Subependymoma of the septum pellucidum radiologically indistinguishable from cavernous angioma--case report.
A case of subependymoma of the septum pellucidum in a 54-year-old female is presented. Computed tomography and magnetic resonance imaging revealed a partially calcified mass with intratumoral hematomas, and cerebral angiograms disclosed a relatively hypovascular lesion. Preoperatively, a cavernous angioma was suspected. The tumor was removed, and histological examination proved it to be a subependymoma containing a fine fibrillary matrix. On immunohistochemical analysis, both the matrix and the tumor cells were positive for glial fibrillary acidic protein staining.


Mutual regulation of MDM4 and TOP2A in cancer cell proliferation.
MDM4 and topoisomerase IIα (TOP2A) are overexpressed in various human cancers. MDM4 acts as an oncoprotein which promotes cancer progression by inhibiting tumor suppressor p53. As a DNA replication- and cell division-regulating enzyme, TOP2A is the main target of many anticancer therapy regimens; however, the exact role of TOP2A in cancer remains elusive. Herein, we report that MDM4 and TOP2A bind to each other and are mutually upregulated at the post-translational level, leading to TOP2A protein stabilization, inhibition of p53, and increased tumor-cell proliferation. We demonstrate that the C-terminal region (CTR) of TOP2A binds to a unique sequence (residues: 188-238) of MDM4, which contains an auto-inhibitory segment regulating the MDM4-p53 interaction. TOP2A binding in turn activates MDM4 for p53 binding, resulting in enhanced inhibition of p53 and cancer cell proliferation. Conversely, binding of the MDM4 sequence to the CTR of TOP2A stabilizes TOP2A protein, leading to increased TOP2A protein expression. These results reveal novel functions of MDM4 and TOP2A as well as their interactions in oncogenesis, suggesting that inhibition of the MDM4-TOP2A interaction may represent a novel strategy in specifically and simultaneously targeting TOP2A and MDM4 for cancer treatment.


Topological aspects of microsomal N-acetyltransferase, an enzyme responsible for the acetylation of cysteine S-conjugates of xenobiotics.
Acetylation of cysteine S-conjugates of xenobiotics by microsomal N-acetyltransferase is the final step of detoxicative metabolism leading to mercapturic acid biosynthesis. To elucidate the subcellular site of N-acetylation and the effective mechanism by which the final metabolites are eliminated from the organisms, topological aspects and catalytic properties of microsomal N-acetyltransferase and mercapturic acid biosynthesis in vivo were investigated. Intravenous administration of radioactive S-benzyl-L-cysteine, a model compound of cysteine S-conjugates, resulted in rapid acetylation of the conjugate in liver and kidney to a similar extent. The acetylation was followed by a rapid excretion of the metabolite, a mercapturic acid, into the urine; about 60% of the injected dose appeared in urine within 60 min of administration. Limited proteolysis of microsomal vesicles obtained from liver and kidney by chymotrypsin or trypsin inactivated the transferase by 49-62% and 62-73%, respectively. Proteolytic inactivation of the transferase was not significantly affected by the presence of 0.04% sodium deoxycholate by which the vesicles became permeable to macromolecules due to its detergent action. To determine the sidedness of the active site of N-acetyltransferase on the microsomal membranes, two S-acetyldextran polymer derivatives (Mr 500 000) of cysteine and N-acetylcysteine which represent an nonpermeant substrate and product for this enzyme, respectively, were examined for their effects on the vesicle-associated enzyme activity. Both derivatives inhibited the transferase activity in a dose-dependent fashion; maximum inhibition of the enzyme activity was 40% by the former and 60% by the latter. Sulfobromophthalein strongly inhibited the enzyme activity and this inhibition was completely reversed by adding an equimolar amount of hepatic glutathione S-transferases (ligandins). In contrast to the strong inhibition by sulfobromophthalein itself, its glutathione S-conjugate did not inhibit the enzyme activity. These results indicate that the active site and the protease-sensitive domain(s) of the microsomal N-acetyltransferase are localized on the outer surface (cytoplasmic side) of endoplasmic reticulum and that the ligandin(s) might protect membranous N-acetyltransferase from inhibition by organic anions by binding them and catalyzing the conjugation with glutathione.


The relation between intracrainal pressure, mean arterial pressure and cerebral blood flow in patients with severe head injury.
In patients with severe head injuries ICP, MAP and CBF were measured continuously. In most patients there was a positive vasopressor response to increasing ICP, but the ICP/MAP ratio varied considerably in individual cases. CBF was diminished either by increasing ICP or by decreasing MAP. This effect was more marked with ICP above 40 mm Hg or MAP below 110 mm Hg. In terminal stages there was often a negative MAP/ICP ratio accompanied by massive cerebral hyperaemia. Key words: Severe head injury--intracranial pressure--mean arterial pressure--cerebral blood flow--cerebral perfusion pressure--critical limit of ICP and CBF. ICP equals intracranial pressure (mm Hg); CBF, Flow equals cerebral blood flow (ml/min); MAP equals mean arterial pressure (mm Hg); CPP equals cerebral perfusion pressure (mm Hg) (difference between MAP and ICP); BP equals blood pressure.


Atypical GLUT1 deficiency with prominent movement disorder responsive to ketogenic diet.
Glucose transport protein deficiency due to mutation in the GLUT1 gene is characterized by infantile onset and chronic seizure disorder, microcephaly, global developmental delays, and hypoglycorrhachia. We describe a 10-year-old normocephalic male with prominent ataxia, dystonia, choreoathetosis, and GLUT1 deficiency whose motor abnormalities improved with a ketogenic diet. We illustrate the motor abnormalities, at baseline and after ketogenic diet, that characterize this unusual case. This case broadens the phenotype of GLUT1 deficiency and illustrates the importance of cerebrospinal fluid (CSF) evaluation in detecting potentially treatable conditions in children with undiagnosed movement disorders.


Environmental pollutant ENU induced leukemic NF-kB signaling amelioration by Eclipta alba in murine model.
Exposure to N-nitroso compounds (NOCs) in our environment via pesticides, tobacco, and smoked meat can be potentially carcinogenic. The induction of N-N' ethylnitrosourea (ENU), a genotoxic NOC, leads to leukemogenesis. The study aimed to explore the ameliorating effect of the Ayurvedic herb Eclipta alba on the bone marrow cells of ENU-induced leukemic mice. Eclipta alba is investigated for its anti-cancer effect on various cell lines, but never on haematological malignant models. Theefficacy of the extract was explored on leukemia by changes in body weight, survivability, peripheral blood hemogram, bone marrow cytological, histological, and cell culture studies pre-and post-treatment. The treated group revealed significant immunomodulation of the expressional profile of NF-kB family and IL-1β in marrow cells, by flow-cytometry, and immunofluorescence study. Through our experimental endeavour we depicted the cellular mechanism, signaling modality and tried to establish the anti-cancer potency of Eclipta alba on ENU-induced leukemia.


[The impact of multiple vaccinations on vaccine schedule adherence and parental attitudes in Monteregie].
This study aimed to explore the impact of adding new vaccines on schedule adherence and parental opinion of multiple injections. A descriptive cross-sectional study by self-administered questionnaire mailed to a stratified random sample of each of two cohorts of children drawn from the Montérégie Birth Register: the 2002-2003 cohort (old vaccination schedule) and the 2004-2005 cohort (new schedule). Two surveys were done: Survey 1 (fall 2005-winter 2006) questioned parents whose address could be validated by Canada411.ca; Survey 2 (fall 2006) surveyed parents whose address was validated by the Quebec health insurance board (RAMQ). Incomplete or missing vaccine data were completed by verifying the vaccinators' files. Analysis of schedule adherence by the Kaplan-Meier survival approach showed that the 2nd and 3rd doses of the DTaP-P-Hib vaccine were received late by the youngest children compared to the oldest (median number of days late: 2 days for the 2nd vaccine (p = 0.013) and 4 days for the 3rd vaccine (p < 0.001)). Many parents (76%) prefer 2 to 3 injections during a single visit, and 61% fear an increase in the risk of side effects. Even if the evaluated lateness has only a small public health impact, parents must be reassured about the safety of multiple vaccines.


Binding of acetylcholinesterase to multiwall carbon nanotube-cross-linked chitosan composite for flow-injection amperometric detection of an organophosphorous insecticide.
A novel method for immobilization of acetylcholinesterase (AChE) by binding covalently to a cross-linked chitosan-multiwall carbon nanotube (MWNT) composite is described. In addition a sensitive, fast, cheap and automatizable flow injection detection of an organophosphorous insecticide was developed. The MWNTs were homogeneously distributed in the chitosan membrane which showed a homogeneous porous structure. The immobilized AChE could catalyze the hydrolysis of acetylthiocholine with a K(M)app value of 177 microM to form thiocholine, which was then oxidized to produce detectable signal in a linear range of 1.0-500 microM and fast response. MWNTs could catalyze the electrooxidation of thiocholine, thus increasing detection sensitivity. Based on the inhibition of an organophosphorous insecticide on the enzymatic activity of AChE, using Sulfotep as a model compound, the conditions for the flow-injection detection of the insecticide were optimized. Both biocompatibility of chitosan and inherent conductive properties of MWNTs favored the detection of the insecticide from 1.5 to 80 microM along with good stability and reproducibility. 95 % reactivation from inhibited AChE could be regenerated by using 2-pyridinealdoxime methiodide within 15 min for 15 times. The detection of Sulfotep samples exhibited satisfactory results. The proposed flow-injection analysis device can be applied to automated determination and characterization of enzyme inhibitors.


Husband's esteem predicts his mate retention tactics.
Men sometimes enact mate retention tactics to thwart a partner's infidelity or prevent their defection from the relationship. These tactics include low-risk acts that render the current relationship more attractive by bestowing benefits on the woman, as well as cost-inflicting acts that render defection from the relationship risky or dangerous for her. Previous research has linked men's mate retention behavior with men's mate value (value as a current or potential partner) using women's reports. The current research addresses limitations of that research using self-reports and cross-spousal reports from 107 married couples concerning their self-esteem and their esteem for their partner. The results indicate that the level of esteem that wives have for their husbands is positively associated with their perception of their husband's use of positive inducements and negatively associated with their husband's self-reported use of cost-inflicting mate retention behaviors (i.e., Direct Guarding, Intersexual Negative Inducements, and Intrasexual Negative Inducements). The level of self-esteem reported by men was negatively associated with their self-reported direct guarding behavior. Discussion explores the possibility that esteem-both self-esteem and esteem from one's partner-functions as an internal gauge of relative mate value.


