Clustering by multiple long-term conditions and social care needs: a cross-sectional study among 10 026 older adults in England.
BACKGROUND : People with multiple long-term conditions (MLTC) face health and social care challenges. This study aimed to classify people by MLTC and social care needs (SCN) into distinct clusters and quantify the association between derived clusters and care outcomes. METHODS : A cross-sectional study was conducted using the English Longitudinal Study of Ageing, including people with up to 10 MLTC. Self-reported SCN was assessed through 13 measures of difficulty with activities of daily living, 10 measures of mobility difficulties and whether health status was limiting earning capability. Latent class analysis was performed to identify clusters. Multivariable logistic regression quantified associations between derived MLTC/SCN clusters, all-cause mortality and nursing home admission. RESULTS: Our study included 9171 people at baseline with a mean age of 66.3 years; 44.5% were men. Nearly 70.8% had two or more MLTC, the most frequent being hypertension, arthritis and cardiovascular disease. We identified five distinct clusters classified as high SCN/MLTC through to low SCN/MLTC clusters. The high SCN/MLTC included mainly women aged 70-79 years who were white and educated to the upper secondary level. This cluster was significantly associated with higher nursing home admission (OR=8.71; 95% CI: 4.22 to 18). We found no association between clusters and all-cause mortality. CONCLUSIONS: We have highlighted those at risk of worse care outcomes, including nursing home admission. Distinct clusters of individuals with shared sociodemographic characteristics can help identify at-risk individuals with MLTC and SCN at primary care level.


Analysis of the enhanced oral bioavailability of fenofibrate lipid formulations in fasted humans using an in vitro-in silico-in vivo approach.
Lipid-based formulations have established a significant role in the formulation of poorly soluble drugs for oral administration. In order to better understand their potential advantages over solid oral dosage forms, we studied the solubility and dissolution/precipitation characteristics of three self-microemulsifying drug delivery system (SMEDDS) formulations and one suspension of micronized fenofibrate in lipid excipients, for which pharmacokinetic studies had already been reported in the open literature. The in vitro dispersion/dissolution studies were carried out in biorelevant media using USP II apparatus. These were followed up by in silico simulations using STELLA® software, in which not only dispersion/dissolution, but also the precipitation and re-dissolution of fenofibrate was taken into account. While unformulated drug exhibited poor solubility (0.22 μg/mL in FaSSGF and 4.31 μg/mL in FaSSIF-V2(PO4)) and dissolved less than 2% in dissolution tests, the solubility of fenofibrate in the presence of the lipid excipients increased dramatically (e.g., to 65.44 μg/mL in the presence of the Myritol 318/TPGS/Tween 80 SMEDDS) and there was an attendant increase in the dissolution (over 80% from capsules containing the Myritol 318/TPGS/Tween 80 SMEDDS and about 20% from the dispersion of fenofibrate in lipid excipients). For the four lipid-based fenofibrate formulations studied, combining in vitro data in biorelevant media with in silico simulation resulted in accurate prediction of the in vivo human plasma profiles. The point estimates of C(max) and AUC ratio calculated from the in silico and in vivo plasma profiles fell within the 0.8-1.25 range for the SMEDDS solution and capsule formulations, suggesting an accurate simulation of the in vivo profiles. This similarity was confirmed by calculation of the respective f2 factors. Sensitivity analysis of the simulation profiles revealed that the SMEDDS formulations had virtually removed any dependency of absorption on the dissolution rate in the small intestine, whereas for the dispersion in lipid excipients, this barrier remained. Such results pave the way to optimizing the performance of oral lipid-based formulations via an in vitro-in silico-in vivo approach.


Effects of vlsE complementation on the infectivity of Borrelia burgdorferi lacking the linear plasmid lp28-1.
The loss of linear plasmid lp28-1, which contains the vls antigenic variation locus, is associated with reduced infectivity of Borrelia burgdorferi in immunocompetent mice. The recombinant shuttle vector pBBE22, which includes the virulence determinant BBE22 from lp25 and restores infectivity to readily transformable B. burgdorferi lacking lp25 and lp56, was used to determine the effect of trans expression of vlsE on virulence. Spirochetes lacking lp28-1 were complemented with the plasmid pBBE22:vlsE, containing both BBE22 and vlsE. VlsE protein produced by this construct was expressed and surface accessible in in vitro-cultured B. burgdorferi, as determined by surface proteolysis and immunoblot analysis. Clones lacking lp25 but containing lp28-1 and either pBBE22 or pBBE22:vlsE were reisolated consistently from immunocompetent mice 8 weeks after infection. In contrast, a clone lacking both lp25 and lp28-1 and complemented with pBBE22:vlsE was isolated from only a single tissue of one of six C3H/HeN mice 8 weeks postinfection. These results indicate that either an intact vls antigenic variation locus or another determinant on lp28-1 is required to restore complete infectivity. In addition, an isogenic clone that retained lp28-1 was complemented with the vlsE shuttle plasmid and was examined for vlsE sequence variation and infectivity. Sequence variation was not observed for the shuttle plasmid, indicating that the cis arrangement of vlsE and the vls silent cassettes in lp28-1 facilitate vlsE gene conversion. Lack of vlsE sequence variation on the shuttle plasmid thus did not result in clearance of the trans-complemented strain in immunocompetent mice under the conditions tested.


A survey of motor vehicle burn accidents in children: report of 45 cases.
The association of burns with motor vehicles was reviewed from the records of 1,532 children treated at the Galveston Shriners Burns Institute since 1966. Forty-five children were burned in or about a motor vehicle. The most common causes were gasoline spillage in moving vehicle accidents, and small children playing with matches unattended in a stationary vehicle. Motor vehicle burn patients had more serious and larger burns than in the general burn population. Of the 34 children burned within the confined space of a motor vehicle, 94% suffered face and/or hand burns. There was a high incidence of respiratory problems. In the moving motor-vehicle fire accident group there were 13 major injuries seen in 17 patients. Of the total motor vehicle occupancy in 38 separate accidents, 19 people died and 66 were hospitalized at the SBI or elsewhere.


Stroop process dissociations: the relationship between facilitation and interference.
L.L. Jacoby's (1991) "process dissociation procedure" was used to quantitatively estimate the contributions of color-naming and word-reading processes to responding on the Stroop task. The results show that color naming and word reading can operate independently to determine responses. Degrading stimulus colors eliminated the typical asymmetry between Stroop facilitation and interference, as predicted by the equations (Experiments 1 and 2). Degrading stimulus colors reduced the estimated contribution of color naming to responding but had no effect on the estimated contribution of word reading (Experiment 2). In contrast, increasing the proportion of incongruent items reduced the estimated contribution of word reading but had no effect on the estimated contribution of color naming (Experiments 3 and 4). The results indicate that the facilitating and interfering effects of automatic processes cannot be accurately measured in terms of differences from baseline.


Mediterranean diet interventions to prevent cognitive decline--opportunities and challenges.
Cognitive decline has a profound impact on the health and quality of life of older people and their caregivers. Exploring mechanisms to delay cognitive decline has become an urgent economic priority, given the projected changes in population demographics. Systematic reviews and meta-analyses of observational studies suggest that adherence to a Mediterranean Diet (MD) is associated with reduced cognitive decline, but such an observation needs to be tested in randomised controlled trials. Intervention evidence is currently limited, and future studies need to be adequately powered, with careful attention given to choice of participants, outcomes being assessed, study duration and strategies to achieve compliance. Alongside these studies, consideration has to be given to how best promote and encourage dietary change in older people in general, and particularly in those experiencing the early stages of cognitive decline, as there may be specific factors that need to be considered when designing lifestyle behaviour change interventions in this group.


Structure and function of glucose binding protein-single walled carbon nanotube complexes.
Understanding the structure and function of glucose binding proteins (GBP) complexed with single walled carbon nanotubes (SWNTs) is important for the development of applications including fluorescent sensors and nanostructure particle tracking. Herein, circular dichroism (CD), thermal denaturation, photo-absorption spectroscopy and atomic force microscopy are used to study these nanostructures. The protein retains its glucose-binding activity after complexation and is thermally stable below 36 °C. However, the SWNT lowers the midpoint denaturation temperature (Tm) by 5 °C and 4 °C in the absence and presence of 10 mM glucose, respectively. This data highlights that using techniques such as CD and thermal denaturation may be necessary to fully characterize such protein-nanomaterial nanostructures.


Revision total hip arthroplasty after removal of a fractured well-fixed extensively porous-coated femoral component using a trephine.
When fracture of an extensively porous-coated femoral component occurs, its removal at revision total hip arthroplasty (THA) may require a femoral osteotomy and the use of a trephine. The remaining cortical bone after using the trephine may develop thermally induced necrosis. A retrospective review identified 11 fractured, well-fixed, uncemented, extensively porous-coated femoral components requiring removal using a trephine with a minimum of two years of follow-up. The mean time to failure was 4.6 years (1.7 to 9.1, standard deviation (sd) 2.3). These were revised using a larger extensively porous coated component, fluted tapered modular component, a proximally coated modular component, or a proximal femoral replacement. The mean clinical follow-up after revision THA was 4.9 years (2 to 22, sd 3.1). The mean diameter of the femoral component increased from 12.7 mm (sd 1.9) to 16.2 mm (sd 3.4; p > 0.001). Two revision components had radiographic evidence of subsidence that remained radiographically stable at final follow-up. The most common post-operative complication was instability affecting six patients (54.5%) on at least one occasion. A total of four patients (36.4%) required further revision: three for instability and one for fracture of the revision component. There was no statistically significant difference in the mean Harris hip score before implant fracture (82.4; sd 18.3) and after trephine removal and revision THA (81.2; sd 14.8, p = 0.918). These findings suggest that removal of a fractured, well-fixed, uncemented, extensively porous-coated femoral component using a trephine does not compromise subsequent fixation at revision THA and the patient's pre-operative level of function can be restored. However, the loss of proximal bone stock before revision may be associated with a high rate of dislocation post-operatively.


