Vitamin A supplementation redirects the flow of retinyl esters from peripheral to central organs of neonatal rats raised under vitamin A-marginal conditions.
Background: Vitamin A (VA; retinol) supplementation is used to reduce child mortality in countries with high rates of malnutrition. Existing research suggests that neonates (<1 mo old) may have a limited capacity to store VA in organs other than the liver; however, knowledge about VA distribution and kinetics in individual, nonhepatic organs is limited.Objective: We examined retinol uptake and turnover in nonhepatic organs, including skin, brain, and adipose tissue, in neonatal rats without and after VA supplementation.Design: Sprague-Dawley neonatal rats (n = 104) were nursed by mothers fed a VA-marginal diet (0.35 mg retinol/kg diet) and treated on postnatal day 4 with an oral dose of either VA (6 μg retinyl palmitate/g body weight) or canola oil (control), both containing 1.8 μCi of [3H]retinol. Subsequently, pups (n = 4 · group-1 · time-1) were killed at 13 different times from 30 min to 24 d after dosing. The fractional and absolute transfer of chylomicron retinyl esters (CM-REs), retinol bound to retinol-binding protein (RBP-ROH), and total retinol were estimated in WinSAAM software.Results: VA supplementation redirected the flow of CM-REs from peripheral to central organs and accumulated mainly in the liver. The RBP-ROH released from the liver was acquired mainly by the peripheral tissues but not retained efficiently, causing repeated recycling of retinol between plasma and tissues (541 compared with 5 times in the supplemented group and control group, respectively) and its rapid turnover in all organs, except the brain and white adipose tissue. Retinol stores in the liver lasted for ∼2 wk before being gradually transferred to other organs.Conclusions: VA supplementation administered in a single high dose during the first month after birth is readily acquired but not retained efficiently in peripheral tissues of neonatal rats, suggesting that a more frequent, lower-dose supplementation may be necessary to maintain steady VA concentrations in rapidly developing neonatal tissues.


Local Insect Availability Partly Explains Geographical Differences in Floral Visitor Assemblages of Arum maculatum L. (Araceae).
Geographical variation in abundance and composition of pollinator assemblages may result in variable selection pressures among plant populations and drive plant diversification. However, there is limited knowledge on whether differences in local visitor and pollinator assemblages are the result of site-specific strategies of plants to interact with their pollinators and/or merely reflect the pollinator availability at a given locality. To address this question, we compared locally available insect communities obtained by light-trapping with assemblages of floral visitors in populations of Arum maculatum (Araceae) from north vs. south of the Alps. We further investigated whether and how the abundance of different visitors affects plants' female reproductive success and examined the pollen loads of abundant visitors. Local insect availability explained inter-regional differences in total visitor abundance, but only partly the composition of visitor assemblages. Northern populations predominantly attracted females of Psychoda phalaenoides (Psychodidae, Diptera), reflecting the high availability of this moth fly in this region. More generalized visitor assemblages, including other psychodid and non-psychodid groups, were observed in the south, where the availability of P. phalaenoides/Psychodidae was limited. Fruit set was higher in the north than in the south but correlated positively in both regions with the abundance of total visitors and psychodids; in the north, however, this relationship disappeared when visitor abundances were too high. High pollen loads were recorded on both psychodids and other Diptera. We demonstrate for the first time that the quantitative assessment of floral visitor assemblages in relation to locally available insect communities is helpful to understand patterns of geographical variation in plant-pollinator interactions. This combined approach revealed that geographical differences in floral visitors of A. maculatum are only partly shaped by the local insect availability. Potential other factors that may contribute to the geographical pattern of visitor assemblages include the region-specific attractiveness of this plant species to flower visitors and the population-specific behavior of pollinators.


Reduced ex vivo interleukin-8 production by neutrophils in septic and nonseptic systemic inflammatory response syndrome.
Ex vivo cytokine production by circulating lymphocytes and monocytes is reduced in patients with infectious or noninfectious systemic inflammatory response syndrome. Very few studies have addressed the reactivity of polymorphonuclear cells (PMN). To analyze further the relative contribution of systemic inflammatory response syndrome alone or in combination with infection we studied the interleukin-8 (IL-8) production by PMN isolated from patients who had undergone cardiac surgery with cardiopulmonary bypass (CPB) and patients with sepsis. Cells were activated with either lipopolysaccharide (LPS) or heat-killed streptococci. Compared with healthy controls, the release of IL-8 by PMN in both groups of patients was significantly reduced whether activated by LPS, independently of its concentration and origin, or by heat-killed streptococci. These observations suggest that stressful conditions related to inflammation, independently of infection, rapidly dampened the reactivity of circulating PMN. We investigated whether the observed diminished reactivity of PMN might reflect an endotoxin tolerance phenomenon. Our in vitro experiments with PMN from healthy controls indicated that PMN could not be rendered tolerant stricto sensu. However, our data suggested that LPS-induced mediators such as IL-10 may be responsible for the observed anergy in patients.


Differential language expertise related to white matter architecture in regions subserving sensory-motor coupling, articulation, and interhemispheric transfer.
The technique of diffusion tensor imaging (DTI) has been used to investigate alterations in white matter architecture following long-term training and expertise. Professional simultaneous interpreters (SI) provide an ideal model for the investigation of training-induced plasticity due to the high demands placed on sound to motor mapping mechanisms, which are vital for executing fast interpretations. In line with our hypothesis, we found clusters with decreased fractional anisotropy (FA) in the SI group in brain regions previously shown to support sensory-motor coupling mechanisms and speech articulation (cluster extent family-wise error corrected, P < 0.01). Furthermore, we found an altered white matter architecture indicated by lower FA values in the SI group in the most anterior and posterior parts of the corpus callosum. Our results suggest that language expertise is accompanied by plastic adaptations in regions strongly involved in motor aspects of speech and in interhemispheric information transfer. These results have implications for our understanding of language expertise in relation to white matter adaptations.


Effect of Synthetic Low-Odor Thiol-Based Hardeners Containing Hydroxyl and Methyl Groups on the Curing Behavior, Thermal, and Mechanical Properties of Epoxy Resins.
A novel thiol-functionalized polysilsesqioxane containing hydroxyl and methyl groups was synthesized using a simple acid-catalyzed sol-gel method to develop an epoxy hardener with low odor, low volatile organic compound (VOC) emissions, and fast curing at low temperatures. The synthesized thiol-based hardeners were characterized using Fourier transform infrared spectroscopy, nuclear magnetic resonance, thermogravimetric analysis (TGA), and gel permeation chromatography and compared with commercially available hardeners in terms of odor intensity and VOC emissions using the air dilution olfaction method and VOC analysis. The curing behavior and thermal and mechanical properties of the epoxy compounds prepared with the synthesized thiol-based hardeners were also evaluated. The results showed that synthetic thiol-based hardeners containing methyl and hydroxyl groups initiated the curing reaction of epoxy compounds at 53 °C and 45 °C, respectively. In contrast, commercial thiol-based hardeners initiated the curing reaction at 67 °C. Additionally, epoxy compounds with methyl-containing synthetic thiol-based hardeners exhibited higher TGA at a 5% weight loss temperature (>50 °C) and lap shear strength (20%) than those of the epoxy compounds with commercial thiol-based hardeners.


Regulation of parathyroid hormone-related peptide production in normal human mammary epithelial cells in vitro.
We have examined the expression and production of parathyroid hormone-related peptide (PTHRP) in primary cultures of normal human mammary epithelial cells (HMEC) derived from nonlactating breast tissue. In response to growth factors such as insulin, insulin-like growth factor I (IGF-I), and epidermal growth factor (EGF), immunoreactive PTHRP was released into conditioned medium, and PTHRP mRNA rapidly increased. In contrast, hydrocortisone and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] inhibited these effects in a dose-dependent manner. Addition of prolactin (PRL) in the presence or absence of insulin, IGF-I, or EGF did not influence PTHRP production during the time course studied. To investigate whether these factors were acting at the transcriptional level, we performed nuclear run-on assays and demonstrated that IGF-I increased PTHRP gene transcription whereas hydrocortisone and 1,25(OH)2D3 inhibited this effect. These studies therefore demonstrate that IGF-I, EGF, 1,25(OH)2D3, and hydrocortisone modulate PTHRP expression in HMEC and that these effects occur in part at the level of gene transcription. Additionally, PRL, a known stimulator of PTHRP expression in vivo, has no effect in this in vitro model.


Total Synthesis of Isohericenone J via a Stille Coupling Reaction.
The first total synthesis of isohericenone J is reported. Key features of this synthetic strategy are a Friedel-Crafts reaction to construct the isobenzofuranone unit and a Pd-catalyzed Stille coupling reaction for the formation of the C5-C1' bond, generating the natural product, as well as one of its isomers, in 6.0% overall yield in eight steps. This strategy provides a foundation for the synthesis of challenging isobenzofuranone and isoindolinone-type derivatives.


Integrated cardiothoracic team approach for complex lung transplantation procedures in Japan-current status and future direction.
The first lung transplant procedure in the world was performed in 1983, while in Japan that was first accomplished in 1998. Over the following 25 years, lung transplantation has become a viable treatment option for Japanese patients with a variety of end-stage lung diseases. Seventy cadaveric-donor lung (41 single, 29 bilateral), 11 bilateral living-donor lobar lung, and three heart-lung transplants have been performed with use of an integrated cardiothoracic team approach at medical facilities associated with Osaka University. Extremely advanced clinical and surgical skill sets are required to complete a lung transplant procedure, including surgical knowledge and techniques, as well as management of cardiovascular surgery, especially in regard to mechanical circulatory support (MCS), vascular anastomosis in difficult cases, and concomitant cardiac surgery. We have found that a collaborative effort by general thoracic and cardiac surgeons is an important key for success with lung transplantation. Complex lung transplant surgery and management in Japan are performed by use of an integrated cardiothoracic team approach, which has led to a synergistic impact on successful lung transplantation cases by capitalizing greatly on the experiences, techniques, and expertise of cardiac and thoracic experts. The present review is focused on the role of cardiac surgeons from the viewpoint of our experience with these cases.


