Tissue-specific expression of human provirus ERV3 mRNA in human placenta: two of the three ERV3 mRNAs contain human cellular sequences.
Three polyadenylated RNAs, 9, 7.3, and 3.5 kilobases long, of a human endogenous retrovirus, ERV3, are abundant in human placental chorion, representing about 0.03 to 0.05% of the total mRNA. We characterized the structure of these mRNAs by Northern blot and S1 nuclease mapping analyses. We found that all three RNAs were spliced mRNAs that lacked 5.9 kilobases of proviral sequence, including the gag gene and most of the pol gene. In contrast to the transcription pattern usual for other retroviruses, the transcription pattern of the ERV3 provirus did not include a genome-length mRNA. All three of the ERV3 mRNAs initiated transcription at the same point in the 5' long terminal repeat (LTR) and contained identical splice junctions in the provirus. The 3.5-kilobase RNA was a typical subgenomic proviral mRNA, with its polyadenylation site in the 3' LTR. The two larger ERV3 mRNAs, however, extended through the polyadenylation site in the 3' LTR and were spliced at a second position approximately 370 nucleotides downstream from the 3' LTR. This finding suggests that when the ERV3 retrovirus integrated at this genomic locus in an ancestor of humans, it integrated within or adjacent to a cellular gene.


An experimental compartmental flow model for assessing the hemodynamic response of intracranial arteriovenous malformations to stereotactic radiosurgery.
Stereotactic radiosurgery has proven to be an effective method of treating selected inaccessible or inoperable arteriovenous malformations (AVMs) of the brain. Radiation-induced obliteration of successfully-treated AVMs, however, occurs only after some latent period after treatment, depending on size, location, and dose. An experimental compartmental flow model is proposed to describe the hemodynamic alterations in the AVM as a result of the pathophysiological changes after radiosurgery, and to analyze temporal alterations in AVM blood flow rates and pressure gradients before complete obliteration. In representative small (low-flow, 150 ml/min) and large (high-flow, 440 ml/min) AVMs, it is found that increases in pressure gradients across certain vascular structures within the AVM occur during the normal course of radiation-induced flow decrease and AVM obliteration. The magnitude of these pressure alterations, however, may be within the normal physiological variations in cerebrovascular blood pressure. The effects of partial-volume irradiation of the AVM is examined by limiting radiosurgical treatment to varying portions of the flow compartments within the model. It is found that alterations in pressure gradients persist in unirradiated vascular shunts, even after complete obliteration of the treated AVM volume. These pressure alterations may increase the probability of hemorrhage from the untreated shunts of the AVM and cause redistribution of regional cerebral blood flow resulting in increased flow through these untreated shunts.


Adiposity and risk of oesophageal cancer subtypes in the Million Women Study.
The strong association of body mass index (BMI) with increased oesophageal adenocarcinoma risk is established, but its relationship with oesophageal squamous cell carcinoma is less clear. There is little evidence regarding the association of abdominal adiposity with either subtype. In a large prospective cohort of women in the UK, mean age 56.2 [standard deviation (SD) = 4.9] years, we investigated the risk of oesophageal adenocarcinoma and squamous cell carcinoma in relation to self-reported BMI, waist circumference (WC) and waist-hip ratio (WHR), using Cox regression to estimate adjusted relative risks (RR) and 95% confidence intervals (CIs), taking account of potential reverse causation bias. During mean follow-up of 17.7 (SD = 4.9) years, 1386 adenocarcinomas and 1799 squamous cell carcinomas of the oesophagus were registered among 1 255 529 women. Compared with women of BMI 22.5 to <25 kg/m2, those with BMI ≥35 kg/m2 had a 2.5-fold risk of adenocarcinoma (adjusted RR = 2.46, 95% CI = 1.99-3.05) and an almost 70% reduction in risk of squamous cell carcinoma (RR = 0.32, 95% CI = 0.22-0.46). These associations were broadly similar in each 5-year follow-up period, and were evident in both never and ever smokers, although somewhat stronger for squamous cell carcinoma among current and past smokers than in never smokers (Pheterogeneity = 0.007). After controlling for BMI, WC and WHR were associated with risk of squamous cell carcinoma but not adenocarcinoma. In this population of middle-aged women, there was robust evidence that greater BMI is associated with an increased risk of oesophageal adenocarcinoma and a reduced risk of squamous cell carcinoma.


[Saccular aneurysm of the azygos vein in a patient with azygos accessory fissure].
The saccular aneurysm of the azygos vein is an extremely rare condition, which when located in the path of an accesory pulmonary fissure, becomes a diagnostic challenge because it can be mistaken for tumors arising from the accesory pleura, like solitary fibrous tumor of the pleura or mesothelioma. The diagnosis should ideally be done by non-invasive methods such as CT or MR angiographic technique in multiple phases, thus avoiding unnecessary surgical intervention. This case is exceptional because, to our knowledge, it is the first to report both concomitant clinical situations, an aneurysm of the azygos vein in the pathway of its accessory fissure.


Alcohol-induced changes in cerebral blood flow and cerebral blood volume in social drinkers.
Although it is known that alcohol has vasoactive properties, previous studies have not investigated the relationship between cerebral blood flow (CBF) and cerebral blood volume (CBV) after alcohol consumption. The aim of this study was to investigate effects of alcohol on CBF and CBV, both globally and regionally, in social drinkers. The method of choice was dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). Eight males were scanned twice on two separate days; once after consumption of alcohol (blood-alcohol concentration (BAC) of 0.08%) and once sober. The results showed an average increase of CBF after alcohol consumption, both in grey matter (GM) and in white matter (WM), with a CBF(BAC of 0.08%)/CBF(baseline) ratio of 1.2. Regional increases in CBF were seen in areas close to where the large brain-feeding blood vessels enter the brain, in the thalamus region and in the frontal brain regions. The lowest CBF changes were seen in the occipital brain regions. There was also an increase in CBV after alcohol consumption, in particular across WM regions. In conclusion, a BAC of 0.08% causes both an average increase in global and regional CBF. There was stronger correlation between alcohol-induced changes in CBF and CBV in WM than in GM, suggesting the vasculature in the WM to be relatively more affected than the GM. Simultaneous measurements of CBF and CBV after acute alcohol intoxication in social drinkers are important in basic human neuroscience research to elucidate and understand brain physiology in the presence of exogenous neuro-pharmaceutical manipulations.


On the performance of compressed sensing-based methods for millimeter-wave holographic imaging.
This paper investigates compressed sensing (CS) based methods for reducing data-acquisition time in 2D millimeter-wave holographic imaging systems. Specific attention is paid to situations where the array element spacing does not satisfy the Nyquist criterion due to physical limitations. Simulation and experimental results demonstrate that CS methods achieve better reconstruction than the conventional backpropagation method with undersampled data at the cost of increased computational complexity. Specifically, the definition-based CS (D-CS) method derived by discretizing the scattering model achieves the best image resolution but can produce ghost targets when the sampling interval is greater than approximately twice the Nyquist sampling interval. On the contrary, the Fourier-transform-based CS (FT-CS) method has relatively lower resolution but performs well in the case of low number of measurements, large sampling interval, and low transmit power. In addition, the D-CS method requires much higher time complexity and space complexity than the FT-CS method because the 2D data needs to be processed in vector form. Particularly, the space complexity of constructing and loading the dictionary matrix makes the D-CS method extremely inefficient in dealing with real-time applications. The overall algorithm running time of the D-CS method can be up to 50 times greater than the FT-CS method with a scanning aperture of 81×81 and 121×121 grid size in reconstruction. An efficient method is to use the FT-CS method for coarse imaging and then use the D-CS method for specific regions where better precision is required.


[Enhanced Ca2+-sensing receptor function in pulmonary hypertension].
Pulmonary arterial hypertension (PAH) is a rare, progressive, and fetal disease. The five-year survival rate after diagnosis is ~50%. In Japan, PAH is listed in the Specified Rare and Intractable Diseases. Pulmonary vascular remodeling and sustained pulmonary vasoconstriction are the major causes for the elevated pulmonary vascular resistance (PVR) in PAH. The pathogenic mechanisms involved in the pulmonary vascular abnormalities in PAH remain unclear. Sustained vasoconstriction and vascular remodeling owing to proliferation of pulmonary arterial smooth muscle cells (PASMCs) are key pathogenic events that lead to early morbidity and mortality. These events have been closely linked to Ca(2+) mobilization and signaling in PASMCs. An increase in cytosolic Ca(2+) concentration ([Ca(2+)]cyt) in PASMCs is an important stimulus for pulmonary vasoconstriction and cell proliferation which subsequently cause pulmonary vascular wall thickening followed by the increase in PVR. Increased resting [Ca(2+)]cyt and enhanced Ca(2+) influx have been implicated in PASMCs from PAH patients, but precise therapeutic targets to interrupt these signal pathways have not been identified. We recently found that the extracellular Ca(2+)-sensing receptor (CaSR), a G protein-coupled receptor (GPCR), is upregulated in PASMCs from patients with idiopathic pulmonary arterial hypertension (IPAH). In addition, blockage of the CaSR with an antagonist (NPS2143) prevents the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The functionally upregulated CaSR in PASMCs is a novel pathogenic mechanism contributing to the augmented Ca(2+) signaling and excessive cell proliferation in IPAH. Targeting CaSR in PASMCs may help develop novel therapeutic approach for PAH.


Anxiety disorders during pregnancy: a systematic review.
To systematically evaluate the literature on anxiety disorders during pregnancy. MEDLINE, PsycINFO, and CINAHL were searched through October 2013 for original research studies published in English using combinations of the terms pregnancy, prenatal, or pregnancy outcomes; anxiety disorder; and generalized anxiety. Reference lists of included studies were hand-searched and a PubMed search for in-process reports was conducted. Relevant studies of anxiety disorders during pregnancy as determined by diagnostic interview were included if they reported on prevalence; course, onset, and/or risk factors; maternal, obstetric, or fetal/child outcomes; and/or treatment trial results. Two reviewers independently extracted relevant data and assessed methodological quality of each study. Fifty-seven reports were included. Reports provided information on panic disorder (25 reports), generalized anxiety disorder (17 reports), obsessive-compulsive disorder (OCD) (23 reports), agoraphobia (6 reports), specific phobia (10 reports), social phobia (14 reports), posttraumatic stress disorder (14 reports), and any anxiety disorder (18 reports). Twenty reports provided information on prevalence, 16 on course, 10 on risk factors, and 22 on outcomes. Only 1 treatment study was identified. High anxiety disorder prevalence in pregnancy was found; however, estimates vary considerably, and evidence is inconclusive as to whether prevalence among pregnant women differs from that of nonpregnant populations. Considerable variation in prenatal course of OCD and panic disorder was found. Substantial heterogeneity limits conclusions regarding risk factors or outcomes. Additional research of higher methodological quality is required to more accurately determine prevalence, understand course, identify risk factors and outcomes, and determine effective treatments for anxiety disorders in pregnancy.


