Increased risk of hypertension after gestational diabetes mellitus: findings from a large prospective cohort study.
Whether a history of gestational diabetes mellitus (GDM) is associated with an increased risk of hypertension after the index pregnancy is not well established. We investigated the association between GDM and subsequent risk of hypertension after the index pregnancy among 25,305 women who reported at least one singleton pregnancy between 1991 and 2007 in the Nurses' Health Study II. During 16 years of follow-up, GDM developed in 1,414 women (5.6%) and hypertension developed in 3,138. A multivariable Cox proportional hazards model showed women with a history of GDM had a 26% increased risk of developing hypertension compared with those without a history of GDM (hazard ratio 1.26 [95% CI 1.11-1.43]; P=0.0004). These results were independent of pregnancy hypertension or subsequent type 2 diabetes. These results indicate that women with GDM are at a significant increased risk of developing hypertension after the index pregnancy.


Design study of piezoelectric energy-harvesting devices for generation of higher electrical power using a coupled piezoelectric-circuit finite element method.
This paper presents a design study on the geometric parameters of a cantilever-based piezoelectric energy-harvesting devices (EHD), which harvest energy from motion (vibration), for the purpose of scavenging more energy from ambient vibration energy sources. The design study is based on the coupled piezoelectric-circuit finite element method (CPCFEM), previously presented by Dr. Zhu. This model can calculate the power output of piezoelectric EHDS directly connected to a load resistor and is used in this paper to obtain the following simulation results for variations in geometric parameters such as the beam length, width and thickness, and the mass length, width, and height: 1) the current flowing through and the voltage developed across the load resistor, 2) the power dissipated by the resistor and the corresponding vibrational displacement amplitude, and 3) the resonant frequency. By studying these results, straightforward design strategies that enable the generation of more power are obtained for each geometric parameter, and a physical understanding of how each parameter affects the output power is given. It is suggested that, in designing with the aim of generating more power, the following strategies be used: 1) for the beam, a shorter length, larger width, and lower ratio of piezoelectric layer thickness to total beam thickness are preferred in the case of a fixed mass; 2) for the mass, a shortened mass length and a higher mass height are preferred in the case of variation in the mass length and the mass height with mass width and mass value remain fixed, and a wider width and small mass height are preferred in the case of variation in mass width and height (mass length and value remain fixed; and 3) for the case of a fixed total length, a shorter beam length and longer mass length are preferred. With the design strategies, output powers from the device can reach above 1 to 2 mW/cm(3), much higher than the 200 microW/cm(3) currently achieved in the published literature. This is an encouraging prospect for enabling a wider range of applications of the EHDs. In addition, physical insights into how each parameter influences output power are also discussed in detail.


Advanced medical students' experiences and views on professionalism at Kuwait University.
Professionalism is a core competency in the medical profession worldwide. Numerous studies investigate how this competency is taught and learned. However, there are few reports on the students' views and experiences with professionalism especially in the Arab world. Our aim was to explore the experiences and views of Kuwait final-year medical students on professionalism. This was a questionnaire study of final-year medical students at Kuwait University (n = 95). Open- and close-ended questions were used to determine the students' experiences and views on: definition, teaching, learning, and assessment of professionalism. Eighty-five of the students completed the questionnaire (89.5%). A total of 252 attributes defining professionalism were listed by our respondents. The majority (98.0%) of these attributes were categorized under the CanMEDS theme describing professionalism as commitment to patients, profession, and society through ethical practice. The most helpful methods in learning about professionalism for the students were contact with positive role models, patients and families, and with their own families, relatives and peers. The students' rating of the quality and quantity of teaching professionalism in the institution was quite variable. Despite this, 68.2% of the students felt very or somewhat comfortable explaining the meaning of medical professionalism to junior medical students. Almost half of the students felt that their education had always or sometimes helped them deal with professionally-challenging situations. Majority (77.6%) of the students thought that their academic assessments should include assessment of professionalism and should be used as a selection criterion in their future academic careers (62.3%). Most of the students discussed and sought advice regarding professionally-challenging situations from their fellow medical students and colleagues. Seventy-five (88.2%) students did not know which organizational body in the institution deals with matters pertaining to medical professionalism. This study highlights the influence of the curriculum, the hidden curriculum, and culture on medical students' perception of professionalism. Medical educators should take in account such influences when teaching and assessing professionalism. Future research should aim at creating a framework of competencies that addresses professionalism in a context suitable for the Arabian culture.


Magnetoelectric Memory Based on Ferromagnetic/Ferroelectric Multiferroic Heterostructure.
Electric-field control of magnetism is significant for the next generation of large-capacity and low-power data storage technology. In this regard, the renaissance of a multiferroic compound provides an elegant platform owing to the coexistence and coupling of ferroelectric (FE) and magnetic orders. However, the scarcity of single-phase multiferroics at room temperature spurs zealous research in pursuit of composite systems combining a ferromagnet with FE or piezoelectric materials. So far, electric-field control of magnetism has been achieved in the exchange-mediated, charge-mediated, and strain-mediated ferromagnetic (FM)/FE multiferroic heterostructures. Concerning the giant, nonvolatile, and reversible electric-field control of magnetism at room temperature, we first review the theoretical and representative experiments on the electric-field control of magnetism via strain coupling in the FM/FE multiferroic heterostructures, especially the CoFeB/PMN-PT [where PMN-PT denotes the (PbMn1/3Nb2/3O3)1-x-(PbTiO3)x] heterostructure. Then, the application in the prototype spintronic devices, i.e., spin valves and magnetic tunnel junctions, is introduced. The nonvolatile and reversible electric-field control of tunneling magnetoresistance without assistant magnetic field in the magnetic tunnel junction (MTJ)/FE architecture shows great promise for the future of data storage technology. We close by providing the main challenges of this and the different perspectives for straintronics and spintronics.


Effect of music-movement synchrony on exercise oxygen consumption.
Past research indicates that endurance is improved when exercise movements are synchronised with a musical beat, however it is unclear whether such benefits are associated with reduced metabolic cost. We compared oxygen consumption (.VO2) and related physiological effects of exercise conducted synchronously and asynchronously with music. Three music tracks, each recorded at three different tempi (123, 130, and 137 beats.min-1), accompanied cycle ergometry at 65 pedal revolutions.min-1. Thus three randomly-assigned experimental conditions were administered: slow tempo asynchronous, synchronous, and fast tempo asynchronous. Exercise response of .VO2, HR, and ratings of perceived exertion (RPE), to each condition was monitored in 10 untrained male participants aged 21.7±0.8 years (mean±SD) who cycled for 12 min at 70% maximal heart rate (HR). Mean .VO2 differed among conditions (P=0.008), being lower in the synchronous (1.80±0.22 L.min-1) compared to the slow tempo asynchronous condition (1.94±0.21 L.min-1; P<0.05). There was no difference in HR or RPE among conditions, although HR showed a similar trend to .VO2. The present results indicate that exercise is more efficient when performed synchronously with music than when musical tempo is slightly slower than the rate of cyclical movement.


[Pyrimethamine and sulfadoxine as a preventive treatment for Pneumocystis carinii and Toxoplasma encephalitis].
Few studies have been reported on the potential usefulness of Fansidar combination at a fixed doses of pyrimethamine and sulfadoxine as prophylaxis for pneumonia by Pneumocystis carinii and toxoplasmic encephalitis. The clinical histories of the patients seen in our department from January, 1992 to December, 1994 who were prescribed pyrimethamine and sulfadoxine for the above prophylactic treatment were reviewed. One hundred fifty clinical histories fulfilled the requisites for evaluation. Thirty-seven patients (24%) had a previous diagnosis of AIDS, with the median CD4 count being of 134/mm3. The median follow up of treatment with Fansidar was of 31 months. Twenty-eight cases of pneumonia by Pneumocystis carinii (6.9 cases for 100 patients-years) and 10 cases of toxoplasmic encephalitis (2.5 cases for 100 patients-years) were diagnosed. These values are similar to those presented with respect to other pharmacologic interventions commonly used for the prevention of pneumonia by Pneumocystis carinii and toxoplasmic encephalitis and suggest that pyrimethamine and sulfadoxine is a useful alternative and requires consideration in individualized cases for the prophylaxis of these diseases.


Effect of dietary inclusion of pumpkin (Cucurbita pepo L) seed on nephrotoxicity occasioned by cisplatin in experimental rats.
The study evaluated the effect of dietary inclusion of pumpkin (Cucurbita pepo L) seed (raw and roasted) on nephrotoxicity caused by cisplatin in rats. Rats were divided into control group, cisplatin-induced nephrotoxic untreated group, nephrotoxic-treated groups with Methimazole, dietary regimen containing raw pumpkin seed (5% and 10%) and roasted pumpkin seed (5% and 10%) for 14 days. Results acquired uncovered that cisplatin intoxication significantly increased (p ≤ .05) the levels of renal biomarkers, arginase activity, 8-hydroxy-21 -deoxy guanosine (8-OHdG), malondialdehyde (MDA), and reactive oxygen species (ROS) levels as well as significant decrease in functional sulfhydryl groups, nitric oxide levels, and antioxidant enzyme activities in rats' kidney when compared to the control group. These adverse changes, due to cisplatin inebriation in rodents, were in any case, forestalled by pre-treatment with pumpkin seed inclusive diet. This holds promise for the use of pumpkin seed as a food supplement in the management of nephrotoxic-related disorders. PRACTICAL APPLICATIONS: These results suggest that roasted pumpkin seed appears to be more nephroprotective than the raw pumpkin seed through regulations of arginase activity, enhancement in the antioxidant system, suppression of renal markers and lipid peroxidation. This holds p-omise for the use of roasted pumpkin seed as a food supplement in the management nephrotoxic-related disorders.