Utility of transesophageal echocardiography in the diagnosis of disease of the thoracic aorta.
Transesophageal echocardiography (TEE) offers a rapid, minimally invasive method for diagnosing thoracic aortic disease. High-resolution images are possible because of the close proximity of the esophagus and vascular structures within the chest. Lung and chest wall components have little influence on the image quality and a virtually unobstructed view of the heart, thoracic aorta, and pulmonary vasculature is seen. The role of TEE in diagnosing diseases of the thoracic aorta is rapidly developing. The purpose of this study is to define the role of TEE in the diagnosis of thoracic aortic disease. Between July 1, 1989 and December 31, 1992, 1005 TEEs were performed at our center. Of these, 199 (125 men, 74 women) were entered into our aortic disease registry. Indications for the studies included 37 referrals to rule out aortic dissection, 18 to assess aortic aneurysm, 55 to assess for an intraaortic source of embolus, 9 to rule out intraaortic thrombus, and 13 with familial hyperlipidemia being followed to mark response to low-density lipoprotein apheresis. In 67 cases, subclinical aortic plaquing was found incidentally. No complications from the TEE procedure were encountered. In cases of suspected aortic dissection, TEE was equal to computed tomography (CT) scanning in identifying the type (DeBakey) and extent of thoracic aortic dissection. In addition, TEE provided information regarding functional status of the aortic valve, identified interluminal communications, and assessed blood flow and thrombus burden in the false lumen. TEE correctly identified true aneurysms, intraluminal thrombus, and plaques as possible sources of emboli. One false-positive CT scan result for aortic dissection was seen and was ruled out both by TEE and angiography. Biplane TEE can be considered the method of choice in diagnosing disease of the thoracic aorta. Information from TEE can be obtained at the patient's bedside or in the operating suite, to assess surgical results before procedure termination and afterward for follow-up. Adjunctive magnetic resonance imaging, CT scanning, or aortography may be needed to assess extension of the disease process into the abdomen or pelvis or to plan surgical intervention.


Unique cardioprotective potential of angiotensin converting enzyme inhibitors: a hypothesis still to be tested on humans.
'Primary cardioprotection' has, arguably, already been shown with thiazide diuretics and probably with beta-blockers. The proven safety and efficacy of these established drugs override any theoretical or experimental considerations in favour of ACE inhibitors. It is unfortunate that, as yet, the number of hypotheses generated in support of ACE inhibitors has not been matched by large scale clinical trials employing these drugs. The first report of the clinical use of an ACE inhibitor was in 1984; it is high time comparative studies with conventional, and proven, agents were undertaken. With regard to 'secondary cardioprotection', there is overwhelming evidence in favour of the use of beta-blockers in patients with myocardial ischaemia. Indeed, we would argue that ACE inhibitors should be used with caution in such patients to avoid impairment of coronary infusion. In the patient with acute myocardial infarction, intravenous nitrates are cheap, easy to use, safe and seem to be effective (in preventing early remodelling and reducing mortality). In the subacute phase, beta-blockers improve prognosis and, according to the currently available evidence in humans, nitrates are as effective as captopril in altering late remodelling; as in the acute situation, nitrates are cheaper, simpler to use and have a track record of long-term safety. ACE inhibitors improve symptoms, exercise capacity and prognosis in chronic heart failure. In this condition, they have been a major therapeutic advance and, on the available evidence, are to be initially preferred to other vasodilators though they should be given in addition to diuretics.(ABSTRACT TRUNCATED AT 250 WORDS)


Photodynamic therapy with chloroaluminum-sulfonated phthalocyanine.
To study the vascular effects of a new photosensitizing agent independent of the influence of tumor growth, a cutaneous wound model was used. Six-week-old Harlan-Sprague-Dawley "Fuzzy" rats were surgically wounded in a standard fashion. The animals were then divided into three groups: the first group received chloroaluminum-sulfonated phthalocyanine only, the second group was treated with light only, and a third group was treated with both chloroaluminum-sulfonated phthalocyanine and light. Photodynamic therapy with chloroaluminum-sulfonated phthalocyanine had a direct effect on the neovasculature of a healing wound. The vasodilatation that was seen in the wound neovasculature that occurred 12 hours after the completion of chloroaluminum-sulfonated phthalocyanine-photodynamic therapy may have indicated a therapeutic "window" at which other therapies can be employed to improve clinical efficacy.


Zooming X-rays with a single rotation in X-ray prism zoom lenses (XPZL).
Prism arrays arranged to form a slightly open alligator mouth were found to focus incident X-rays, as with increasing distance from the object symmetry axis these rays hit an increasing number of refracting prism tips. Such an object is then formally a refractive lens. Due to the strong energy dependence of the refractive index of material for X-rays a refractive X-ray lens is chromatically focusing. The attractive feature of the alligator lens is the inherent zoomability possible as the mouth can easily be opened or closed. However, the required tolerances for the jaw rotations and the jaw positioning are so stringent, that the routine use of such systems has not been reported yet. This study will show that the related technical problems can be overcome by proper object fabrication. In fact the here presented objects can already be aligned in the production stage. Then the assembly can be made with simple tools. And the zooming is achieved by just a simple rotation. The transmission through the devices was found to be as expected, and thus performance-wise these objects can directly compete with other refractive X-ray focusing systems.


Association between Sense of Coherence Associated with Mental Health in Caregivers of Older Adults.
The purpose of this study was to analyze association between sense of coherence and perceived burden, anxiety, depression, and quality of life in caregivers of older adults. A cross-sectional study was carried out with a probabilistic sample of 132 caregivers of older relatives from the regions of Jaén, Spain. The measures assessed were sense of coherence (Life Orientation Questionnaire), subjective burden (Caregiver Strain Index of Robinson), anxiety and depression (Goldberg Scale), and quality of life (Health Questionnaire SF-12). The main analyses included bivariate analysis using Pearson's correlation coefficient and multivariate analysis through canonical correlation analysis. Our findings show that the sense of coherence explained 50.8% of the variance shared between subjective burden, anxiety, depression, and quality of life. We highlighted manageability as the variable within the dimensions of the sense of coherence with the greatest participation in the model. The sense of coherence may be an important protective factor for the mental health of the caregiver of dependent elderly relatives.


Hepatic dysfunction after open-heart surgery.
In a prospective study, 93 patients were observed up to nine months after open-heart surgery using hypothermia, hemodilution and cold cardioplegia. In the first two weeks frequent determinations were made of serum aminotransferase, alkaline phosphatases (ALP), lactic dehydrogenase isoenzymes, gamma glutamyltransferase (GT), total and free bilirubin and bile acids. Plasma hemoglobin was measured at the end of the operation. After the first period, aminotransferases, alkaline phosphatases and bilirubin were determined monthly. On the first postoperative day almost all of the patients showed abnormal aspartate aminotransferase (ASAT) activity and ASAT/ALAT (alanine aminotransferase) greater than 1, and about 25% had hyperbilirubinemia. The findings suggested early postoperative leakage of enzymes not only from the myocardium, but also from the liver. After two weeks the patients presented another pattern of liver dysfunction, with abnormal ALAT in 50%, ASAT/ALAT less than 1, and abnormal ALP and GT in 28 and 45%, respectively. Eight patients were judged to have post-transfusion hepatitis of non-A, non-B type. Six of them had abnormal aminotransferases for more than six months.


Brain abscess and subdural empyema. Factors influencing mortality and results of various surgical techniques.
The authors review the results of various surgical techniques in relation to mortality and morbidity in 100 consecutive cases of brain abscess and subdural empyema. The mortality rate is the same with total excision and fractional drainage of brain abscesses, although in acute and subacute cases slight differences between both techniques are seen. In terms of morbidity, fractional drainage appears to be more favourable than total excision. The authors believe that factors other than surgical procedure influence mortality in cases of brain abscess and subdural empyema. These factors are defined in detail.


Clinicians' perspectives on motor learning strategy selection and application in occupational therapy and speech-language pathology interventions for children with acquired brain injury.
Explore occupational therapists' (OTs) and speech language pathologists' (SLPs) process of selecting and applying motor learning strategies (MLS) in their interventions for children with acquired brain injury (ABI), and identify similarities and differences between OTs and SLPs in MLS selection and application. This qualitative descriptive study involved individual semi-structured interviews with OTs and SLPs from the ABI program at Holland Bloorview Kids Rehabilitation Hospital (Toronto, Canada). Interviews were analyzed using thematic analysis. A modified constant comparison method permitted comparison within and between professions. Four OTs and three SLPs were interviewed. Four themes were developed: aligning MLS application with the child's cognitive ability, using MLS to promote success within a single session, adjusting MLS across treatment sessions, and promoting generalization and transfer of motor skills beyond the therapy session. MLS application was predominately based on child-specific factors with task-specific considerations. OTs and SLPs used similar clinical reasoning processes for selecting and applying MLS. This study provides a greater understanding of OTs' and SLPs' clinical reasoning process when applying MLS in pediatric ABI interventions. The similarities in MLS selection and application between disciplines suggest that an interprofessional approach to MLS is suitable for pediatric ABI rehabilitation.


Identification of obstructive sleep apnea in patients who snore.
As the field of sleep medicine has evolved, the clinical implications of obstructive sleep apnea (OSA) in snoring patients have become well accepted. Recent advances in surgical therapy for snoring allow otolaryngologists to offer simple outpatient treatment to patients with this problem. However, because the incidence of OSA in snorers seeking medical attention is unknown, the appropriate pretreatment evaluation of these patients is a subject of continued debate. Ninety-four snoring patients were recruited for a study to determine the incidence of OSA in this highly selected population. Subjects answered an extensive sleep questionnaire to determine factors that might suggest a diagnosis of OSA. Level III ambulatory sleep studies were performed on each participant. The incidence of OSA in this group was 72% (42% severe and 30% mild to moderate). Twenty of the subjects with OSA also underwent formal level I sleep studies, and the diagnosis of OSA was confirmed in each instance. Although there was a relationship between body mass index and OSA and certain questions correlated with OSA, the sensitivity and specificity of these data alone or in combination were too low to recommend their use in lieu of a formal sleep study. Given the remarkably high incidence of OSA in this group, which may reflect that seen by otolaryngologists who treat snoring, a sleep study should be performed to diagnose OSA and institute therapy for this condition. Level III ambulatory monitoring devices may be the most cost-effective alternative for evaluating this high-risk population.