Essential fatty acids, immune function, and exercise.
The immunologic response to exercise comprises numerous alterations within the immune system, but how these processes are regulated is still largely unknown. Exercise-related immunological changes include signs of inflammation, such as release of inflammatory mediators, activation of various white blood cell lines and complement, and induction of acute phase proteins. Nevertheless, signs of immunosuppression, such as decreased T and B cell function or impaired cytotoxic or phagocytic activity, can also be observed. Some data suggest that essential fatty acids help regulate inflammatory processes, modulating both cytokine release and the acute phase response. Positive effects of changing dietary essential fatty acids have been demonstrated in chronic inflammatory diseases. In contrast, little is known about the contribution of fatty acids to the exercise-induced immunologic reaction. Essential fatty acids may determine alterations within the immune system following exercise. Therefore, future studies are necessary to evaluate the influence of the fatty acid composition on the inflammatory or immunosuppressive component following heavy exertion.


Problem-solving training as an active ingredient of treatment for youth depression: a scoping review and exploratory meta-analysis.
Problem-solving training is a common ingredient of evidence-based therapies for youth depression and has shown effectiveness as a versatile stand-alone intervention in adults. This scoping review provided a first overview of the evidence supporting problem solving as a mechanism for treating depression in youth aged 14 to 24 years. Five bibliographic databases (APA PsycINFO, CINAHL, Embase, MEDLINE, Web of Science) and the grey literature were systematically searched for controlled trials of stand-alone problem-solving therapy; secondary analyses of trial data exploring problem-solving-related concepts as predictors, moderators, or mediators of treatment response within broader therapies; and clinical practice guidelines for youth depression. Following the scoping review, an exploratory meta-analysis examined the overall effectiveness of stand-alone problem-solving therapy. Inclusion criteria were met by four randomized trials of problem-solving therapy (524 participants); four secondary analyses of problem-solving-related concepts as predictors, moderators, or mediators; and 23 practice guidelines. The only clinical trial rated as having a low risk of bias found problem-solving training helped youth solve personal problems but was not significantly more effective than the control at reducing emotional symptoms. An exploratory meta-analysis showed a small and non-significant effect on self-reported depression or emotional symptoms (Hedges' g = - 0.34; 95% CI: - 0.92 to 0.23) with high heterogeneity. Removing one study at high risk of bias led to a decrease in effect size and heterogeneity (g = - 0.08; 95% CI: - 0.26 to 0.10). A GRADE appraisal suggested a low overall quality of the evidence. Tentative evidence from secondary analyses suggested problem-solving training might enhance outcomes in cognitive-behavioural therapy and family therapy, but dedicated dismantling studies are needed to corroborate these findings. Clinical practice guidelines did not recommend problem-solving training as a stand-alone treatment for youth depression, but five mentioned it as a treatment ingredient. On its own, problem-solving training may be beneficial for helping youth solve personal challenges, but it may not measurably reduce depressive symptoms. Youth experiencing elevated depressive symptoms may require more comprehensive psychotherapeutic support alongside problem-solving training. High-quality studies are needed to examine the effectiveness of problem-solving training as a stand-alone approach and as a treatment ingredient.


Mesoporous TiO2 Coatings Regulate ZnO Nanoparticle Loading and Zn2+ Release on Titanium Dental Implants for Sustained Osteogenic and Antibacterial Activity.
Two major issues are currently hindering the clinical practice of titanium dental implants for the lack of biological activities: immediate/early loading risks and peri-implantitis. To solve these issues, it is urgent to develop multifunctional implants modified with effective osteogenic and antibacterial properties. Zinc oxide nanoparticles (ZnO NPs) possess superior antibacterial activity; however, they can rapidly release Zn2+, causing cytotoxicity. In this study, a potential dental implant modification was creatively developed as ZnO nanoparticle-loaded mesoporous TiO2 coatings (nZnO/MTC-Ti) via the evaporation-induced self-assembly method (EISA) and one-step spin coating. The mesoporous TiO2 coatings (MTCs) regulated the synthesis and loading of ZnO NPs inside the nanosized pores. The synergistic effects of MTC and ZnO NPs on nZnO/MTC-Ti not only controlled the long-term steady-state release of Zn2+ but also optimized the charge distribution on the surface. Therefore, the cytotoxicity of ZnO NPs was resolved without triggering excessive reactive oxygen species (ROS). The increased extracellular Zn2+ further promoted a favorable intracellular zinc ion microenvironment through the modulation of zinc transporters (ZIP1 and ZnT1). Owing to that, the adhesion, proliferation, and osteogenic activity of bone mesenchymal stem cells (BMSCs) were improved. Additionally, nZnO/MTC-Ti inhibited the proliferation of oral pathogens (Pg and Aa) by inducing bacterial ROS production. For in vivo experiments, different implants were implanted into the alveolar fossa of Sprague-Dawley rats immediately after tooth extraction. The nZnO/MTC-Ti implants were found to possess a higher capability for enhancing bone regeneration, antibiosis, and osseointegration in vivo. These findings suggested the outstanding performance of nZnO/MTC-Ti implants in accelerating osseointegration and inhibiting bacterial infection, indicating a huge potential for solving immediate/early loading risks and peri-implantitis of dental implants.


Earth history. U-Pb geochronology of the Deccan Traps and relation to the end-Cretaceous mass extinction.
The Chicxulub asteroid impact (Mexico) and the eruption of the massive Deccan volcanic province (India) are two proposed causes of the end-Cretaceous mass extinction, which includes the demise of nonavian dinosaurs. Despite widespread acceptance of the impact hypothesis, the lack of a high-resolution eruption timeline for the Deccan basalts has prevented full assessment of their relationship to the mass extinction. Here we apply uranium-lead (U-Pb) zircon geochronology to Deccan rocks and show that the main phase of eruptions initiated ~250,000 years before the Cretaceous-Paleogene boundary and that >1.1 million cubic kilometers of basalt erupted in ~750,000 years. Our results are consistent with the hypothesis that the Deccan Traps contributed to the latest Cretaceous environmental change and biologic turnover that culminated in the marine and terrestrial mass extinctions.


Full Functional Sex Reversal Achieved Through Silencing of MroDmrt11E Gene in Macrobrachium rosenbergii: Production of All-Male Monosex Freshwater Prawn.
The freshwater prawn Macrobrachium rosenbergii is one kind of important economic aquaculture species and displays remarkable sexual dimorphism. The molecular mechanism of sexual differentiation in M. rosenbergii has been primarily unraveled through the research efforts of the androgenic gland and its related genes. However, the understanding of conserved genes involved in the molecular mechanism underpinning sex determination and sexual differentiation of M. rosenbergii is still fragmentary. MroDmrt11E is a member of the doublesex and mab-3-related transcription factor (Dmrt) gene family and is prominently expressed in the testis. In the present study, in vivo knockdown of MroDmrt11E at the postlarva stage in male prawn induced a complete and functional sex reversal and achieved the production of an all-male monosex population. Furthermore, a great deal of new information of upregulated and downregulated transcriptions involved in sexual differentiation of MroDmrt11E knockdown was enriched by comparative transcriptomic analysis. The effects of RNAi-mediated gene knockdown of MroDmrt11E on the differentially expressed and sex-related candidate genes, such as transformer, fruitless, feminization, insulin-like androgenic gland gene, Dmrt gene family, were primarily focused on, and their possible molecular regulatory relationships in sexual differentiation were analyzed. Meanwhile, the response of primary Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathways was investigated to expound the potential roles of MroDmrt11E in male sexual differentiation, which provided a deeper understanding of the molecular regulatory network underlying sexual differentiation of M. rosenbergii. The finding provided a novel sexual manipulation technique through silencing of Dmrt gene family for achieving a complete and functional sex reversal and offered a new insight regarding the mechanism of the Dmrt gene family in the sexual differentiation of crustaceans.


Intraarticular interferon-beta gene therapy ameliorates adjuvant arthritis in rats.
Interferon (IFN)-beta has significant immunomodulatory properties and has received much interest as a potentially therapeutic agent for rheumatoid arthritis (RA). Systemic IFN-beta treatment of patients with RA was not effective, probably because of pharmacokinetic issues. Therefore, we studied the effect of local IFN-beta production by adenovirus-mediated gene transfer to the ankle joints of arthritic rats. Adjuvant arthritis (AA) in rats was used as a model to study intraarticular gene therapy with an adenoviral vector encoding the rat IFN-beta gene (Ad.IFN-beta). The effect on paw swelling was measured by water displacement plethysmometry. Synovial tissue of the hind paws was examined by immunohistochemistry. Bone destruction was analyzed on the basis of radiographs. In addition, quantitative real-time polymerase chain reaction was used to assess IFN-beta expression. Levels of IFN-beta mRNA and protein peaked 2 days after intraarticular injection and declined thereafter. Local delivery of Ad.IFN-beta after the onset of disease reduced paw swelling significantly. This was accompanied by a reduction in synovial inflammation. The clinical effects in rat AA lasted up to 9 days. Strikingly, Ad.IFN-beta treatment protected bone from erosion, reduced levels of c-Cbl and Cbl-b (both signaling molecules essential for osteoclast activity), and reduced the matrix metalloproteinase-3:tissue inhibitor of metalloproteinase-1 ratio in the joint. Immunohistochemical analysis of the synovial tissue revealed a clear shift toward a more antiinflammatory cytokine profile. Local overexpression of IFN-beta inhibits arthritis progression and protects against bone destruction in rat AA. These findings validate IFN-beta as a therapeutic molecule for intraarticular gene therapy of arthritis.


The History of Surgery at the Montreal Heart Institute.
The Montreal Heart Institute (MHI) is a specialty hospital dedicated to cardiology and heart surgery. Founded in 1954 by Paul David, it is currently affiliated with the Université de Montréal. The Montreal Heart Institute is a center that has rested on the shoulders of multiple pioneers over the past 63 years. Renowned for its sustained excellence and commitment to patient care, the MHI also focuses on research and innovation. It has become one of the leading heart institutions in modern cardiac surgery and also one of the busiest cardiac surgery centers in the country. Our leaders have impacted the treatment of patients with heart diseases through clinical care and education. Staff surgeons have been trained at top centers across the world for the benefit of Canadian patients. The MHI was a pioneer in heart transplantation and CABG surgery and focuses on evaluative research of new technology.


