Japanese infants' attachment insecurity and externalizing/internalizing problems: Using strange situation and attachment Q-sort methods.
According to attachment theory, an infant-mother attachment is universal, and infants who develop an insecure attachment relationship with their mother are likely to show mental health problems compared to those who develop a secure attachment relationship. These hypotheses have been empirically supported in Western cultures. However, the cross-cultural evidence is still insufficient. The purpose of this study was to examine the association between Japanese infants' attachment insecurity and mental health problems. We studied 81 Japanese infants (Mage = 14.64 months, SD = 1.43, females = 54%) mostly from middle-class families. The Strange Situation Procedure (SSP) and Attachment Q-sort (AQS) assessed infant attachment security. Infant externalizing and internalizing problems were rated concurrently by the mother and 6 months later by the mother and another adult (father or grandmother). Japanese infants' attachment insecurity measured by the AQS was associated with their externalizing problems concurrently and 6 months later. Infants with insecure-resistant attachment measured by the SSP had higher externalizing problems compared to those with secure attachment concurrently (not 6 months later). Attachment insecurity was not related to internalizing problems. These findings partly supported the association between attachment insecurity and mental health problems. This research also recommends observing infant attachment at home.


Sterilization of teeth by gamma radiation.
Clinical simulations and restorative materials research and development conducted in vitro require the use of large numbers of extracted teeth. The simultaneous need for infection control procedures and minimal alterations of structure and properties of the tissue prompted this study of gamma irradiation as a method to eliminate microbes associated with extracted teeth and their storage solutions. Evaluations of potential change in structure of dentin were conducted in terms of permeability, Fourier transform infrared spectroscopy (FTIR), and optical properties. The dose required for sterilization by gamma irradiation was established by means of a tooth model inoculated with Bacillus subtilis (10(8) organisms/mL). Sterilization occurred at a dose above 173 krad with use of a Cesium (Cs137) radiation source. Gamma irradiation did not affect permeability of crown segments of dentin. A comparative evaluation of the effects of four sterilization methods on dentin disks was based on FTIR and ultraviolet-visible-near infrared (UV/VIS/NIR) spectra before and after sterilization by (1) gamma irradiation; (2) ethylene oxide; (3) dry heat; and (4) autoclaving. No detectable changes were found with gamma irradiation, but all other methods introduced some detectable change in the spectra. This suggests that common methods of sterilization alter the structure of the dentin, but gamma irradiation shows promise as a method which both is effective and introduces no detectable changes as measured by FTIR, UV/VIS/NIR, or permeability.


Pituitary stalk lesions.
To describe the diverse causes of pituitary stalk lesions, their diagnosis, and treatment. Pathology of the pituitary stalk is often distinct from disease processes that affect the hypothalamus and/or pituitary. Pituitary stalk lesions fall into one of three categories: congenital, inflammatory/infectious, and neoplastic lesions. Stalk thickening may be found incidentally or when evaluating pituitary functional abnormalities. The precise cause must be looked for to enable the proper form of therapy of the underlying process. Hormone replacement is often also necessary.


Bronchial responses to enalapril in asthmatic, hypertensive patients.
The subjects, six asthmatic patients with mild essential hypertension, were aged 48 to 63 years and each was being treated with theophylline. Five patients received 10 mg of enalapril daily for two weeks and one received 5 mg for four weeks. Their bronchial responses to inhaled methacholine were measured with a modification of the 3-Hz oscillation method before and after the enalapril treatment. The patients' mean blood pressures decreased significantly from 180.7/100.3 to 152.0/93.3 mmHg after treatment. No treatment-associated changes in the frequency of coughing, the number of asthmatic attacks, or use of antiasthmatic drugs were noted. The results of the bronchial provocation tests revealed no changes in bronchial sensitivity or reactivity during treatment. Serum substance P levels were 61.3 pg/ml before treatment and 60.2 pg/ml after treatment. It is concluded that therapeutic doses of enalapril did not exacerbate asthmatic attacks or increase bronchial hypersensitivity in these asthmatic, hypertensive patients.


Role of DNA methyltransferase 1 on the altered eNOS expression in human umbilical endothelium from intrauterine growth restricted fetuses.
Reduced fetal growth associates with endothelial dysfunction and cardiovascular risk in both young and adult offspring and the nitric oxide (NO) system has been implicated in these effects. Epigenetic processes are likely to underlie such effects, but there is to date no evidence that endothelial dysfunction in early life results from epigenetic processes on key genes in the NO system, such as NOS3 (eNOS) and ARG2 (arginase-2). We determined basal DNA methylation status in NOS3 and ARG2 promoters, and DNA methyltransferase 1 (DNMT1) effect on eNOS and arginase-2 expression using human endothelial cells isolated from umbilical arteries (HUAEC) and veins (HUVEC) from control and intrauterine growth restricted (IUGR) fetuses. Compared with cells from control pregnancies, eNOS protein and mRNA levels were increased in HUAEC, but decreased in HUVEC, from IUGR, while arginase-2 levels were increased in IUGR-HUVEC. The NOS3 promoter showed a decrease in DNA methylation at CpG -352 in IUGR-HUAEC, and an increase in IUGR-HUVEC, when compared with control cells. Methylation in the hypoxia response element of the NOS3 promoter was increased in IUGR-HUAEC and decreased in HUVEC. Methylation in the AGR2 promoter in IUGR-HUVEC was decreased in a putative HRE, and without changes in IUGR-HUAEC. Silencing of DNMT1 expression normalized eNOS expression in IUGR endothelial cells, and restored the normal response to hypoxia in HUVEC, without effects on arginase-2. This data suggest that eNOS expression in IUGR-derived endothelial cells is programmed by altered DNA methylation, and can be reversed by transient silencing of the DNA methylation machinery.


Doctors' attitudes and confidence towards providing nutrition care in practice: Comparison of New Zealand medical students, general practice registrars and general practitioners.
Improvements in individuals' nutrition behaviour can improve risk factors and outcomes associated with lifestyle-related chronic diseases. This study describes and compares New Zealand medical students, general practice registrars and general practitioners' (GPs') attitudes towards incorporating nutrition care into practice, and self-perceived skills in providing nutrition care. A total of 183 New Zealand medical students, 51 general practice registrars and 57 GPs completed a 60-item questionnaire investigating attitudes towards incorporating nutrition care into practice and self-perceived skills in providing nutrition care. Items were scored using a 5-point Likert scale. Factor analysis was conducted to group questionnaire items and a generalised linear model compared differences between medical students, general practice registrars and GPs. All groups indicated that incorporating nutrition care into practice is important. GPs displayed more positive attitudes than students towards incorporating nutrition in routine care (p<0.0001) and performing nutrition recommendations (p<0.0001). General practice registrars were more positive than students towards performing nutrition recommendations (p=0.004), specified practices (p=0.037), and eliciting behaviour change (p=0.024). All groups displayed moderate confidence towards providing nutrition care. GPs were more confident than students in areas relating to wellness and disease (p<0.0001); macronutrients (p=0.030); micronutrients (p=0.010); and women, infants and children (p<0.0001). New Zealand medical students, general practice registrars and GPs have positive attitudes and moderate confidence towards incorporating nutrition care into practice. It is possible that GPs' experience providing nutrition care contributes to greater confidence. Strategies to facilitate medical students developing confidence in providing nutrition care are warranted.


On the biologically active structures of cholecystokinin, little gastrin, and enkephalin in the gastrointestinal system.
The biologically active conformations of a series of four peptides [four cholecystokinin (CCK)-related peptides and enkephalin] in their interactions with gastrointestinal receptors have been deduced using conformational computational analysis. The two peptides that interact exclusively with peripheral-type CCK receptors are the heptapeptide COOH-terminal fragment from CCK (CCK-7) and the analogous sequence from cerulein (CER-7) in which threonine replaces the methionine proximal to the NH2 terminus. The two peptides that interact exclusively with the gastrin receptor in the stomach are the active COOH-terminal fragment of little gastrin and the COOH-terminal tetrapeptide sequence common to all of these peptides, CCK-4. We find that preferred conformations for the peripherally active peptides CCK-7 and CER-7 are principally beta-bends, whereas little gastrin and CCK-4 are fundamentally helical. In the class of lowest energy structures for both CCK-7 and CER-7, the aromatic rings of the tyrosine and phenylalanine lie close to one another whereas the tryptophan indole ring points in the opposite direction. This structure is superimposable on the structures of a set of rigid indolyl benzodiazepine derivatives that interact with complete specificity and high affinity with peripheral CCK receptors further suggesting that the computed beta-bends are the biologically active conformation. The biologically active conformation for CCK-4 and the little gastrin hexapeptide has also been deduced. By excluding conformations common to CCK-7 and CCK-4, which do not bond to each other's receptors, and then by selecting conformations in common to CCK-4 and the gastrin-related hexapeptide, which do bind to each other's receptors, we deduce that the biologically active conformation at the gastrin receptor is partly helical and one in which the indole of tryptophan and the aromatic ring of phenylalanine are close to one another while the methionine and aspartic acid side chains point in the opposite direction. These major differences in preferred structures between the common CCK-7/CER-7 peptides and the common CCK-4/little gastrin peptides explain the mutually exclusive activities of these two sets of peptides. We have observed that [Met]enkephalin strongly antagonizes the action of the naturally occurring peripherally active CCK-8 (CCK-7 with an NH2-terminal aspartic acid residue added). The computed lowest energy structures for this opiate peptide closely resemble key features of the computed CCK-7/CER-7 structure, further supporting the proposed structure.


Effects of Parent Immigration Status on Mental Health Service Use Among Latino Children Referred to Child Welfare.
Latino families may be at risk of experiencing stressors resulting from the immigration process, such as those related to documentation status and acculturation, that may increase their need for mental health services. However, little research exists on the mental health needs and service use of Latino children. This study examined how parental nativity and legal status influence mental health needs and service utilization among children in Latino families investigated by child welfare. Data from the second National Survey of Child and Adolescent Well-Being, a nationally representative, prospective study of families investigated by child welfare agencies for maltreatment, were used to examine mental health need and service use in a subset of Latino children who remained in the home following a maltreatment investigation (N=390). Although children of immigrants did not differ from children of U.S.-born parents in levels of clinical need, they had lower rates of mental health service receipt. After the analyses accounted for other relevant variables, the odds of receiving services were significantly lower (odds ratio=.09) for children whose parents were undocumented compared with children whose parents were U.S. citizens. This study contributes to growing discourse on Latino family needs within the child welfare system. Analyses support earlier research regarding the effects of parent nativity on mental health service use and advance the literature by identifying parent legal status as a unique barrier to child service receipt.