Drug-induced epidermolysis bullosa acquisita with antibodies to type VII collagen.
We describe a 73-year-old patient who had a subepidermal bullous eruption develop after a course of antibiotics, including vancomycin. The patient had deposits of IgA and IgG in the cutaneous basement membrane zone that were located on the dermal side of 1 M NaCl-treated autologous skin. By an enzyme-linked immunosorbent assay, the patient was found to have circulating IgG antibodies directed against type VII collagen, the target antigen of epidermolysis bullosa acquisita. Our observation expands the spectrum of immune-mediated subepidermal bullous skin eruptions precipitated by drugs and lends support to the idea that a subset of these cases represents an unusual variant of drug-triggered epidermolysis bullosa acquisita.


Correlation dimension-based classifier.
Correlation dimension (CD), singularity exponents, also called scaling exponents, are widely used in multifractal chaotic series analysis. CD and other measures of effective dimensionality are used for characterization of data in applications. A direct use of CD to multidimensional data classification has not been hitherto presented. There are observations that the correlation integral is a distribution function of distances between all pairs of data points, and that by using polynomial expansion of distance with exponent equal to the CD this distribution is transformed into locally uniform. The classifier is based on consideration that the influence of neighbor points of some class on the probability that the query point belongs to this class is inversely proportional to its distance to the CD, power. New classification approach is based on summing up all these influences for each class. We prove that a resulting formula gives an estimate of probability of the class, not a measure of membership to a class only, to which the query point belongs. For this assertion to be valid, it is necessary that exponent of the polynomial transformation must be the CD. We also propose an averaging approach that speeds up computation of the CD especially for large data sets. It is demonstrated that the CD-based classifier can outperform more sophisticated classifiers.


Expression of connexins 26 and 43 in canine hyperplastic and neoplastic mammary glands.
Gap junctions are the only communicating junctions found in animal tissues and are composed of proteins known as connexins. Alterations in connexin expression have been associated with oncogenesis; reported studies in rodent and human mammary glands, which normally express connexins 26 and 43, confirm these alterations in malignancies. Mammary neoplasms represent the second most frequent neoplasm in dogs, and since there are no reports on the study of connexins in canine mammary glands, the present study investigated the expression of connexins 26 and 43 in normal, hyperplastic, and neoplastic mammary glands of this species, to verify if altered patterns of connexin staining are related to higher cell proliferation and malignant phenotypes. A total of 4 normal, 8 hyperplastic mammary glands, 9 benign, and 51 malignant mammary gland neoplasms were submitted for the immunostaining of connexins 26 and 43, E-cadherin, and proliferating cell nuclear antigen (PCNA). Normal, hyperplastic, and benign neoplastic mammary glands showed a punctate pattern for connexin 26 and 43 staining and an intercellular E-cadherin staining. Malignant neoplasms, especially the most aggressive cases with high cell proliferation rates, presented either fewer gap junction spots on the cell membranes or increased cytoplasmic immunostaining. Malignant tumors also expressed a less intense immunostaining of E-cadherin; the expression of this adhesion molecule is important for the transportation of connexins to cell membranes and in forming communicating gap junctions. Deficient expression of E-cadherin could be related to the aberrant connexin localization and may contribute to the malignant phenotype. In conclusion, the expression and distribution of connexins and E-cadherin are inversely correlated to cell proliferation in malignant mammary neoplasms of dogs and may well be related to their more aggressive histologic type and biologic behavior.


The diagnostic value of serum CEA, NSE and MMP-9 for on-small cell lung cancer.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer related deaths worldwide. But no one type of serum biomarker was found to be highly sensitive and specific for detection of lung cancer at present. So, the aim of this study was to evaluate a diagnostic value of serum carcinoembryonic antigen (CEA), neuron specific enolase (NSE) and matrix metallo-proteinase (MMP-9) for non-small cell lung cancer. Thirty-six cases with pathology confirmed non-small cell lung cancer and thirty-two of subjects with benign lung disease were reviewed in our hospital and included in this retrospective study. The serum level of CEA, NSE and MMP-9 were tested and compared between the non-small cell lung cancer patients and benign lung disease. The diagnosis sensitivity, specificity and area under the receiver-operating characteristic (ROC) curve (AUC) for serum CEA, NSE and MMP-9 were calculated with STATA10.0 software. The serum CEA, NSE and MMP-9 were 32.0±16.7 ng/mL, 51.6±68.3 ng/mL, 30.6 ±15.7 μg/L for the NSCLC patients and 15.1±10.9 ng/mL, 4.9±3.1 ng/mL, 9.3±5.9 μg/L for the benign lung disease patients with statistical difference (Pall<0.05); The diagnosis sensitivity, specificity and AUC were 80.0%, 72.2%, 0.84 for the serum CEA; 71.0%, 83.3% and 0.80 for NSE and 87.1%, 80.56%, 0.89 for MMP-9, respectively. The serum CEA, NSE and MMP-9 were generally elevated in patients with non-small cell lung cancer and could be used as potential bio-markers for non-small cell lung cancer diagnosis.


Evaluation of ergonomic physical risk factors in a truck manufacturing plant: case study in SCANIA Production Angers.
The aims of this study were 1) to assess the ergonomic physical risk factors from practitioner's viewpoint in a truck assembly plant with an in-house observational method and the NIOSH lifting equation, and 2) to compare the results of both methods and their differences. The in-house ergonomic observational method for truck assembly i.e. the SCANIA Ergonomics Standard (SES) and the NIOSH lifting equation were applied to evaluate physical risk factors and lifting of loads by operators. Both risk assessment approaches revealed various levels of risk, ranging from low to high. Two workstations were identified by the SES method as high risk. The NIOSH lifting index (LI) was greater than two for four lifting tasks. The results of the SES method disagreed with the NIOSH lifting equation for lifting tasks. Moreover, meaningful variations in ergonomic risk patterns were found for various truck models at each workstation. These results provide a better understanding of the physical ergonomic exposure from practitioner's point of view in the automotive assembly plant.


The role of signal transducers and activators of transcription in T inflammatory bowel diseases.
Signal transducers and activators of transcription (STAT) proteins are intracellular effector molecules of cytokine-modulated signaling. On the one hand, they play an important role in hematopoiesis and the development of the human immune system. STAT transcription factors are necessary for embryogenesis and the maintenance of the mammalian immune response. In the adult, STAT signaling is responsible for T-cell polarization toward interferon gamma-secreting Th1 T cells or interleukin 4-producing Th2 cells. On the other hand, these proteins are involved in the regulation of T-cell survival. STAT activation is strongly associated with tyrosine phosphorylation by tyrosine kinases, namely Jak1, Jak2, Jak3, and Tyk2. Counterregulatory mechanisms protecting from overwhelming STAT activation are represented by protein inhibitors of activated STATs and the SOCS family proteins. Because STAT proteins are key response elements of cytokine-induced T-cell activation, the characterization of STAT proteins is one step to elucidate disturbed T-cell function in inflammatory bowel disease. In particular, an activation of STAT-4 and STAT-3 in T cells seems to play a key pathogenic role in Crohn's disease.


Early Lipid Metabolic Effects of the Anti-Psychotic Drug Olanzapine on Weight Gain and the Associated Gene Expression.
Atypical antipsychotics such as olanzapine often cause metabolic side effects such as obesity and diabetes, leading to an increased risk of nonalcoholic fatty liver disease. The aim of the present study was to investigate the effects of olanzapine treatment on hepatic lipid metabolism and its possible relationship with adipose tissue status. Using a female rat model, we investigated the effects of chronic olanzapine administration on the regulation of carbohydrate and lipid metabolism including lipid biosynthesis, oxidation, efflux, and lipolysis in liver and adipose tissue. The body weight, liver mass and visceral adiposity after olanzapine treatment (2 mg/kg) for five weeks were not significantly different compared with vehicle controls. The serum level of triglycerides was higher in the vehicle controls than in olanzapine-treated rats. Unexpectedly, olanzapine treatment did not reduce glucose tolerance in our model. The expression of functional thermogenic protein uncoupling protein 1 (UCP1) was increased in brown adipose tissue (BAT) of the olanzapine group. Additionally, olanzapine treatment also reduced adipose inflammation in white adipose tissue (WAT). The transcription factor sterol regulatory element-binding protein (SREBP)-1c, a key early regulator of lipogenesis, was downregulated following olanzapine treatment. The expression of genes related to the triglycerides synthesis apparatus in the liver was upregulated in the olanzapine group. Olanzapine treatment induced genes involved in PPAR-α signaling and mitochondrial fatty acid oxidation in response to increased ATGL-mediated lipolysis in the liver. Together, our findings suggest a complicated link between olanzapine therapy and metabolic disturbance and may garner interest in assessing the action of antipsychotic-induced metabolic disturbances.


[Comparison of salicylazosulfapyridine bioavailability following oral and rectal administration in patients with ulcerative colitis].
Salicylazosulfapyridine--a drug commonly used in the ulcerative colitis--is effective following both oral and rectal administration. Pharmacokinetics of the drug given per rectum (in the form of suppositories) has not been investigated so far. The present study aims at comparing bioavailability of salicylazosulfapyridine following oral and rectal administration to patients with the ulcerative colitis and healthy volunteers. It was found, that following rectal administration the drug is not so readily absorbed as in oral dosage form. No sulfapyridine and 5-aminosalicylic acid have been detected in blood serum, when the drug was given in the form of rectal suppositories. Clinical stage of the disease did not affect absorption of both unchanged drug and its metabolites. Due to the fact, that the drug is active locally, rectal suppositories seem a therapeutical alternative in patients only with lesions localized in the rectum.


The nociception genes painless and Piezo are required for the cellular immune response of Drosophila larvae to wasp parasitization.
In vertebrates, interaction between the nervous system and immune system is important to protect a challenged host from stress inputs from external sources. In this study, we demonstrate that sensory neurons are involved in the cellular immune response elicited by wasp infestation of Drosophila larvae. Multidendritic class IV neurons sense contacts from external stimuli and induce avoidance behaviors for host defense. Our findings show that inactivation of these sensory neurons impairs the cellular response against wasp parasitization. We also demonstrate that the nociception genes encoding the mechanosensory receptors Painless and Piezo, both expressed in class IV neurons, are essential for the normal cellular immune response to parasite challenge.