Microhomology-mediated end joining: Good, bad and ugly.
DNA double-strand breaks (DSBs) are induced by a variety of genotoxic agents, including ionizing radiation and chemotherapy drugs for treating cancers. The elimination of DSBs proceeds via distinctive error-free and error-prone pathways. Repair by homologous recombination (HR) is largely error-free and mediated by RAD51/BRCA2 gene products. Classical non-homologous end joining (C-NHEJ) requires the Ku heterodimer and can efficiently rejoin breaks, with occasional loss or gain of DNA information. Recently, evidence has unveiled another DNA end-joining mechanism that is independent of recombination factors and Ku proteins, termed alternative non-homologous end joining (A-NHEJ). While A-NHEJ-mediated repair does not require homology, in a subtype of A-NHEJ, DSB breaks are sealed by microhomology (MH)-mediated base-pairing of DNA single strands, followed by nucleolytic trimming of DNA flaps, DNA gap filling, and DNA ligation, yielding products that are always associated with DNA deletion. This highly error-prone DSB repair pathway is termed microhomology-mediated end joining (MMEJ). Dissecting the mechanisms of MMEJ is of great interest because of its potential to destabilize the genome through gene deletions and chromosomal rearrangements in cells deficient in canonical repair pathways, including HR and C-NHEJ. In addition, evidence now suggests that MMEJ plays a physiological role in normal cells.


Functional copy-number alterations in cancer.
Understanding the molecular basis of cancer requires characterization of its genetic defects. DNA microarray technologies can provide detailed raw data about chromosomal aberrations in tumor samples. Computational analysis is needed (1) to deduce from raw array data actual amplification or deletion events for chromosomal fragments and (2) to distinguish causal chromosomal alterations from functionally neutral ones. We present a comprehensive computational approach, RAE, designed to robustly map chromosomal alterations in tumor samples and assess their functional importance in cancer. To demonstrate the methodology, we experimentally profile copy number changes in a clinically aggressive subtype of soft-tissue sarcoma, pleomorphic liposarcoma, and computationally derive a portrait of candidate oncogenic alterations and their target genes. Many affected genes are known to be involved in sarcomagenesis; others are novel, including mediators of adipocyte differentiation, and may include valuable therapeutic targets. Taken together, we present a statistically robust methodology applicable to high-resolution genomic data to assess the extent and function of copy-number alterations in cancer.


Cell clusters adopt a collective amoeboid mode of migration in confined nonadhesive environments.
Cell migration is essential to living organisms and deregulated in cancer. Single cell's migration ranges from traction-dependent mesenchymal motility to contractility-driven propulsive amoeboid locomotion, but collective cell migration has only been described as a focal adhesion-dependent and traction-dependent process. Here, we show that cancer cell clusters, from patients and cell lines, migrate without focal adhesions when confined into nonadhesive microfabricated channels. Clusters coordinate and behave like giant super cells, mobilizing their actomyosin contractility at the rear to power their migration. This polarized cortex does not sustain persistent retrograde flows, of cells or actin, like in the other modes of migration but rather harnesses fluctuating cell deformations, or jiggling. Theoretical physical modeling shows this is sufficient to create a gradient of friction forces and trigger directed cluster motion. This collective amoeboid mode of migration could foster metastatic spread by enabling cells to cross a wide spectrum of environments.


Identification of a protein-protein interaction between KCNE1 and the activation gate machinery of KCNQ1.
KCNQ1 channels assemble with KCNE1 transmembrane (TM) peptides to form voltage-gated K(+) channel complexes with slow activation gate opening. The cytoplasmic C-terminal domain that abuts the KCNE1 TM segment has been implicated in regulating KCNQ1 gating, yet its interaction with KCNQ1 has not been described. Here, we identified a protein-protein interaction between the KCNE1 C-terminal domain and the KCNQ1 S6 activation gate and S4-S5 linker. Using cysteine cross-linking, we biochemically screened over 300 cysteine pairs in the KCNQ1-KCNE1 complex and identified three residues in KCNQ1 (H363C, P369C, and I257C) that formed disulfide bonds with cysteine residues in the KCNE1 C-terminal domain. Statistical analysis of cross-link efficiency showed that H363C preferentially reacted with KCNE1 residues H73C, S74C, and D76C, whereas P369C showed preference for only D76C. Electrophysiological investigation of the mutant K(+) channel complexes revealed that the KCNQ1 residue, H363C, formed cross-links not only with KCNE1 subunits, but also with neighboring KCNQ1 subunits in the complex. Cross-link formation involving the H363C residue was state dependent, primarily occurring when the KCNQ1-KCNE1 complex was closed. Based on these biochemical and electrophysiological data, we generated a closed-state model of the KCNQ1-KCNE1 cytoplasmic region where these protein-protein interactions are poised to slow activation gate opening.


Subjective emotion trajectories in couple therapy and associations with improvement in relationship satisfaction.
Existing couple therapies are generally effective for reducing romantic relationship distress and divorce, but therapy outcomes remain poor for many. Outcomes can be improved through greater understanding of session-by-session therapeutic processes, particularly in real-world treatment settings. Modern couple therapy models commonly emphasize the importance of emotional experiences as key change processes, yet few empirical studies have tested the merits of this focus. The present study addresses this limitation by examining trajectories of subjective emotions and their association with change in a key relationship outcome, relationship satisfaction, among military veterans and their partners at a VA Medical Center. Partners rated their relationship satisfaction prior to couple therapy sessions and subjective emotions immediately after sessions. Consistent with hypotheses, both hard (e.g., anger) and soft (e.g., sadness) negative emotions decreased significantly over the course of therapy. Those couples with greater decreases in hard negative, but not soft negative, emotions showed significantly more improvement in relationship satisfaction. Positive emotions did not significantly change across couples in general, but those couples whose positive emotions did increase also showed more improvement in relationship satisfaction. These results suggest change in subjective emotions may be one process underlying improvement in couple therapy and lend empirical support to the emphasis on emotion-based change processes underlying acceptance-based and emotion-focused couple therapies.


Conformal field theories in fractional dimensions.
We study the conformal bootstrap in fractional space-time dimensions, obtaining rigorous bounds on operator dimensions. Our results show strong evidence that there is a family of unitary conformal field theories connecting the 2D Ising model, the 3D Ising model, and the free scalar theory in 4D. We give numerical predictions for the leading operator dimensions and central charge in this family at different values of D and compare these to calculations of ϕ4 theory in the ϵ expansion.


[Hereditary drusen in Bruch's membrane].
The left eye of a 71-year-old patient who had suffered from choroiditis guttata was removed immediately after death by enucleation. Histopathological studies revealed numerous nodular (hard) drusen, a wide variety of senile alterations of the pigment epithelium and Bruch's membrane, and the presence of multiple corpora arenacea in the subarachnoid space of the optic nerve. A new hypothesis concerning the development of hereditary drusen is advanced, postulating a disturbance of the lysosomal enzyme/inhibitor balance.


Predictors of the first heart failure hospitalization in patients who are stable survivors of myocardial infarction complicated by pulmonary congestion and/or left ventricular dysfunction: a VALIANT study.
We sought to assess the incidence of and prognostic factors for heart failure (HF) hospitalization among survivors of high-risk acute myocardial infarction (MI). We assessed the risk of an initial hospitalization for HF in 11 040 stable MI patients (no major non-fatal cardiovascular events or deaths within 45 days of randomization) without a prior history of HF enrolled in the VALIANT trial. Multivariable models were developed to identify independent predictors of HF and HF or cardiovascular death. Of 11 040 stable post-MI patients, 1139 (10.3%) developed HF during the median 25-month follow-up at a rate of approximately 3.4% per year. Most patients, 824 (72.3%), did not have a symptomatic recurrent MI between randomization and the onset of HF. The most important predictors of HF were older age, antecedent diabetes, prior MI before index MI, and reduced renal function. HF markedly increased the risk of death [HR(hazard ratio) 8.22; 95% CI(confidence interval), 7.49-9.01]. HF post high risk-MI occurs in a time-dependent fashion and is usually not directly related to re-infarction. Patients who experience HF beyond the acute phase have increased mortality. Long-term survivors of high-risk MI should be followed closely and treated aggressively beyond the acute MI period.


Inherent polarization entanglement generated from a monolithic semiconductor chip.
Creating miniature chip scale implementations of optical quantum information protocols is a dream for many in the quantum optics community. This is largely because of the promise of stability and scalability. Here we present a monolithically integratable chip architecture upon which is built a photonic device primitive called a Bragg reflection waveguide (BRW). Implemented in gallium arsenide, we show that, via the process of spontaneous parametric down conversion, the BRW is capable of directly producing polarization entangled photons without additional path difference compensation, spectral filtering or post-selection. After splitting the twin-photons immediately after they emerge from the chip, we perform a variety of correlation tests on the photon pairs and show non-classical behaviour in their polarization. Combined with the BRW's versatile architecture our results signify the BRW design as a serious contender on which to build large scale implementations of optical quantum processing devices.


[Debatable questions of strophanthin and spironolactone treatment in certain forms of acute myocardial infarct].
The results of clinical and instrumental examination of 67 patients and experimental findings provide evidence of myocardial resistance to cardiac glycosides in acute myocardial infarction complicated by the initial stage of cardiac insufficiency. It is suggested that symptoms of secondary hyperaldosteronism may develop in acute myocardial infarction and that medication with cardiac glycosides in combination with spironolactones is expedient.


Enhancing the Behaviour Change Wheel with synthesis, stakeholder involvement and decision-making: a case example using the 'Enhancing the Quality of Psychological Interventions Delivered by Telephone' (EQUITy) research programme.
Using frameworks such as the Behaviour Change Wheel to develop behaviour change interventions can be challenging because judgement is needed at various points in the process and it is not always clear how uncertainties can be resolved. We propose a transparent and systematic three-phase process to transition from a research evidence base to a behaviour change intervention. The three phases entail evidence synthesis, stakeholder involvement and decision-making. We present the systematic development of an intervention to enhance the quality of psychological treatment delivered by telephone, as a worked example of this process. In phase 1 (evidence synthesis), we propose that the capabilities (C), opportunities (O) and motivations (M) model of behaviour change (COM-B) can be used to support the synthesis of a varied corpus of empirical evidence and to identify domains to be included in a proposed behaviour change intervention. In phase 2 (stakeholder involvement), we propose that formal consensus procedures (e.g. the RAND Health/University of California-Los Angeles Appropriateness Methodology) can be used to facilitate discussions of proposed domains with stakeholder groups. In phase 3 (decision-making), we propose that behavioural scientists identify (with public/patient input) intervention functions and behaviour change techniques using the acceptability, practicability, effectiveness/cost-effectiveness, affordability, safety/side-effects and equity (APEASE) criteria. The COM-B model was a useful tool that allowed a multidisciplinary research team, many of whom had no prior knowledge of behavioural science, to synthesise effectively a varied corpus of evidence (phase 1: evidence synthesis). The RAND Health/University of California-Los Angeles Appropriateness Methodology provided a transparent means of involving stakeholders (patients, practitioners and key informants in the present example), a structured way in which they could identify which of 93 domains identified in phase 1 were essential for inclusion in the intervention (phase 2: stakeholder involvement). Phase 3 (decision-making) was able to draw on existing Behaviour Change Wheel resources to revisit phases 1 and 2 and facilitate agreement among behavioural scientists on the final intervention modules. Behaviour changes were required at service, practitioner, patient and community levels. Frameworks offer a foundation for intervention development but require additional elucidation at each stage of the process. The decisions adopted in this study are designed to provide an example on how to resolve challenges while designing a behaviour change intervention. We propose a three-phase process, which represents a transparent and systematic framework for developing behaviour change interventions in any setting.