Assessing patients' attitudes towards dietary supplements.
There is currently many over the counter products on the market that exert nutritional or physiological effects on the human body. The differences between dietary supplements and non-prescription drugs are however poorly understood by the average consumer and may thus affect their expectations as to the desired effect produced on the body. To evaluate patients' knowledge and attitudes towards dietary supplements as compared to non-prescription drugs. Subjects were 335 patients of the Mazowiecki Voivodeship Hospital in Warsaw, Poland. The data were collected from a face-to-face interview using a single and multiple choice questionnaire with 10 questions on dietary supplements. Statistical analysis used the Chi-square (χ2) test. The majority of respondents were found to be familiar with the term 'dietary supplements', but had difficulties in classifying these products into appropriate categories. Over 55% do not consider dietary supplements to be foodstuffs and more than 40% considered such products to be drugs. Most respondents thought that the main purpose of taking dietary supplements is to improve nutrition, but over one third expected them to also treat disease. Over 70% declared taking notice to which category the non-prescription products they bought belongs to ie. whether non-prescription drugs (medicinal products) or dietary supplements. Many patients mistakenly believe that dietary supplements are drugs and can be used to treat disease and health disorders. dietary supplements, opinion on dietary supplements, nutrition, dietary supplement vs. medicinal product.


Treatment of deep vein thrombosis with low-molecular-weight heparins: a consensus statement of the Gesellschaft für Thrombose-und Hämostaseforschung (GTH).
Recent studies have led to a new concept for the management of deep vein thrombosis. The German Society on Thrombosis and Haemostasis decided to work up the clinical studies in this field published until June 1996 for a consensus statement. The consensus group concluded that (1) high-dose, APTT-controlled subcutaneous administration of unfractionated heparin is as effective as high-dose, APTT-controlled continuous intravenous infusion of unfractionated heparin (grade B recommendation); (2) the anticoagulation with heparin may start at day 1 or 2, overlapping with oral anticoagulants for 7 to 10 days (grade C recommendation); (3) high-dose subcutaneous low-molecular-weight heparins are almost as effective and safe as continuous intravenous infusion of unfractionated heparins (grade B recommendation); (4) no agreement was obtained for the other concomitant treatments of DVT, such as duration of bed rest, use of antiphlogistic drugs, whether LMW heparins are comparable, and whether outpatient treatment can be recommended using LMW heparins.


Simulation analysis of contact angles and retention forces of liquid drops on inclined surfaces.
A simulation study of liquid drops on inclined surfaces is performed in order to understand the evolution of drop shapes, contact angles, and retention forces with the tilt angle. The simulations are made by means of a method recently developed for dealing with contact angle hysteresis in the public-domain Surface Evolver software. The results of our simulations are highly dependent on the initial contact angle of the drop. For a drop with an initial contact angle equal to the advancing angle, we obtain results similar to those of experiments in which a drop is placed on a horizontal surface that is slowly tilted. For drops with an initial contact angle equal to the mean between the advancing and the receding contact angles, we recover previous results of finite element studies of drops on inclined surfaces. Comparison with experimental results for molten Sn-Ag-Cu on a tilted Cu substrate shows excellent agreement.


Human herpes virus-8-associated multicentric Castleman's disease in an HIV-positive patient presenting with relapsing and remitting hyponatraemia.
We report a case of human herpes virus-8-associated multicentric Castleman's disease in an HIV-positive patient with hyponatraemia. A 65-year-old man was admitted with relapsing and remitting fever, scattered skin eruptions and hepatosplenomegaly following combination antiretroviral therapy for his HIV infection. Based on histopathological findings, he was diagnosed as having human herpes virus-8-associated multicentric Castleman's disease and was treated with four-weekly infusions of rituximab. Prior to receiving chemotherapy, we observed several suspected biomarkers of disease activity, positive correlations between plasma human herpes virus-8 viral load and the levels of plasma interleukin-6, C-reactive protein and soluble interleukin-2 receptor, and negative correlations between platelet count, albumin levels and especially serum sodium levels. We hypothesize that non-osmotic release of plasma antidiuretic hormone is a cause of hyponatraemia in human herpes virus-8-associated multicentric Castleman's disease and that relapsing and remitting hyponatraemia could be correlated with plasma human herpes virus-8 viral load.


Heterogeneity of protein kinase C isoenzyme gene expression in human T cell lines. Protein kinase C-beta is not required for several T cell functions.
An early consequence of stimulation of T cells via their Ag receptor is the activation of protein kinase C (PKC). It has recently been shown that PKC activity resides in a family of homologous proteins. Inasmuch as T cells are phenotypically and functionally heterogeneous, we examined the possibility that this heterogeneity may be reflected in differential expression of message for PKC isoenzyme genes. RNA from six leukemic T cell lines was probed for PKC-alpha, -beta, and -gamma message before and after activation. These studies revealed significant differences among these lines. None expressed mRNA for PKC-gamma. Whereas all cells possessed message for PKC-alpha, there was consistent variability in the level expressed. The greatest heterogeneity was seen with PKC-beta. Two cell lines, HUT 78 and HPB-ALL, did not hybridize with the beta probe under any conditions tested. We subsequently used these PKC-beta negative cells to study the role of this isoenzyme in mediating some of the effects seen with phorbol esters that directly bind to and activate PKC. Our results indicate that PKC-beta, which is expressed in some T cells, is not necessary for PMA-induced CD3 or CD4 internalization, IL-2 production, or acquisition of the p55 chain of the IL-2 receptor.


Functional outcome of supratrigonal cystectomy and augmentation ileocystoplasty in adult patients with refractory neurogenic lower urinary tract dysfunction.
To investigate the functional outcome after supratrigonal cystectomy and augmentation ileocystoplasty in adult patients with refractory neurogenic lower urinary tract dysfunction (NLUTD). Retrospective follow-up investigation in a single spinal cord injury rehabilitation center. In 29 patients, urodynamic data before and after supratrigonal cystectomy and augmentation ileocystoplasty, clinical outcome and post-operative complications were evaluated. The median age of the 29 patients at the time of surgery was 31 years, a median 14 years after NLUTD had occurred. At the last follow-up visit (median 2.4, range 0.4-9.0 years post-operatively), 20/29 patients (69%) were continent compared to 2/29 pre-operatively (P = 0.001). Furthermore, 16 patients required no or less detrusor relaxation therapy after augmentation ileocystoplasty. Augmentation cystoplasty resulted in a significant (P = 0.001) increase in the median bladder capacity (from 240 ml to 500 ml) and compliance (from 13 ml/cm H2 O to 50 ml/cm H2 O). The median maximum detrusor pressure had decreased significantly (P = 0.001) from 38 cm H2 O to 15 cm H2 O. Significantly (P = 0.001) fewer patients presented with a risk for renal damage (1 vs. 15 with maximum detrusor pressure >40 cm H2 O and 1 vs. 12 with detrusor compliance <20 ml/cm H2 O) at the last follow-up. The following complications were observed in 11/29 (38%) patients: paralytic and obstructive ileus, impaired bowel function, bladder stones, dehiscence, metabolic acidosis and autonomic dysreflexia. Protection of renal function, adequate bladder capacity and low detrusor pressure can be achieved using supratrigonal cystectomy and augmentation ileocystoplasty in patients suffering from refractory NLUTD.


Iris neovascularisation in eyes with pseudoexfoliation syndrome.
The iris vascular bed of eyes with pseudoexfoliation syndrome has been studied with electron microscopy. Two of the eyes suffered from painful glaucoma, whereas the third showed normal intraocular pressure. The following changes were observed: (1) deposits of pseudoexfoliation material lying adjacent to the endothelial wall; (2) thin vessel basement membrane, sometimes even interrupted; (3) extreme reduction of vessel lumina through increased volume of the endothelial cells; (4) fenestration of the endothelial wall. It is suggested that the iris neovascularisation in eyes with pseudoexfoliation syndrome is due to an obstruction of iris vessels causing tissue hypoxia.


An unusual etiology of posttraumatic Collet-Sicard Syndrome: a case report.
Posttraumatic Unilateral paralysis of the last four cranial nerves (IX-XI), known as collet-Sicard syndrome, is rare following closed head injury. A 21-year-old man presented with slurred speech, hoarseness voice and difficulty swallowing his saliva following closed head trauma. The cranial nerve examination revealed left sided severe dysfunction of cranial nerves VII, IX, X, XI, and XII. A CT-Scan of the neck was performed demonstrating a fracture of the left styloid process at the base of the skull. The Magnetic Resonance Imaging showed unusually well seen lower cranial nerves due to nerve edema. The patient was managed conservatively with steroids and regular sessions of neuromuscular and orthophonic rehabilitation. The nutrition had to be administered by gastrostomy since he was unable to swallow. Six months after the injury a total neurological recovery was noted. We present the exceptional case of Collet-Sicard Syndrome caused by styloid process fracture.


Acrylamide Content of Experimental Flatbreads Prepared from Potato, Quinoa, and Wheat Flours with Added Fruit and Vegetable Peels and Mushroom Powders.
Flatbreads are a major food consumed worldwide. To mitigate an undesirable safety aspect of flatbreads that might be associated with the potentially-toxic compound acrylamide, we recently developed recipes using a variety of grains that resulted in the production of low-acrylamide flatbreads. To further enhance the functionality of flatbreads, we have developed, in this work, new experimental flatbreads using potato, quinoa, and wheat flours supplemented with peel powders prepared from commercial nonorganic and organic fruits and vegetables (apples, cherry tomatoes, melons, oranges, pepino melons, sweet potato yams), potato peels, and mushroom powders (Lion's Mane, Hericium erinaceus; Reishi, Ganoderma lucidum; and Turkey Tail, Trametes versicolor). These additives have all been reported to contain beneficial compositional and health properties. The results of fortification of the baked flatbreads showed either no effect or increases in acrylamide content by unknown mechanisms. Since the additives did not increase the acrylamide content of the quinoa flour flatbreads for the most part, such supplemented quinoa flatbreads have the potential to serve as a nutritional, gluten-free, low-acrylamide, and health-promoting functional food. Mushroom powder-fortified wheat flatbreads with relatively low acrylamide content may also have health benefits.


