Limitations of paperless on-line reporting of diagnostic bacteriology culture results.
To estimate the extent to which microbiology laboratory results made available on a computerised reporting system do not reach their intended destination. Prospective observational study of 180 urine cultures submitted from patients seen at the accident and emergency department of a 250 bed university affiliated general hospital. Observations were made of: telephone requests for results; whether results were noted in patients' charts; and antibiotic administration to patients sent home. Results were requested/recorded for 73% of 37 patients admitted to hospital and for only 23% of 143 patients sent home (p < 1 x 10(-7)). Overall, results were more frequently recorded for patients with positive cultures (p = 0.04). When determined separately for admitted and discharged groups, this association was not shown. Three of 14 culture positive patients sent home and for whom results were not recorded received inappropriate therapy; 19 culture negative patients were given antibiotics. In view of the results, measures were instituted to ensure delivery of printed reports to the health care providers of patients not admitted from the accident and emergency department. Organisations operating computerised reporting systems in evolving health care settings must ensure that system design guarantees delivery of reports to all end-users. This will minimise therapeutic problems, reduce wastage of laboratory resources, and limit risks of litigation.


Coherent transfer of electron spin correlations assisted by dephasing noise.
Quantum coherence of superposed states, especially of entangled states, is indispensable for many quantum technologies. However, it is vulnerable to environmental noises, posing a fundamental challenge in solid-state systems including spin qubits. Here we show a scheme of entanglement engineering where pure dephasing assists the generation of quantum entanglement at distant sites in a chain of electron spins confined in semiconductor quantum dots. One party of an entangled spin pair, prepared at a single site, is transferred to the next site and then adiabatically swapped with a third spin using a transition across a multi-level avoided crossing. This process is accelerated by the noise-induced dephasing through a variant of the quantum Zeno effect, without sacrificing the coherence of the entangled state. Our finding brings insight into the spin dynamics in open quantum systems coupled to noisy environments, opening an avenue to quantum state manipulation utilizing decoherence effects.


Commissioning of a 3D image-based treatment planning system for high-dose-rate brachytherapy of cervical cancer.
The objective of this work is to present commissioning procedures to clinically implement a three-dimensional (3D), image-based, treatment-planning system (TPS) for high-dose-rate (HDR) brachytherapy (BT) for gynecological (GYN) cancer. The physical dimensions of the GYN applicators and their values in the virtual applicator library were varied by 0.4 mm of their nominal values. Reconstruction uncertainties of the titanium tandem and ovoids (T&O) were less than 0.4 mm on CT phantom studies and on average between 0.8-1.0 mm on MRI when compared with X-rays. In-house software, HDRCalculator, was developed to check HDR plan parameters such as independently verifying active tandem or cylinder probe length and ovoid or cylinder size, source calibration and treatment date, and differences between average Point A dose and prescription dose. Dose-volume histograms were validated using another independent TPS. Comprehensive procedures to commission volume optimization algorithms and process in 3D image-based planning were presented. For the difference between line and volume optimizations, the average absolute differences as a percentage were 1.4% for total reference air KERMA (TRAK) and 1.1% for Point A dose. Volume optimization consistency tests between versions resulted in average absolute differences in 0.2% for TRAK and 0.9 s (0.2%) for total treatment time. The data revealed that the optimizer should run for at least 1 min in order to avoid more than 0.6% dwell time changes. For clinical GYN T&O cases, three different volume optimization techniques (graphical optimization, pure inverse planning, and hybrid inverse optimization) were investigated by comparing them against a conventional Point A technique. End-to-end testing was performed using a T&O phantom to ensure no errors or inconsistencies occurred from imaging through to planning and delivery. The proposed commissioning procedures provide a clinically safe implementation technique for 3D image-based TPS for HDR BT for GYN cancer.


The mechanism of proton translocation by the cytochrome system of mitochondria. Characterization of proton-transfer reactions associated with oxidoreductions of terminal respiratory carriers.
A direct kinetic analysis is presented of rapid proton-releasing reactions at the outer or C-side of the membrane, in ox heart and rat liver mitochondria, associated with aerobic oxidation of reduced terminal respiratory carriers in the presence of antimycin. Valinomycin plus K+ enhances the rate of cytochrome c oxidation and the rate and extent of H+ release. In the presence of valinomycin the leads to H+/e- ratio, computed on the basis of total electron flow from respiratory carriers to oxygen, varies with pH, remaining always lower than 1, and is unaffected by N-ethylmaleimide. 2-Heptyl-4-hydroxyquinoline N-oxide and 5-(n-undecyl)-6-hydroxy-4,7-dioxobenzothiazole, at concentrations which inhibit in the presence of antimycin the oxygen-induced reduction of b cytochromes, cause also a marked depression of the H+ release associated with aerobic oxidation of terminal respiratory carriers. Aerobic oxidation of the cytochrome system in mitochondria and of isolated b-c1 complex and cytochrome c oxidase results in scalar proton release from ionizable groups (redox Bohr effects). In mitochondria and submitochondrial particles, about 70% of the oxidoreductions of the components of the cytochrome system are linked to scalar proton transfer by ionizable groups. In isolated b-c1 complex scalar proton transfer, resulting from redox Bohr effect, amounts to 0.9H+ per Fe-S protein (190 muT). In isolated cytochrome c oxidase, Bohr protons amount to 0.8 per haem a + a3. The results presented indicate that the H+ release from mitochondria during oxidation of terminal respiratory carriers derives from residual antimycin-insensitive electron flow in the quinone-cytochrome c span and from redox Bohr effects in the b-c1 complex and cytochrome c oxidase. There is no sign of proton pumping by cytochrome oxidase during its transition from the reduced to the active 'pulsed' state and the first one or two turnovers.


[Scanning electron microscope study of unerupted enamel surface in adult patients].
We have undertaken a scanning electron microscope study of the enamel surface of the third molar in adult patients. The enamel surface are partially covered by a thin cuticle. The arrangement of the enamel prisms was clearly observed in the basal region of the cusps.


Impact of India's National Tobacco Control Programme on bidi and cigarette consumption: a difference-in-differences analysis.
Despite the importance of decreasing tobacco use to achieve mortality reduction targets of the Sustainable Development Goals in low-income and middle-income countries (LMICs), evaluations of tobacco control programmes in these settings are scarce. We assessed the impacts of India's National Tobacco Control Programme (NTCP), as implemented in 42 districts during 2007-2009, on household-reported consumption of bidis and cigarettes. Secondary analysis of cross-sectional data from nationally representative Household Consumer Expenditure Surveys (1999-2000; 2004-2005 and 2011-2012). Outcomes were: any bidi/cigarette consumption in the household and monthly consumption of bidi/cigarette sticks per person. A difference-in-differences two-part model was used to compare changes in bidi/cigarette consumption between NTCP intervention and control districts, adjusting for sociodemographic characteristics and time-based heterogeneity. There was an overall decline in household-reported bidi and cigarette consumption between 1999-2000 and 2011-2012. However, compared with control districts, NTCP districts had no significantly different reductions in the proportions of households reporting bidi (adjusted OR (AOR): 1.03, 95% CI: 0.84 to 1.28) or cigarette (AOR: 1.01 to 95% CI: 0.82 to 1.26) consumption, or for the monthly per person consumption of bidi (adjusted coefficient: 0.07, 95% CI: -0.13 to 0.28) or cigarette (adjusted coefficient: -0.002, 95% CI: -0.26 to 0.26) sticks among bidi/cigarette consuming households. Our findings indicate that early implementation of the NTCP may not have produced reductions in tobacco use reflecting generally poor performance against the Framework Convention for Tobacco Control objectives in India. This study highlights the importance of strengthening the implementation and enforcement of tobacco control policies in LMICs to achieve national and international child health and premature NCD mortality reduction targets.


CO-binding c-type cytochromes and a high-potential cytochrome c in Nitrosomonas europaea.
The purification of two soluble CO-binding cytochromes c from Nitrosomonas europaea is described. Cytochrome cCO-550 ran on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis with an apparent Mr of 32 000, whereas for cytochrome cCO-552 the apparent Mr was 16 000. Redox potentials (Em, 7) were determined as +140 and -50mV respectively. Cytochrome cCO-550 was co-purified with a cytochrome c-553, for which an unusually high redox potential of +450mV was measured. These latter components were not resolved by gel-filtration chromatography or electrophoresis under denaturing conditions.


Skin inflammation arising from cutaneous regulatory T cell deficiency leads to impaired viral immune responses.
Individuals with atopic dermatitis immunized with the small pox vaccine, vaccinia virus (VV), are susceptible to eczema vaccinatum (EV), a potentially fatal disseminated infection. Dysfunction of Forkhead box P3 (FoxP3)-positive regulatory T cells (Treg) has been implicated in the pathogenesis of atopic dermatitis. To test whether Treg deficiency predisposes to EV, we percutaneously VV infected FoxP3-deficient (FoxP3(KO)) mice, which completely lack FoxP3(+) Treg. These animals generated both fewer VV-specific CD8(+) effector T cells and IFN-gamma-producing CD8(+) T cells than controls, had higher viral loads, and exhibited abnormal Th2-polarized responses to the virus. To focus on the consequences of Treg deficiency confined to the skin, we generated mixed CCR4(KO) FoxP3(KO) bone marrow (CCR4/FoxP3) chimeras in which skin, but not other tissues or central lymphoid organs, lack Treg. Like FoxP3(KO) mice, the chimeras had impaired VV-specific effector T cell responses and higher viral loads. Skin cytokine expression was significantly altered in infected chimeras compared with controls. Levels of the antiviral cytokines, type I and II IFNs and IL-12, were reduced, whereas expression of the proinflammatory cytokines, IL-6, IL-10, TGF-beta, and IL-23, was increased. Importantly, infection of CCR4/FoxP3 chimeras by a noncutaneous route (i.p.) induced immune responses comparable to controls. Our findings implicate allergic skin inflammation resulting from local Treg deficiency in the pathogenesis of EV.