Effect of rehabilitation facility location on outcomes in head and neck surgical patients.
The objective of this study was to determine the significance of in-hospital rehabilitation facility vs. distant rehabilitation facilities in the outcomes and complications of post-operative head and neck surgical patients. Retrospective review of head and neck surgical patients was conducted over a 5-year period at a tertiary care medical centre. Fifty patients met criteria for this study (35 males, 15 females). Forty-two patients had a primary squamous cell carcinoma and eight patients had other primary malignancies of the head and neck. Thirty-two patients were placed in an in-hospital rehabilitation facility and 18 patients were placed in distant rehabilitation facilities (average distance 40.9 miles). Seventeen patients (34%) had complications including infection/drainage (seven patients), fistula (six patients), pneumonia (two patients), wound dehiscence (two patients) and other minor complications. The difference complication rate among the two groups was not statistically significant (37.5% in-hospital rehabilitation, 27.8% distant rehabilitation; P=0.496). The rate of hospital re-admission was not statistically significant (25% in-hospital rehabilitation patients, 16.7% distant rehabilitation patients; P=0.505). The average length of stay of patients without complications was 18.5 days (SD=5.8) for in-hospital rehabilitation and 12.9 days (SD=17) for distant rehabilitation. This difference was not statistically significant (P=0.346). In summary, one-third of post-operative head and neck surgical patients developed complications while in a rehabilitation facility. The length of stay, hospital re-admission rate and frequency of complications does not correlate with the proximity of the rehabilitation facility to the hospital where the patients received their surgery.


Seasonal variation in chemical properties and degradability by anaerobic digestion of landfill leachate at Benowo in Surabaya, Indonesia.
Seasonal variations in the physical and chemical characteristics of leachate taken from Benowo landfill in Indonesia, including factors likely to inhibit anaerobic digestion, were investigated to determine the impacts on the stability of anaerobic treatment. To evaluate the biodegradability of the leachate, a continuous experiment was conducted by changing the organic loading rate (OLR). Chemical oxygen demand (COD) ranged between 2621 and 16,832 mg L(-1), and COD in the dry season was twice the level in the rainy season owing to reduced rainwater input and significant evaporation. COD, pH, and the concentrations of ammonium ion, and metals in the leachate were within acceptable ranges for decomposition by anaerobic digestion. However, the Na(+) and Cl(-) in the leachate are high enough to inhibit anaerobic digestion. From chemical investigation of leachate at six monitoring wells in Benowo, food waste accumulation and seawater intrusion might cause high salinity in the leachate. In the continuous experiment, COD removal efficiency was maintained at 40% regardless of OLR, suggesting that at least 40% of the leachate contained biodegradable substances. Based on these results, issues surrounding the biological treatment of saline and refractory substances in landfill leachate were discussed. It is suggested that high salinity and refractory substances in the leachate are common issues during the leachate treatment by anaerobic digestion as the implications for similar landfills in other countries around the world.


[Possible oral transmission of Chagas disease among hydrocarbons sector workers in Casanare, Colombia, 2014].
Trypanosoma cruzi, the etiological agent for Chagas disease, can be transmitted by oral intake of contaminated food or drinks. During epidemiological week 14 of 2014, two cases of acute Chagas disease were notified among hydrocarbons sector workers in Paz de Ariporo, Casanare. To characterize the affected population, to establish control and prevention measures and to confirm the outbreak. We conducted an outbreak investigation that included the following components: a) Search for symptomatic people compatible with Chagas disease according to the case definition for their referral to medical services; b) entomological survey (192/197 houses); c) sanitary inspection and microbiological analysis of food samples; and d) study of reservoirs. Data management and analysis were done with Epi-Info 7.1.5 using descriptive statistics. We also calculated intradomicile and peridomicile triatomine infestation indexes. We detected 552 exposed people; 40 had the disease (7.2%), of whom seven were women (17,5%) and 33, men (82.5%), i.e., a male-female ratio of 5:1. The mean age was 39.1 ± 10.8 years; the attack rate was 7.2% and lethality, 5% (2/40). Symptoms included fever (100% of cases), headache (80%), myalgia and arthralgia (65%), facial edema (55%), and abdominal pain (37.5%). The mean incubation time was 17 days (range: 3-21). Rhodnius prolixus domiciliary infestation index was 3.3 % and 2.2% in the peridomicile. In the five restaurants inspected sanitary conditions were deficient and food samples were microbiologically non-conforming. We found a dog and two opossums positive for IgG antibodies by ELISA. Environmental, sanitary and epidemiological conditions at the place confirmed an outbreak of Chagas diseases related to occupational exposure, possibly by oral transmission, which may be the largest to date in Colombia.


"Please, I want to go home": ethical issues raised when considering choice of place of care in palliative care.
Many palliative care patients would prefer to receive care, and to die, at home. Despite this many die in institutions. In response to this, politicians and charities have adopted policies aimed at increasing the opportunities for care and death at home. The need to discuss plans for discharge with most inpatients reinforces expectations of a choice of place of care. However, many palliative patients do not have a choice of care at home. This article will explore the circumstances in which patients are unable to choose home care and consider changes in clinical practice that can help to maximise choice. We shall argue that there is a distinction between the preferences of patients and the choices actually available to them. In attempting to make this distinction we advocate consideration of the balance between the ethical principles relevant to each case.


Retinoic acid upregulates cone arrestin expression in retinoblastoma cells through a Cis element in the distal promoter region.
This study was initiated to investigate the molecular mechanisms of activation of expression of the human cone arrestin (hCAR) gene by retinoic acid (RA), in an in vitro model of retinoblastoma cells. Human retinoblastoma Weri-Rb-1 or Y79 cell lines were cultured in the absence or presence of RA analogues with transcription or translation inhibitors for various periods. The mRNAs encoding hCAR, retinoic acid receptor (RAR), and retinoid X receptor (RXR) subtypes were analyzed by Northern blot. Immunoblot analysis of hCAR protein was also performed. The hCAR promoter's activity and its responsiveness to RA treatment was evaluated by transient transfection of the hCAR promotor-luciferase reporter constructs, followed by promoter deletion analysis to map the specific regions responsible for the RA response. In our in vitro model, both all-trans RA and 9-cis RA induced hCAR mRNA in a time- and dose-dependent manner. RA's effect was blocked by either RNA or protein synthesis inhibitors; however, hCAR mRNA's stability was not affected by RA, as determined by RNA decay experiments. Although all RAR and RXR subtypes were detected, only RXRgamma and RARalpha increased dramatically after treatment with RA. An RXR-specific agonist, but not an RAR-specific agonist, also increased hCAR mRNA and protein expression in both Weri-Rb-1 and Y79 cells. RA stimulated hCAR promoter-luciferase activity in transient transfection studies. Subsequently, a region between -852 and -702 of the hCAR promoter, with RA-responsive elements (RAREs), was discovered to be responsible for the RA response. The hCAR gene is transcriptionally upregulated by RA acting through cis elements within -852 to -702 of the hCAR 5' flanking region. Based on the cumulative data, RXRgamma is most likely the RA receptor subtype involved in hCAR regulation by RA.


Effects of geometric form features on three-dimensional object categorization.
The purpose was to investigate the effects of 3-D form features on the object-categorization process. 30 subjects [17 male and 13 female undergraduate industrial design students whose mean age was 20.7 yr. (SD= 1.5)] were asked to classify 32 3-D prismatic images according to their similarity. Multidimensional scaling and cluster analyses indicated that the classification process was strongly related to the prisms' compounded features. The attention-weighting of each individual form feature was calculated by regression analysis which further indicated that each feature had a different effect on the categorizing process.


Reproducibility of Her2/neu scoring in gastric cancer and assessment of the 10% cut-off rule.
The application of Trastuzumab on gastric cancer patients is based on Her2/neu immunostaining. The testing method relies on visual estimation of both membranous staining intensity, and positive tumor ratio with respect to a 10% cutoff. We evaluated the effect of inter- and intraobserver variations of both factors on therapeutic decision, especially if the positive tumor ratio hovers around the 10% cutoff. Ten pathologists scored 12 Her2/neu immunohistologically stained whole sections of gastric cancer. Applying the common rules for Her2/neu testing for gastric cancer, they separately noted the strongest identifiable staining intensity and the corresponding positive tumor ratio. Scoring was done repeatedly using the microscope, plain virtual microscopy, and virtual microscopy with a manual outline drawing function. Agreements on the strongest identified staining intensities were moderate. Overall concordance correlation coefficients of positive tumor ratios ranged from 0.55 to 0.81. Reproducibility was not improved by virtual microscopy. Pathologists have a good ability to estimate ratios of clearly demarcated areas, but gradients in staining intensities hinder reproducible visual demarcation of positive tumor areas. When hovering around the 10% positive tumor ratio cutoff there is a risk of misinterpretation of the staining results. This could lead to a denial of Trastuzumab therapy. Assessment of Her2/neu expression should be carried out by experienced pathologists because they can more reproducibly rate membranous staining intensities. The low reproducibility of positive tumor ratio is inherent in the testing method and cannot be improved by virtual microscopy. Therefore, we propose to reconsider the 10% cut-off limit.


The role of teacher behavior management in the development of disruptive behaviors: an intervention study with the good behavior game.
The role of teacher behavior management for children's disruptive behavior development (hyperactive and oppositional behavior) was investigated using a universal classroom preventive intervention study. Five-hundred seventy children were followed from second to third grade of elementary school. Observations of teacher behavior management and children's on-task and off-task classroom behavior and peer reports of hyperactive and oppositional behavior were available. Results showed that the reduced use of negative remarks of intervention teachers predicted children's increase in on-task behavior and decrease in talking-out behavior. These improved children's classroom behaviors in turn mediated the impact of the intervention on the development of hyperactive and oppositional behavior over the studied period. These results were similar for girls and boys. The results underscore the role of teachers' classroom management strategies in improving children's classroom behavior, which, in turn is an important component in the reduction of disruptive behavior development.


Direct-to-implant Breast Reconstruction with Autoderm.
Traditional transverse mastectomies yield suboptimal results in women with higher body mass index, wide breast footprint, and ptotic breasts. An option for this patient population is a reduction-pattern style mastectomy, and recruiting an inferiorly based dermal flap using the lower mastectomy flap. This is analogous to a vascularized dermal matrix supporting the lower pole of the implant, termed "Autoderm" breast reconstruction. This allows for aesthetically appealing skin reduction mastectomies with the added safety of a vascularized dermal flap to facilitate an immediate direct-to-implant breast reconstruction. This study assesses patient satisfaction using the validated BRECON-31 questionnaire to enhance shared-decision making with women contemplating breast reconstruction. A 2-year retrospective review of women who underwent Autoderm direct-to-implant breast reconstruction comparing patients who underwent unilateral and bilateral reconstruction in terms of characteristics, complications, and BRECON-31 scoring. Overall patient scores were high (81.6 of 100). In particular, women scored very high on self-image (85.0), arm concerns (86.4), intimacy (87.4), satisfaction (88.3), and expectations subscales (85.5). Women choosing bilateral reconstruction outperformed unilateral reconstruction in every subgroup, but only attained statistical significance in the "self-consciousness" subgroup. Compared with a historical cohort of a mix of implant reconstruction types, Autoderm patients showed improved satisfaction (88.3 versus 82.5; P = 0.07) and breast appearance (73.9 versus 66.8; P = 0.06), approaching significance. Safety was demonstrated by low major complications (4.7%) and low implant loss rates (2.3%). Autoderm breast reconstruction is a safe option in women with large, ptotic breasts, with patients reporting high satisfaction using a validated instrument.