Controllability analysis of the directed human protein interaction network identifies disease genes and drug targets.
The protein-protein interaction (PPI) network is crucial for cellular information processing and decision-making. With suitable inputs, PPI networks drive the cells to diverse functional outcomes such as cell proliferation or cell death. Here, we characterize the structural controllability of a large directed human PPI network comprising 6,339 proteins and 34,813 interactions. This network allows us to classify proteins as "indispensable," "neutral," or "dispensable," which correlates to increasing, no effect, or decreasing the number of driver nodes in the network upon removal of that protein. We find that 21% of the proteins in the PPI network are indispensable. Interestingly, these indispensable proteins are the primary targets of disease-causing mutations, human viruses, and drugs, suggesting that altering a network's control property is critical for the transition between healthy and disease states. Furthermore, analyzing copy number alterations data from 1,547 cancer patients reveals that 56 genes that are frequently amplified or deleted in nine different cancers are indispensable. Among the 56 genes, 46 of them have not been previously associated with cancer. This suggests that controllability analysis is very useful in identifying novel disease genes and potential drug targets.


Program Factors That Influence American Board of Surgery In-Training Examination Performance: A Multi-Institutional Study.
To determine the influence of program strategies, such as program directors' (PD) attitudes about the American Board of Surgery In-Training Examination (ABSITE) and approach to ABSITE preparation, on residents' ABSITE performance. A 17-item questionnaire was sent to PDs at surgical residency programs. The questions were designed to elicit information regarding the educational curriculum, remediation protocols, and opinions relating to the ABSITE. Main outcome measure was categorical resident ABSITE percentile scores from the January 2014 examination. Statistical analysis was performed using the Student t-test, analysis of variance, and linear regression as appropriate. The study was carried out at general surgery residency programs across the country. In total, 15 general surgery residency PDs participated in the study. The PD response rate was 100%. All 460 resident ABSITE scores from the 15 programs were obtained. In total, 10 programs (67%) identified as university affiliated, 4 programs (27%) as independent academic, and 1 program (7%) as hybrid. The mean number of residents per program was 30.7 (range: 15-57). In total, 14 PDs (93%) indicated that an ABSITE review curriculum was in place and 13 PDs (87%) indicated they had a remediation protocol for residents with low ABSITE scores (with differing thresholds of <30th, <35th, and <40th percentile). The median overall ABSITE score for all residents was 61st percentile (interquartile range = 39.5). The mean ABSITE score for each program ranged from 39th to 75th percentile. Program factors associated with higher ABSITE scores included tracking resident reading throughout the year (median 63rd percentile with tracking vs 59th percentile without, p = 0.040) and the type of remediation (by PD: 77th percentile, by PD and faculty: 57th percentile, faculty only: 64th percentile, with Surgical Education and Self-Assessment Program (SESAP): 63rd percentile, outside review course: 43rd percentile; p < 0.001). Programs with a remediation protocol trended toward higher ABSITE scores compared with programs without remediation protocols (median 61st percentile vs 53rd percentile, p = 0.098). Factors not significantly associated with ABSITE performance included number of structured educational hours per week and frequency of ABSITE review sessions. Program factors appear to significantly influence ABSITE performance. Programs where the PD was actively involved in remediation mentorship and the tracking of resident reading achieved higher ABSITE percentile scores on the January 2014 examination. Counterintuitively, residents from programs with a lower ABSITE threshold for remediation performed better on the examination.


Localization of glutathione and induction of glutathione synthesis-related proteins in mouse brain by low doses of gamma-rays.
First, we determined the cerebral localization of reduced glutathione (GSH) in normal mice by means of autoradiography using 99mTc-meso-hexamethyl propylene oxime. A highly specific localization of GSH in the cerebellum and hippocampus was observed. Secondly, we measured the elevation of GSH level in the brain after low-dose gamma-irradiation. The cerebral GSH levels increased soon after irradiation with 50 cGy of gamma-rays, reaching a maximum at 3 h post-treatment, then remaining significantly higher than that of the non-irradiated control until 12 h and returning to the control level by 24 h. Thirdly, we examined the induction of the activities and the mRNAs of proteins involved in the synthesis and regeneration of GSH in the brain of mice subjected to low-dose gamma-ray irradiation. The level of mRNA for gamma-glutamylcysteine synthetase was significantly increased at 0.5 h, and remained high until 2 h post-irradiation (50 cGy). The level was transiently lowered to the non-irradiated control level at 3 h and slightly increased again after 6 h post-irradiation. gamma-Glutamylcysteine synthetase activity was significantly increased 3 h after irradiation, and remained high up to 24 h post-irradiation. As for glutathione reductase, the mRNA level was increased at 0.5 h, and peaked strongly at 2 h, while the enzyme activity was significantly increased at 6 h after irradiation, and continued to increase up to 24 h. The level of mRNA for thioredoxin, which contributes to GSH biosynthesis by supplying cysteine to the de novo pathway, peaked between 0.5 h and 2 h post-irradiation, and rapidly declined thereafter. The content of thioredoxin showed a transient decrease immediately after irradiation, but was then remarkably elevated, reaching a maximum at 3 h, and thereafter declining sharply. These results indicate that the increase in endogenous GSH in mouse brain soon after low-dose gamma-ray irradiation is a consequence of the induction of GSH synthesis-related proteins and occurs via both the de novo synthesis and the regeneration pathways.


Follow-up recatheterization after balloon aortic valvuloplasty. Mansfield Scientific Aortic Valvuloplasty Registry Investigators.
The results of recatheterization were assessed in a select group of 95 patients enrolled in the Mansfield Scientific Aortic Valvuloplasty Registry to determine whether any procedural or patient-related variables at baseline predicted either initial immediate or follow-up (6.2 +/- 3.3 months) results. At the follow-up catheterization, 39 (41%) of the patients were in improved condition and 56 patients (59%) had recurrence of symptoms, allowing for analysis of the effect of the procedure in two symptomatic patient subsets. In the total group the aortic valve area increased initially from 0.56 +/- 0.16 to 0.87 +/- 0.27 cm2 but partial return to the baseline valve area was evident at follow-up (0.63 +/- 0.25 cm2). Similarly, the mean aortic gradient initially decreased from 72 +/- 30 to 35 +/- 16 mm Hg but then increased to 55 +/- 25 mm Hg at follow-up. Neither the initial nor the late hemodynamic results appeared affected by any definable procedural variable at the time of valvuloplasty, including the maximal diameter of balloons, number of balloons simultaneously used, mean inflation time or total number of inflations. Such technical concerns also did not seem to affect short- or long-term outcome. Similarly, no baseline hemodynamic variable clearly separated those who became increasingly symptomatic from those whose condition was improved at the 6 month interval. At recatheterization, a reduction in the aortic valve area toward baseline was observed in 24 (62%) of the 39 improved patients and in 45 (80%) of the 56 who were symptomatic.(ABSTRACT TRUNCATED AT 250 WORDS)


Use of oral sodium cromoglycate in persistent diarrhoea.
Twenty patients with persistent diarrhoea participated in a randomised, double-blind trial of oral sodium cromoglycate and placebo. Eight patients noted significant improvement in their diarrhoea while taking sodium cromoglycate and this did not correlate with the presence of other atopic diseases, a history of food intolerance, or the presence of lactase deficiency. The results suggest that some patients with diarrhoea of unknown cause may have food allergy as a major contributing cause for their diarrhoea.


Validation of contrast-enhanced magnetic resonance imaging to monitor regenerative efficacy after cell therapy in a porcine model of convalescent myocardial infarction.
Magnetic resonance imaging (MRI) in the CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial revealed that cardiosphere-derived cells (CDCs) decrease scar size and increase viable myocardium after myocardial infarction (MI), but MRI has not been validated as an index of regeneration after cell therapy. We tested the validity of contrast-enhanced MRI in quantifying scarred and viable myocardium after cell therapy in a porcine model of convalescent MI. Yucatan minipigs underwent induction of MI and 2-3 weeks later were randomized to receive intracoronary infusion of 12.5×10(6) mismatched allogeneic CDCs or vehicle. Allogeneic CDCs induced mild local mononuclear infiltration but no systemic immunogenicity. MRI revealed that allogeneic CDCs attenuated remodeling, improved global and regional function, decreased scar size, and increased viable myocardium compared with placebo 2 months post-treatment. Extensive histological analysis validated quantitatively the MRI measurements of scar size, scar mass, and viable mass. CDCs neither altered gadolinium contrast myocardial kinetics nor induced changes in vascular density or architecture in viable and scarred myocardium. Histology demonstrated that CDCs lead to cardiomyocyte hyperplasia in the border zone, consistent with the observed stimulation of endogenous regenerative mechanisms (cardiomyocyte cycling, upregulation of endogenous progenitors, angiogenesis). Contrast-enhanced MRI accurately measures scarred and viable myocardium after cell therapy in a porcine model of convalescent MI. MRI represents a useful tool for assessing dynamic changes in the infarct and monitoring regenerative efficacy.


