) than either the digital Brix (Se = 90.5% and Sp = 65.5%) or optical STP (Se = 81% and Sp = 73.7%) refractometers for assessing alpacas with low IgG. In conclusion, the Brix and STP refractometers lack accuracy in measuring alpaca IgG concentrations, but may be useful for screening animals for low serum IgG. However, the TIR assay with a cutoff point of 13 g/L was more appropriate for identifying low IgG than either refractometer. Another study that focuses on neonatal crias is recommended in order to evaluate the usefulness of these assays for field diagnosing of failure of transfer of passive immunity (FTPI).


Trend in and Correlates of Undergoing Radiotherapy in Taiwanese Cancer Patients' Last Month of Life.
A significant proportion of cancer patients at end of life (EOL) undergo radiotherapy, but this evidence is not from nationwide population-based studies. The aims of this population-based study were to investigate the trend in undergoing radiotherapy among Taiwanese cancer patients' last month of life (EOL radiotherapy) in 2001-2010 and to identify factors associated with EOL radiotherapy. This was a population-based retrospective cohort study analyzing data from Taiwan's national death registry, cancer registry, and National Health Insurance claims for EOL radiotherapy using multilevel generalized linear mixed modeling. Participants were Taiwanese cancer patients (N = 339,546) who died in 2001-2010. Overall, 8.59% (7.97%-9.85%) of patients underwent EOL radiotherapy with a decreasing trend over time. Correlates of EOL radiotherapy included male gender, younger age, residing in less urbanized areas, diagnosis of lung cancer, metastatic disease, death within two years of diagnosis, and without comorbidities. Cancer patients were more likely to undergo EOL radiotherapy if they received primary care from medical oncologists and pediatricians, in a nonprofit, teaching hospital with a larger case volume of terminally ill cancer patients, and greater EOL care intensity. Approximately one-tenth of Taiwanese cancer patients underwent EOL radiotherapy with a decreasing trend over time. Undergoing EOL radiotherapy was associated with demographics, disease characteristics, physician specialty, and primary hospital's characteristics and EOL care practice patterns. Clinical and financial interventions should target hospitals/physicians that tend to aggressively treat at-risk cancer patients at EOL to carefully evaluate the appropriateness and effectiveness of using EOL radiotherapy.


[Accuracy of prostatic ultrasonography versus MRI in measuring prostate volume].
To compare the accuracy of different methods of measuring the prostate volume (PV) based on the manifestations of prostatic ultrasonography and MRI. Using the drainage method, we measured the volumes of 101 prostatic specimens collected from radical prostatectomy. And with the measures obtained as reference standards, we calculated the PV of the patients with the maximum width (W), height (H) and length (L) of the prostates obtained preoperatively by transabdominal ultrasonography (TAUS), transrectal ultrasonography (TRUS) and MRI using the ellipsoidal formula (PV = W × H × L × 0.52), bullet formula (PV = W × H × L × 0.65) and 3D reconstruction technology. We evaluated the accuracy of the above methods using the Mann-Whitney U test, intraclass correlation coefficient (ICC), and Bland-Altman scatterplot. No statistically significant differences were observed between the specimen and preoperative PVs. The ICCs of the specimen PVs obtained by MRI 3D reconstruction, TRUS bullet formula, MRI ellipsoidal formula and TAUS ellipsoidal formula were 0.978, 0.862, 0.857 and 0.745, respectively. The Bland-Altman scatterplot exhibited that the preoperative PV calculated by MRI 3D reconstruction had the highest consistency with that of the specimen PV, followed by that measured by TRUS bullet formula and that obtained by MRI ellipsoidal formula, while that determined by TAUS ellipsoidal formula had a low consistency. The MRI 3D reconstruction technology is the most reliable method for the measurement of PV, followed by TRUS bullet formula, but the latter is recommended for its high applicability in clinical practice.