Restricted versus Usual/Liberal Maintenance Fluid Strategy in Mechanically Ventilated Children: An Open-Label Randomized Trial (ReLiSCh Trial).
To assess the impact of restricted vs. usual/liberal maintenance fluid strategy on fluid overload (FO) among mechanically ventilated children. This open-label randomized controlled trial was conducted over a period of 1 y (October 2020-September 2021) in a Pediatric intensive care unit (PICU) in North India. Hemodynamically stable mechanically ventilated children were randomized to 40% (restricted group, n = 50) and 70-80% (usual/liberal group, n = 50) of maintenance fluids. The primary outcome was cumulative fluid overload percentage (FO%) on day 7. Secondary outcomes were FO% >10%; vasoactive inotropic score, sequential organ failure assessment score, pediatric logistic organ dysfunction score and oxygenation index from day 1-7; ventilation free days (VFDs) and PICU free days (PFDs) through day 28; and mortality. The restricted group had statistically non-significant trend towards lower cumulative FO% at day 7 [7.6 vs. 9.5, p = 0.40]; and proportion of children with FO% >10% (12% vs. 26%, p = 0.21) as compared to usual/liberal group. The increase in FO% from day 1-7 was significant in usual/liberal group as compared to restricted group (p <0.001 and p = 0.134, respectively). Restricted group received significantly lower amount of fluid in the first 5 d; had significantly higher VFDs (23 vs. 17 d, p = 0.008) and PFDs (19 vs. 15 d, p = 0.007); and trend towards lower mortality (8% vs. 16%, p = 0.21). Restricted as compared to usual/liberal maintenance fluid strategy among mechanically ventilated children was associated with a trend towards lower rate and severity of FO and mortality; and significantly lower fluid volume received, and higher VFDs and PFDs.


Temporal effects of maternal and pregnancy characteristics on serum pregnancy-associated plasma protein-A and free β-human chorionic gonadotropin at 7-14 weeks' gestation.
The aim of this study was to investigate gestational age-dependent effects of racial origin, smoking status and mode of conception on maternal serum levels of free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 7-14 weeks' gestation. This was an analysis of data from prospective first-trimester combined screening for aneuploidies in singleton pregnancies, with β-hCG and PAPP-A measured at 7 + 1 to 14 + 3 weeks' gestation. We included 27,908 pregnancies from three centers in the U.K. and 125,461 pregnancies from 22 centers in Denmark, all with known normal fetal karyotype or resulting in the birth of a phenotypically normal neonate. Multiple regression modelling of log10 -transformed marker concentrations was used to produce log10 multiple of the median (MoM) values for free β-hCG and PAPP-A and to examine pregnancy characteristics that have significant effects on marker concentrations. Serum free β-hCG and PAPP-A concentrations were significantly affected by gestational age, maternal weight, racial origin, parity, smoking and mode of conception. There were significant gestational age-dependent effects attributed to Afro-Caribbean race, smoking and conception through in-vitro fertilization (IVF) on PAPP-A and free β-hCG levels. In women of Afro-Caribbean race there was a weekly increase in PAPP-A of 5.3% and in free β-hCG of 1.8%. In smokers there was a weekly decrease in PAPP-A of 2.4% and in free β-hCG of 1.6%. In cases of IVF conceptions there was a weekly increase in PAPP-A of 4.5% and in free β-hCG of 4.6%. Serum free β-hCG and PAPP-A concentrations at 7-14 weeks' gestation are affected by several pregnancy characteristics. The effects of Afro-Caribbean race, smoking and IVF conception change with gestational age.


Personal space of incarcerated offenders.
Administered the proxemic test (Kinzel, 1970) and a psychometric test battery to 49 incarcerated offenders on two occasions. Offenders also were rated by staff on their interpersonal behavior, and a 3-year follow-up was undertaken to assess recidivism. Immediate test-retest reliabilities were extremely high in all four directions (.93 to .97), but lower over a 10-week period (.65 to .89). The Behind distance was largest on both occasions. There were no changes in the four distance measures over time. An algebraic formula was devised to calculate Personal Space Area. Age was related inversely to offender's Personal Space (r = -.32, p less than .03). Personality measures, observation ratings, and follow-up outcome data were related inconsistently to Personal Space Area, although there was some indication that offenders with a large personal space were less empathic, less socialized, less accepting of others, received poor evaluations, and were more likely to recidivate. The utility of personal space in the assessment of offenders is discussed.


Delays in diagnosis and treatment of pulmonary tuberculosis in AFB smear-negative patients with pneumonia.
Diagnostic and treatment delays increase the severity and transmission of pulmonary tuberculosis (PTB). This study aimed to evaluate TB diagnostic and treatment delays in acid-fast bacilli (AFB) smear-negative patients. This was a retrospective observational study. Patients with positive AFB culture of Mycobacterium tuberculosis complex (MTC) were selected from among hospitalised patients with a diagnosis of pneumonia. Admission ward, anti-tuberculosis treatment and the duration of AFB culture were compared between smear-positive and smear-negative patients. Of the 70 patients with positive isolation of MTC in AFB culture, 27 (38.5%) were smear-negative; of these, 18 (66.7%) were not isolated while in hospital, and 17 (63%) were neither diagnosed nor treated for TB. In contrast, 41 of the 43 smear-positive patients (95.3%) were directly admitted or quickly transferred to the isolation room and started on anti-tuberculosis treatment (P < 0.001). Samples from smear-negative patients required more time to grow MTC in AFB culture than those of smear-positive patients (23 days vs. 14 days, P < 0.001). Diabetes was significantly associated with AFB smear positivity, with an odds ratio of 12.2. Negative AFB smears caused significant diagnostic and treatment delay. Patients staying in the general ward were exposed to TB patients who were not diagnosed in time.


Clinical and psychopathological characteristics of the autoagressive behavior in patients with the first psychotic episode with considering circadian rhythms.
The high rate of autoagressive action in patients with psychotic symptoms manifested during the beginning of active psychopharmatherapy, and they are often the reason for psychiatric help. The continuous growth of autoagressive behavior indicates the number of unsolved problems in clinical suicidology. The aim of this research was to explore the clinical and psychopathological characteristics of the autoagressive behavior in patients with the first psychotic episode with considering circadian rhythms. There was a research in regional clinical psychiatric hospital and 130 patients were involved in the research with autoagressive behavior during the first psychotic episodes. Clinical and psychopathological, psychodiagnostic and statistical methods were used. Characteristic clinical manifestations of first psychotic episode is determined by PANSS [1986] and BPRS [1962], level of suicidal risk is determined by Lyuban-Plotstsa's scale [2000], characteristics of biological rhythms is established by Estberg's questionnaire [1986]. Certain psychiatric symptoms were associated with the level of suicide risk in the first episode of psychosis, such as ≪tension", ≪hostility", ≪mannerisms and posturing, ≪excitement≫, ≪suspiciousness≫, ≪somatic concern≫, ≪anxiety≫, ≪depression≫, ≪guilt≫. Circadian rhythms include the level of risk occurrence and severity autoagressive behavior such as clearly and dimly expressed evening types of daily activity. Therefore, further research of autoagression during the first psychotic episode with considering the influence of biological rhythms is a given area of current research in psychiatry aimed to improve the prevention, treatment and rehabilitation.


Cell-cycle disturbance and induction of programmed death by new formamidine analogs of daunorubicin.
Structural modifications of daunorubicin are an important way to change its anticancer activity. For this reason, formamidinodaunorubicins have been synthesized. The present study was undertaken to determine and compare the in vitro effects of daunorubicin and its new formamidine derivatives on human acute leukemia MOLT-4 and ML-1 cells. The experiments were performed on human acute lymphoblastic leukemia MOLT-4 cells and human acute myeloblastic leukemia ML-1 cells. The study was conducted using flow cytometry and light microscopy methods. The various patterns of temporary changes in the cell cycle and DNA fragmentation, as well as the extent of mitotic catastrophe, apoptosis, and necrosis, were determined. The anti-leukemic activities of the new daunorubicin analogs were weaker than that of daunorubicin. The influence of these anthracyclines on cell-cycle progression, DNA damage, and induction of mitotic catastrophe and cell death depended on the agent and its concentration, the time interval after application, and the cell line used. The structural modifications of daunorubicin were responsible for the different cytotoxic effects of the two formamidinodaunorubicins.


[Primary testicular lymphoma. Report of two cases and bibliographic review].
We report two cases of primary testicular lymphoma and performed a bibliography review about this pathology. We describe two cases of primary testicular lymphoma in two male patients 69 and 61 yr. old respectively. In both cases, reason for consultation was increase of the right testicular size. After inguinal orchyectomy the diagnosis for the first case was large and medium T cell diffuse lymphoma, stage I (E)-A; three years after chemotherapy (R-CHOP) the patient is in complete remission. In the second case, the diagnosis was diffuse large B-cell lymphoma, and after receiving various chemotherapy regimens died 14 months after diagnosis. Testicular lymphoma is a very rare entity, despite being considered the most common testicular tumor in patients over the age of 60 years. Most of them are non-Hodgkin diffuse, intermediate or high grade of malignancy, B-cell immunophenotype, being T cell exceptional. Prognosis is poor due to their high tendency to systemic dissemination. The treatment is based on orchiectomy, chemotherapy and radiotherapy, although there is not a standardized regimen.