Postoperative Complications of Ab Interno Gelatin Microstent.
To report 4 previously undescribed postoperative complications in 4 cases of ab interno XEN45 Gel Stent (XEN) implantation following uncomplicated surgeries. A total of 51 consecutive XEN implantations performed between July 1, 2017 and April 30, 2018 were reviewed. All cases were performed by 7 experienced glaucoma surgeons affiliated with the William Beaumont Hospital, Department of Ophthalmology. Cases with postoperative complications were identified, and a literature review was performed on PubMed.gov between April 5, 2018 and June 2, 2018 to identify previously unreported XEN complications. Case 1 consisted of an 86-year-old woman who suffered a suprachoroidal hemorrhage and associated rhegmatogenous retinal detachment following XEN implantation. One month after sclerotomy drainage and pars plana vitrectomy repair, an amputated XEN was found to have eroded through the conjunctiva. Case 2 consisted of a 68-year-old man with persistent elevated intraocular pressure due to recurrent Tenon's capsule fibrosis who developed complete XEN retraction into the subconjunctival space. Cases 3 and 4 consisted of a 68-year-old man and a 78-year-old woman who developed occlusion of the microstent's internal ostium by a partially detached Descemet's membrane. Case 3 maintained normal intraocular pressure on timolol, whereas case 4 resulted in bleb failure, despite Nd:YAG laser lysis of the occluded XEN internal ostium. Although the XEN is a promising new surgical option for the management of primary open-angle glaucoma, it can present unique postoperative challenges that are still being elucidated. Timely intervention or prevention of these complications can be improved by early surgeon recognition and effective communication with comanaging ophthalmologists.


Characterization of cytotoxic T lymphocytes recognizing autologous tumor cells with plural HLA-class I alleles in a patient with esophageal cancer.
T cell sublines and clones were established from the parental HLA-A2601-restricted cytotoxic T lymphocyte line (KE-4 CTL, HLA-A2601/2402, -B5101/40012, -Cw0102/0302) to investigate their capability to recognize tumor antigens on HLA-class I alleles other than HLA-A2601. Thirty-nine of 52 (75%) sublines or 30 of 83 (36%) clones produced interferon (IFN)-gamma by recognition of the autologous KE-4 tumor cells. Among these 39 CTL sublines, 22, 22, and 2 sublines produced IFN-gamma by recognition of HLA-A2402+, -B5101+, and Cw0102+ allogenic tumor cells, respectively. Four, 8, and 4 of these 30 CTL clones also produced IFN-gamma by recognition of HLA-A2402+, -B5101+, and Cw0102+ allogenic tumor cells, respectively. The other 13 sublines or 53 clones failed to produce IFN-gamma by recognition of the autologous tumor cells, respectively. These results suggest the presence of CTL recognizing shared tumor antigens on autologous tumor cells expressed by plural HLA-class I alleles in a patient with esophageal SCC.


Repression of bax gene expression by the HTLV-1 Tax protein: implications for suppression of apoptosis in virally infected cells.
The human T-cell leukemia virus-encoded oncoprotein Tax is a potent deregulator of cellular gene expression. Here we report that Tax represses transcription of the human bax gene, a gene whose protein product accelerates apoptosis. This repression is mediated through a 27-bp sequence in the bax promoter that contains a putative basic helix-loop-helix binding site. Deletion of this sequence abolishes Tax-mediated repression of bax. Repression of the bax gene may be biologically significant, as we also show that HTLV-I-infected cell lines are resistant to a variety of physical, chemical, and biological stimuli which induce apoptosis in uninfected T-cells. The repression of genes involved in promoting apoptosis, including the bax gene, may contribute to retroviral survival, and initiate a pathway toward malignant transformation.


Amphetamine sensitization and cross-sensitization with acute restraint stress: impact of prenatal alcohol exposure in male and female rats.
Individuals with fetal alcohol spectrum disorder (FASD) are at increased risk for substance use disorders (SUD). In typically developing individuals, susceptibility to SUD is associated with alterations in dopamine and hypothalamic-pituitary-adrenal (HPA) systems, and their interactions. Prenatal alcohol exposure (PAE) alters dopamine and HPA systems, yet effects of PAE on dopamine-HPA interactions are unknown. Amphetamine-stress cross-sensitization paradigms were utilized to investigate sensitivity of dopamine and stress (HPA) systems, and their interactions following PAE. Adult Sprague-Dawley offspring from PAE, pair-fed, and ad libitum-fed control groups were assigned to amphetamine-(1-2 mg/kg) or saline-treated conditions, with injections every other day for 15 days. Fourteen days later, all animals received an amphetamine challenge (1 mg/kg) and 5 days later, hormones were measured under basal or acute stress conditions. Amphetamine sensitization (augmented locomotion, days 1-29) and cross-sensitization with acute restraint stress (increased stress hormones, day 34) were assessed. PAE rats exhibited a lower threshold for amphetamine sensitization compared to controls, suggesting enhanced sensitivity of dopaminergic systems to stimulant-induced changes. Cross-sensitization between amphetamine (dopamine) and stress (HPA hormone) systems was evident in PAE, but not in control rats. PAE males exhibited increased dopamine receptor expression (medial prefrontal cortex (mPFC)) compared to controls. PAE alters induction and expression of sensitization/cross-sensitization, as reflected in locomotor, neural, and endocrine changes, in a manner consistent with increased sensitivity of dopamine and stress systems. These results provide insight into possible mechanisms that could underlie increased prevalence of SUD, as well as the impact of widely prescribed stimulant medications among adolescents with FASD.


Myocardial fibrosis in transforming growth factor-beta(1) (TGF-beta(1)) transgenic mice is associated with inhibition of interstitial collagenase.
TGF-beta(1) mediates effects on fibroblast proliferation and collagen synthesis in the myocardium. The extracellular matrix remodeling depends on the fibrillar collagen degrading matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). The in vivo effects of TGF-beta(1) on the MMP/TIMP system in TGF-beta(1) overexpressing transgenic mice were studied. Male Alb/TGF-beta(1)(cys(223,225)ser) transgenic mice (TG) and nontransgenic controls (C; 8 weeks) were examined. Protein expression of collagen type I, -III, interstitial collagenase (Int Coll), MMP-2, -9, TIMP-1, -2, -4 and TGF-beta(1) as well as enzyme activity (MMP-2, -9) were measured (Western blots, zymographic assays). mRNA expression of the interstitial collagenase and MMP-9 was studied with the Light-Cycler based real-time PCR. Overexpression of TGF-beta(1) resulted in a 10-fold increase in plasma and a seven-fold increase in myocardial TGF-beta(1) concentrations. Relative heart weights increased (mg g(-1): 7.8 +/- 0.4 vs. 4.8 +/- 0.6, n = 6; P < 0.01) in TG compared to C. Collagen type I and III increased in TG (1.9-fold and 1.7-fold) compared to controls. Interstitial collagenase protein activity (- 91%) and mRNA expression (-75%) in TG were reduced (P < 0.05-P < 0.001). Gelatinase (MMP-2, MMP-9) expression and activity were not significantly alterated. MMP-inhibitors were increased 2.5-fold (TIMP-1, -4) and 6-fold (TIMP-2) in TG. TGF-beta(1) produces myocardial fibrosis in vivo. This effect is not only produced by a stimulation of matrix protein formation: a complex regulation of MMP and TIMP interaction, namely decrease of expression and activity of interstitial collagenase and an enhanced inhibition by increased levels of TIMPs, are involved. These mechanisms are optional targets for therapeutic interventions in myocardial diseases.


The dopamine D4 receptor and the hyperactivity phenotype: a developmental-epidemiological study.
Attention-deficit hyperactivity disorder (ADHD) affects 2-6% of school-age children and is a precursor of behavioural problems in adolescence and adulthood. Underlying the categorical definition of ADHD are the quantitative traits of activity, impulsivity, and inattention which vary continuously in the population. Both ADHD and quantitative measures of hyperactivity are heritable, and influenced by multiple genes of small effect. Several studies have reported an association between clinically defined ADHD and the seven-repeat allele of a 48-bp tandem repeat polymorphism in the third exon of the dopamine D4 receptor gene (DRD4). We tested this association in a large, unselected birth cohort (n = 1037) using multiple measures of the hyperactivity phenotype taken at multiple assessment ages across 20 years. This longitudinal approach allowed us to ascertain whether or not DRD4 has a general effect on the diagnosed (n = 49) or continuously distributed hyperactivity phenotype, and related personality traits. We found no evidence to support this association.


Early nasogastric enteral nutrition for severe acute pancreatitis: a systematic review.
To evaluate the effectiveness and safety of early nasogastric enteral nutrition (NGEN) for patients with severe acute pancreatitis (SAP). We searched Cochrane Central Register of Controlled Trials (Issue 2, 2006), Pub-Medline (1966-2006), and references from relevant articles. We included randomized controlled trials (RCTs) only, which reported the mortality of SAP patients at least. Two reviewers assessed the quality of each trial and collected data independently. The Cochrane Collaboration's RevMan 4.2.9 software was used for statistical analysis. Three RCTs were included, involving 131 patients. The baselines of each trial were comparable. Meta-analysis showed no significant differences in mortality rate of SAP patients between nasogastric and conventional routes (RR = 0.76, 95% CI = 0.37 and 1.55, P = 0.45), and in other outcomes, including time of hospital stay (weighted mean difference = -5.87, 95% CI = -20.58 and 8.84, P = 0.43), complication rate of infection (RR = 1.41, 95% CI = 0.62 and 3.23, P = 0.41) or multiple organ deficiency syndrome (RR = 0.97, 95% CI = 0.27 and 3.47, P = 0.97), rate of admission to ICU (RR = 1.00, 95% CI = 0.48 and 2.09, P = 0.99) or conversion to surgery (RR = 0.66, 95% CI = 0.12 and 3.69, P = 0.64), as well as recurrence of re-feeding pain and adverse events associated with nutrition. Early NGEN is a breakthrough in the management of SAP. Based on current studies, early NGEN appears effective and safe. Since the available evidence is poor in quantity, it is hard to make an accurate evaluation of the role of early NGEN in SAP. Before recommendation to clinical practice, further high qualified, large scale, randomized controlled trials are needed.


Molecular Prediction of the O157:H-Negative Phenotype Prevalent in Australian Shiga Toxin-Producing Escherichia coli Cases Improves Concordance of In Silico Serotyping with Phenotypic Motility.
Shiga toxin-producing Escherichia coli (STEC) is a foodborne pathogen, and serotype O157:H7 is typically associated with severe disease. Australia is unique in its STEC epidemiology, as severe cases are typically associated with non-O157 serogroups, and locally acquired O157 isolates are H-negative/nonmotile. The H-negative phenotype and reduced severity of disease compared to that associated with H7/motile strains are distinct features of Australian O157 strains, but the molecular mechanism behind this phenotype has not been reported. Accurate characterization of the H-negative phenotype is important in epidemiological surveillance of STEC. Serotyping is moving away from phenotype-based methods, as next generation sequencing allows rapid extrapolation of serotype through in silico detection of the O-antigen processing genes, wzx, wzy, wzm, and wzt, and the H-antigen gene, fliC The detection and genotyping of fliC alone is unable to determine the motility of the strain. Typically, most Australian O157:H-negative strains carry an H7 genotype yet phenotypically are nonmotile; thus, many are mischaracterized as H7 strains by in silico serotyping tools. Comparative genomic analysis of flagellar genes between Australian and international isolates was performed and an insertion at nucleotide (nt) 125 in the flgF gene was identified in H-negative isolates. Chi-square results showed that this insertion was significantly associated with the H-negative phenotype (P < 0.0001). Phylogenetic analysis was also completed and showed that the Australian H-negative isolates with the insertion in flgF represent a clade within the O157 serogroup, distinct from O157:H7 serotypes. This study provides a genetic target for inferring the nonmotile phenotype of Australian O157 STEC, which increases the predictive value of in silico serotyping.