COVID-19 Pandemic-Related Financial Hardships and Adolescents' Adjustment: A Longitudinal Family Stress Approach.
Restrictions associated with the onset of the COVID-19 pandemic created a host of short- and long-term economic challenges for families. Despite their ubiquity during the early pandemic, knowledge on the developmental impacts of pandemic-related financial hardships on adolescents' adjustment is lacking. Guided by family stress and life course perspectives, this study investigated direct and indirect relations between pandemic-related financial hardships and adolescents' later depressive symptoms, delinquency, and academic performance via parents' depressive symptoms and acceptance. Data were drawn from three waves of a longitudinal study; participants completed online surveys at Wave 1, COVID-19 Wave (seven months later) and Wave 2 (five months later). Participants were two adolescent-aged siblings (n = 1364; 50% female; Mage = 14.45, SD = 1.55 years) and one parent (n = 682; 85% female; Mage = 45.15, SD = 5.37 years) from 682 families (N = 2048). Structural equation modeling results indicated that pandemic-related financial hardships were indirectly linked to greater adolescent delinquency and lower academic performance by adversely shaping parents' mental health and parent-adolescent relationship quality. The findings highlight financial hardships as critical family stressors for adolescent adjustment during the COVID-19 pandemic.


The hormone replacement therapy self-efficacy scale.
This study describes the initial development and psychometric evaluations of an instrument to measure self-efficacy in hormone replacement therapy (HRT) use. The development of the scale was based upon Bandura's self-efficacy construct. The sample was 116 women who were 50 years old and above and who were current or past users of HRT. Factor analysis was used to develop construct validity and Cronbach's alpha was used to compute reliabilities. Factor analysis isolated two factors, efficacy beliefs in HRT (EBs-HRT) and outcome expectations in HRT (OEs-HRT). The developed tool contains 14 items, eight items compose the EBs-HRT subscale and six items make-up the OEs-HRT subscale. The two subscales and total instrument were found to have good internal reliabilities. Implications for HRT intervention using the developed tool are discussed.


Erk-independent partial activation of AP-1 sites by the hepatitis B virus HBx protein.
The hepatitis B virus X protein (HBx) is suggested to regulate transcription by stimulation of intracellular signalling pathways. We have analysed the effects of HBx on activation of the MAP kinase (Erk) and JNK/SAPK signalling pathways and confirm a stimulation of the Erk/MAP kinase in quiescent cells. However, a substantial Erk-independent activation of AP-1, and phosphorylation of c-Jun (serine-63), but not Erk-2, was induced by HBx in dividing, serum-maintained cells. These data suggest that HBx promiscuously activates Erk and JNK responsive pathways and that its overall effect on signalling may be influenced by external mitogenic stimuli.


Diagnosis and Prognosis in Sudden Cardiac Arrest Survivors Without Coronary Artery Disease: Utility of a Clinical Approach Using Cardiac Magnetic Resonance Imaging.
Determining the pathogenesis of sudden cardiac arrest or periarrest without significant coronary artery disease is crucial for management and prognosis. Cardiovascular magnetic resonance (CMR) can detect morphological, functional, or tissue abnormalities, and we sought to evaluate the role of CMR in determining sudden cardiac arrest pathogenesis and prognosis in survivors. We retrospectively reviewed cardiac investigations and clinical outcomes in consecutive survivors of potentially fatal arrhythmias without coronary artery disease admitted to our institutions from 2008 to 2014. After coronary angiography and echocardiography, all underwent CMR and, when indicated, electrophysiology studies. Major adverse cardiac events (MACE), comprising significant nonfatal ventricular arrhythmia or death, was the primary outcome. Of 164 included subjects (65% men; mean age 48 [18-80] years), CMR contributed to the diagnosis in 80 (49%) and was decisive in 50 cases (30%). Dilated cardiomyopathy (n=27), myocarditis or sarcoidosis (n=22), occult myocardial infarction (n=13), and hypertrophic cardiomyopathy (n=9) were most frequent. Arrhythmic causes were found in 14% while no cause was identified in 36%. MACE occurred in 31% of subjects during a median follow-up of 32 months. MACE associated with presence of a CMR diagnosis, extent of late gadolinium enhancement, and left and right ventricular ejection fractions. Right ventricular ejection fraction was an independent predictor of MACE. CMR identified a likely pathogenesis for sudden cardiac arrest in nearly half of survivors in whom coronary artery disease had been excluded. One in 3 subjects had MACE; risk doubled in those with a CMR diagnosis and some CMR parameters-late gadolinium enhancement, left ventricular ejection fraction, and especially right ventricular ejection fraction-associated with prognosis.


Cytokine mRNA profiling identifies B cells as a major source of RANKL in rheumatoid arthritis.
In rheumatoid arthritis (RA), a complex cytokine network drives chronic inflammation and joint destruction. So far, few attempts have been made to identify the cellular sources of individual cytokines systematically. Therefore, the primary objective of this study was systematically to assess the cytokine messenger RNA expression profiles in the five largest cell populations in the synovial fluid and peripheral blood of RA patients. To reflect the in vivo situation as closely as possible, the cells were neither cultured nor stimulated ex vivo. Inflammatory cells from 12 RA patients were sorted into CD4 and CD8 T cells, B cells, macrophages and neutrophils. mRNA expression for 41 cytokines was determined by real-time PCR using microfluidic cards. Receptor activator nuclear factor kappa B ligand (RANKL) (TNFSF11) expression by B cells was further confirmed by flow cytometry and by immunofluorescence staining of frozen sections of synovial tissue from patients with RA. The detection of cytokines characteristic for T cells and myeloid cells in the expected populations validated this methodology. Beyond the expected cytokine patterns, novel observations were made. Striking among these was the high expression of mRNA for RANKL in B cells from synovial fluid. This observation was validated at the protein level in synovial tissue and fluid. RANKL, the key cytokine driving bone destruction by osteoclast activation, is produced by synovial B cells in RA. This observation is of importance for our understanding of the role of B cells in RA and their therapeutic targeting.


[Consensus on national criteria for transthoracic echocardiography competence].
Standardised competence assessment in transthoracic echocardiography (TTE) is increasingly demanded. Danish Cardiology Society working group on echocardiography initiated a Delphi study among departments involved in resident TTE training to obtain consensus on national criteria for TTE competence. Consensus was obtained on a list of 21 items relevant for TTE competence assessment. Three items should be performed with great routine after two years and 16 items after five years of training. The working group recommends the list being used for competence assessment of cardiology residents.


How stiff is the armadillo? A comparison with the allometrics of mammalian respiratory mechanics.
Static respiratory mechanics were examined in the armadillo (Dasypus novemcinctus) and compared with allometric relationships newly derived for adult mammals from values in the literature. Normalised by body weight, chest wall compliance (Cw) in the armadillo is lower than predicted. Lung compliance (Cl) is also low in the armadillo, however it is appropriately matched to the resting lung volume (Vr) (ie. Cl/Vr infinity Mass0.0) and the ratio of Cw/Cl is appropriate for the size of the animal. Respiratory system resistance is high in the armadillo, presumably because of smaller airways associated with the small lung. The power of breathing in the armadillo is comparatively high, mainly due to the high resistive forces. Indeed, the oxidative cost of breathing is approximately double that of a mammal with similar Vr. Hypoxia or hypercapnia are known to invoke an attenuated ventilatory response in the armadillo and one that relies more on changes in frequency rather than volume. While such a breathing pattern helps to reduce the power of breathing it also compromises the degree of hyperventilation achieved.


Controlling workers' compensation costs.
Providers should try to prevent as many losses as possible through inservices on proper lifting techniques, placing wet-floor signs while mopping, etc. The losses which can't be prevented must be controlled. Implement easy-to-understand, yet effective, policies and procedures, making the injured employees and insurance carrier accountable. Stop relying exclusively on those traditionally relied upon to provide risk management services. Brokers/agents seldom have the technical training in all aspects of insurance or the knowledge of the day-to-day operations of an employer. Insurance companies are more concerned about their costs than how ineffective claims handling and inadvertent over-reserving affects a facility's day-to-day operations and premiums. If an employer is large enough, it should hire someone in-house or subcontract risk management services if the service company proves that it knows how to implement and monitor a cost-effective risk management program. Taking the old adage, "you have to spend money to make money," one step further: "you have to spend a little money to save lots of money."


Patients' Perspectives on Approaches to Facilitate Completion of Advance Directives.
Little is understood about the different ways patients complete advance directives (ADs), which is most commonly through lawyers and increasingly using websites. To understand patients' perspectives on different approaches to facilitating AD completion, the value of legal regulation of ADs, and the use of a web-based platform to create an AD. Semi-structured interviews with patients. We purposively sampled 25 patients at least 70 years of age or with a chronic disease from 2 internal medicine clinics. Interviews focused on experiences and perspectives creating ADs, including facilitation by lawyers, health-care professionals, and websites. Feedback on a website prototype was also obtained. Responses were analyzed with modified grounded theory until thematic saturation was achieved. Although a majority of participants with ADs had used lawyers, participants were ambivalent about the benefits of lawyer facilitation. Most valued both the medical perspective of a health-care professional and a lawyer's attention to legal requirements for AD validity. Participants had positive impressions of the web platform, but some were concerned about privacy with online storage. Trust emerged as an overarching theme, and participants valued legal regulation of ADs to ensure document authenticity and delivery of preference-concordant care. Efforts to improve documentation of care planning need to address the disparate methods by which participants complete ADs. Creating options that combine the perceived benefits of a legal approach with greater health professional involvement could appeal to participants. Privacy concerns may limit web use by some patients.


[Lethal and mutagenic photodynamic effect of acridine orange on bacteriophage cd].
Both acridine-sensitized inactivation and mutagenesis in phage sd have been studied and compared with the effect of other mutagens. Inactivation curve was not stictly exponential, with a small shoulder at short light doses and deviation of survival lower than 10(-5). The lethal effect was not reactivated by multiplicity reactivation. Photodynamic damage in phage sd was accompanied by the increase of the rise (but not of the latent) period in the one-step curve of phage multiplication and increase of the burst size. Experiments were carried out at dye concentration of 1-10(-5) M or lower; a strong dark effect of the dye being observed under 2-fold increase of the dye concentration. Plaque-type mutants were formed up to the maximum approximately 1% at the survival approximately 2--10(-5); in comparison with other mutagens photo-sensitized mutagenesis in phage sd was lower. The significant increase in the number of plaque mutants was observed after the illumination of phage fraction surviving the pre-treatment with higher acridine orange concentration (greater than or equal to 2-10(-5)M).