Predictors of Placebo Response in Pharmacological Clinical Trials of Negative Symptoms in Schizophrenia: A Meta-regression Analysis.
We conducted a meta-regression analysis of all double-blind, randomized, placebo-controlled clinical trials (DBRCTs) reporting effects of drug and placebo on negative symptoms in people with stable schizophrenia and predominant or prominent negative symptoms to assess predictors of placebo response in these individuals. We used Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for systematic reviews and meta-analyses to conduct a systematic literature search to identify DBRCTs assessing treatment efficacy on negative symptoms, as primary outcome, in patients with stable schizophrenia and predominant or prominent negative symptoms. We used Cohen's d, with 95% CIs, as the effect size measure for placebo response, based on negative symptom change scores from baseline to endpoint (range 4 to 24 wk) in the placebo-treated group. We included 18 DBRCTs from 17 publications, assessing the effect of 13 drugs vs placebo on negative symptoms and comprising 998 patients, in the meta-regression analyses. Overall, drugs showed greater efficacy than placebo in reducing negative symptoms, with small effect size (Cohen's d: 0.208, P = .020). Placebo response was significant (P < .001) and clinically relevant (Cohen's d: 2.909), but there was significant heterogeneity and high risk of publication bias. Multivariable meta-regression analyses showed that larger numbers of arms in the trial, larger numbers of study sites and industry sponsorship were significant moderators of placebo response in this population. Our results suggest that some clinical trial design and operational factors affect the level of placebo response in such studies, thus highlighting the need for designs better suited to assess these outcomes.


Distinct Functional Modules for Discrete and Rhythmic Forelimb Movements in the Mouse Motor Cortex.
Movements of animals are composed of two fundamental dynamics: discrete and rhythmic movements. Although the movements with distinct dynamics are thought to be differently processed in the CNS, it is unclear how they are represented in the cerebral cortex. Here, we investigated the cortical representation of movement dynamics by developing prolonged transcranial optogenetic stimulation (pTOS) using awake, channelrhodopsin-2 transgenic mice. We found two domains that induced discrete forelimb movements in the forward and backward directions, and these sandwiched a domain that generated rhythmic forelimb movements. The forward discrete movement had an intrinsic velocity profile and the rhythmic movement had an intrinsic oscillation frequency. Each of the forward discrete and rhythmic domains possessed intracortical synaptic connections within its own domain, independently projected to the spinal cord, and weakened the neuronal activity and movement induction of the other domain. pTOS-induced movements were also classified as ethologically relevant movements. Forepaw-to-mouth movement was mapped in a part of the forward discrete domain, while locomotion-like movement was in a part of the rhythmic domain. Interestingly, photostimulation of the rhythmic domain resulted in a nonrhythmic, continuous lever-pull movement when a lever was present. The motor cortex possesses functional modules for distinct movement dynamics, and these can adapt to environmental constraints for purposeful movements. Significance statement: Animal behavior has discrete and rhythmic components, such as reaching and locomotion. It is unclear how these movements with distinct dynamics are represented in the cerebral cortex. We investigated the dynamics of movements induced by long-duration transcranial photostimulation on the dorsal cortex of awake channelrhodopsin-2 transgenic mice. We found two domains causing forward and backward discrete forelimb movements and a domain for rhythmic forelimb movements. A domain for forward discrete movement and a domain for rhythmic movement mutually weakened neuronal activity and movement size. The photostimulation of the rhythmic domain also induced nonrhythmic, lever-pull movement, when the lever was present. Thus, the motor cortex has functional modules with distinct dynamics, and each module retains flexibility for adaptation to different environments.


Measurement of Temperature and Relative Humidity with Polymer Optical Fiber Sensors Based on the Induced Stress-Optic Effect.
This paper presents a system capable of measuring temperature and relative humidity with polymer optical fiber (POF) sensors. The sensors are based on variations of the Young's and shear moduli of the POF with variations in temperature and relative humidity. The system comprises two POFs, each with a predefined torsion stress that resulted in a variation in the fiber refractive index due to the stress-optic effect. Because there is a correlation between stress and material properties, the variation in temperature and humidity causes a variation in the fiber's stress, which leads to variations in the fiber refractive index. Only two photodiodes comprise the sensor interrogation, resulting in a simple and low-cost system capable of measuring humidity in the range of 5-97% and temperature in the range of 21-46 °C. The root mean squared errors (RMSEs) between the proposed sensors and the reference were 1.12 °C and 1.36% for the measurements of temperature and relative humidity, respectively. In addition, fiber etching resulted in a sensor with a 2 s response time for a relative humidity variation of 10%, which is one of the lowest recorded response times for intrinsic POF humidity sensors.


Design and synthesis of mucoadhesive nanogel containing farnesol: investigation of the effect on HWP1, SAP6 and Rim101 genes expression of Candida albicans in vitro.
The evolution of drug resistance of Candida species to conventional antifungal agents has been a major medical challenge worldwide; attempt to use the potential antifungal agents with appropriate therapy efficacy and minimum effects is considerably growing. This study was conducted to evaluate the use of nanogel as a nanocarrier for pharmaceutical application of farnesol. The nanogels were synthetized using alginate (AL) and chitosan (CS) polymers containing 300 µM of farnesol in the nano-range 42-70 nm size. In vitro release studies indicated that release of farnesol from CS and AL nanogels was as 58% and 37%, respectively. Chitosan nanogel showed more in inhibitory zone as compared to AL nanogel (9 mm). Also, cytotoxicity assay showed no significant difference between control and treatment groups (p>.05). Finally, the effect of nanogels on genes expression of HWP1, SAP6 and Rim101 in Candida albicans ATCC10231 was assessed using real-time polymerase chain reaction (PCR). Expression of HWP1 and SAP6 genes in C. albicans treated with CS nanogel was significantly decreased (p<.01). In general, the obtained finding showed that, CS nanogel contains farnesol with proper antifungal activity and as a new approach used in pharmaceutical applications against C. albicans; however, more studies in vitro and in vivo are needed in the future.


Effective Hamiltonian for Ga1-x MnxAs in the dilute limit.
We derive an effective Hamiltonian for Ga(1-x)Mn(x)As in the dilute limit, where Ga(1-x)Mn(x)As can be described in terms of spin F=3/2 polarons hopping between the Mn sites and coupled to the local Mn spins. We determine the parameters of our model from microscopic calculations. Our approach treats the large Coulomb interaction in a nonperturbative way, captures the effects of spin-orbit coupling and disorder, and is appropriate for other p-doped magnetic semiconductors.


Celecoxib targets breast cancer stem cells by inhibiting the synthesis of prostaglandin E2 and down-regulating the Wnt pathway activity.
Pharmacological targeting of breast cancer stem cells (CSCs) is highly promising for the treatment of breast cancer, as the small population of CSCs is responsible for tumor initiation, progression, recurrence and chemo-resistance. Celecoxib is one of the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs), which have chemo-preventive activity against cancers, including breast cancer and colorectal cancer. However, the mechanisms by which NSAIDs exert its cancer prevention effects have yet been completely understood. In the present study, we investigated for the first time the effect of celecoxib on breast CSCs inhibition and its potential molecular mechanisms. Our results demonstrated that celecoxib suppresses CSC self-renewal, sensitizes chemo-resistance, inhibits epithelial to mesenchymal transition (EMT), and attenuates metastasis and tumorigenesis. Further exploring the underlying mechanism revealed that celecoxib targets breast CSCs by inhibiting the synthesis of prostaglandin E2 and down-regulating the Wnt pathway activity. Our findings suggest that celecoxib, by targeting CSCs, may be used as an adjuvant chemotherapy drug to improve breast cancer treatment outcomes.


Influence of two cultivars of persimmon on atherosclerosis indices in rats fed cholesterol-containing diets: Investigation in vitro and in vivo.
To assess the influence of two persimmon cultivars on some atherosclerosis indices in rats fed cholesterol (Chol)-containing diets. Persimmon cultivars "Fuyu" and "Jiro" as supplementation to rats' diets were investigated in vitro to compare the contents of their bioactive compounds (polyphenols, flavonoids, flavanols, tannins, carotenoids, and ascorbic acid) and antioxidant potentials. In the in vivo investigation, 36 male Wistar rats were randomly divided into six diet groups, each with six rats: control, control/Fuyu, control/Jiro, Chol, Chol/Fuyu, and Chol/Jiro. During a period of 47 d (42 d of feeding and 5-d adaptation before the experiment) of the trial, rats in the control group were fed a basal diet and two additional control groups (control/Fuyu and control/Jiro) a basal diet plus 5% of lyophilized Fuyu and Jiro, respectively. The Chol, Chol/Fuyu, and Chol/Jiro rat groups were fed a basal diet supplemented with 1% Chol (Chol group) and 1% Chol plus 5% lyophilized Fuyu (Chol/Fuyu group) and plus 5% lyophilized Jiro (Chol/Jiro group), respectively. After completion of the experiment, the rats were anesthetized using Narcotan (halothane) and sacrificed and the atherosclerotic lesions in the aorta were assessed. The obtained results of the investigation of all six groups were compared. Testing of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerols, total cholesterol in the liver, electrophoretic patterns of liver tissue, and three-dimensional fluorescence of serum protein fractions was performed. The polyphenols and tannins were significantly higher in the Fuyu cultivar (P<0.05). The antioxidant potential of persimmon Fuyu was higher than in the Jiro cultivar, but the difference was significant only according to the 2,2-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assay (P<0.05). Supplementation of diets with 5% of the lyophilized Fuyu and Jiro hindered the increase in plasma lipids versus the Chol group (total cholesterol 19.4% and 9.5%, low-density lipoprotein cholesterol 25.6% and 13.1%, respectively, P<0.05) and hindered the decrease in plasma antioxidant activity versus the Chol group by 40.0% and 16.8% and by 39.6% and 11.3% for the ABTS and 1,1-diphenyl-2-picrylhydrazyl assays, respectively. The atherosclerotic lesions in the aortas of the Chol/Fuyu and Chol/Jiro groups were significantly less than in the Chol group (P<0.05). Electrophoresis of the proteins from rats' liver tissue showed changes in 14-kDa bands after persimmon supplementation. A shift in maximum wavelengths in three-dimensional fluorescence of serum protein fractions after persimmon supplementation was found in comparison with the control group and an increase in fluorescence intensity compared with the Chol groups. The contents of polyphenols and tannins were significantly higher in the Fuyu cultivar (P<0.05). The antioxidant potentials of Fuyu were higher than those of the Jiro cultivar, but the difference was significant only according to the ABTS assay (P<0.05). Supplementation of 5% lyophilized Fuyu and Jiro to diets of rats fed Chol-containing diets 1) hindered the increase in plasma lipids levels and the decrease in plasma antioxidant activity and 2) significantly decreased the atherosclerotic lesions in the aorta (P<0.05). Electrophoretic patterns of liver tissue and fluorescence spectra can be used as additional biomarkers for determination of atherosclerosis indices.