Comparative analysis of signature genes in PRRSV-infected porcine monocyte-derived cells to different stimuli.
Monocyte-derived DCs (mDCs) are major target cells in porcine reproductive and respiratory syndrome virus (PRRSV) pathogenesis; however, the plasticity of mDCs in response to activation stimuli and PRRSV infection remains unstudied. In this study, we polarized mDCs, and applied genome-wide transcriptomic analysis and predicted protein-protein interaction networks to compare signature genes involved in mDCs activation and response to PRRSV infection. Porcine mDCs were polarized with mediators for 30 hours, then mock-infected, infected with PRRSV strain VR2332, or a highly pathogenic PRRSV strain (rJXwn06), for 5 h. Total RNA was extracted and used to construct sequencing libraries for RNA-Seq. Comparisons were made between each polarized and unpolarized group (i.e. mediator vs. PBS), and between PRRSV-infected and uninfected cells stimulated with the same mediator. Differentially expressed genes (DEG) from the comparisons were used for prediction of interaction networks affected by the viruses and mediators. The results showed that PRRSV infection inhibited M1-prone immune activity, downregulated genes, predicted network interactions related to cellular integrity, and inflammatory signaling in favor of M2 activity. Additionally, the number of DEG and predicted network interactions stimulated in HP-PRRSV infected mDCs was superior to the VR-2332 infected mDCs and conformed with HP-PRRSV pathogenicity.


Association of Medication Treatment for Opioid Use Disorder With Suicide Mortality.
Understanding the effectiveness of medication treatment for opioid use disorder to decrease the risk of suicide mortality may inform clinical and policy decisions. The authors sought to describe the effect of medications for opioid use disorder (MOUD) on risk of suicide mortality. This was a retrospective cohort study in Department of Veterans Affairs (VA) patients from 2003 to 2017. The authors linked three data sources: the VA Corporate Data Warehouse, Centers for Medicare and Medicaid Services Claims Data, and the VA-Department of Defense Mortality Data Repository. The exposure of interest was MOUD, including starting periods (first 14 days on treatment), stopping periods (first 14 days off treatment), stable time on treatment, and stable time off treatment (reference category). The main outcome measures included suicide mortality, external-cause mortality, and all-cause mortality in the 5 years following initiation of MOUD. Over 60,000 VA patients received MOUD. Patients were typically male (92.8%) and their mean age was 46.5 years (SD=13.1). After adjusting for demographic characteristics, mental health and physical health conditions, and health care utilization, the adjusted hazard ratio during stable MOUD was 0.45 (95% CI=0.32, 0.63) for suicide mortality, 0.35 (95% CI=0.31, 0.40) for external-cause mortality, and 0.34 (95% CI=0.31, 0.37) for all-cause mortality. MOUD starting periods were associated with an adjusted hazard ratio for suicide mortality of 0.55 (95% CI=0.25, 1.21), and MOUD stopping periods were associated with an adjusted hazard ratio for suicide mortality of 1.38 (95% CI=0.82, 2.34). Treatment with MOUD was associated with a substantial reduction in suicide mortality as well external causes of mortality and all-cause mortality.


Monotypic epithelioid angiomyolipoma of the kidney: a case report.
A case of monotypic variant of epithelioid angiomyolipoma (AML) observed in a 62-year old woman is reported. The patient complained of abdominal fullness caused by a huge left renal mass without evidence of tuberous sclerosis complex. Imaging studies showed a left renal mass with an area showing hemorrhage and necrosis. The left renal mass, spleen and pancreatic tail were removed en bloc transabdominally. The resected tumor weighed 1200 g and showed focal necrosis and hemorrhage. Microscopically, the tumor was composed exclusively of atypical polygonal cells with copious eosinophilic cytoplasm, pleomorphic nuclei and prominent nucleoli. Tumor cells were considered to derive from perivascular epithelioid cells, and exhibited strong positive staining for HMB-45 and c-KIT, but were negative for epithelial, smooth muscle, and neural markers. As this tumor had none of the typical elements of classic AML, the final pathological diagnosis was monotypic epithelioid AML.


Neuronal control of astrocytic respiration through a variant of the Crabtree effect.
Aerobic glycolysis is a phenomenon that in the long term contributes to synaptic formation and growth, is reduced by normal aging, and correlates with amyloid beta deposition. Aerobic glycolysis starts within seconds of neural activity and it is not obvious why energetic efficiency should be compromised precisely when energy demand is highest. Using genetically encoded FRET nanosensors and real-time oxygen measurements in culture and in hippocampal slices, we show here that astrocytes respond to physiological extracellular K+ with an acute rise in cytosolic ATP and a parallel inhibition of oxygen consumption, explained by glycolytic stimulation via the Na+-bicarbonate cotransporter NBCe1. This control of mitochondrial respiration via glycolysis modulation is reminiscent of a phenomenon previously described in proliferating cells, known as the Crabtree effect. Fast brain aerobic glycolysis may be interpreted as a strategy whereby neurons manipulate neighboring astrocytes to obtain oxygen, thus maximizing information processing.


Emulating learning behavior in a flexible device with self-formed Ag dewetted nanostructure as active element.
Neuromorphic devices are a promising alternative to the traditional von Neumann architecture. These devices have the potential to achieve high-speed, efficient, and low-power artificial intelligence. Flexibility is required in these devices so that they can bend and flex without causing damage to the underlying electronics. This feature shows a possible use in applications that require flexible electronics, such as robotics and wearable electronics. Here, we report a flexible self-formed Ag-based neuromorphic device that emulates various brain-inspired synaptic activities, such as short-term plasticity and long-term potentiation (STP and LTP) in both the flat and bent states. Half and full-integer quantum conductance jumps were also observed in the flat and bent states. The device showed excellent switching and endurance behaviors. The classical conditioning could be emulated even in the bent state.


Immunogold-silver staining of mesangial antigen in lowicryl K4M- and LR gold-embedded renal tissue using epipolarization microscopy.
We examined the localization of a glomerular mesangial antigen with a Thy-1.1 monoclonal antibody by epipolarization microscopy (EPI) of silver-enhanced, immunogold-stained renal tissue embedded in LR Gold and Lowicryl K4M, and compared the attributes of these hydrophilic resins. Antigen was well preserved in tissue embedded in both resins. LR Gold-embedded tissue demonstrated excellent immunostaining properties, sectioned more easily, and showed better durability during staining than K4M. Lowicryl K4M-embedded tissue, however, displayed a phenomenon of self-illumination when counterstained with eosin which was not seen with LR Gold. This enabled immunostaining to be precisely related to tissue morphology without the necessity of simultaneous transillumination, which can be problematic when used in combination with EPI because of reflection of incident illumination from sub-stage optical surfaces.


Impact of pre-hospital handling and initial time to cranial computed tomography on outcome in aneurysmal subarachnoid hemorrhage patients with out-of-hospital sudden cardiac arrest-a retrospective bi-centric study.
Aneurysmal subarachnoid hemorrhage (SAH) presents occasionally with cardiac arrest (CA). The impact of pre-hospital and emergency room (ER) treatment on outcome remains unclear. Therefore, we investigated the impact of pre-hospital treatment, focusing on lay cardiopulmonary resuscitation (CPR), and ER handling on the outcome of SAH patients with out-of-hospital CA (OHCA). In this bi-centric retrospective analysis, we reviewed SAH databases for OHCA and CPR from January 2011 to June 2021. Patients were analyzed for general clinical and epidemiological parameters. CPR data were obtained from ambulance reports and information on ER handling from the medical records. Data were correlated with patient survival at hospital discharge as a predefined outcome parameter. Of 1,120 patients with SAH, 45 (4.0%) were identified with OHCA and CPR, 38 of whom provided all required information and were included in this study. Time to resuscitation was significantly shorter with lay resuscitation (5.3 ± 5.2 min vs. 0.3 ± 1.2 min, p = 0.003). Nineteen patients were not initially scheduled for cranial computed tomography (CCT), resulting in a significantly longer time interval to first CCT (mean ± SD: 154 ± 217 min vs. 40 ± 23 min; p < 0.001). Overall survival to discharge was 31.6%. Pre-hospital lay CPR was not associated with higher survival (p = 0.632). However, we observed a shorter time to first CCT in surviving patients (p = 0.065). OHCA in SAH patients is not uncommon. Besides high-quality CPR, time to diagnosis of SAH appears to play an important role. We therefore recommend considering CCT diagnostics as part of the diagnostic algorithm in patients with OHCA.


Removal of glucose from the cardiopulmonary bypass prime: a prospective clinical audit.
To quantify our decision for the removal of glucose and the use of mannitol as a substitute osmotic agent in the cardiopulmonary bypass prime, we conducted a prospective clinical audit to evaluate the effects of this change on patient outcomes. Data were prospectively collected for 172 consecutive routine cardiac surgery patients. The first 85 patients (Surgeon A, 42 patients [Group 1], Surgeon B, 43 patients [Group 2]) received 1000 mL Plasmalyte 148 + 5% glucose as per institutional protocol. The remaining priming volume for each group consisted of 500 mL hemaccel or 4% albumin, 50 mL 8.4% sodium bicarbonate, 100 mL Hartmann's solution. The change to a glucose-free prime was then initiated, substituting Plasmalyte 148 (without 5% glucose) for the Plasmalyte 148 + 5% glucose, in addition 12.5 g mannitol was administered following delivery of cardioplegia to the patients operated on by Surgeon B. Surgeon A would not include mannitol at this time. Forty-one patients operated by Surgeon A (Group 3) subsequently received Plasmalyte 148, and 46 patients operated on by Surgeon B (Group 4) received Plasmalyte 148 plus mannitol. Analysis was performed stratified by surgeon to quantify the effects of removing glucose from the prime. Comparisons were made between groups 1 and 3, and 2 and 4. Net fluid changes were recorded from pre-CPB, up to 24-h postoperatively. Intraoperative data collection included serum glucose, hematocrit, osmolality, return to rhythm, arrhythmias, and blood transfusions. Post-operative variables, including cardiac enzymes, arrhythmias, intubation time, length of stay, and mortality were also collected. Removal of glucose from the CPB prime resulted in a lower serum glucose concentration (mmol/L) during CPB (Gp 1 [13.6] vs. Gp 3 [5.4]; Gp 2 [14.7] vs. Gp 4 [5.4], p < .05). The addition of 12.5 g of mannitol to the CPB prime resulted in a significantly lower net fluid gain (mL) 24 h postoperatively (Gp 2[2792] vs. Gp 4 [1970], p < .05) and greater CPB hematocrit (%) (Gp 2 [24.3] vs. Gp 4 [26], p < .05). No other results were found to be significant (except CPB plasma osmolality (Groups 2 and 4) and sodium concentration [Groups 1 and 3]). The results of our audit provide an evidence base to support our change in practice to utilize nonglucose primes.