Parsing nucleic acid pseudoknotted secondary structure: algorithm and applications.
Accurate prediction of pseudoknotted nucleic acid secondary structure is an important computational challenge. Prediction algorithms based on dynamic programming aim to find a structure with minimum free energy according to some thermodynamic ("sum of loop energies") model that is implicit in the recurrences of the algorithm. However, a clear definition of what exactly are the loops in pseudoknotted structures, and their associated energies, has been lacking. In this work, we present a complete classification of loops in pseudoknotted nucleic secondary structures, and describe the Rivas and Eddy and other energy models as sum-of-loops energy models. We give a linear time algorithm for parsing a pseudoknotted secondary structure into its component loops. We give two applications of our parsing algorithm. The first is a linear time algorithm to calculate the free energy of a pseudoknotted secondary structure. This is useful for heuristic prediction algorithms, which are widely used since (pseudoknotted) RNA secondary structure prediction is NP-hard. The second application is a linear time algorithm to test the generality of the dynamic programming algorithm of Akutsu for secondary structure prediction. Together with previous work, we use this algorithm to compare the generality of state-of-the-art algorithms on real biological structures.


Dimethyl Fumarate Suppresses the Proliferation of HTLV-1-infected T Cells by Inhibiting CBM Complex-triggered NF-B Signaling.
Adult T-cell leukemia (ATL) is a peripheral T-lymphocytic malignancy influenced by human T-cell leukemia virus type 1 (HTLV-1) infection. Aggressive ATL has a poor prognosis, therefore newer agents are desperately needed. We revealed that dimethyl fumarate (DMF) causes ATL cell death via inhibition of nuclear factor-kappa B (NF-B) and signal transducer and activator of transcription 3 signaling. Here, we evaluated the specific mechanism of DMF effects on NF-B signaling in MT-2 HTLV-1-infected T-cells. We examined the effects of DMF on the caspase recruitment domain family member 11 (CARD11)-BCL10 immune signaling adaptor (BCL10)-mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) (CBM) complex and upstream signaling molecules which are critical for NF-B signaling in MT-2 cells by immunoblotting. We also explored its effects on cell-cycle distribution. Furthermore, we assessed whether the BCL2 apoptosis regulator (BCL2)/BCL2-like 1 (BCL-xL) inhibitor navitoclax promoted the inhibitory effect of DMF on cell proliferation and apoptosis-associated proteins by trypan blue exclusion test and immunoblotting, respectively. DMF inhibited constitutive phosphorylation of CARD11 followed by suppression of inhibitory-B kinase α/β phosphorylation at serine in a dose-dependent fashion in MT-2 cells. Furthermore, DMF inhibited MALT1 and BCL10 expression in the same fashion. However, DMF did not prevent the phosphorylation of protein kinase C-β, an upstream signaling molecule of CARD11. Cell-cycle analysis highlighted that DMF treatment at 75 μM resulted in the accumulation of cells at the sub-G1 and G2/M phases. Navitoclax modestly promoted DMF-induced suppression of MT-2 cells via inhibition of cellular inhibitor of apoptosis protein-2 expression and c-JUN N-terminal kinase phosphorylation. The suppression of MT-2 cell proliferation by DMF makes its further evaluation as an innovative agent for therapy of ATL worthwhile.


The nature of the court today.
This article surveys the current landscape of the juvenile court. The original concept of this court, when implemented by state legislatures, took different organizational forms. The length of judges' assignments to this court varies as does the extent of their specialization. These courts differ from one another in numerous ways such as the minimum and maximum ages of their delinquency jurisdictions, the types of cases they are authorized to hear in addition to delinquency and child abuse and neglect, the extent to which referees or quasi-judicial hearing officers hear cases, whether or not the juvenile probation department is administered by the court, and the individual practices that constitute particular court cultures. Today change in one form or another is common to all juvenile courts as this institution adapts to contend with the delinquent behavior of young people and with the failures of adults responsible for the well-being of their children.


Method of surface energy investigation by lateral AFM: application to control growth mechanism of nanostructured NiFe films.
A new method for the specific surface energy investigation based on a combination of the force spectroscopy and the method of nanofriction study using atomic force microscopy was proposed. It was shown that air humidity does not affect the results of investigation by the proposed method as opposed to the previously used methods. Therefore, the method has high accuracy and repeatability in air without use of climate chambers and liquid cells. The proposed method has a high local resolution and is suitable for investigation of the specific surface energy of individual nanograins or fixed nanoparticles. The achievements described in the paper demonstrate one of the method capabilities, which is to control the growth mechanism of thin magnetic films. The conditions for the transition of the growth mechanism of thin Ni80Fe20 films from island to layer-by-layer obtained via electrolyte deposition have been determined using the proposed method and the purpose made probes with Ni coating.


Biodistribution, metabolism, and excretion of radioiodinated phospholipid ether analogs in tumor-bearing rats.
The phospholipid ether analog, [125I]-1-O-[12-(m-iodophenyl)dodecyl]propanediol-3-phosphocholine (NM-295) was synthesized and evaluated for its ability to visualize tumors. Preliminary studies were performed in rats bearing the Walker 256 carcinosarcoma. Most of the radioactivity was cleared from the animals during the first 24 hours. However, the tumor showed a decreased rate of clearance of radioactivity when compared with non-target tissue. This difference in the clearance rate allowed for excellent images of the tumor at 24 hours. Scintigraphic images compared favorably with other radioiodinated phospholipid ether analogs such as [125I-rac-1-O-[12-(m-iodophenyl)dodecyl]-2-O-methylglycero-3- phosphocholine (NM-294) and [125I]-12-(m-iodophenyl)dodecyl phosphocholine (NM-324). In contrast with the latter two compounds, however, tissue distribution studies revealed that NM-295 cleared at a much faster rate from all tissues, including tumor. In addition, within 24 hours following administration of NM-295, over 70% of the radioactivity was excreted as compared to 50% and 20% for NM-294 and NM-324, respectively. The majority of excreted radioactivity appeared in the urine for all three compounds. Thin-layer chromatography of urine and fecal extracts showed the presence of metabolites only. In contrast, lipid extracts of either liver or tumor demonstrated only the presence of the parent compound. Therefore, these data suggest that in each case it was the parent phospholipid analog that was taken up and retained by the tissues, while the metabolic product(s) was cleared and excreted from the animal.


Utilization of Objective Structured Clinical Examinations (OSCE) as an Assessment for Clinical Competency and Licensure: A survey of dental hygiene director's knowledge and attitudes.
Purpose: Objective Structured Clinical Examinations (OSCEs) have been established as a gold standard assessment for determining clinical competence. The Coalition for Dental Licensure Reform called for the acceptance of the Dental Licensure Objective Structured Clinical Examination (DLOSCE) to replace the live-patient examinations (LPE) for dental licensure, which are often viewed as biased, unreliable, and in some cases unethical. The purpose of this study was to assess dental hygiene program directors' awareness of and attitudes toward the DLOSCE, whether their curricula included OSCEs, and perceived barriers to implementing OSCEs.Methods: A nine-question electronic survey was developed, and pilot tested by five-dental hygiene program directors across three-dental hygiene institutions. The survey was emailed to the directors of all dental hygiene program directors in the United States (n=332). Descriptive statistics were used to analyze the data.Results: A response rate of 36% (n=121) was achieved. Nearly 30% of respondents were unaware of the developing DLOSCE, however, the majority (80%) were in favor of the acceptance of the examination. Nearly three-quarters of the respondents considered OSCEs as valid assessments of clinical competence, however, over half of the respondents reported not currently utilizing OSCEs in their curricula. Barriers reported were time (22%), perceived lack of best practices (21%), and lack of resources (18%). Respondents who currently employed OSCEs were more likely to agree they were both valid and reliable assessments (p=0.05).Conclusion: The majority of dental hygiene program directors were in favor of eliminating the single-encounter LPE in favor of an OSCE for licensure. However, more than half do not currently utilize OSCEs for clinical assessments. Further studies are needed to explore implementation of OSCEs in dental hygiene education, and how a potential dental hygiene licensure OSCE might impact the current curricula and licensure of dental hygienists in the United States.


The socioeconomic within-gender gap in informal caregiving among middle-aged women: Evidence from a Japanese nationwide survey.
Caregiving to older people with needs has been mainly dependent on informal care provision by female caregivers. Compared with the care burden gender gap, the within-gender gap in women's socioeconomic status (SES) has attracted less policy attention. We investigated the association between middle-aged women's SES and the likelihood of being a primary caregiver for elderly informal care, focusing on household income, women's marital status, work status, and educational background under the universal and public system of formal long-term care provision in Japan. We used repeated cross-sectional data from nationally representative household surveys conducted between 2010 and 2013 to obtain a sample of 2399 women aged between 40 and 60 years living in the same household as a care recipient. We conducted multiple logistic regression analysis to obtain odds ratios of being a primary caregiver in the household regressed on women's SES variables, adjusting for the characteristics of care recipients and household composition. The results showed that single women with lower education were likely to be primary caregivers when the care recipients had severe levels of care needs, whereas the association was null in the case of care recipients with milder conditions. The results indicated that women's low education and non-married status were related to a higher likelihood of becoming a primary caregiver of severely disabled elderly for reasons other than lower economic power. To emancipate socioeconomically vulnerable women from the care burden, a broader set of social, economic, and welfare policies are needed.


Glucose utilization by skeletal muscles in vivo in experimental hyperthyroidism in the rat.
In the fed state, hyperthyroidism increased glucose utilization indices (GUIs) of skeletal muscles containing a lower proportion of oxidative fibres. Glycogen concentrations were unchanged, but active pyruvate dehydrogenase (PDHa) activities were decreased. Hyperthyroidism attenuated the effects of 48 h of starvation to decrease muscle GUI. Glycogen concentrations and PDHa activities after 48 h of starvation were low and similar in euthyroid and hyperthyroid rats. The increase in glucose uptake and phosphorylation relative to oxidation and storage in skeletal muscle induced by hyperthyroidism may contribute to increased glucose re-cycling in the fed hyperthyroid state and to glucose turnover in the starved hyperthyroid state.


Influenza virus infection induces widespread alterations of host cell splicing.
Influenza A viruses (IAVs) use diverse mechanisms to interfere with cellular gene expression. Although many RNA-seq studies have documented IAV-induced changes in host mRNA abundance, few were designed to allow an accurate quantification of changes in host mRNA splicing. Here, we show that IAV infection of human lung cells induces widespread alterations of cellular splicing, with an overall increase in exon inclusion and decrease in intron retention. Over half of the mRNAs that show differential splicing undergo no significant changes in abundance or in their 3' end termination site, suggesting that IAVs can specifically manipulate cellular splicing. Among a randomly selected subset of 21 IAV-sensitive alternative splicing events, most are specific to IAV infection as they are not observed upon infection with VSV, induction of interferon expression or induction of an osmotic stress. Finally, the analysis of splicing changes in RED-depleted cells reveals a limited but significant overlap with the splicing changes in IAV-infected cells. This observation suggests that hijacking of RED by IAVs to promote splicing of the abundant viral NS1 mRNAs could partially divert RED from its target mRNAs. All our RNA-seq datasets and analyses are made accessible for browsing through a user-friendly Shiny interface (http://virhostnet.prabi.fr:3838/shinyapps/flu-splicing or https://github.com/cbenoitp/flu-splicing).