The French Society of Neonatology's proposals for neonatal end-of-life decision-making.
Opinions and practice regarding end-of-life decisions in neonatal medicine show considerable variations between countries. A recent change of the legal framework, together with an ongoing debate among French neonatologists, led the French Society of Neonatology to reconsider and update its previous recommendations. To propose a set of recommendations on the ethical principles to be respected in the making and application of end-of-life decisions. A multidisciplinary working group on ethical issues in perinatal medicine composed of neonatologists, obstetricians and ethicists. Withholding or withdrawing life-sustaining treatment may be acceptable, and unreasonable therapeutic obstinacy is condemned. This implies that the child's best interests must always be the central consideration. Although the parents must be involved in the decision process so that they form an alliance with the healthcare team, and a collegial approach is of utmost importance, any crucial decision affecting the patient's life calls for individual medical responsibility. Because every newborn is rightfully an integral member of a human family, his or her dignity must be preserved. The goal of palliative care is to preserve the quality of a life, also at its end. The intention underlying an act has to be analyzed perceptively. Euthanasia, i.e. to perform an act with the deliberate intention to cause or hasten a patient's death, is legally and morally forbidden. Conversely, to withhold or withdraw a life-sustaining treatment can be justified when the intention is to cease opposing, in an unreasonable manner, the natural course of a disease. This statement provides the principles identified by French neonatologists on which to base their decisions concerning the ending of life. Arguments are set forth, discussed and compared with international statements and previously published considerations.


Synthetic amphiphilic peptide models for protein ion channels.
Ion channel proteins are important for the conduction of ions across biological membranes. Recent analyses of their sequences have suggested that they are composed of bundles of alpha-helices that associate to form ion-conducting channels. To gain insight into the mechanisms by which alpha-helices can aggregate and conduct ions, three model peptides containing only leucine and serine residues were synthesized and characterized. A 21-residue peptide, H2N-(Leu-Ser-Ser-Leu-Leu-Ser-Leu)3-CONH2, which was designed to be a membrane-spanning amphiphilic alpha-helix, formed well-defined ion channels with ion permeability and lifetime characteristics resembling the acetylcholine receptor. In contrast, a 14-residue version of this peptide, which was too short to span the phospolipid bilayer as an alpha-helix, failed to form discrete, stable channels. A third peptide, H2N-(Leu-Ser-Leu-Leu-Leu-Ser-Leu)3-CONH2, in which one serine per heptad repeat was replaced by leucine, produced proton-selective channels. Computer graphics and energy minimization were used to create molecular models that were consistent with the observed properties of the channels.


Syntheses, structures and magnetic properties of the lanthanide complexes of the pyrimidyl-substituted nitronyl nitroxide radical.
Four 2p-4f LnIII-radical complexes, [(NIT-2-Pm)Ln(hfac)3]·0.5C7H16 (NIT-2-Pm = 2-pyrimidyl-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxy-3-oxide, hfac = hexafluoroacetylacetonato, Ln = Tb (1), Dy (2), Ho (3) and Er (4)), and four 4f-2p-4f LnIII-radical-LnIII complexes, [(μ-NIT-2-Pm)Ln2(hfac)6(H2O)2]·0.5C7H16 (Ln = Tb (5), Dy (6), Ho (7) and Er (8)) have been synthesized and characterized structurally and magnetically. These compounds can be selectively obtained by controlling the reaction ratio of Ln(hfac)3·2H2O to the radical ligand NIT-2-Pm. The crystal structures show that in the former four complexes 1-4, the NIT-2-Pm radical acts as a terminal bidentate ligand chelating to one LnIII ion, while in 5-8, the NIT-2-Pm acts as a bridging ligand linking two LnIII ions to form a binuclear three-spin system. Magnetic studies revealed that complexes 1-4 and 6 show frequency-dependent ac magnetic susceptibilities, suggesting a possible single-molecule magnet behavior. To the best of our knowledge, complexes 3 and 4 are the first Ho-NIT and Er-NIT compounds showing slow magnetic relaxation. Compounds 5-8 represent a rare family of compounds showing the NIT bridged 4f-2p-4f three-spin motif, while complex 6 is a rare NIT bridged multinuclear lanthanide compound possessing SMM-like behaviour. Ab initio calculations were performed on all these complexes. The fitting of the magnetic susceptibilities of these compounds suggests weak antiferromagnetic coupling between the LnIII and NIT radical in 1-8 and weak ferromagnetic LnIII-LnIII interactions in 5-8.


Importance of microscopic stool examination in patients with diarrhoea.
Loose motion is a common symptom in patients reporting to our hospital. As it is a small set up where only facility for microscopic stool examination is available, we designed this study to know how much microscopic stool examination can help us in management of patients with diarrhoea. This cross-sectional descriptive study was conducted from January 2010 to April 2012, at Thall Scout Hospital, Hangoo, Khyber Pukhtoon Khwa, Pakistan. All the patients presenting with acute diarrhoea were included in the study. Patients older than 12 years of age were labelled as adults and those 12 years or younger as child. Stool specimens were collected using proper procedure and were examined microscopically. Of 494 stool specimens examined, 117 (23.68%) were positive for parasites or their ova, 34 (6.88%) had numerous pus and red blood cells and 343 (69.43%) patients had only stool of loose/soft consistency. Of 117 stool specimens positive for parasites, Giardia lamblia was detected in 67 (57.26%) patients, Entamoeba histolytica in 22 (18.80%) patients, H. nana in 10 (8.55%) patients, Tenea saginata in 8(6.84%) patients, hook worm in 6 (5.13%) patients, ascarids in 2 (1.71%) and Trichuris trichura in 2 (1.71%) patients. Among the parasitic causes of diarrhoea, giardia is the most common cause in our study with entameoba the second most common cause.


Psychological "resilience" and its correlates in chronic pain: findings from a national community sample.
The display of effective functioning despite exposure to stressful circumstances and/or internal distress is often termed 'resilience'. The study of resilience is believed to provide information about the nature of illness adaptation that is distinct from that obtained via the analysis of clinically impaired groups. In recent years, the concept of resilience has seen only limited exploration in the chronic pain literature. This article describes a multi-step procedure that first identifies resilience among chronic pain sufferers selected from a national sample of adults and then examines a set of its psychological correlates. Using the Profile of Chronic Pain:Screen (PCP:S), administered to a national sample of adults with chronic pain, a resilient subsample was identified on the basis of high scores on a Severity scale (at least 1 SD above the mean) combined with low scores (at least 1 SD below the mean) on scales assessing Interference and Emotional Burden. An age- and gender-matched non-resilient subsample was then selected who scored high (at least one standard deviation above the mean) on Severity, Interference, and Emotional Burden. The results of a series of comparisons between the resilient and non-resilient groups revealed significant differences favoring resilient individuals in coping style, pain attitudes and beliefs, catastrophizing tendencies, positive and negative social responses to pain, and health care and medication utilization patterns. The findings provide a preliminary foundation for further research aimed at understanding the nature and causal underpinnings of resilience in persons with chronic pain.


[Myositis ossifications progressiva].
Myositis ossificans progressiva (MOP) is a rare hereditary connective tissue disorder. Skeletal abnormalities and progressive ectopic ossifications are features of this condition. Diagnosis is often delayed because of heterogenous picture of MOP. Treatment is unknown, so MOP leads to prolonged disability.


Choristoma of the optic nerve: case report.
Optic nerve choristoma is a rare lesion composed of adipose tissue and smooth muscle involving the optic nerve. Few cases have been reported. A 20-year-old woman presented with a history of slowly progressive visual loss in the left eye. On T1-weighted magnetic resonance imaging studies, after frequency-selective fat saturation, an optic nerve mass was detected at the level of the optic canal with signal characteristics suggesting the diagnosis of optic nerve lipoma. At left frontotemporal craniotomy, the intracranial optic nerve appeared thin and atrophic proximally and was covered by abundant adipose tissue distally. Because no cleavage plane could be identified between the fatty lesion and the optic nerve, which appeared splayed within the adipose tissue, the nerve was resected after an intraoperative biopsy. The presence of two heterotopic mesodermal elements, a rim of adipose tissue admixed with bundles of mature smooth muscle, extending into the nerve septa, warranted a diagnosis of optic nerve choristoma. Optic nerve choristoma is an uncommon optic nerve lesion. Even if imaging studies are highly suggestive of the diagnosis, pathological confirmation is required because of the high adipose tissue content in the majority of cases. The lesion, most likely malformative and nonneoplastic in nature, can be the cause of progressive visual loss.


High-sensitivity troponin I in persistent atrial fibrillation - relation to NT-proBNP and markers of inflammation and haemostasis.
As cardiac troponins emerge as prognostic markers in atrial fibrillation (AF), it is important to identify mechanisms initiating and perpetuating cardiac troponin release, including its relations to other circulating biomarkers, in AF populations. We studied associations between high-sensitivity troponin I (hs-TnI) and markers representing myocardial wall tension, inflammation and haemostasis in persistent AF. In a double blind, placebo-controlled study, 171 patients referred for electrical cardioversion for persistent AF were randomised to receive candesartan or placebo for 3-6 weeks before and 6 months after cardioversion. Associations between baseline levels of hs-TnI and other biomarkers were investigated by bivariate non-parametric correlations (Spearman's correlation coefficient denoted rs). Baseline levels of hs-TnI correlated significantly, although weakly, with interleukin-6 (rs = 0.260, p = .003), N-terminal pro-B-type natriuretic peptide (rs = 0.251, p = .004), tissue-plasminogen activator antigen (rs = 0.233, p = .008), D-dimer (rs = 0.220, p = .013), E-selectin (rs = 0.207, p = .019), high-sensitivity C-reactive protein (rs = 0.202, p = .022) and vascular cell adhesion molecule-1 (rs = 0.189, p = .032). Hs-TnI correlated weakly with biomarkers representing myocardial wall tension, inflammation and haemostasis in persistent AF. The lack of any strong correlation between hs-TnI and the investigated biomarkers is in concert with the idea that hs-TnI release is an independent process parallel to other pathophysiological mechanisms associated with AF.


