The performance of 11C-Methionine PET in the differential diagnosis of glioma recurrence.
Despite the advancement of neuroimaging techniques, it often remains a diagnostic challenge to distinguish recurrent glioma from lesions representing treatment effect. Preliminary reports suggest that 11C-methionine Positron emission tomography (PET) can assist in diagnosing true glioma recurrence. We present here a meta-analysis to assess the accuracy of 11C-methionine PET in identifying recurrent glioma in patients who had undergone prior therapy. A comprehensive search of the PubMed, Embase and Chinese Biomedical (CBM) databases yielded 23 eligible articles comprising 29 studies listed prior to November 20, 2016, representing 891 patients. In this report, we assess the methodological quality of each article individually and perform a meta-analysis to obtain the summary diagnostic accuracy of 11C-methionine PET in correctly identifying recurrent glioma. The pooled sensitivity and specificity are 0.88 (95% CI: 0.85, 0.91) and 0.85 (95% CI: 0.80, 0.89), respectively, with an area under the curve (AUC) for the summary receiver-operating characteristic curve (SROC) of 0.9352. We conclude that 11C-methionine PET has excellent diagnostic performance for differentiating glioma recurrence from treatment effect.


Cause of spectral variation in the luminescence of semisynthetic aequorins.
Aequorin emits light in the presence of Ca2+, decomposing into apoaequorin, coelenteramide and CO2. Semisynthetic aequorins, produced by replacing the coelenterazine moiety in aequorin with analogues of coelenterazine, showed widely different sensitivities to Ca2+ as well as certain spectral variations. A group of semisynthetic aequorins, e-type aequorins, showed bimodal luminescence, with peaks at 400-405 nm and 440-475 nm in various intensity ratios, whereas all other aequorins luminesced with only one peak, in the range 440-475 nm. The cause of the spectral variation was studied by various experiments including: (1) comparison with the fluorescence of the spent solution and the luminescence of the spent solution produced by added coelenterazine; (2) luminescence in 2H2O; (3) the rate of conformational change of apoaequorin; (4) the rates of regeneration in the presence and absence of O2. The results suggested that the spectrum of Ca(2+)-triggered luminescence is strongly affected by the ionic charge on the amide N atom of the coelenteramide that is bound to apoaequorin. When the amide N atom is negatively charged, light is emitted with a 440-475 nm peak. In the case of e-type aequorins, the negative charge on the amide N atom is less because of the structure of e-coelenterazine involved, resulting in the emission of a 400-405 nm peak from the uncharged form of coelenteramide; the intensity ratio of 400-405 nm peak to 440-475 nm peak is determined by the amount of negative charge resting on the amide N atom of e-coelenteramide at the time of light emission. Most of the spectral variations in luminescence and fluorescence can be explained on the basis of ionic and hydrophobic interaction between a coelenteramide and apoaequorin.


Dental anomalies in panoramic radiographs of pediatric patients.
A panoramic radiograph is more likely utilized in children with high caries risk and mixed dentition, and it can be complemented by other X-rays (such as periapical and/or bitewings). This study analyzed 1359 panoramic radiographs taken over 33 years at the Pedodontics Clinic of the State University of Rio de Janeiro in order to determine the prevalence of dental anomalies in mixed dentition children. The population evaluated had 670 (49.3%) boys and 689 (50.7%) girls, ranging in age from 5-12 years, with a median age of 8 years. The total prevalence of anomalies detected was 11.72%; anodontia and supernumerary teeth were the most reported (4.63% and 3.31%, respectively). Statistical differences noted were in the presence of supernumary teeth in males (4.9%, P <.001) and the presence of anodontia in females (6.1%, P = .009). Based on these findings, a panoramic radiograph can help to analyze transitional dentition, as well as complement the clinical examination at the first dental visit of a pediatric patient with a high risk for caries.


Incidence, Predictors, and Outcome of In-Hospital Bleeding in Patients With Cardiogenic Shock Complicating Acute Myocardial Infarction.
Bleeding after acute myocardial infarction (AMI) is associated with an increased morbidity and mortality. The frequency and consequences of bleeding events in patients with AMICS are not well described. The objective was to investigate incidence and outcome of bleeding complications among unselected patients with AMI complicated by cardiogenic shock (AMICS) and referred for immediate revascularization. Bleeding events were assessed by review of medical records in consecutive AMICS patients admitted between 2010 and 2017. Bleedings during admission were classified according to Bleeding Academic Research Consortium classification. Patients who did not survive to admission in the intensive care unit were excluded. Of the 1,716 patients admitted with AMICS, 1,532 patients (89%) survived to ICU admission. At 30 days, mortality was 48%. Severe bleedings classified as BARC 3/5 were seen in 87 non-coronary bypass grafting patients (6.1%). Co-morbidity did not differ among patients; however, patients who had a BARC 3/5 bleeding had significantly higher lactate and lower systolic blood pressure at admission, indicating a more severe state of shock. The use of mechanical assist devices was significantly associated with severe bleeding events. Univariable analysis showed that patients with a BARC 3/5 bleeding had a significantly higher 30-day mortality hazard compared with patients without severe bleedings. The association did not sustain after multivariable adjustment (hazard ratio 0.90, 95% confidence interval 0.64; 1.26, p = 0.52). In conclusion, severe bleeding events according to BARC classification in an all-comer population of patients with AMICS were not associated with higher mortality when adjusting for immediate management, hemodynamic, and metabolic state. This indicates that mortality in these patients is primarily related to other factors.


Oxidation induced by dielectric barrier discharge (DBD) plasma treatment reduces IgG/IgE binding capacity and improves the functionality of glycinin.
The effect of dielectric barrier discharge (DBD) plasma treatment times from 2 to 5 min at 40 kV on IgG/IgE binding capacity and functionality of soybean glycinin was examined. A substantial reduction in the binding capacity (91.64% for IgG and 81.49% for IgE) was obtained after 5 min of plasma treatment, as determined by western-blot and ELISA analyses. Further studies demonstrated that the elimination of antigenicity and allergenicity of glycinin was directly related to plasma-induced structural changes on two aspects. A conformational alteration caused by oxidation of peptide bond amino groups, accompanied with an oxidation of Trp, Tyr, and Phe amino acid residues, which was confirmed by surface hydrophobicity, multi-spectroscopic analysis, and amino acid analysis. The cleavage of polypeptide chains inevitably partially diminished the linear epitopes, resulting in a primary decline in IgG/IgE binding capacity. Additionally, an increase in the solubility from 10.78 ± 0.35 to 65.96 ± 1.86% and significant increase in the emulsifying ability from 21.08 ± 2.64 to 160.29 ± 4.12 m2/g were observed after treatment of the plasma for 2 min. The present results confirm the potential use of DBD for the production of hypoallergenic soy protein-based products and improving their technical functions such as solubility and emulsifying ability.


Clinical evidence of initiating a very low dose of sacubitril/valsartan: a prospective observational analysis.
Sacubitril/valsartan is superior to enalapril in reducing the risks of cardiovascular death and preventing hospitalization in patients with heart failure and reduced ejection fraction (HFrEF). However, patients often do not receive sacubitril/valsartan because of concerns about hypotension. We examined the feasibility of initiating sacubitril/valsartan at a very low dose (VLD) in potentially intolerant patients with HFrEF and subsequent dose up-titration, treatment persistence and outcomes. We analyzed 206 patients with HFrEF grouped according to starting sacubitril/valsartan dose. The VLD group (n = 106) commenced 25 mg twice daily, and the standard-dose (SD) group (n = 100) started on ≥ 50 mg twice daily. Baseline systolic blood pressure was 103 ± 12 mmHg vs. 119 ± 14 mmHg in the SD group (P < 0.001). The maximal target dose achievement rate was higher in the SD group (27.0% vs 9.4%, p = 0.001) and the VLD group experienced more dose up-titrations and fewer down-titrations than the SD group. The VLD group had a decrease in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) similar to the SD group and a similar increase in left ventricular ejection fraction. There were no significant differences in symptomatic hypotension, worsening renal function, hyperkalemia, cardiovascular mortality, and rehospitalization due to HF between the two groups during follow-up period. In patients considered by the treating physician likely to be intolerant of sacubitril/valsartan, initiation with 25 mg twice daily was generally possible and patients remained in therapy, with similar decreases in NT-proBNP and increases in left ventricular ejection fraction to those observed in patients receiving SD sacubitril/valsartan.


Dietary Genistein Reduces Methylglyoxal and Advanced Glycation End Product Accumulation in Obese Mice Treated with High-Fat Diet.
Our previous study has found that dietary genistein could ameliorate high-fat diet (HFD)-induced obesity and especially lower methylglyoxal (MGO) and advanced glycation end product (AGE) accumulation in healthy mice exposed to genistein and HFD. However, it is still unclear whether dietary genistein intervention has a similar beneficial effect in obese mice. In this study, the mice were induced with obesity after being fed a HFD for nine weeks before being administered with two doses of genistein, 0.1% (G 0.1) and 0.2% (G 0.2), in the HFD for additional 19 weeks. After 19 week treatment, genistein supplementation reduced body and liver weights, plasma and liver MGO levels, and kidney AGE levels in mice. Mechanistically, genistein upregulated the expressions of glyoxalase I and II and aldose reductase to detoxify MGO, and genistein and its microbial metabolites, dihydrogenistein and 6'-hydroxy-O-demethylangolensin, were able to trap endogenous MGO via formation of MGO conjugates. Taken together, our results provide novel insights into the antiobesity and antiglycation roles of dietary genistein in obese subjects.