Reduced sleep spindle activity in schizophrenia patients.
High-density EEG during sleep represents a powerful new tool to reveal potential abnormalities in rhythm-generating mechanisms while avoiding confounding factors associated with waking activities. As a first step in this direction, the authors employed high-density EEG to explore whether sleep rhythms differ between schizophrenia subjects, healthy individuals, and a psychiatric control group with a history of depression. Healthy comparison subjects (N=17), medicated schizophrenia patients (N=18), and subjects with a history of depression (N=15) were recruited. Subjects were recorded during the first sleep episode of the night with a 256-electrode high-density EEG. Recordings were analyzed for changes in EEG power spectra, power topography, and sleep-specific cortical oscillations. The authors found that the schizophrenia group had a significant reduction in centroparietal EEG power, from 13.75 to 15.00 Hz, in relation to both the comparison and depression groups. No significant difference in EEG power between the comparison and depression groups was identified. The authors also found a decrease in sleep spindle number, amplitude, duration, and integrated spindle activity in schizophrenia patients. Furthermore, integrated spindle activity had an effect size corresponding to 93.0% or 90.2% separation of the schizophrenia from the comparison or depression group. Sleep spindles are generated by the thalamic reticular nucleus in conjunction with specific thalamic nuclei and are modulated by corticothalamic and thalamocortical connections. The deficit in sleep spindles in schizophrenia subjects may reflect dysfunction in thalamic-reticular and thalamocortical mechanisms and could represent a biological marker of illness.


Management of patients with unprovoked venous thromboembolism: an evidence-based and practical approach.
The management of patients with unprovoked venous thromboembolism is a common and challenging clinical problem. Although the initial antithrombotic management is well-established, there is uncertainty about the optimal long-term anticoagulant management, specifically whether patients should receive a short (i.e., 3- to 6-month) duration of anticoagulant therapy or indefinite anticoagulation. Factors that may be considered to estimate patients' risk for recurrent thromboembolism include the mode of initial clinical presentation, as deep vein thrombosis or pulmonary embolism, patient sex, antecedent hormonal therapy use, thrombophilia, D-dimer levels, and residual vein occlusion in patients with deep vein thrombosis. Many of these factors have been integrated into clinical prediction guides which stratify patients with unprovoked venous thromboembolism according to their risk for disease recurrence and, thereby, can assist clinicians in decisions about the duration of anticoagulation. The objective of this review is to consider the evidence relating to the clinical significance of purported risk factors and provide a practical case-based approach to guide decisions on duration of anticoagulation for patients with unprovoked venous thromboembolism.


Validating an interlingual metanorm for emotional analysis of texts.
In this article, we present a set of 12 norms that characterize emotional terms in French, English, German, Spanish, Italian, and Finnish. The high correlation between the norm values in the two emotional dimensions of valence and arousal suggests an interlingual homogeneity of emotional representations and allows a significant metanorm-EMONORM-to be established with 6,383 terms characterized in valence and 4,345 terms characterized in arousal. This metanorm is a resource for creating experimental materials in studies on language and emotions. Furthermore, we perform three tests using EMONORM, with the objectives of (1) identifying basic emotions from their valence and arousal values, (2) determining the orientation of texts referring to positive and negative emotions, and (3) evaluating the intensity of emotions expressed in texts. The results are highly similar to those for human judgments. Finally, we present EMOVAL/SEMOTEX, a Web application for static and dynamic valence and arousal emotional analysis of texts using EMONORM ( http://www.semotex.fr ).


Theoretical analysis of thermal boundary conductance of MoS2-SiO2 and WS2-SiO2 interface.
Understanding the physical processes involved in interfacial heat transfer is critical for the interpretation of thermometric measurements and the optimization of heat dissipation in nanoelectronic devices that are based on transition metal dichalcogenide (TMD) semiconductors. We model the phononic and electronic contributions to the thermal boundary conductance (TBC) variability for the MoS2-SiO2 and WS2-SiO2 interface. A phenomenological theory to model diffuse phonon transport at disordered interfaces is introduced and yields G = 13.5 and 12.4 MW K-1 m-2 at 300 K for the MoS2-SiO2 and WS2-SiO2 interface, respectively. We compare its predictions to those of the coherent phonon model and find that the former fits the MoS2-SiO2 data from experiments and simulations significantly better. Our analysis suggests that heat dissipation at the TMD-SiO2 interface is dominated by phonons scattered diffusely by the rough interface although the electronic TBC contribution can be significant even at low electron densities (n ≤ 1012 cm-2) and may explain some of the variation in the experimental TBC data from the literature. The physical insights from our study can be useful for the development of thermally aware designs in TMD-based nanoelectronics.


Distributed interfacing by nanoscale photodiodes enables single-neuron light activation and sensory enhancement in 3D spinal explants.
Among emerging technologies developed to interface neuronal signaling, engineering electrodes at the nanoscale would yield more precise biodevices opening to progress in neural circuit investigations and to new therapeutic potential. Despite remarkable progress in miniature electronics for less invasive neurostimulation, most nano-enabled, optically triggered interfaces are demonstrated in cultured cells, which precludes the studies of natural neural circuits. We exploit here free-standing silicon-based nanoscale photodiodes to optically modulate single, identified neurons in mammalian spinal cord explants. With near-infrared light stimulation, we show that activating single excitatory or inhibitory neurons differently affects sensory circuits processing in the dorsal horn. We successfully functionalize nano-photodiodes to target single molecules, such as glutamate AMPA receptor subunits, thus enabling light activation of specific synaptic pathways. We conclude that nano-enabled neural interfaces can modulate selected sensory networks with low invasiveness. The use of nanoscale photodiodes can thus provide original perspective in linking neural activity to specific behavioral outcome.


Category-specific naming deficit following cerebral infarction.
Studies aimed at characterizing the operation of cognitive functions in normal individuals have examined data from patients with focal cerebral insult. These studies assume that brain damage impairs functions of the cognitive processes along lines that honour the 'normal' pre-morbid organization of the cognitive system. For example, detailed study of individual brain-damaged patients has revealed apparently selective disruption of cognitive functions such as auditory/verbal working memory, phonological processing ability, grapheme-to-phoneme translation procedures and semantic processing. Warrington et al. have studied patients with even more fine-grained selective disturbances of the semantic system. The most selective deficits have been reported for four patients who were significantly better at identifying inanimate objects than they were at identifying living things and foods. These patterns of selective deficit after localized brain damage provide important information about the normal organization of the lexicon, and ultimately about how components of the lexical system are related to particular neural substrates. Here, we report a case study of a patient demonstrating a very selective disturbance of the ability to name items from two related semantic categories. Despite normal performance on a large battery of lexical/semantic tasks, the patient shows a consistent and striking disability in naming members of the semantic categories of 'fruits' and 'vegetables'. The selectivity of this deficit supports a category-specific organization of the mental lexicon, and suggests independence of the processing routes involving naming and name recognition.


Investigation and treatment of renal calculi.
We have investigated and treated 176 patients who were suffering from renal calculi. The stones contained calcium in 87% of patients, predominantly urate in 11%, and rarely contained magnesium ammonium phosphate or cystine. Of the patients with calcium stones, hypercalciuria was present in 75% and was identified in 57% by the measurement of the 24-hour urinary calcium excretion, and in a further 18% by a standardization calcium "fast-and-load" test. Nine patients were found to have primary hyperparathyroidism and were treated surgically. A further 21% were suspected to have normocalcaemic hyperparathyroidism, and metabolic studies are being developed to clarify this. The treatment of hypercalciuria included a low-calcium diet, and various combinations of a thiazide diuretic, phosphate supplements and sodium cellulose phosphate. Hypercalciuria was controlled in all compliant patients, and only two developed further stones. Hyperuricosuria was rarely the sole metabolic abnormality in patients with calcium stones, though this might reflect the referral pattern of the Unit. Uric acid stones were frequently, but not invariably, associated with hyperuricosuria and acid urine, and even large uric acid calculi dissolved with a combined therapy of high fluid intake, allopurinol and an alkalinizing agent. Surgical treatment was rarely required in these patients. A stone in the renal pelvis of one patient was removed percutaneously and did not require ultrasonic fragmentation. Modern methods of investigation and treatment have greatly improved the outlook for patients with recurrent renal calculi.


Cesarean section without clinical indication versus vaginal delivery as a paradigmatic model in the discourse of medical setting decisions.
Natural childbirth has ceased to be considered the gold standard in the delivery room. For this reason cesarean section on demand is increasing. Many obstetricians justify this phenomenon on evidence-based obstetrical practice. However, other pieces of evidence demonstrate that the data are often a product of the social milieu, and as stated by Wendland, "technology magically wards off the unpredictability and danger of birth". In a recent paper, Kalish pointed out several problems with cesarean deliveries in the absence of medical indications regarding issues of good clinical practice, autonomy, and informed consent. From the late 1990s, the medical community began to speak in favor of women's autonomy in childbirth decisions thus supporting the maternal choice and request for a cesarean section. Starting from these new considerations, it is of primary importance to understand whether emphasizing patient's autonomy is the best, or the only, way to helping the medical decisional process. This general approach may be helpful in all the other cases in which patient's autonomy and physician's responsibility appear to be intertwined in an apparent conflicting manner. We fear that the rhetoric of autonomous choice represents a fundamental shift from medicine-based beneficence toward a perilous relationship founded mainly on patient's wishes, representing a dangerous slippery slope where the physician could be reduced to the role of a functionary delegated to execute patient's claims and demands.


Neuropsychiatric symptoms from the temporolimbic lobes.
Neuropsychiatric symptoms are common manifestations of temporolimbic lesions. These neuropsychiatric symptoms result from disturbances of specific temporolimbic networks, including medial limbic circuits, lateral limbic circuits, and the "extended" amygdala. Moreover, temporolimbic networks interface with multiple cortical and subcortical circuits that modulate emotional behavior and affect. This article not only reviews these behaviorally relevant aspects of temporolimbic neuroanatomy, but also describes positive, productive symptoms from the temporal lobes. The Klüver-Bucy syndrome, the Gastaut-Geschwind syndrome, emotional or mood disorders, delusions, anxiety and associative disorders, and neurovegetative symptoms are discussed, as well as amnesia, the signature temporolimbic disturbance of cognition. The temporolimbic lobe is a classic example of a widely distributed circuit within the brain that has behaviorally relevant manifestations.