Multiscale-Engineered Muscle Constructs: PEG Hydrogel Micro-Patterning on an Electrospun PCL Mat Functionalized with Gold Nanoparticles.
The development of new, viable, and functional engineered tissue is a complex and challenging task. Skeletal muscle constructs have specific requirements as cells are sensitive to the stiffness, geometry of the materials, and biological micro-environment. The aim of this study was thus to design and characterize a multi-scale scaffold and to evaluate it regarding the differentiation process of C2C12 skeletal myoblasts. The significance of the work lies in the microfabrication of lines of polyethylene glycol, on poly(ε-caprolactone) nanofiber sheets obtained using the electrospinning process, coated or not with gold nanoparticles to act as a potential substrate for electrical stimulation. The differentiation of C2C12 cells was studied over a period of seven days and quantified through both expression of specific genes, and analysis of the myotubes' alignment and length using confocal microscopy. We demonstrated that our multiscale bio-construct presented tunable mechanical properties and supported the different stages skeletal muscle, as well as improving the parallel orientation of the myotubes with a variation of less than 15°. These scaffolds showed the ability of sustained myogenic differentiation by enhancing the organization of reconstructed skeletal muscle. Moreover, they may be suitable for applications in mechanical and electrical stimulation to mimic the muscle's physiological functions.


Relationship between evaluation of the teaching environment using DREEM scores and students' school learning scores.
This article was migrated. The article was marked as recommended. The results from a comprehensive survey of students' perceptions of their educational environment using the Dundee Ready Educational Environment Measure (DREEM) in our Medical School were compared with students' school learning scores. The subjects (n=495) were medical students beyond their first year of medical school. The students were asked to read each DREEM statement carefully and respond using a 5-point Likert-type scale, with responses ranging from strongly agree to strongly disagree. The mean total DREEM score was 113.4, and there was no significant difference among total DREEM scores for students in different school years. Sixth-year students scored significantly higher than those in the second year for the Academic Self-Perception and Social Self-Perception domains. Females had higher school learning scores and also had better total and Perception of Course Organizers DREEM scores. The DREEM score tended to be lower for those with lower school learning scores, with significant differences found for total, Academic Self-Perception and Social Self-Perception scores. This is the first study to use the DREEM score for Japanese medical students, and further prospective research is required to obtain a complete understanding of the results.


The role of joint engagement in the development of language in a community-derived sample of slow-to-talk children.
We explored whether supported (SJE) or coordinated joint engagement (CJE) between mothers recruited from the community and their 24-month-old children who were slow-to-talk at 18 months old were associated with child language scores at ages 24, 36, and 48 months (n = 197). We further explored whether SJE or CJE modified the concurrent positive associations between maternal responsive behaviours and language scores. Previous research has shown that SJE, maternal expansions, imitations, and responsive questions were associated with better language scores. Our main finding was that SJE but not CJE was consistently positively associated with 24- and 36-month-old expressive and receptive language scores, but not with 48-month-old language scores. SJE modified how expansions and imitations, but not responsive questions, were associated with language scores; the associations were evident in all but the highest levels of SJE. Further research is necessary to test these findings in other samples before clinical recommendations can be made.


How should we deal with misattributed paternity? A survey of lay public attitudes.
Increasing use of genetic technologies in clinical and research settings increases the potential for misattributed paternity to be identified. Yet existing guidance from the President's Commission for the Study of Ethical Problems in Biomedical and Behavioral Research and the Institute of Medicine (among others) offers contradictory advice. Genetic health professionals are thus likely to vary in their practice when misattributed paternity is identified, and empirical investigation into the disclosure of misattributed paternity is scarce. Given the relevance of this ethical dilemma and its significance to users of genetic services, this study aimed to investigate the attitudes of lay people with regard to the disclosure of misattributed paternity. An online questionnaire was hosted and advertised through Amazon's Mechanical Turk to 200 United States residents aged 18 years or older. Respondents were asked to rate (via a Likert scale) the ethical permissibility of possible actions a clinician may carry out when misattributed paternity is identified. Data analysis consisted of preliminary descriptive analysis, chi-squared analysis, and Wilcoxon signed-rank tests. There was no clear majority support for many of the options surveyed across different contexts, with only six out of ten scenarios displaying some general consensus. Men were more likely to support scenarios where the father is informed of paternity. Importantly, participants' views varied according to whether the desires of the father were previously expressed, suggesting that perceptions of the permissibility of a clinician's action will depend on the interests of all parties affected. This sample of the general public showed attitudes that were, at least to some degree, at variance with some professional guidelines. We give arguments for why at least some of these attitudes might be justified. We argue that case-specific judgments should be made and outline some of the relevant ethical considerations. While general guidelines ought to be considered, context-specific moral judgments cannot be avoided.


Imaging and therapy of gastrointestinal cancers with radiolabeled antibodies.
Radiolabeled antibodies are gaining in application for the imaging and therapy of cancers. Much progress has been made in the use of these new biological reagents for tumors of the gastrointestinal system, and the current status, problems and prospects are reviewed in this paper. It is apparent that murine monoclonal antibodies against cancer-associated antigens are safe and useful for revealing a high percentage of sites of tumor, including some missed by conventional radiological methods. Tumors as small as 0.5 cm can be disclosed, even in organs that are difficult for CT scan interpretation. Major advances in cancer imaging have involved the use of antibody fragments and simple, direct labeling methods for 99mTc, the most widely used radionuclide in nuclear medicine. The use of radiolabeled antibodies for cancer therapy has been a more difficult endeavor, particularly because of the delivery of inadequate rad doses to tumor. Advances include humanization of monoclonal antibodies and the improved attachment of therapeutic radionuclides, such as 90Y and 186Re or 188Re.


Prognosis of patients with benign paroxysmal positional vertigo treated with repositioning manoeuvres.
To evaluate the prognostic factors in benign paroxysmal positional vertigo (BPPV) treated with canalith repositioning procedures (CRPs). Retrospective study of consecutive BPPV cases diagnosed over three years. All patients underwent a complete otolaryngologic, audiologic and neurotologic evaluation. The appropriate CRP was performed, depending on the type of BPPV. Prognostic factors studied included age, sex, aetiology, duration of disease, abnormal electronystagmographic findings, canal involvement, improper performance of manoeuvres, response on first or repeat treatment, and presence of recurrences. One hundred and fifty-five patients were studied, 66 men and 89 women, with mean ages of 58.7 and 60.4 years, respectively. Age and the involvement of two canals or bilateral disease had an effect on initial treatment outcome and were correlated to increased recurrences but not to repeat treatment outcome. Secondary BPPV, abnormal electronystagmographic findings and improper performance of manoeuvres had a significant effect both on initial and repeat treatment, but not on recurrences. Sex and duration of symptoms had no effect. Canalith repositioning procedures provide fast and long-lasting treatment of BPPV in most patients. However, in a small subgroup of patients, failures may be noticed that may be attributed to various prognostic factors.


Positive and Negative Peer Influence in Residential Care.
The potential for negative peer influence has been well established in research, and there is a growing interest in how positive peer influence also impacts youth. No research, however, has concurrently examined positive and negative peer influence in the context of residential care. Clinical records for 886 residential care youth were used in a Hierarchical Linear Model analysis to examine the impact of negative and positive peer influence on naturally occurring patterns of serious problem behavior over time. Negative peer influence, where the majority of youth in a home manifested above the average number of serious behavior problems, occurred 13.7% of the time. Positive peer influence, where the majority of youth manifested no serious problem behaviors for the month, occurred 47.7% of the time. Overall, youth problem behavior improved over time. There were significantly lower rates of serious problem behavior in target youth during positive peer influence months. Conversely, there were significantly higher rates of serious problem behaviors in target youth during negative peer influence months. Negative peer influence had a relatively greater impact on target peers' serious behavior problems than did positive peer influence. Caregiver experience significantly reduced the impact of negative peer influence, but did not significantly augment positive peer influence. Months where negative peer influence was combined with inexperienced caregivers produced the highest rates of serious problem behavior. Our results support the view that residential programs for troubled youth need to create circumstances that promote positive and control for negative peer influence.


Isolation and expression of cDNA encoding the murine homologues of CD1.
The cDNA encoding the murine CD1.1 and CD1.2 gene products were isolated and their complete nucleotide sequence was determined. The nucleotide sequence and genomic organization of these molecules were similar to human CD1. The sequences in the alpha 1- alpha 3 domains were almost identical to previously reported genomic clones from a different strain, indicating limited polymorphism among these molecules. The predicted amino acid sequence in the transmembrane region and in the cytoplasmic tail was identical for CD1.1 and CD1.2. The two cDNA were also homologous in the 5' untranslated region but diverged in the 3' untranslated region. In contrast to human CD1, which is expressed at high levels in thymus, the expression of CD1 message in murine thymus was not detected in either thymus leukemia Ag positive or negative strains. Cell expressing murine CD1.1 were generated after transfer of the CD1.1 cDNA into murine cell lines. Immunoprecipitation with a rat anti-mouse CD1.1 mAb showed that the transfected CD1 was expressed on the cell surface as a beta 2-microglobulin-linked heterodimer. These results demonstrate that the murine and human CD1 genes, although encoding homologous transmembrane glycoproteins, are expressed in distinct tissues and may serve different functions.