Antibodies against neuroactive amino acids and neuropeptides. I. A new two-step procedure for their conjugation to carrier proteins and the production of an anti-Met-enkephalin antibody reactive with glutaraldehyde-fixed tissues.
We developed a new two-step procedure to couple haptens to bovine serum albumin (BSA) via glutaraldehyde (GA). After activation of BSA with excess GA and removal of unreacted GA, the hapten was bound to the activated protein in a second step. This two-step procedure is easy to use, the desired molecular ratio of coupled hapten to protein is conveniently adjusted, and no visible precipitation of the conjugate is detected. Using a low peptide concentration, nearly 50% of the inserted haptens are bound to the protein, and unbound expensive peptide can be recovered after Sephadex chromatography. Antisera to neuroactive amino acids (GABA, glycine, and glutamate) and neuropeptides (Met-enkephalin) were prepared by immunization of rabbits with these conjugates. Immunological analysis of immune sera by dot-blot and ELISA techniques and subsequent removal of crossreactivities by solid-phase adsorption yielded monospecific antibodies, which were further purified by affinity chromatography. The immunocytochemical specificities of these purified antibodies were verified in adjacent sections of GA-fixed rat spinal cord. Pre-embedding staining with anti-Met-enkephalin in combination with post-embedding staining for amino acids such as GABA allowed double staining of the two antigens in a single semi-thin section.


"I Miss My Liver." Nonmedical Sources in the History of Hepatocentrism.
Hepatocentrism was a medical doctrine that considered the liver the center of the whole human being. It originated in ancient populations (Mesopotamic civilization) and persisted in Western countries until the seventeenth century. Hidden references to hepatocentrism may be found in artistic representations and literary works, from the myth of Prometheus in the Greco-Roman world to the crucifixion iconography throughout the Middle Ages. In the mid-1600s, fundamental discoveries irrefutably demonstrated the central role of the heart in human physiology, which laid the foundations for creating cardiocentrism, shifting the life's center from the liver to the heart. The advent of cardiocentrism immediately restricted the importance given to the liver, favoring the heart in the fine arts. Nevertheless, the liver maintained its importance in literature and popular belief as is evidenced by the widely acclaimed literary texts "Snow White" by the Brothers Grimm, "Moby Dick" by Herman Melville, and "Ode to the Liver" by Pablo Neruda. Our aim is to analyze the most significant artistic representations and literary works that contain references to hepatocentrism, evaluating the changing ideas and beliefs regarding the role and function of the liver throughout history. We want to underline the tight relationship between art and medicine; fine art and literature could be a valuable source for understanding the history of hepatology. (Hepatology Communications 2018; 00:000-000).


Controlled spherical deuterium droplets as Lagrangian tracers for cryogenic turbulence experiments.
The study of the smallest scales of turbulence by (Lagrangian) particle tracking faces two major challenges: the requirement of a 2D or 3D optical imaging system with sufficiently high spatial and temporal resolution and the need for particles that behave as passive tracers when seeded into the flow. While recent advances in the past decade have led to the development of fast cameras, there is still a lack of suitable methods to seed cryogenic liquid helium flows with mono-disperse particles of sufficiently small size, of the order of a few micrometers, and a density close enough to that of helium. Taking advantage of the surface tension, we propose two different techniques to generate controlled liquid spherical droplets of deuterium over a liquid helium bath. The first technique operates in a continuous mode by fragmenting a liquid jet, thanks to the Rayleigh-Taylor instability. This results in the formation of droplets with a diameter distribution of 2 ± 0.25DN, where DN is the diameter of the jet nozzle (DN = 20 μm in the present experiment). This method offers a high production rate, greater than 30 kHz. The second technique operates in a drop-on-demand mode by detaching droplets from the nozzle using pressure pulses generated using a piezoelectric transducer. This approach yields a much narrower diameter distribution of 2.1 ± 0.05DN but at a smaller production rate, in the range 500 Hz-2 kHz. The initial trajectories and shapes of the droplets, from the moment they are released from the nozzle until they fall 3 mm below, are investigated and discussed based on back-light illumination images.


The purification and properties of formate dehydrogenase and nitrate reductase from Escherichia coli.
The membrane-bound formate dehydrogenase of Escherichia coli grown anaerobically in the presence of nitrate was solubilized with deoxycholate and purified to near homogeneity. The purification procedure included ammonium sulfate fractionation and chromatography on Bio-Gel A-1.5m and DEAE Bio-Gel A in the presence of the nonionic detergent, Triton X-100. This detergent caused a significant decrease in the molecular weight of the soluble formate dehydrogenase complex and allowed the enzyme then to be resolved from other membrane components. Anaerobic conditions were required throughout due to the sensitivity of the enzyme to oxygen inactivation. Formate dehydrogenase was judged to be at least 93 to 99% pure by the following procedures: polyacrylamide gel electrophoresis in the presence of Triton X-100 and sodium dodecyl sulfate, gel filtration, and sedimentation velocity studies. The purified enzyme exists as a detergent-protein complex (0.20 +/- 0.03 g of Triton X-100/g of protein) which has an S20,w of 18.1 S and a Stokes radius of 76 A. This corresponds to a molecular weight of 590,000 +/- 59,000. The enzyme had an absorbance spectrum of a b-type cytochrome which could be completely reduced by formate. The heme content corresponds to an equivalent weight of 154,000 which suggests a tetrameric structure for the enzyme. Formate dehydrogenase was found to contain (in relative molar amounts): 1.0 heme, 0.95 molybdenum, 0.96 selenium, 14 non-heme iron, and 13 acid-labile sulfide. Neither FAD nor FMN could be detected. The enzyme contains three polypeptides, designated alpha, beta, and gamma, whose molecular weights were estimated by gel electrophoresis in the presence of sodium dodecyl sulfate to be 110,000, 32,000, and 20,000, respectively. After separation of the polypeptides by gel filtration in the presence of sodium dodecyl sulfate alpha, beta, and gamma were found in 1:1.2:0.55 molar ratios. A study of the enzyme obtained from cells grown with [75Se]selenite showed that only the alpha polypeptide contained significant amounts of selenium. The enzyme will catalyze the formate-dependent reduction of phenazine methosulfate, dichlorophenolindophenol, methylene blue, nitroblue tetrazolium, benzyl viologen, methyl viologen, ferricyanide, and coenzyme Q6. Cyanide, azide, p-hydroxymercuribenzoate, iodoacetamide, and oxygen inhibit the enzyme. The procedure which was designed for the purification of formate dehydrogenase also yields a highly purified preparation of nitrate reductase. This nitrate reductase has been shown to contain significant amounts of heme (Enoch, H. G., and Lester, R. L. (1974) Biochem. Biophys. Res Commun. 61,1234-1241). The enzyme contains three polypeptides with molecular weights of 155,000, 63,000, and 19,000. When measured in the presence of Trition X-100 the Stokes radius of nitrate reductase is 75 A and the S20,w is 16 S which corresponds to a molecular weight of 498,000.


Comparison of four serological tests for the detection of specific immunoglobulin M in cord sera of infants congenitally infected with cytomegalovirus.
Four serological tests (3 immunoassays using enzyme-labelled antigen and 1 radioimmunoassay) were compared as regards the detection of cytomegalovirus (CMV) immunoglobulin M in cord sera. 68 cord sera from infants congenitally infected by CMV were included in the study. The infections were primarily diagnosed by virus isolation close to birth. Four laboratories in 3 countries were involved, each laboratory using its own or a commercial test. Of the sera tested in the different laboratories 50-80% were found to be reactive. Both qualitatively and quantitatively there was a good correlation between the 3 enzyme-immunoassays. The RIA results differed to some extent from the enzyme tests as regards the quantification of IgM. The advantage of prospective IgM screening in undiluted cord sera followed by confirmatory virus isolation test in the neonatal period in IgM-positive cases is discussed.


Fecal Metabolomics of Type 2 Diabetic Rats and Treatment with Gardenia jasminoides Ellis Based on Mass Spectrometry Technique.
Modern studies have indicated Gardenia jasminoides Ellis (G. jasminoides) showed positive effect in treating type 2 diabetes mellitus (T2DM). In this study, 60 streptozotocin-induced T2DM rats were divided into four groups: type 2 diabetes control group, geniposide-treated group, total iridoid glycosides-treated group, and crude extraction of gardenlae fructus-treated group. The other ten healthy rats were the healthy control group. During 12 weeks of treatment, rat's feces samples were collected for the metabolomics study based on mass spectrometry technique. On the basis of the fecal metabolomics method, 19 potential biomarkers were screened and their relative intensities in each group were compared. The results revealed G. jasminoides mainly regulated dysfunctions in phenylalanine metabolism, tryptophan metabolism, and secondary bile acid biosynthesis pathways induced by diabetes. The current study provides new insight for metabonomics methodology toward T2DM, and the results show that feces can preferably reflect the liver and intestines disorders.


The human CDK8 subcomplex is a histone kinase that requires Med12 for activity and can function independently of mediator.
The four proteins CDK8, cyclin C, Med12, and Med13 can associate with Mediator and are presumed to form a stable "CDK8 subcomplex" in cells. We describe here the isolation and enzymatic activity of the 600-kDa CDK8 subcomplex purified directly from human cells and also via recombinant expression in insect cells. Biochemical analysis of the recombinant CDK8 subcomplex identifies predicted (TFIIH and RNA polymerase II C-terminal domain [Pol II CTD]) and novel (histone H3, Med13, and CDK8 itself) substrates for the CDK8 kinase. Notably, these novel substrates appear to be metazoan-specific. Such diverse targets imply strict regulation of CDK8 kinase activity. Along these lines, we observe that Mediator itself enables CDK8 kinase activity on chromatin, and we identify Med12--but not Med13--to be essential for activating the CDK8 kinase. Moreover, mass spectrometry analysis of the endogenous CDK8 subcomplex reveals several associated factors, including GCN1L1 and the TRiC chaperonin, that may help control its biological function. In support of this, electron microscopy analysis suggests TRiC sequesters the CDK8 subcomplex and kinase assays reveal the endogenous CDK8 subcomplex--unlike the recombinant submodule--is unable to phosphorylate the Pol II CTD.


Targeting Swine Leukocyte Antigen Class I Molecules for Proteasomal Degradation by the nsp1α Replicase Protein of the Chinese Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Strain JXwn06.
Porcine reproductive and respiratory syndrome virus (PRRSV) is a critical pathogen of swine, and infections by this virus often result in delayed, low-level induction of cytotoxic T lymphocyte (CTL) responses in pigs. Here, we report that a Chinese highly pathogenic PRRSV strain possessed the ability to downregulate swine leukocyte antigen class I (SLA-I) molecules on the cell surface of porcine alveolar macrophages and target them for degradation in a manner that was dependent on the ubiquitin-proteasome system. Moreover, we found that the nsp1α replicase protein contributed to this property of PRRSV. Further mutagenesis analyses revealed that this function of nsp1α required the intact molecule, including the zinc finger domain, but not the cysteine protease activity. More importantly, we found that nsp1α was able to interact with both chains of SLA-I, a requirement that is commonly needed for many viral proteins to target their cellular substrates for proteasomal degradation. Together, our findings provide critical insights into the mechanisms of how PRRSV might evade cellular immunity and also add a new role for nsp1α in PRRSV infection. PRRSV infections often result in delayed, low-level induction of CTL responses in pigs. Deregulation of this immunity is thought to prevent the virus from clearance in an efficient and timely manner, contributing to persistent infections in swineherds. Our studies in this report provide critical insight into the mechanism of how PRRSV might evade CTL responses. In addition, our findings add a new role for nsp1α, a critical viral factor involved in antagonizing host innate immunity.