Physical performance and frailty in chronic kidney disease.
Poor physical performance and frailty are associated with elevated risks of death and disability. Chronic kidney disease (CKD) is also strongly associated with these outcomes. The risks of poor physical performance and frailty among CKD patients, however, are not well established. We measured the Short Physical Performance Battery (SPPB; a summary test of gait speed, chair raises and balance; range 0-12) and the five elements of frailty among 1,111 Chronic Renal Insufficiency Cohort participants. Adjusting for demographics and multiple comorbidities, we fit a linear regression model for the outcome of SPPB score and an ordinal logistic regression model for frailty status. Median (interquartile range, IQR) age was 65 (57-71) years, median estimated glomerular filtration rate (eGFR) for non-dialysis patients was 49 (36-62) ml/min/1.73 m(2), and median SPPB score was 9 (7-10). Seven percent of participants were frail and 43% were pre-frail. Compared with the SPPB score for eGFR >60 ml/min/1.73 m(2), the SPPB was 0.51 points lower for eGFR 30-59; 0.61 points lower for eGFR 15-29, and 1.75 points lower for eGFR <15 (p < 0.01 for all comparisons). eGFR 30-59 (odds ratio, OR 1.45; p = 0.024), eGFR 15-29 (OR 2.02; p = 0.002) and eGFR <15 (OR 4.83; p < 0.001) were associated with worse frailty status compared with eGFR >60 ml/min/1.73 m(2). CKD severity was associated with poor physical performance and frailty in a graded fashion. Future trials should determine if outcomes for CKD patients with frailty and poor physical performance are improved by targeted interventions.


Impact of Intensive Care Unit Readmissions on Patient Outcomes and the Evaluation of the National Early Warning Score to Prevent Readmissions: Literature Review.
Intensive care unit (ICU) readmissions have been shown to increase a patient's in-hospital mortality and length of stay (LOS). Despite this, no methods have been set in place to prevent readmissions from occurring. The aim of this literature review was to evaluate the impact of ICU readmission on patient outcomes and to evaluate the effect of using a risk stratification tool, the National Early Warning Score (NEWS), on ICU readmissions. A database search was performed on PubMed, Cumulative Index of Nursing and Allied Health Literature, Google Scholar, and ProQuest. In the initial search, 2028 articles were retrieved; after inclusion and exclusion criteria were applied, 12 articles were ultimately used in this literature review. This literature review found that patients readmitted to the ICU have an increased mortality rate and LOS at the hospital. The sample sizes in the reviewed studies ranged from 158 to 745,187 patients. Readmissions were most commonly associated with respiratory issues about 18% to 59% of the time. The NEWS has been shown to detect early clinical deterioration in a patient within 24 hours of transfer, with a 95% CI of 0.89 to 0.94 (P<.001), a sensitivity of 93.6% , and a specificity of 82.2%. ICU readmissions are associated with worse patient outcomes, including hospital mortality and increased LOS. Without the use of an objective screening tool, the provider has been solely responsible for the decision of patient transfer. Assessment with the NEWS could be helpful in decreasing the frequency of inappropriate transfers and ultimately ICU readmission.


The unique hypusine modification of eIF5A promotes islet beta cell inflammation and dysfunction in mice.
In both type 1 and type 2 diabetes, pancreatic islet dysfunction results in part from cytokine-mediated inflammation. The ubiquitous eukaryotic translation initiation factor 5A (eIF5A), which is the only protein to contain the amino acid hypusine, contributes to the production of proinflammatory cytokines. We therefore investigated whether eIF5A participates in the inflammatory cascade leading to islet dysfunction during the development of diabetes. As described herein, we found that eIF5A regulates iNOS levels and that eIF5A depletion as well as the inhibition of hypusination protects against glucose intolerance in inflammatory mouse models of diabetes. We observed that following knockdown of eIF5A expression, mice were resistant to beta cell loss and the development of hyperglycemia in the low-dose streptozotocin model of diabetes. The depletion of eIF5A led to impaired translation of iNOS-encoding mRNA within the islet. A role for the hypusine residue of eIF5A in islet inflammatory responses was suggested by the observation that inhibition of hypusine synthesis reduced translation of iNOS-encoding mRNA in rodent beta cells and human islets and protected mice against the development of glucose intolerance the low-dose streptozotocin model of diabetes. Further analysis revealed that hypusine is required in part for nuclear export of iNOS-encoding mRNA, a process that involved the export protein exportin1. These observations identify the hypusine modification of eIF5A as a potential therapeutic target for preserving islet function under inflammatory conditions.


The implication of obesity on total antioxidant capacity in apparently healthy men and women: the ATTICA study.
We evaluated the association of obesity with serum total antioxidant capacity (TAC), in a population-based sample of 3042 adults. During 2001-2002 we randomly enrolled 1514 men (18-87 years old) and 1528 women (18-89 years old), from the Attica area in Greece into the study, and the sample was stratified by the age-sex distribution of the region (census 2001). Among several variables we also measured serum TAC and weight, height, waist and hip circumferences. Waist circumference greater than 102 cm for men and 88 cm for women was considered an indicator of central fat. Mean waist circumference was 98+/-13 cm in men and 84+/-22 cm in women (P<0.001), while mean hip circumference was 106+/-28 cm in men and 103+/-13 cm in women (P<0.001). Central fat prevailed in 53% of men and 45% of women (P<0.001). Male participants with central fat exhibited 5% lower TAC concentrations compared to leaner individuals (214+/-35 vs. 226+/-33 micromol/L, P=0.04) and female participants with central fat exhibited 7% lower TAC concentrations (256+/-38 vs. 239+/-27 micromol/L, P=0.03). Similarly, obese or overweight male participants had 6% lower TAC concentrations compared to normal weight (217+/-33 vs. 234+/-39 micromol/L, P=0.03) and female obese or overweight participants had 10% lower TAC concentrations (226+/-32 vs. 250+/-30 micromol/L, P=0.02) compared to the others. Our results suggest an inverse relationship between body fat, central adiposity and antioxidant capacity, irrespective of age and various other potential confounders, namely smoking, physical activity, dietary habits, blood pressure, glucose levels, and lipid concentrations.


Myocardial Performance Index for Patients with Overt and Subclinical Hypothyroidism.
BACKGROUND Hypothyroid has several effects on the cardiovascular system. Global myocardial performance index (MPI) is used in assessment of both left ventricular (LV) systolic and diastolic function. We compared MPI in hypothyroidism patients vs. normal control subjects. MATERIAL AND METHODS Eighty-two hypothyroid patients were divided into 2 groups: a subclinical hypothyroid (SH) group (n=50), and an overt hypothyroid (OH) group (n=32). The healthy control group (CG) constituted of 37 patients. TSH, FT3, and FT4, anti-TPO, anti-TG, insulin, lipid values, and fasting glucose levels were studied. All patients underwent an echocardiographic examination. Myocardial performance indexes were assessed and standard echocardiographic examinations were investigated. RESULTS MPI averages in OH, SH, and control groups were 0.53±0.06, 0.51±0.05, and 0.44±0.75 mm, respectively. MPI was increased in the OH and SH groups in comparison to CG (p<0.001, p<0.001, respectively). CONCLUSIONS MPI value was significantly higher in hypothyroid patients in comparison to the control group, showing that regression in global left ventricular functions is an important echocardiographic finding. Future studies are required to determine the effects of this finding on long-term cardiovascular outcomes.


The effects of CD40- and interleukin (IL-4)-activated CD23+ cells on the production of IL-10 by mononuclear cells in Graves' disease: the role of CD8+ cells.
The possible roles of CD8+ cells in the abnormal T cell-dependent B-cell activation in Graves' disease were investigated by analysing lymphocyte subsets in peripheral blood mononuclear cells (PBMC) and their production of soluble factors and cytokines such as IL-10 in patients with Graves' disease, Hashimoto's thyroiditis and normal controls. The PBMC were separated into CD8+ and CD8-depleted cells by magnetic separation columns, and cultured for 7 days with or without anti-CD40 monoclonal antibodies and IL-4. The culture supernatant was assayed for sCD23 and IL-10 using EIA, and the remaining cells were analysed by flow cytometry. Stimulation with anti-CD40 antibody together with IL-4 increased sCD23 levels and the number of CD23+ cells. The latter was further augmented by depletion of CD8+ cells. This combination of B cell stimulants increased production of IL-10 by PBMC from patients with Graves' disease. The CD40- and IL-4-activated production of IL-10 was decreased by CD8+ cell depletion. In contrast, constitutive production of IL-10 was increased after CD8+ cell depletion in a group of patients with low basal secretion levels (<35 ng/ml). It was, however, decreased in a group with higher basal production levels, but such a relationship was not found in the normal control group. Thus, T cell-dependent B-cell activation via a CD40 pathway activates CD23+ cells, leading to over-production of IL-10 and a shift of the Th1/Th2 balance to Th2 dominance, while CD8+ cells may suppress this activation to counteract the Th2 deviation in Graves' disease.


Tooth wear: attrition, erosion, and abrasion.
Attrition, erosion, and abrasion result in alterations to the tooth and manifest as tooth wear. Each classification acts through a distinct process that is associated with unique clinical characteristics. Accurate prevalence data for each classification are not available since indices do not necessarily measure one specific etiology, or the study populations may be too diverse in age and characteristics. The treatment of teeth in each classification will depend on identifying the factors associated with each etiology. Some cases may require specific restorative procedures, while others will not require treatment. A review of the literature points to the interaction of the three entities in the initiation and progression of lesions that may act synchronously or sequentially, synergistically or additively, or in conjunction with other entities to mask the true nature of tooth wear, which appears to be multifactorial.


Post-mastectomy radiation therapy in breast reconstruction: a patterns of care study of the Korean Radiation Oncology Group.
The details of breast reconstruction and radiation therapy (RT) vary between institutions; therefore, we sought to investigate the practice patterns of radiation oncologists who specialize in breast cancer. We identified the practice patterns and inter-hospital variations from a multi-center cohort of women with breast cancer who underwent post-mastectomy RT (PMRT) to the reconstructed breast at 16 institutions between 2015 and 2016. The institutions were requested to contour the target volume and produce RT plans for one representative case with five different clinical scenarios and answer questionnaires which elicited infrastructural information. We assessed the inter-institutional variations in RT in terms of the target, normal organ delineation, and dose-volume histograms. Three hundred fourteen patients were included; 99% of them underwent immediate reconstruction. The most irradiated material was tissue expander (36.9%) followed by transverse rectus abdominis musculocutaneous flap (23.9%) and silicone implant (12.1%). In prosthetic-based reconstruction with tissue expander, most patients received PMRT following partial deflation. Conventional fractionation and hypofractionation RT were used in 66.6% and 33.4% patients, respectively (commonest: 40.05 Gy in 15 fractions [17.5%]). Furthermore, 15.6% of the patients received boost RT and 53.5% were treated with bolus. Overall, 15 physicians responded to the questionnaires and six submitted their contours and RT plans. There was a significant variability in target delineations and RT plans between physicians, and between clinical scenarios. Adjuvant RT following post-mastectomy reconstruction has become a common practice in Korea. The details vary significantly between institutions, which highlights an urgent need for standard protocol in this clinical setting.