Chemical analysis of whale breath volatiles: a case study for non-invasive field health diagnostics of marine mammals.
We explored the feasibility of collecting exhaled breath from a moribund gray whale (Eschrichtius robustus) for potential non-invasive health monitoring of marine mammals. Biogenic volatile organic compound (VOC) profiling is a relatively new field of research, in which the chemical composition of breath is used to non-invasively assess the health and physiological processes on-going within an animal or human. In this study, two telescopic sampling poles were designed and tested with the primary aim of collecting whale breath exhalations (WBEs). Once the WBEs were successfully collected, they were immediately transferred onto a stable matrix sorbent through a custom manifold system. A total of two large volume WBEs were successfully captured and pre-concentrated onto two Tenax®-TA traps (one exhalation per trap). The samples were then returned to the laboratory where they were analyzed using solid phase micro extraction (SPME) and gas chromatography/mass spectrometry (GC/MS). A total of 70 chemicals were identified (58 positively identified) in the whale breath samples. These chemicals were also matched against a database of VOCs found in humans, and 44% of chemicals found in the whale breath are also released by healthy humans. The exhaled gray whale breath showed a rich diversity of chemicals, indicating the analysis of whale breath exhalations is a promising new field of research.


Predictors of outcome after hyperthermic isolated limb perfusion: role of tumor response.
Analysis of multiple clinical and pathological factors in patients undergoing therapeutic hyperthermic isolated limb perfusion for extremity melanoma can identify variables with prognostic significance. Retrospective review of a prospectively collected limb perfusion database with a median follow-up interval of 32.2 months. Single-institution tertiary care surgical oncology unit. We report a series of 59 consecutive therapeutic hyperthermic isolated limb perfusion treatments (14 upper extremity and 45 lower extremity) in 54 patients with melanoma from January 1, 1995, through December 31, 2002, using a standard melphalan dosing protocol. At the time of perfusion, 31 cases had fewer than 10 lesions, with none greater than 3 cm in diameter. The remaining 28 cases had 10 or more lesions or at least 1 lesion greater than 3 cm in diameter. Response, recurrence, and survival were assessed in relation to multiple demographic, clinical, and technical variables using chi2, log-rank, and Kaplan-Meier survival analyses. The 3-year survival for the entire cohort was 54%. Thirty-three (56%) of the 59 perfusion treatments resulted in a persistent complete response of at least 6 months' duration. Statistical analysis showed that patients with no evidence of regional nodal involvement had a significantly lower incidence of distant recurrence (P = .02). Those patients achieving a complete response to therapy had a survival advantage (P = .03). In patients undergoing therapeutic hyperthermic isolated limb perfusion for in-transit melanoma, the ability to achieve a complete response following treatment, independent of regional nodal status, was the strongest predictor of long-term survival.


Being surveyed can change later behavior and related parameter estimates.
Does completing a household survey change the later behavior of those surveyed? In three field studies of health and two of microlending, we randomly assigned subjects to be surveyed about health and/or household finances and then measured subsequent use of a related product with data that does not rely on subjects' self-reports. In the three health experiments, we find that being surveyed increases use of water treatment products and take-up of medical insurance. Frequent surveys on reported diarrhea also led to biased estimates of the impact of improved source water quality. In two microlending studies, we do not find an effect of being surveyed on borrowing behavior. The results suggest that limited attention could play an important but context-dependent role in consumer choice, with the implication that researchers should reconsider whether, how, and how much to survey their subjects.


Functional Tests in Chronic Obstructive Pulmonary Disease, Part 1: Clinical Relevance and Links to the International Classification of Functioning, Disability, and Health.
Chronic obstructive pulmonary disease is a major cause of morbidity and mortality worldwide and an important cause of disability. A thorough patient-centered outcome assessment, including not only measures of lung function, exercise capacity, and health-related quality of life, but also functional capacity and performance in activities of daily life, is imperative for a comprehensive management of chronic obstructive pulmonary disease. This American Thoracic Society Seminar Series is devoted to help clinicians substantiate their choice of functional outcome measures in this population. In Part 1 of this two-part seminar series, we describe the various domains of functional status to elucidate terms and key concepts intertwined with functioning and to demonstrate the clinical relevance of assessing functional capacity in the context of activities of daily living in agreement with the International Classification of Functioning, Disability, and Health. We hope that a better understanding of the various defining components of functional status will be instrumental to healthcare providers to optimize chronic obstructive pulmonary disease evaluation and management, ultimately leading to improved quality of life of patients afflicted by this condition. This first article also serves as an introduction to Part 2 of this seminar series, in which the main functional tests available to assess upper and lower body functional capacity of these patients are discussed.


Circadian variation of mineral and bone parameters in end-stage renal disease.
Mineral and bone parameters are actively managed in end-stage renal disease (ESRD). However, whether these undergo circadian variation is not known. We investigated the circadian variation of mineral and bone parameters in patients on long-term hemodialysis. Seventeen ESRD patients on long-term hemodialysis and eight volunteers without kidney disease were enrolled. Subjects had all medications that affect calcium-phosphate-parathyroid hormone balance (phosphate binders, vitamin D analogues, and calcimimetics) discontinued. Thereafter, for a period of 5 days, subjects consumed a diet controlled in calcium (1,200 mg per day) and phosphorus (1,000 mg per day) content. On the sixth day (a non-dialysis day for the ESRD patients), enrollees underwent twelve 2-h blood draws for phosphate, ionized calcium, parathyroid hormone (PTH), total 25-hydroxy vitamin D (25OHD), and fibroblast growth factor-23 (FGF-23). In the ESRD patients plasma phosphate demonstrated significant circadian variation (P < 0.00001). The peak occurred around 3:30 am and nadir occurred around 11:00 am. Ionized calcium (P = 0.0036), PTH (P = 0.0004) and 25OHD (P = 0.009) also varied significantly during the circadian period; for ionized calcium peak and nadir occurred around 12:15 pm and 8:00 pm, parathyroid hormone 5:45 pm and 10:15 am, and 25OHD 9:45 am and 4:00 pm respectively. FGF-23 did not show a significant circadian variation. Only phosphate (P < 0.0001) and PTH (P = 0.00008) demonstrated circadian variation in the control group. Blood concentrations of phosphate, calcium, PTH and 25-hydroxy vitamin D, exhibit a circadian variation in patients with ESRD. Knowledge of these phenomena is pertinent for the interpretation of clinical testing.


Cochlear Implantation in Extraordinary Cases.
Although cochlear implantation has been almost a standard otological procedure worldwide, it may still create a dilemma for the surgeon in some unusual instances such as Seckel syndrome, aural atresia and posterior fossa arachnoid cyst. Three extraordinary cases of cochlear implantation were reported. The first case was a case of Seckel syndrome with a cardiac pacemaker due to complete atrioventricular block. The second case had posterior fossa arachnoid cyst that had retrosigmoid cyst removal and cochlear implantation simultaneously. The last case had cochlear implantation in the ear with congenital aural atresia. All cases could be implanted successfully with full electrode insertion and good audiological outcome. Delayed facial paralysis that occurred in the patient with arachnoid cyst resolved spontaneously. This study addressed the efficiency of cochlear implantation in cases of Seckel syndrome, complete atrioventricular block managed with cardiac pacemaker, congenital aural atresia and posterior fossa arachnoid cyst. In addition, the retrosigmoid approach and cochlear implantation can be performed simultaneously.


Eukaryotic DNA polymerases.
Any living cell is faced with the fundamental task of keeping the genome intact in order to develop in an organized manner, to function in a complex environment, to divide at the right time, and to die when it is appropriate. To achieve this goal, an efficient machinery is required to maintain the genetic information encoded in DNA during cell division, DNA repair, DNA recombination, and the bypassing of damage in DNA. DNA polymerases (pols) alpha, beta, gamma, delta, and epsilon are the key enzymes required to maintain the integrity of the genome under all these circumstances. In the last few years the number of known pols, including terminal transferase and telomerase, has increased to at least 19. A particular pol might have more than one functional task in a cell and a particular DNA synthetic event may require more than one pol, which suggests that nature has provided various safety mechanisms. This multi-functional feature is especially valid for the variety of novel pols identified in the last three years. These are the lesion-replicating enzymes pol zeta, pol eta, pol iota, pol kappa, and Rev1, and a group of pols called pol theta;, pol lambda, pol micro, pol sigma, and pol phi that fulfill a variety of other tasks.


Psychosis and autism as diametrical disorders of the social brain.
Autistic-spectrum conditions and psychotic-spectrum conditions (mainly schizophrenia, bipolar disorder, and major depression) represent two major suites of disorders of human cognition, affect, and behavior that involve altered development and function of the social brain. We describe evidence that a large set of phenotypic traits exhibit diametrically opposite phenotypes in autistic-spectrum versus psychotic-spectrum conditions, with a focus on schizophrenia. This suite of traits is inter-correlated, in that autism involves a general pattern of constrained overgrowth, whereas schizophrenia involves undergrowth. These disorders also exhibit diametric patterns for traits related to social brain development, including aspects of gaze, agency, social cognition, local versus global processing, language, and behavior. Social cognition is thus underdeveloped in autistic-spectrum conditions and hyper-developed on the psychotic spectrum.;>We propose and evaluate a novel hypothesis that may help to explain these diametric phenotypes: that the development of these two sets of conditions is mediated in part by alterations of genomic imprinting. Evidence regarding the genetic, physiological, neurological, and psychological underpinnings of psychotic-spectrum conditions supports the hypothesis that the etiologies of these conditions involve biases towards increased relative effects from imprinted genes with maternal expression, which engender a general pattern of undergrowth. By contrast, autistic-spectrum conditions appear to involve increased relative bias towards effects of paternally expressed genes, which mediate overgrowth. This hypothesis provides a simple yet comprehensive theory, grounded in evolutionary biology and genetics, for understanding the causes and phenotypes of autistic-spectrum and psychotic-spectrum conditions.


Leaving school: a comparison of the worries held by adolescents with and without intellectual disabilities.
Leaving school is an important time for adolescents, with increasing autonomy and developing adult identities. The present study sought to shed light on the content and emotional impact of worries amongst adolescents with and without intellectual disabilities (IDs) at this time of change. Twenty-five adolescents with mild to moderate IDs and 27 adolescents without IDs, aged 15 to 18 years, took part in the study. Participants' worries were elicited using a structured interview. The levels of rumination and distress related to their most salient worries were also examined, along with their self-reported levels of anxiety. Content analysis of the interviews identified differences between the worries of the two groups of participants, with the adolescents with IDs expressing more general worries about failure and personal threat. Level of distress about worries was positively correlated with anxiety in both groups. The adolescents with IDs were significantly more anxious than their non-disabled peers. The differences between the groups' worries may be linked to differences in life experience and expectations. Consideration should be given to the specific worries of adolescents at the stage of leaving school. Doing so may allow solutions for their concerns to be identified, thus easing distress and leading to a less stressful transition.