Torsional angular dependence of 1J(Se,Se) and Fermi contact control of 4J(Se,Se): analysis of nJ(Se,Se) (n=1-4) based on molecular orbital theory.
(n)J(Se,Se) (n=1-4) nuclear couplings between Se atoms were analyzed by using molecular orbital (MO) theory as the first step to investigating the nature of bonded and nonbonded (n)J(Se,Se) interactions between Se atoms. The values were calculated by employing Slater-type triple xi basis sets at the DFT level, which were applied to structures optimized with the Gaussian 03 program. The contribution from each occupied MO (psi(i)) and psi(i)-->psi(a) (psi(a)=unoccupied MO) transition was evaluated separately. 1J(Se,Se) was calculated for the MeSeSeMe model compound, which showed a typical dependence on the torsion angle (phi(C(Me)SeSeC(Me))). This dependence explains the small values (< or =64 Hz) of 1Jobsd(Se,Se) observed for RSeSeR' and large values (330-380 Hz) of 1Jobsd(Se,Se) observed for 4-substituted naphtho[1,8-c,d]-1,2-diselenoles, which correspond to synperiplanar diselenides. The HOMO-->LUMO and HOMO-1-->LUMO transitions contribute the most to 1J(Se,Se) at phi=0 and 180 degrees to give large values of 1J(Se,Se), whereas various transitions contribute and cancel each other out at phi=90 degrees to give small values of 1J(Se,Se). Large 4Jobsd(Se,Se) values were also observed in the nonbonded Se...Se, Se...Se=O, and O=Se...Se=O interactions at naphthalene 1,8-positions. The Fermi contact (FC) term contributes significantly to 4J(Se,Se), whereas the paramagnetic spin-orbit (PSO) term contributes significantly to 1J(Se,Se). 2J(Se,Se) and 3J(Se,Se) were analyzed in a similar manner and a torsional angular dependence was confirmed for 3J(Se,Se). Depending on the structure, the main contribution to (n)J(Se,Se) (n=2, 3) is from the FC term, with a lesser contribution from the PSO term. Analysis of each transition enabled us to identify and clearly visualize the origin and mechanism of the couplings.


Skin vascular bed is a potential blood reservoir during heat stress.
To determine the potential role of the skin vasculature as a blood reservoir, we measured venous compliance (Cv), resistance (Rv), and their product, the time constant of venous drainage (tau sk = RvCv), in skin flaps from the hindlimbs of 15 dogs anesthetized with pentobarbital sodium at different core temperatures (Tc, 37-42 degrees C), skin temperature (Ts, 25.3-50.0 degrees C), and during an infusion of papaverine (5%). The vasculature of the flap was isolated, and a double-occlusion technique was used to measure the static pressure in the venous compartment. The blood volume of the flap was altered by changing either flow or outflow pressure (Pv). The change in volume was estimated from the change in weight of the flap with a force transducer. At Tc = 37 degrees C, Rv was 2.27 +/- 0.81 mmHg.min.ml-1.100 g-1 (means +/- SD), Cv was 0.17 +/- 0.06 ml.mmHg-1.100 g-1, and tau sk was 28.0 +/- 8.8 s. Rv decreased with elevated Tc, Ts, and with papaverine. Cv increased with a rise in Tc and Ts. Increasing Tc and Ts did not change tau sk, but the papaverine infusion shortened it. The lowest tau sk (20 s) occurred during maximal vasodilatation. This long tau sk indicates that the skin could serve as a blood reservoir during heat stress.


POH1 facilitates pancreatic carcinogenesis through MYC-driven acinar-to-ductal metaplasia and is a potential therapeutic target.
Pancreatic acinar cells undergo acinar-to-ductal metaplasia (ADM), a necessary process for pancreatic ductal adenocarcinoma (PDAC) initiation. However, the regulatory role of POH1, a deubiquitinase linked to several types of cancer, in ADM and PDAC is unclear. In this study, we investigated the role of POH1 in ADM and PDAC using murine models. Our findings suggest that pancreatic-specific deletion of Poh1 alleles attenuates ADM and impairs pancreatic carcinogenesis, improving murine survival. Mechanistically, POH1 deubiquitinates and stabilizes the MYC protein, which potentiates ADM and PDAC. Furthermore, POH1 is highly expressed in PDAC samples, and clinical evidence establishes a positive correlation between aberrantly expressed POH1 and poor prognosis in PDAC patients. Targeting POH1 with a specific small-molecule inhibitor significantly reduces pancreatic tumor formation, highlighting POH1 as a promising therapeutic target for PDAC treatment. Overall, POH1-mediated MYC deubiquitination is crucial for ADM and PDAC onset, and targeting POH1 could be an effective strategy for PDAC treatment, offering new avenues for PDAC targeted therapy.


Developing communicative competence: a longitudinal study of the acquisition of mental state terms and indirect requests.
This longitudinal study involving 101 Dutch four- and five-year-olds charts indirect request (IR) and mental state term (MST) understanding and investigates the role that Theory of Mind (ToM) and general linguistic ability (vocabulary, syntax, and spatial language) play in this development. The results showed basic understanding of IR and MST in four-year-olds, but full understanding had not been reached even at five years old. Furthermore, although ToM predicted both IR and MST when linguistic ability was not taken into account, this relationship was no longer significant once the language measures were added. Linguistic ability thus seems to play an important role in the development of both IR and MST. Additional analyses revealed that whereas syntactic ability was the primary predictor of IR, spatial language was the best predictor of MST, suggesting that IR relies primarily on general linguistic skills, but that more specific aspects of language may bootstrap MST.


Characterization of 4 mantle cell lymphoma cell lines.
Mantle cell lymphoma (MCL) is a distinct type of B-cell non-Hodgkin lymphoma characterized by t(11;14)(q13;q32) and cyclin D1 overexpression. The pathogenesis of MCL has not been comprehensively studied, which can be attributed in part to the paucity of well-characterized MCL cell lines. We collected 4 previously developed MCL cell lines and performed extensive characterization, including the susceptibly of these cell lines to transduction by adenovirus vectors. Our aim was to facilitate the establishment of an in vitro model that can be reliably used to study the pathogenesis of MCL. Standard techniques were used to compare the morphologic, immunophenotypic, and cytogenetic features of the 4 cell lines. In addition, Western blotting was used to investigate the presence of several cell cycle- and apoptosis-related proteins. TP53 DNA sequencing was also performed on the cell lines. The adenoviral transduction efficiency was assessed using an adenoviral vector carrying the gene encoding for the green fluorescence protein (Ad-GFP). All cell lines demonstrated evidence of t(11;14)(q13;q32) and overexpression of cyclin D1. Cyclin D2 was not detectable in all cell lines, whereas cyclin D3 was weakly expressed in JeKo-1 and SP-53. Other abnormalities of the cell cycle G1 phase regulatory pathway were detected, including loss of expression of p53 (JeKo-1) and p16(INK4a) (SP-53 and Granta 519), as well as TP53 mutation (Mino). All cell lines express high levels of cyclin E, c-Myc, Bcl-2, Bax, Bcl-x(L), and Mcl-1. Retinoblastoma protein is hyperphosphorylated in all cell lines. With the exception of Mino, MCL cell lines are highly transducible with adenoviral vectors. These cell lines are representative of MCL and can be used as an in vitro model to further explore the pathogenesis of this disease. The susceptibility of these cell lines to gene transfer provides opportunities to evaluate the importance of various oncogenes and tumor suppressor genes that may have an impact on developing effective therapeutic regimens for MCL.


Depression, anxiety, stress, and satisfaction with life: Moderating role of interpersonal needs among university students.
Depression, anxiety, and stress are ranked among the top mental health concerns faced by university students in recent times perpetuated by the proliferation of digitalization. Thus, this study was performed to assess the relationship between depression, anxiety, stress, and satisfaction with life, with interpersonal needs (perceived burdensomeness and thwarted belongingness) as moderators. A cross-sectional study using a convenient sampling method was conducted among 430 Malaysian private university students (Mean aged= 20.73 years; SD = 1.26 years). A self-administered questionnaire comprising the Depression, Anxiety and Stress Scale (DASS-21), Satisfaction with Life Scale, and Interpersonal Needs Questionnaire were used. Students who experienced lower depression and anxiety reported higher satisfaction with life under the influence of low perceived burdensomeness. Perceived burdensomeness, when coupled with depression (β = 0.76, p < 0.01) and anxiety (β = 0.79, p < 0.01), contributed 15.8% of variance in satisfaction with life. Students who experienced stress reported higher satisfaction with life under the influence of high thwarted belongingness (β = 0.73, p < 0.01), contributing 17.3% of the variance in satisfaction with life. For university students who experienced depression and anxiety symptoms, mental health practitioners may need to be cognizant of how to support students' education and management of their perceived burdensomeness perceptions.


Improving domain definition and outcome instrument selection: Lessons learned for OMERACT from imaging.
Imaging is one of the most rapidly evolving fields in medicine. Unfortunately, many imaging technologies have been applied as measurement instruments without rigorous evaluation of the evidence supporting their truth, discriminatory capability and feasibility for that context of use. The Outcome Measures in Rheumatology (OMERACT) Filter 2.1 Instrument Selection Algorithm (OFISA) is used to evaluate such evidence for use of an instrument in a research setting. The objectives of this work are to: [1] define and describe the key conceptual aspects that are essential for the evaluation of imaging as an outcome measurement instrument and [2] describe how these aspects can be assessed through OFISA. Experts in imaging and/or methodology met to formalize concepts and define key steps. These concepts were discussed with a team of patient research partners with interest in imaging to refine technical and methodological aspects into comprehensible information. A workshop was held at OMERACT2020 and feedback was incorporated into existing OMERACT process for domain and instrument selection. Three key lessons were identified: (1) a clear definition of the domain we want to measure is a necessary prerequisite to the selection of a good instrument, (2) the sources of variability that can directly influence the instrument should be clearly identified, (3) incorporating these first two lessons into OFISA improves the quality of every instrument selection process. The incorporation of these lessons in the updated OMERACT Filter (now 2.2) will improve the quality of the selection process for all types of outcome measurement instruments.


[Targeted parasite control of arthropod vectors' behavior].
The paper gives examples of targeted pathogenic modification of the behavior of arthropod vectors (insects and ticks). Behavior control by a vector occurs towards its increased contact with a host, thereby raising the likelihood of successful transmission of a parasite and completion of the latter's life cycle.