The ultra-high risk concept-a review.
Attempts to identify people at imminent risk of psychotic disorder have been made during the past 20 years. High-risk criteria have been developed, and despite findings of a recent decline in the rate of onset of psychosis associated with these criteria, people identified still have a significantly greater risk, compared with the general population. Intervention studies in this group indicate that psychological treatments and fish oil appear to be just as effective as antipsychotics. Future research should refine risk factors for psychosis and examine outcomes other than psychosis. Research is also needed into what harms and benefits are associated with making the high-risk criteria into a formal diagnosis.


Digital Biobanking and Big Data as a New Research Tool: A Position Paper.
Big data analytics in medicine is driving significant change, as it offers vital information for improving functions, developing cutting-edge solutions and overcoming inefficiencies. With the right archiving and analysis tools, all players in the healthcare system, from hospitals to patients and from medical personnel to the pharmaceutical industry, can yield numerous benefits. Therefore, to analyze and interpret these analytics effectively, so that they can be useful for the advancement of scientific knowledge, we require information sharing, specific skills, training, integration between all system players, unique infrastructures and security. All these characteristics will make it possible to establish and harmonize real big data biobanks, for which it will be appropriate to consider new forms of governance compared to those traditionally conceived for large-sample biobanks.


Parametric analysis of gastric distension responses in the parabrachial nucleus.
The parabrachial nucleus (PBN) is regarded as an important locus for the processing and integration of sensory inputs from oral, gastrointestinal, and postabsorptive receptor sites and is thus thought to play an important role in regulating food intake. Gastric distension is an important satiation cue; however, such responses have been qualitatively characterized only over a limited area of the PBN. To more fully characterize gastric distension responses throughout the PBN, the responses of single units to gastric distension were tested using computer-controlled balloon inflation (3-18 ml air) in pentobarbital sodium- and/or urethan-anesthetized male rats. Distension-responsive neurons were indeed distributed throughout the nucleus from rostral areas typically considered to be visceral to more caudal areas associated with gustatory function, providing further anatomical support for the hypothesis that the PBN integrates taste and visceral signals that control feeding. Most PBN neurons had thresholds of 6 ml or less, similar to vagal afferent fibers. However, in contrast to the periphery, there were both excitatory and inhibitory responses. Increases in volume were associated with two distinct effects. First, as volume increased, the response rate increased; second, the duration of the response increased. In fact, in a subset of cells, responses to gastric distension lasted well beyond the stimulation period, particularly at larger volumes. Prolonged gastric distension responses are not common in the periphery and may constitute a central mechanism that contributes to satiation processes.


Unconstrained Monitoring Method for Heartbeat Signals Measurement using Pressure Sensors Array.
An unconstrained monitoring method for a driver's heartbeat is investigated in this paper. Signal measurement was carried out by using pressure sensors array. Due to the inevitable changes of posture during driving, the monitoring place for heartbeat measurement needs to be adjusted accordingly. An experiment was conducted to attach a pressure sensors array to the backrest of a seat. On the basis of the extreme learning machine classification method, driving posture can be recognized by monitoring the distribution of pressure signals. Then, a band-pass filter in heart rate range is adapted to the pressure signals in the frequency domain. Furthermore, a peak point array of the processed pressure frequency spectrum is derived and has the same distribution as the pressure signals. Thus, the heartbeat signals can be extracted from pressure sensors. Then, the correlation coefficient analysis of heartbeat signals and electrocardio-signals is performed. The results show a high level of correlation. Finally, the effects of driving posture on heartbeat signal extraction are discussed to obtain a theoretical foundation for measuring point real-time adjustment.


9-fluorenylphosphines for the Pd-catalyzed sonogashira, suzuki, and Buchwald-Hartwig coupling reactions in organic solvents and water.
The lithiation/alkylation of fluorene leads to various 9-alkyl-fluorenes (alkyl=Me, Et, iPr, -Pr, -C18H25) in>95% yields, for which lithiation and reaction with R2PCl (R=Cy, iPr, tBu) generates 9-alkyl, 9-PR2-fluorenes which constitute electron-rich and bulky phosphine ligands. The in-situ-formed palladium-phosphine complexes ([Na2PdCl4], phosphonium salt, base, substrates) were tested in the Sonogashira, Suzuki, and Buchwald-Hartwig reactions of aryl chlorides and aryl bromides in organic solvents. The Sonogashira coupling of aryl chlorides at 100-120 degrees C leads to>90% yields with 1 mol% of Pd catalyst. The Suzuki coupling of aryl chlorides typically requires 0.05 mol% of Pd catalyst at 100 degrees C in dioxane for quantitative product formation. To carry out "green" cross-coupling reactions in water, 9-ethylfluorenyldicyclohexylphosphine was reacted in sulphuric acid to generate the respective 2-sulfonated phosphonium salt. The Suzuki coupling of activated aryl chlorides by using this water-soluble catalyst requires only 0.01 mol% of Pd catalyst, while a wide range of aryl chlorides can be quantitatively converted into the respective coupling products by using 0.1-0.5 mol% of catalyst in pure water at 100 degrees C. Difficult substrate combinations, such as naphthylboronic acid or 3-pyridylboronic acid and aryl chlorides are coupled at 100 degrees C by using 0.1-0.5 mol% of catalyst in pure water to obtain the respective N-heterocycles in quantitative yields. The copper-free aqueous Sonogashira coupling of aryl bromides generates the respective tolane derivatives in>95% yield.


Planning primary health-care services for South Australian young offenders: a preliminary study.
Although many young offenders receive health care during periods of detention, addressing their health needs after release from secure care is a key strategy for successful rehabilitation and reintegration into the community. The purpose of this preliminary study was to examine current discharge planning practices for young offenders in Youth Training Centres in South Australia with a view to improving offenders' connection with primary health-care services on discharge. To determine the strengths and weaknesses of current discharge planning practices, this exploratory study involved in-depth review of literature and a semistructured focus group of stakeholders. Findings were discussed with an expert advisory group before final recommendations were made. This study identified a service model approach to discharge planning that recommended a nurse located within the Divisions of General Practice as the coordinator. The study found that trusted staff in detention centres, with an awareness of services available in the location of release, influence young offenders' decision-making in relation to health-care services. Awareness and recognition of young offenders' health beyond periods of juvenile detention and into their adult lives is valuable in that it has the potential to establish lifelong healthy behaviours. Bonding with young offenders and gaining their trust increases their likelihood of attending primary health-care services.


The distribution and structure of FTS immunoreactive cells in the thymus of the mouse.
The intrathymic distributions of facteur thymique sérique (FTS)-containing cells and Ia-expressing cells were examined by a double immunofluorescence technique in C57BL/6 mice of various ages. In the thymic medulla of all the mice examined, there were both FTS-immunoreactive cells and Ia-immunoreactive cells. The former cells, epithelial in nature, extended elongate cytoplasmic processes, while the latter were connected with each other by their spiny processes. The FTS-immunoreactive epithelial cells were all Ia-negative. The FTS-immunoreactive cells and Ia-immunoreactive cells were located in close proximity to each other. The cortex of the adult mice contained no FTS-immunoreactive epithelial cells. The cortex of the newborn and old mice, however, contained scattered FTS-immunoreactive epithelial cells with processes. FTS-immunoreactive cells in the cortex of the old mice possessed Ia-immunoreactive partner cells, while those in the cortex of newborn mice did not. In the marginal zone of the medulla of old mice, there were several cavities bounded by a partly ciliated epithelium and containing lymphocytes. The epithelial cells lining the cavities showed intense immunofluorescence for FTS. In addition to the epithelial cells, a certain population of round cells with thin cytoplasm lacking in discernible processes immunofluoresced for FTS. Located both in the medulla and in the cortex, these round cells were postulated to be thymocytes, the target cells of FTS, binding FTS on their cell surface.


The study of waiting time to first pregnancy in the south of Iran: A parametric frailty model approach.
Time to first pregnancy (TTFP) has never been studied in an Iranian setting. Lifestyle, occupational and environmental factors have been suggested to affect the female reproduction. This study was conducted to measure TTFP in the south of Iran and survey the effects of several similar factors on TTFP by frailty models. The data on TTFP were available for 882 women who were randomly selected from the rural population (the south of Iran). Only the first and the planned pregnancies of every woman were included. The data were collected retrospectively by using self-administered questionnaires. Frailty and shared frailty models were used to determine which factors had the highest impact on TTFP. The median TTFP was 6.4 months and several factors were surveyed. However, only the age of marriage, height, maternal education and regularity of menstruation prior to conception were selected in the multivariable models. Among the several factors which were included in the study, the result of frailty model showed that the height, age of marriage and regular menstruation seemed more notable predictors of TTFP.