Evidence for involvement of Wnt signalling in body polarities, cell proliferation, and the neuro-sensory system in an adult ctenophore.
Signalling through the Wnt family of secreted proteins originated in a common metazoan ancestor and greatly influenced the evolution of animal body plans. In bilaterians, Wnt signalling plays multiple fundamental roles during embryonic development and in adult tissues, notably in axial patterning, neural development and stem cell regulation. Studies in various cnidarian species have particularly highlighted the evolutionarily conserved role of the Wnt/β-catenin pathway in specification and patterning of the primary embryonic axis. However in another key non-bilaterian phylum, Ctenophora, Wnts are not involved in early establishment of the body axis during embryogenesis. We analysed the expression in the adult of the ctenophore Pleurobrachia pileus of 11 orthologues of Wnt signalling genes including all ctenophore Wnt ligands and Fz receptors and several members of the intracellular β-catenin pathway machinery. All genes are strongly expressed around the mouth margin at the oral pole, evoking the Wnt oral centre of cnidarians. This observation is consistent with primary axis polarisation by the Wnts being a universal metazoan feature, secondarily lost in ctenophores during early development but retained in the adult. In addition, local expression of Wnt signalling genes was seen in various anatomical structures of the body including in the locomotory comb rows, where their complex deployment suggests control by the Wnts of local comb polarity. Other important contexts of Wnt involvement which probably evolved before the ctenophore/cnidarian/bilaterian split include proliferating stem cells and progenitors irrespective of cell types, and developing as well as differentiated neuro-sensory structures.


The oncogenic MicroRNA Hsa-miR-155-5p targets the transcription factor ELK3 and links it to the hypoxia response.
The molecular response to hypoxia is a critical cellular process implicated in cancer, and a target for drug development. The activity of the major player, HIF1α, is regulated at different levels by various factors, including the transcription factor ELK3. The molecular mechanisms of this intimate connection remain largely unknown. Whilst investigating global ELK3-chromatin interactions, we uncovered an unexpected connection that involves the microRNA hsa-miR-155-5p, a hypoxia-inducible oncomir that targets HIF1α. One of the ELK3 chromatin binding sites, detected by Chromatin Immuno-Precipitation Sequencing (ChIP-seq) of normal Human Umbilical Vein Endothelial Cells (HUVEC), is located at the transcription start site of the MIR155HG genes that expresses hsa-miR-155-5p. We confirmed that ELK3 binds to this promoter by ChIP and quantitative polymerase chain reaction (QPCR). We showed that ELK3 and hsa-miR-155-5p form a double-negative regulatory loop, in that ELK3 depletion induced hsa-miR-155-5p expression and hsa-miR-155-5p expression decreased ELK3 expression at the RNA level through a conserved target sequence in its 3'-UTR. We further showed that the activities of hsa-miR-155-5p and ELK3 are functionally linked. Pathway analysis indicates that both factors are implicated in related processes, including cancer and angiogenesis. Hsa-miR-155-5p expression and ELK3 depletion have similar effects on expression of known ELK3 target genes, and on in-vitro angiogenesis and wound closure. Bioinformatic analysis of cancer RNA-seq data shows that hsa-miR-155-5p and ELK3 expression are significantly anti-correlated, as would be expected from hsa-miR-155-5p targeting ELK3 RNA. Finally, hypoxia (0% oxygen) down-regulates ELK3 mRNA in a microRNA and hsa-miR-155-5p dependent manner. These results tie ELK3 into the hypoxia response pathway through an oncogenic microRNA and into a circuit implicated in the dynamics of the hypoxic response. This crosstalk could be important for the development of new treatments for a range of pathologies.


The Contribution of Sources to the Sustained Elevated Inventory of (137)Cs in Offshore Waters East of Japan after the Fukushima Dai-ichi Nuclear Power Station Accident.
We have evaluated the contribution of sources of (137)Cs to the inventory of radiocesium in waters (surface area: 6160 km(2), water volume: 753 km(3)) off Fukushima Prefecture and neighboring prefectures from May 2011 to February 2015. A time-series of the inventory of (137)Cs in the offshore waters revealed a clearly decreasing trend from May 2011 (283.4 TBq) to February 2015 (1.89 TBq). The (137)Cs inventory about four years after the accident was approximately twice the background inventory of 1.1 TBq. The magnitudes of the (137)Cs influxes from sources into offshore waters for periods of 182-183 days were estimated from the first period (1 October 2011 to 31 March 2012: 15.3 TBq) to the last period (1 October 2014 to 31 March 2015: 0.41 TBq). We assumed that three sources contributed (137)Cs: continuous direct discharge from the Fukushima Dai-ichi Nuclear Power Station (FNPS) even after the massive discharge in late March 2011, desorption/dissolution from sediments, and fluvial input. Quantification of these sources indicated that the direct discharge from the FNPS is the principal source of (137)Cs to maintain the relatively high inventory in the offshore area.