Intrinsic tumor necrosis factor-α pathway is activated in a subset of patients with focal segmental glomerulosclerosis.
Focal segmental glomerulosclerosis (FSGS) is frequently found in biopsies of patients with steroid resistant nephrotic syndrome (SRNS). The pathogenesis of SRNS/FSGS is often unknown and the disease will recur in up to 50% of patients post-transplant, indicating the presence of circulating podocyte-toxic factor(s). Several studies have reported clinical improvement after anti-TNFα therapy. However, prediction of the clinical outcome in SRNS/FSGS is difficult, and novel predictive biomarkers are needed. An image-based assay, which measures disassembly of focal adhesion complexes in cultured podocytes, was used to ascertain the presence of podocyte toxic activity in SRNS/FSGS sera. Expression of TNFα pathway genes was analysed in the Nephroseq FSGS cohort and in cultured podocytes treated with SRNS/FSGS sera. Podocyte toxic activity was detected in 48/96 SRNS/FSGS patients. It did not correlate with serum TNFα levels, age, sex, ethnicity or glomerular filtration rate. In ~25% of the toxic samples, the toxicity was strongly inhibited by blockade of TNFα signaling. Transcriptional profiling of human FSGS biopsies and podocytes treated with FSGS sera revealed significant increases in expression of TNFα pathway genes. We identified patients with serum podocyte toxic activity who may be at risk for FSGS recurrence, and those patients in whom serum podocyte toxicity may be reversed by TNFα blockade. Activation of TNFα pathway genes occurs in podocytes of FSGS patients suggesting a causative effect of this pathway in response to circulating factor(s). In vitro analyses of patient sera may stratify patients according to prognostic outcomes and potential responses to specific clinical interventions.


Determination and analysis of the complete nucleotide sequence of human herpesvirus.
Human herpesvirus 7 (HHV-7) is a recently isolated betaherpesvirus that is prevalent in the human population, with primary infection usually occurring in early childhood. HHV-7 is related to human herpesvirus 6 (HHV-6) in terms of both biological and, from limited prior DNA sequence analysis, genetic criteria. However, extensive analysis of the HHV-7 genome has not been reported, and the precise phylogenetic relationship of HHV-7 to the other human betaherpesviruses HHV-6 and human cytomegalovirus has not been determined. Here I report on the determination and analysis of the complete DNA sequence of HHV-7 strain JI. The data establish that the close biological relationship of HHV-6 and HHV-7 is reflected at the genetic level, where there is a very high degree of conservation of genetic content and encoded amino acid sequences. The data also delineate loci of divergence between the HHV-6 and HHV-7 genomes, which occur at the genome terminal in the region of the terminal direct-repeat elements and within limited regions of the unique component. Of potential significance with respect to biological and evolutionary divergence of HHV-6 and HHV-7 are notable structural differences in putative transcriptional regulatory genes specified by the direct-repeat and immediate-early region A loci of these viruses and the absence of an equivalent of the HHV-6 adeno-associated virus type 2 rep gene homolog in HHV-7.


An experiment with community health funds in Afghanistan.
As Afghanistan rebuilds its health system, it faces key challenges in financing health services. To reduce dependence on donor funds, it is important to develop sustainable local financing mechanisms. A second challenge is to reduce high levels of out-of-pocket payments. Community-based health insurance (CBHI) schemes offer the possibility of raising revenues from communities and at the same time providing financial protection. This paper describes the performance of one type of CBHI scheme, the Community Health Fund (CHF), which was piloted for the first time in five provinces of Afghanistan between June 2005 and October 2006. The performance of the CHF programme demonstrates that complex community-based health financing schemes can be implemented in post-conflict settings like Afghanistan, except in areas of high insecurity. The funds raised from the community, via premiums and user fees, enabled the pilot facilities to overcome temporary shortages of drugs and supplies, and to conduct outreach services via mobile clinics. However, enrolment and cost-recovery were modest. The median enrolment rate for premium-paying households was 6% of eligible households in the catchment areas of the clinics. Cost recovery rates ranged up to 16% of total operating costs and 32% of non-salary operating costs. No evidence of reduced out-of-pocket health expenditures was observed at the community level, though CHF members had markedly higher utilization of health services. The main reasons among non-members for not enrolling were being unaware of the programme; high premiums; and perceived low quality of services at the CHF clinics. The performance of Afghanistan's CHF was similar to other CHF-type programmes operating at the primary care level internationally. The solution to building local capacity to finance health services lies in a combination of financing sources rather than any single mechanism. In this context, it is critical that international assistance for Afghanistan's health sector continues.


Short review on the diagnosis and treatment of bronchiectasis.
Bronchiectasis refers to the permanent dilation of the bronchi. It is often a sequel of insufficiently treated lung disease that develops into a pathological pattern of dilated bronchi, which heightens susceptibility to further lung infections. Modernization of diagnostic procedures (computed tomography scan) and definition of a clinical picture (repeated lung infections with a chronic cough and persistent sputum production) have raised international awareness of the prevalence of the disease, leading to increasing interest in reviewing and renewing the treatment guidelines. We selectively conducted a research on PubMed using the following keywords: "bronchiectasis", "diagnosis", "treatment", "management", "antibiotics". This review focuses solely on bronchiectasis not due to cystic fibrosis. All relevant articles published after the year of 2000 were included. The aim of this review is to provide an analytical update on the management of bronchiectasis, focusing on etiological factors as well as existing and developing treatment options for the disease.


Lack of a role for natural killer cells in early control of Brucella abortus 2308 infections in mice.
Studies were conducted to determine if natural killer (NK) cells are important for early control of the virulent strain Brucella abortus 2308 following infection of mice with high or low challenge doses. Splenocytes from C57BL/10 and BALB/c mice that had been infected with the lower dose of B. abortus displayed increased cytotoxicity against YAC-1 cells during the first week after infection, while infection of C57BL/10 mice with the higher challenge dose either did not alter the level of NK cytotoxic activity or decreased it, depending upon the time postinfection. In vivo depletion of NK cells by monoclonal antibody anti-NK1.1 or polyclonal anti-asialoGM1 antiserum did not result in an increase in the number of brucellae recovered from the spleens or livers of the brucella-resistant C57BL/10 mice or from the spleens of the susceptible BALB/c mice during the first week after infection. Treatment of control mice with the NK-reactive antibodies, however, decreased killing of the NK-sensitive target YAC-1, indicating that the NK cell depletion regimes were effective. Our results suggest that NK cells are not crucial for early control of B. abortus 2308 even though they may be activated following infection. Further experiments indicated that treatment of C57BL/10 mice with poly(A:U) did not decrease the number of brucellae recovered from their spleens although it did decrease the CFU in livers of mice infected with the high challenge dose.


Madagascar's grasses and grasslands: anthropogenic or natural?
Grasses, by their high productivity even under very low pCO2, their ability to survive repeated burning and to tolerate long dry seasons, have transformed the terrestrial biomes in the Neogene and Quaternary. The expansion of grasslands at the cost of biodiverse forest biomes in Madagascar is often postulated as a consequence of the Holocene settlement of the island by humans. However, we show that the Malagasy grass flora has many indications of being ancient with a long local evolutionary history, much predating the Holocene arrival of humans. First, the level of endemism in the Madagascar grass flora is well above the global average for large islands. Second, a survey of many of the more diverse areas indicates that there is a very high spatial and ecological turnover in the grass flora, indicating a high degree of niche specialization. We also find some evidence that there are both recently disturbed and natural stable grasslands: phylogenetic community assembly indicates that recently severely disturbed grasslands are phylogenetically clustered, whereas more undisturbed grasslands tend to be phylogenetically more evenly distributed. From this evidence, it is likely that grass communities existed in Madagascar long before human arrival and so were determined by climate, natural grazing and other natural factors. Humans introduced zebu cattle farming and increased fire frequency, and may have triggered an expansion of the grasslands. Grasses probably played the same role in the modification of the Malagasy environments as elsewhere in the tropics.


Which observed behaviours may reassure physicians that a child is not septic? An international Delphi study.
In an attempt to improve the diagnosis of sepsis in children, diagnostic aids have concentrated on clinical features that suggest that sepsis is present. Clinicians need to be able to clinically rule out sepsis as well as rule it in. Little is known about which features are consistent with wellness and/or absence of sepsis. Guidelines are therefore likely to improve sensitivity without preserving specificity. We aimed to gather expert opinion on which (if any) features would make clinicians consider a child to be unlikely to have sepsis. We undertook a modified two-round international Delphi study, where clinicians were asked for features they believed were indicators of wellness in an ill child. One hundred and ninety-five clinicians (predominantly physicians) who routinely assessed unwell children and had been doing so for most of their careers. Over 90% of respondents rated age-appropriate verbalisation, playing, smiling and activity as reassuring that a child was unlikely to have sepsis. Eating, spontaneous interaction and normal movement were also agreed to be reassuring by over 70% of participants. Consolability and showing fear of the clinician were not felt to be adequately reassuring. There was wide range of opinion on how reassuring the use of an electronic device was thought to be. This study confirms that physicians are reassured by specific behaviours in ill children, and provides a framework which may be used to help guide the assessment of the unwell child. Validation of individual features could lead to improved specificity of diagnostic aids for diagnosing sepsis.