Knee function among elite handball and football players 1-6 years after anterior cruciate ligament injury.
The aim of the study was to describe objective and self-reported knee function for athletes who have returned to elite handball and football play after an ACL injury, comparing these to non-injured players at the same level. A total of 414 handball and 444 football players completed baseline tests from 2007 through 2014, examining lower extremity strength, dynamic balance, knee laxity, and knee function (KOOS questionnaire). Measures were compared between injured and non-injured legs and between injured legs and legs of controls. Eighty (9.3%) of the 858 players reported a previous ACL injury, 1-6 years post-injury (3.5±2.5 years), 49 handball (61.3%) and 31 football players (38.7%). We found no difference in strength or dynamic balance between previously ACL-injured (N=80) and non-injured players legs (N=1556). However, lower quadriceps (6.3%, 95% CI: 3.2-9.2) and hamstrings muscle strength (6.1%, 95% CI: 3.3-8.1) were observed in previously ACL-injured legs compared to the non-injured contralateral side (N=80). ACL-injured knees displayed greater joint laxity than the contralateral knee (N=80, 17%, 95% CI: 8-26) and healthy knees (N=1556, 23%, 95% CI: 14-33). KOOS scores were significantly lower for injured knees compared to knees of non-injured players. ACL-injured players who have successfully returned to elite sport have comparable strength and balance measures as their non-injured teammates. Subjective perception of knee function is strongly affected by injury history, with clinically relevant lower scores for the KOOS subscores Pain, Function, Sport, and Quality Of Life.


Is Maternal Income in Childhood Associated With Adolescent Health and Behavioral Outcomes?
Maternal income increases immediate investment in children for food, child care, and health care, but whether maternal income influences longer term health and behavioral outcomes is unknown. Using data from the NICHD Study of Early Child Care and Youth Development, we examine the association between maternal income in early and later childhood on body mass index percentile, problem behaviors, and self-reported health status at age 15 among a sample of children (N = 1,283) whose mothers were employed at at least one observation time point between birth and age 15 (1991-2005). When controlling for family income (minus maternal income) and maternal employment characteristics, higher maternal income during early childhood was significantly associated with fewer adolescent problem behaviors. Maternal income during early childhood may influence adolescent behavioral outcomes. These findings suggest that increased maternal income, a positive externality of maternal employment, may increase the net benefit of maternal employment for child behavior.


Activation of the retinoid X receptor modulates angiotensin II-induced smooth muscle gene expression and inflammation in vascular smooth muscle cells.
The retinoid X receptor (RXR) partners with numerous nuclear receptors, such as the peroxisome proliferator activated receptor (PPAR) family, liver X receptors (LXRs), and farnesoid X receptor (FXR). Although each heterodimer can be activated by specific ligands, a subset of these receptors, defined as permissive nuclear receptors, can also be activated by RXR agonists known as rexinoids. Many individual RXR heterodimers have beneficial effects in vascular smooth muscle cells (SMCs). Because rexinoids can potently activate multiple RXR pathways, we hypothesized that treating SMCs with rexinoids would more effectively reverse the pathophysiologic effects of angiotensin II than an individual heterodimer agonist. Cultured rat aortic SMCs were pretreated with either an RXR agonist (bexarotene or 9-cis retinoic acid) or vehicle (dimethylsulfoxide) for 24 hours before stimulation with angiotensin II. Compared with dimethylsulfoxide, bexarotene blocked angiotensin II-induced SM contractile gene induction (calponin and smooth muscle-α-actin) and protein synthesis ([(3)H]leucine incorporation). Bexarotene also decreased angiotensin II-mediated inflammation, as measured by decreased expression of monocyte chemoattractant protein-1 (MCP-1). Activation of p38 mitogen-activated protein (MAP) kinase but not extracellular signal-related kinase (ERK) or protein kinase B (Akt) was also blunted by bexarotene. We compared bexarotene to five agonists of nuclear receptors (PPARα, PPARγ, PPARδ, LXR, and FXR). Bexarotene had a greater effect on calponin reduction, MCP-1 inhibition, and p38 MAP kinase inhibition than any individual agonist. PPARγ knockout cells demonstrated blunted responses to bexarotene, indicating that PPARγ is necessary for the effects of bexarotene. These data demonstrate that RXR is a potent modulator of angiotensin II-mediated responses in the vasculature, partially through inhibition of p38.


Right ventricular diastolic dysfunction and the acute effects of sildenafil in pulmonary hypertension patients.
This study investigated whether right ventricular (RV) diastolic function is impaired in pulmonary hypertension (PH) patients, and whether it is related to RV mass and afterload. In addition, the effects of an acute reduction of RV afterload by the oral intake of sildenafil were studied. Finally, we assessed whether diastolic function is related to cardiac parameters of disease severity. Twenty-five PH patients and 11 control subjects were studied. Right-heart catheterization and N-terminal pro-brain natriuretic peptide (NT-proBNP) sampling were performed in patients. MRI measured RV ejection fraction, mass, and diastolic function. Isovolumic relaxation time (IVRT), normalized early peak filling rate (E), atrium-induced peak filling rate (A), and E/A ratio described diastolic function. Compared to control subjects, patients had prolonged mean (+/- SD) IVRT (133.5 +/- 53.2 vs 29.3 +/- 20.8 ms, respectively; p < 0.001), decreased E (3.0 +/- 1.6 vs 6.4 +/- 2.5 s(-1), respectively; p < 0.001) and E/A ratio (1.1 +/- 0.7 vs 5.3 +/- 4.9, respectively; p < 0.001), and increased A (3.0 +/- 1.4 vs 1.5 +/- 0.9 s(-1), respectively; p = 0.001). IVRT was related to RV mass (r(25) = 0.56; p = 0.005) and pulmonary vascular resistance (r(25) = 0.74; p < 0.0001). Sildenafil therapy reduced RV afterload and improved RV diastolic and systolic function. IVRT was correlated with NT-proBNP level (r = 0.70; p < 0.001), and was inversely related to cardiac index (r = -0.70; p < 0.001) and RV ejection fraction (r = -0.69; p < 0.001). In PH patients, RV diastolic dysfunction is related to RV mass and afterload. RV diastolic function improves by reducing afterload. The correlations between diastolic function and prognostic parameters showed that diastolic function is most impaired in patients with severe disease.


Clustering of social disadvantage with attention-deficit/hyperactivity disorder in young adults: A register-based study in Sweden.
The clustering of social disadvantage with attention-deficit/hyperactivity disorder (ADHD) in young adulthood is not well understood. We examined the clustering of ADHD with low educational attainment and unemployment in young adulthood; whether such clustering is stronger when unemployment is prolonged; and whether further clustering of disability pensioning, low education and unemployment occurs among those with ADHD. Data were obtained from Swedish health, demographic and social security registers from which 8,990 individuals with recorded ADHD diagnoses at the age of 10-35 and their 44,387 matched referents without mental disorders. Social disadvantage was measured using data on educational attainment, unemployment and disability pension from the diagnosis year or age 19 if diagnosed at younger age. Clustering was examined by comparing observed and expected occurrence (O/E ratio) of all possible combinations of ADHD, low education and unemployment, and, among those with ADHD, additional combinations with new-onset disability pension. The likelihood of having neither ADHD, low education nor unemployment was increased (O/E ratio = 1.20, 95% confidence interval 1.19-1.20 at baseline; 1.18, 1.17-1.18 at follow-up), as well as having all three characteristics (O/E ratio = 3.99, 3.89-4.10 at baseline; 5.68, 5.47-5.89 at follow-up). This clustering was stronger among women than men and when unemployment was prolonged. The results suggest that low education and unemployment appear to cluster remarkably with ADHD among young adults, more so among women and when unemployment is prolonged.


Couples' self-control and marital conflict: Does similarity, complementarity, or totality matter more?
Research that approached self-control as a dyad-level predictor of relationship outcomes is hitherto scarce. To address this research gap, this study investigates three configurations of couples' level of self-control on marital conflict. We test three competing hypotheses suggested in the literature: similarity hypothesis, complementarity hypothesis, and totality hypothesis. The data used to test these hypotheses is a unique couple data (N = 1698 individuals from 894 married couples) of husbands and wives from a representative sample in Hong Kong. Two-level random-intercept models were employed. Based on our analysis with the difference-score method and response surface analysis, we find evidence to support the similarity hypothesis. The similarity of self-control between husband and wife is important in predicting marital conflict. In contrast, the total level of self-control is not predictive of marital conflict. This study highlights that marital conflict is strongly associated with the mismatch of self-control between partners.


Laser ablation studies of the role of the Drosophila oocyte nucleus in pattern formation.
Somatic and germline cells interact during oogenesis to establish the pattern axes of the Drosophila eggshell and embryo. The role of the oocyte nucleus in pattern formation was tested with the use of laser ablation. Ablation in stage 6 to 9 egg chambers caused partial or complete ventralization of the eggshell, phenotypes similar to those of eggs produced by gurken or torpedo females. Accumulation of vasa protein at the posterior pole of treated oocytes was also disrupted. Thus the oocyte nucleus is required as late as stage 9 for dorsoventral patterning within the follicle cells and for polar plasm assembly in the oocyte.


Observational study of a new modular femoral revision system.
The uncemented ArcosTM Modular Femoral Revision System (ARCOS) is a new comprehensive, press-fit revision design. The modular design offers a wide range of possible combinations to accommodate different variations of anatomy and bone stock. The ARCOS is made by a proximal body and a distal stem. As probably the only ones worldwide we predominantly use a combination of body and stem which supports proximal fixation and load, since this mimics the concept of the primary total hip arthroplasty with proximal weight-bearing, leading to bone stock preservation and no stress shielding or thigh pain. To evaluate the early results after femoral revision in a consecutive series of patients undergoing surgery over 3 years. We included 116 patients in the study. They were operated in the period August 2011 to December 2014 and we got a clinical mean observation time of 4 (0.5-6) years. Clinical and radiographical follow-up included present function of the hip assessed by Harris Hip Score, Oxford Hip Score, and EQ5D (measure of health outcome). Of the 116 patients, 17 died in the interim and were consequently included only in the implant survivorship analysis; 46 patients attended the follow-up control. In total 6 (5%) hips were re-revised due to infection (n = 3), fracture (n = 2) or subsidence (n = 1). No patient was re-revised due to aseptic loosening. The 1-, 2- and 5-year probability of implant survival (95%CI) were 97% (93%-100%), 97% (93%-100%) and 96% (92%-99%), respectively. In this cohort 95 patients received a combination of a proximal broach and a distal curved and slotted stem (BS), aiming for proximal fixation and load bearing; 21 patients received a different combination. When comparing these two groups the BS-group had a 5-year implant survival probability (95%CI) of 97% (93%-100%) compared with the group of other combinations with a 5-year implant survival probability (95%CI) of 90% (78%-100%) (P = 0.3). Our regression analysis showed that periprosthetic fracture as an indication for the ARCOS operation was the only significant negative outcome predictor. The mean Harris Hip Score result (100 points being best) was 83 (range 5-98). The mean Oxford Hip Score result (48 points being best) was 40 (range 19-48). The early results of the ARCOS are promising compared with similar studies. We encourage the use of the BS combination whenever the bone stock proximally is adequate.