Distribution of Vernix Caseosa and Associated Factors Among Newborns Delivered at Adama Comprehensive Specialized Hospital Medical College, Ethiopia, in 2022: Cross-Sectional Study.
Vernix caseosa is a complex proteolipid material synthesized partly by fetal sebaceous glands during the last trimester of pregnancy. Understanding the structure and function of newborn skin is crucial for determining optimal thermal support, infection control, and skin moisturization. So far, in Ethiopia, there is no research done related to the distribution of vernix caseosa and associated factors on newborn skin. Doing such research could give awareness about factors associated with the distribution of vernix caseosa on newborns' skin and to take necessary protective measures for those that may be affected. The objective of this study is to assess the distribution of vernix caseosa and associated factors among newborns delivered at Adama Comprehensive Specialized Hospital Medical College from November to December 1, 2021. Hospital-based cross-sectional study design was conducted from November to December 1, 2021 at Adama Comprehensive Specialized Hospital Medical College (ACSHMC). Four hundred twenty-two eligible newborns were selected by a systematic sampling method. Data were collected by four data collectors by using a pretested questionnaire. The distribution of vernix caseosa on the different regions of the neonate was assessed, by exposing their whole body for a minute. Data entry was done by EPI data version 4.6 and analyzed by using SPSS version 25. A logistic regression of P-value of <0.25 during bivariate and P < 0.05 during multivariate analysis at a 95% confidence level was considered statistically significant. Out of 422 study participants 231 (54.7%) with 95% CI (49.8, 59.8) babies had vernix caseosa. Being primiparous with (AOR = 1.9, PV = 0.013, 95% CI: 1.141, 2.92), being multiparous with (AOR = 1.98, PV = 0.04, CI: 1.29, 3.225), being females with (AOR = 2.1, PV = 0.001, CI: 1.39, 3.18), being preterm with (AOR = 2.98, PV = 0.036, 95% CI: 1.08, 10.72), non-diseased newborns with (AOR = 1.6, PV = 0.046, 95% CI: 1.07, 2.7) were identified as associated factors for the distribution of vernix caseosa on the newborn skin. This study showed that the distribution of vernix caseosa on the skin of the newborns was associated with parity, sex, gestational age, and absence of disease.


Simple model on debonding of soft adhesives.
We propose a simple theoretical model describing the debonding process of soft adhesives in the probe-tack test. In this model, the expansion dynamics of interfacial cavities is determined by the balance between the strain energy release rate and the rate-dependent fracture energy. As a result, we obtain analytical solutions for the cavity size, stress-strain curve, peak stress, strain at the peak stress, maximum strain, as well as the adhesion energy. Furthermore, we discuss the validity of our theoretical results by comparing them with experiments.


Complexes comprised of a dendrimer and a vesicle: role of vesicle size and the surface tension of the vesicle membrane.
Mesoscale simulations are performed to study the complexes between a dendrimer and a vesicle of amphiphilic molecules. In particular, the assembled structures and dynamics of these complexes are investigated by tuning vesicle size and the surface tension of vesicle membrane. Our simulations demonstrate that a dendrimer-based bulge containing amphiphilic molecules forms in the vesicle membrane when a dendrimer adheres to a vesicle. We find that vesicle size and the surface tension of the vesicle membrane permit effective accesses to control the shape change of the bulge structure with respect to various hydrophobic interactions in the complexes. The analysis for the energy of the vesicle reveals that the change of elastic energy induced by various densities of amphiphilic molecules in the membrane plays an important role in this bulge-shape control. Because both charged dendrimers and vesicles are effective nanodevices for targeted drug delivery, our findings shed light on the effective means of developing multitasking nanocarriers as targeted drug delivery platforms.


Multivariate analysis to simplify the differential diagnosis of broad complex tachycardia.
Univariate analysis has identified several criteria that aid the differential diagnosis of broad complex tachycardia. In this study of 102 consecutive patients multivariate analysis was performed to identify which of 15 clinical and 11 electrocardiographic variables were independent predictors of ventricular tachycardia. These were shown to be a history of myocardial infarction, the QRS waveforms in leads aVF and V1, and a change in axis from sinus rhythm to tachycardia of more than 40 degrees. If none of the criteria was met, the diagnosis was almost certainly supraventricular tachycardia. If one criterion was met the diagnosis was probably supraventricular tachycardia. If two criteria were met then the diagnosis was probably ventricular tachycardia. If three or four criteria were met, the diagnosis was almost certainly ventricular tachycardia. The predictive accuracy was 93%. This was increased to 95% by including two other criteria--definite independent P wave activity and ventricular extrasystoles with the same QRS configuration as that in tachycardia. These criteria were not included in the multivariate analysis because though they were 100% specific they were seldom seen. These four criteria can be used as simple rules in determining the origin of a broad complex tachycardia.


Isoform-selective Genetic Inhibition of Constitutive Cytosolic Hsp70 Activity Promotes Client Tau Degradation Using an Altered Co-chaperone Complement.
The constitutively expressed heat shock protein 70 kDa (Hsc70) is a major chaperone protein responsible for maintaining proteostasis, yet how its structure translates into functional decisions regarding client fate is still unclear. We previously showed that Hsc70 preserved aberrant Tau, but it remained unknown if selective inhibition of the activity of this Hsp70 isoform could facilitate Tau clearance. Using single point mutations in the nucleotide binding domain, we assessed the effect of several mutations on the functions of human Hsc70. Biochemical characterization revealed that one mutation abolished both Hsc70 ATPase and refolding activities. This variant resembled the ADP-bound conformer at all times yet remained able to interact with cofactors, nucleotides, and substrates appropriately, resembling a dominant negative Hsc70 (DN-Hsc70). We then assessed the effects of this DN-Hsc70 on its client Tau. DN-Hsc70 potently facilitated Tau clearance via the proteasome in cells and brain tissue, in contrast to wild type Hsc70 that stabilized Tau. Thus, DN-Hsc70 mimics the action of small molecule pan Hsp70 inhibitors with regard to Tau metabolism. This shift in Hsc70 function by a single point mutation was the result of a change in the chaperome associated with Hsc70 such that DN-Hsc70 associated more with Hsp90 and DnaJ proteins, whereas wild type Hsc70 was more associated with other Hsp70 isoforms. Thus, isoform-selective targeting of Hsc70 could be a viable therapeutic strategy for tauopathies and possibly lead to new insights in chaperone complex biology.


How Does the Death Conscious Culture of Iran Affect Experiences of Depression?
This paper is divided into two parts. First I argue for the existence of a death-conscious culture in Iran, traceable in religious and literary texts, and manifested strongly in the discourse following the Iran-Iraq war. I then look at how this culture influences articulations and experiences of depression as felt by Iranian patients. Adopting a phenomenological perspective and drawing on empirical data, I show how death-consciousness, as a point of cultural divergence between the UK and Iran, can be used to account for some of the phenomenologically significant cultural variations in the experience of depression. These include attitudes towards suicide, the significance of feelings of hopelessness, and the existence of a sense of absurdity among Iranian patients.


Ezidi voices: The communication of COVID-19 information amongst a refugee community in rural Australia- a qualitative study.
There is growing evidence that government health information related to COVID-19 has failed to adequately reach culturally and linguistically diverse (CALD) populations in Australia. Refugees are a unique sub-set of the CALD communities and are subject to numerous barriers preventing adequate health care, both pre- and post-migration. The barriers are accentuated during emergencies, such as a pandemic, as a result of an intersection of various social and economic inequalities. The recently resettled Ezidi refugee community in a regional area of Australia is an example of a community sitting at the intersection of various inequities and thus at greater risk from COVID-19. The purpose of this study is to describe the experiences of the Ezidi in a regional area with COVID-19 information and how this has been communicated to and shared within this group; what barriers the community may experience in accessing COVID-19 information; and how the government-led COVID-19 information communication could be improved. This qualitative study was designed to explore the perceptions and views of the Ezidi and service providers regarding COVID-19 messaging. Multicultural and Refugee Health staff facilitated interviews with four local service providers and ten Ezidi community members, including seven influential leaders. Thematic analysis was employed across individual, pair and group data analysis. Similar categories were grouped into themes. The main findings of the study are: the refugee experience influences the communication of COVID-19 messages; cultural, social and gender norms influence responses to COVID-19; trusted individuals and service providers are key in communities' uptake of COVID-19 messages; currently available governmental COVID-19 information resources and sharing strategies were found unhelpful and inappropriate; COVID-19 communiqués and message delivery for this regional minority refugee community can be improved. The recently resettled Ezidi community, and likely other similar communities, would benefit from tailored engagement by government organisations, as well as settlement services to improve the communication of COVID-19 health information and reduce related inequities.


Cholecystokinin is a potent protective agent against alcohol-induced gastric injury in the rat. Role of endogenous prostaglandins.
Cholecystokinin is a gastrointestinal hormone known to physiologically regulate pancreatic protein secretion and gallbladder contractility. Some evidence suggests that cholecystokinin is also involved in the maintenance of gastrointestinal mucosal integrity. This study was undertaken to ascertain whether cholecystokinin could prevent the gastric mucosal injury induced by acidified ethanol and what role prostaglandins, and type A and type B cholecystokinin receptors might play in this process. Conscious, fasted rats were given subcutaneous saline or cholecystokinin octapeptide (10-100 micrograms/kg) 30 min before a 1-ml oral gastric bolus of acidified ethanol (150 mM HCl/50% ethanol). Five minutes later, rats were sacrificed and the total area of macroscopic injury quantitated (square millimeters). In additional experiments using a similar protocol, 1 ml of either the cyclooxygenase inhibitor, indomethacin (5 mg/kg), a type A cholecystokinin receptor antagonist, L-364,718 (0.01-1 mg/kg), or the type B cholecystokinin receptor antagonist, L-365,260 (12.5-25 mg/kg) was given intraperitoneally 30 min prior to pretreatment with cholecystokinin octapeptide. Cholecystokinin octapeptide dose-dependently prevented mucosal injury from acidified ethanol (corroborated by histology). The protective effect of cholecystokinin octapeptide was completely negated by L-364,718 and partially reversed by indomethacin, while L-365,260 had no discernible effect in this process. In a further study, cholecystokinin was unable to prevent the damaging effects of aspirin and the inhibition of endogenous prostaglandins. This, it appears that cholecystokinin is able to maintain mucosal integrity in the face of a damaging insult by activation of type A cholecystokinin receptors, an effect mediated, at least in part, through the release of endogenous prostaglandins.


In vitro antifungal activity and mechanism of essential oil from fennel (Foeniculum vulgare L.) on dermatophyte species.
Fennel seed essential oil (FSEO) is a plant-derived natural therapeutic against dermatophytes. In this study, the antifungal effects of FSEO were investigated from varied aspects, such as MIC and minimum fungicidal concentration, mycelia growth, spore germination and biomass. The results indicated that FSEO had potent antifungal activities on Trichophyton rubrum ATCC 40051, Trichophyton tonsurans 10-0400, Microsporum gypseum 44693-1 and Trichophyton mentagrophytes 10-0060, which is better than the commonly used antifungal agents fluconazole and amphotericin B. Flow cytometry and transmission electron microscopy experiments suggested that the antifungal mechanism of FSEO was to damage the plasma membrane and intracellular organelles. Further study revealed that it could also inhibit the mitochondrial enzyme activities, such as succinate dehydrogenase, malate dehydrogenase and ATPase. With better antifungal activity than the commonly used antifungal agents and less possibility of inducing drug resistance, FSEO could be used as a potential antidermatophytic agent.