Minimal clinically important differences for the EQ-5D and QWB-SA in Post-traumatic Stress Disorder (PTSD): results from a Doubly Randomized Preference Trial (DRPT).
To determine the minimal clinically important difference (MCID) for the health-utility measures EuroQol-5 dimensions (EQ-5D) and Quality of Well Being Self-Administered (QWB-SA) Scale in PTSD patients. Two hundred patients aged 18 to 65 years with PTSD enrolled in a doubly randomized preference trial (DRPT) examining the treatment and treatment-preference effects between cognitive behavioral therapy and pharmacotherapy with sertraline and completed the EQ-5D and QWB-SA at baseline and 10-week post-treatment. The anchor-based methods utilized a Clinical Global Impression-Improvement (CGI-I) and Clinical Global Impression-Severity. We regressed the changes in EQ-5D and QWB-SA scores on changes in the anchors using ordinary least squares regression. The slopes (beta coefficients) were the rates of change in the anchors as functions of change in EQ-5D and QWB, which represent our estimates of MCID. In addition, we performed receiver operating characteristic (ROC) curve analysis to examine the relationship between the changes in EQ-5D and QWB-SA scores and treatment-response status. The MCIDs were estimated from the ROC curve where they best discriminate between treatment responders and non-responders. The distribution-based methods used small to moderate effect size in terms of 0.2 and 0.5 of standard deviation of the pre-treatment EQ-5D and QWB-SA scores. The anchor-based methods estimated the MCID ranges of 0.05 to 0.08 for the EQ-5D and 0.03 to 0.05 for the QWB. The MCID ranges were higher with the distribution-based methods, ranging from 0.04 to 0.10 for the EQ-5D and 0.02 to 0.05 for the QWB-SA. The established MCID ranges of EQ-5D and QWB-SA can be a useful tool in assessing meaningful changes in patient's quality of life for researchers and clinicians, and assisting health-policy makers to make informing decision in mental health treatment. Clinicaltrials.gov; Identifier: NCT00127673.


Pulmonary metabolism of exogenous enkephalins in isolated perfused rat lungs.
Metabolism of enkephalins during transit through the pulmonary circulation may be of significance in regulating systemic levels of these opioids. To determine whether Leu- and Met-enkephalin are metabolized by the pulmonary circulation, [3H]Tyr-Leu-enkephalin (10 microM) or [3H]Tyr-Met-enkephalin (10 microM) were each administered to isolated rat lungs perfused in a recirculating manner with a physiologic salt solution and a recently developed high-performance liquid radiochromatographic analytical method was used to identify and quantitate metabolites in the perfusion medium. Both Leu- and Met-enkephalin were metabolized in a curvilinear, time-dependent manner. The principal metabolites were identified as tyrosine and Tyr-Gly-Gly. Neither Tyr-Gly nor Tyr-Gly-Gly-Phe were detected in significant amounts. After a 20-min perfusion, residual Leu- or Met-enkephalin accounted for 28.4 and 21.5%, respectively, of the radioactivity present in the perfusate. In addition, 97% of the initial radioactivity for both Leu- and Met-enkephalin were found in the perfusion medium, indicating that neither the parent compounds nor metabolites were avidly sequestered in pulmonary tissue. The angiotensin converting enzyme inhibitor, captopril (18 microM) blocked the formation of Tyr-Gly-Gly and attenuated slightly the production of tyrosine. Inhibition of aminopeptidase with bestatin (116 microM) blocked the formation of tyrosine and enhanced production of Tyr-Gly-Gly. Inhibition of enkephalinase with thiorphan (0.3 microM) did not appear to affect Met-enkephalin metabolism. These observations indicate that in isolated, buffer perfused rat lungs Leu- and Met-enkephalin are metabolized during pulmonary transit by at least two enzymes, angiotensin converting enzyme and aminopeptidase.


Spatial-phase-shift imaging interferometry using a spectrally modulated white light source.
An extension of the white light spatial-phase-shift (WLSPS) for object surface measurements is described. Using WLSPS, surface measurements can be obtained from any real object image without the need of a reference beam, thus achieving inherent vibration cancellation. The surface topography is obtained by acquiring multiple images of an object illuminated by a spectrally modulated white light source and using an appropriate algorithm. The modulation of the light source obviates the need for the continuous phase delay to obtain the interferograms.


The association between area deprivation and dental caries in groups with and without fluoride in their drinking water.
In order to determine the association between social background and dental caries for subjects living in areas with and without fluoride in the drinking water, lifetime residents from Anglesey (0.7 mg/l F-, n = 196) and Chester/Bala (< 0.1 mg/l F-, n = 267) were examined. The mean age overall was 14.1 (+/- 0.3) years. For the Anglesey group, when differences in material deprivation were controlled, the mean DMFS was 2.9 compared with 4.3 in Chester/Bala, a difference of 33 per cent. Using multiple linear regression it was found that there was no interaction between material deprivation and water fluoridation. This suggested that absolute differences in dental caries between these areas with and without fluoride in the drinking water were similar for different strata of deprivation. It follows that percentage reductions in dental caries resulting from fluoridation of water supplies tended to be less in deprived than non deprived groups.


Is there a relationship between Haller Index and cardiopulmonary function in children with pectus excavatum?
This study aims to systematically examine the cardiopulmonary functions in children with pectus excavatum and to compare the obtained findings with the Haller Index. Between September 2017 and June 2018, medical records of a total of 31 patients (27 males, 4 females; mean age: 14.8±2.0 years; range, 9 to 18 years) with pectus excavatum were retrospectively analyzed. The patients were divided into Group 1 (<2.5), Group 2 (2.5 to 3.19), and Group 3 (>3.2) according to the Haller Index. All groups were systematically evaluated based on pulmonary function tests and echocardiography. Forced vital capacity, forced expiratory volume in 1 second, and the forced expiratory volume in 1 second/ forced vital capacity ratio were calculated. Left ventricular enddiastolic diameter, ejection fraction, mitral valve prolapses, and right ventricular cavity in the apical four-chamber position were evaluated with echocardiography. Of the patients, 19.4% were in Group 1, 38.7% in Group 2, and 41.9% in Group 3. The mean Haller Index value was 3.09±0.64. According to pulmonary function test results, 16.1% of the patients had restrictive disease and 6.5% had obstructive disease. There was a negative correlation between the index and forced expiratory volume in 1 second and forced vital capacity, and there was a statistically significant decrease in these values, as the Haller Index increased (p<0.017). There was a significant difference in the ejection fraction among the groups (p<0.001) and, as the Haller Index increased, ejection fraction statistically significantly decreased. Our study results show a negative correlation between the severity of pectus excavatum and pulmonary dysfunction and, as the severity increases, left ventricular function may be affected by the deformity. As a result, there seems to be a significant relationship between the severity of the deformity and cardiopulmonary functions.


Increased levels of tumor necrosis alpha and soluble vascular endothelial adhesion molecule-1 in the cerebrospinal fluid of patients with connective tissue diseases and multiple sclerosis.
The aim of the present study was to investigate the serum and cerebrospinal fluid (CSF) concentrations of tumor necrosis factor alpha (TNF-alpha) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with primary progressive form of multiple sclerosis (MS) and in patients with connective tissue diseases (CTDs) complicated with central nervous system (CNS) involvement. Stimulation of sVCAM-1 release by TNF-alpha was demonstrated on endothelial cells of brain vessels. We intended to present the TNF-alpha stimulated elevation of sVCAM-1 in the serum and CSF in any cases of CNS lesion. Fifty patients with several CTDs complicated with neuropsychiatric symptoms and 25 MS patients with primary chronic progressive form of the disease were selected. Determinations of TNF-alpha and sVCAM-1 were performed using ELISA methods. TNF-alpha and sVCAM-1 concentrations were elevated in the CSF of all patients, intrathecal synthesis of sVCAM-1 was demonstrated in MS patients. The changes in the TNF-alpha and sVCAM-1 concentrations were independent from the clinical manifestations, immunoserological changes and quality of neuropsychiatric symptoms of the CTDs. The stimulatory effect of TNF-alpha was more pronounced in the CSF of MS patients.


Metabolism studies of unformulated internally [3H]-labeled short interfering RNAs in mice.
Absorption, distribution, metabolism, and excretion properties of two unformulated model short interfering RNA (siRNAs) were determined using a single internal [(3)H]-radiolabeling procedure, in which the full-length oligonucleotides were radiolabeled by Br/(3)H -exchange. Tissue distribution, excretion, and mass balance of radioactivity were investigated in male CD-1 mice after a single intravenous administration of the [(3)H]siRNAs, at a target dose level of 5 mg/kg. Quantitative whole-body autoradiography and liquid scintillation counting techniques were used to determine tissue distribution. Radiochromatogram profiles were determined in plasma, tissue extracts, and urine. Metabolites were separated by liquid chromatography and identified by radiodetection and high-resolution accurate mass spectrometry. In general, there was little difference in the distribution of total radiolabeled components after administration of the two unformulated [(3)H]siRNAs. The radioactivity was rapidly and widely distributed throughout the body and remained detectable in all tissues investigated at later time points (24 and 48 hours for [(3)H]MRP4 (multidrug resistance protein isoform 4) and [(3)H]SSB (Sjögren Syndrome antigen B) siRNA, respectively). After an initial rapid decrease, concentrations of total radiolabeled components in dried blood decreased at a much slower rate. A nearly complete mass balance was obtained for the [(3)H]SSB siRNA, and renal excretion was the main route of elimination (38%). The metabolism of the two model siRNAs was rapid and extensive. Five minutes after administration, no parent compound could be detected in plasma. Instead, radiolabeled nucleosides resulting from nuclease hydrolysis were observed. In the metabolism profiles obtained from various tissues, only radiolabeled nucleosides were found, suggesting that siRNAs are rapidly metabolized and that the distribution pattern of total radiolabeled components can be ascribed to small molecular weight metabolites.