Establishment of a canine cell line: derivation, characterization, and viral spectrum.
A cell line, designated A-72, for virus studies was established from a tumor surgically removed from a female, 8-year-old Golden Retriever dog. Following explant culture, the cells were serially passaged 135 times. The A-72 cells maintained a fibroblastic appearance and, at the 123rd passage, had a population doubling time of approximately 27 hours. Karyotypic analysis of the high passage cells showed the modal 2n chromosome number was 92 to 93. Using starch gel electrophoresis for enzyme characterization, the electrophoretic mobilities of enzymes extracted from A-72 cells were identical with those of canine peritoneal fibroblasts and primary canine kidney cells. The A-72 cells were susceptible to infection with infectious canine hepatitis virus, canine adenovirus type II, canine herpesvirus, canine parainfluenza virus, and canine coronavirus, but were not susceptible to canine distemper virus or the minute virus of canines. These cells have been particularly useful for studies of the fastidious canine coronaviruses, as the commonly used primary canine kidney cells exhibit varied susceptibility to these viruses.


Resorption of a sequestered cervical disc confirmed by magnetic resonance imaging: long term follow-up. Case report.
In literature cervical disc extrusions are considered by most neurosurgeons a definitive indication for surgery. This approach may stem from a fear of disc fragment migration with neurological deterioration. We report a rare case of cervical disc sequestration with a seldom prognosis which resolved spontaneously in a two-month follow-up on magnetic resonance imaging (MRI), emphasizing the efficacy and applicability of conservative treatment in cervical disc herniations. Even with the basic conservative treatment methods we observed the prominent decrease in symptoms and spontaneous total resorption of the sequestered fragment. Conservative treatment in sequestered cervical discs with no neurological deficit can be an alternative therapeutic approach with the guidance of MRI.


Study of the kinematic variables of unilateral and habitual mastication of healthy individuals.
To describe and compare the temporal-spatial kinematic variables of mandibular movement during deliberate unilateral and habitual mastication in healthy young-adult individuals. The study sample was composed of eight male healthy volunteers aged 19 to 24 years. The kinematic data were obtained using a motion analysis system - Qualisys Track Manager (QTM) ProReflex MCU. Recordings were performed during deliberate unilateral mastication (UM) and habitual mastication (HM) of firm-consistency gummy candy. The following variables were analyzed: (1) masticatory sequence: duration, number of masticatory cycles, and chewing rate; (2) masticatory cycle: duration, vertical and medial-lateral mandibular range of motion in relation to the skull, and maximum velocity during the opening and closing phases. Data of the variables were compared during UM and HM by the paired t test, and the effect sizes ('d' Cohen) were calculated. Regarding the variables of the masticatory sequence, smaller chewing rate was observed for UM compared with that for HM (1.19±0.21Hz and 1.29±0.16Hz, respectively, p=0.004, d=0.53). Smaller values of maximum velocity during the opening (MU=67.4 mm/s and MH=80.02, p=0.053, d=0.80) and closing (MU=71.77±9.35mm/s and MH=3.51±7mm/s, p=0.014, d=0.79) phases of the masticatory cycle were observed in deliberate unilateral mastication compared with those in habitual mastication. Kinematic variables associated with the sequence and cycle of mastication are influenced by the chewing pattern adopted - deliberate unilateral or habitual.


Cataract development in diabetic sand rats treated with alpha-lipoic acid and its gamma-linolenic acid conjugate.
Diabetes commonly leads to long-term complications such as cataract. This study investigated the effects of alpha-lipoic acid (LPA) and its gamma-linolenic acid (GLA) conjugate on cataract development in diabetic sand rats. Two separate experiments were conducted. In Experiment 1, sand rats were fed a "high-energy" diet (70% starch), an acute model of Type 2 diabetes, and injected with LPA. In Experiment 2, the animals received a "medium-energy" diet (59% starch), a chronic diabetic model, and were intubated with LPA or its GLA conjugate. Throughout the experiments, blood glucose levels and cataract development were measured. At the termination of the experiments, lens aldose reductase (AR) activity and lenticular reduced glutathione (GSH) levels were analyzed. LPA injection significantly inhibited cataract development and reduced blood glucose levels in rats fed the "high-energy" diet. Lens AR activity tended to be lower, while lenticular GSH levels increased. In sand rats fed a "medium-energy" diet (59% starch), LPA intubation had no effect on blood glucose levels and cataract development but GSH levels were increased. In contrast, sand rats intubated with GLA conjugate showed the highest blood glucose levels and accelerated cataract development. The conjugate treatment also decreased lenticular GSH content. The hypoglycemic effects of LPA are beneficial in the prevention of acute symptoms of Type 2 diabetes. It remains to be shown that the antioxidant activity of LPA is responsible for prevention or inhibition of cataract progression in sand rats.


Appropriately regularized OSEM can improve the reconstructed PET images of data with low count statistics.
With the increasing number of patients undergoing positron emission tomography (PET) scans and the fact that multiple whole body acquisitions are performed during therapy monitoring, the reduction of scan time as well as of the injected radioactive dose are important issues. However, short scan time and reduction of the injected radiation dose result in low count statistics, which significantly affects the quality of the reconstructed images and accurate diagnosis. The aim of this study was to explore the effect of low count statistics on ordered subset expectation maximization regularized with median root prior (OS-MRP-OSL) reconstructed images. By optimizing OS-MRP-OSL we determine whether a satisfactory handling of the noise properties and bias can be achieved compared to post-filtered ordered subset expectation maximization (OSEM), which will lead to improved image quality in simulations with more noise. We used realistic simulated PET data of a thorax with lesions corresponding to tumors with different intensities. OS-MRP-OSL provided reduced noise from post-filtered OSEM, without having the negative effect of blurring. On the other hand, bias presented no significant difference. This work is relevant to future PET reconstruction of clinical images and PET-magnetic resonance investigations where the reduced injected dose will allow imaging a larger cohort of humans.


Thrombospondins are astrocyte-secreted proteins that promote CNS synaptogenesis.
The establishment of neural circuitry requires vast numbers of synapses to be generated during a specific window of brain development, but it is not known why the developing mammalian brain has a much greater capacity to generate new synapses than the adult brain. Here we report that immature but not mature astrocytes express thrombospondins (TSPs)-1 and -2 and that these TSPs promote CNS synaptogenesis in vitro and in vivo. TSPs induce ultrastructurally normal synapses that are presynaptically active but postsynaptically silent and work in concert with other, as yet unidentified, astrocyte-derived signals to produce functional synapses. These studies identify TSPs as CNS synaptogenic proteins, provide evidence that astrocytes are important contributors to synaptogenesis within the developing CNS, and suggest that TSP-1 and -2 act as a permissive switch that times CNS synaptogenesis by enabling neuronal molecules to assemble into synapses within a specific window of CNS development.


Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts.
Genome-wide association studies (GWAS) have yielded significant insights into the genetic architecture of myocardial infarction (MI), although studies in non-European populations are still lacking. Saudi Arabian cohorts offer an opportunity to discover novel genetic variants impacting disease risk due to a high rate of consanguinity. Genome-wide genotyping (GWG), imputation and GWAS followed by meta-analysis were performed based on two independent Saudi Arabian studies comprising 3950 MI patients and 2324 non-MI controls. Meta-analyses were then performed with these two Saudi MI studies and the CardioGRAMplusC4D and UK BioBank GWAS as controls. Meta-analyses of the two Saudi MI studies resulted in 17 SNPs with genome-wide significance. Meta-analyses of all 4 studies revealed 66 loci with genome-wide significance levels of p < 5 × 10-8. All of these variants, except rs2764203, have previously been reported as MI-associated loci or to have high linkage disequilibrium with known loci. One SNP association in Shisa family member 5 (SHISA5) (rs11707229) was evident at a much higher frequency in the Saudi MI populations (> 12% MAF). In conclusion, our results replicated many MI associations, whereas in Saudi-only GWAS (meta-analyses), several new loci were implicated that require future validation and functional analyses.


No evidence for a polyomavirus association or aetiology in AIDS-associated nonsmall cell lung cancer.
AIDS-associated lung cancer has an increasing incidence, unaccounted for by smoking, and occurs consistently at a younger age than matched controls. We investigated whether known and new cancer-associated polyomaviruses, including the newly identified Merkel cell virus, may play a role in its etiopathogenesis. Although viruses target conserved pathways in cellular evolution, we are unable to suggest that the viruses studied here induce novel mechanisms of oncogenic dysregulation in AIDS-associated lung cancer.


Analysis of MHC class II genes in the susceptibility to lupus in New Zealand mice.
Hybrids of New Zealand Black (NZB) and New Zealand White (NZW) mice spontaneously develop a disease similar to human systemic lupus erythematosus. MHC and non-MHC genes contribute to disease susceptibility in this murine model. Multiple studies have shown that the NZW H2z locus is strongly associated with the development of lupus-like disease in these mice. The susceptibility gene(s) within H2z is not known, but different lines of evidence have pointed to class II MHC genes, either H2-E or H2-A (Ez or Az in NZW). Recent studies from our laboratory showed that Ez does not supplant H2z in the contribution to lupus-like disease. In the present work we generated C57BL/10 (B10) mice transgenic for Aaz and Abz genes (designated B10.Az mice) and used a (B10.Az x NZB)F1 x NZB backcross to assess the contributions of Az genes to disease. A subset of backcross mice produced high levels of IgG autoantibodies and developed severe nephritis. However, no autoimmune phenotype was linked to the Az transgenes. Surprisingly, in the same backcross mice, inheritance of H2b from the nonautoimmune B10 strain was strongly linked with both autoantibody production and nephritis. Taken together with our previous Ez studies, the present work calls into question the importance of class II MHC genes for lupus susceptibility in this model and provides new insight into the role of MHC in lupus-like autoimmunity.