Information Symmetry Matters: A Modal-Alternating Propagation Network for Few-Shot Learning.
Semantic information provides intra-class consistency and inter-class discriminability beyond visual concepts, which has been employed in Few-Shot Learning (FSL) to achieve further gains. However, semantic information is only available for labeled samples but absent for unlabeled samples, in which the embeddings are rectified unilaterally by guiding the few labeled samples with semantics. Therefore, it is inevitable to bring a cross-modal bias between semantic-guided samples and nonsemantic-guided samples, which results in an information asymmetry problem. To address this problem, we propose a Modal-Alternating Propagation Network (MAP-Net) to supplement the absent semantic information of unlabeled samples, which builds information symmetry among all samples in both visual and semantic modalities. Specifically, the MAP-Net transfers the neighbor information by the graph propagation to generate the pseudo-semantics for unlabeled samples guided by the completed visual relationships and rectify the feature embeddings. In addition, due to the large discrepancy between visual and semantic modalities, we design a Relation Guidance (RG) strategy to guide the visual relation vectors via semantics so that the propagated information is more beneficial. Extensive experimental results on three semantic-labeled datasets, i.e., Caltech-UCSD-Birds 200-2011, SUN Attribute Database and Oxford 102 Flower, have demonstrated that our proposed method achieves promising performance and outperforms the state-of-the-art approaches, which indicates the necessity of information symmetry.


Efficacy of Interventions to Reduce Resident Physician Burnout: A Systematic Review.
Studies report high burnout prevalence among resident physicians, with little consensus on methods to effectively reduce it. This systematic literature review explores the efficacy of interventions in reducing resident burnout. PubMed, Embase, and Web of Science were searched using these key words: burnout and resident, intern, or residency. We excluded review articles, editorials, letters, and non-English-language articles. We abstracted data on study characteristics, population, interventions, and outcomes. When appropriate, data were pooled using random effects meta-analysis to account for between-study heterogeneity. Study quality was assessed using Newcastle-Ottawa Scale (cohort studies) and Jadad scale (randomized control trials [RCTs]). Of 1294 retrieved articles, 19 (6 RCTs, 13 cohort studies) enrolling 2030 residents and examining 12 interventions met criteria, with 9 studying the 2003 and 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour restrictions. Work hour reductions were associated with score decrease (mean difference, -2.73; 95% confidence interval (CI) -4.12 to -1.34; P < .001) and lower odds ratio (OR) for residents reporting emotional exhaustion (42%; OR = 0.58; 95% CI 0.43-0.77; P < .001); a small, significant decrease in depersonalization score (-1.73; 95% CI -3.00 to -0.46; P = .008); and no effect on mean personal accomplishment score (0.93; 95% CI -0.19-2.06; P = .10) or for residents with high levels of personal accomplishment (OR = 1.01; 95% CI 0.67-1.54; P = .95). Among interventions, self-care workshops showed decreases in depersonalization scores, and a meditation intervention reduced emotional exhaustion. The ACGME work hour limits were associated with improvement in emotional exhaustion and burnout.


Trigger sequence can influence final morphology in the self-assembly of asymmetric telechelic polymers.
We report on a numerical study of polymer network formation of asymmetric biomimetic telechelic polymers with two reactive ends based on a self-assembling collagen, elastin or silk-like polypeptide sequence. The two reactive ends of the polymer can be activated independently using physicochemical triggers such as temperature and pH. We show, using a simple coarse grained model that the order in which this triggering occurs influences the final morphology. For both of collagen-silk and elastin-silk topologies we find that for relatively short connector chains the morphology of the assembly is greatly influenced by the order of the trigger, whereas for longer chains the equilibrium situation is more easily achieved. Moreover, self-assembly is greatly enhanced at moderate collagen interaction strength, due to facilitated binding and unbinding of the peptides. This finding indicates that both the trigger sequence and strength can be used to steer self-assembly in these biomimetic polymer systems.


[Different gene expression during hepatocarcinogenesis in tree shrew induced by aflatoxin B1].
To understand the molecular mechanism and find out the responsible genes for liver cancer by exploring the regulation of gene expression during hepatocarcinogenesis in tree shrew induced by aflatoxin B1 (AFB1). The tissues from tree shrew of different stages during the pathogenesis and development of hepatocellular carcinoma (HCC), liver cancer tissue, para-cancerous tissues, pre-cancerous liver tissues, liver tissues of the same stage from normal controls and the liver tissues taken before AFB1-treatment were analyzed for gene expression by cDNA array. Four patterns of gene expression were observed during AFB1-induced hepatocarcinogenesis. They were: genes up-regulated in HCC tissue and para-cancerous tissue, especially in HCC tissues; genes with similar expressing level in both HCC tissue and para-cancerous tissue, but higher than that in pre-cancerous tissue; genes down-regulated in HCC tissue; genes up-regulated before HCC appeared but down-regulated after HCC appeared. Dynamic observation of gene expression will be beneficial to elucidate the mechanisms of AFB1- induced hepatocarcinogenesis and locate the responsible genes.


Engineering double-well potentials with variable-width annular Josephson tunnel junctions.
Long Josephson tunnel junctions are non-linear transmission lines that allow propagation of current vortices (fluxons) and electromagnetic waves and are used in various applications within superconductive electronics. Recently, the Josephson vortex has been proposed as a new superconducting qubit. We describe a simple method to create a double-well potential for an individual fluxon trapped in a long elliptic annular Josephson tunnel junction characterized by an intrinsic non-uniform width. The distance between the potential wells and the height of the inter-well potential barrier are controlled by the strength of an in-plane magnetic field. The manipulation of the vortex states can be achieved by applying a proper current ramp across the junction. The read-out of the state is accomplished by measuring the vortex depinning current in a small magnetic field. An accurate one-dimensional sine-Gordon model for this strongly non-linear system is presented, from which we calculate the position-dependent fluxon rest-mass, its Hamiltonian density and the corresponding trajectories in the phase space. We examine the dependence of the potential properties on the annulus eccentricity and its electrical parameters and address the requirements for observing quantum-mechanical effects, as discrete energy levels and tunneling, in this two-state system.


Can skin wrinkling in a site that has received limited sun exposure be used as a marker of health status and biological age?
to determine if skin wrinkling in a site that had received limited sun exposure may be a marker of health status and biological age. population-based, cross-sectional study. we evaluated the health status of representative samples of elderly Greek-born people living in Melbourne, Greeks living in rural Greece, Anglo-Celtic Australians living in Melbourne and Swedes living in Sweden. We carried out microtopographic assessment of their skin and measured plasma dehydroepiandrosterone concentrations. we derived activities of daily living, well-being, memory and general health status scores from a cross-cultural questionnaire. We measured skin wrinkling using cutaneous microtopographic methods and plasma dehydroepiandrosterone by enzyme immuno-assay. skin wrinkling was positively correlated with age (r(s)=0.27, P<0.0001) and negatively with body mass index (r(s)=-0.19, P<0.0001). Therefore, all analyses were controlled for these variables. Plasma dehydroepiandrosterone was higher in smokers than non-smokers (2.86 vs 2.08; P<0.001) and men had significantly higher plasma dehydroepiandrosterone than women (2.74 vs 1.69; P<0.0001). In the pooled data, skin wrinkling was negatively associated with general health score (r(s)=-0.13, P<0.01) and activities of daily living score (r(s)=-0.14, P<0.05) after controlling for age, body mass index and smoking. These associations were more pronounced in women. Finally, those with the least skin wrinkling had the highest dehydroepiandrosterone level (r(s)=-0.12, P=0.06) after adjusting for age, smoking and sex. skin wrinkling in a site with limited sun exposure might be used as a marker of health status and, to some extent, biological age--particularly for women.


Microbiological transformations of delta6a10a-tetrahydrocannabinol.
A screening program was conducted to find microorganisms that catalyze transformation reactions with cannabinoids. Three hundred fifty-eight cultures, consisting of 97 bacteria, 175 actinomycetes, and 86 molds, were incubated in media containing 0.5 mg of Delta(6a,10a)-tetrahydrocannabinol (Delta(6a,10a)-THC) per ml. After 120 h of cultivation, ethyl acetate extracts of the cultures were examined by thin-layer chromatography (TLC) for transformation products. About 18% of the cultures modified Delta(6a,10a)-THC. The ability to modify the substrate did not predominate among any particular group of microorganisms. After purification, the products from three cultures were analyzed by high-resolution mass spectrometry, 100-mHz proton magnetic resonance spectrometry, ultraviolet spectrometry, and infrared spectrometry. These spectral data indicated that a Mycobacterium sp. oxidized Delta(6a,10a)-THC to cannabinol and a diastereomeric pair of 6a-hydroxy-Delta(10,10a)-THC isomers; a Streptomyces sp. and a Bacillus sp. oxidized Delta(6a,10a)-THC to 7-keto-Delta(6a,10a)-THC and 4'-hydroxy-Delta(6a,10a)-THC, respectively. The occurrence of these products and the presence of others that have not yet been isolated or identified indicate that microbial transformation may be a useful tool for the preparation of new cannabinoids that have desirable pharmacological properties.


Iodine nutritional status and risk factors for goitre among schoolchildren in South Tajikistan.
Iodine deficiency affects nearly 1.9 billion people worldwide, but it can be prevented by salt iodization. This cross-sectional survey assessed current iodine status, iodized salt coverage and risk factors for goitre among schoolchildren in South Tajikistan. Ten primary schools in four districts in South Tajikistan were randomly selected. In schoolchildren aged 7 to 11 years, a spot urine sample was collected for measurement of urinary iodine, dried blood spots were collected for measurement of thyroglobulin, and goitre was assessed by palpation. Iodine content of salt samples and local selling points was determined by coloration using rapid test kits and titration method. Of 623 schoolchildren enrolled, complete data was obtained from 589. The overall median urinary iodine concentration (UIC) was 51.2 μg/L indicating mild-to-moderate iodine deficiency. Among all children, 46.6% (95% Confidence Interval (CI) = 42.4%-50.6%) of children were found to be goitrous (grade 1 goitre: 30.6%, 95% CI = 26.9%-34.5%; grade 2 goitre: 16.0%, 95% CI = 13.1%-19.2%). The risk factor for goitre remaining significant in the multivariable logistic regression model was 'buying salt once a month' (OR = 2.89, 95% CI = 1.01-8.22) and 'buying salt once every six months' (OR = 2.26, 95% CI = 1.01-5.04) compared to 'buying salt every one or two weeks'. The overall median thyroglobulin concentration was elevated at 13.9 μg/L. Of the salt samples from households and selling points, one third were adequately iodised, one third insufficiently and one third were not iodised. Iodine deficiency remains a serious health issue among children in southern Tajikistan. There is a persisting high prevalence of goitre, elevated thyroglobulin and low UIC despite interventions implemented by Tajikistan and international partners. Quality control of salt iodine content needs to be improved. Continued efforts to raise awareness of the health effects of iodine deficiency are needed to increase consumer demand for iodised salt.