Treatment of only the fractional curve for radiculopathy in adult scoliosis: comparison to lower thoracic and upper thoracic fusions.
OBJECTIVEMany options exist for the surgical management of adult spinal deformity. Radiculopathy and lumbosacral pain from the fractional curve (FC), typically from L4 to S1, is frequently a reason for scoliosis patients to pursue surgical intervention. The purpose of this study was to evaluate the outcomes of limited fusion of the FC only versus treatment of the entire deformity with long fusions.METHODSAll adult scoliosis patients treated at the authors' institution in the period from 2006 to 2016 were retrospectively analyzed. Patients with FCs from L4 to S1 > 10° and radiculopathy ipsilateral to the concavity of the FC were eligible for study inclusion and had undergone three categories of surgery: 1) FC only (FC group), 2) lower thoracic to sacrum (LT group), or 3) upper thoracic to sacrum (UT group). Primary outcomes were the rates of revision surgery and complications. Secondary outcomes were estimated blood loss, length of hospital stay, and discharge destination. Spinopelvic parameters were measured, and patients were stratified accordingly.RESULTSOf the 99 patients eligible for inclusion in the study, 27 were in the FC group, 46 in the LT group, and 26 in the UT group. There were no significant preoperative differences in age, sex, smoking status, prior operation, FC magnitude, pelvic tilt (PT), sagittal vertical axis (SVA), coronal balance, pelvic incidence-lumbar lordosis (PI-LL) mismatch, or proportion of well-aligned spines (SVA < 5 cm, PI-LL mismatch < 10°, and PT < 20°) among the three treatment groups. Mean follow-up was 30 (range 12-112) months, with a minimum 1-year follow-up. The FC group had a lower medical complication rate (22% [FC] vs 57% [LT] vs 58% [UT], p = 0.009) but a higher rate of extension surgery (26% [FC] vs 13% [LT] vs 4% [UT], p = 0.068). The respective average estimated blood loss (592 vs 1950 vs 2634 ml, p < 0.001), length of hospital stay (5.5 vs 8.3 vs 8.3 days, p < 0.001), and rate of discharge to acute rehabilitation (30% vs 46% vs 85%, p < 0.001) were all lower for FC and highest for UT.CONCLUSIONSTreatment of the FC only is associated with a lower complication rate, shorter hospital stay, and less blood loss than complete scoliosis treatment. However, there is a higher associated rate of extension of the construct to the lower or upper thoracic levels, and patients should be counseled when considering their options.


Plasmodium falciparum and Plasmodium vivax Demonstrate Contrasting Chloroquine Resistance Reversal Phenotypes.
High-grade chloroquine (CQ) resistance has emerged in both Plasmodium falciparum and P. vivax The aim of the present study was to investigate the phenotypic differences of CQ resistance in both of these species and the ability of known CQ resistance reversal agents (CQRRAs) to alter CQ susceptibility. Between April 2015 and April 2016, the potential of verapamil (VP), mibefradil (MF), L703,606 (L7), and primaquine (PQ) to reverse CQ resistance was assessed in 46 P. falciparum and 34 P. vivax clinical isolates in Papua, Indonesia, where CQ resistance is present in both species, using a modified schizont maturation assay. In P. falciparum, CQ 50% inhibitory concentrations (IC50s) were reduced when CQ was combined with VP (1.4-fold), MF (1.2-fold), L7 (4.2-fold), or PQ (1.8-fold). The degree of CQ resistance reversal in P. falciparum was highly correlated with CQ susceptibility for all CQRRAs (R2 = 0.951, 0.852, 0.962, and 0.901 for VP, MF, L7, and PQ, respectively), in line with observations in P. falciparum laboratory strains. In contrast, no reduction in the CQ IC50s was observed with any of the CQRRAs in P. vivax, even in those isolates with high chloroquine IC50s. The differential effect of CQRRAs in P. falciparum and P. vivax suggests significant differences in CQ kinetics and, potentially, the likely mechanism of CQ resistance between these two species.


Modern management of primary B-cell immunodeficiencies.
B-cell defects constitute the majority of primary immunodeficiencies. Although a heterogeneous group of diseases, all are characterized by the reduction in or absence of immunoglobulins and/or specific antimicrobial antibodies. Substitution of immunoglobulin G (IgG) is therefore the mainstay of treatment. While from the late 1970s, the intravenous route of administration was the most common, in the past decades, subcutaneous immunoglobulin replacement therapy has become more popular among patients and physicians. Independently of the optimal route of administration, dosage and IgG trough level remain subjects of debate. Higher IgG trough levels seem to improve the protection against recurrent infections and thus better prevent complications such as bronchiectasis. Some patients, however, achieve protection with IgG trough levels on the lower IgG limit of healthy persons. Therefore, an individual protective IgG trough level needs to be defined for each patient. Use of additional prophylactic antibiotics and immunosuppressive drugs differs amongst specialized immunodeficiency centres and clearly requires future investigation in multi-centre trials. Haematopoietic stem cell transplantation (HSCT) is to date indicated as curative treatment in certain patients with B-cell defects associated with cell deficiencies, for example in two class-switch recombination defects and in selected severe forms of common variable immunodeficiency.


ATP-sensitive potassium channel modulation of the guinea pig ventricular action potential and contraction.
The role of ATP-sensitive potassium (KATP) channels in modulating the action potential and contraction of guinea pig ventricular myocytes was investigated. Under voltage clamp, the maximum whole-cell KATP channel conductance was estimated (195 +/- 10 nS, n = 6) by exposing the cells to complete metabolic blockade (2 mM cyanide in the presence of 10 mM 2-deoxy-glucose). In isolated inside-out membrane patches, the ATP dependence of KATP channel activity under relevant conditions was measured (half-maximal inhibition at 114 microM). Under current clamp (with intracellular ATP concentration = 5 mM), the effect of graded KATP channel activation on the action potential and the twitch was estimated by injection of a current (proportional to voltage) that simulated the KATP conductance. As this "conductance" was increased, the action potential was shortened, and contractile amplitude declined, as expected. From the results of these experiments, the quantitative dependence of the action potential duration on intracellular ATP concentration was estimated, without relying on a mathematical model of the cell membrane. The results imply that KATP-dependent action potential shortening is likely to occur if ATP concentration falls below normal levels (approximately 5 mM), as may happen regionally, or globally, during myocardial ischemia.


Remote Sensing Phenology of Antarctic Green and Red Snow Algae Using WorldView Satellites.
Snow algae are an important group of terrestrial photosynthetic organisms in Antarctica, where they mostly grow in low lying coastal snow fields. Reliable observations of Antarctic snow algae are difficult owing to the transient nature of their blooms and the logistics involved to travel and work there. Previous studies have used Sentinel 2 satellite imagery to detect and monitor snow algal blooms remotely, but were limited by the coarse spatial resolution and difficulties detecting red blooms. Here, for the first time, we use high-resolution WorldView multispectral satellite imagery to study Antarctic snow algal blooms in detail, tracking the growth of red and green blooms throughout the summer. Our remote sensing approach was developed alongside two Antarctic field seasons, where field spectroscopy was used to build a detection model capable of estimating cell density. Global Positioning System (GPS) tagging of blooms and in situ life cycle analysis was used to validate and verify our model output. WorldView imagery was then used successfully to identify red and green snow algae on Anchorage Island (Ryder Bay, 67°S), estimating peak coverage to be 9.48 × 104 and 6.26 × 104 m2, respectively. Combined, this was greater than terrestrial vegetation area coverage for the island, measured using a normalized difference vegetation index. Green snow algae had greater cell density and average layer thickness than red blooms (6.0 × 104 vs. 4.3 × 104 cells ml-1) and so for Anchorage Island we estimated that green algae dry biomass was over three times that of red algae (567 vs. 180 kg, respectively). Because the high spatial resolution of the WorldView imagery and its ability to detect red blooms, calculated snow algal area was 17.5 times greater than estimated with Sentinel 2 imagery. This highlights a scaling problem of using coarse resolution imagery and suggests snow algal contribution to net primary productivity on Antarctica may be far greater than previously recognized.


Non-invasive diagnostic tests for Helicobacter pylori infection.
Helicobacter pylori (H pylori) infection has been implicated in a number of malignancies and non-malignant conditions including peptic ulcers, non-ulcer dyspepsia, recurrent peptic ulcer bleeding, unexplained iron deficiency anaemia, idiopathic thrombocytopaenia purpura, and colorectal adenomas. The confirmatory diagnosis of H pylori is by endoscopic biopsy, followed by histopathological examination using haemotoxylin and eosin (H & E) stain or special stains such as Giemsa stain and Warthin-Starry stain. Special stains are more accurate than H & E stain. There is significant uncertainty about the diagnostic accuracy of non-invasive tests for diagnosis of H pylori. To compare the diagnostic accuracy of urea breath test, serology, and stool antigen test, used alone or in combination, for diagnosis of H pylori infection in symptomatic and asymptomatic people, so that eradication therapy for H pylori can be started. We searched MEDLINE, Embase, the Science Citation Index and the National Institute for Health Research Health Technology Assessment Database on 4 March 2016. We screened references in the included studies to identify additional studies. We also conducted citation searches of relevant studies, most recently on 4 December 2016. We did not restrict studies by language or publication status, or whether data were collected prospectively or retrospectively. We included diagnostic accuracy studies that evaluated at least one of the index tests (urea breath test using isotopes such as 13C or 14C, serology and stool antigen test) against the reference standard (histopathological examination using H & E stain, special stains or immunohistochemical stain) in people suspected of having H pylori infection. Two review authors independently screened the references to identify relevant studies and independently extracted data. We assessed the methodological quality of studies using the QUADAS-2 tool. We performed meta-analysis by using the hierarchical summary receiver operating characteristic (HSROC) model to estimate and compare SROC curves. Where appropriate, we used bivariate or univariate logistic regression models to estimate summary sensitivities and specificities. We included 101 studies involving 11,003 participants, of which 5839 participants (53.1%) had H pylori infection. The prevalence of H pylori infection in the studies ranged from 15.2% to 94.7%, with a median prevalence of 53.7% (interquartile range 42.0% to 66.5%). Most of the studies (57%) included participants with dyspepsia and 53 studies excluded participants who recently had proton pump inhibitors or antibiotics.There was at least an unclear risk of bias or unclear applicability concern for each study.Of the 101 studies, 15 compared the accuracy of two index tests and two studies compared the accuracy of three index tests. Thirty-four studies (4242 participants) evaluated serology; 29 studies (2988 participants) evaluated stool antigen test; 34 studies (3139 participants) evaluated urea breath test-13C; 21 studies (1810 participants) evaluated urea breath test-14C; and two studies (127 participants) evaluated urea breath test but did not report the isotope used. The thresholds used to define test positivity and the staining techniques used for histopathological examination (reference standard) varied between studies. Due to sparse data for each threshold reported, it was not possible to identify the best threshold for each test.Using data from 99 studies in an indirect test comparison, there was statistical evidence of a difference in diagnostic accuracy between urea breath test-13C, urea breath test-14C, serology and stool antigen test (P = 0.024). The diagnostic odds ratios for urea breath test-13C, urea breath test-14C, serology, and stool antigen test were 153 (95% confidence interval (CI) 73.7 to 316), 105 (95% CI 74.0 to 150), 47.4 (95% CI 25.5 to 88.1) and 45.1 (95% CI 24.2 to 84.1). The sensitivity (95% CI) estimated at a fixed specificity of 0.90 (median from studies across the four tests), was 0.94 (95% CI 0.89 to 0.97) for urea breath test-13C, 0.92 (95% CI 0.89 to 0.94) for urea breath test-14C, 0.84 (95% CI 0.74 to 0.91) for serology, and 0.83 (95% CI 0.73 to 0.90) for stool antigen test. This implies that on average, given a specificity of 0.90 and prevalence of 53.7% (median specificity and prevalence in the studies), out of 1000 people tested for H pylori infection, there will be 46 false positives (people without H pylori infection who will be diagnosed as having H pylori infection). In this hypothetical cohort, urea breath test-13C, urea breath test-14C, serology, and stool antigen test will give 30 (95% CI 15 to 58), 42 (95% CI 30 to 58), 86 (95% CI 50 to 140), and 89 (95% CI 52 to 146) false negatives respectively (people with H pylori infection for whom the diagnosis of H pylori will be missed).Direct comparisons were based on few head-to-head studies. The ratios of diagnostic odds ratios (DORs) were 0.68 (95% CI 0.12 to 3.70; P = 0.56) for urea breath test-13C versus serology (seven studies), and 0.88 (95% CI 0.14 to 5.56; P = 0.84) for urea breath test-13C versus stool antigen test (seven studies). The 95% CIs of these estimates overlap with those of the ratios of DORs from the indirect comparison. Data were limited or unavailable for meta-analysis of other direct comparisons. In people without a history of gastrectomy and those who have not recently had antibiotics or proton ,pump inhibitors, urea breath tests had high diagnostic accuracy while serology and stool antigen tests were less accurate for diagnosis of Helicobacter pylori infection.This is based on an indirect test comparison (with potential for bias due to confounding), as evidence from direct comparisons was limited or unavailable. The thresholds used for these tests were highly variable and we were unable to identify specific thresholds that might be useful in clinical practice.We need further comparative studies of high methodological quality to obtain more reliable evidence of relative accuracy between the tests. Such studies should be conducted prospectively in a representative spectrum of participants and clearly reported to ensure low risk of bias. Most importantly, studies should prespecify and clearly report thresholds used, and should avoid inappropriate exclusions.