Disorders of micturition in neurological patients. A clinical study of 786 patients.
Our aim was to evaluate the utility and effectiveness of a study protocol for neurological involvement in neurological disorders. We studied a sample of 786 patients with neurological disorders followed by the Neurological Department of Catania University and applied to them a four-step diagnostic protocol. Fifty-six per cent of the sample showed urological functional abnormalities; only 78 patients (9.9%) presented with an organic urological disease. Among the vesicosphincteric dysfunctions, bladder hyperreflexia was the most common pattern with remarkable differences between diseases. The present study demonstrated the utility of a standardized urological protocol in the screening and detection of neurological involvement in neurological diseases. Our protocol showed good specificity and reasonable low costs.


Ponderal index (PI) vs birth weight centiles in the low-risk primigravid population: which is the better predictor of fetal wellbeing?
Our objective was to compare Ponderal index (PI) with birth weight centiles as predictors of perinatal morbidity and to determine which best reflects the presence of placental disease. We prospectively recruited 1,011 low-risk primigravidas and calculated PI and birth weight centiles following delivery. Perinatal morbidity was defined as: pre-term birth (PTB); fetal acidosis; an Apgar score <7 at 5 min or neonatal resuscitation. Placental disease was defined as chronic uteroplacental insufficiency (CUPI); villous dysmaturity; infection or vascular pathology. Ponderal index was statistically reduced (25.33 vs 27.79 p =0.001) and the incidence of infant birth weight <9th centile was statistically higher (11.1% vs 5.1%; p =0.004) in cases with PTB and in CUPI (26.23 vs 27.84; p =0.001 and 28.2.1% vs 10.4%; p =0.002). Both PI and infant birth weight centile <9th centile for gestational age correlate with PTB, however overall, both are poor predictors of neonatal and placental disease.


Nurses' perspectives on the suffering of preterm infants.
The concept of suffering is discussed among those who are cognitively aware and verbally capable to express their suffering. Due to immaturity, preterm infants' abilities to express suffering are limited. Relieving suffering is an ethical and juridical demand of good nursing care. The purpose of this study is to describe nurses' perceptions of the suffering of preterm infants. A descriptive qualitative approach was selected. Data were collected from essays written by nurses (n = 19) working in the neonatal intensive care unit. Inductive content analysis guided by the research question was performed. The nurses described individually determined suffering of the preterm infants according to four categories: suffering ruled by maturation, existence of suffering, individual threshold of suffering and interpreting the cues of suffering. Suffering of preterm infants is manifested by population-specific features, emphasising the need to develop sensitive interventions for relieving their suffering.


Recent Advances in Scanning Electrochemical Microscopy for Biological Applications.
Scanning electrochemical microscopy (SECM) is a chemical microscopy technique with high spatial resolution for imaging sample topography and mapping specific chemical species in liquid environments. With the development of smaller, more sensitive ultramicroelectrodes (UMEs) and more precise computer-controlled measurements, SECM has been widely used to study biological systems over the past three decades. Recent methodological breakthroughs have popularized SECM as a tool for investigating molecular-level chemical reactions. The most common applications include monitoring and analyzing the biological processes associated with enzymatic activity and DNA, and the physiological activity of living cells and other microorganisms. The present article first introduces the basic principles of SECM, followed by an updated review of the applications of SECM in biological studies on enzymes, DNA, proteins, and living cells. Particularly, the potential of SECM for investigating bacterial and biofilm activities is discussed.


NASN Special Interest Groups: Their Growth and Development Through the Years.
Over the past 25 years, the roles of school nurses have been both expanding and specializing in public and non-public school settings. To help meet the ever-changing and demanding challenges that specialized school nurses encounter in their unique settings, NASN embraced the idea that school nurses need a way to connect with colleagues working in similar practices. Thus, special interest groups (SIGs) were established, and the SIGs have become an integral part of NASN.