Cement selection for implant-supported crowns fabricated with different luting space settings.
To measure and compare the retentive strength of cements specifically formulated for luting restorations onto implant abutments and to investigate the effect of varying cement gap on retention strength of implant-supported crowns. Standard titanium abutments were scanned by means of a 3D digital laser scanner. One hundred and sixty standard metal copings were designed by a Computer Aided Design/Computer Aided Manufacturing (CAD/CAM) system with two cement gap values (20 and 40 μm). The copings were cemented to the abutments using the following eight cements with one being the control, zinc oxide temporary cement, while the other seven were specifically formulated implant cements (n = 10): Premier Implant Cement, ImProv, Multilink Implant, EsTemp Implant, Cem-Implant, ImplaTemp, MIS Crown Set, and TempBond NE. The specimens were placed in 100% humidity for 24 hours, and subjected to a pull-out test using a universal testing machine at a 0.5 mm/min crosshead speed. The test results were analyzed with two-way ANOVA, one-way ANOVA, post hoc Tamhane' s T2, and student's t-tests at a significance level of 0.05. Statistical analysis revealed significant differences in retention strength across the cement groups (p < 0.01). Resin-based cements showed significantly higher decementation loads than a noneugenol zinc oxide provisional cement (TempBond NE) (p < 0.01), with the highest tensile resistance seen with Multilink Implant, followed by Cem-Implant, MIS Crown Set, ImProv, Premier Implant Cement, EsTemp Implant, and ImplaTemp. Increasing the cement gap from 20 to 40 μm improved retention significantly for the higher strength cements: Multilink Implant, Premier Implant Cement, ImProv, Cem-Implant, and MIS Crown Set (p < 0.01), while it had no significant effect on retention for the lower strength cements: EsTemp Implant, ImplaTemp, and TempBond NE (p > 0.05). Resin cements specifically formulated for implant-supported restorations demonstrated significant differences in retention strength. The ranking of cements presented in the study is meant to be an arbitrary guide for the clinician in deciding the appropriate cement selection for CAD/CAM-fabricated metal copings onto implant abutments with different luting space settings.


A Dissection of Oligomerization by the TRIM28 Tripartite Motif and the Interaction with Members of the Krab-ZFP Family.
TRIM28 (also known as KAP1 or TIF1β) is the universal co-repressor of the Krüppel-associated box-containing zinc finger proteins (Krab-ZFPs), the largest family of transcription factors in mammals. During early embryogenesis, TRIM28 mediates the transcriptional silencing of many endogenous retroviral elements and genomic imprinted sites. Silencing is initiated by the recruitment of TRIM28 to a target locus by members of the Krab-ZFP. Subsequently, TRIM28 functions as a scaffold protein to recruit chromatin modifying effectors featuring SETDB1, HP1 and the NuRD complex. Although many protein partners involved in silencing have been identified, the molecular basis of the protein interactions that mediate silencing remains largely unclear. In the present study, we identified the first Bbox domain (T28_B1 135-203) as a molecular interface responsible for the formation of higher-order oligomers of TRIM28. The structure of this domain reveals a new interface on the surface of the Bbox domain. Mutants disrupting the interface disrupt the formation of oligomers but have no observed effect on transcriptional silencing defining a single TRIM28 dimer as the functional unit for silencing. Using assembly-deficient mutants, we employed small-angle X-ray scattering and biophysical techniques to characterize binding to member of the Krab-ZFP family. This allows us to narrow and define the binding interface to the center of the coiled-coil region (residues 294-321) of TRIM28 and define mutants that abolish binding to the Krab-ZFP proteins.


Renal impairment in chronic cigarette smokers.
To determine the effect of chronic cigarette smoking on renal function, a cross-sectional study was carried out with 30 subjects who had no known vascular disease risk factor other than cigarette smoking, and 24 age- and sex-matched controls without any vascular risk factor including cigarette smoking. Renal function by radionuclide studies of renal plasma flow, GFR, and plasma endothelin-1 concentration was determined. Compared with nonsmokers, smokers had a renal function impairment characterized by a normal GFR and a significant reduction in renal plasma flow as reflected by MAG3 clearance (199.20 +/- 58.85 ml/min per 1.73 m2 versus 256.54 +/- 60.14 ml/min per 1.73 m2; t = 3.52, P < 0.001). MAG3 clearance was significantly correlated with age and smoking. The renal dysfunction was associated with an increase in plasma endothelin-1 concentration (21.56 +/- 1.15 pmol/L versus 25.01 +/- 3.21 pmol/L; t = 5.00, P < 0.001). Former smokers as well had similar, although milder, abnormalities. In conclusion, cigarette smokers manifest an impairment of renal function, suggesting that smoke may have a detrimental effect on renal function.


Neuroimaging findings in Emanuel Syndrome.
Emanuel syndrome is a rare inherited chromosomal abnormality caused by an unbalanced translocation of chromosomes 11 and 22. Clinically, Emanuel syndrome is characterized by a wide spectrum of congenital anomalies, dysmorphisms, and developmental disability often confused with other similar syndromes. Outside of genetic testing, diagnosis remains challenging and current literature on typical radiologic findings is limited. We present classic neuroimaging findings of Emanuel syndrome consistent with prior literature including microcephaly, microretrognathia, external auditory canal stenosis, and cleft palate; and also introduce the additional maxillofacial anomaly of dysplastic middle ear ossicles, to our knowledge not previously described in the literature. Recognition of findings leading to earlier diagnosis of Emanuel syndrome may improve outcomes and quality of life for patients and their families.


Working with our communities: moving from service to scholarship in the health professions.
As faculty at health professionals schools have become increasingly engaged with their communities in partnerships to improve health, new questions have arisen about faculty rewards for such activities. To sustain the community work of their faculty, institutions need to reconceptualize faculty rewards, promotion, and tenure that are relevant to community activities. Scholarship has evolved since the 17th century from a focus on character-building to the practical needs of the nation to an emphasis on research. In 1990, Boyer proposed four interrelated dimensions of scholarship: (1) discovery; (2) integration;(3) application; and (4) teaching. The challenge became the development of criteria and innovative and creative ways to assess community scholarship. This paper reviews four evidence-based models to document and evaluate scholarly activities that are applicable to community scholarship. We propose a new model for community scholarship that focuses on both processes and outcomes, crosses the boundaries of teaching, research, and service, and reshapes and integrates them through community partnership. We hope this model will generate national discussion about community scholarship and provide thought-provoking information that will move the idea of community scholarship to its next stage of development.


[The silent yet successful revolution of mechanical ventilation in patients with neuromuscular disorders, in particular Duchenne muscular dystrophy].
While developments in molecular biology have been giving rise to breakthroughs in diagnosis, management and promising treatment approaches for neuromuscular disorders, there has been a silent revolution in ventilatory support of patients with a range of neuromuscular disorders with respiratory insufficiency. In a Dutch retrospective study on ventilatory support in 48 boys with Duchenne muscular dystrophy, a 5-year survival rate of 75% was found, with 67% of the patients still living with their relatives. These data are in line with reports from Great Britain. The significant impact of ventilatory support on the natural history of various neuromuscular disorders with respiratory insufficiency is a major breakthrough.


mu-CS: an extension of the TM4 platform to manage Affymetrix binary data.
A main goal in understanding cell mechanisms is to explain the relationship among genes and related molecular processes through the combined use of technological platforms and bioinformatics analysis. High throughput platforms, such as microarrays, enable the investigation of the whole genome in a single experiment. There exist different kind of microarray platforms, that produce different types of binary data (images and raw data). Moreover, also considering a single vendor, different chips are available. The analysis of microarray data requires an initial preprocessing phase (i.e. normalization and summarization) of raw data that makes them suitable for use on existing platforms, such as the TIGR M4 Suite. Nevertheless, the annotations of data with additional information such as gene function, is needed to perform more powerful analysis. Raw data preprocessing and annotation is often performed in a manual and error prone way. Moreover, many available preprocessing tools do not support annotation. Thus novel, platform independent, and possibly open source tools enabling the semi-automatic preprocessing and annotation of microarray data are needed. The paper presents mu-CS (Microarray Cel file Summarizer), a cross-platform tool for the automatic normalization, summarization and annotation of Affymetrix binary data. mu-CS is based on a client-server architecture. The mu-CS client is provided both as a plug-in of the TIGR M4 platform and as a Java standalone tool and enables users to read, preprocess and analyse binary microarray data, avoiding the manual invocation of external tools (e.g. the Affymetrix Power Tools), the manual loading of preprocessing libraries, and the management of intermediate files. The mu-CS server automatically updates the references to the summarization and annotation libraries that are provided to the mu-CS client before the preprocessing. The mu-CS server is based on the web services technology and can be easily extended to support more microarray vendors (e.g. Illumina). Thus mu-CS users can directly manage binary data without worrying about locating and invoking the proper preprocessing tools and chip-specific libraries. Moreover, users of the mu-CS plugin for TM4 can manage Affymetrix binary files without using external tools, such as APT (Affymetrix Power Tools) and related libraries. Consequently, mu-CS offers four main advantages: (i) it avoids to waste time for searching the correct libraries, (ii) it reduces possible errors in the preprocessing and further analysis phases, e.g. due to the incorrect choice of parameters or the use of old libraries, (iii) it implements the annotation of preprocessed data, and finally, (iv) it may enhance the quality of further analysis since it provides the most updated annotation libraries. The mu-CS client is freely available as a plugin of the TM4 platform as well as a standalone application at the project web site (http://bioingegneria.unicz.it/M-CS).