The role of interleukin-2 during homeostasis and activation of the immune system.
Interleukin-2 (IL-2) signals influence various lymphocyte subsets during differentiation, immune responses and homeostasis. As discussed in this Review, stimulation with IL-2 is crucial for the maintenance of regulatory T (T(Reg)) cells and for the differentiation of CD4(+) T cells into defined effector T cell subsets following antigen-mediated activation. For CD8(+) T cells, IL-2 signals optimize both effector T cell generation and differentiation into memory cells. IL-2 is presented in soluble form or bound to dendritic cells and the extracellular matrix. Use of IL-2 - either alone or in complex with particular neutralizing IL-2-specific antibodies - can amplify CD8(+) T cell responses or induce the expansion of the T(Reg) cell population, thus favouring either immune stimulation or suppression.


Hypergraph Spectral Analysis and Processing in 3D Point Cloud.
Along with increasingly popular virtual reality applications, the three-dimensional (3D) point cloud has become a fundamental data structure to characterize 3D objects and surroundings. To process 3D point clouds efficiently, a suitable model for the underlying structure and outlier noises is always critical. In this work, we propose a hypergraph-based new point cloud model that is amenable to efficient analysis and processing. We introduce tensor-based methods to estimate hypergraph spectrum components and frequency coefficients of point clouds in both ideal and noisy settings. We establish an analytical connection between hypergraph frequencies and structural features. We further evaluate the efficacy of hypergraph spectrum estimation in two common applications of sampling and denoising of point clouds for which we provide specific hypergraph filter design and spectral properties. Experimental results demonstrate the strength of hypergraph signal processing as a tool in characterizing the underlying properties of 3D point clouds.


Exposure and acceptance in the rehabilitation of adolescents with idiopathic chronic pain - a pilot study.
For chronic pain of unclear origin (idiopathic), pharmacological therapy is often insufficient. Psychological treatment strategies have been developed and evaluated for adults with chronic pain. However, few such studies are seen with youths, and to date there is limited empirical evidence regarding the effectiveness of psychological treatment for generalized musculoskeletal pain syndromes in adolescents. Acceptance and commitment therapy (ACT) is a development of cognitive behaviour therapy emphasizing exposure and acceptance. In this pilot study, 14 adolescents referred to the pain treatment service due to chronic debilitating pain were treated using an ACT-based approach. It was hypothesized that avoidance of pain and related stimuli was central to the disability seen among these patients, and that exposure and acceptance strategies could increase functioning and decrease pain. In contrast to emphasizing reductions in pain and distress, the treatment objective was to improve functioning by increasing the patient's ability to act in line with personal values in the presence of negative thoughts, emotions or bodily sensations. Following treatment, and retained at 3- and 6-month follow-up, improvements in functional ability, school attendance, catastrophizing and pain (i.e., intensity and interference) were seen. The outcome of this pilot study indicates that exposure and acceptance can been useful in the rehabilitation of adolescents with chronic debilitating pain. Randomized controlled studies are needed to empirically evaluate the effectiveness of this approach.


Real-time, non-destructive and in-field foliage yield and growth rate measurement in perennial ryegrass (Lolium perenne L.).
In-field measurement of yield and growth rate in pasture species is imprecise and costly, limiting scientific and commercial application. Our study proposed a LiDAR-based mobile platform for non-invasive vegetative biomass and growth rate estimation in perennial ryegrass (Lolium perenne L.). This included design and build of the platform, development of an algorithm for volumetric estimation, and field validation of the system. The LiDAR-based volumetric estimates were compared against fresh weight and dry weight data across different ages of plants, seasons, stages of regrowth, sites, and row configurations. The project had three phases, the last one comprising four experiments. Phase 1: a LiDAR-based, field-ready prototype mobile platform for perennial ryegrassrecognition in single row plots was developed. Phase 2: real-time volumetric data capture, modelling and analysis software were developed and integrated and the resultant algorithm was validated in the field. Phase 3. LiDAR Volume data were collected via the LiDAR platform and field-validated in four experiments. Expt.1: single-row plots of cultivars and experimental diploid breeding populations were scanned in the southern hemisphere spring for biomass estimation. Significant (P < 0.001) correlations were observed between LiDAR Volume and both fresh and dry weight data from 360 individual plots (R2 = 0.89 and 0.86 respectively). Expt 2: recurrent scanning of single row plots over long time intervals of a few weeks was conducted, and growth was estimated over an 83 day period. Expt 3: recurrent scanning of single-row plots over nine short time intervals of 2 to 5 days was conducted, and growth rate was observed over a 26 day period. Expt 4: recurrent scanning of paired-row plots over an annual cycle of repeated growth and defoliation was conducted, showing an overall mean correlation of LiDAR Volume and fresh weight of R2 = 0.79 for 1008 observations made across seven different harvests between March and December 2018. Here we report development and validation of LiDAR-based volumetric estimation as an efficient and effective tool for measuring fresh weight, dry weight and growth rate in single and paired-row plots of perennial ryegrass for the first time, with a consistently high level of accuracy. This development offers precise, non-destructive and cost-effective estimation of these economic traits in the field for ryegrass and potentially other pasture grasses in the future, based on the platform and algorithm developed for ryegrass.


Enhanced Electron Transfer Mediated by Conjugated Polyelectrolyte and Its Application to Washing-Free DNA Detection.
Direct electron transfer between a redox label and an electrode requires a short working distance (<1-2 nm), and in general an affinity biosensor based on direct electron transfer requires a finely smoothed Au electrode to support efficient target binding. Here we report that direct electron transfer over a longer working distance is possible between (i) an anionic π-conjugated polyelectrolyte (CPE) label having many redox-active sites and (ii) a readily prepared, thin polymeric monolayer-modified indium-tin oxide electrode. In addition, the long CPE label (∼18 nm for 10 kDa) can approach the electrode within the working distance after sandwich-type target-specific binding, and fast CPE-mediated oxidation of ammonia borane along the entire CPE backbone affords high signal amplification.


Murine leukemia virus mutant with a frameshift in the reverse transcriptase coding region: implications for pol gene structure.
The molecular defect in the nonconditional B-tropic MuLV pol mutant, clone 23 (Gerwin et al., J. Virol. 31:741-751, 1979), has been characterized by recombinant DNA technology. The entire mutant genome was cloned from an EcoRI digest of integrated cellular DNA into bacteriophage lambda Charon 4A and then subcloned at the EcoRI site of pBR322. NIH-3T3 cells transfected with the plasmid clone, termed pRTM (RTM, reverse transcriptase mutant), reproduced the properties of clone 23 virus-infected cells. In vivo ligation experiments involving cotransfection of subclones of pRTM and wild-type murine leukemia virus localized the defect in the clone 23 genome to an approximately 400-base-pair region in the pol gene between the SalI and XhoI sites. Sequence analysis of this region in the wild-type and mutant genomes revealed that the mutant has one additional C residue located 231 bases downstream of the last base of the SalI recognition site. This 1-base insertion brings three TGA termination codons into phase. Thus, the mutation in clone 23 leads to premature termination of translation, explaining the presence in clone 23 virions of a truncated polymerase with low levels of enzymatic activity. It was previously shown that the gag precursor is cleaved normally in clone 23-infected cells; therefore, if a virus-coded protease is involved in this cleavage, it must be encoded by sequences upstream of the reverse transcriptase region of the pol gene. This consideration, coupled with the observed molecular weight of the mutant polymerase and our precise determination of its C terminus, have led to a proposal for the genetic organization of the murine leukemia virus pol gene.


The cerebellum in sagittal plane--anatomic-MR correlation: 1. The vermis.
Correlation of thin (5-mm) sagittal high-field (1.5-T) MR images of three brain specimens and 11 normal volunteers with microtome sections of the human cerebellar vermis and hemispheres demonstrates that proton-density-weighted (long TR/short TE) and T2-weighted (long TR/long TE) spin-echo pulse sequences provide the greatest contrast between gray and white matter. These images also can display (1) the corpus medullare and primary white-matter branches to the vermian lobules, including the lingula, centralis, culmen, declive, folium, tuber, pyramis, uvula, and nodulus; and (2) several finer secondary branches to individual folia within the lobules. Surface features of the vermis including the deeper fissures (e.g., preculminate, primary, horizontal, and prepyramidal) and shallower sulci are best delineated by T1-weighted (short TR/short TE) and T2-weighted images, which provide greatest contrast between CSF and parenchyma. Given that the width of the normal vermis varied from 6 to 12 mm in our volunteers, the acquisition of thin slices (less than or equal to 5 mm) was required to minimize volume averaging of the cerebellar hemispheres with the vermis on a midline sagittal MR section. Knowledge of the detailed normal anatomy of the cerebellar vermis on sagittal MR images can assist in the identification of various pathologic alterations.


Multiple roles of vertebrate REV genes in DNA repair and recombination.
In yeast, Rev1, Rev3, and Rev7 are involved in translesion synthesis over various kinds of DNA damage and spontaneous and UV-induced mutagenesis. Here, we disrupted Rev1, Rev3, and Rev7 in the chicken B-lymphocyte line DT40. REV1-/- REV3-/- REV7-/- cells showed spontaneous cell death, chromosomal instability/fragility, and hypersensitivity to various genotoxic treatments as observed in each of the single mutants. Surprisingly, the triple-knockout cells showed a suppressed level of sister chromatid exchanges (SCEs), which may reflect postreplication repair events mediated by homologous recombination, while each single mutant showed an elevated SCE level. Furthermore, REV1-/- cells as well as triple mutants showed a decreased level of immunoglobulin gene conversion, suggesting participation of Rev1 in a recombination-based pathway. The present study gives us a new insight into cooperative function of three Rev molecules and the Polzeta (Rev3-Rev7)-independent role of Rev1 in vertebrate cells.


Spatial Metabolomics and Lipidomics Reveal the Mechanisms of the Enhanced Growth of Breast Cancer Cell Spheroids Exposed to Triclosan.
Triclosan (TCS), an antimicrobial compound, is known to have potential endocrine-disruptive properties, but the underlying toxic mechanisms at the metabolic level are not well understood. Here, we applied metabolomics and lipidomics combined with mass spectrometry imaging (MSI) to unveil the mechanisms of the enhanced growth of MCF-7 breast cancer cell spheroids (CCS) exposed to TCS. To obtain a wide coverage of metabolites and lipids by using MSI, we used techniques of matrix-assisted laser desorption/ionization (MALDI) and MALDI coupled with laser-postionization. The results showed that TCS and TCS sulfate penetrated into the entire area at 0-3 h and both localized in the inner area at 6 h. After 24 h, a portion of two compounds was released from CCS. Omic data indicated that TCS exposure induced alterations via several pathways, including energy metabolism and biosynthesis of glycerophospholipids and glycerolipids. Further MSI data revealed that the enhancement of energy supply in the peripheral area and the increase of energy storage in the inner area might contribute to the enhanced growth of MCF-7 breast CCS exposed to TCS. This study highlights the importance of integrating metabolite distributions and metabolic profiles to reveal the novel mechanisms of TCS-triggered endocrine disrupting effects.