Pharmacokinetic optimisation of therapy with beta-adrenergic blocking agents.
beta-Adrenergic blockade has provided one of the major pharmacotherapeutic advances of this century. The drugs in this class have the common property of blocking the binding of catecholamines to beta-adrenergic receptor sites; however, there are pharmacodynamic and pharmacokinetic differences between the individual agents which are of clinical importance. Among these differences are the completeness of gastrointestinal absorption, degree of hepatic first-pass metabolism, lipid solubility, protein binding, brain penetration, concentration within cardiac tissue, rate of hepatic biotransformation, and renal clearance of drug and/or metabolites. Long-acting formulations of existing beta-blockers are currently in use, and ultrashort-acting agents are also available. The pharmacokinetics of beta-blocking drugs can also be influenced by race, age, cigarette smoking and concomitant drug therapy. The wide interpatient variability in plasma drug concentration observed with beta-blockers makes this parameter unreliable in routine patient management. Despite the pharmacokinetic differences among the beta-blockers, these drugs should always be titrated in the individual patient to achieve the desired clinical response.


The diagnostic value of scoring models for organic and non-organic gastrointestinal disease, including the irritable-bowel syndrome.
Scoring models based on history and physical examination have been developed to discriminate patients with non-organic gastrointestinal disease from those who have organic disease. The application of these models may lead to more efficient diagnosis and prevent somatization. Although the models have high diagnostic accuracy in the population in which they have been developed, their value in other populations has not been established. In this study previously developed models were tested in validation populations defined by the original selection criteria from the studies in which the models were developed and in unselected general practice and outpatient populations. The diagnostic performance of the models are expressed in terms of odds ratio and sensitivity and specificity for the classification of patients as having organic and non-organic disease. The diagnostic performance of all the models were rather low in the validation populations. Relatively few elements of the models had independent diagnostic value. In addition, the correlation between the scoring models, expressed in Cohen's kappa, was extremely low. The diagnostic values of the scoring models were not reproduced in comparable and unselected populations. Therefore, it is concluded that the diagnostic value of such a model has little external validity.


Hippocampal synaptic connectivity in phenylketonuria.
In humans, lack of phenylalanine hydroxylase (Pah) activity results in phenylketonuria (PKU), which is associated with the development of severe mental retardation after birth. The underlying mechanisms, however, are poorly understood. Mutations of the Pah gene in Pah(enu2)/c57bl6 mice result in elevated levels of phenylalanine in serum similar to those in humans suffering from PKU. In our study, long-term potentiation (LTP) and paired-pulse facilitation, measured at CA3-CA1 Schaffer collateral synapses, were impaired in acute hippocampal slices of Pah(enu2)/c57bl6 mice. In addition, we found reduced expression of presynaptic proteins, such as synaptophysin and the synaptosomal-associated protein 25 (SNAP-25), and enhanced expression of postsynaptic marker proteins, such as synaptopodin and spinophilin. Stereological counting of spine synapses at the ultrastructural level revealed higher synaptic density in the hippocampus, commencing at 3 weeks and persisting up to 12 weeks after birth. Consistent effects were seen in response to phenylalanine treatment in cultures of dissociated hippocampal neurones. Most importantly, in the hippocampus of Pah(enu2)/c57bl6 mice, we found a significant reduction in microglia activity. Reorganization of hippocampal circuitry after birth, namely synaptic pruning, relies on elimination of weak synapses by activated microglia in response to neuronal activity. Hence, our data strongly suggest that reduced microglial activity in response to impaired synaptic transmission affects physiological postnatal remodelling of synapses in the hippocampus and may trigger the development of mental retardation in PKU patients after birth.


Exploring oxidative stress pathways in Geobacter sulfurreducens: the redox network between MacA peroxidase and triheme periplasmic cytochromes.
The recent reclassification of the strict anaerobe Geobacter sulfurreducens bacterium as aerotolerant brought attention for oxidative stress protection pathways. Although the electron transfer pathways for oxygen detoxification are not well established, evidence was obtained for the formation of a redox complex between the periplasmic triheme cytochrome PpcA and the diheme cytochrome peroxidase MacA. In the latter, the reduction of the high-potential heme triggers a conformational change that displaces the axial histidine of the low-potential heme with peroxidase activity. More recently, a possible involvement of the triheme periplasmic cytochrome family (PpcA-E) in the protection from oxidative stress in G. sulfurreducens was suggested. To evaluate this hypothesis, we investigated the electron transfer reaction and the biomolecular interaction between each PpcA-E cytochrome and MacA. Using a newly developed method that relies on the different NMR spectral signatures of the heme proteins, we directly monitored the electron transfer reaction from reduced PpcA-E cytochromes to oxidized MacA. The results obtained showed a complete electron transfer from the cytochromes to the high-potential heme of MacA. This highlights PpcA-E cytochromes' efficient role in providing the necessary reducing power to mitigate oxidative stress situations, hence contributing to a better knowledge of oxidative stress protection pathways in G. sulfurreducens.


Bed Bug (Hemiptera: Cimicidae) Detection in Low-Income, High-Rise Apartments Using Four or Fewer Passive Monitors.
Bed bug, Cimex lectularius L., management in low-income, high-rise housing for the elderly and disabled can be difficult. Early detection is key to slowing their spread, and reducing management cost and time needed for control. To determine the minimum number of passive monitors needed to detect low-level bed bug infestations in this environment, we evaluated three monitors placed one, two, or four per apartment in a 3 by 3 experimental design. One sticky monitor, The Bedbug Detection System, and the two pitfall monitors, ClimbUp Insect Interceptors BG and BlackOut BedBug Detectors, were evaluated. Bed bugs were trapped by the ClimbUp Insect Interceptors BG and the BlackOut BedBug Detector in 88% and 79% of apartments, respectively, but only in 39% of the apartments monitored with The Bedbug Detection System. The Bedbug Detection System required significantly longer time to detect bed bugs than either the ClimbUp Insect Interceptor BG or the BlackOut BedBug Detector. With the less effective Bedbug Detection System data removed from analyses, detection rates ranged from 80 to 90%, with no significant differences among one, two, or four monitors per apartment. Results indicate it is especially important to include a bed placement when only placing a few monitors. Future work should compare the combination of cursory visual inspections with various monitor numbers and placements per apartment to determine the most efficient, cost-effective system that will be accepted and implemented in low-income housing.


Associations of Maternal Serum Iodine Concentration with Obstetric Complications and Birth Outcomes-Longitudinal Analysis Based on the Huizhou Mother-Infant Cohort, South China.
This study aimed to explore the temporal associations between maternal serum iodine concentration (SIC) and common pregnancy outcomes in Chinese women. Eligible singleton pregnant women aged 20-34 years were selected, and their fasting blood samples were collected during early (T1, n = 1101) and mid-pregnancy (T2, n = 403) for SIC testing by inductively coupled plasma mass spectrometry. Multivariable linear regression indicated that log10SIC at T1 (β = -0.082), T2 (β = -0.198), and their % change (β = -0.131) were inversely associated with gestational weight gain (GWG, all p < 0.05). Maternal log10SIC at both T1 (β = 0.077) and T2 (β = 0.105) were positively associated with the Apgar score at 1 min (both p < 0.05). Women in the third quartile (Q3) of SIC at T1 had a lower risk of small for gestational age (SGA, OR = 0.405, 95% CI: 0.198-0.829) compared with those in Q4. Restricted cubic spline regression suggested a U-shaped association between SIC and SGA risk, and SIC above 94 μg/L at T1 was the starting point for an increased risk of SGA. The risk of premature rupture of membrane (PROM) increased by 96% (OR = 1.960, 95% CI: 1.010-3.804) in Q4 compared to that in Q1. Our longitudinal data from an iodine-replete region of China indicated that high maternal SIC could restrict GWG and improve Apgar scores at delivery, but might increase the risk of SGA and PROM.


The orphan solute carrier SLC10A7 is a novel negative regulator of intracellular calcium signaling.
SLC10A7 represents an orphan member of the Solute Carrier Family SLC10. Recently, mutations in the human SLC10A7 gene were associated with skeletal dysplasia, amelogenesis imperfecta, and decreased bone mineral density. However, the exact molecular function of SLC10A7 and the mechanisms underlying these pathologies are still unknown. For this reason, the role of SLC10A7 on intracellular calcium signaling was investigated. SLC10A7 protein expression was negatively correlated with store-operated calcium entry (SOCE) via the plasma membrane. Whereas SLC10A7 knockout HAP1 cells showed significantly increased calcium influx after thapsigargin, ionomycin and ATP/carbachol treatment, SLC10A7 overexpression reduced this calcium influx. Intracellular Ca2+ levels were higher in the SLC10A7 knockout cells and lower in the SLC10A7-overexpressing cells. The SLC10A7 protein co-localized with STIM1, Orai1, and SERCA2. Most of the previously described human SLC10A7 mutations had no effect on the calcium influx and thus were confirmed to be functionally inactive. In the present study, SLC10A7 was established as a novel negative regulator of intracellular calcium signaling that most likely acts via STIM1, Orai1 and/or SERCA2 inhibition. Based on this, SLC10A7 is suggested to be named as negative regulator of intracellular calcium signaling (in short: RCAS).


Dietary-induced changes in the fatty acid composition of human cheek cell phospholipids: correlation with changes in the dietary polyunsaturated/saturated fat ratio.
Healthy normotensive volunteers aged 20 to 59 yr were randomly allocated either to a control group or to one of two experimental groups. The control group ate a low P/S ratio diet for 12 wk while the first experimental group ate a high P/S ratio diet for 6 wk followed by a low P/S ratio diet for the next 6 wk. The second experimental group ate a low P/S ratio diet in the first 6 wk followed by a high P/S ratio diet for the next 6 wk. Dietary P/S ratio, plasma linoleic acid (18:2), and cheek cell phospholipid 18:2 levels were compared in each dietary group at the end of the 1st and 2nd 6 wk. On change from a low to a high P/S ratio diet, there was a 36% increase in the proportion of 18:2 in the cheek cell phospholipids in comparison with the proportion existing before the change. This was associated with an increase in the proportion of 18:2 in the plasma lipids of this group. No reduction in the proportion of 18:2 in the cheek cell phospholipids was apparent in the control group or the group which changed from a high to a low P/S ratio diet, although in the latter group there was a reduction in the proportion of 18:2 in the plasma lipids. As the phospholipid fatty acid composition of human cheek cells reflects dietary lipid status under certain conditions, this observation may be useful in dietary and nutritional studies, particularly as human cheek cells can be obtained in a noninvasive manner.