Supplement of tetrahydrobiopterin by a gene transfer of GTP cyclohydrolase I cDNA improves vascular dysfunction in insulin-resistant rats.
Deficiency of tetrahydrobiopterin (BH4) in the vascular tissue contributes to endothelial dysfunction in the insulin-resistant state. We intended to develop a new gene transfer method by overexpression of its biosynthetic enzyme, GTP cyclohydrolase I (GTP-CH1). The GTP-CH1 cDNA was inserted into a pCAGGS vector, and then plasmid DNA was mixed with atelocollagen, and the aliquot was injected into thigh muscles of insulin-resistant Zucker fatty rats. After 4 weeks, pteridine derivative levels, superoxide anion (O2-), activity of endothelial nitric oxide synthase (eNOS), and endothelium-dependent relaxation were evaluated in the aortas obtained from Zucker lean or fatty rats. The BH4 contents and GTP-CH1 activity in Zucker fatty rats were 50%-55% less than those of Zucker lean rats. However, those impairments were significantly improved by a plasmid DNA injection, and aortic BH4 content reached more than 80% of the level of Zucker lean rats. Increased A23187-stimulated O2- production as well as decreased eNOS activity and endothelial function in insulin-resistant Zucker fatty rats were improved by a plasmid DNA injection to a level similar to that in Zucker lean rats. These findings suggest that intramuscular GTP-CH1 gene transfer using atelocollagen serves as a useful method of long-term systemic delivery of BH4 and the treatment of endothelial dysfunction.


Highly reactive trans-cyclooctene tags with improved stability for Diels-Alder chemistry in living systems.
One of the challenges of pretargeted radioimmunotherapy, which centers on the capture of a radiolabeled probe by a preinjected tumor-bound antibody, is the potential immunogenicity of biological capturing systems. A bioorthogonal chemical approach may circumvent this drawback, but effective in vivo chemistry in mice, larger animals, and eventually humans, requires very high reagent reactivity, sufficient stability, and retained selectivity. We report here that the reactivity of the fastest bioorthogonal reaction, the inverse-electron-demand-Diels-Alder cycloaddition between a tetrazine probe and a trans-cyclooctene-tagged antibody, can be increased 10-fold (k2 = 2.7 × 10(5) M(-1) s(-1)) via the trans-cyclooctene, approaching the speed of biological interactions, while also increasing its stability. This was enabled by the finding that the trans-cyclooctene tag is probably deactivated through isomerization to the unreactive cis-cyclooctene isomer by interactions with copper-containing proteins, and that increasing the steric hindrance on the tag can impede this process. Next, we found that the higher reactivity of axial vs equatorial linked TCO can be augmented by the choice of linker. The new, stabilized, and more reactive tag allowed for improved tumor-to-nontumor ratios in pretargeted tumor-bearing mice.


[Correction of hemodynamics after peritoneoatrial shunt in liver cirrhosis with resistant ascites].
Complex examination of hemodynamics was performed in 26 patients with cirrhosis of the liver with portal hypertension after operation of peritoneoatrial shunt using the methods of integral rheography, probing of heart cavities and pulmonary artery. Clinical results of the operations were analyzed. A conclusion was made of the absence of substantial alterations of gas exchange and hemodynamics of the lesser circulation. The alteration of the colloido-oncotic properties of blood are thought to be the leading factor in pathogenesis of the appearance of postoperative cardiopulmonary complications.


Properties of the background global aerosol and their effects on climate.
Properties of the aerosols above Hawaii, Alaska, and the South Pole are derived from sun photometry at several wavelengths. The mass loading of aerosol material is several milligrams per square meter. At the South Pole the mean particle radius is 0.04 micrometer; at Hawaii in March 1975 there was a thin volcanic layer with a mean particle radius of 0.1 micrometer. The aerosols cause heating of the earth-atmosphere system at the poles and cooling at low latitudes.


Well-done meat intake and the risk of breast cancer.
Heterocyclic amines, mutagens formed in meats cooked at high temperatures, have been demonstrated as mammary carcinogens in animals. We conducted a nested, case-control study among 41836 cohort members of the Iowa Women's Health Study to evaluate the potential role of heterocyclic amines and intake of well-done meat in the risk for human breast cancer. A questionnaire was mailed to individuals in the cohort who had breast cancer diagnosed during the period from 1992 through 1994 and a random sample of cancer-free cohort members to obtain information on usual intake of meats and on meat preparation practices. Color photographs showing various doneness levels of hamburger, beefsteak, and bacon were included. Multivariate analysis was performed on data from 273 case subjects and 657 control subjects who completed the survey. A dose-response relationship was found between doneness levels of meat consumed and breast cancer risk. The adjusted odds ratios (ORs) for very well-done meat versus rare or medium-done meat were 1.54 (95% confidence interval [CI]=0.96-2.47) for hamburger, 2.21 (95% CI=1.30-3.77) for beef steak, and 1.64 (95% CI=0.92-2.93) for bacon. Women who consumed these three meats consistently very well done had a 4.62 times higher risk (95% CI=1.36-15.70) than that of women who consumed the meats rare or medium done. Risk of breast cancer was also elevated with increasing intake of well-done to very well-done meat. Consumption of well-done meats and, thus, exposures to heterocyclic amines (or other compounds) formed during high-temperature cooking may play an important role in the risk of breast cancer.


The meanings and experiences of cesarean birth among Cambodian, Lao and Vietnamese immigrant women in Australia.
We examined the experience of cesarean birth among 67 Cambodian, Lao and Vietnamese women who are now living in Melbourne, Australia, based on a larger ethnographic research project on childbearing, childrearing and motherhood among Southeast Asian women in Australia. We found a range of responses in the discourses of the women: some women preferred cesarean birth, but others resisted it. Women's social construction of their feelings stemmed from three interpretive frameworks: trust in medical knowledge, expectations (personal ideology of reproduction and motherhood) and communication with an understanding of their caregivers' preferences (as opposed to choice). Our findings have ramifications for health care providers working in multicultural settings. An effective dialogue between women and their health caregivers is required to keep the cesarean section rates down. In the case of immigrant women in a multicultural society like Australia, it is not the passive receipt of information but a two-way communication with adequate interpreter support that will lead to informed choice, fewer cesarean births, more satisfaction and less regret.


Effect of suvorexant on morphine tolerance and dependence in mice: Role of NMDA, AMPA, ERK and CREB proteins.
The major problems of morphine use in the clinic are its tolerance and dependence. This study aimed to investigate the effect of suvorexant, a dual orexin receptor antagonist, on morphine-induced dependence and tolerance in mice and evaluate the level of NMDA, AMPA, ERK, p-ERK, CREB and p-CREB proteins in the brain. Tolerance and dependence were induced by repeated injection of morphine in mice (three times a day for 3 days, 50, 50, and 75 mg/kg /day). To evaluate the effects of the drugs on morphine-induced tolerance and dependence, suvorexant (30, 60 and 90 mg/kg), clonidine (positive control, 0.1 mg/kg) and saline were injected intraperitoneally 30 min before each injection of morphine. Tolerance and locomotor activity were assessed by tail-flick and open-field tests, respectively. The effect of suvorexant on the naloxone (5 mg/kg, ip)-induced morphine withdrawal, was also evaluated. Finally, the expression of proteins in the brain of mice was measured by western blot. Administration of suvorexant with morphine significantly reduced morphine-induced tolerance. Also, suvorexant attenuated the naloxone-precipitated opioid withdrawal. Suvorexant decreased morphine-enhanced levels of CREB and p-ERK proteins but did not affect the expression of NMDA and AMPA proteins compared to the morphine group. Suvorexant reduced morphine-induced tolerance and dependence through the inhibition of orexin receptors as well as changes in CREB and p-ERK protein levels in the brain.


[Diagnostic value of changes in Q wave amplitude in left thoracic leads during physical loading].
The informative value of stress-induced changes in Q wave amplitude and ST segment for the diagnosis of coronary heart disease was compared in records from left chest leads. Bicycle ergometry was conducted in 74 patients with coronary angiographically documented stenosis (more than 70% of the lumen) of one or more coronary arteries, and 28 subjects showing no apparent coronary arterial changes. The lack of increment in Q wave amplitude was shown to be a fairly sensitive sign of myocardial ischemia. Yet, its specificity is relatively low, much inferior to that of ST changes. The predictive value of changes in ST segment is significantly higher, as compared to that of changes in Q wave amplitude during exercise. Simultaneous assessment of ST and Q wave changes in response to stress failed to improve the predictive accuracy, as compared to the interpretation of ST changes alone.


Improving health and well-being through community health champions: a thematic evaluation of a programme in Yorkshire and Humber.
The contribution that lay people can make to the public health agenda is being increasingly recognised in research and policy literature. This paper examines the role of lay workers (referred to as 'community health champions') involved in community projects delivered by Altogether Better across Yorkshire and Humber. The aim of the paper is to describe key features of the community health champion approach and to examine the evidence that this type of intervention can have an impact on health. A qualitative approach was taken to the evaluation, with two strands to gathering evidence: interviews conducted with different stakeholder groups including project leads, key partners from community and statutory sectors and community workers, plus two participatory workshops to gather the views of community health champions. Seven projects (from a possible 12) were identified to be involved in the evaluation. Those projects that allowed the evaluation team to explore fully the champion role (training, infrastructure, etc.) and how that works in practice as a mechanism for empowerment were selected. In total, 29 semi-structured interviews were conducted with project staff and partners, and 30 champions, varying in terms of age, gender, ethnicity and disability, took part in the workshops. Becoming a community health champion has health benefits such as increased self-esteem and confidence and improved well-being. For some champions, this was the start of a journey to other opportunities such as education or paid employment. There were many examples of the influence of champions extending to the wider community of family, friends and neighbours, including helping to support people to take part in community life. Champions recognised the value of connecting people through social networks, group activities, and linking people into services and the impact that that had on health and well-being. Project staff and partners also recognised that champions were promoting social cohesiveness and helping to integrate people into their community. The recent public health White Paper suggested that the Altogether Better programme is improving individual and community health as well as increasing social capital, voluntary activity and wider civic participation. This evaluation supports this statement and suggests that the community health champion role can be a catalyst for change for both individuals and communities.