Increased fat mass is associated with increased bone size but reduced volumetric density in pre pubertal children.
Recent studies have shown that obesity is associated with an increased risk of fracture in both adults and children. It has been suggested that, despite greater bone size, obese individuals may have reduced true volumetric density; however this is difficult to assess using two dimensional techniques such as DXA. We evaluated the relationship between fat mass, and bone size and density, in a population cohort of children in whom DXA and pQCT measurements had been acquired. We recruited 530 children at 6 years old from the Southampton Women's Survey. The children underwent measurement of bone mass at the whole body, lumbar spine and hip, together with body composition, by DXA (Hologic Discovery, Hologic Inc., Bedford, MA, USA). In addition 132 of these children underwent pQCT measurements at the tibia (Stratec XCT2000, Stratec Biomedical Systems, Birkenfeld, Germany). Significant positive associations were observed between total fat mass and both bone area (BA) and bone mineral content (BMC) at the whole body minus head, lumbar spine and hip sites (all p<0.0001). When true volumetric density was assessed using pQCT data from the tibia, fat mass (adjusted for lean mass) was negatively associated with both trabecular and cortical density (β=-14.6 mg/mm(3) per sd, p=0.003; β=-7.7 mg/mm(3) per sd, p=0.02 respectively). These results suggest that fat mass is negatively associated with volumetric bone density at 6 years old, independent of lean mass, despite positive associations with bone size.


Nonradiative recombination--critical in choosing quantum well number for InGaN/GaN light-emitting diodes.
In this work, InGaN/GaN light-emitting diodes (LEDs) possessing varied quantum well (QW) numbers were systematically investigated both numerically and experimentally. The numerical computations show that with the increased QW number, a reduced electron leakage can be achieved and hence the efficiency droop can be reduced when a constant Shockley-Read-Hall (SRH) nonradiative recombination lifetime is used for all the samples. However, the experimental results indicate that, though the efficiency droop is suppressed, the LED optical power is first improved and then degraded with the increasing QW number. The analysis of the measured external quantum efficiency (EQE) with the increasing current revealed that an increasingly dominant SRH nonradiative recombination is induced with more epitaxial QWs, which can be related to the defect generation due to the strain relaxation, especially when the effective thickness exceeds the critical thickness. These observations were further supported by the carrier lifetime measurement using a pico-second time-resolved photoluminescence (TRPL) system, which allowed for a revised numerical modeling with the different SRH lifetimes considered. This work provides useful guidelines on choosing the critical QW number when designing LED structures.


Novel molecular aspects of ghrelin and leptin in the control of adipobiology and the cardiovascular system.
Ghrelin and leptin show opposite effects on energy balance. Ghrelin constitutes a gut hormone that is secreted to the bloodstream in two major forms, acylated and desacyl ghrelin. The isoforms of ghrelin not only promote adiposity by the activation of hypothalamic orexigenic neurons but also directly stimulate the expression of several fat storage-related proteins in adipocytes, including ACC, FAS, LPL and perilipin, thereby stimulating intracytoplasmic lipid accumulation. Moreover, both acylated and desacyl ghrelin reduce TNF-α-induced apoptosis and autophagy in adipocytes, suggesting an anti-inflammatory role of ghrelin in human adipose tissue. On the other hand, leptin is an adipokine with lipolytic effects. In this sense, leptin modulates via PI3K/Akt/mTOR the expression of aquaglyceroporins such as AQP3 and AQP7 that facilitate glycerol efflux from adipocytes in response to the lipolytic stimuli via its translocation from the cytosolic fraction (AQP3) or lipid droplets (AQP7) to the plasma membrane. Ghrelin and leptin also participate in the homeostasis of the cardiovascular system. Ghrelin operates as a cardioprotective factor with increased circulating acylated ghrelin concentrations in patients with left ventricular hypertrophy (LVH) causally related to LV remodeling during the progression to LVH. Additionally, leptin induces vasodilation by inducible NO synthase expression (iNOS) in the vascular wall. In this sense, leptin inhibits the angiotensin II-induced Ca(2+) increase, contraction and proliferation of VSMC through NO-dependent mechanisms. Together, dysregulation of circulating ghrelin isoforms and leptin resistance associated to obesity, type 2 diabetes, or the metabolic syndrome contribute to cardiometabolic derangements observed in these pathologies.


The functional BPV-1 E2 trans-activating protein can act as a repressor by preventing formation of the initiation complex.
The products encoded by the E2 open reading frame of the papillomaviruses are DNA-binding transcription factors involved in the positive or negative regulation of multiple viral promoters. To further understand the mechanisms by which the same transcription factor may act differentially, the full-length BPV-1 E2 protein was expressed and purified from yeast and assayed in vitro for its capacity to modulate transcription. E2 stimulated transcription of the HSV thymidine kinase (TK) promoter when E2-binding sites were positioned in an enhancer configuration approximately 100 bp upstream of the promoter start site. In contrast, the same full-length E2 protein repressed transcription of the HPV-18 E6/E7 P105 promoter. This repression was mediated through binding to the E2 DNA-binding site immediately upstream of the P105 promoter TATA box and could be abrogated by preincubation of the HPV-18 P105 promoter template with the nuclear extract allowing the formation of the preinitiation complex. In vitro DNA-binding experiments with purified E2 and TFIID showed that binding of E2 to its DNA target placed at different positions with respect to the TATA box differentially affects binding of TFIID to its cognate site. In these respects, E2 is similar to the bacteriophage lambda repressor, which can act either as a repressor or an activator of transcription depending on the position of its binding sites relative to the promoter sequences.


Deficiency of intramuscular ICC increases fundic muscle excitability but does not impede nitrergic innervation.
The motility of the gastrointestinal tract is generated by smooth muscle cells and is controlled to a large extent by an intrinsic neural network. A gap of approximately 200 nm usually separates nerve varicosities from smooth muscle cells, which suggests that direct innervation of the smooth muscle by synapses does not occur. Enteric nerves do make synapse-like contact with proposed regulatory cells, the interstitial cells of Cajal (ICC), which in turn may be in gap junction contact with smooth muscle cells. The role played by ICC in enteric innervation is controversial. Experimental evidence has been presented in vitro for the hypothesis that nitrergic inhibitory innervation is strongly reduced in the absence of ICC. However, in vivo data appear to dispute that. The present report provides evidence that explains the discrepancy between in vivo and in vitro data and provides evidence that inhibitory neurotransmitters can reach smooth muscle cells without hindrance when ICC are absent. The fundic musculature shows increased responses to substance P-mediated innervation and shows marked spontaneous activity, which is consistent with increased muscle excitability.


Gingival recession: epidemiology and risk indicators in a university dental hospital in Turkey.
Gingival recession is a common manifestation of periodontal disease, but is also associated with several risk factors. In this study, we investigated prevalence of gingival recession and assessed various risk indicators in a university dental hospital in Turkey. The study group consisted of 831 persons (537 females, 294 males). Gingival recession, dental plaque, calculus, tobacco consumption, toothbrushing frequency, traumatic toothbrushing and high frenum were assessed. Gingival recession scored as present whenever the free gingival margin was apical to the cemento-enamel junction and root surface was exposed. Overall, the prevalence of gingival recession was 78.2%. The gingival recession for buccal surfaces measured approximately between 1 and 2 mm was 17.4%. The number of gingival recession site of male subjects was significantly higher than that of the female ones (P < 0.05). The dental calculus and plaque levels of mandibular teeth were significantly higher than those of the maxillary teeth (P < 0.05). The multiple regression analyses showed that age, smoking duration, traumatic toothbrushing and high frenum are significant contributors to gingival recession. Periodontal condition is very high in this population. High level of gingival recession in this population is significantly associated with a high level of dental plaque and calculus, male gender, smoking duration, toothbrushing frequency, traumatic toothbrushing and high frenum.