Operando Characterization of Iron Phthalocyanine Deactivation during Oxygen Reduction Reaction Using Electrochemical Tip-Enhanced Raman Spectroscopy.
Electrochemical tip-enhanced Raman spectroscopy (EC-TERS) has been implemented to investigate the structure and activity of iron(II) phthalocyanine (FePc)-a model catalyst for the oxygen reduction reaction (ORR). Using EC-TERS, both reversible change and irreversible degradation to FePc have been observed during ORR. The reversible change in the Raman spectrum of FePc can be related to the FePc molecules that adapt a nonplanar geometry during catalysis. In contrast, the irreversible degradation of FePc is a consequence of FePc demetalation, leading to the subsequent formation of free base phthalocyanine. This observation affirms that FePc demetalation during ORR proceeds via a direct loss of Fe2+ and that carbon corrosion is not the operative mechanism. Importantly, the FePc demetalation process can be correlated with a loss of ORR activity suggesting that Fe-containing sites are essential for FePc to achieve high catalytic activity. This study establishes EC-TERS as a promising technique for the operando characterization of electrocatalytic reactions at the molecular scale.


The conserved C2 phospholipid-binding domain in Delta contributes to robust Notch signalling.
Accurate Notch signalling is critical for development and homeostasis. Fine-tuning of Notch-ligand interactions has substantial impact on signalling outputs. Recent structural studies have identified a conserved N-terminal C2 domain in human Notch ligands which confers phospholipid binding in vitro. Here, we show that Drosophila ligands Delta and Serrate adopt the same C2 domain structure with analogous variations in the loop regions, including the so-called β1-2 loop that is involved in phospholipid binding. Mutations in the β1-2 loop of the Delta C2 domain retain Notch binding but have impaired ability to interact with phospholipids in vitro. To investigate its role in vivo, we deleted five residues within the β1-2 loop of endogenous Delta. Strikingly, this change compromises ligand function. The modified Delta enhances phenotypes produced by Delta loss-of-function alleles and suppresses that of Notch alleles. As the modified protein is present on the cell surface in normal amounts, these results argue that C2 domain phospholipid binding is necessary for robust signalling in vivo fine-tuning the balance of trans and cis ligand-receptor interactions.


SERCA overexpression reduces reperfusion-mediated cardiac microvascular damage through inhibition of the calcium/MCU/mPTP/necroptosis signaling pathways.
Endothelial cells lining the microvasculature are particularly vulnerable to the deleterious effects of cardiac ischemia/reperfusion (I/R) injury, a susceptibility that is partially mediated by dysregulated intracellular calcium signals. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) functions to recycle calcium from the cytosol back to the endoplasmic reticulum. The purpose of this study is to explore the roles and mechanisms of SERCA in protecting microcirculation against cardiac I/R injury. Our data showed that overexpression of SERCA significantly reduced I/R-induced luminal stenosis and vascular wall edema, possibly through normalization of the ratio between eNOS and ET-1. I/R-induced erythrocyte morphological changes in micro-vessels could be reversed by SERCA overexpression through transcriptional inhibition of the expression of adhesive factors. In addition, SERCA-sustained endothelial barrier integrity reduced the likelihood of inflammatory cells infiltrating the myocardium. Furthermore, we found that SERCA overexpression attenuated intracellular calcium overload, suppressed mitochondrial calcium uniporter (MCU) expression, and prevented the abnormal opening of mitochondrial permeability transition pores (mPTP) in I/R-treated cardiac microvascular endothelial cells (CMECs). Interestingly, the administration of calcium activator or MCU agonist induced endothelial necroptosis in vitro and thus abolished the microvascular protection afforded by SERCA in reperfused heart tissue in vivo. In conclusion, by using gene delivery strategies to specifically target SERCA in vitro and in vivo, we identify a potential novel pathway by which SERCA overexpression protects microcirculation against cardiac I/R injury in a manner dependent on the calcium/MCU/necroptosis pathway. These findings should be taken into consideration in the development of pharmacological strategies for therapeutic interventions against cardiac microvascular I/R injury.


Calcitonin measurement in pediatrics: reference ranges are gender-dependent, validation in medullary thyroid cancer and thyroid diseases.
There is only limited information on serum reference ranges of calcitonin (CT) in infants, children and adolescents. This gap hampers valid diagnostics in patients with multiple endocrine neoplasia type 2 (MEN 2) and planned prophylactic thyroidectomy. In addition, age-dependent reference ranges for CT are necessary to define a cure in medullary thyroid carcinoma (MTC). We asked whether the reference ranges for CT levels were age- and gender-dependent in the serum of a pediatric cohort. A total of 6090 serum samples of 2639 subjects of the LIFE-Child cohort aged between 1 month and 17.9 years were analyzed by the CT electrochemiluminescence immunoassay (ECLIA). Reference intervals were estimated using the LMS method. For clinical validation the serum of 28 patients (61 samples) with MEN 2 and 106 patients (136 samples) with thyroid diseases were analyzed. CT levels showed a clear age- and gender-dependence with significantly higher values in boys (p<0.01). An accelerated decline of CT levels from newborn to children at the age of 4 and 5 years was observed for both sexes. A cure for MTC was demonstrated in 71% of MEN 2 patients after thyroidectomy, whereas 5 patients remained suspicious for micrometastasis or relapse. Only 1.5% of our patients with thyroid diseases revealed increased CT levels. This is the largest study to establish novel pediatric reference ranges from the CT values of healthy subjects. It allows a precise laboratory monitoring of CT in pediatric patients with MEN 2. Thyroid diseases did not have a relevant influence on CT levels in our pediatric cohort.


Primary tooth radicular resorption as a consequence of self-corrected ectopic eruption: 2 unusual cases.
Resorption of the distal root of primary second molars is a common consequence of ectopically erupting permanent first molars. Here, we report 2 unusual cases of primary molar root resorption caused by reversible (self-correcting) ectopic eruption of premolar and canine teeth. In both cases, severe pathological resorption of the mesial roots of primary molars was detected on routine dental radiographs, and the affected molars remained asymptomatic until exfoliation. The purpose of this paper was, using 2 case studies, to highlight the possibility of primary root resorption as a sequel of self-corrected ectopic eruption in locations not frequently diagnosed or reported.


Microvascular function and rheologic changes in hyperdynamic sepsis.
To investigate the rheologic changes and circulatory abnormalities at the microvascular level during severe sepsis. Prospective, controlled trial. Medical and surgical intensive care units of a university-affiliated hospital. Nine normal controls and eight adult patients with severe sepsis who met the study entrance criteria. Forearm blood flow was measured at rest and during reactive hyperemia by air plethysmography. Simultaneous hemodynamic measurements and blood samples for rheologic measurements were taken. Red blood cell deformability index was determined using a simple filtration procedure. Leukocyte aggregation in whole human blood was detected by using a leukergy test. Expression of the neutrophil adhesion molecule CD11b/CD18 was measured using a monoclonal antibody and flow cytometry. All data were taken within 24 hrs of the patient meeting criteria for entrance into the study. Cardiac output, oxygen delivery, and oxygen consumption measurements were consistent with the hyperdynamic phase of severe sepsis. Forearm blood flow was significantly (p < .05) greater in septic patients (21 +/- 3 mL/min) than in controls (12 +/- 2 to 36 +/- 5 mL/min (p < .05), while in the septic patients, forearm blood flow during reactive hyperemia increased from 21 +/- 3 to 32 +/- 4 mL/min. The ratio of forearm blood flow during reactive hyperemia to forearm blood flow at rest was 3.2 +/- 0.1 in the controls and 1.6 +/- 0.1 in the septic patients (p < .01). The red blood cell deformability index in whole blood was significantly (p < .01) decreased in the septic patients compared with the control subjects (0.41 +/- 0.07 vs. 0.98 +/- 0.08 mL/min). This difference remained true when the hematocrit was adjusted to 45% (0.82 +/- 0.06 vs. 1.04 +/- 0.06 mL/min; p < .05). Increased expression of the neutrophil adhesion molecule CD11b/CD18 was observed in septic patients (349 +/- 46 logarithmic fluorescence units) as compared with control subjects (233 +/- 26 logarithmic fluorescence units; p < .05). Leukergy was also significantly (p < .05) increased in septic patients (17.7 +/- 3.8%) as compared with control subjects (8.9 +/- 1.6%). A significant correlation was observed between leukergy and the expression of the neutrophil adhesion molecule CD11b/CD18 in controls and septic patients (r2 = .62; p < .01). Leukergy was also inversely correlated with whole blood red blood cell deformability index (r2 = .28; p < .05). Reactive hyperemia in the forearm is significantly diminished in patients with sepsis, suggesting impaired microvascular blood flow. Rheologic changes, including impaired red blood cell deformability, increased leukocyte aggregation, and endothelial adherence, may contribute to this abnormality by compromising effective capillary cross-sectional area.


Sleep influences on diaphragmatic motor unit discharge.
The discharge of motor units in the costal and crural regions of the diaphragm was studied in unrestrained cats during defined sleep and waking states. Changes in motor unit recruitment and pattern of activity were observed for different sleep-waking states. During periods of active waking, many motor units were recruited and discrimination of single-unit waveforms was difficult. However, in the transition from active to quiet waking, many diaphragmatic motor units ceased discharging, thus making it possible to discern single-unit waveforms. This cessation of motor unit activity continued during the transition from quiet waking (AW) to quiet sleep (QS) and from QS to rapid eye movement (REM) sleep. In some diaphragmatic motor units, discharge stopped completely during REM sleep and resumed only upon arousal. Thus, it was apparent that the recruitment of diaphragmatic motor units was markedly affected by the sleep-waking state. Changes in the patterns of discharge of diaphragmatic motor units also occurred during different sleep-waking states. Motor unit firing rate was typically slower in QS than AW. The rate of motor unit discharge during REM sleep varied considerably. Autocorrelation histograms demonstrated periodic patterns of motor unit discharge within inspiratory bursts. Intervals of repetitive peaks in the autocorrelation histograms ranged from 40 to 110 ms. These periodic patterns were strongest during AW and REM sleep and generally attenuated during QS. Cross-correlation histograms revealed the presence of synchronous activity between motor units in the diaphragm. This coupling of diaphragmatic motor unit discharge was also attenuated during QS compared with AW and REM sleep. Together, these results demonstrated a marked influence of the sleep-waking state on the neuromotor control of the diaphragm.