Activity-dependent heterogeneous populations of nitric oxide synthase neurons in the rat dorsal raphe nucleus.
The brainstem dorsal raphe nucleus (DRN) contains an abundant distribution of nitric oxide (NO) synthase (NOS)-containing neuronal profiles in two distinct populations: faint- and intense-immunoreactive cells in midline (ventromedial and dorsomedial) and lateral wing subregions, respectively. This study tested the hypothesis that different functional dynamics underlie the topography of NOS-containing cells in the DRN rostrocaudal and mediolateral neuraxis by using a capsaicin challenge paradigm (50 mg/kg, subcutaneous). Compared with vehicle, capsaicin significantly and preferentially increased nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d, an index of constitutive NOS) reactivity in the rostral midline and caudal lateral wing subregions. Furthermore, capsaicin activated more Fos-positive cells than vehicle within all subregions of the DRN but with a caudal versus rostral predominance in activation pattern. In addition, a high proportion of capsaicin-induced Fos cells in the midline but almost none in lateral wing stained for NADPH-d. These observations suggest the existence of two functionally distinct populations of NOS neurons in the DRN. Furthermore, capsaicin increased galanin immunoreactivity with predominant staining in cell soma and fiber processes in midline and lateral wing subregions of the nucleus, respectively. The total capsaicin-induced galanin immunoreactivity was higher in rostral versus caudal DRN, and a high proportion of galanin-positive cells in the midline also contained NADPH-d and neuronal NOS, thus suggesting a potential NO-galanin interaction in these neurons. The differential pattern of Fos/NADPH-d colocalization across the nucleus suggests that midline and lateral wing NOS neurons of the DRN express their neuromodulatory actions on discrete efferent targets via different intracellular mechanisms.


Analysis of cardiac substructure dose in a large, multi-centre danish breast cancer cohort (the DBCG HYPO trial): Trends and predictive modelling.
Radiotherapy for breast cancer can increase the risks of heart disease. Patient-specific risk assessment may be improved with the inclusion of doses to cardiac substructures. The purpose of this work was to use automatic segmentation to evaluate substructure doses and develop predictive models for these based on the dose to the whole heart. Automatic segmentation was used to delineate cardiac substructures in a Danish breast cancer trial (DBCG HYPO) dataset comprising over 1500 Danish women treated between 2009 and 2014. Trends in contouring practices and cardiac doses over time were investigated, and models to predict substructure doses from whole heart dose parameters were fit to the data. Manual contouring consistency improved over the study period when compared with automatic segmentation; systematic differences between automatically and manually defined heart volume decreased from 106 cm3 to 12.0 cm3. Doses to the heart and cardiac substructures also decreased. Mean whole heart doses for left-sided treatments in 2009 and 2014 were 1.94±1.19 Gy and 1.29±0.69 Gy (average ± SD), respectively. Prediction of mean substructure doses is accurate, with R2 scores in the range 0.45-0.95 (average 0.77), depending on the particular structure. This study reports heart and cardiac substructure doses in a large breast cancer cohort. Predictive models generated in this work can be used to estimate mean cardiac substructure doses for datasets where patient imaging and dose distributions are not available, provided the tangential field techniques are consistent with those used in the trial.


Environmental Risks of Nano Zerovalent Iron for Arsenate Remediation: Impacts on Cytosolic Levels of Inorganic Phosphate and MgATP2- in Arabidopsis thaliana.
The use of nano zerovalent iron (nZVI) for arsenate (As(V)) remediation has proven effective, but full-scale injection of nZVI into the subsurface has aroused serious concerns for associated environmental risks. This study evaluated the efficacy of nZVI treatment for arsenate remediation and its potential hazards to plants using Arabidopsis thaliana grown in a hydroponic system. Biosensors for inorganic phosphate (Pi) and MgATP2- were used to monitor in vivo Pi and MgATP2- levels in plant cells. The results showed that nZVI could remove As(V) from growth media, decrease As uptake by plants, and mitigate As(V) toxicity to plants. However, excess nZVI could cause Pi starvation in plants leading to detrimental effects on plant growth. Due to the competitive adsorption of As(V) and Pi on nZVI, removing As(V) via nZVI treatment at an upstream site could relieve downstream plants from As(V) toxicity and Pi deprivation, in which case 100 mg/L of nZVI was the optimal dosage for remediation of As(V) at a concentration around 16.13 mg/L.


Volumetric computerized tomography as a measurement of periprosthetic acetabular osteolysis and its correlation with wear.
Osteolysis, which is considered to be a major source of morbidity following total hip joint replacement, has been notoriously difficult to measure accurately, particularly in the acetabular area. In order to study periacetabular osteolysis, specialized software for computerized tomography (CT) scan image analysis has been developed. This software (3D-CT) eliminates metal artifacts, allows three-dimensional segmentation of the CT image, and reconstructs the segmented image to provide an accurate representation and measurement of volume for osteolytic lesions. In the present study, 20 patients underwent periacetabular osteolytic volume determination using 3D-CT, functional assessment (using the Harris Hip Scale, the Western Ontario and McMaster University Osteoarthritis Index, and the short form 36 questionnaire), and two-dimensional analysis of volumetic polyethylene wear using digitalized plain films. Periacetabular osteolysis correlated directly with the polyethylene wear rate (relative risk [RR] = 0.494, P = 0.027). If one patient with an acetabular revision, one patient with recurrent dislocation, and one patient with a Biomet prosthesis are excluded, then the correlation between wear and osteolysis is improved (RR = 0.685, P = 0.002). In summary, the current study demonstrates both the feasibility of CT imaging of periacetabular osteolysis and the correlation between polyethylene wear and osteolytic volume, providing a potential outcome measure for clinical trials that are designed to examine interventions in this complex disease process.


Frequency of Non-motor Symptoms in Parkinson's Patients With Motor Fluctuations.
Background: Non-motor symptoms (NMS), including neuropsychiatric, sleep, autonomic, and sensory domains, are an integral aspect of the clinical presentation of Parkinson disease (PD) and affect neurocognitive functioning as well as patients' and caregivers' well-being. Objective: To describe the occurrence of NMS in PD patients with motor fluctuations in real-life condition. Methods: The present study is a secondary analysis of a previous multinational, multicenter, retrospective-prospective cohort observational study (SYNAPSES). Patients with PD diagnosis and motor fluctuations aged ≥18 years were included. Data collected at the baseline visit were used for this study, and descriptive analyzes were conducted to describe the distribution of NMS in motor-fluctuating PD patients distributed according to different clinical characteristics. Results: Of the 1,610 patients enrolled, 1,589 were included for the analysis (978 males and 611 females), with a mean age of 68.4 (SD = 9.6). Most patients had at least one NMS (88.5%). Sleep problems and psychiatric symptoms were the most prevalent NMS in motor fluctuating PD patients in all H and Y stages. Psychiatric disorders were more frequent in older patients and in patients with a larger number of years of PD diagnosis, while sleep problems were more preeminent in younger patients and with inferior disease duration. Conclusions: The present findings further support the high prevalence of NMS in PD patients with motor fluctuations, thus reinforcing the need for assessing them for diagnostic accuracy and for delivering holistic care.


Epilepsy in glioblastoma patients: basic mechanisms and current problems in treatment.
Glioblastoma-related epilepsy requires paying careful attention to a combination of factors with an integrated approach. Major interrelated issues must be considered in the seizure care of glioblastoma patients. Seizure control frequently requires the administration of antiepileptic drugs simultaneously with other treatments, including surgery, radiotherapy and chemotherapy, with complete seizure relief often being difficult to achieve. The pharmacological interactions between antiepileptic drugs and antineoplastic agents can modify the activity of both treatments, compromising their efficacy and increasing the probability of developing adverse events related to both therapies. This review summarizes the new pathophysiological pathways involved in the epileptogenesis of glioblastoma-related seizures and the interactions between antiepileptic drugs and oncological treatment, paying special attention to its impact on survival and the current evidence of the antiepileptic treatment efficacy, including the potential usefulness of new third-generation compounds.


A pancreatic tumor-specific biomarker characterized in humans and mice as an immunogenic onco-glycoprotein is efficient in dendritic cell vaccination.
Oncofetal fucose-rich glycovariants of the pathological bile salt-dependent lipase (pBSDL) appear during human pancreatic oncogenesis and are detected by themonoclonal antibody J28 (mAbJ28). We aimed to identify murine counterparts onpancreatic ductal adenocarcinoma (PDAC) cells and tissue and investigate the potential of dendritic cells (DC) loaded with this unique pancreatic tumor antigen to promote immunotherapy in preclinical trials. Pathological BSDLs purified from pancreatic juices of patients with PDAC were cleaved to generate glycosylated C-terminal moieties (C-ter) containing mAbJ28-reactive glycoepitopes. Immunoreactivity of the murine PDAC line Panc02 and tumor tissue to mAbJ28 was detected by immunohistochemistry and flow cytometry. C-ter-J28+ immunization promoted Th1-dominated immune responses. In vitro C-ter-J28+-loaded DCskewed CD3+ T-cells toward Th1 polarization. C-ter-J28+-DC-vaccinations selectively enhanced cell immunoreactivity to Panc02, as demonstrated by CD4+- and CD8+-T-cell activation, increased percentages of CD4+- and CD8+-T-cells and NK1.1+ cells expressing granzyme B, and T-cell cytotoxicity. Prophylactic and therapeutic C-ter-J28+-DC-vaccinations reduced ectopic Panc02-tumor growth, provided long-lasting protection from Panc02-tumor development in 100% of micebut not from melanoma, and attenuated progression of orthotopic tumors as revealed by MRI. Thusmurine DC loaded with pancreatic tumor-specific glycoepitope C-ter-J28+ induce efficient anticancer adaptive immunity and represent a potential adjuvant therapy for patients afflicted with PDAC.


Cortical strut allografts in the reconstruction of the femur in revision total hip arthroplasty. A basic science and clinical study.
Repeated total hip arthroplasties cause a loss of bone stock that will produce diminished component support, and can compromise implant function. There is, therefore, a compelling argument to return bone stock to the femur at the time of revision arthroplasty. Cortical strut allografts serve this purpose. They unite consistently and reliably, by 8.4 months on average. The overall rate of strut union is 96.6%. The sequence of healing events starts with round-off, followed by partial bridging and complete bridging. The repair process includes remodeling of the host femur, as well as the graft. Although there is variable resorption of some grafts, usually where not opposed to the host bone, there is also extension of others from host callus build-up such that, on average, there is no significant measurable loss of graft length or width. Most of the allograft struts, 78%, maintained a radiodense appearance. Clinical results of femoral revision with strut allografting have shown satisfactory end results compared with historic controls, with an average Harris score of 79.6 and a 2.7% subsidence rate. Of particular note is that the subsidence rate and clinical scores did not vary with the state of the preoperative femur, as has been shown repeatedly in the past. The canine model shows that the strut allografts are biologically active. Through mobilization of mesenchymal tissue, they are transformed into vascularized calluslike structures while maintaining good strength, and then further remodel to lamellar bone.


Salaries in psychiatric hospitals.
The National Association of Private Psychiatric Hospitals has been surveying hospitals for the past several years. This paper focuses on the salary levels and average annual rates of increase for a few selected positions. Comparisons are made with data from surveys covering similar positions in other settings and with the Consumer Price Index. Annual rates of increase are reported for five- and ten-year periods.