A study of the mechanism of ferritin formation. The effect of pH, ionic strength and temperature, inhibition by imidazole and kinetic analysis.
The rate of ferritin formation in the buffers 4-morpholinepropanesulphonic acid (Mops), 4-morpholineethanesulphonic acid (Mes) and imidazole at pH values from 5.0 to 6.5 is quite similar. However, the rate of iron deposition is much greater in Mops and Mes at pH values above 6.5 than in imidazole. Increasing the concentration of imidazole inhibits ferritin formation and also leads to a transformation in the shape of the kinetic curves observed. This inhibiton is also observed at constant ionic strength but is not found for non-complexing buffers such as Mops. An inhibition of ferritin formation in imidazole and in Mops buffers is also observed with increasing ionic strength. We conclude that the unprotonated form of imidazole inhibits iron deposition, possibly by binding to the active site of the apoferritin molecule. The temperature dependence of iron deposition was examined. An optimum temperature of 50 degrees C was found but the Arrhenius plots were non-linear. On the basis of these and previous results, a kinetic model is developed which accounts well for ferritin formation at pH values below 6.5 and above 7.0 in non-complexing buffers. The model does not account for the kinetics observed at pH values close to neutrality.


Noncolonic diverticular disease.
Diverticula occur throughout the gastrointestinal tract. A high index of suspicion is necessary to diagnose and treat complications arising from diverticula. Presented is a review of gastrointestinal diverticular disease exclusive from the more common diverticular disease of the colon.


Inconsistent condom use among young men who have sex with men, male sex workers, and transgenders in Thailand.
Young men who have sex with men (MSM) are at risk for HIV infection. We investigated inconsistent condom use among 827 sexually active young MSM (15-24 years), enrolled using venue-day-time sampling in Bangkok, Chiang Mai and Phuket, Thailand. Data was collected using palmtop computer-assisted self-interviewing. Of participants, 33.1% were regular MSM, 37.7% were male sex workers (MSWs) and 29.1% were transgenders (TGs). Of MSM, 46.7%, of MSWs, 34.9% and of TGs, 52.3% reported recent inconsistent condom use. In multivariate analysis, receptive anal intercourse (MSM, MSWs), receptive and insertive anal intercourse, living alone and a history of sexual coercion (MSWs), not carrying a condom when interviewed (MSM, TGs), lower education, worrying about HIV infection and a history of sexually transmitted infections (TGs) were significantly and independently associated with inconsistent condom use. Interventions for young MSM are needed and must consider the distinct risk factors of MSM, MSWs, and TGs.


Combinatorial action of Grainyhead, Extradenticle and Notch in regulating Hox mediated apoptosis in Drosophila larval CNS.
Hox mediated neuroblast apoptosis is a prevalent way to pattern larval central nervous system (CNS) by different Hox genes, but the mechanism of this apoptosis is not understood. Our studies with Abdominal-A (Abd-A) mediated larval neuroblast (pNB) apoptosis suggests that AbdA, its cofactor Extradenticle (Exd), a helix-loop-helix transcription factor Grainyhead (Grh), and Notch signaling transcriptionally contribute to expression of RHG family of apoptotic genes. We find that Grh, AbdA, and Exd function together at multiple motifs on the apoptotic enhancer. In vivo mutagenesis of these motifs suggest that they are important for the maintenance of the activity of the enhancer rather than its initiation. We also find that Exd function is independent of its known partner homothorax in this apoptosis. We extend some of our findings to Deformed expressing region of sub-esophageal ganglia where pNBs undergo a similar Hox dependent apoptosis. We propose a mechanism where common players like Exd-Grh-Notch work with different Hox genes through region specific enhancers to pattern respective segments of larval central nervous system.


Phenylephrine alleviates 131I damage in submandibular gland through promoting endogenous stem cell regeneration via lissencephaly-1 upregulation.
Thyroid cancer is the most common endocrine malignancy. 131I ablation therapy is an effective treatment for patients with differentiated thyroid cancer (DTC) but frequently causes radiation damage in salivary glands (SGs). Stem cell-based regenerative therapy has been found to reduce radiation sialadenitis. We hypothesize that microtubule motor-regulating protein lissencephaly-1 (LIS1) may be a key stem cell regulator responsible for its efficacy and that upregulating LIS1 would decrease131I-induced radiation sialadenitis. Here, we report that LIS1 was reduced by 131I in submandibular glands (SMGs) of rats, using both proteomic analysis and Western blot approach. Moreover, the levels of LIS1-Sca-1 and LIS1-SOX2 were downregulated by 131I together with the decrease of LIS1. In contrast, phenylephrine pretreatment enhanced LIS1 and improved the co-expressions and co-localizations of LIS1-Sca-1 and LIS1-SOX2 in 131I-irradiated SMGs. Since Sca-1 and SOX2 are the established stem cell biomarkers in salivary gland, our findings demonstrate that LIS1 may be a potential target for regulating stem cell maintenance in irradiated SGs. Importantly, phenylephrine may have the ability to promote endogenous stem cell regeneration in SMGs via upregulating the LIS1/Sca-1 and LIS1/SOX2 signaling pathways, suggesting that phenylephrine application before 131I ablation therapy may provide a practical and effective way to prevent radiation sialadenitis for DTC patients.


Global Health Law and the Climate Crisis: An Unfulfilled Opportunity.
The emerging global climate crisis threatens human health in unprecedented ways, yet global health concerns have not been sufficiently considered within international climate change efforts. A more collaborative pathway could advance efforts to mitigate and adapt to climate change while protecting public health and social justice.


An examination of two positive organizational interventions: For whom do these interventions work?
Owing to the importance of employee psychological well-being for a variety of work- and non-work-related outcomes, practitioners and scholars have begun to broaden the scope of workplace well-being interventions by incorporating principles from positive psychology. Among such positive interventions, gratitude exercises have arguably emerged as the "gold standard" practice, with much research pointing to their effectiveness. However, existing workplace interventions lack a true (i.e., no intervention) control group, and effects have been observed for some-but not all-outcomes tested. Therefore, the purpose of this brief report was to conduct a concise but methodologically rigorous evaluation of the effectiveness of 2 positive psychology workplace interventions in improving employee affect, and to examine potential moderators of intervention effectiveness. Ninety-two employees in a large social services agency were assigned to (a) a gratitude intervention, (b) an intervention in which participants alternated between the gratitude activity and one involving increasing social connectedness, or (c) a wait list control condition, for 1 month. Neither intervention produced a main effect on any of the 3 affective outcomes measured. However, agreeableness, conscientiousness, and job tenure were significant moderators of intervention effectiveness. We discuss the implications of these preliminary results in an effort to advance the literature on workplace positive psychology interventions. (PsycINFO Database Record


Life threatening diarrhoea ultimately cured by surgery.
A 30-year-old previously healthy woman was diagnosed as having a vasoactive intestinal polypeptide (VIP)-producing tumour of the pancreas. Her medical history was typical for neuroendocrine gastrointestinal tumours, presenting initially with non-specific symptoms but eventually she developed life-threatening manifestations requiring intensive care due to severe dehydration. She immediately recovered following surgical resection. The patient had elevated serum concentrations of VIP as well as pancreastatin, and post-operatively elevated concentrations of three growth factors, IGF-I, EGF and TGF-alpha, were seen. The importance of the alterations in plasma concentrations of the different peptides for her symptomatology are discussed.


Direct communication, the unquestionable ideal? Oncologists' accounts of communication of bleak prognoses.
To explore the factors that influence the clinical practice of oncologists concerning disclosure of prognostic information. Focus group interviews with oncologists in three Norwegian university hospitals. Interview guide consisting of three patient cases where challenging aspects of prognostic information delivery were presented to the participants. Each group consisted of six participants, all groups with a mix of men and women, and ranging from very experienced consultants to relatively inexperienced residents in oncology. Transcribed interviews were qualitatively analyzed through categorization and condensation. The importance of openness when dealing with prognostic information towards the end of life was strongly advocated by all participants. However, there was a reluctance to give tangible information regarding survival, and a feeling that this part of clinical practice was a challenge. Skills in how to communicate negative prognostic information were attained primarily by observing colleagues, but also from personal experience. Existing guidelines for communication were not perceived as useful. Primarily focusing on open communication regarding bleak prospects of life expectancy entails a risk of overrunning the information needs of individual patients. Oncologists still see communication skills primarily as personal, and are at risk of not exploring and responding to the individual patient's wish for information.


Untargeted profiling of field cultivated bush tea (Athrixia phylicoides DC.) based on metabolite analysis.
Bush tea (Athrixia phylicoides DC.) is an aromatic South African indigenous plant used for many decades as a health beverage and medicine. Several studies have extensively investigated wild bush tea's secondary metabolites, but the entire profiling of cultivated bush tea's metabolites is limited in the literature. Thus, the objective of this study was to profile cultivated bush tea metabolites using liquid chromatography-quadrupole time of flight-tandem mass spectrometry (LC-QTOF-MS). The 31 metabolites profiled included; benjaminamide, chlorogenate, chrysosplenetin, coumarin, 6Z-docosenamide, naringenin 7-O-β-d-glucoside, 5-p-coumaroylquinic acid, integrastatin A, luteolin 7-O-(6-O-malonyl-β-d-glucoside), 1,3-dicaffeoylquinic acid, magnoshinin, okanin, (2S)-5-hydroxy-7-methoxy-6,8-dimethylflavanone, (9Z,12Z,15Z)-octadecatrienoic acid, 2″-deamino-2″-hydroxy-6″-dehydroparomamine, O-butanoylcarnitine, myricitrin, gorlic acid, tetracenomycin X, sakuranin, d-tryptophan, linoleamide, laricitrin 7-monoglucoside, l-β-phenylalanine, l-proline, pheophytin A, pheophorbide A, PI(18:0/20:4(8Z,11Z,14Z,17Z), stearidonic acid, and gibberellin A14 aldehyde. These annotated metabolites included phenolics, flavonoids, and quinic acids, indicating that bush tea is rich in metabolites, which have a potential wide range of health benefits.