How much medium do you use for cell culture? Medium volume influences mineralization and osteoclastogenesis in vitro.
Bone is maintained by a balance between bone formation and resorption. This remodeling is controlled by a wide variety of systemic and local factors including hormones, cytokines and mechanical stresses. The present in vitro study examined the impact of medium volume, using 0.4, 0.6, 0.8, 1.0, 1.5 and 2.0 ml/well in a 24‑well plate, on the differentiation of osteoblasts and osteoclasts. There were no differences in the alkaline phosphatase activity of osteoblasts amongst the groups; however, the area of mineral deposition was decreased in a media volume‑dependent manner. A co‑culture of osteoblastic cells with bone marrow cells revealed a reduction in the total number of osteoclastic tartrate‑resistant acid phosphatase (TRAP)‑positive multinuclear cells (≥2 nuclei), whereas the formation of large osteoclastic TRAP‑positive multinuclear cells (≥8 nuclei) was increased, in a media volume‑dependent manner. There were also no differences in receptor activator of nuclear factor‑κB ligand mRNA and total osteoprotegerin (OPG) protein expression levels amongst the groups, however the concentration of OPG decreased in a media volume‑dependent manner. In conclusion, the present study demonstrated that the suppression of mineralization in osteoblastic cells and the stimulation of osteoclast fusion are dependent on the medium volume, indicating that media volume is an important factor in in vitro cell culture systems.


Observability in strategic models of viability selection.
Strategic models of frequency-dependent viability selection, in terms of mathematical systems theory, are considered as a dynamic observation system. Using a general sufficient condition for observability of nonlinear systems with invariant manifold, it is studied whether, observing certain phenotypic characteristics of the population, the development of its genetic state can be recovered, at least near equilibrium.


Does patient-physiotherapist agreement influence the outcome of low back pain? A prospective cohort study.
Recent research suggests that agreement between patients' and health professionals' perceptions may influence the outcome of various painful conditions. This issue has received little attention in the context of low back pain and physiotherapy interventions. The current study aimed at exploring the relationship between patient-physiotherapist agreement on baseline low back pain intensity and related functional limitations, and changes in patient outcomes four weeks later. Seventy-eight patient-physiotherapist dyads were included in the study. At baseline, patients and physiotherapists completed a Numerical Rating Scale and the Roland-Morris Disability Questionnaire. Patients' perceptions were reassessed over the phone at follow-up. Using multiple regression, baseline level of patient-physiotherapist agreement on pain intensity was associated with both outcome measures at follow-up. Agreement on functional limitations had no impact on outcomes. The results of this study indicate that patient-physiotherapist agreement has some impacts on the short-term outcomes of low back pain. Further research is needed to confirm these findings.


A one-year audit of specialist psycho-oncology services in an Irish tertiary referral centre.
Psychological services to patients with cancer are very limited in Ireland. A dedicated psycho-oncology service was established at our Institution 18 months ago. The aim of this study was to examine referral rates, psychiatric diagnoses and treatment interventions in this patient group. The clinical and psychiatric characteristics of consecutive patients (n = 63) referred to a recently established specialist psycho-oncology service in an Irish university teaching hospital over a one-year period were examined prospectively. International diagnostic criteria were applied. Forms of treatment instituted and clinical response to same were also audited. Over half (54%) of patients presented with affective disorder spectrum illnesses. The remaining referrals represented a diverse group of psychiatric diagnoses, but included a large proportion of patients with delirium. Approximately 20% of patients did not meet criteria for a psychiatric diagnosis. There was an over-representation of breast cancer and lymphoma. Thirty-eight per cent of patients were on prescribed corticosteroids at the time of referral. Eighty-two per cent of patients required some form of psychiatric intervention, and 86% of these benefited clinically from our intervention. The data suggest that even in oncology services with good existing support networks, such as this one, the role of an additional input from liaison psychiatry is considerable.


Peptides panned from a phage-displayed random peptide library are useful for the detection of Bacillus anthracis surrogates B. cereus 4342 and B. anthracis Sterne.
Recent use of Bacillus anthracis as a bioweapon has highlighted the need for a sensitive monitoring system. Current bacterial detection tests use antibodies as bio-molecular recognition elements which have limitations with regard to time, specificity and sensitivity, creating the need for new and improved cost-effective high-affinity detection probes. In this study, we screened a commercially available bacteriophage-displayed random peptide library using Bacillus cereus 4342 cells as bait to identify peptides that could be used for detection of Bacillus. The method enabled us to identify two 12-amino acid consensus peptide sequences that specifically bind to B. cereus 4342 and B. anthracis Sterne, the nonpathogenic surrogates of B. anthracis strain. The two Bacillus-binding peptides (named BBP-1 and BBP-2) were synthesized with biotin tag to confirm their binding by four independent detection assays. Dot-blot analysis revealed that the peptides bind specifically to B. cereus 4342 and B. anthracis Sterne. Quantitative analysis of this interaction by ELISA and fluorometry demonstrated a detection sensitivity of 10(2) colony forming U/ml (CFU/ml) by both assays. When the peptides were used in combination with Qdots, the sensitivity was enhanced further by enabling detection of even a single bacterium by fluorescence microscopy. Immunoblot analysis and protein sequencing showed that BBP-1 and BBP-2 bound to the S-layer protein of B. anthracis Sterne. Overall, our findings validate the usefulness of synthetic versions of phage-derived peptides in combination with Qdot-liquid nanocrystals as high sensitivity bioprobes for various microbial detection platforms.


Prescription and intake patterns in long-term and ultra-long-term benzodiazepine treatment in primary care practice.
Pharmacoepidemiological data show that long-term treatment accounts for a considerable part of benzodiazepine prescriptions in primary care practice. Prescription and intake patterns were, therefore, investigated in a study of 196 patients who had been treated with benzodiazepines for longer than six months by internists or general physicians in private practice. Patients were 64 years of age on average, half of them being 65 years or older. Females were in the majority (73.5%). The average duration of tranquilizer or hypnotic intake was 11.0 years, or 5.3 years for the current benzodiazepine medication. The mean daily dose was 9 mg diazepam equivalent. All benzodiazepine hypnotics and 61% of benzodiazepine tranquilizers had been prescribed solely for night-time use. Only 6% of the patients were taking benzodiazepines as single medication: on average they were taking 3.1 additional types of medication for other conditions, these being predominantly cardiac and antirheumatic/analgesic in nature. One in five patients was taking additional psychotropic medication. The compliance coefficient was on average 0.8, showing that patients did not tend to abuse benzodiazepines, with noncompliance generally being similar to noncompliance with other forms of medication.


Principles of pharmacoeconomic analysis: the case of pharmacist-led interventions.
In the past years, several factors such as evidence-based healthcare culture, quality-linked incentives, and patient-centered actions, associated with an important increase of financial constraints and pressures on healthcare budgets, resulted in a growing interest by policy-makers in enlarging pharmacists' roles in care. Numerous studies have demonstrated positive therapeutic outcomes associated with pharmaceutical services in a wide array of diseases. Yet, the evidence of the economic impact of the pharmacist in decreasing total health expenditures, unnecessary care, and societal costs relies on well-performed, reliable, and transparent economic evaluations, which are scarce. Pharmacoeconomics is a branch of health economics that usually focuses on balancing the costs and benefits of an intervention towards the use of limited resources, aiming at maximizing value to patients, healthcare payers and society through data driven decision making. These decisions can be guide by a health technology assessment (HTA) process that inform governmental players about medical, social, and economic implications of development, diffusion, and use of health technologies - including clinical pharmacy interventions. This paper aims to provide an overview of the important concepts in costing in healthcare, including studies classification according to the type of analysis method (e.g. budget-impact analysis, cost-minimization analysis, cost-effectiveness analysis, cost-utility analysis), types of costs (e.g. direct, indirect and intangible costs) and outcomes (e.g. events prevented, quality adjusted life year - QALY, disability adjusted life year - DALY). Other key components of an economic evaluation such as the models' perspective, time horizon, modelling approaches (e.g. decision trees or simulation models as the Markov model) and sensitivity analysis are also briefly covered. Finally, we discuss the methodological issues for the identification, measurement and valuation of costs and benefits of pharmacy services, and suggest some recommendations for future studies, including the use of Value of Assessment Frameworks.


Use of topical negative pressure with a lipidocolloid dressing: results of a clinical evaluation.
To evaluate the protection and acceptability of Urgotul wound dressing in the local management of acute or chronic wounds receiving topical negative pressure (TNP) therapy. This was a prospective multicentre non-comparative open-label trial. At each dressing change the investigating physician clinically evaluated and photographed the wound. Planimetric measurement was undertaken and wound depth was assessed at the start and end of the treatment. Follow-up was undertaken until deemed clinically unnecessary by the investigator. Sixty-six patients were included (42 acute wounds and 24 chronic wounds) and followed up for an average of 17 days. Dressing changes were deemed entirely painless in 52% of cases (compared with 18% at baseline) and pain between two consecutive dressing changes was absent in 66% of cases (34% at baseline). Removal of the TNP-interface dressing combination was considered'very easy' or 'easy' in 94% of cases and adherence to the wound was recorded as 'absent' in 88%. On average, the dressings were changed every 3.8 +/- 1.1 days (all wounds were considered), and wound area and depth were reduced by 19% and 54% respectively by the end of the follow-up period. Use of the interface dressing in combination with TNP substantially reduced the pain caused by dressing changes. It therefore makes more acceptable the use of this technique, which aims to optimise the management of wounds that are sometimes considered to be in a therapeutic impasse.