A CT scan technique for quantitative volumetric assessment of the mandible after distraction osteogenesis.
Distraction osteogenesis has become an accepted method of treatment for patients requiring reconstruction of hypoplastic mandibles. We present a quantitative analysis of volumetric changes after distraction osteogenesis in a series of 10 patients. Group I (n = 5 patients, 3 unilateral craniofacial microsomia, 1 Goldenhaar syndrome, and 1 bilateral craniofacial microsomia) underwent unilateral distraction of the mandible. Group II (n = 5 patients, 1 Nager syndrome, 1 bilateral craniofacial microsomia, 1 developmental micrognathia, and 2 Treacher Collins syndrome) underwent bilateral distraction of the mandible. Predistraction and postdistraction axial and three-dimensional computed tomographic (CT) scans were digitized and transferred to a computer for analysis with image-processing software to determine the changes in volume of the mandible and bony regenerate. The CT-derived volume method was validated by scanning three dry cadaver mandible specimens and comparing the volume data with those derived from a water-displacement method. The difference between the two methods was less than 5 percent. The mean distracted length, as recorded from the calibrated device, was 22.6 mm in the 10 patients. In the unilateral distraction group, the mean increase in hemimandibular bone volume was 2.8 cc, with a mean percentage increase of 27 percent in the distracted hemimandible. In the bilaterally distracted patients, the mean increase in total mandibular volume was 7.9 cc, with a mean percentage increase in bone volume of 25 percent. This study represents the first attempt to quantify the increase in bone volume resulting from distraction osteogenesis. Quantitative volumetric analysis of CT scans is an accurate method to measure the amount of bone regenerate in patients undergoing distraction osteogenesis of the mandible or the extremities. The concept and utility of quantifying the volumetric changes in bone following distraction osteogenesis may become more important as multiplanar devices are developed and used in other areas of the craniofacial skeleton.


Methods for functional magnetic resonance imaging in normal and lesioned behaving monkeys.
Methods for performing functional magnetic resonance imaging (fMRI) studies in behaving and lesioned monkeys using a human MR scanner are reported. Materials for head implant surgery were selected based on tests for magnetic susceptibility. A primate chair with a rigid head fixation system and a mock scanner environment for training were developed. To perform controlled visual studies, monkeys were trained to maintain fixation for several minutes using a novel training technique that utilized continuous juice rewards. A surface coil was used to acquire anatomical and functional images in four monkeys, one with a partial lesion of striate cortex. High-resolution anatomical images were used after non-uniform intensity correction to create cortical surface reconstructions of both lesioned and normal hemispheres. Our methods were confirmed in two visual experiments, in which functional activations were obtained during both free viewing and fixation conditions. In one experiment, face-selective activity was found in the fundus and banks of the superior temporal sulcus and the middle temporal gyrus in monkeys viewing pictures of faces and objects while maintaining fixation. In a second experiment, regions in occipital, parietal, and frontal cortex were activated in lesioned and normal animals viewing a cartoon movie. Importantly, in the animal with the striate lesion, fMRI signals were obtained in the immediate vicinity of the lesion. Our results extend those previously reported by providing a detailed account of the technique and by demonstrating the feasibility of fMRI in monkeys with lesions.


Loss of Mtmr2 phosphatase in Schwann cells but not in motor neurons causes Charcot-Marie-Tooth type 4B1 neuropathy with myelin outfoldings.
Mutations in MTMR2, the myotubularin-related 2 gene, cause autosomal recessive Charcot-Marie-Tooth type 4B1 (CMT4B1). This disorder is characterized by childhood onset of weakness and sensory loss, severely decreased nerve conduction velocity, demyelination in the nerve with myelin outfoldings, and severe functional impairment of affected patients, mainly resulting from loss of myelinated fibers in the nerve. We recently generated Mtmr2-null(neo) mice, which show a dysmyelinating neuropathy with myelin outfoldings, thus reproducing human CMT4B1. Mtmr2 is detected in both Schwann cells and neurons, in which it interacts with discs large 1/synapse-associated protein 97 and neurofilament light chain, respectively. Here, we specifically ablated Mtmr2 in either Schwann cells or motor neurons. Disruption of Mtmr2 in Schwann cells produced a dysmyelinating phenotype very similar to that of the Mtmr2-null(neo) mouse. Disruption of Mtmr2 in motor neurons does not provoke myelin outfoldings nor axonal defects. We propose that loss of Mtmr2 in Schwann cells, but not in motor neurons, is both sufficient and necessary to cause CMT4B1 neuropathy. Thus, therapeutical approaches might be designed in the future to specifically deliver the Mtmr2 phospholipid phosphatase to Schwann cells in affected nerves.


Determining epistatic selection in admixed populations.
When two diverging species begin hybridizing, selection against hybridization is likely driven not by single substitutions, but by interactions between incompatible mutations. To identify these incompatibilities in natural populations, researchers examine the extent of nonrandom associations between ancestry at physically unlinked loci in admixed populations. In this approach, which we call 'AD scans', locus pairs with significantly positive 'ancestry disequilibrium' (AD, i.e. locus pairs that positively covary by ancestry) represent incompatible alleles. Past research has uniformly revealed an excess of locus pairs with significantly positive AD, suggesting that dozens to hundreds of incompatibilities separate species. With forward simulations, we show that many realistic demographic scenarios, including recent and/or ongoing hybridization, generate a bias towards positive ancestry disequilibrium. We suggest steps that researchers can take to avoid pitfalls in interpreting AD scans, and present a novel measure of AD, which minimizes but does not fully eliminate bias in the AD distribution. We also show, by simulation, that the tail of the AD distribution is enriched for true incompatibilities. To illustrate the potential power and appropriate caution in interpretation of AD scans, we reanalyse previously published data from two admixed populations of Xiphophorus fishes. Our results imply that the prevalence of positive LD in admixed populations does not in itself support the idea that two-locus incompatibilities are widespread, but the co-enrichment of top AD hits across the two Xiphophorus populations supports the idea that AD scans can identify candidate interspecific incompatibilities.


[Snacking food pattern among Chinese children and adolescents in twelve provinces].
To examine and characterize the snacking patterns of Chinese children and adolescents. A total of 1195 subjects from the China Health and Nutrition Survey 2011 were included in the study. A multistage, stratified, sampling design was used. 24-h dietary recall method was used to collect food intake information in3 consecutive days. Snacking patterns were analyzed using cluster analysis. The highest consumption rates of snacks were fruits and products in 4-10 years old and 11-17 years old groups of urban and rural areas( 77%-84%). The major snacking food pattern of more than 90% children aged 4-10 years old in ubran and rual areas were fruits and dairy products. The major snacking food pattern of 82. 6% adolescents aged11-17 years old in ubran area were fruits products. And 47. 4% adolescents in rural area were beverage and fruits products. Four types of snacking food patterns are identified in 4-10 years old and 11-17 years old groups of urban and rural areas intwelve provinces of China.


Photo-Degradable Protein-Polymer Hybrid Shells for Caging Living Cells.
There is growing demand for the precise remote control of cellular functions in various fields. Herein, a method for caging mammalian cells by coating with photodegradable protein-polymer hybrid shells to photo-control their functions without genetic engineering is reported. A layer-by-layer assembly of photocleavable synthetic materials through biotin-streptavidin (SA) binding was employed for cell coating. The cell surfaces were first biotinylated with photocleavable biotinylated poly(ethylene glycol)(PEG)-lipid and then coated by repeatedly layering SA and micelles of the PEG-lipid and photocleavable biotinylated four-arm PEG. The cell extension and adhesion were suppressed with the shells and then triggered with the degradation of the shells by light exposure. Macrophage phagocytosis was also stopped by caging with the shells and restarted by light-guided uncaging. This study provides the first proof of principle that cellular functions can be remotely controlled by steric hinderance of cell surfaces with photodegradable materials.


Systemic lupus erythematosus: The search for the ideal biomarker.
During the last decades, there has been an increased interest in the discovery and validation of biomarkers that reliably reflect specific aspects of lupus. Although many biomarkers have been developed, few of them have been validated and used in clinical practice, but with unsatisfactory performances. Thus, there is still a need to rigorously validate many of these novel promising biomarkers in large-scale longitudinal studies and also identify better biomarkers not only for lupus diagnosis but also for monitoring and predicting upcoming flares and response to treatment. Besides serological biomarkers, urinary and cerebrospinal fluid biomarkers have emerged for assessing both renal and central nervous system involvement in systemic lupus erythematosus, respectively. Also, novel omics techniques help us to understand the molecular basis of the disease and also allow the identification of novel biomarkers which may be potentially useful for guiding new therapeutic targets.


Advance directives in the UK: legal, ethical, and practical considerations for doctors.
In the United Kingdom (UK), advance directives have recently received considerable attention from professional and voluntary organizations as well as medical journals and the media. However, despite such exposure, many doctors remain uncertain of the importance or relevance of advance directives with regard to their own clinical practice. This paper addresses these uncertainties by first explaining what advance directives are and then describing the current legal status of such directives in the UK. Examination of the cases underpinning this status reveals several key elements: competence, information, anticipation, applicability, and freedom from duress. Each is discussed. Although this paper focuses on legal issues, it is important that medical law does not dominate medical ethics. Accordingly, the paper also discusses some important philosophical and sociological considerations that have remained largely unexplored in the medical press. Finally, the paper deals with practical matters, including how the general practitioner might be involved.


Pyeloplasty for hydronephrosis: Issues of double J stent versus nephrostomy tube as drainage technique.
To compare the efficacy, complications, cost analysis and hospital stay between two methods of drainage of the kidney: double J (DJ) stent versus nephrostomy tube following open pyeloplasty for ureteropelvic junction obstruction hydronephrosis. This was a prospective randomized study of 20 patients in each group over 14 months. Pre and post-operative (3 months) function and drainage were assessed by ethylenedicysteine scan and intravenous urogram. Both groups showed similar good improvement in function and drainage. Nephrostomy group had significantly longer hospital stay (P < 0.001) but incurred less cost. Complications with nephrostomy included tube breakage (n = 1) and urine leak after tube removal (n = 2). DJ stents were associated with stent migration (n = 4), increased frequency of micturition (n = 9), dysuria (n = 4) and urinary tract infection (n = 1). Both methods of drainage did not interfere with improvement after pyeloplasty. Minor complications were more with DJ stent (P = 0.0003). Although overall cost of treatment was more with stents, they reduced length of hospital stay. Optimal length of stent is essential to reduce complications secondary to migration and bladder irritation.