Exposure to parental separation in childhood and later parenting quality as an adult: evidence from a 30-year longitudinal study.
Previous research has documented that exposure to parental separation/divorce during childhood can be associated with long-term consequences into adulthood. This study sought to extend this literature by examining associations between childhood exposure to parental separation/divorce and later parenting behavior as an adult in a New Zealand birth cohort. Data were drawn from the Christchurch Health and Development Study (CHDS), a longitudinal study of a birth cohort of 1,265 children born in 1977 in Christchurch, New Zealand. Information about exposure to parental separation and divorce was gathered annually from birth to 15 years. At the 30-year follow-up, all cohort members who had become parents (biological or nonbiological) were assessed on several parenting dimensions (sensitivity, warmth, overreactivity, inconsistency, quality of child management, and physical punishment). The analyses showed that exposure to more frequent parental separation in childhood and adolescence was associated with lower levels of parental sensitivity and warmth, greater overreactivity, and an increased use of physical punishment as a parent, after controlling for a wide range of family socioeconomic and psychosocial factors, and individual child characteristics. The findings suggest that as exposure to parental separation increases, so does the likelihood of experiencing multiple developmental challenges in childhood and adolescence. As an adult, these life-course experiences can have small but significant associations with the quality of parenting behavior.


Diallyl Disulfide From Garlic Oil Inhibits Pseudomonas aeruginosa Quorum Sensing Systems and Corresponding Virulence Factors.
Previously, we determined that diallyl disulfide (DADS) from garlic oil can inhibit Pseudomonas aeruginosa PAO1 pathogenic factors by inactivating the transcription of key genes from three quorum sensing (QS) systems (las, rhl, and pqs) based on the effects of DADS on growth, virulence factor production (elastase, pyocyanin, biofilm, and swarming motility), and RNA transcription (real-time q-PCR). To further investigate the mechanisms underlying the inhibition of the three P. aeruginosa QS systems by DADS, high-throughput RNA and proteome sequencing techniques were used to study differences in the transcriptional and proteome expression of P. aeruginosa PAO1 following treatment with DADS. The RNA-seq and proteomic data are available via NCBI Gene Expression Omnibus database with accession number GSE118801 and ProteomeXchange with identifier PXD011144, respectively. The experimental results indicated that all key genes of the three QS systems (las, rhl, and pqs) of P. aeruginosa PAO1 as well as the virulence factors (including exoprotease LasA, elastase LasB, lectin LecA and LecB, pyocyanin biosynthesis, and biofilm formation) regulated by these three QS systems were inhibited. This is consistent with our previous studies on the physiology, biochemistry, and RNA expression of P. aeruginosa treated with DADS. Additionally, our results also indicated that bacterial motility, chemotaxis, and two-component systems were inhibited by DADS treatment. All these changes abolish the sensitivity of P. aeruginosa PAO1 to environmental stimuli and cause the cells to be in a state of passivation. Further research is needed to determine how QS systems regulate these functions. Our findings could potentially contribute to the treatment and control of P. aeruginosa infection, virulence, and pathogenicity.


New information and social trust: asymmetry and perseverance of attributions about hazard managers.
It has been argued that news about negative events has a much stronger effect on decreasing social trust than does news about positive events on increasing it. This asymmetry principle of trust was investigated in two surveys that also investigated the perseverance of trust. The possibility that established trust attributions persevere in the face of new information raises questions about the limits of trust asymmetry. The two studies yielded evidence that both type of news (good versus bad) and initial general trust in the nuclear power industry or the food supply industry affected level of trust. Compared to individuals trusting the industry, those distrusting the industry exhibited less trust following both bad and good news events. Study I also found that judged informativeness and judged positiveness of news events were affected by type of news and general trust of the industry. Individuals low in general trust of the nuclear power industry judged both bad news and good news as less positive than did those high in general trust. Those low in general trust judged bad news as more informative than good news and than did those high in general trust. An important implication of the perseverance of trust is to focus attention on including not only the effects of information about specific events and actions, but also on the judgment processes underlying social trust. The Salient Value Similarity model is suggested as one way of accounting for these psychological processes.


In vivo: maternal betaine supplementation normalized fetal growth in diabetic pregnancy.
Diabetes alters maternal metabolism and can lead to aberrant fetal growth. In addition to insulin treatment, nutritional diet interventions are recommended for promoting fetal health against diabetes-induced adverse effects. Therefore, we conducted an in vivo study to investigate betaine efficacy on fetal development against maternal diabetes. Thirty-two dams were divided into four equal groups: control (C), betaine supplementation (BS), diabetic pregnancy (DP) and diabetic pregnancy plus betaine supplementation (DP + BS). Fasting blood sugar (FBS) and body weight (BW) were monitored during pregnancy. After physiological delivery, dams glycated hemoglobin (HbA1c) concentrations were measured, followed by fetal development indices including litter size (LS), neonatal weight (NW) and crown-rump (CR). Also, maternal oxidative status was assessed by evaluating glutathione (GSH) content, glutathione peroxidase (GSH-Px) and catalase (CAT) activities, and malondialdehyde (MDA) concentration in the erythrocytes. Betaine supplementation significantly alleviated FBS and tended to recover BW loss. It also significantly decreased HbA1c values in dams of DP + BS compared to DP group. Normalized fetal indices such as LS, NW and CR under betaine supplementation were associated with a significant increase in GSH content and GSH-Px activity, as well as decreased MDA concentrations in erythrocytes of dams in the DP + BS versus the DP group, indicating improved redox balance in the dams. We indicated for the first time that betaine supplementation improved the maternal glucose metabolism and redox balance associated with normalized fetal growth. Nevertheless, further studies are required to investigate the mechanisms through which betaine protects fetal growth in diabetic pregnancy.


Rapid catastrophic onset of Wegener's granulomatosis in a renal transplant.
A 62-year-old man with chronic renal failure secondary to Wegener's granulomatosis received a cadaveric renal graft in December 1990 after 2 years' treatment with continuous ambulatory peritoneal dialysis. Early graft function was good and serum creatinine fell steadily. On day 5 he became anuric and the graft became swollen and tender. Isotope renography showed no perfusion and the kidney was removed. Pathological examination showed widespread acute arteritis consistent with recurrent Wegener's granulomatosis. Recurrence of Wegener's granulomatosis in renal grafts is rare. The 4 previously reported cases are reviewed.


Total implantation of the active hearing implant TICA for middle ear disease: a temporal bone study.
A subpopulation of hearing-impaired patients has conductive hearing loss that cannot be improved by classic tympanoplasty. Other patients have a mixed hearing loss and cannot be helped by present forms of ear surgery or by hearing aids. Possible help for some patients may come from current implantable hearing devices if these are modified for the patient's specific anatomic situation. The TICA LZ 3001 is a hearing implant for total implantation used to treat moderate to severe sensorineural hearing loss. Most patients who use it have a normal ossicular chain that allows coupling of the implant to the incus. The present temporal bone study demonstrates that the TICA can also be used in patients with an interrupted ossicular chain. If the incus long process shows a defect, the TICA may be coupled to the incus body, and connection between the stapes and the long process of the incus can be achieved with a commercially available titanium-angle prosthesis or liquid ionomeric cement. In cases of an absent incus, the coupling axis of the transducer may be coupled to the stapes head via a modified coupling element. With an absent stapes, the coupling axis may be coupled directly to the perilymph by a coupling element similar to a gold stapes prosthesis.


LIMS for Lasers 2015 for achieving long-term accuracy and precision of δ(2)H, δ(17)O, and δ(18)O of waters using laser absorption spectrometry.
Although laser absorption spectrometry (LAS) instrumentation is easy to use, its incorporation into laboratory operations is not easy, owing to extensive offline manipulation of comma-separated-values files for outlier detection, between-sample memory correction, nonlinearity (δ-variation with water amount) correction, drift correction, normalization to VSMOW-SLAP scales, and difficulty in performing long-term QA/QC audits. A Microsoft Access relational-database application, LIMS (Laboratory Information Management System) for Lasers 2015, was developed. It automates LAS data corrections and manages clients, projects, samples, instrument-sample lists, and triple-isotope (δ(17)O, δ(18)O, and δ(2)H values) instrumental data for liquid-water samples. It enables users to (1) graphically evaluate sample injections for variable water yields and high isotope-delta variance; (2) correct for between-sample carryover, instrumental drift, and δ nonlinearity; and (3) normalize final results to VSMOW-SLAP scales. Cost-free LIMS for Lasers 2015 enables users to obtain improved δ(17)O, δ(18)O, and δ(2)H values with liquid-water LAS instruments, even those with under-performing syringes. For example, LAS δ(2) HVSMOW measurements of USGS50 Lake Kyoga (Uganda) water using an under-performing syringe having ±10 % variation in water concentration gave +31.7 ± 1.6 ‰ (2-σ standard deviation), compared with the reference value of +32.8 ± 0.4 ‰, after correction for variation in δ value with water concentration, between-sample memory, and normalization to the VSMOW-SLAP scale. LIMS for Lasers 2015 enables users to create systematic, well-founded instrument templates, import δ(2) H, δ(17) O, and δ(18) O results, evaluate performance with automatic graphical plots, correct for δ nonlinearity due to variable water concentration, correct for between-sample memory, adjust for drift, perform VSMOW-SLAP normalization, and perform long-term QA/QC audits easily.


Laparoscopic Ventral Rectopexy Versus Laparoscopic Wells Rectopexy for Complete Rectal Prolapse: Long-Term Results.
There is no agreement about which laparoscopic rectopexy technique is best for treating complete rectal prolapse. Purpose was to compare functional outcome, the recurrence rate, and quality of life in patients treated with laparoscopic ventral rectopexy (LVR) versus the laparoscopic Wells rectopexy (LWR) for complete rectal prolapse. A retrospective review of a prospectively maintained database of consecutive patients who presented with complete rectal prolapse. Patients were divided into two cohorts: first one had LVR and the other one had LWR. Exclusion criteria were previous major abdominal surgery, slow transit constipation, Hirschsprung's disease, inflammatory bowel disease, pregnancy, and patients on drugs that cause constipation. Patients were assessed preoperatively by clinical examination to evaluate constipation using the Wexner constipation scale (WCS), incontinence using the Wexner incontinence score (WIS), and quality of life using the gastrointestinal quality of life index (GIQOL). The primary outcome measures were disappearance of prolapse and recurrences. Secondary outcome parameters were operative time, complications, length of hospital stay, effect on perineal descent, functional outcome (constipation and continence), and quality of life. A total of 74 patients (mean age of 55 years) with complete rectal prolapse had LVR (n = 41) and LWR (n = 33). Sixty (81%) patients were females. Operative time was significantly longer in LVR (122 minutes versus 105 minutes; P = .001). Also, length of stay was significantly longer in LVR (4.5 days versus 3.7 days; P = .04). Recurrences were reported in 1 patient in each group. Perineal descent improved >50% in defecogram 6 months postoperatively in 79% in LVR versus 21% in LWR. In LVR, mean WCS decreased from 11.3 to 5.1 postoperatively (P < .0001), while in LWR it decreased from 8.9 to 6.9 (P = .11). Mean WIS decreased in LVR from 5.9 to 3.8, P = .01, while in LWR, it decreased from 6.6 to 2.8; P = .001. GIQOL improved from 74.4 to 124.9 in LVR and from 79.3 to 112.6 in LWR. The change in both groups was statistically significant (P = .0001). In this study, both LVR and LWR successfully and safely corrected the prolapse and prevented recurrence in patients after long-term follow-up. Operative time and hospital length of stay are significantly shorter in LWR. High incontinence scores and age >70 are potential predictors of bad continence postoperatively. LVR appears to be more suitable for patients with a high constipation score and abnormal perineal descent.