The Breakdown of Stored Triacylglycerols Is Required during Light-Induced Stomatal Opening.
Stomata regulate the uptake of CO2 and the loss of water vapor [1] and contribute to the control of water-use efficiency [2] in plants. Although the guard-cell-signaling pathway coupling blue light perception to ion channel activity is relatively well understood [3], we know less about the sources of ATP required to drive K(+) uptake [3-6]. Here, we show that triacylglycerols (TAGs), present in Arabidopsis guard cells as lipid droplets (LDs), are involved in light-induced stomatal opening. Illumination induces reductions in LD abundance, and this involves the PHOT1 and PHOT2 blue light receptors [3]. Light also induces decreases in specific TAG molecular species. We hypothesized that TAG-derived fatty acids are metabolized by peroxisomal β-oxidation to produce ATP required for stomatal opening. In silico analysis revealed that guard cells express all the genes required for β-oxidation, and we showed that light-induced stomatal opening is delayed in three TAG catabolism mutants (sdp1, pxa1, and cgi-58) and in stomata treated with a TAG breakdown inhibitor. We reasoned that, if ATP supply was delaying light-induced stomatal opening, then the activity of the plasma membrane H(+)-ATPase should be reduced at this time. Monitoring changes in apoplastic pH in the mutants showed that this was the case. Together, our results reveal a new role for TAGs in vegetative tissue and show that PHOT1 and PHOT2 are involved in reductions in LD abundance. Reductions in LD abundance in guard cells of the lycophyte Selaginella suggest that TAG breakdown may represent an evolutionarily conserved mechanism in light-induced stomatal opening.


Cell cycle effects of nitric oxide on vascular smooth muscle cells.
We characterized the cell cycle block induced by nitric oxide (NO) on smooth muscle cells (SMC). We hypothesized that the inhibition of SMC proliferation by NO was due to a specific block in cell cycle progression. Treatment of cultured rat aortic SMC with the NO donors S-nitroso-N-acetylpenicillamine or S-nitrosoglutathione (0.1 mM for 48 h) resulted in a 50% decrease (P < 0.05) in the fraction of cells in the S and G2 + M phases and a corresponding increase in the G1 fraction, suggesting that NO inhibits entry into S phase, causing accumulation of cells in G1 phase. Application of both NO donors to cycling SMC resulted in a short-term, concentration-dependent (0.06-0.3 mM) inhibition of ongoing DNA synthesis as measured by radiothymidine incorporation, demonstrating that NO causes an S-phase arrest. The S-phase arrest by NO was not mimicked by exogenous guanosine 3',5'-cyclic monophosphate (cGMP, 10 mM) and was associated with, but not due to, a 20% inhibition of RNA synthesis. The S-phase block was completely reversed within 2 h of removal of the NO donors, similar to inhibition by the ribonucleotide reductase inhibitor hydroxyurea. Prolonged treatment of SMC with either NO donor (0.1 mM) did not synchronize cells at the G1-S boundary as expected after a prolonged S-phase arrest, but instead induced a quiescent G0-like state characterized by a 12- to 18-h lag before DNA synthesis returned to normal levels after NO removal. These findings demonstrate that NO inhibition of SMC proliferation is associated with two distinct and reversible cell cycle arrests, an immediate cGMP-independent S-phase block followed by a shift back in the cell cycle from the G1-S boundary to a quiescent G0-like state.


Exact stochastic unraveling of an optical coherence dynamics by cumulant expansion.
A numerically exact Monte Carlo scheme for calculation of open quantum system dynamics is proposed and implemented. The method consists of a Monte Carlo summation of a perturbation expansion in terms of trajectories in Liouville phase-space with respect to the coupling between the excited states of the molecule. The trajectories are weighted by a complex decoherence factor based on the second-order cumulant expansion of the environmental evolution. The method can be used with an arbitrary environment characterized by a general correlation function and arbitrary coupling strength. It is formally exact for harmonic environments, and it can be used with arbitrary temperature. Time evolution of an optically excited Frenkel exciton dimer representing a molecular exciton interacting with a charge transfer state is calculated by the proposed method. We calculate the evolution of the optical coherence elements of the density matrix and linear absorption spectrum, and compare them with the predictions of standard simulation methods.


Root chemistry in Populus tremuloides: effects of soil nutrients, defoliation, and genotype.
Although genetic, environmental, and G x E effects on aboveground phytochemistry have been well documented in trembling aspen (Populus tremuloides), little work has focused on the same factors affecting tissues underground. Belowground plant defenses are likely important mediators of root-feeding herbivores that can strongly influence plant fitness. We used a common garden of potted aspen trees to explore the individual and interactive effects of soil nutrient availability, foliar damage, genotype, and their interactions, on concentrations of phytochemicals in aspen roots. Our common garden experiment employed 12 aspen genotypes that were planted into either low- or high-nutrient soil environments. Half of the trees were subjected to defoliation for two successive years, while the others were protected from damage. At the end of the growing season after the second defoliation, we harvested the trees to obtain root samples for which we assessed levels of phenolic glycosides, condensed tannins, nitrogen, and starch. Phenolic glycosides were most affected by genotype, while the other root phytochemicals were most responsive to soil nutrient conditions. The effects of defoliation were observed in interaction with soil nutrient environment and/or genotype. Interestingly, the effect of defoliation on phenolic glycosides was mediated by soil nutrients, whereas the effect of defoliation on condensed tannins was observed in concert with effects of both soil nutrients and genotype. Comparison of data from this study with an earlier, related study revealed that concentrations of phenolic glycosides and condensed tannins are lower in roots than leaves, and less responsive to defoliation. That soil nutrient environment affects root phytochemical concentrations is not unexpected given the intimate association of roots and soil, but the complex interactions between soil nutrients, aboveground damage, and genotype, and their effects on root phytochemistry, are intriguing. Variation in root chemistry could have wide-reaching effects on soil microbial communities, nutrient cycling, and herbivores. Additionally, the response of phytochemicals to damage across organs can link different, spatially separated herbivores as they use different parts of the same plant resource.


Peptidyl-Prolyl Model Study: How Does the Electronic Effect Influence the Amide Bond Conformation?
The triple-helical structure of collagen, the most abundant protein in animal bodies, owes its stability to post-translationally installed hydroxyl groups at position 4 of prolyl residues. To shed light on the nature of this phenomenon, we have examined the influence of the 4-substituent on the amide isomerism in peptidyl-prolyl analogues. The rigid bicyclic skeleton of 2,4-methanoprolines allowed us to follow the through-bond impact of the substituent group (electronic effect) without the side-chain conformation being affected by a stereoelectronic effect. These proline analogues were prepared by [2 + 2] photocycloaddition of (2-allylamino)acrylic acid derivatives. Subsequent pKa studies demonstrated a remarkable electronic effect of the 4-fluorine substitution, while the effect of the 4-methyl group was negligible. The trans/cis amide ratio was measured in model compounds under low temperature conditions. The observed prevalence for a trans-amide is extraordinary, and in this regard, 2,4-methanoproline is closer to primary α-amino acids than to proline. At the same time the amide rotation velocities were 3-4 orders of magnitude higher when compared to N-acetylprolyl. Finally, our results indicate that the electronic effect of the 4-substituent only affects the kinetics of the amide isomerization but not the thermodynamic prevalence for the trans-rotamer.


The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol.
Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread "natural experiment" of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.


Erosion-protecting effect of oral-care products available on the Swiss market. A pilot study
The present study sought to test oral-care products available on the Swiss market, such as toothpastes and gels, with respect to the protection of enamel against erosive tooth wear. A total of 56 enamel specimens were divided into 7 groups (n = 8): F-TP = Migros Budget Anti-Caries Toothpaste (Negative Control); F+Sn3500-TP = Elmex Erosion Protection Toothpaste (Positive Control); F-TP + F+Oligopep-Gel = Migros Budget Anti-Caries Toothpaste + Emofluor Protect Gel Professional; F+Sn3120-Gel = Emofluor Gel Intensive Care; F+Oligopep-TP = Candida Protect Professional Toothpaste; F+Sn1260-TP = Emoform-F Protect Toothpaste; and F+Sn3440-TP = Sensodyne Repair & Protect Toothpaste. The specimens were incubated in artificial saliva for 30 min and then brushed in a toothbrushing machine (10 s brushing; total 2 min exposure to the product). After the toothbrush abrasion, the specimens were rinsed, dried and submitted to an erosive challenge (2 min; 1% citric acid; pH 3.6). This sequence was repeated 4 times, and the total enamel surface loss was calculated using indentation measurements before and after the brushing period. All groups presented progressive surface loss throughout the experiment; after 4 cycles, total surface loss values ranged from 0.11 µm (F+Sn3120-Gel) to 0.89 µm (F+Sn1260-TP). Regarding the total surface loss values (median; interquartile range), F-TP (0.54; 0.42–0.59) presented no significant differences compared to any of the other groups. F+Sn3500-TP (0.33; 0.30–0.40), F-TP + F+Oligopep-Gel (0.34; 0.29–0.42) and F+Sn3120-Gel (0.11; 0.09–0.15) presented lower surface loss than F+Oligopep-TP (0.75; 0.59–0.98), F+Sn1260-TP (0.89; 0.68–1.13) and F+Sn3440-TP (0.69; 0.66–0.78). Conclusion: Although some of the oral-care products containing stannous ions or oligopeptide-104 presented numerically lower SL values, they did not present significantly better protection than a regular fluoride toothpaste. The gels showed a general trend of better enamel protection against ETW.