Dietary intakes among Siberian Yupiks of Alaska and implications for cardiovascular disease.
We describe dietary intake for 65 Siberian Yupik residents of Gambell, AK using 24-h recalls and annual food frequencies collected in October 1992. The objectives were to describe dietary characteristics important in risk of cardiovascular disease, determine the extent that their diet differs from the diet of general US and northern populations, assess how the diet met national guidelines for the prevention of cardiovascular disease, and propose dietary recommendations. Compared to US intakes in general (NHANES III), intakes of Siberian Yupiks expressed as percent of energy were: 8-10% higher in fat, 6% higher in protein, 5-7% higher in monounsaturated fats and 12-15% lower in carbohydrate. Energy from saturated and polyunsaturated fats was similar (11% and 8% respectively). Cholesterol intakes were not significantly different. Mean intakes of selenium, a-topocopherol, folacin (men), and vitamin C (men) met Recommended Dietary Allowances, which may contribute to cardiovascular health. Mean intake of n-3 fatty acids (7.0 g/d), twice the 3 g/d associated with favorable effects, was comparable with intake of Greenlandic Eskimos. Dietary risk factors included high intakes of % energy from fat and saturated fat, and low intakes of fiber. Native foods were important sources of monounsaturated fats, n-3 fatty acids and selenium.


Effects of the applied ancient boxing exercise on leg strength and quality of life in patients with osteoarthritis.
This study aimed to investigate the effect of ancient boxing exercise on the strength of leg muscles and quality of life in patients with osteoarthritis. The subjects were divided into 2 groups, control group (CG) and experimental group (EG). The average aged of control and experimental group were 60.3±6.8 and 59.0±7.8 years, respectively. All volunteers were interviewed for basic information, evaluation of the criteria of research and sign consent to participate in the research. The outcome measurement consisted of five time sit to stand test, 6-min walk test, flexibility by sit and reach test, Berg Balance Scale, Timed Up and Go Test, knee injury and osteoarthritis outcomes score (KOOS) and quality of life of World Health Organization Thai brief version (WHOQOL-BERF-THAI). Prior and posttest measurements were performed at 0, 4, 8, and 12 weeks, and those who received ancient boxing exercise were given 60 min 3 times per week for 12 weeks. The results of the study showed that postexercise leg muscle strength, physical performances, quality of life and KOOS increased significantly after exercise. In conclusion, the ancient boxing exercise could increase the strength of leg muscles physical performances, quality of life in people with knee osteoarthritis. This exercise can be used as a long lasting exercise in the future.


Desorption atmospheric pressure photoionization and direct analysis in real time coupled with travelling wave ion mobility mass spectrometry.
Ambient mass spectrometry (MS) is a tool for screening analytes directly from sample surfaces. However, background impurities may complicate the spectra and therefore fast separation techniques are needed. Here, we demonstrate the use of travelling wave ion mobility spectrometry in a comparative study of two ambient MS techniques. Desorption atmospheric pressure photoionization (DAPPI) and direct analysis in real time (DART) were coupled with travelling wave ion mobility mass spectrometry (TWIM-MS) for highly selective surface analysis. The ionization efficiencies of DAPPI and DART were compared. Test compounds were: bisphenol A, benzo[a]pyrene, ranitidine, cortisol and α-tocopherol. DAPPI-MS and DART-TWIM-MS were also applied to the analysis of chloroquine from dried blood spots, and α-tocopherol from almond surface, and DAPPI-TWIM-MS was applied to analysis of pharmaceuticals and multivitamin tablets. DAPPI was approximately 100 times more sensitive than DART for bisphenol A and 10-20 times more sensitive for the other compounds. The limits of detection were between 30-290 and 330-8200 fmol for DAPPI and DART, respectively. Also, from the authentic samples, DAPPI ionized chloroquine and α-tocopherol more efficiently than DART. The mobility separation enabled the detection of species with low signal intensities, e.g. thiamine and cholecalciferol, in the DAPPI-TWIM-MS analysis of multivitamin tablets. DAPPI ionized the studied compounds of interest more efficiently than DART. For both DAPPI and DART, the mobility separation prior to MS analysis reduced the amount of chemical noise in the mass spectrum and significantly increased the signal-to-noise ratio for the analytes.


Immunity to and infant mortality from measles.
The age-related sequential immune response to natural measles was investigated in order to establish the role of immunodeficiency in the high infant mortality from infectious diseases. There was no difference in lymphocyte transformation, complement-fixing antibody titres, serum IgG, IgM, IgA, C3 and factor B levels, total haemolytic complement and the alternative pathway of complement over a 6-week period after onset of the rash in those younger than 12 months (group A) compared with children older than 12 months (group B). The absolute number of peripheral blood lymphocytes, comprising T, B and null cells, was higher on different days in group A compared with group B. Throughout the 6 weeks group A had higher haemagglutination inhibition antibody levels and lower serum C4 levels than Group B. The inhibition of leucocyte migration to measles antigen was similar in the two groups, except on day 28 when it was significantly higher in group B. There were 5 deaths, all in infants younger than 15 months of age. Most immunological reactions studied were not age-dependent, while those differences detected in the younger age group involved factors known to indicate a good prognosis. Therefore, the high mortality rate reported for measles in infants is unlikely to be due to immunodeficiency in this age group.


Purposes of health identification cards in belgium.
Although other alternatives might exist, identification cards have been chosen as an acceptable and adequate tool to be used to identify patients and health professionals.They are planned for a digital signature and for access to electronic health records as well as for health information exchange and for databases querying. Local applications might exist independently, but the Federal State has now developed BeHealth, a platform for health professionals, social security personnel as well as the great public to facilitate a common access to some health data. Security conditions have been defined and are described.


Cloning and expression in Enterobacteriaceae of the extended-spectrum beta-lactamase gene from a Pseudomonas aeruginosa plasmid.
An extended-spectrum beta-lactamase, the gene for which is located on plasmid pMS350 in Pseudomonas aeruginosa strains, hydrolyzes carbapenems and other extended-spectrum beta-lactam antibiotics. We cloned the pMS350 beta-lactamase gene in an Escherichia coli K-12 strain using the vector plasmid pHSG398, and subcloned it into pMS360, a plasmid with a wide host-range. This resulted in the formation of the recombinant plasmid, pMS363, containing a 4.1-kb DNA insert that includes the extended-spectrum beta-lactamase gene. Plasmid pMS363 was introduced into the P. aeruginosa PAO strain or into six species of Enterobacteriaceae, and the specific activities of the beta-lactamase and MICs of various beta-lactam antibiotics were estimated. The cloned gene was capable of expression in these strains and caused resistance to carbapenem, penem and other beta-lactam antibiotics, with the exception of aztreonam.


Gene expression profiling of the human natural killer cell response to Fc receptor activation: unique enhancement in the presence of interleukin-12.
Traditionally, the CD56(dim)CD16(+) subset of Natural Killer (NK) cells has been thought to mediate cellular cytotoxicity with modest cytokine secretion capacity. However, studies have suggested that this subset may exert a more diverse array of immunological functions. There exists a lack of well-developed functional models to describe the behavior of activated NK cells, and the interactions between signaling pathways that facilitate effector functions are not well understood. In the present study, a combination of genome-wide microarray analyses and systems-level bioinformatics approaches were utilized to elucidate the transcriptional landscape of NK cells activated via interactions with antibody-coated targets in the presence of interleukin-12 (IL-12). We conducted differential gene expression analysis of CD56(dim)CD16(+) NK cells following FcR stimulation in the presence or absence of IL-12. Next, we functionally characterized gene sets according to patterns of gene expression and validated representative genes using RT-PCR. IPA was utilized for biological pathway analysis, and an enriched network of interacting genes was generated using GeneMANIA. Furthermore, PAJEK and the HITS algorithm were employed to identify important genes in the network according to betweeness centrality, hub, and authority node metrics. Analyses revealed that CD56(dim)CD16(+) NK cells co-stimulated via the Fc receptor (FcR) and IL-12R led to the expression of a unique set of genes, including genes encoding cytotoxicity receptors, apoptotic proteins, intracellular signaling molecules, and cytokines that may mediate enhanced cytotoxicity and interactions with other immune cells within inflammatory tissues. Network analyses identified a novel set of connected key players, BATF, IRF4, TBX21, and IFNG, within an integrated network composed of differentially expressed genes in NK cells stimulated by various conditions (immobilized IgG, IL-12, or the combination of IgG and IL-12). These results are the first to address the global mechanisms by which NK cells mediate their biological functions when encountering antibody-coated targets within inflammatory sites. Moreover, this study has identified a set of high-priority targets for subsequent investigation into strategies to combat cancer by enhancing the anti-tumor activity of CD56(dim)CD16(+) NK cells.


Absence of Meckel Cave: A Rare Cause of Trigeminal Neuralgia.
Trigeminal neuralgia is a debilitating condition with numerous etiologies. In this retrospective case series, we report a cohort of patients with a rarely described entity, absence of Meckel cave, and propose this as a rare cause of trigeminal neuralgia. A search of the electronic medical record was performed between 2000 and 2020 to identify MR imaging reports with terms including "Meckel's cave" and "hypoplasia," "atresia," "collapse," or "asymmetry." Images were reviewed by 2 blinded, board-certified neuroradiologists. Seven cases of the absence of Meckel cave were identified. Seven patients (100%) had ipsilateral trigeminal neuralgia and ipsilateral trigeminal nerve atrophy, suggesting an association between absence of Meckel cave and trigeminal neuralgia. Absence of Meckel cave is a rare entity of unknown etiology, with few existing reports that suggest the possibility of an association with trigeminal neuralgia. Its recognition may have important implications in patient management. Future studies and longitudinal data are needed to assess treatment outcomes and added risks from surgical intervention in these patients.