Stereological comparison of intraprostatic injection of alcohol and bleomycin with finasteride gavages in rats.
Resection of the prostate is one of the standard surgical treatments for symptomatic Benign Prostatic Hyperplasia (BPH). To evaluate minimally invasive treatments, intraprostatic injections of ethanol and bleomycin were compared with oral finasteride administration in rats with BPH. The rats were divided into six groups. The control rats received no BPH/no treatment. BPH was induced using injections of testosterone (2 mg/day/rat for 4 weeks) in groups II-VI. After 4 weeks, Group II received no treatment while Group III received oral finasteride (10 mg/kg/day). Moreover, Groups IV-VI received a single injection of ethanol (95%), bleomycin (5 mg/kg) and normal saline 25 mm3 in each ventral lobe of the prostate respectively. Two weeks after the injections, the ventral lobes underwent a quantitative stereological study. The volume of the ventral lobes, glandular epithelium, fibromuscular tissue and microvessles increased by 1.7, 3.1, 2.4 and 1.6 times in BPH rats respectively (P <0.01). Alcohol or bleomycin injection in PBH rats induced drastic recession of the increased volume of the ventral lobe, glandular epithelium and fibromuscular tissue (P <0.01). Regarding the BPH+alcohol group, the glandular epithelium volume restored to the normal values of the control rats (P <0.01). BPH+finasteride also incited an atrophic change in the volume of the whole prostate and glandular epithelium, but not the fibromuscular tissue and microvessels (P <0.01). Injection of alcohol and bleomycin (approximately 10% of the volume of ventral prostatic) as well as consuming finasteride can induce a reduction of 1/3, 1/4 and 1/5 in the hypertrophied gland respectively.


DGDFT: A massively parallel method for large scale density functional theory calculations.
We describe a massively parallel implementation of the recently developed discontinuous Galerkin density functional theory (DGDFT) method, for efficient large-scale Kohn-Sham DFT based electronic structure calculations. The DGDFT method uses adaptive local basis (ALB) functions generated on-the-fly during the self-consistent field iteration to represent the solution to the Kohn-Sham equations. The use of the ALB set provides a systematic way to improve the accuracy of the approximation. By using the pole expansion and selected inversion technique to compute electron density, energy, and atomic forces, we can make the computational complexity of DGDFT scale at most quadratically with respect to the number of electrons for both insulating and metallic systems. We show that for the two-dimensional (2D) phosphorene systems studied here, using 37 basis functions per atom allows us to reach an accuracy level of 1.3 × 10(-4) Hartree/atom in terms of the error of energy and 6.2 × 10(-4) Hartree/bohr in terms of the error of atomic force, respectively. DGDFT can achieve 80% parallel efficiency on 128,000 high performance computing cores when it is used to study the electronic structure of 2D phosphorene systems with 3500-14 000 atoms. This high parallel efficiency results from a two-level parallelization scheme that we will describe in detail.


Sequence of extracellular mouse protein BM-90/fibulin and its calcium-dependent binding to other basement-membrane ligands.
Partial sequence comparisons have recently indicated that two extracellular components, fibulin from human placenta and BM-90 from a basement-membrane-producing mouse tumor, are either identical or closely related proteins. In this study, a complete sequence analysis of mouse BM-90 cDNA showed a 539-residue N-terminal core structure (domains I and II), which was 85% identical with the same core structure of human fibulin. A 137-residue C-terminal sequence (domain III) was unique for BM-90 and could also be identified by Edman degradation. This suggested a novel splice product, variant D, which is characteristic for the mouse tumor. A second 117-residue C-terminal sequence (domain III) was identified in additional mouse cDNA clones and showed 91% identity with the region specific for variant C of fibulin. Northern blots using mouse cells demonstrated two mRNA species, 2.7 kb and 2.3 kb, which encoded the variants D and C, respectively. The sequence of BM-90/fibulin indicates the presence of nine epidermal-growth-factor-like repeats in the core domain-II structure, eight of which contain consensus motifs for calcium binding. This binding is apparently important for the interaction of BM-90 with laminin and nidogen and for some weaker interactions with collagen IV. Further binding of BM-90 was demonstrated to fibronectin and BM-90 itself, but did not depend on calcium. Major binding sites for BM-90 were identified at a C-terminal segment of laminin A chain and at the N-terminus of nidogen. The broad interaction repertoire of BM-90 is comparable to that of nidogen and both proteins may have similar roles as connecting elements in the extracellular matrix.


Treatment adherence in schizophrenia. Spanish clinical consensus.
Objective. Establish a Spanish Consensus on Therapeutic Compliance in Schizophrenia.
 Material and methods. An experts committee designed a specific questionnaire having 40 questions and 293 options. The questions referred to the definition and general assessment of compliance in schizophrenia, factors involved, intervention strategies in outpatients and in acute units and management of oral and long duration injectable antipsychotic drugs and other non-pharmacological therapies. First, second or third line strategy values of choice were assigned according to the answers obtained for each item. The questionnaire was sent to 383 psychiatrists of a Therapeutic Compliance Work Group. A total of 326 answers were received with an electronic system that guaranteed their confidentiality.

 Results and conclusions. There is maximum agreement on considering the seriousness of the compliance problem, its repercussion in relapses, the patient's course and increase in health care costs. The strategies preferred to evaluate compliance are: counting of the injectable drug administration and determination of plasma concentrations. The Consensus considers that specific intervention is necessary when the patient has already suffered several relapses due to low therapeutic compliance, when null awareness of disease is detected or if there is comorbidity with toxic consumption. Psychoeducational is the non-pharmacological strategy having the greatest consensus grade if intervention is needed. Treatments with atypical injectable, long duration, antipsychotic drugs obtain the best grade in accordance with pharmacological strategies of first choice, in different clinical situations to avoid or improve therapeutic adherence.

 Key words:
 Adherence. Compliance. Schizophrenia. Consensus.


Criteria for detection of possible risk factors for mental health problems in undergraduate university students.
Developing approaches for early detection of possible risk clusters for mental health problems among undergraduate university students is warranted to reduce the duration of untreated illness (DUI). However, little is known about indicators of need for care by others. Herein, we aimed to clarify the specific value of study engagement and lifestyle habit variables in predicting potentially high-risk cluster of mental health problems among undergraduate university students. This cross-sectional study used a web-based demographic questionnaire [the Utrecht Work Engagement Scale for Students (UWES-S-J)] as study engagement scale. Moreover, information regarding life habits such as sleep duration and meal frequency, along with mental health problems such as depression and fatigue were also collected. Students with both mental health problems were classified as high risk. Characteristics of students in the two groups were compared. Univariate logistic regression was performed to identify predictors of membership. Receiver Operating Characteristic (ROC) curve was used to clarify the specific values that differentiated the groups in terms of significant predictors in univariate logistic analysis. Cut-off point was calculated using Youden index. Statistical significance was set at p < 0.05. A total of 1,644 students were assessed, and 30.1% were classified as high-risk for mental health problems. Significant differences were found between the two groups in terms of sex, age, study engagement, weekday sleep duration, and meal frequency. In the ROC curve, students who had lower study engagement with UWES-S-J score < 37.5 points (sensitivity, 81.5%; specificity, 38.0%), <6 h sleep duration on weekdays (sensitivity, 82.0%; specificity, 24.0%), and < 2.5 times of meals per day (sensitivity, 73.3%; specificity, 35.8%), were more likely to be classified into the high-risk group for mental health problems. Academic staff should detect students who meet these criteria at the earliest and provide mental health support to reduce DUI among undergraduate university students.


Pulse wave analysis with diffusing-wave spectroscopy.
Hypertension is a major risk factor for cardiovascular disease and thus at the origin of many deaths by e.g. heart attack or stroke. Hypertension is caused by many factors including an increase in arterial stiffness which leads to changes in pulse wave velocity and wave reflections. Those often result in an increased left ventricular load which may result in heart failure as well as an increased pulsatile pressure in the microcirculation l to damage to blood vessels. In order to specifically treat the different causes of hypertension it is desirable to perform a pulse wave analysis as a complement to measurements of systolic and diastolic pressure by brachial cuff sphygmomanometry. Here we show that Diffusing Wave Spectroscopy, a novel non-invasive portable tool, is able to monitor blood flow changes with a high temporal resolution. The measured pulse travel times give detailed information of the pulse wave blood flow profile.


Hypothalamic dopaminergic neurons in transgenic dwarf mice: histofluorescence, immunocytochemical, and in situ hybridization studies.
Spontaneous dwarf mice, in which both growth hormone (GH) and prolactin (PRL) are undetectable, are severely deficient in the PRL-inhibiting catecholamine dopamine (DA), as well as its synthetic enzyme, tyrosine hydroxylase (TH), in the basal hypothalamus (Phelps et al., Cell Tissue Res., 240:19-25, 1985; Phelps, Brain Res., 416:354-358, 1987). In contrast, transgenically constructed dwarf mice (Behringer et al., Genes Dev., 2:453-461, 1988) show complete ablation of pituitary GH cells, but PRL cells are retained at a level of approximately 10% of normal. In order to determine the feedback effect of this reduced, rather than absent, PRL on hypothalamic DA neurons, brains of transgenic dwarf mice were examined for catecholamine transmitters by histofluorescence, for the synthetic enzyme TH by immunocytochemistry, and for TH mRNA expression by in situ hybridization. DA histofluorescence in transgenic dwarfs was comparable to that of normal littermate mice in nonpituitary regulating areas (perikarya of zona incerta [A13] of hypothalamus and in midbrain substantia nigra area [A9]). Arcuate nucleus (A12) DA neurons that inhibit PRL secretion, however, showed dim to absent fluorescence in perikarya and in external median eminence terminals in dwarfs. There were reduced (P less than 0.05) numbers of A12 TH-immunoreactive neurons in transgenic dwarfs, to approximately 60% of those in normal mice. In contrast, TH-positive neurons in other hypothalamic areas (A13, A14) had average populations equivalent to those in normal mice. Quantification of TH mRNA abundance by in situ hybridization using both image analysis of hybridization over the arcuate nucleus, and grain counts per individual A12 cell in this nucleus, indicated that relative mRNA levels were the same in normal and transgenic dwarfs. The observations indicate that reduction in pituitary PRL is accompanied by defective expression in hypothalamic tuberoinfundibular neurons, which is severe at the DA neurotransmitter level, significant regarding observable TH immunoreactivity, and undetectable with regard to TH mRNA expression. Collectively, the findings suggest that posttranscriptional processes are involved with the mediation of PRL feedback upon hypothalamic neurons. Technically and quantitatively, the report presents the feasibility of simultaneous evaluation of transmitter histofluorescence, synthetic enzyme immunocytochemistry, and mRNA expression in individual animals.