Usefulness of multiplex PCR methods and respiratory viruses' distribution in children below 15 years old according to age, seasons and clinical units in France: A 3 years retrospective study.
To date, only influenza and RSV testing are recommended for respiratory viruses' detection in paediatric units. In this study, we described, according to seasons, ages and clinical units, the results obtained in children (<15 years old) by multiplex-PCR (mPCR) tests allowing a quick and wide range detection of all respiratory viruses. These results were also compared with RSV specific detection. All nasopharyngeal mPCR and RSV tests requested by clinicians in our French teaching hospitals group between 2011 and 2014 were retrospectively included. All repeated samples for the same children in the same month were discarded. Of the 381 mPCR tests (344 children) performed, 51.4% were positive. Positivity and viral co-infection rates were higher in the 6-36 months old strata (81% and 25%, p<0.0001 and p = 0.04, respectively). Viral distribution showed strong variations across ages. During specific influenza epidemic periods, only 1/39 (2.5%) mPCR tests were positive for influenza and 19/39 (48.7%) for other viruses. During specific RSV epidemic periods, only 8/46 (17.4%) mPCR tests were positive for RSV and 14/46 (30.4%) for other viruses. 477/1529 (31.2%) of RSV immunochromatography-tests were positive. Among the negatives immunochromatography-test also explored by mPCR, 28/62 (31%) were positive for other respiratory viruses. This study provides a wide description of respiratory viruses' distribution among children in hospital settings using mPCR over 3 years. It emphasizes the number of undiagnosed respiratory viruses according to the current diagnosis practice in France and gives a better picture of respiratory viruses identified in hospital settings by mPCR all over the year in France.


Research and development of an electron beam focusing system for a high-brightness X-ray generator.
A new type of rotating anticathode X-ray generator, where an electron beam of up to 60 keV irradiates the inner surface of a U-shaped Cu anticathode, has achieved a beam brilliance of 130 kW mm(-2) (at 2.3 kW). A higher-flux electron beam is expected from simulation by optimizing the geometry of a combined-function-type magnet instead of the fringing field of the bending magnet. In order to minimize the size of the X-ray source the electron beam has been focused over a short distance by a new combined-function bending magnet, whose geometrical shape was determined by simulation using the Opera-3D, General Particle Tracer and CST-STUDIO codes. The result of the simulation clearly shows that the role of combined functions in both the bending and the steering magnets is important for focusing the beam to a small size. FWHM sizes of the beam are predicted by simulation to be 0.45 mm (horizontal) and 0.05 mm (vertical) for a 120 keV/75 mA beam, of which the effective brilliance is about 500 kW mm(-2) on the supposition of a two-dimensional Gaussian distribution. High-power tests have begun using a high-voltage 120 kV/75 mA power supply for the X-ray generator instead of 60 kV/100 mA. The beam focus size on the target will be verified in the experiments.


Use of the NOSIE to predict assaults among acute psychiatric patients. Nurses' Observational Scale for Inpatient Evaluation.
The study evaluated the Nurses' Observational Scale for Inpatient Evaluation (NOSIE), the Brief Psychiatric Rating Scale (BPRS), the Mini Mental State Examination (MMSE), and other measures as predictors of assaults that occurred during psychiatric hospitalization. On admission, the MMSE was administered to 335 acutely ill psychiatric patients, and diagnostic and demographic data were recorded. Immediately after admission, patients were rated by nurses using the NOSIE and by psychologists using the BPRS. Patients who committed assaults during hospitalization (N = 47) and those who did not were compared, and relationships between several variables and assaults were evaluated by t tests, Mann-Whitney U tests, chi square tests, and analyses of variance. A high score on the irritability factor of the NOSIE and failure to complete the MMSE correctly predicted the occurrence or nonoccurrence of assault 81 percent of the time. None of the other variables examined were significantly related to assaults, including total scores on the BPRS and MMSE, psychiatric diagnosis, and several demographic variables. Scores on a test of distress level shortly after admission and failure to complete the MMSE on admission can help the clinician predict who will later engage in an assault.


Placebo analgesia: a PET study.
Placebo analgesia involves complex mechanisms and sometimes has a marked effect on patients in pain. In this study we examined changes in regional cerebral blood flow (rCBF) under three different conditions (resting, hot, painful) before and after placebo administration using H(2)(15)O and positron emission tomography in ten healthy subjects. In five subjects, placebo administration significantly decreased pain-intensity score (placebo responders), and rCBF in the medial prefrontal cortex (MPFC), posterior parietal cortex (PPC), and inferior parietal lobe (IPL) increased after placebo administration compared with before placebo administration under the painful condition. Furthermore, in the placebo responders, rCBF in the MPFC, PPC and IPL also increased under the resting condition (without sensory stimulation) after placebo administration compared with before placebo administration. However, there was no rCBF change under the rest condition in the placebo nonresponders after placebo administration. These results suggest that placebo analgesia has its effect under the resting condition and MPFC, IPL and PPC may have an important role in placebo analgesia.


Chemically cross-linked poly(acrylic-co-vinylsulfonic) acid hydrogel for the delivery of isosorbide mononitrate.
We report synthesis, characterization, and drug release attributes of a series of novel pH-sensitive poly(acrylic-co-vinylsulfonic) acid hydrogels. These hydrogels were prepared by employing free radical polymerization using ethylene glycol dimethacrylate (EGDMA) and benzyl peroxide (BPO) as cross-linker and initiator, respectively. Effect of acrylic acid (AA), polyvinylsulfonic acid (PVSA), and EGDMA on prepared hydrogels was investigated. All formulations showed higher swelling at high pHs and vice versa. Formulations containing higher content of AA and EGDMA show reduced swelling, but one with higher content of PVSA showed increased swelling. Hydrogel network was characterized by determining structural parameters and loaded with isosorbide mononitrate. FTIR confirmed absence of drug polymer interaction while DSC and TGA demonstrated molecular dispersion of drug in a thermally stable polymeric network. All the hydrogel formulations exhibited a pH dependent release of isosorbide mononitrate which was found to be directly proportional to pH of the medium and PVSA content and inversely proportional to the AA contents. Drug release data were fitted to various kinetics models. Results indicated that release of isosorbide mononitrate from poly(AA-co-VSA) hydrogels was non-Fickian and that the mechanism was diffusion-controlled.


Local differences in electrogastrographic indices associated with total gastrectomy, total colectomy, distal gastrectomy and colonic replacement.
The electrogastrographic indices of spectral frequency, instability factor (IF), power amplitude, and power content (%) were compared between control subjects (C), and subjects following either total gastrectomy (TG), total colectomy (TC), distal gastrectomy (DG) or colonic replacement surgery (CR). In the fasting state, both the spectral frequency and IF of the epigastric 3-cycle per minute (cpm) group of the TC subjects were significantly lower than those indices in C, TG, DG, and CR subjects. In contrast, the power amplitude and power content of the epigastric 3-cpm group of both TG and DG subjects were significantly lower than those of C and TC subjects. The original epigastric waves of TG had remarkably high amplitudes. Furthermore, the absolute power of the epigastric 3-cpm of the TC subjects was 10 times higher than that in either the C or TG subjects. These results may be partially explained by the assumption that the recorded epigastric electrogastrography (EGG) is mainly contributed to by the 3-cpm myoelectric activity of the stomach and colon, while the infraumbilical EGG is mainly contributed to by the 3-cpm myoelectric activity of the colon. Topographic EGG maps visually supported these assumptions.


Granulocyte colony-stimulating factor (G-CSF) in the mechanism of human ovulation and its clinical usefulness.
In 1980, Espey proposed a famous hypothesis that mammalian ovulation is comparable to an inflammatory reaction and many researches have proved the validity of his hypothesis in the last three decades. For example, interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)- alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and other inflammatory cytokines presence was proven in the preovulatory follicle. Since granulocyte is the major leukocyte and it plays a very important role during inflammation, the importance of granulocyte and its related cytokine, granulocyte colony-stimulating factor (G-CSF) in the mechanism of human ovulation is easily predictable. G-CSF is one of the hemopoietic cytokines and it has strong positive effects on granulocytes. G-CSF increases the number of granulocytes and it improves the function of granulocytes. In this review, the participation of leukocytes in the ovulation mechanism is demonstrated first. Second, the participation of G-CSF is shown in comparison with the above mentioned cytokines. Finally, since G-CSF has been used for more than 20 years as a medicine without severe side effects in the field of oncology, the clinical application of G-CSF for the treatment of an ovulation disorder, luteinized unruptured follicle (LUF), will be discussed.


A four-year prospective study of the respiratory effects of volcanic ash from Mt. St. Helens.
This report describes the 4-yr follow-up of 712 loggers exposed over an extended period to varying levels of fresh volcanic ash from the 1980 eruptions of Mt. St. Helens. Concerns related to the irritant effect the ash might have on the airways and also to its fibrogenic potential if exposures were intense and continued over many years. Our subjects were divided into 3 groups: high, low, and no exposure. Baseline testing was begun in June 1980, 1 month after the major eruption, and follow-up testing continued on an annual basis through 1984; 88% of the loggers have been tested at least 3 times. Analysis of lung function data showed that a significant, exposure-related decline in FEV1 occurred during the first year after the eruption. The decline was short-lived, however, and by 1984 the differences between exposure groups were no longer significant. Self-reported symptoms of cough, phlegm, and wheeze showed a similar pattern. No ash-related changes were seen in chest roentgenograms taken in 1980 and in 1984. Our findings are consistent with the hypothesis that the inhaled ash caused mucus hypersecretion and/or airway inflammation that reversed when the exposure levels decreased. The ash levels to which the loggers were exposed were low compared with permissible occupational levels for nuisance dusts, but generally higher than the total suspended particulate levels permissible in ambient air.


Band-Gap Tunability in Partially Amorphous Silicon Nanoparticles Using Single-Dot Correlative Microscopy.
Silicon nanoparticles (Si-NPs) represent one of many types of nanomaterials, where the origin of emission is difficult to assess due to a complex interplay between the core and surface chemistry. Band-gap tunability in Si-NPs is predicted to span from the infrared to the ultraviolet spectral range, which is rarely observed in practice. In this work, we directly assess the size dependence of the optical band gap using a single-dot correlative microscopy tool, where the size of the individual NPs is measured using atomic force microscopy (AFM) and the optical band gap is evaluated from single-dot photoluminescence measured on the very same NPs. We analyze 2-8 nm alkyl-capped Si-NPs prepared by a sol-gel method, followed by annealing at 1300 °C. Surprisingly, we find that the optical band gap is given by the amorphous shell, as evidenced by the convergence of the optical band gap size dependence toward the amorphous Si band gap of ∼1.56 eV. We propose that the structural disorder might be the reason behind the often reported limited emission tunability from various Si-NPs in the literature. We believe that our message points toward a pressing need for development and broader use of such direct correlative single-dot microscopy methods to avoid possible misinterpretations that could arise from attempts to recover size-band gap relation from ensemble methods, as practiced nowadays.