A bioinformatic approach to the identification of candidate genes for the development of new cancer diagnostics.
A multivariate analysis of the National Cancer Institute gene expression database is reported here. The soft independent modelling of a class analogy approach achieved cell line classification according to histological origin. With the PCA method, based on the expression of 9605 genes and ESTs, classification of colon, leukaemia, renal, melanoma and CNS cells could be performed, but not of lung, breast and ovarian cells. Another multivariate procedure, called partial least squares discriminant analysis (PLS-DA), provides bioinformatic clues for the selection of a limited number of gene transcripts most effective in discriminating different tumoral histotypes. Among them it is possible to identify candidates in the development of new diagnostic tests for cancer detection and unknown genes deserving high priority in further studies. In particular, melan-A, acid phosphatase 5, dopachrome tautomerase, S100-beta and acid ceramidase were found to be among the most important genes for melanoma. The potential of the present bioinformatic approach is exemplified by its ability to identify differentiation and diagnostic markers already in use in clinical settings, such as protein S-100, a prognostic parameter in patients with metastatic melanoma and a screening marker for melanoma metastasis.


Early prognosis of epilepsy.
In 94 previously untreated new referrals to a neurological clinic with tonic-clonic or partial seizures or both the failure rate for optimum single-drug treatment with phenytoin or carbamazepine after a median of 32 months was 17%. Failure of single-drug treatment was associated especially with the presence of additional neuropsychiatric handicaps but also with partial or mixed seizures, symptomatic epilepsy, and a higher number and frequency of tonic-clonic or partial seizures before treatment. Analysis of the recurrence of seizures suggested that the first year of treatment may be crucial in determining the long-term prognosis. These findings are in keeping with the concept that seizures may predispose to further seizures, and imply that early, effective treatment may be important to prevent evolution into chronic and more intractable epilepsy.


B12-dependent radical SAM enzymes: Ever expanding structural and mechanistic diversity.
In the last decade, B12-dependent radical SAM enzymes have emerged as central biocatalysts in the biosynthesis of a myriad of natural products. Notably, these enzymes have been shown to catalyze carbon-carbon bond formation on unactivated carbon atoms leading to unusual methylations. Recently, structural studies have revealed unprecedented insights into the complex chemistry catalyzed by these enzymes. In this review, we cover recent advances in our understanding of B12-dependent radical SAM enzymes from a mechanistic and structural perspective. We discuss the unanticipated diversity of these enzymes which suggests evolutionary links between various biosynthetic and metabolic pathways from antibiotic to RiPP and methane biosynthesis.


Prevalence of depression in individuals with impaired glucose metabolism or undiagnosed diabetes: a systematic review and meta-analysis of the European Depression in Diabetes (EDID) Research Consortium.
Meta-analyses have shown that the risk for depression is elevated in type 2 diabetes. Whether this risk in individuals with impaired glucose metabolism (IGM) or undiagnosed diabetes (UDD) is elevated relative to normal glucose metabolism (NGM) or decreased relative to previously diagnosed type 2 diabetes (PDD) has not been the subject of a systematic review/meta-analysis. This study examined the prevalence of depression in IGM and UDD subjects relative to each other and to NGM and PDD subjects by reviewing the literature and conducting a meta-analysis of studies on this topic. EMBASE and MEDLINE databases were searched for articles published up to May 2010. All studies that compared the prevalence of depression in subjects with IGM and UDD were included. Odds ratios (ORs) were calculated using fixed and random-effects models. The meta-analysis showed that the risk for depression was not increased in IGM versus NGM subjects (OR 0.96, 95% CI 0.85-1.08). Risk for depression did not differ between individuals with UDD and individuals with either NGM (OR 0.94, 95% CI 0.71-1.25) or IGM (OR 1.16, 95% CI 0.88-1.54). Finally, individuals with IGM or UDD both had a significantly lower risk of depression than individuals with PDD (OR 0.59, 95% CI 0.48-0.73, and OR 0.57, 95% CI 0.45-0.74, respectively). Results of this meta-analysis show that the risk of depression is similar for NGM, IGM, and UDD subjects. PDD subjects have an increased risk of depression relative to IGM and UDD subjects.


[Nutrition and chronic liver disease].
The prevalence, causes, and consequences of energy-protein malnutrition (EPM) are reviewed in cirrhosis and its treatment, with special emphasis on those aspects that can be carried out in the ambulatory regime. EPM is a highly prevalent situation in advanced cirrhosis, but it probably already occurs in early stages of the disease. EPM has an important prognosis in cirrhosis. Specifically, the nutritional status could be a better predictor of the evolution after a liver transplant than the conventional prognostic indicators. The increase in the oxidation of fats and proteins is the most important mechanisms in EPM in these patients. The hypermetabolism and the deficit in ingestion are also relevant factors in the EPM in cirrhosis. Conventional diet therapy is the most important tool in the long term nutritional treatment in cirrhosis. The administration of nightly carbohydrate supplements could partially revert the alteration in the oxidation of the energetic substrates in these patients. Also, oral supplements of chemically defined diets could improve the quality of life and the long term survival of these patients. When artificial nutrition is indicated, enteral nutrition is the modality of choice in these patients. Enteral nutrition in cirrhosis is safe, nutritionally effective (as it guarantees an adequate energetic-proteineic ingestion), and in some studies it has been associated with a better short term survival. Adding branched chain amino acids to the diets or enteral supplements meant for cirrhotics would only be essential in patients who show intolerance to the conventional protein. Other changes in the components of the diet formulae meant for cirrhotics are open to further research.


Pancreatic juice cytology and subclassification of intraductal papillary mucinous neoplasms of the pancreas.
Histological subclassification of intraductal papillary mucinous neoplasms (IPMNs) is important because the malignant potential of each subtype is different. We investigated whether pancreatic juice cytology can be used to define the subtypes of IPMNs preoperatively. The cytological findings and pathological parameters in 19 cases of IPMN were analyzed for correlations. Pancreatic juice cytology specimens were reviewed and classified into 4 types according to the criteria previously described for histological diagnosis: intestinal (Int), gastric foveolar (GF), oncocytic (Onc), and pancreatobiliary (PB), and the resected IPMNs were classified histologically using the same criteria for comparison. Immunochemical testing for MUC proteins was also performed. In 15 cases (79%), the cytological and histological subclassifications were in agreement. The cytology specimens displayed different features corresponded to their histological subtypes. The sensitivities of the cytological diagnosis of each subtype were 80.0% (Int), 72.7% (GF), and 100% (Onc/PB); and the specificities were 85.7% (Int), 87.5% (GF), and 93.8% (Onc/PB). The cytoplasm of the Int-type cells in the pancreatic juice cytology specimens was positive for MUC2. Most of the cytological findings of IPMNs corresponded to the histological findings. The use of MUC2 immunocytochemistry in IPMN subtyping was also demonstrated. Subtyping of IPMNs is useful for preoperative evaluation in addition to cytomorphological grading.


Choroidal thickness and primary open-angle glaucoma: a cross-sectional study and meta-analysis.
The purpose of this study was to examine the choroidal thickness of patients with POAG using enhanced depth imaging optical coherence tomography (EDI-OCT) and compare them with healthy subjects. We first conducted a cross-sectional study and then performed a meta-analysis to address this issue further. Enhanced depth imaging optical coherence tomography was used to measure the macular choroidal thickness of the POAG and healthy eyes. Univariate and multivariate linear regression analyses were performed to assess the association between choroidal thickness and clinical factors. The meta-analysis was managed with Stata 12.0 software. Seventy-six healthy and 52 POAG subjects were recruited for this study. Age and axial length were the significant factors associated with subfoveal choroidal thickness in each group. There were no significant differences in choroidal thickness at any of the nine points between the POAG and healthy eyes after adjusting for IOP, age, and axial length (all P > 0.05). Similarly, there was no association between choroidal thickness and visual field defects (all P > 0.05). Our cross-sectional study indicated no significant difference in choroidal thickness between the POAG and healthy eyes, consistent with the results of the further meta-analysis involving 875 patients and 871 controls (weighted mean difference [WMD] for subfoveal choroidal thickness = -7.36 [95% confidence interval (CI): -24.39 to 9.67], WMD for mean macular choroidal thickness = 6.67 [95% CI: -2.45 to 15.79]). Six studies also provided data on average peripapillary choroidal thickness, and the pooled estimate was -8.15 (95% CI: -16.16 to -0.13, P = 0.046). However, considering that the precision of the OCT was 10 μm, this difference could have been caused by instrument error. Our study of Chinese POAG patients, along with the meta-analysis, suggested that POAG was not significantly associated with a marked thinning or thickening of the choroid based on EDI-OCT measurements.


Rethinking Body Ownership in Schizophrenia: Experimental and Meta-analytical Approaches Show no Evidence for Deficits.
Schizophrenia is a severe psychiatric disorder, in which patients experience an abnormal sense of self. While deficits in sensorimotor self-representation (agency) are well documented in schizophrenia, less is known about other aspects of bodily self-representation (body ownership). Here, we tested a large cohort (N = 59) of chronic schizophrenia patients and matched controls (N = 30) on a well-established body illusion paradigm, the Full Body Illusion (FBI). In this paradigm, changes in body ownership are induced through prolonged multisensory stimulation, in which participants are stroked on their back while seeing the stroking on the back of a virtual body. When the felt and seen stroking are synchronous, participants typically feel higher identification with the seen body as well as a drift in self-location towards it. However, when the stroking is asynchronous, no such changes occur. Our results show no evidence for abnormal body ownership in schizophrenia patients. A meta-analysis of previous work corroborates this result. Thus, while schizophrenia patients may be impaired in the sense of agency, their multisensory bodily self-representation, as tested here, seems to be unaffected by the illness.


Oral contraceptives and the risk of breast cancer.
It is uncertain whether the use of an oral contraceptive increases the risk of breast cancer later in life, when the incidence of breast cancer is increased. We conducted a population-based, case-control study to determine the risk of breast cancer among former and current users of oral contraceptives. We interviewed women who were 35 to 64 years old. A total of 4575 women with breast cancer and 4682 controls were interviewed. Conditional logistic regression was used to calculate odds ratios as estimates of the relative risk (incidence-density ratios) of breast cancer. The relative risk was 1.0 (95 percent confidence interval, 0.8 to 1.3) for women who were currently using oral contraceptives and 0.9 (95 percent confidence interval, 0.8 to 1.0) for those who had previously used them. The relative risk did not increase consistently with longer periods of use or with higher doses of estrogen. The results were similar among white and black women. Use of oral contraceptives by women with a family history of breast cancer was not associated with an increased risk of breast cancer, nor was the initiation of oral-contraceptive use at a young age. Among women from 35 to 64 years of age, current or former oral-contraceptive use was not associated with a significantly increased risk of breast cancer.