Interferon and growth factor activity for human lung fibroblasts. Release from bronchoalveolar cells from patients with active sarcoidosis.
Pulmonary sarcoidosis is a granulomatous disorder of unknown etiology characterized by both an active cellular immune process and interstitial fibrosis. It has recently been demonstrated that gamma-interferon (the type of interferon associated with an active cellular immune process) is also a potent growth factor for human lung fibroblasts. To evaluate the hypothesis that there is an association between the release of immune interferon and the release of growth factor activity for fibroblasts, bronchoalveolar cells from patients with sarcoidosis were studied for the spontaneous release of both immune interferon and growth factor activity for fibroblasts. Bronchoalveolar cells from 11 of the 24 patients spontaneously released gamma-interferon in vitro. Supernatants from sarcoidosis patients whose bronchoalveolar cells released interferon contained a significantly higher percentage of lymphocytes than those whose bronchoalveolar cell supernatants did not contain interferon (p less than 0.01). Fibroblast growth was also significantly augmented by supernatants from sarcoidosis patients whose bronchoalveolar cells released gamma-interferon compared to supernatants which did not contain interferon (p less than 0.05). In patients with focal abnormalities on chest x-ray films, there was significantly more interferon released by bronchoalveolar cells from the areas that were most abnormal compared to more normal areas of the lung. These studies suggest that there is an association between the release of immune interferon and release of growth factor activity for fibroblasts by bronchoalveolar cells from patients with active pulmonary sarcoidosis.


The effect of concealed carry weapons laws on firearm sales.
Despite numerous studies exploring the link between concealed carry weapons (CCW) laws and the effect of "more guns, more/less crime" it is unknown if liberalizing CCW laws indeed influences legal firearm sales. Building on previous research, I hypothesize that liberal CWW laws are associated with increases in handgun sales while having no association with long gun sales. Using National Instant Background Check System (NICS) data as a proxy for firearm sales and state fixed-effects regression models to examine the effect of CCW laws on gun sales in all 50 states the results can be simply put: liberal CCW laws are associated with increases in handgun sales, are not associated with long gun sales, and are associated with an increase in the overall share of firearms sold that are handguns. This work supports the idea that the expansion of gun rights via liberal CCW laws has increased the rate of handgun sales in the United States, but not the rate of long gun sales. Implications for future research on firearms and policy are discussed.


[Psychosocial aspects of chronic respiratory tract diseases (COPD): relevance and consequences for pulmonary rehabilitation].
As a part of the Davoser-Reha-Study, the significance of psychosocial aspects on the course of chronic pulmonary disease has been investigated on 414 patients (mean age = 47.1 years) with COPD (mean duration = 16 years) and a high percentage of multimorbidity (75%). Of special interest was the question, what kind of impact coping strategies do have on certain aspects of quality of life, in the sense of outcome criterias of the medical rehabilitation. Also it is not possible for the moment to draw final conclusions, because the knowledge about coping strategies and their adaptability is still very limited, the current study indicates, that some coping strategies are more supportive for adaptation than others. Positive for adaptation are strategies, which can be described as active exposition with the disease (fighting spirit, information seeking and active problem solving). Depressive coping strategies and the tendency to deny the disease seem to have a negative effect. All in all the results verify the strong necessity of taking psychosocial aspects into account for the complete treatment of chronically ill patients with COPD.


3-Bromomethyl-propyphenazone as a new derivatization reagent for high performance liquid chromatography of captopril and hydrochlorothiazide with UV-detection.
3-Bromomethyl-propyphenazone (BMP) was used as a derivatization reagent for the detection and quantification of captopril (CAP) and hydrochlorothiazide (HCT) by high performance liquid chromatography using Zorbax C8 column, and 0.05M sodium acetate, acetonitrile, methanol (14:17:4; pH 6.5) as mobile phase system with UV-detection at 254 nm. The cited reagent reacts with the mercapto and amino groups of CAP and HCT in acetone using anhydrous potassium carbonate as hydrobromide acceptor. The reaction was completed within 30 min for CAP and 60 min for HCT with heating at 105 +/- 5 degrees C in mini-reaction vial. The linear concentration ranges for both CAP and HCT were 8 to 160 and 6 to 140 ng per injection, respectively. The derivatized captopril was synthesized and confirmed with spectral analysis. This method was applied for determination of spiked captopril in human urine after extraction with Extrelut-20 column using ethyl acetate:isopropanol (85:15 v/v) as eluant.


Patients' descriptions of specific factors leading to modality selection of chronic peritoneal dialysis or hemodialysis.
There has been increasing interest in understanding how patients with chronic renal failure choose between chronic peritoneal dialysis (CPD) and hemodialysis (HD) for renal replacement therapy. The purpose of the present study was to examine the influences and specific factors that patients identify as significant in choosing a specific dialysis modality for treatment of their end-stage renal disease (ESRD). 40 patients (20 CPD, 20 HD) who had started dialysis within the preceding 6 months were randomly selected to participate in the study. A structured interview was conducted with the patients, discussing and exploring what factors patients thought were important in helping them decide their treatment modality. The format of the interview was open-ended. Based on patients' comments, a taxonomy of the specific factors that influenced the patients' decisions was developed. The study was conducted in a freestanding CPD unit and two freestanding HD units. All 20 CPD patients reported choosing their treatment modality; only 8 of the 20 HD patients reported having a choice of treatment modality. 18 of the 22 patients who participated in predialysis educational programs opted for CPD. 83% of the patients reported that their physician was important in influencing their treatment choice; however, the CPD patients relied more on written material and the opinions of their spouse/significant other or other family members in making their decisions. Issues of autonomy and control were important for 95% of patients choosing CPD. Both CPD and HD patients cited a variety of treatment-specific factors. The three most frequently cited reasons for choosing CPD were (1) flexibility of schedule (19 patients), (2) convenience of performing CPD in their own home (19 patients), and (3) the option of doing dialysis at night while sleeping (8 patients). The 8 HD patients who selected their treatment modality cited the desirability of having a planned schedule (7 patients) and letting nurses or other take care of them (5 patients). The present study explored factors perceived by patients as being important in determining their choice of renal replacement therapy. A taxonomy of patient influences and concerns has been developed to provide caregivers with a framework to structure their educational strategies and assist patients with progressive renal failure in making an informed choice of therapeutic modality for their ESRD treatment.


How We Make DNA Origami.
DNA origami has attracted substantial attention since its invention ten years ago, due to the seemingly infinite possibilities that it affords for creating customized nanoscale objects. Although the basic concept of DNA origami is easy to understand, using custom DNA origami in practical applications requires detailed know-how for designing and producing the particles with sufficient quality and for preparing them at appropriate concentrations with the necessary degree of purity in custom environments. Such know-how is not readily available for newcomers to the field, thus slowing down the rate at which new applications outside the field of DNA nanotechnology may emerge. To foster faster progress, we share in this article the experience in making and preparing DNA origami that we have accumulated over recent years. We discuss design solutions for creating advanced structural motifs including corners and various types of hinges that expand the design space for the more rigid multilayer DNA origami and provide guidelines for preventing undesired aggregation and on how to induce specific oligomerization of multiple DNA origami building blocks. In addition, we provide detailed protocols and discuss the expected results for five key methods that allow efficient and damage-free preparation of DNA origami. These methods are agarose-gel purification, filtration through molecular cut-off membranes, PEG precipitation, size-exclusion chromatography, and ultracentrifugation-based sedimentation. The guide for creating advanced design motifs and the detailed protocols with their experimental characterization that we describe here should lower the barrier for researchers to accomplish the full DNA origami production workflow.


Referring physicians underestimate the extent of abnormalities in final reports from myocardial perfusion imaging.
It is important that referring physicians and other treating clinicians properly understand the final reports from diagnostic tests. The aim of the study was to investigate whether referring physicians interpret a final report for a myocardial perfusion scintigraphy (MPS) test in the same way that the reading nuclear medicine physician intended. After viewing final reports containing only typical clinical verbiage and images, physicians in nuclear medicine and referring physicians (physicians in cardiology, internal medicine, and general practitioners) independently classified 60 MPS tests for the presence versus absence of ischemia/infarction according to objective grades of 1-5 (1 = No ischemia/infarction, 2 = Probably no ischemia/infarction 3 = Equivocal, 4 = Probable ischemia/infarction, and 5 = Certain ischemia/infarction). When ischemia and/or infarction were thought to be present in the left ventricle, all physicians were also asked to mark the involved segments based on the 17-segment model. There was good diagnostic agreement between physicians in nuclear medicine and referring physicians when assessing the general presence versus absence of both ischemia and infarction (median squared kappa coefficient of 0.92 for both). However, when using the 17-segment model, compared to the physicians in nuclear medicine, 12 of 23 referring physicians underestimated the extent of ischemic area while 6 underestimated and 1 overestimated the extent of infarcted area. Whereas referring physicians gain a good understanding of the general presence versus absence of ischemia and infarction from MPS test reports, they often underestimate the extent of any ischemic or infarcted areas. This may have adverse clinical consequences and thus the language in final reports from MPS tests might be further improved and standardized.