Postpartum responses of dairy cows supplemented with n-3 fatty acids for different durations during the peripartal period.
The objective of this study was to determine the effect of different durations of n-3 supplementation during the peripartal period on production and reproduction performance of Holstein dairy cows. Thirty-two Holstein dry cows (16 multiparous and 16 primiparous) were blocked within parity for similar expected calving dates 8 wk before calving. Cows within blocks were assigned randomly to 1 of 4 treatments: (1) control without n-3 fatty acid (FA) supplementation during the dry period; (2) n-3 FA supplementation during the whole dry period (8 wk); and (3) n-3 FA supplementation during the early dry period (first 5 wk; far-off), or (4) n-3 FA supplementation during the late dry period (last 3 wk; close-up). All cows received the same diet without n-3 FA after calving for the first 6 wk of lactation. Ovaries of each cow were examined 10, 17, 24, and 34 d from calving (calving=d 0) by transrectal ultrasonography to determine follicular development. Blood samples were collected at 14-d intervals starting on the first day of the dry period (8 wk before expected calving) to determine plasma concentrations of glucose, β-hydroxybutyrate, nonesterified fatty acids, urea N, aspartate aminotransferase, and insulin. Blood samples were also collected on d 1, 10, 17, 24, 31, and 38 postpartum for determination of progesterone concentration. Milk yield was recorded daily throughout the experiment and samples were taken twice weekly (Monday and Thursday mornings) for analysis of fat, protein, and lactose. Yields of milk and 4% fat-corrected milk and milk composition were similar among treatments except for fat proportion, which tended to be lower in cows that were fed n-3 FA throughout the dry period. We observed no differences among treatments for plasma concentrations of metabolites and hormones. The cows that were fed in the 3 n-3 FA treatments had larger ovulatory follicles compared with those fed the controlled diet. Treatments did not differ significantly in terms of the number of days open, day to first service, or number of services per pregnancy. In conclusion, n-3 FA supplementation throughout the dry period or in the early or late prepartal period had no carryover reproductive postpartum benefits and no effect on the production of Holstein dairy cows.


Transcriptional regulation of cannabinoid receptor-1 expression in the liver by retinoic acid acting via retinoic acid receptor-gamma.
Alcoholism can result in fatty liver that can progress to steatohepatitis, cirrhosis, and liver cancer. Mice fed alcohol develop fatty liver through endocannabinoid activation of hepatic CB(1) cannabinoid receptors (CB(1)R), which increases lipogenesis and decreases fatty acid oxidation. Chronic alcohol feeding also up-regulates CB(1)R in hepatocytes in vivo, which could be replicated in vitro by co-culturing control hepatocytes with hepatic stellate cells (HSC) isolated from ethanol-fed mice, implicating HSC-derived mediator(s) in the regulation of hepatic CB(1)R (Jeong, W. I., Osei-Hyiaman, D., Park, O., Liu, J., Bátkai, S., Mukhopadhyay, P., Horiguchi, N., Harvey-White, J., Marsicano, G., Lutz, B., Gao, B., and Kunos, G. (2008) Cell Metab. 7, 227-235). HSC being a rich source of retinoic acid (RA), we tested whether RA and its receptors may regulate CB(1)R expression in cultured mouse hepatocytes. Incubation of hepatocytes with RA or RA receptor (RAR) agonists increased CB(1)R mRNA and protein, the most efficacious being the RARgamma agonist CD437 and the pan-RAR agonist TTNPB. The endocannabinoid 2-arachidonoylglycerol (2-AG) also increased hepatic CB(1)R expression, which was mediated indirectly via RA, because it was absent in hepatocytes from mice lacking retinaldehyde dehydrogenase 1, the enzyme catalyzing the generation of RA from retinaldehyde. The binding of RARgamma to the CB(1)R gene 5' upstream domain in hepatocytes treated with RAR agonists or 2-AG was confirmed by chromatin immunoprecipitation and electrophoretic mobility shift and antibody supershift assays. Finally, TTNPB-induced CB(1)R expression was attenuated by small interfering RNA knockdown of RARgamma in hepatocytes. We conclude that RARgamma regulates CB(1)R expression and is thus involved in the control of hepatic fat metabolism by endocannabinoids.


Cannabidiol Drugs Clinical Trial Outcomes and Adverse Effects.
This review aims to present completed clinical trial data surrounding the medicinal benefits and potential side effects of the increasingly popular cannabidiol (CBD)-based drug products, specifically Epidiolex. The article is divided into two sections based on if the ailment being treated by this cannabinoid is classified as either physiological or neurological conditions. In addition to describing the current status, we also examined the different primary and secondary outcomes recorded for each study, which varies greatly depending on the funding source of the clinical trial. With the recent FDA-approval of Epidiolex, this review mainly focused on trials involving this specific formulation since it is the only CBD-based drug currently available to clinicians, although all other clinically trialed CBD(A) drugs were also examined. We hope this review will help guide future research and clinical trials by providing the various outcomes measured in a single review.


Local Cellular Responses to Titanium Dioxide from Orthopedic Implants.
We evaluated recently published articles relevant to the biological effects of titanium dioxide (TiO2) particles on local endogenous cells required for normal bone homeostasis, repair, and implant osseointegration. Structural characteristics, size, stability, and agglomeration of TiO2 particles alter the viability and behavior of multiple bone-related cell types. Resulting shifts in bone homeostasis may increase bone resorption and lead to clinical incidents of osteolysis, implant loosening, and joint pain. TiO2 particles that enter cells (through endocytosis or Trojan horse mechanism) may further disrupt implant retention. We propose that cellular responses to titanium-based nanoparticles contribute to pathological mechanisms underlying the aseptic loosening of titanium-based metal implants.


Influence of closed skill and open skill warm-ups on the performance of speed, change of direction speed, vertical jump, and reactive agility in team sport athletes.
In this study, we evaluated the efficacy of two different dynamic warm-up conditions, one that was inclusive of open skills (i.e., reactive movements) and one that included only preplanned dynamic activities (i.e., closed skills) on the performance of speed, change of direction speed, vertical jump, and reactive agility in team sport athletes. Fourteen (six male, eight female) junior (mean +/- SD age, 16.3 +/- 0.7 year) basketball players participated in this study. Testing was conducted on 2 separate days using a within-subjects cross-over study design. Each athlete performed a standardized 7-minute warm-up consisting of general dynamic movements and stretching. After the general warm-up, athletes were randomly allocated into one of two groups that performed a dynamic 15-minute warm-up consisting entirely of open or closed skills. Each of the warm-up conditions consisted of five activities of 3 minute duration. At the completion of the warm-up protocol, players completed assessments of reactive agility, speed (5-, 10-, and 20-m sprints), change of direction speed (T-test), and vertical jump. No significant differences (p > 0.05) were detected among warm-up conditions for speed, vertical jump, change of direction speed, and reactive agility performances. The results of this study demonstrate that either open skill or closed skill warm-ups can be used effectively for team sport athletes without compromising performance on open skill and closed skill tasks.


Transmission and dose-response experiments for social animals: a reappraisal of the colonization biology of Campylobacter jejuni in chickens.
Dose-response experiments characterize the relationship between infectious agents and their hosts. These experiments are routinely used to estimate the minimum effective infectious dose for an infectious agent, which is most commonly characterized by the dose at which 50 per cent of challenged hosts become infected-the ID(50). In turn, the ID(50) is often used to compare between different agents and quantify the effect of treatment regimes. The statistical analysis of dose-response data typically makes the assumption that hosts within a given dose group are independent. For social animals, in particular avian species, hosts are routinely housed together in groups during experimental studies. For experiments with non-infectious agents, this poses no practical or theoretical problems. However, transmission of infectious agents between co-housed animals will modify the observed dose-response relationship with implications for the estimation of the ID(50) and the comparison between different agents and treatments. We derive a simple correction to the likelihood for standard dose-response models that allows us to estimate dose-response and transmission parameters simultaneously. We use this model to show that: transmission between co-housed animals reduces the apparent value of the ID(50) and increases the variability between replicates leading to a distinctive all-or-nothing response; in terms of the total number of animals used, individual housing is always the most efficient experimental design for ascertaining dose-response relationships; estimates of transmission from previously published experimental data for Campylobacter spp. in chickens suggest that considerable transmission occurred, greatly increasing the uncertainty in the estimates of dose-response parameters reported in the literature. Furthermore, we demonstrate that accounting for transmission in the analysis of dose-response data for Campylobacter spp. challenges our current understanding of the differing response of chickens with respect to host-age and in vivo passage of bacteria. Our findings suggest that the age-dependence of transmissibility between hosts-rather than their susceptibility to colonization-is the mechanism behind the 'lag-phase' reported in commercial flocks, which are typically found to be Campylobacter free for the first 14-21 days of life.


Human infections with liver and minute intestinal flukes in Guangxi, China: analysis by DNA sequencing, ultrasonography, and immunoaffinity chromatography.
The prevalence of liver and intestinal fluke infections was determined by surveying inhabitants of Hengxuan, Fusui, and Shanglin villages which were known to be endemic for liver flukes in Guangxi, China in May 2010. A total of 718 people were examined for helminth eggs by the Kato-Katz thick smear technique, ultrasonography, immunoaffinity chromatography, and DNA sequencing. The overall egg positive rate was found to be 59.6% (28.0-70.6%) that included mixed infections with liver and intestinal flukes. Cases showing higher than 20,000 eggs per gram of feces (EPG) were detected between 1.3% and 16.2%. Ultrasonographic findings exhibited overall 28.2% (72 of 255 cases) dilatation rate of the intrahepatic bile duct. Clonorchis sinensis infection was detected serologically in 88.3% (38 of 43 cases) among C. sinensis egg positive subjects by the immunoaffinity chromatography using a specific antigen for C. sinensis. For differential diagnosis of the liver and intestinal flukes, more precise PCR and nucleotide sequencing for copro-DNA were performed for 46 egg positive cases. Mixed infections with C. sinensis and Metagonimus yokogawai were detected in 8 of 46 egg positive cases, whereas 29 specimens were positive for Haplorchis taichui. Ultrasonographic findings and immunoaffinity chromatography results showed usefulness, even in a limited way, in figuring out of the liver fluke endemicity.