Plasmodium sporozoite invasion into insect and mammalian cells is directed by the same dual binding system.
Plasmodium sporozoites, the transmission form of the malaria parasite, successively invade salivary glands in the mosquito vector and the liver in the mammalian host. Sporozoite capacity to invade host cells is mechanistically related to their ability to glide on solid substrates, both activities depending on the transmembrane protein TRAP. Here, we show that loss-of- function mutations in two adhesive modules of the TRAP ectodomain, an integrin-like A-domain and a thrombospondin type I repeat, specifically decrease sporozoite invasion of host cells but do not affect sporozoite gliding and adhesion to cells. Irrespective of the target cell, i.e. in mosquitoes, rodents and cultured human or hamster cells, sporozoites bearing mutations in one module are less invasive, while those bearing mutations in both modules are non-invasive. In Chinese hamster ovary cells, the TRAP modules interact with distinct cell receptors during sporozoite invasion, and thus act as independently active pass keys. As these modules are also present in other members of the TRAP family of proteins in Apicomplexa, they may account for the capacity of these parasites to enter many cell types of phylogenetically distant origins.


Comparison of acute rapamycin nephrotoxicity with cyclosporine and FK506.
Acute cyclosporine (CsA) nephrotoxicity is characterized by a reduction of glomerular filtration rate (GFR), hypomagnesemia and tubular injury. The mechanisms of CsA's immunosuppressive action and presumably its nephrotoxicity are mediated through inhibition of the renal phosphatase, calcineurin. FK506 (FK), which has a different chemical structure and binding immunophilin, also inhibits calcineurin. We compared the renal effects of these drugs to those of rapamycin (RAPA), which although similar in structure and intracellular binding to FK, does not work by changing calcineurin activity. Rats were given CsA (15 mg/kg/s.c.), FK (6 mg/kg/p.o.), RAPA (3 mg/kg/p.o.) or vehicle (V) for two weeks on a low salt diet. CsA and FK strikingly decreased urinary excretion of nitric oxide, renal blood flow and GFR, whereas RAPA did not. In contrast, all these three drugs caused significant hypomagnesemia associated with inappropriately high fractional excretion of magnesium, suggesting renal magnesium wasting. In addition, with all three drugs there were lesions in the rat kidneys consisting of tubular collapse, vacuolization and nephrocalcinosis. We thus showed that only the calcineurin inhibitors produced glomerular dysfunction in an acute experimental model of nephrotoxicity. The mechanism of hypomagnesemia and tubular injury induced by all three immunosuppressive drugs is unclear but may be independent of calcineurin. The mechanism of renal vasoconstriction on the other hand may be related to inhibition of calcineurin.


Tooth formation and the mandibular symphysis during the first five postnatal months.
Schedules based on tooth development are useful in age assessments of children, but in early infancy they are based on only a few studies. The radiographic appearance of the mandibular symphysis during the first postnatal months has not gained attention. The present study describes the formation of teeth and the development of fusion between the mandibular halves during the first five postnatal months, as seen in panoramic tomograms taken in medicolegal autopsies of 29 ethnic Finns, 19 boys and 10 girls, at the Department of Forensic Medicine, University of Helsinki. In the majority of the infants, the criteria of sudden infant death (SID) were fulfilled. The stages of tooth formation used were those applied by Moorrees et al. with one modification (Nyström et al.). Mineralization of all primary teeth proceeded rapidly during the first postnatal months, the change being on average two developmental stages in four months. Considerable variation in tooth development existed in infancy. The mandibular halves were separated at birth. Complete fusion had occurred in the majority of infants aged four months, and the tomograms of the remaining infants showed a thin vertical line in a part of the symphysis. The marked changes, which during the first postnatal months occur in the radiographical appearance of the mandibular symphysis, and in the formation of primary teeth, provide valuable information for age assessments of infants.


Regulation of fibrillar collagen gene expression and protein accumulation in volume-overloaded cardiac hypertrophy.
Interstitial collagen accumulation has been extensively demonstrated to be increased at both mRNA and protein levels in pressure-overloaded cardiac hypertrophy. However, few data are available regarding the effects of volume overload on myocardial collagens. To determine whether the alterations of collagens may occur in volume-overloaded cardiac hypertrophy, we measured collagen types I and III mRNA levels and protein accumulation in left ventricular (LV) myocardium of rats at 3, 7, and 28 days after the creation of an aortocaval (AC) shunt. Eccentric LV hypertrophy was produced in rats with AC shunting. Northern blot analysis on RNA extracted from LV tissue indicated that the steady state mRNA levels for both type I and III collagen were persistently upregulated in AC shunt rats compared with sham-operated operated control rats. In contrast, the biochemical collagen protein concentration and morphometric collagen volume fraction were comparable between sham-operated control and AC shunt rats at any study time point. Furthermore, the immunohistochemical staining of types I and III collagen and Sirius red staining on myocardial tissue sections revealed no significant alterations in the distribution or density of fibrillar collagens in AC shunt rats. Tissue collagenase activity was not different between control and AC shunt rats after 28 days. Cardiac volume overload increases LV collagen mRNA as does pressure overload. However, in contrast to pressure-overloaded hypertrophy, the upregulation of collagen transcriptional activity does not result in subsequent myocardial fibrosis in volume-overloaded hypertrophy due to AC shunting. Therefore, the upregulation of collagen gene expression and protein accumulation might be different in pressure-overloaded and volume overloaded hypertrophy.


[Mitomycin C Treatment of Stromal Layers Enhances the Support of In Vitro Hematopoiesis in Co-Culture Systems].
A study was made of the effect that mitomycin C (MitC) treatment of stromal layers of NIH 3T3 cells expressing Jagged1, a ligand of the Notch receptor, exerts on the growth of hematopoietic Lin(-) mouse bone marrow cells in a co-culture system. MitC treatment of stromal cells significantly increased the number of hematopoietic cells and the frequency of colony-forming cells in stromal co-cultures. Transcriptome analysis of control and MitC-treated stromal cell samples was performed by differential RNA sequencing, and genes downregulated by MitC treatment were predominantly associated with the control of cell proliferation, the cell cycle, chromosome segregation, and DNA metabolism. Induction of key hematopoietic cytokines by MitC was not detected by the transcriptome analysis and was therefore not a main factor in the activation of hematopoiesis on the treated stroma. At the same time, the set of the genes most strongly upregulated by MitC treatment is enriched in the genes for cytokines, growth factors, and cell surface proteins, which presumably contribute to enhanced hematopoiesis support on the MitC-treated stroma. Products of some of these genes have been implicated in expansion of hematopoietic stem/progenitor cells in vitro or in vivo.


Internal recycling of respiratory CO2 in pods of chickpea (Cicer arietinum L.): the role of pod wall, seed coat, and embryo.
It has previously been proposed that respiratory CO2 released from the embryo in grain legume pods is refixed by a layer of cells on the inner pod wall. In chickpea this refixation process is thought to be of significance to the seed carbon budget, particularly under drought. In this study it is reported that the excised embryo, seed coat, and pod wall in chickpea are all photosynthetically competent, but the pod wall alone is capable of net O2 evolution over and above respiration. The predominant role of the pod wall in refixation is supported by measurements of fixation of isotopically labelled CO2, which show that more than 80% of CO2 is fixed by this tissue when provided to the pod interior. Chlorophyll concentrations are of the same order for embryo, seed coat, and pod wall tissues in younger pods on both an area and a fresh weight basis, but decline differentially with development from 12-30 d after podding. Imaging of chlorophyll distribution in the pod wall suggests that less than 15% of chloroplasts are located in the inner layer of cells thought to refix CO2 in legumes; this would be sufficient to refix less than 40% of respired CO2. It is concluded that while all tissues of the pod are capable of refixing respiratory carbon, the entire pod wall is responsible for the majority of this process, rather than a specialized layer of cells on the inner epidermis. The role of this fixed carbon in the pod for reallocation to the seed is discussed


Social and familial context of prenatal genetic testing decisions: are there racial/ethnic differences?
The purpose of this cross-sectional study of 999 socioeconomically and racially/ethnically diverse pregnant women was to explore prenatal genetic testing attitudes and beliefs and the role of external influences. Surveys in English, Spanish, and Chinese included questions regarding the value of testing, pregnancy, and motherhood; the acceptability of Down syndrome in the subject's community; and the role of social and cultural influences in prenatal testing decisions. We analyzed racial/ethnic differences in all attitudinal and external influence variables, controlling for age, relationship status, and socioeconomic status. We found statistically significant racial/ethnic group differences in familiarity with an individual with Down syndrome and in 10 of 12 attitude, belief, and external influence variables, even after controlling for other sociodemographic characteristics. We also observed substantial variation within racial/ethnic groups for each of these measures. Despite the statistically significant group differences observed, R(2) values for all multivariate models were modest and response distributions overlapped substantially. Social and familial contexts for prenatal testing decisions differ among racial/ethnic groups even after accounting for age, marital status, and other socioeconomic factors. However, substantial variation within groups and overlap between groups suggest that racial/ethnic differences play a small role in the social and familial context of prenatal genetic testing decisions.


[Surgical tactics in the treatment of postoperative thrombosis of reconstructed arteries].
The trial included 894 patients in postoperative period with thrombosis of reconstructed arteries, who had undergone since 1975 1100 repeated reconstructive operations. Vast experience of reoperations on the vessels allowed to summarize various types of reoperations, to systematize them and to propose new classification. Surgical policy was determined by the causes of acute thrombosis and the time of its duration. Evaluation of the results of repeated reconstructions has revealed, that patency of the by-passes in the aorto-femoro-popliteal area in long-term postoperative period is significantly lower than after surgery on renal arteries and brachiocephalic branches. A significant difference in patency in femoro-popliteal and tibial segments is revealed since the 2nd year, in aorto-femoral-since the 4th year after surgery. The function of the shunts in patients with nonspecific aortic arteritis in follow up period is significantly lower than in patients with atherosclerosis beginning from the 2nd year of follow-up. The repeated reconstructive operations for early and late thromboses in femoro-tibial segment are almost ineffective. Up to year 3 after the repeated operation patients with stage II of ischemia after Fontaine make up 19%, and up to year 5--only 9%. In the rest of the patients chronic critical ischemia with the loss of the limb is develops.