Postnatal lesion evidence against a primary role for the corpus callosum in mouse sociability.
The BTBR T+tf/J (BTBR) strain is an inbred strain of mice that displays prominent social deficits and repetitive behaviors analogous to the defining symptoms of autism, along with complete congenital agenesis of the corpus callosum (CC). The BTBR strain is genetically distant from the widely used C57BL/6J (B6) strain, which exhibits high levels of sociability, a low level of repetitive behaviors, and an intact CC. Emerging evidence implicates compromised interhemispherical connectivity in some cases of autism. We investigated the hypothesis that the disconnection of CC fiber tracts contributes to behavioral traits in mice that are relevant to the behavioral symptoms of autism. Surgical lesion of the CC in B6 mice at postnatal day 7 had no effect on juvenile play and adult social approaches, and did not elevate repetitive self-grooming. In addition, LP/J, the strain that is genetically closest to the BTBR strain but has an intact CC, displayed juvenile play deficits and repetitive self-grooming similar to those seen in BTBR mice. These corroborative results offer evidence against the hypothesis that the CC disconnection is a primary cause of low sociability and a high level of repetitive behaviors in inbred mice. Our findings indicate that genes mediating other aspects of neurodevelopment, including those whose mutations underlie more subtle disruptions in white matter pathways and connectivity, are more likely to contribute to the aberrant behavioral phenotypes in the BTBR mouse model of autism.


Intratumoral heterogeneity of the tumor cells based on in situ cortisol excess in cortisol-producing adenomas; ∼An association among morphometry, genotype and cellular senescence∼.
Cortisol-producing adrenocortical adenomas (CPAs) are associated with ACTH-independent Cushing's syndrome and histologically composed of two cellular subtypes: compact (lipid-poor) and clear (lipid-rich) tumor cells. However, the details of hormonal and biological activities of these tumor cells have remained unknown, especially in CPAs. CPAs frequently harbored unique histological features different from those of aldosterone-producing adenomas (APAs) including a senescent phenotype. Therefore, we explored the association between morphological features and the immunoreactivity of steroidogenic enzymes in CPAs with different genotypes and compared them with cellular senescence markers as well as clinicopathological factors of the cases. Hormonal activities (3βHSD, CYP21A, CYP17A1, CYP11B1 and DHEA-ST) and cellular senescence markers (p16, p21 and Ki-67) within different morphological features (clear and compact) were evaluated in 40 CPAs. CPA genotypes (PRKACA, GNAS and CTNNB1) were examined by Sanger sequencing and then compared them with the factors above. p21 immunoreactivity was significantly positively correlated with that of CYP21A (p = 0.0110), CYP17A1 (p = 0.0356) and DHEA-ST (p = 0.0420) but inversely with tumor size (p = 0.0015). CYP21A (p = 0.0016), CYP11B1 (p = 0.0001), CYP17A1 (p < 0.0001) and p16 (p = 0.0137) immunoreactivity were all significantly higher in compact cells than those in clear cells. CYP17A1 (p = 0.0056) and 3βHSD (p = 0.0437) immunoreactivity was significantly higher in PRKACA-mutated than wild type CPAs. p16 immunoreactivity and serum DHEA-S level were both significantly higher in GNAS-mutated than PRKACA-mutated (p = 0.0250) and wild type (p = 0.0180) CPAs. Results of our present study did demonstrate that compact tumor cells were hormonally active and more senescent than clear tumor cells in CPAs. PRKACA- and GNAS-mutated tumor cells were more hormonally active and senescent than those without mutations despite the similar morphological features. We herein proposed a novel histological classification of the tumor cell subtypes based on in situ cortisol excess, genotypes and the status of cell senescence in CPAs.


Transcriptional regulation of the phosphotransacetylase-encoding and acetate kinase-encoding genes (pta and ack) from Methanosarcina thermophila.
Phosphotransacetylase and acetate kinase catalyze the activation of acetate to acetyl coenzyme A in the first step of methanogenesis from acetate in Methanosarcina thermophila. The genes encoding these enzymes (pta and ack) have been cloned and sequenced. They are arranged on the chromosome with pta upstream of ack (M.T. Latimer, and J. G. Ferry, J. Bacteriol. 175:6822-6829, 1993). The activities of phosphotransacetylase and acetate kinase are at least 8- to 11-fold higher in acetate-grown cells than in cells grown on methanol, monomethylamine, dimethylamine, or trimethylamine. Northern blot (RNA) analyses demonstrated that pta and ack are transcribed as an approximately 2.4-kb polycistronic message and that the regulation of enzyme synthesis occurs at the mRNA level. Primer extension analyses revealed a transcriptional start site located 27 bp upstream from the translational start of the pta gene and 24 bp downstream from a consensus archaeal boxA promoter sequence. S1 nuclease protection assays detected transcripts with four different 3' ends, each of which mapped to the beginning of four consecutive direct repeats. Northern blot analysis using an ack-specific probe detected both the 2.4-kb polycistronic transcript and a smaller 1.4-kb transcript which is the estimated size of monocistronic ack mRNA. A primer extension product was detected with an ack-specific primer; the 5' end of the product was in the intergenic region between the pta and ack genes but did not follow a consensus archaeal boxA sequence. This result, as well as detection of an additional 1.4-kb mRNA species, suggests processing of the polycistronic 2.4-kb transcript.


[Unilateral agenesis of the main branch of the pulmonary artery].
We studied ten patients with unilateral absence of main branch of pulmonary artery (UAMBPA). Six patients with absent right pulmonary artery (ARPA) and four with the left pulmonary artery (ALPA). The presence of either atrial septal defect, ventricular septal defect and patent ductus arteriosus alone or combinated were associated with pulmonary hypertension (mean pressure of the pulmonary artery greater than 48 mm Hg). The patients without associated cardiac defects were asymptomatic and with little elevation of the pulmonary arterial pressure (mean pressure of the pulmonary artery less than 26 mmHg).


Response-specific inhibition during general facilitation of defensive responses in Aplysia.
Siphon responses of Aplysia have been used to examine the neural basis of nociceptive behavioral inhibition. The authors tested the response specificity and functional significance of this inhibition. Video analysis showed that strong tail-nerve shock decreased the duration of siphon constriction evoked by weak siphon shock. Tail-nerve shock also caused the appearance of a novel flaring response to the test stimulus, which resembled the siphon response to tail-nerve shock. Novel flaring responses were expressed to both mechanical and electrical siphon stimuli. Tailshock facilitated another defensive response, inking, during the period of inhibited siphon constriction. Tailshock also facilitated tail contractions evoked by weak contralateral tail stimulation during this period. These results indicate that inhibition is not generalized across defensive responses and is specific to siphon responses that interfere with directed ink ejection toward an injured site.


Multiscale modeling of fiber optic gyroscope temperature drift based on improved ensemble empirical mode decomposition.
Temperature drift is a major error source of the fiber optic gyroscope (FOG), and the method of modeling is important in eliminating it. A method of multiscale modeling based on improved ensemble empirical mode decomposition (EEMD) is proposed in this paper. First, in order to improve the ability of eliminating mode mixing, the influence of the frequency of the masking signal on mode mixing is analyzed. Then we conclude that the frequency of the masking signal should be higher than that of the signal, and an improved EEMD is proposed based on the conclusion. Second, the temperature drift of FOG is filtered by applying the permutation entropy to the intrinsic mode functions (IMFs). Third, the IMFs are divided into several scales according to the mean value and the distribution of instantaneous frequency of IMFs. Finally, the algorithm of the support vector machine is used to model each scale, and the models are accumulated into a total model. The regression error after compensation of the proposed method (in the case of the mean squared error indicator) increased by more than two orders of magnitude compared to the original temperature drift.


The Pediatric Pain Screening Tool (PPST) can Rapidly Identify Elevated Pain and Psychosocial Symptomatology in Treatment-Seeking Youth with Acute Musculoskeletal Pain.
This cross-sectional study examines the utility of the Pediatric Pain Screening Tool (PPST) for rapidly assessing pain and psychosocial symptomatology in treatment-seeking youth with acute musculoskeletal pain. Participants were 166 youth (10-18 years, 53.6% female) participating in one of two larger cohort studies of youth with acute musculoskeletal pain. Youth completed the PPST and measures of pain, pain-related fear, pain catastrophizing, pain-related disability, and sleep quality. Participants were categorized into PPST risk groups using published cut-offs. ANOVA and chi-square examined associations between PPST risk groups and self-report measures; receiver operating characteristic (ROC) analyses examined associations among PPST scores and clinical reference cut-offs. The PPST classified 28.3% of youth as high, 23.5% as moderate, and 48.2% as low-risk. Females were more likely to be high-risk. ANOVAs revealed differences in clinical factors by PPST risk group particularly differences among youth labeled high versus low-risk. ROC analyses showed the PPST is effective in discriminating "cases" versus "non-cases" on pain-related disability, pain-fear and catastrophizing. Results reveal the PPST is effective for rapidly screening youth with acute pain for pain and psychosocial symptomatology. An important next step will be to examine the validity of the PPST in predicting recovery outcomes of acute pain samples. PERSPECTIVE: This article presents the Pediatric Pain Screening Tool (PPST) as a measure for rapidly screening youth with acute pain for pain and psychosocial symptomatology. The tool categorizes youth into low, moderate or high-risk groups and discriminates among those with versus without clinically significant levels of disability, pain-related fear and catastrophizing.


Intrapleural tetracycline for the prevention of recurrent spontaneous pneumothorax. Results of a Department of Veterans Affairs cooperative study.
This prospective, multicenter, randomized, "unblinded," controlled clinical trial was designed to determine if the intrapleural instillation of 1500 mg of tetracycline hydrochloride would be effective in diminishing the ipsilateral rate of recurrence for spontaneous pneumothorax. During the 4-year enrollment period, 113 patients were assigned to the tetracycline group; 116 patients were assigned to the control group. During the 5-year study period, the recurrence rate in the tetracycline group (25%) was significantly less than that in the control group (41%). Use of tetracycline seemed to reduce the recurrence rates for patients with either primary or secondary spontaneous pneumothorax and for patients with either an initial or a recurrent pneumothorax. We conclude that the intrapleural administration of tetracycline in patients with spontaneous pneumothorax significantly reduces the rate of ipsilateral recurrence but is associated with intense chest pain. Intrapleural tetracycline therapy is indicated for patients with a spontaneous pneumothorax who are hospitalized and are treated with tube thoracostomy.