Implementation of mother-training program to improve parenting in pre-school age children: a randomized-controlled trial.
Preventing child abuse is an area of evaluation that should be deeply considered. The enhancing skill of maternal child care is also useful in this field. The aim of this study was to assess the impact of a training strategy to improve parenting in the families identified as at risk of child maltreatment. This randomized and controlled trial was conducted in 60 mothers allocated in the experimental and controlled group by a simple random allocation in Amirkola Children's Hospital in North Iran from January 2009 to December 2009. Mean score of maternal child abuse before and after intervention has been assessed by Conflict Tactics Scale for Parent and Child. Data analysis was based on the independent t-test, the paired t-test and one way analysis of variance. The mean and standard deviation of maternal child abuse score in the experimental group before and after intervention were 30.21 ± 1.21 and 23.31 ± 1.52, respectively, (P < 0.001, t = 6.63), but no difference was found in the control group. The training program on maternal skills to prevent child abuse was a powerful resource. Therefore, healthcare providers in the field of pediatric about parenting skills should be taught with a specific consideration.


Dural sac area is a more sensitive parameter for evaluating lumbar spinal stenosis than spinal canal area: A retrospective study.
Narrowing of the dural sac cross-sectional area (DSCSA) and spinal canal cross-sectional area (SCCSA) have been considered major causes of lumbar central canal spinal stenosis (LCCSS). DSCSA and SCCSA were previously correlated with subjective walking distance before claudication occurs, aging, and disc degeneration. DSCSA and SCCSA have been ideal morphological parameters for evaluating LCCSS. However, the comparative value of these parameters is unknown and no studies have evaluated the clinical optimal cut-off values of DSCSA and SCCSA. This study assessed which parameter is more sensitive.Both DSCSA and SCCSA samples were collected from 135 patients with LCCSS, and from 130 control subjects who underwent lumbar magnetic resonance imaging (MRI) as part of a medical examination. Axial T2-weighted MRI scans were acquired at the level of facet joint from each subject. DSCSA and SCCSA were measured at the L4-L5 intervertebral level on MRI using a picture archiving and communications system.The average DSCSA value was 151.67 ± 53.59 mm in the control group and 80.04 ± 35.36 mm in the LCCSS group. The corresponding average SCCSA values were 199.95 ± 60.96 and 119.17 ± 49.41 mm. LCCSS patients had significantly lower DSCSA and SCCSA (both P < .001). Regarding the validity of both DSCSA and SCCSA as predictors of LCCSS, Receiver operating characteristic curve analysis revealed an optimal cut-off value for DSCSA of 111.09 mm, with 80.0% sensitivity, 80.8% specificity, and an area under the curve (AUC) of 0.87 (95% confidence interval, 0.83-0.92). The best cut off-point of SCCSA was 147.12 mm, with 74.8% sensitivity, 78.5% specificity, and AUC of 0.85 (95% confidence interval, 0.81-0.89).DSCSA and SCCSA were both significantly associated with LCCSS, with DSCSA being a more sensitive measurement parameter. Thus, to evaluate LCCSS patients, pain specialists should more carefully investigate the DSCSA than SCCSA.


Test-retest reliability of the clinical, factor, and localization scales of the Luria-Nebraska Neuropsychological Battery.
Comparisons were made between initial test scores of the Luria-Nebraska Neuropsychological Battery, the Factor scales and the Localization scales, and a second set of scores derived from a readministration of the battery. Thirty random, unscreened, psychiatric inpatients with a wide variety of diagnoses served as subjects. Patient condition was not controlled, and no subjects were dropped from the data pool. Sixteen males and 14 females with a mean age of 31.8 years (SD = 12.7), mean education of 9.3 years (SD = 3.2), and a test-retest interval mean of 8.1 months (SD = 6.0) participated. All patients had significant emotional difficulties which resulted in repeated hospitalization, and all were cooperative with test procedures. Test-retest scores for the 14 Luria scales ranged from .83 to .96, averaging .89 and for the eight Localization scales, and the reliability ranged from a low of .78 to a high of .95, with a mean of .89. The factor scales test-retest reliability coefficients ranged from .01 to .96, with a .75 average for the 30 scales. All the correlations, except two on the Factor Scales, were significant at p less than .001. These results support the findings of an earlier study which focused on the 14 Luria scaled scores only. The data suggest that the Luria Battery is reliable over time.


[Experience of pregnancy, delivery, motherhood and knowledge transfer in 3 generations of mothers].
The purpose of the study was to describe how three generations of mothers have reacted to their pregnancies and deliveries and also how they feel about their maternity. Furthermore, the purpose was to illustrate the transfer of knowledge from one generation to another. Interviews have been made with three triads of generations, in all nine mothers. A phenomenological-hermeneutic onset has been chosen in order to analyse the narratives of the mothers. In the structural analyses the following themes came to hand: positive experiences/feelings, negative experiences/feelings, internal and external network and knowledge. The life-experiences of the maternity of the mothers were chiefly positive while experiences from pregnancy and childbirth were positive as well as negative. The knowledge of the mothers regarding childbirth and the bringing up of children were mostly conveyed in the everyday-contact during their early years, amongst mother-daughter-granddaughter. For the feeling of a successful experience during pregnancy, delivery and maternity, the internal network as well as the external turned out to be of great importance. In order to even better be able to provide for the needs of the expectant mothers or of those who have recently become mothers, an individual planning of care of both in- and out-patients within maternity- and childwelfare can be valuable.


Taming the technological tiger.
The proliferation of technology in hospitals has reached a point where care must be observed both in the introduction of new technology and in the use of existing technology. To achieve this goal, a behavioral modification on the part of hospitals, physicians, and the public must be brought about. Such a modification is best accomplished by the promotion of incentives within the system rather than by the imposition of stringent regulations that relegate provider and regulator to adversary positions.


Passive Smokers' Support for Stronger Tobacco Control in Indonesia.
Secondhand smoke exposure in Indonesia is high, especially compared to other Southeast Asian countries. Passive smoking leads to negative impacts on health and socio-economic well-being. Therefore, increasing the price of cigarettes and, thereby, increasing barriers to access to cigarettes could be an effective way to reduce smoking prevalence and protect people from second-hand smoke. This study aims to assess passive smokers' support for cigarette price increases in Indonesia. We perform a quantitative analysis with a cross-sectional design. The data were obtained through phone-based interviews of 1000 respondents aged 18 and older in Indonesia. Only 596 nonsmokers were included to be further analyzed in this study. This study found that 44.1% respondents have at least one family member who smokes. We considered the respondents' age, gender, education level, employment, and the number of people living in the respondent's household that are exposed to passive smoking. Our results demonstrate that passive smokers support stronger tobacco control such as increasing cigarette prices, regulating smoking behavior using a religious approach (Fatwa), and applying more effective pictorial health warnings.


Racial and Socioeconomic Disparities in Patients With Meningioma: A Retrospective Cohort Study.
Meningiomas are the most common intracranial neoplasms. Although genomic analysis has helped elucidate differences in survival, there is evidence that racial disparities may influence outcomes. African Americans have a higher incidence of meningiomas and poorer survival outcomes. The etiology of these disparities remains unclear, but may include a combination of pathophysiology and other factors. To determine factors that contribute to different clinical outcomes in racial populations. We retrospectively reviewed 305 patients who underwent resection for meningiomas at a single tertiary care facility. We used descriptive statistics and univariate, multivariable, and Kaplan-Meier analyses to study clinical, radiographical, and histopathological differences. Minority patients were more likely to present through the emergency department than an outpatient clinic (P < .0001). They were more likely to present with more advanced clinical symptoms with lower Karnofsky Performance scores, more frequently had peritumoral edema (P = .0031), and experienced longer postoperative stays in the hospital (P = .0053), and African-American patients had higher hospitalization costs (P = .046) and were more likely to be publicly insured. Extent of resection was an independent predictor of recurrence freedom (P = .039). Presentation in clinic setting trended toward an association with recurrence-free survival (P = .055). We observed no significant difference in gross total resection rates, postoperative recurrence, or recurrence-free survival. Minority patients are more likely to present with severe symptoms, require longer perioperative hospitalization, and generate higher hospitalization costs. This may be due to socioeconomic factors that affect access to health care. Targeting barriers to access, especially to subspecialty care, may facilitate more appropriate and timely diagnosis, thereby improving patient care and outcomes.


Radiofrequency ablation vs radiation therapy vs transarterial chemoembolization vs yttrium 90 for local treatment of liver cancer - a systematic review and network meta-analysis of survival data.
The comparative effectiveness of radiofrequency ablation (RFA), radiation therapy (RT), transarterial chemoembolization (TACE) and transarterial radioembolization with Yttrium-90 (Y90) relative to one another for the treatment of hepatocellular carcinoma (HCC) is unclear. The aim of this systematic review and network meta-analysis is to compare RFA to RT to TACE to Y90 in the treatment of HCC. Pubmed, Embase and Cochrane CENTRAL were searched up until April 19, 2021. Observational analyses with propensity score matched (PSM) cohort analyses and randomized controlled trials (RCT) reporting on two or more treatments relative to one another with respect to overall survival (OS) and/or progression free survival (PFS) were included. Survival data were extracted from Kaplan-Meier survival curves, and meta-analyzed using a multivariate network meta-analysis. After exclusions, 24 RCTs or PSM observational studies reporting on 5549 patients were included. While 1-year OS was greater for Y90 than TACE (RR 0.85, 95% CI: 0.72-0.99), all other 1-year OS comparisons across the 4 modalities yielded similar OS, and there were no differences across any modalities in 2-year and 3-year OS. TACE had a modest PFS advantage relative to RFA (RR 0.81, 95% CI: 0.68-0.95) and RT (RR 0.65, 95% CI: 0.51-0.83) at 2 years. All modalities assessed resulted in similar OS, which explains the current heterogenous practice patterns. This conclusion may assist in decision making based on administrative and patient costs, and implementation of these modalities. Other factors such as toxicity rate specific to individual patients could not be assessed using network meta-analysis and may also play a role in selection of modality. Further studies, ideally using PSM cohort analyses or RCT study design, reporting on OS, PFS, local control, complete response and toxicity are needed prior to drawing definitive conclusions.