Utility and feasibility of integrating pulse oximetry into the routine assessment of young infants at primary care clinics in Karachi, Pakistan: a cross-sectional study.
Hypoxemia may occur in young infants with severe acute illnesses or congenital cardiac anomalies, but is not reliably detected on physical exam. Pulse oximetry (PO) can be used to detect hypoxemia, but its application in low-income countries has been limited, and its feasibility in the routine assessment of young infants (aged 0-59 days) has not been previously studied. The aim of this study was to characterize the operational feasibility and parent/guardian acceptability of incorporating PO into the routine clinical assessment of young infants in a primary care setting in a low-income country. This was a cross-sectional study of 862 visits by 529 infants at two primary care clinics in Karachi, Pakistan (March to June, 2013). After clinical assessment, oxygen saturation (Sp02) was measured by a handheld PO device (Rad-5v, Masimo Corporation) according to a standardized protocol. Performance time (PT) was the time between sensor placement and attainment of an acceptable PO reading (i.e., stable SpO2 + 1% for at least 10 s, heart rate displayed, and adequate signal indicators). PT included the time for one repeat attempt at a different anatomical site if the first attempt did not yield an acceptable reading within 1 min. Parent/guardian acceptability of PO was based on a questionnaire and unprompted comments about the procedure. All infants underwent physician assessment. Acceptable PO readings were obtained in ≤ 1 and ≤ 5 min at 94.4% and 99.8% of visits, respectively (n = 862). Median PT was 42 s (interquartile range 37; 50). Parents/guardians overwhelmingly accepted PO (99.6% overall satisfaction, n = 528 first visits). Of 10 infants with at least one visit with Sp02 <92% on a first PO attempt, 3 did not have a significant acute illness on physician assessment. There were no PO-related adverse events. Using a commercially available handheld pulse oximeter, acceptable Sp02 measurements were obtained in nearly all infants in under 1 minute. The procedure was readily integrated into existing assessment pathways and parents/guardians had positive views of the technology. When incorporated into routine clinical assessment of young infants at primary care clinics in a low-income country, PO was feasible and acceptable to parents/guardians. Future research is needed to determine if the introduction of routine PO screening of young infants will improve outcomes in low-resource settings.


The effects of denitrification parameterization and potential benefits of spatially targeted regulation for the reduction of N-discharges from agriculture.
Diffuse nitrate leaching from agricultural areas is a major environmental problem in many parts of the world. Understanding where in a catchment nitrate is removed is key for designing effective land use management strategies that protect water quality, while minimizing the impact on economic development. In this study we assess the effects of spatially targeted nitrate leaching regulation in a basin with limited knowledge of the complexity of chemical heterogeneity. Three alternative nitrate reactivity spatial parameterizations were incorporated in a catchment-scale flow and transport model and used to evaluate the effectiveness of four possible spatially targeted regulation options. Our findings confirm that denitrification parameterization cannot be numerically determined based on model inversion alone. Detailed field based characterization using physical and geochemical methods should be considered and incorporated in the numerical inversion scheme. We also demonstrate that there are potential benefits of implementing spatially targeted regulation compared to spatially uniform regulation. Focusing regulation in areas where nitrate residence time is short, such as riparian zones or areas with low natural N-reduction, results in greater reduction of N-discharges through groundwater. Significantly improved efficiencies can be expected when delineation of management zones considers the chemical heterogeneity and groundwater flow paths. These improved efficiencies are achieved by adopting management rules that regulate land use in discharge sensitive areas, where leaching changes contribute the most to the catchment nitrate discharges. In our case study, regulation in discharge sensitive zones was twice as efficient compared to other management options.


Selective suppression of resting B cell function in patients with systemic lupus erythematosus treated with cyclophosphamide.
The immunological function of patients with inactive systemic lupus erythematosus (SLE) receiving chronically administered, low-dose cyclophosphamide (CY) together with prednisolone (PSL) was compared with that of inactive patients receiving PSL alone. A striking selective suppression of "genuine" resting, but not "partially" or "fully" activated, B cell function was noted in the patients receiving PSL + CY as measured by Staphylococcus aureus Cowan I (SAC)-induced proliferative responses by Percoll-separated small resting B cells of high density; the small resting B cells sedimenting in a high density fraction were more responsive to SAC in patients treated with PSL alone than those in normal controls. However, the spontaneous proliferation and spontaneous secretion of immunoglobulins by peripheral blood B cells were elevated in both the patient groups. The proliferative responses to phytohaemagglutinin and concanavalin A by T cells were not significantly different between both patient groups. The data indicate that the genuine resting B cells may be the major target for the CY effect in SLE, and thus such selective suppression may help explain the efficacy of CY and PSL together in treating SLE.


Photochemical Hydrogen Doping Induced Embedded Two-Dimensional Metallic Channel Formation in InGaZnO at Room Temperature.
The photochemical tunability of the charge-transport mechanism in metal-oxide semiconductors is of great interest since it may offer a facile but effective semiconductor-to-metal transition, which results from photochemically modified electronic structures for various oxide-based device applications. This might provide a feasible hydrogen (H)-radical doping to realize the effectively H-doped metal oxides, which has not been achieved by thermal and ion-implantation technique in a reliable and controllable way. In this study, we report a photochemical conversion of InGaZnO (IGZO) semiconductor to a transparent conductor via hydrogen doping to the local nanocrystallites formed at the IGZO/glass interface at room temperature. In contrast to thermal or ionic hydrogen doping, ultraviolet exposure of the IGZO surface promotes a photochemical reaction with H radical incorporation to surface metal-OH layer formation and bulk H-doping which acts as a tunable and stable highly doped n-type doping channel and turns IGZO to a transparent conductor. This results in the total conversion of carrier conduction property to the level of metallic conduction with sheet resistance of ∼16 Ω/□, room temperature Hall mobility of 11.8 cm(2) V(-1) sec(-1), the carrier concentration at ∼10(20) cm(-3) without any loss of optical transparency. We demonstrated successful applications of photochemically highly n-doped metal oxide via optical dose control to transparent conductor with excellent chemical and optical doping stability.


Reduction of plasma lecithin--cholesterol acyltransferase activity by acute magnesium deficiency in the rat.
Weanling Wistar rats were pair-fed for 8 days control and magnesium-deficient diets. Acute magnesium deficiency increased plasma triglycerides and free cholesterol levels and decreased esterified cholesterol levels. The plasma activity of lecithin--cholesterol acyltransferase was markedly diminished in fasting magnesium-deficient rats (54% reduction) and plasma high density lipoprotein (HDL) free cholesterol was significantly increased in the HDL fraction. The results of this study showing that dietary magnesium affects the activity of the enzyme involved in the esterification of free cholesterol to cholesterol ester provide a possible basis for the reduced plasma cholesterol esterification and hyperlipidemia associated with acute magnesium deficiency.


A signal peptide peptidase (SPP) reporter activity assay based on the cleavage of type II membrane protein substrates provides further evidence for an inverted orientation of the SPP active site relative to presenilin.
Signal peptide peptidase (SPP) is an intramembrane-cleaving protease identified by its cleavage of several type II membrane signal peptides after signal peptidase cleavage. Here we describe a novel, quantitative, cell-based SPP reporter assay. This assay utilizes a substrate consisting of the NH2 terminus of the ATF6 transcription factor fused to a transmembrane domain susceptible to SPP cleavage in vitro. In cells, cleavage of the substrate releases ATF6 from the membrane. This cleavage can be monitored by detection of an epitope that is unmasked in the cleaved substrate or by luciferase activity induced by the cleaved ATF6 substrate binding to and activating an ATF6 luciferase reporter construct. Using this assay we show that (i) SPP is the first aspartyl intramembrane-cleaving protease whose activity increases proportionally to its overexpression and (ii) selectivity of various SPP and gamma-secretase inhibitors can be rapidly evaluated. Because this assay was designed based on data suggesting that SPP has an orientation distinct from presenilin and cleaves type II membrane proteins, we determined whether the segment of SPP located between the two presumptive catalytic aspartates was in the lumen or cytoplasm. Using site-directed mutagenesis to insert an N-linked glycosylation site we show that a portion of this region is present in the lumen. These data provide strong evidence that although the SPP and presenilin active sites have some similarities, their presumptive catalytic domains are inverted. This assay should prove useful for additional functional studies of SPP as well as evaluation of SPP and gamma-secretase inhibitors.


MR in patients with pacemakers and ICDs: Defining the issues.
There has been great controversy related to performance of magnetic resonance imaging in patients with pacemakers and implantable cardiac defibrillators. Recent questions have been raised regarding whether contraindications are absolute or relative. Although there are theoretical as well as documented issues relating to device malfunction, data suggest that scanning patients with devices may be feasible when important clinical questions need to be addressed by following strict guidelines. Advanced knowledge and understanding of electrophysiologic as well as magnetic resonance imaging-related issues, and a multidisciplinary, collaborative approach is required to further define the role of MR in patients with pacemakers and implantable cardiac defibrillators.


Impaired gastric gland differentiation in Peutz-Jeghers syndrome.
Gastrointestinal hamartomatous polyps in the Peutz-Jeghers cancer predisposition syndrome and its mouse model (Lkb1(+/-)) are presumed to contain all cell types native to the site of their occurrence. This study aimed to explore the pathogenesis of Peutz-Jeghers syndrome polyposis by characterizing cell types and differentiation of the epithelium of gastric polyps and predisposed mucosa. Both antral and fundic polyps were characterized by a deficit of pepsinogen C-expressing differentiated gland cells (antral gland, mucopeptic, and chief cells); in large fundic polyps, parietal cells were also absent. Gland cell loss was associated with an increase in precursor neck cells, an expansion of the proliferative zone, and an increase in smooth muscle alpha-actin expressing myofibroblasts in the polyp stroma. Lack of pepsinogen C-positive gland cells identified incipient polyps, and even the unaffected mucosa of young predisposed mice displayed an increase in pepsinogen C negative glands (25%; P = 0045). In addition, in small intestinal polyps, gland cell differentiation was defective, with the absence of Paneth cells. There were no signs of metaplastic differentiation in any of the tissues studied, and both the gastric and small intestinal defects were seen in Lkb1(+/-) mice, as well as polyps from patients with Peutz-Jeghers syndrome. These results identify impaired epithelial differentiation as the earliest pathological sign likely to contribute to tumorigenesis in individuals with inherited Lkb1 mutations.