Total syntheses of lyconadins A-C.
The total synthesis of the Lycopodium alkaloid lyconadin A was accomplished and it was applied to the total syntheses of the related congeners, lyconadins B and C. Lyconadin A has attracted attention as a challenging target for total synthesis due to the unprecedented pentacyclic skeleton. Our synthesis of lyconadin A features a facile construction of the highly fused tetracyclic skeleton through a combination of an aza-Prins reaction and an electrocyclic ring opening, followed by formation of a C-N bond. Transformation of the bromoalkene moiety of the tetracycle to a key enone intermediate was extensively investigated, and three methods via sulfide, oxime, or azide intermediates were established. A pyridone ring was constructed from the key enone intermediate to complete the synthesis of lyconadin A. A dihydropyridone ring could also be formed from the same enone intermediate, leading to a synthesis of lyconadin B. Establishment of the conditions for an electrocyclic ring opening without formation of the C-N bond resulted in completion of the total synthesis of lyconadin C.


SHARPIN Enhances Ferroptosis in Synovial Sarcoma Cells via NF-κB- and PRMT5-Mediated PGC1α Reduction.
Sarcoma is a rare type of cancer for which new therapeutic agents are required. Ferroptosis is a nonapoptotic cell death triggered by iron-mediated lipid peroxidation. We found that TFRC, an iron uptake protein, was expressed at higher levels in sarcoma cell lines than in noncancer and carcinoma cell lines. Glutathione peroxidase 4 (GPX4) protects cells against ferroptosis, and its inhibition using RAS-selective lethal 3 (RSL3) had an antitumor effect that was more pronounced in sarcoma cell lines, particularly synovial sarcoma cells, compared to non-sarcoma cells. Because NF-κB can provoke ferroptosis, we examined the role of SHARPIN, an activator of NF-κB, in sarcoma. We found that SHARPIN expression was significantly associated with reduced survival in cohorts of patients with cancer, including sarcoma. In addition, SHARPIN promoted the sensitivity of sarcoma cells to ferroptosis. Further analyses revealed that the PGC1α/NRF2/SLC7A11 axis and BNIP3L/NIX-mediated mitophagy are regulated through NF-κB and PRMT5 downstream of SHARPIN. Our findings suggest that ferroptosis could have a therapeutic effect in sarcoma, particularly in subpopulations with high TFRC and SHARPIN expression.


Alternative methods for determining resource requirements: the Chile example.
Many more or less attractive techniques have been proposed for statistical analyses involving multiple sources of variation, for example in examing the possible contributors to differential patterns of health services utilization and expenditure. A large scale investigation of such patterns among 10,000 household in Chile provided a useful basis for comparison of alternative analytical approaches. The multiple regression, Automatic Interaction Detection, and Multisort techniques were applied to the survey data deparately and in combination and results were compared. The Multisort technique was found to be the single most useful and convenient approach, but the most meaningful results were obtained from the systematic application of the three approaches combined.


Setting up a buddy scheme for pulmonary rehabilitation.
North East Lincolnshire Care Trust Plus's HOPE specialist service has developed one of the most successful pulmonary rehabilitation (PR) programmes nationally. One element of this service is the use of buddies (expert patients with COPD), who assist with the design and delivery of the programme, alongside the specialist multidisciplinary team. This service has some of the best patient outcomes seen nationally; it won two awards in December 2007. This article outlines how the service was established and its outcomes.


A Rare Case of Recurrent Hematometra of Unknown Etiology.
An abnormal blood collection in the uterus is referred to as hematometra. Obstruction of the genitourinary outflow system caused by earlier surgeries or congenital defects is most frequently related to this rare disorder. The symptoms of hematometra include acute pelvic pain and a history of absent menarche. Here is a case of a 42-year-old female who presented with complaints of severe lower abdominal pain, and pain during urination that was accompanied by vulval itching in June 2021. She had undergone two Caesarean sections and a myomectomy in the past. She was given three monthly injections of gonadotropin-releasing hormone (GnRH) analogue after receiving USG-guided drainage because of a diagnosis of hematometra in January 2021. However, in June 2021, she experienced a recurrence of the same symptoms, necessitating a total abdominal hysterectomy and bilateral salpingo-oophorectomy, which completely resolved the patient's complaints. For a deeper understanding of this issue, further case reporting is necessary.