Rare disease: a national survey of paediatricians' experiences and needs.
To describe the experiences of Australian paediatricians while caring for children with rare diseases, and their educational and resource needs. A brief online survey was developed and deployed to a representative sample of 679 paediatricians from the Australian Paediatric Surveillance Unit database. Of the 679 paediatricians, 242 (36%) completed the survey. The respondents were representative of all states and territories of Australia, urban and rural regions, and hospital and private practice. Almost all respondents (93%) had seen children with one or more of >350 different rare diseases during their career; 74% had seen a new patient with rare disease in the last 6 months. The most common problems encountered while caring for patients were: diagnostic delays (65%), lack of available treatments (40%), clinical guidelines (36%) and uncertainty where to refer for peer support (35%). Few paediatricians said that rare diseases were adequately covered during university (40%) or the Fellowship of the Royal Australasian College of Physicians (50%) training, and 28% felt unprepared to care for patients with rare diseases. Paediatricians wanted lists of specialist referral services (82%) and online educational modules about rare diseases (78%) that could be accessed via one online portal that consolidated multiple resources. Smartphone applications on rare diseases were favoured by paediatricians aged <50 years and by female paediatricians. An online educational portal should be developed and maintained for accuracy and currency of information to support dissemination of rare disease guidelines, referral pathways and coordination services relevant to Australian paediatricians and other health professionals who care for children with rare diseases.


Genetic and nosological aspects of schizotypal and borderline personality disorders. A twin study.
The aim of this study was to investigate etiological and nosological aspects of the schizotypal and borderline personality disorders. The sample consisted of 44 schizotypal, 15 schizotypal and borderline, and ten borderline same-sexed twin probands. The investigation of the co-twins indicated that genetic factors seemed to influence the development of the schizotypal, but not the borderline, personality disorders. The basic genetic core of the schizotypal syndrome seemed to consist of schizoid and paranoidlike features, and not psychoticlike cognitive and perceptual distortions. The study did not indicate any relationship between schizotypal and borderline personality disorders and affective and schizophrenic disorders. Further research is needed to confirm the independent status of the schizotypal syndrome in relation to the schizoid, avoidant, and paranoid personality disorders, and the borderline syndrome in relation to the histrionic , narcissistic, and antisocial personality disorders.


Intraoperative Parathyroid Hormone Levels at 5 min Can Identify Multigland Disease.
Intraoperative parathyroid hormone (IOPTH) monitoring is crucial in the treatment of primary hyperparathyroidism (PHPT). Often, the 5 min IOPTH levels fall, but not by the requisite 50 %. In such cases, the surgeon must decide whether to wait for additional levels or to continue exploration. This study aimed to evaluate the 5 min drop in IOPTH for distinguishing single adenomas (SA) from multigland disease. A retrospective analysis of a prospectively collected database was performed on PHPT patients who underwent initial curative parathyroidectomy between 2001 and 2013. Those with familial disease and those taking lithium or undergoing concomitant thyroidectomy were excluded from the analysis. For cases of double adenomas (DA) or hyperplasia (HA), the IOPTH values indicating additional glands were analyzed. The inclusion criteria were met by 1021 patients: 817 patients with SA (82.2 %), 99 patients with DA (10 %), and 78 with HA (7.9 %). The SA patients exhibited a 56.6 ± 4.9 % decline in IOPTH at 5 min compared with 21.3 ± 4.5 % of the DA patients and 22.5 ± 4.3 % of the HA patients (p < 0.01). Post hoc comparisons showed that the 5 min decrease in the SA group was significantly greater than in either the DA group or the HA group (p < 0.01). A 5 min percentage decline of 35 % best distinguished SA from multiglandular disease (85.3 vs. 24.9 %). The data suggest that when IOPTH level does not drop by at least 35 % at 5 min after excision, the surgeon should consider further exploration rather than wait for additional levels.


Influence of Conducting Polymer as Filler and Matrix on the Spectral, Morphological and Fluorescent Properties of Sonochemically Intercalated poly(o-phenylenediamine)/Montmorillonite Nanocomposites.
Nanocomposites consisting of spatially confined polymeric chains are of great interest due to their application in optoelectronic and photonics devices. Polymer layered silicate nanocomposites have attracted much attention in industry as well as academia owing to their remarkable physical and chemical properties as compared to conventional polymer nanocomposites. In present study, comparative investigation of the in-situ polymerization of poly(ophenylenediamine) intercalated montmorillonite has been done via two methods i.e using poly(o-phenylenediamine) as filler for MMT in one case and as matrix in the other. Intercalation and in-situ polymerization was confirmed by FT-IR, UV-Visible spectroscopy and XRD studies. TEM and optical microscopy studies confirmed the self-assembled morphology of nanocomposites while the fluorescence properties revealed that controlled emission could be achieved by confining poly(o-phenylenediamine) in MMT galleries. Intercalation and in-situ polymerization of o-phenylenediamine within MMT was successfully carried out using sonochemical technique. The growth of conducting polymers in the interlayer region of the clays has been shown to dramatically improve the properties of conducting polymers. Also, the loading of the polymer in the MMT has shown to influence the optical properties of the nanocomposite. IR spectra and XRD analysis confirmed the intercalation of POPD and its polymerization within the clay galleries. UV spectra revealed the doped state of POPD within clay galleries. Highest oscillator strength of 0.0137 was observed for POPD:MMT-1:0.25. Spherical self-assembled morphology was attained for POPD:MMT-1:0.25. XRD revealed major shift of 82.5 Å for the nanocomposite POPD:MMT-1:1, POPD:MMT-1:0.5 and MMT:POPD-1:0.25. Blue shift of 20 nm was noticed in the fluorescence spectra of POPD:MMT-1:0.25 and POPD:MMT-1:0.5 which was correlated to the intense interaction between NH of POPD with SiO of MMT. Highest quantum yield of 0.345 was achieved in case of POPD:MMT-1:0.25. The gallery confinement was found to control the optical as well as morphological characteristics of the nanocomposite. The controlled growth of POPD chains and their minimum aggregation resulted in the formation of self-assembled morphology. Thus, by choosing the optimum filler loading and by controlling its interaction with the matrix, nanocomposites with controlled architecture can be designed. It can be concluded that intercalation and exfoliation of nanocomposites largely depends on the experimental conditions such as type of conducting monomer, clay and organic modifier etc. The preparation technique and processing conditions influence the overall properties of the nanocomposites. Thus, by choosing the optimum filler loading and by controlling its interaction with the matrix, nanocomposites with controlled architecture can be designed. Few relevant patents to the topic have been reviewed and cited.


Reference values for fasting insulin in 75 year old females and males.
Reference intervals for insulin are often based on fairly small study groups with unknown body mass index (BMI). They are also much younger than most patients seeking care. These values are not optimal for elderly patients, as many biological markers change over time and adequate reference intervals are important for correct clinical decisions. We studied fasting insulin (f-insulin) values in a cohort of 698 75-year old non-diabetic males and females. The 2.5th and 97.5th percentiles for all individuals, males and females were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference intervals. There was a strong positive correlation between BMI and f-insulin, which led to the calculation of separate reference intervals for individuals with BMI ≤ 30. The reference interval for f-insulin for all study subjects was 1.74-18.27 mIU/L and for individuals with BMI ≤ 30 (n=574) the reference interval was 1.66-15.05 mIU/L.


Disorder-to-order transition in the CyaA toxin RTX domain: implications for toxin secretion.
The past decade has seen a fundamental reappraisal of the protein structure-to-function paradigm because it became evident that a significant fraction of polypeptides are lacking ordered structures under physiological conditions. Ligand-induced disorder-to-order transition plays a key role in the biological functions of many proteins that contain intrinsically disordered regions. This trait is exhibited by RTX (Repeat in ToXin) motifs found in more than 250 virulence factors secreted by Gram-negative pathogenic bacteria. We have investigated several RTX-containing polypeptides of different lengths, all derived from the Bordetella pertussis adenylate cyclase toxin, CyaA. Using a combination of experimental approaches, we showed that the RTX proteins exhibit the hallmarks of intrinsically disordered proteins in the absence of calcium. This intrinsic disorder mainly results from internal electrostatic repulsions between negatively charged residues of the RTX motifs. Calcium binding triggers a strong reduction of the mean net charge, dehydration and compaction, folding and stabilization of secondary and tertiary structures of the RTX proteins. We propose that the intrinsically disordered character of the RTX proteins may facilitate the uptake and secretion of virulence factors through the bacterial secretion machinery. These results support the hypothesis that the folding reaction is achieved upon protein secretion and, in the case of proteins containing RTX motifs, could be finely regulated by the calcium gradient across bacterial cell wall.


Spinal shortening and monosegmental posterior spondylodesis in the management of dorsal and lumbar unstable injuries.
Patients with spinal injuries have been treated in the past by laminectomy in an attempt to decompress the spinal cord. The results have shown insignificant improvement or even a worsening of neurologic function and decreased stability without effectively removing the anterior bone and disc fragments compressing the spinal cord. The primary indication for anterior decompression and grafting is narrowing of the spinal canal with neurologic deficits that cannot be resolved by any other approach. One must think of subsequent surgical intervention for increased stability and compressive posterior fusion with short-armed internal fixators. To analyze the results and efficacy of spinal shortening combined with interbody fusion technique for the management of dorsal and lumbar unstable injuries. Twenty-three patients with traumatic fractures and or fracture-dislocation of dorsolumbar spine with neurologic deficit are presented. All had radiologic evidence of spinal cord or cauda equina compression, with either paraplegia or paraparesis. Patients underwent recapping laminoplasty in the thoracic or lumbar spine for decompression of spinal cord. The T-saw was used for division of the posterior elements. After decompression of the cord and removal of the extruded bone fragments and disc material, the excised laminae were replaced exactly in situ to their original anatomic position. Then application of a compression force via monosegmental transpedicular fixation was done, allowing vertebral end-plate compression and interbody fusion. Lateral Cobb angle (T(10)-L(2)) was reduced from 26 to 4 degrees after surgery. The shortened vertebral body united and no or minimal loss of correction was seen. The preoperative vertebral kyphosis averaged +17 degrees and was corrected to +7 degrees at follow-up with the sagittal index improving from 0.59 to 0.86. The segmental local kyphosis was reduced from +15 degrees to -3 degrees. Radiography demonstrated anatomically correct reconstruction in all patients, as well as solid fusion. This technique permits circumferential decompression of the spinal cord through a posterior approach and posterior interbody fusion.