A magnetoencephalography spatiotemporal analysis of neural activities during feature binding.
Previous literature shows that feature binding processes elicit fronto-hippocampal areas. The time course of this process, however, remains unknown. This is the first study that investigates feature binding using magnetoencephalography. Synthetic aperture magnetometry analysis was used to localize sources of increased power in the theta band during the encoding phases of a feature-binding task in the left and right medial frontal gyri (Brodmann's area 10) and left and right anterior cingulate gyri. Theta band synchronization was observed in many of these same areas, but also in other areas not noted to have increased theta band power suggesting a broad network of regions subserving the encoding phase of feature binding.


Association between antibody status to bovine herpesvirus 1 and quality of milk in dairy herds in Poland.
Bovine herpesvirus 1 (BoHV1) is one of the most important pathogens of cattle; however, its effect on somatic cell count and milk components is not completely understood. The aim of the current study was to examine the effect of BoHV1 infection on quality of bovine bulk tank milk (BTM). A total of 1,790 individual blood samples collected at 28 dairy farms were used to determine the BoHV1 infection status of the herds with ELISA tests. The quality parameters of milk were evaluated by instrumental methods with BTM samples collected at monthly intervals from May 2011 to May 2012. The statistical analysis was performed to study the associations between BoHV1 herd status, quality of BTM, and herd-specific parameters. The risk factors influencing bulk milk somatic cell count (BMSCC) were estimated using the multivariable mixed-effects maximum likelihood regression model. The true prevalences of BoHV1 infection at the animal and herd levels were 49.3 and 64.6%, respectively. The average BMSCC differed significantly between the herds grouped accordingly to their BoHV1 infection status. Interestingly, the highest BMSCC was observed in the vaccinated herds (240.3×10(3) cells/mL). Additionally, the BoHV1 herd status had a significant effect on the fat content of BTM. The largest herds that were investigated had a BoHV1 seroprevalence over 30%. The herd status was considerably influenced by the numbers of cows in the herds. Besides, no significant differences in total bacterial count or protein content in milk from BoHV1-infected und uninfected herds were observed. An increase in BMSCC was observed during summer compared with the winter months regardless of the BoHV1 status of the herds. In the final multivariable regression model, the main risk factors associated with BMSCC were BoHV1 herd status, the percentage of BoHV1 infected animals in a herd, the number of cows in a herd, and the season. Our study suggests that BoHV1 infection may influence BMSCC levels, which are key parameters of BTM quality and a reference for subclinical mastitis in a herd. In conclusion, BoHV1 infection may cause economic losses by decrease both of quantity and quality of milk.


Ion channel mutations in mouse models of inherited neurological disease.
Analysis of the molecular defects in mouse mutants can identify candidate genes for human neurological disorders. During the past 2 years, mutations in sodium channels, calcium channels and potassium channels have been identified by positional cloning of the spontaneous mouse mutants motor endplate disease, tottering, lethargic and weaver. The phenotypes of four allelic mutations identified in the sodium channel gene Scn8a range from ataxia and muscle weakness through severe dystonia and progressive paralysis, indicating that human mutations in this gene could be associated with a variety of clinical syndromes. Mutations of the calcium channel subunits beta 4 in the lethargic mouse and alpha 1A in the tottering mouse have specific effects on cerebellar function. Targeted mutation of ligand-gated ion channels has also been used to generate new models of neurological disease. We will review these recent achievements and their implications for human neurological disease. The mouse studies indicate that mutations in ion channel genes are likely to be responsible for a broad spectrum of clinical phenotypes in human neurological disorders.


A comparative study on basophil activation test, histamine release assay, and passive sensitization histamine release assay in the diagnosis of peanut allergy.
Allergy can be diagnosed using basophil tests. Several methods measuring basophil activation are available. This study aimed at comparing basophil activation test (BAT), histamine release assay (HR), and passive sensitization histamine release assay (passive HR) in the diagnosis of peanut allergy. BAT, HR, and passive HR were performed on 11 peanut-allergic and 14 nonallergic subjects. Blood was incubated with peanut extract or anti-IgE and tests were performed as follows: BAT-CD63 upregulation was assessed by flow cytometry; HR-released histamine was quantified by a glass fiber-based fluorometric method; passive HR-IgE-stripped donor basophils were incubated with participants' serum and histamine release was quantified as HR. CDsens, a measure of basophil allergen sensitivity, was significantly higher for BAT (80.1±17.4) compared to HR (23.4±10.31) and passive HR (11.1±2.0). BAT, HR, and passive HR had a clinical sensitivity of 100%, 100%, and 82% and specificity of 100%, 100%, and 100%, respectively, when excluding inconclusive results. BAT identified 11 of 11 allergic patients, HR 10, and passive HR 9. Likewise, BAT recognized 12 of 14 nonallergic subjects, HR 10, and passive HR 13. However, the tests' diagnostic performances were not statistically different. Interestingly, nonreleasers in HR but not in BAT had lower basophil count compared to releasers (249 vs 630 counts/min). BAT displayed a significantly higher CDsens compared to HR and passive HR. The basophil tests' diagnostic performances were not significantly different. Still, BAT could diagnose subjects with low basophil number in contrast to HR.


Historical Perspectives on Colorectal Trauma Management.
The authors discuss the history and evolution of management of traumatic wounds to the colon and rectum, summarizing early management parallel with the history of armed conflict followed by the increase in research and management interest by civilian centers in the post-Vietnam era. They explore the strong opinions of the early thought-leaders such as DeBakey and Ogilvie, detailing factors that may have impacted their views. The current literature on optimal management of both colon and rectal trauma is reviewed, including the contentious debate over which patients may benefit from diversion. Current organ injury staging and clinical practice guidelines are also reviewed, as well as lessons learned by the U.S. military in recent conflicts in Iraq and Afghanistan. Understanding of the evolution of colon and rectal trauma management, as well as the current literature, will help surgeons in their decision-making and management of these challenging injuries.


A microwave-assisted multicomponent synthesis of substituted 3,4-dihydroquinazolinones.
A microwave-assisted, multicomponent protocol for the synthesis of substituted 3,4-dihydroquinazolinones via a novel cascade imine/cyclization/aza-Henry reaction sequence is reported. Starting from o-formyl carbamates, a series of structurally diverse 3,4-dihydroquinazolinones was synthesized via a cyclic iminium ion intermediate in moderate to excellent yields. Notably, the reaction is fast, flexible, simple to perform and tolerates a variety of functional groups.


New method of Helmholtz coil alignment.
A new alignment method for Helmholtz coils is proposed. This method is based on a probe, whose axis is the same as the alignment axis. This probe includes one magnetic sensor, whose position is slightly shifted from the probe axis, and which is set perpendicular to the axis. Using this probe, the tilt and shift of the magnetic centre of Helmholtz coils can be aligned to within an order of 0.1 mrad and 0.1 mm, respectively. Moreover, by this method, effects of terrestrial magnetism and tilt of the magnetic sensor can be removed from the measurement. This alignment method is presented along with an estimate of the alignment accuracy of the SPring-8 linac injector.


Primary Tooth Vital Pulp Therapy: A Systematic Review and Meta-analysis.
This systematic review and meta-analysis assessed outcomes in primary teeth for the vital pulp therapy (VPT) options of indirect pulp therapy (IPT), direct pulp capping (DPC), and pulpotomy after a minimum of 12 months to determine whether one VPT was superior. The following databases were searched from 1960 to September 2016: MEDLINE, EMBASE, CENTRAL, EBSCO, ICTRP, Dissertation abstracts, and grey literature for parallel and split-mouth randomized controlled trials of at least 12 months duration comparing the success of IPT, DPC, and pulpotomy in children with deep caries in primary teeth. Our primary outcome measure was overall success (combined clinical and radiographic). Three authors determined the included RCTs, performed data extraction, and assessed the risk of bias (ROB). Meta-analysis and assignment of quality of evidence by Grading of Recommendations Assessment, Development and Evaluation approach were done. Forty-one articles qualified for meta-analysis (six IPT, four DPC, and 31 pulpotomy) from 322 screened articles. The 24-month success rates were: IPT=94.4 percent, and the liner material (calcium hydroxide [CH]/bonding agents) had no effect on success (P=0.88), based on a moderate quality of evidence; DP =88.8 percent, and the capping agent (CH/alternate agent) did not affect success (P=0.56), based on a low quality of evidence. The combined success rate for all pulpotomies was 82.6 percent based on 1,022 teeth. Mineral trioxide aggregate (MTA) (89.6 percent) and formocresol (FC) (85.0 percent) success rates were the highest of all pulpotomy types and were not significantly different (P=0.15), with a high quality of evidence. MTA's success rate (92.2 percent) was higher than ferric sulfate (FS) (79.3 percent) and approached significance (P=0.06), while FS's success rate (84.8 percent) was not significantly different from FC (87.1 percent), both with a moderate quality of evidence. MTA and FC success rates were significantly better than CH (P=0.0001), with a moderate quality of evidence. At 18 months, sodium hypochlorite (NaOCl) success rate was significantly less than FC (P=0.01) with a low quality of evidence. The highest level of success and quality of evidence supported IPT and the pulpotomy techniques of MTA and FC for the treatment of deep caries in primary teeth after 24-months. DPC showed similar success rates to IPT and MTA or FC pulpotomy, but the quality of the evidence was lower. Systematic Review Registration Number: PROSPERO 2015: CRD42015006942.


Characterization of the Aspergillus nidulans 14-3-3 homologue, ArtA.
The 14-3-3 family of proteins function as small adaptors that facilitate a diverse array of cellular processes by mediating specific protein interactions. One such process is the DNA damage checkpoint, where these proteins prevent inappropriate activation of cyclin-dependent kinases. The filamentous fungus Aspergillus nidulans possesses a highly conserved 14-3-3 homologue (artA) that may function in an analogous manner to prevent septum formation. However, instead of blocking septation, over-expression of artA causes a severe delay in the polarization of conidiospores. This observation suggests that these proteins play an important role in hyphal morphogenesis.


Repeated arterial embolization of rat livers by degradable microspheres.
A transient arrest of arterial blood flow can be accomplished by intra-arterial injection of a new type of degradable microsphere. The effects of single and multiple injections of these microspheres into rat hepatic arteries were studied by measurements of fractional cardiac output distribution and 133Xe washout from the liver before and after embolization. Injection of these microspheres into the hepatic artery caused a significant but transient reduction of the arterial blood flow to the liver. Repetition of the injection several times over several days produced identical effects on each embolization. No signs of hepatic cell damage were detected after repeated embolization, as suggested by assay of the serum enzymes or the Bromsulphalein retention test.