Impairment of movement-associated brain deactivation in multiple sclerosis: further evidence for a functional pathology of interhemispheric neuronal inhibition.
Motor control demands coordinated excitation and inhibition across distributed brain neuronal networks. Recent work has suggested that multiple sclerosis (MS) may be associated with impairments of neuronal inhibition as part of more general progressive impairments of connectivity. Here, we report results from a prospective, multi-centre fMRI study designed to characterise the changes in patients relative to healthy controls during a simple cued hand movement task. This study was conducted at eight European sites using 1.5 Tesla scanners. Brain deactivation during right hand movement was assessed in 56 right-handed patients with relapsing-remitting or secondary progressive MS without clinically evident hand impairment and in 60 age-matched, healthy subjects. The MS patients showed reduced task-associated deactivation relative to healthy controls in the pre- and postcentral gyri of the ipsilateral hemisphere in the region functionally specialised for hand movement control. We hypothesise that this impairment of deactivation is related to deficits of transcallosal connectivity and GABAergic neurotransmission occurring with the progression of pathology in the MS patients. This study has substantially extended previous observations with a well-powered, multicentre study. The clinical significance of these deactivation changes is still uncertain, but the functional anatomy of the affected region suggests that they could contribute to impairments of motor control.


Iliac arteriovenous fistula presenting with ascites.
Arteriovenous fistula presents rarely with ascites. Diagnosis, with an elusive clinical presentation, is often incidental or delayed. A 35-year-old woman presented with ascites and cardiac decompensation. Contrast enhanced computed tomography revealed arteriovenous fistula between the left common iliac artery aneurysm and the left common iliac vein. The patient underwent endovascular treatment with arterial access was performed, with implantation of a stent graft in the iliac artery to cover the fistulous communication. At follow-up 1 month later, she was asymptomatic without ascites. Arteriovenous fistula should be considered in the differential diagnosis of patients with ascites and cardiac decompensation. The endovascular treatment of the arteriovenous fistula should be considered as a first line option.


La3+, Mn2+, and Ni2+ effects on Ca2+ pump and on Na+-Ca2+ exchange in bullfrog ventricle.
45Ca washout from ventricles of the bullfrog was followed through an automated technique previously described. Lanthanum decreased the fractional rate of loss of 45Ca (by 67% at the saturating concentration, 1 mM, for this effect of the trivalent cation). In contrast, both manganous and nickel ions decreased the fractional rate of loss of 45Ca in 21 of the 30 ventricles studied. In the remainder of the experiments these ions increased this rate. This augmentation of the rate of 45Ca efflux by manganese and nickel could be converted consistently to an inhibition by experimental maneuvers known to increase the intracellular concentration of sodium-potassium-free washout solution, dihydroouabain. These results are consistent with the hypothesis that manganese and nickel increase 45Ca efflux through a process of sarcolemmal manganese-calcium (or nickel-calcium) exchange, operating through the sodium-calcium exchanger. Support for this interpretation was obtained in the further observation that the rate of loss of radioactive nickel from 63Ni-loaded ventricles was monotonically related to the extracellular concentration of calcium. Thus the augmenting effect of the divalent cations on 45Ca efflux appears to be mediated by the sodium-calcium exchanger. That the inhibitory effect arises from an action of the cations on the ATP-dependent component of 45Ca efflux is indicated by the fact that it disappears after vigorous ATP depletion in the presence of cyanide and 2-deoxy-D-glucose.


Pilot study of the Collaborative Assessment and Management of Suicidality-Group.
Few evidence-based options exist for outpatient treatment of patients at risk of suicide, and to-date almost all research has focused on individually delivered psychotherapy. Group therapy for veterans at risk of suicide is a promising alternative. Thirty veterans receiving care at an urban Veterans Affairs Medical Center in the southern United States were randomized to either care as usual (CAU) or to CAU plus the Collaborative Assessment and Management of Suicide-Group (CAMS-G). Veterans were assessed prior to randomization to condition and at 1, 3, and 6 months post-randomization on a range of suicide-specific measures, burdensomeness, belonging, treatment satisfaction, and group cohesion. Across measures and follow-up assessments, veterans in CAMS-G reported good satisfaction with the intervention, a sense of cohesion with other members of the group, and reduced symptom distress. Veterans in both conditions reported decreases in suicidal ideation and behavior, with CAMS-G participants potentially improving slightly faster. This description of CAMS-G for veterans adds to the growing literature on suicide-specific interventions and supports the need for additional research to determine if wide-spread rollout is justifiable.


[Normalization of the functional regulation of the thyroid as a criterion of the remission of diffuse toxic goiter following antithyroid treatment].
Triiodothyronine test was applied to 72 patients with toxic goiter treated with antithyroid drugs to reveal whether the regulation of thyroid function was normal. During a one-year observation period the patients underwent check-ups every third month, then during three years the examination was performed every half a year. A final examination was 10 years after the treatment. In the process of treatment the regulation of thyroid function recovered in 44 (68.7%) out of 64 patients, but further the relapse of goiter was recorded in 10 of them. Among 20 patients whose regulation of thyroid function failed to be normalized after a 18-months treatment the relapse was noted in 17 patients (85%). 27 patients (42.2%) had a relapse ten years after the exposure. The lack of normal regulation of thyroid function revealed with T3 test permits the relapse of toxic goiter to be predicted.


Outcomes of transcatheter versus surgical aortic valve replacement among solid organ transplant recipients.
There is a paucity of data regarding the outcomes of transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) among solid-organ transplant recipients. Temporal trends in hospitalizations for aortic valve replacement among solid-organ transplant recipients were determined using the National Inpatient Sample database years 2012-2017. Propensity matching was conducted to compare admissions who underwent TAVR versus SAVR. The primary outcome was in-hospital mortality. The analysis included 1,730 hospitalizations for isolated AVR; 920 (53.2%) underwent TAVR and 810 (46.7%) underwent SAVR. TAVR was increasingly utilized for solid-organ transplant recipients (Ptrend = 0.01), while there was no change in the number of SAVR procedures (Ptrend = 0.20). The predictors of undergoing TAVR for solid-organ transplant recipients included older age, diabetes, and prior coronary artery bypass surgery, while TAVR was less likely utilized in small-sized hospitals. TAVR was associated with lower in-hospital mortality after matching (0.9 vs. 4.7%, odds ratio [OR] 0.19; 95% confidence interval [CI] 0.11-0.35, p < .001) and after multivariable adjustment (OR 0.07; 95% CI 0.03-0.21, p < .001). TAVR was associated with lower rate of acute kidney injury, acute stroke, postoperative bleeding, blood transfusion, vascular complications, discharge to nursing facilities, and shorter median length of hospital stay. There was no difference between both groups in the use of mechanical circulatory support, hemodialysis, arrhythmias, or pacemaker insertion. This contemporary observational nationwide analysis showed that TAVR is increasingly performed among solid-organ transplant recipients. Compared with SAVR, TAVR was associated with lower in-hospital mortality, complications, and shorter length of stay.


Non-traumatic myositis ossificans in the paraspinal muscles.
Myositis ossificans circumscripta (MOC) is a benign condition of heterotopic bone formation that remains difficult to distinguish from soft-tissue and bone malignancies. We describe an unusual case of non-traumatic MOC in the cervical paraspinal muscle. The diagnosis could only be established after surgery and histological examination. We present a review of the literature on this subject and discuss some related features (radiological and histological).


Effect of supervised exercise intervention on metabolic risk factors and physical fitness in Chinese obese children in early puberty.
The aim of this paper was to study the effect of long-term supervised exercise-induced weight maintenance on metabolic risk factors and physical fitness in obese children in early puberty. A total of 49 obese children aged 12-14 years were divided into control and exercise groups. The children in the exercise group accepted exercise intervention supervised by a professional sports teacher for 9 of the 12 months. All participants in both groups received health education once every 3 months. Anthropometry and fasting serum lipids, glucose, insulin and homeostatic model assessment for insulin resistance (HOMA-IR) were measured at months 0, 3, 9, 12 of the intervention. Physical fitness was determined before and after intervention. After the intervention (i) BMI was reduced by 0.6 (P < 0.05) in the exercise group, but increased by 0.5 (P < 0.05) in the control group, compared with the pre-intervention level at the end of 9-month intervention; (ii) Triglyceride levels in the exercise group significantly decreased by 23.1% by 3 months (P < 0.05), and by 30.2% after 9 months (P < 0.05), but increased by 50% (P < 0.05) in the control group; high density lipoprotein-cholesterol (HDL-C) decreased more by 35% (P < 0.05) in the controls than in the exercise group (P < 0.05); (iii) Fasting serum glucose, insulin level and HOMA-IR decreased, respectively, by 23.1%, 36.6% and 48.5% in the exercise group at 9 months (P < 0.05), whereas glucose levels increased by 10.9% (P < 0.05) in the control group; (iv) Exercise performance, such as upper- and lower-limb strength, flexibility and endurance, were enhanced by 17.9%, 12.3%, 22.3% and 20.4% (P < 0.01), respectively and (v) At 12 months, i.e. 3 months after terminating the supervised exercise, serum triglycerides, glucose, insulin and HOMA-IR level all returned to the pre-intervention level. Supervised decrement exercise can effectively slow the progress of obesity, improve insulin sensitivity and metabolic risk factors, but once the supervised exercise is stopped, the health benefits weaken or vanish. The key to helping these obese children is for them to cultivate good exercise habits which are sustained throughout their lives.


[Urinary tract infections].
During the past ten years, new concepts on host-parasite interaction have allowed better understanding of the pathogenesis of urinary tract infections (UTI). In addition, significant progress has been achieved with the development of new methods for differentiating upper and lower UTI. This review is intended to discuss current information about virulence factors of Escherichia coli, host genetic risk markers associated to recurrence and complications, and new diagnostic tools for localizing the anatomic place of urinary tract infections.


Organ Length Control by an ADAMTS Extracellular Protease in Caenorhabditis elegans.
MIG-17, a secreted protease of the ADAMTS family, acts in the directed migration of gonadal distal tip cells (DTCs) through regulation of the gonadal basement membrane in Caenorhabditis elegans Here, we show that MIG-17 is also required for the control of pharynx elongation during animal growth. We found that the pharynx was elongated in mig-17 mutants compared with wild type. MIG-17 localized to the pharyngeal basement membrane as well as to the gonadal basement membrane. The number of nuclei in the pharynx, and the pumping rate of the pharynx, were not affected in mig-17 mutants, suggesting that cells constituting the pharynx are elongated, although the pharynx functions normally in these mutants. In contrast to the control of DTC migration, MIG-18, a secreted cofactor of MIG-17, was not essential for pharynx length regulation. In addition, the downstream pathways of MIG-17 involving LET-2/type IV collagen, FBL-1/fibulin-1, and NID-1/nidogen, partly diverged from those in gonad development. These results indicate that basement membrane remodeling is important for organ length regulation, and suggest that MIG-17/ADAMTS functions in similar but distinct molecular machineries in pharyngeal and gonadal basement membranes.