Application progress of intelligent flavor sensing system in the production process of fermented foods based on the flavor properties.
Fermented foods are sensitive to the production conditions because of microbial and enzymatic activities, which requires intelligent flavor sensing system (IFSS) to monitor and optimize the production process based on the flavor properties. As the simulation system of human olfaction and gustation, IFSS has been widely used in the field of food with the characteristics of nondestructive, pollution-free, and real-time detection. This paper reviews the application of IFSS in the control of fermentation, ripening, and shelf life, and the potential in the identification of quality differences and flavor-producing microbes in fermented foods. The survey found that electronic nose (tongue) is suitable to monitor fermentation process and identify food authenticity in real time based on the changes of flavor profile. Gas chromatography-ion mobility spectrometry and nuclear magnetic resonance technology can be used to analyze the flavor metabolism of fermented foods at various production stages and explore the correlation between flavor substances and microorganisms.


[Congenital mesenteric band simulating a small-bowel volvulus in a mesenteric rotation anomaly].
A congenital mesenteric band is a rare cause of intestinal obstruction. We describe a case of upper gastrointestinal obstruction on a jejunal congenital band in a 2-year-old child. The challenge is to make the diagnosis in a patient with no history of previous surgery.


Survey of the degree of examinees' satisfaction with instructions on how to read results of general health checkups at a workplace.
To clarify measures for making clearer instructions on how to read the results of general health checkups in a workplace by surveying the views of workers on these instructions, an anonymous self-administered questionnaire survey was conducted at a Japanese manufacturing plant. The responses of 984 male workers were analyzed. The average age of the subjects was 32.1 yr (range, 19-60 yr). Regarding the instructions, 4.1% of the subjects answered "definitely sufficient," 58.9% "somewhat sufficient," 28.0% "neither sufficient nor insufficient," 8.1% "somewhat insufficient" and 0.8% "definitely insufficient." Multiple regression analysis showed that the degree of examinees' satisfaction significantly correlated with the health condition (standard partial regression coefficient =0.189, p<0.001), knowledge of health management (standard partial regression coefficient =0.095, p=0.014), and fear of lifestyle-related diseases (standard partial regression coefficient =0.095, p=0.009). The adjusted R square value of the multiple regression analysis was 0.064. It is necessary to provide more detailed information to those with poor health. Because the instructions contain many difficult medical terms, health professionals must give instructions that are easy to understand. Those feeling fear of lifestyle-related diseases may already know how to read checkup results. It is necessary to promote awareness of lifestyle-related diseases targeting people unfamiliar with such diseases.


Oncolytic Reovirus Inhibits Immunosuppressive Activity of Myeloid-Derived Suppressor Cells in a TLR3-Dependent Manner.
Oncolytic reovirus, which possesses 10 segments of dsRNA genome, mediates antitumor effects via not only virus replication in a tumor cell-specific manner, but also activation of antitumor immunity; however, the mechanism(s) of reovirus-induced activation of antitumor immunity have not been fully elucidated. Recent studies have demonstrated that overcoming an immunosuppressive environment in tumor-bearing hosts is important to achieve efficient activation of antitumor immunity. Among the various types of cells involved in immunosuppression, it has been revealed that myeloid-derived suppressor cells (MDSCs) are significantly increased in tumor-bearing hosts and play crucial roles in the immunosuppression in tumor-bearing hosts. In this study, we examined whether reovirus inhibits the immunosuppressive activity of MDSCs, resulting in efficient activation of immune cells after in vivo administration. The results showed that splenic MDSCs recovered from PBS-treated tumor-bearing mice significantly suppressed the Ag-specific proliferation of CD8+ T cells. In contrast, the suppressive activity of MDSCs on T cell proliferation was significantly reduced after reovirus administration. Reovirus also inhibited the immunosuppressive activity of MDSCs in IFN-β promoter stimulator-1 knockout (KO) mice and in wild-type mice. In contrast, the immunosuppressive activity of MDSCs in TLR-3 KO mice was not significantly altered by reovirus treatment. The activation levels of CD4+ and CD8+ T cells were significantly lower in TLR3 KO mice than in wild-type mice after reovirus administration. These results indicate that reovirus inhibits the immunosuppressive activity of MDSCs in a TLR3, but not IFN-β promoter stimulator-1, signaling-dependent manner.


Association between tuberculosis and atopy: role of the CD14-159C/T polymorphism.
The development of allergic hypersensitivity depends on both genetic and environmental factors. Different amounts of microbial products could affect patients with atopy and different genotypes. We aimed to evaluate the role of varying degrees of exposure to infection by Mycobacterium tuberculosis (tuberculosis) in atopic patients and analyze the association with genetic factors. We performed CD14-159C/T genotyping in atopic patients (n=118) and healthy individuals (n=62) and recorded the following variables: rural lifestyle, exposure to persons with tuberculosis, bacille Calmette-Guerin (BCG) vaccination, tuberculin skin test (TST), skin prick test, and phenotypes of atopy. Blood samples were analyzed for soluble-CD14 (sCD14), interferon (IFN) y, total immunoglobulin (Ig) E, and eosinophil levels. A score was used to identify the likelihood of exposure to tuberculosis. Almost all the study participants had had a BCG vaccination, and half had a positive TST result. No differences were observed between atopic patients with high/low tuberculosis scores and CD14 genotypes in terms of atopic phenotypes, allergen sensitization, and levels of total IgE, sCD14, and IFN-y. However, the frequency of asthma was higher in atopic patients with a high tuberculosis score and was not associated with CD14 genotypes. Eosinophil counts in blood were higher in atopic patients with a high tuberculosis score and CC+CT genotypes. These results suggest that the C allele of the CD14-159C/T polymorphism has a marked effect on eosinophil levels in atopic patients with increased exposure to tuberculosis. In addition, the degree of exposure to tuberculosis in atopic patients may modify the development of asthma.


Pulmonary embolism presenting as high-altitude pulmonary edema.
High-altitude pulmonary edema (HAPE) is a recognized risk of rapid ascent to high altitude. Since the recognition of this entity more than 30 years ago, most pulmonary deaths at high altitude have been attributed to HAPE. However, as the bodies can almost never be recovered for postmortem examination, rare diagnoses that appear clinically similar to HAPE will not be recognized. A 33-year-old woman climbing on Mt. Everest, and taking oral contraceptive pills, developed what seemed to be severe HAPE. Examination after she was evacuated from the mountain revealed a deep venous thrombosis in her left leg and multiple pulmonary emboli. We propose that multiple pulmonary emboli at high altitude can mimic HAPE, and fatal pulmonary embolism may be an explanation for some alleged victims of HAPE who died despite what should have been adequate descent.


Orthostatic tremor.
Orthostatic tremor is characterised by a feeling of unsteadiness that is accompanied by a high frequency (13-18 Hz) tremor of the legs when standing, and which is relieved by sitting or walking. We describe a typical patient whose condition gradually progressed so that eventually he could no longer stand still. We discuss the clinical features, management and pathogenesis, and highlight the need for awareness of this condition because the diagnosis is often missed or delayed.


Tuning the persistent luminescence property of a Y3Al2Ga3O12:Ce3+,Yb3+ phosphor by controlling the intrinsic oxygen vacancy concentration.
Oxygen vacancies (VO), acting as electron traps, have a significant impact on the persistent luminescence (PersL) property of persistent phosphors. However, the effect of VO on PersL remains still unclear enough to limit the development of PersL materials. In this study, the VO concentration of the Y2.978Ce0.018Yb0.004Al2Ga3O12 phosphor is accurately controlled by annealing in air and 10%H2/90%Ar atmospheres at various temperatures. The results show as the annealing temperature increases during the air annealing the VO concentration, the PersL durations, and the thermoluminescence (TL) intensity constantly decreases, and the three data coincide well with each other, indicating the PersL property of the Y2.978Ce0.018Yb0.004Al2Ga3O12 is successfully tuned. Besides, the trap structure of the Y2.978Ce0.018Yb0.004Al2Ga3O12 and the charge compensation effect of Yb ions on VO defects are also discussed. By deconvoluting the TL curves, the Yb trap with a depth of 0.58 eV has been distinctly separated from the VO traps with a quasi-continuous and broad distribution of depths ranging from 0.58 to 1.21 eV. Our work demonstrates a better understanding of the relationship between VO and PersL is of great significance to design a high-performance phosphor.


An immunohistochemical study of the oviduct in the domestic fowl (Gallus domesticus).
This study describes the distribution of vimentin, desmin, smooth muscle actin (SMA) and laminin in the oviduct of the laying domestic fowl. Vimentin immunostaining was localised in the luminal epithelium of the infundibulum, magnum, magnum-isthmus junction and isthmus. The luminal epithelium of the shell gland regions displayed weak vimentin immunostaining. Vimentin immunostaining was demonstrated in the glandular grooves of the tubular infundibular region. In contrast, gland cells in the magnum, isthmus and shell gland regions were vimentin immunonegative. Fibroblasts and vascular endothelial cells in the lamina propria of the oviductal regions studied exhibited vimentin immunostaining. Strong desmin and SMA immunostaining were present in the smooth muscle cells of the tunica muscularis and vascular tunica media. In this study, basement membranes underlying the luminal and glandular epithelia were immunopositive for laminin. In addition, basement membranes associated with smooth muscle cells exhibited laminin immunostaining. The results of the study indicate that the immunolocalisation of desmin, SMA and laminin in the oviduct of the domestic fowl is similar to that in the mammalian uterus. The immunolocalisation of vimentin in the domestic fowl varies depending on the oviductal region.


Role of stimuli-sensitive polymers in protein refolding: alpha-amylase and CcdB (controller of cell division or death B) as model proteins.
Alginate, a calcium-sensitive polymer, could carry out simultaneous purification and refolding of 8 M urea/100 mM dithiothreitol (DTT) denatured and thermally denatured alpha-amylase present in a commercial preparation. Activity recoveries of 80 and 70% in the former and the latter cases, respectively, were obtained. The fluorescence spectra showed refolding, and PAGE showed the absence of any aggregates in the refolded preparation. As another example, Eudragit S-100, a pH-sensitive poly(methyl methacrylate), was used to refold CcdB (controller of cell division or death B) protein. Initial experiments with wild-type (WT) CcdB showed that Eudragit bound and precipitated (upon lowering the pH to 4.0) CcdB quantitatively from the latter's aqueous solution. The bioconjugate showed DNA gyrase inhibition activity of CcdB and could be recycled. The inclusion bodies of CcdB mutant CcdB-17P were solubilized in 8 M urea/100 mM dithiothreitol. This preparation could be refolded by precipitation with Eudragit. The fluorescence and CD spectra showed that protein refolding has occurred.