Protein kinase C delta modulates endothelial nitric oxide synthase after cardiac arrest.
We previously showed that inhibition of protein kinase C delta (PKCδ) improves brain perfusion 24 hours after asphyxial cardiac arrest (ACA) and confers neuroprotection in the cortex and CA1 region of the hippocampus 7 days after arrest. Therefore, in this study, we investigate the mechanism of action of PKCδ-mediated hypoperfusion after ACA in the rat by using the two-photon laser scanning microscopy (TPLSM) to observe cortical cerebral blood flow (CBF) and laser Doppler flowmetry (LDF) detecting regional CBF in the presence/absence of δV1-1 (specific PKCδ inhibitor), nitric oxide synthase (NOS) substrate (L-arginine, L-arg) and inhibitor (N(ω)-Nitro-L-arginine, NLA), and nitric oxide (NO) donor (sodium nitroprusside, SNP). There was an increase in regional LDF and local (TPLSM) CBF in the presence of δV1-1+L-arg, but only an increase in regional CBF under δV1-1+SNP treatments. Systemic blood nitrite levels were measured 15 minutes and 24 hours after ACA. Nitrite levels were enhanced by pretreatment with δV1-1 30 minutes before ACA possibly attributable to enhanced endothelial NOS protein levels. Our results suggest that PKCδ can modulate NO machinery in cerebral vasculature. Protein kinase C delta can depress endothelial NOS blunting CBF resulting in hypoperfusion, but can be reversed with δV1-1 improving brain perfusion, thus providing subsequent neuroprotection after ACA.


Folate-receptor-positive circulating tumor cells as an efficacious biomarker for the diagnosis of small pulmonary nodules.
The objective of this study is to investigate the clinical significance of folate-receptor-positive circulating tumor cells (FR+CTC) for the diagnosis of lung cancer, especially in early-stage patients. A total of 72 lung cancer patients, including 31 with stage I diseases and two with stage 0 diseases, were enrolled in this study. Twenty-four patients with benign lung diseases and two healthy volunteers served as the control group. Three milliliters of peripheral blood were collected from each participant for FR+CTC analysis on enrollment. FR+CTC enumeration was performed using immunomagnetic leukocyte depletion and ligand-targeted polymerase chain reaction techniques. The study results revealed that using a cutoff value of 8.7 CTC Units/3 mL, the sensitivity, and specificity of FR+CTC for diagnosis of lung cancer were 81.94% and 73.08%, respectively. Such high sensitivity (74.19%) and specificity (73.08%) persisted even if only stage I lung cancer patients were retained in the analysis. In receiver operating characteristic analysis, the performance of FR+CTC (area under the curve = 0.8153) was superior to other clinical biomarkers such as carcinoembryonic antigen, neuron-specific enolase, and cytokeratin 19 fragments. In a subgroup analysis, patients with nodule size of >3 cm showed an improved sensitivity (88.46%); although, the specificity appeared to decrease (40%). All five patients with benign diseases in this subgroup had inflammatory diseases, indicating that large inflammatory nodules may also release FR -expressing cells into the circulatory system. FR+CTC is a reliable biomarker for the early diagnosis of small-sized lung cancer. Further study with larger sample size is required to assess the diagnostic efficiency of FR+CTC in patients with large nodule sizes.


Assessing the Relationship between Neurocognitive Performance and Brain Volume in Chronic Moderate-Severe Traumatic Brain Injury.
Characterize the scale and pattern of long-term atrophy in gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) in chronic moderate-severe traumatic brain injury (TBI) and its relationship to neurocognitive outcomes. The TBI group consisted of 17 males with primary diagnosis of moderate-severe closed head injury. Participants had not received any systematic, post-acute rehabilitation and were recruited on average 8.36 years post-injury. The control group consisted of 15 males matched on age and education. Neurocognitive battery included widely used tests of verbal memory, visual memory, executive functioning, and attention/organization. GM, WM, and CSF volumes were calculated from segmented T1-weighted anatomical MR images. Voxel-based morphometry was employed to identify brain regions with differences in GM and WM between TBI and control groups. Chronic TBI results in significant neurocognitive impairments, and significant loss of GM and WM volume, and significant increase in CSF volume. Brain atrophy is not widespread, but it is rather distributed in a fronto-thalamic network. The extent of volume loss is predictive of performance on the neurocognitive tests. Significant brain atrophy and associated neurocognitive impairments during the chronic stages of TBI support the notion that TBI results in a chronic condition with lifelong implications.


Association between evidence-based standardized protocols in emergency departments with childhood asthma outcomes: a Canadian population-based study.
To determine whether children treated in emergency departments (EDs) with evidence-based standardized protocols (EBSPs) containing evidence-based content and format had lower risk of hospital admission or ED return visit and greater follow-up than children treated in EDs with no standardized protocols in Ontario, Canada. Retrospective population-based cohort study of children with asthma. We used multivariable logistic regression to estimate risk of outcomes. All EDs in Ontario (N = 146) treating childhood asthma from April 2006 to March 2009. Thirty-one thousand one hundred thirty-eight children (aged 2 to 17 years) with asthma. MAIN EXPOSURE Type of standardized protocol (EBSPs, other standardized protocols, or none). Hospital admission, high-acuity 7-day return visit to the ED, and 7-day outpatient follow-up visit. RESULTS The final cohort made 46 510 ED visits in 146 EDs. From the index ED visit, 4211 (9.1%) were admitted to the hospital. Of those discharged, 1778 (4.2%) and 7350 (17.4%) had ED return visits and outpatient follow-up visits, respectively. The EBSPs were not associated with hospitalizations, return visits, or follow-up (adjusted odds ratio, 1.17 [95% CI, 0.91-1.49]; adjusted odds ratio, 1.10 [95% CI, 0.86-1.41]; and adjusted odds ratio, 1.08 [95% CI, 0.87-1.35], respectively). The EBSPs were not associated with improvements in rates of hospital admissions, return visits to the ED, or follow-up. Our findings suggest the need to address gaps linking improved processes of asthma care with outcomes.


The effect of transfer and hospital volume in subarachnoid hemorrhage patients.
Prompt management of aneurysmal subarachnoid hemorrhage (SAH) is critical. Literature is inconclusive regarding outcomes for patients directly admitted to specialized centers versus transferred from lower-volume hospitals. Providers are often unclear about the safety of transferring critical patients. This study evaluated the "transfer effect" in a large sample of aneurysmal SAH patients undergoing treatment. Using Nationwide Inpatient Sample 2002-2007 data, we analyzed outcomes of SAH patients treated with coil or clip procedures. Analyses studied the effect of direct-admit versus transfer admission on mortality, discharge disposition, complications, length of stay (LOS), and total charges. Of 47,114 patients, 31,711 (67.3 %) were direct-admits and 15,403 (32.7 %) were transfers. More transfer patients were coiled than direct-admits (45.3 vs. 33.7 %, p < 0.0001) and fewer underwent ventriculostomy (26.6 vs. 31.5 %, p = 0.003). Older age (OR 1.2, p < 0.0001), higher disease severity (OR 1.4, p < 0.0001), lower volume (OR 1.5, p < 0.0001), and ventriculostomy (OR 2.1, p < 0.0001) increased mortality and predicted non-routine discharge, complications, LOS, and charges. Transfer patients had similar mortality (OR 0.9, p = 0.13) and complications (OR 0.9, p = 0.22) as direct-admits, but incurred higher non-routine discharge (OR 1.3, p = 0.002). Analysis of grade V patients demonstrated similar outcomes between direct-admits and transfers; however, charges for treating transfer patients were notably higher ($401,386 vs. $242,774, p = 0.03). Patients treated in the lowest volume hospitals were 1.6 times more likely to die than those treated at the highest quintile hospitals. Among the critically ill grade V patients, transfer to higher-volume specialized centers did not increase the likelihood of a poor prognosis.


[Intra-arterial DSA versus conventional angiography in assessing the resectability of pancreatic and periampullary carcinomas].
Fifty patients were examined to determine whether intraarterial DSA can replace conventional angiography to assess the resectability of pancreatic and periampullary carcinomas. Intraarterial DSA yielded equivalent diagnostic information in 60% of the cases. As a result of contrast-enhanced visualisation of the splanchnic veins intraarterial DSA was superior to conventional angiography in 26% of the cases, whereas in 14% intraarterial DSA provided less information due to motion artifacts.


Pavlovian-To-Instrumental Transfer and Alcohol Consumption in Young Male Social Drinkers: Behavioral, Neural and Polygenic Correlates.
In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, pSVC = 0.04, x = 26, y = -6, z = -12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (rs = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies.


Upregulated expression of Mina53 in cholangiocarcinoma and its clinical significance.
The aim of this study was to determine the level of expression of Mina53 in human cholangiocarcinoma (CCA) and to explore the role of Mina53 in carcinogenesis and tumor progression and its clinical significance in CCA. The level of expression of Mina53, p53 and Ki67 was investigated by immunohistochemistry in 69 surgically resected CCA tissues and 21 adjacent non-cancerous tissues. The correlation between Mina53 expression and clinicopathological characteristics and the expression of p53 and Ki67 was examined. Positive expression of Mina53 was observed in 61 of 69 CCA cases (88.4%) and 1 case (4.8%) of adjacent non-cancerous tissue. The level of expression of Mina53 in CCA was markedly higher than in the adjacent non-cancerous tissues. An increased level of expression of Mina53 in CCA was significantly associated with histological differentiation (P<0.01), TNM stage (P<0.05) and lymph node metastasis (P<0.01). There was no significant correlation between the level of Mina53 expression and gender, age or distant metastasis (P>0.05). However, the expression of Mina53 was associated with the expression of p53 in CCA (P<0.05). In addition, increased levels of expression of Mina53 in CCA were positively associated with Ki67 levels (r=0.801, P<0.01, as calculated by association analysis). Therefore, the upregulation of Mina53 expression may be significant in the carcinogenesis and development of human CCA and could have significant clinical value.