In vivo studies on the metabolism of the monoterpene pulegone in humans using the metabolism of ingestion-correlated amounts (MICA) approach: explanation for the toxicity differences between (S)-(-)- and (R)-(+)-pulegone.
The major in vivo metabolites of (S)-(-)-pulegone in humans using a metabolism of ingestion-correlated amounts (MICA) experiment were newly identified as 2-(2-hydroxy-1-methylethyl)-5-methylcyclohexanone (8-hydroxymenthone, M1), 3-hydroxy-3-methyl-6-(1-methylethyl)cyclohexanone (1-hydroxymenthone, M2), 3-methyl-6-(1-methylethyl)cyclohexanol (menthol), and E-2-(2-hydroxy-1-methylethylidene)-5-methylcyclohexanone (10-hydroxypulegone, M4) on the basis of mass spectrometric analysis in combination with syntheses and NMR experiments. Minor metabolites were be identified as 3-methyl-6-(1-methylethyl)-2-cyclohexenone (piperitone, M5) and alpha,alpha,4-trimethyl-1-cyclohexene-1-methanol (3-p-menthen-8-ol, M6). Menthofuran was not a major metabolite of pulegone and is most probably an artifact formed during workup from known (M4) and/or unknown precursors. The differences in toxicity between (S)-(-)- and (R)-(+)-pulegone can be explained by the strongly diminished ability for enzymatic reduction of the double bond in (R)-(+)-pulegone. This might lead to further oxidative metabolism of 10-hydroxypulegone (M4) and the formation of further currently undetected metabolites that might account for the observed hepatotoxic and pneumotoxic activity in humans.


Hepatic injury in dermatitis herpetiformis.
Liver function tests were performed in 60 patients with dermatitis herpetiformis. Abnormalities of bilirubin or elevated liver enzyme levels were found in 17% of the patients. 13% had abnormal liver enzymes or elevated bilirubin levels not due to haemolysis. In 8% of patients bilirubin levels were elevated as a result of dapsone-induced haemolysis. The incidence of liver function abnormalities was higher (19%) in those on a normal diet than those on a gluten-free diet (9%). The abnormalities were not associated with the presence of immune complexes, anti-mitochondrial or anti-smooth muscle antibodies.


Bone and joint involvement in primary amyloidosis.
Primary amyloidosis is an interesting clinical entity in which amyloid is deposited in various organs, particularly mesodermderived tissues such as heart, skeletal muscle, skin, connective tissue and bone. A case with multiple lytic bone lesions is presented. Comparison to previous similar cases is made with attention being directed to the typical distribution of lesions about large joints with associated soft-tissue prominence and increase in the articular space. The differentiating radiologic features are compared to those of rheumatoid arthritis, hyperparathyroidism, and lytic metastatic lesions, with particular attention being given to the osteolytic lesions of plasmacytomas associated with multiple myeloma.


Differences in neural response to extinction recall in young adults with or without history of behavioral inhibition.
Behavioral inhibition (BI) is a temperament identified in early childhood that is associated with risk for anxiety disorders, yet only about half of behaviorally inhibited children manifest anxiety later in life. We compared brain function and behavior during extinction recall in a sample of nonanxious young adults characterized in childhood with BI (n = 22) or with no BI (n = 28). Three weeks after undergoing fear conditioning and extinction, participants completed a functional magnetic resonance imaging extinction recall task assessing memory and threat differentiation for conditioned stimuli. While self-report and psychophysiological measures of differential conditioning and extinction were similar across groups, BI-related differences in brain function emerged during extinction recall. Childhood BI was associated with greater activation in subgenual anterior cingulate cortex in response to cues signaling safety. This pattern of results may reflect neural correlates that promote resilience against anxiety in a temperamentally at-risk population.


White Matter Abnormalities in Patients with Treatment-Resistant Genetic Generalized Epilepsies.
BACKGROUND Genetic generalized epilepsies (GGEs) are associated with microstructural brain abnormalities that can be evaluated with diffusion tensor imaging (DTI). Available studies on GGEs have conflicting results. Our primary goal was to compare the white matter structure in a cohort of patients with video/EEG-confirmed GGEs to healthy controls (HCs). Our secondary goal was to assess the potential effect of age at GGE onset on the white matter structure. MATERIAL AND METHODS A convenience sample of 23 patients with well-characterized treatment-resistant GGEs (13 female) was compared to 23 HCs. All participants received MRI at 3T. DTI indices, including fractional anisotropy (FA) and mean diffusivity (MD), were compared between groups using Tract-Based Spatial Statistics (TBSS). RESULTS After controlling for differences between groups, abnormalities in DTI parameters were observed in patients with GGEs, including decreases in functional anisotropy (FA) in the hemispheric (left>right) and brain stem white matter. The examination of the effect of age at GGE onset on the white matter integrity revealed a significant negative correlation in the left parietal white matter region FA (R=-0.504; p=0.017); similar trends were observed in the white matter underlying left motor cortex (R=-0.357; p=0.103) and left posterior limb of the internal capsule (R=-0.319; p=0.148). CONCLUSIONS Our study confirms the presence of widespread white matter abnormalities in patients with GGEs and provides evidence that the age at GGE onset may have an important effect on white matter integrity.


Structural and spectroscopic characterization of two new blue luminescent pyridylbenzimidazole zinc(II) complexes.
Luminescent metal complexes are used in photooptical devices. Zinc(II) complexes are of interest because of the ability to tune their color, their high thermal stability and their favorable carrier transport character. In particular, some zinc(II) complexes with aryl diimine and/or heterocyclic ligands have been shown to emit brightly in the blue region of the spectrum. Zinc(II) complexes bearing derivatized imidazoles have been explored for possible optoelectronic applications. The structures of two zinc(II) complexes of 5,6-dimethyl-2-(pyridin-2-yl)-1-[(pyridin-2-yl)methyl]-1H-benzimidazole (L), namely dichlorido(dimethylformamide-κO){5,6-dimethyl-2-(pyridin-2-yl-κN)-1-[(pyridin-2-yl)methyl]-1H-benzimidazole-κN(3)}zinc(II) dimethylformamide monosolvate, [ZnCl2(C20H18N4)(C3H7NO)]·C3H7NO, (I), and bis(acetato-κ(2)O,O'){5,6-dimethyl-2-(pyridin-2-yl-κN)-1-[(pyridin-2-yl)methyl]-1H-benzimidazole-κN(3)}zinc(II) ethanol monosolvate, [Zn(C2H3O2)2(C20H18N4)]·C2H5OH, (II), are reported. Complex (I) crystallized as a dimethylformamide solvate and exhibits a distorted trigonal bipyramidal coordination geometry. The coordination sphere consists of a bidentate L ligand spanning axial to equatorial sites, two chloride ligands in equatorial sites, and an O-bound dimethylformamide ligand in the remaining axial site. The other complex, (II), crystallized as an ethanol solvate. The Zn(II) atom has a distorted trigonal prismatic coordination geometry, with two bidentate acetate ligands occupying two edges and a bidentate L ligand occupying the third edge of the prism. Complexes (I) and (II) emit in the blue region of the spectrum. The results of density functional theory (DFT) calculations suggest that the luminescence of L results from π*←π transitions and that the luminescence of the complexes results from interligand charge-transfer transitions. The orientation of the 2-(pyridin-2-yl) substituent with respect to the benzimidazole system was found to have an impact on the calculated HOMO-LUMO gap (HOMO is highest occupied molecular orbital and LUMO is lowest unoccupied molecular orbital).


Molecular dynamics study of the density and temperature dependence of bridge functions in normal and supercritical Lennard-Jones fluids.
A systematic study of the density and temperature dependence of bridge functions has been carried out using molecular dynamics simulation studies in one-component Lennard-Jones fluids. In deriving the liquid structure, approximate closures are generally used in integral equation theories of liquids to obtain static density correlations. In the present work, we have directly compared the simulated bridge function to two such commonly used closures, viz., hybrid mean spherical approximation (HMSA) [J. Chem. Phys. 84, 2336 (1986)] and Duh-Henderson [J. Chem. Phys. 104, 6742 (1996)] closures with thermodynamic parameters varying from the normal liquid to the supercritical fluid phase far from and near the critical point. In the normal liquid region, both closures show a qualitative agreement with the simulated bridge function, although the extent of correlation at distances sigma < r < or = 2.5sigma is generally underestimated. A similar behavior is obtained in supercritical fluids far from the critical point where critical fluctuations are no longer important. In contrast, significant deviations are observed in the bridge functions in supercritical fluids near the critical point even at densities as small as 25% or 50% of the critical density. Such behavior appears to have resulted from competing contributions to the bridge function from decreasing indirect correlations and small yet significant cavity correlations persistent even at very low densities.


Self-Efficacy and Short-Term Adherence to Continuous Positive Airway Pressure Treatment in Children.
Infants, children, and adolescents are increasingly being prescribed continuous positive airway pressure (CPAP) for treatment of obstructive sleep apnea syndrome (OSAS), yet adherence is often poor. The purpose of this study was to examine the relationship between caregiver and patient-reported health cognitions about CPAP prior to starting CPAP and CPAP adherence at 1 month. We hypothesized that greater caregiver-reported self-efficacy would be positively associated with CPAP adherence in children. We also evaluated patient-reported self-efficacy and caregiver- and patient-reported risk perception and outcome expectations as they related to adherence, as well as how demographic factors influenced these relationships. A pediatric modification of the Self-Efficacy Measure for Sleep Apnea Questionnaire was administered to children and adolescents with OSAS-prescribed CPAP and their caregivers during the clinical CPAP-initiation visit. The primary outcome variable for adherence was the average total minutes of CPAP usage across all days from the date that CPAP was initiated to 31 days later. Unadjusted ordinary least-square regression showed a significant association between caregiver-reported self-efficacy and adherence (p = .007), indicating that mean daily CPAP usage increased by 48.4 minutes when caregiver-reported self-efficacy increased by one point (95% confidence interval 13.4-83.4 minutes). No other caregiver- or patient-reported cognitive health variables were related to CPAP use. This study indicates that caregiver CPAP-specific self-efficacy is an important factor to consider when starting youth on CPAP therapy for OSAS. Employing strategies to improve caregiver self-efficacy, beginning at CPAP initiation, may promote CPAP adherence.


Novel Pharmacologic Approaches for the Management of Diabetic Retinopathy.
Diabetic retinopathy is the leading cause of vision loss among working-age people in the United States. The hallmark of diabetic retinopathy is vascular compromise. Increased vascular permeability leads to the development of diabetic macular edema, which is the major cause of vision loss in patients with diabetic retinopathy. Vascular occlusion causes retinal ischemia and subsequent angiogenesis (proliferative diabetic retinopathy), which increases the risk for vitreous hemorrhage and retinal detachment. Over the past 30 years our understanding of the pathophysiology of diabetic retinopathy has evolved greatly and has fostered the development of many novel treatments for this condition. This article will review promising new local and systemic pharmacologic treatments for diabetic macular edema and proliferative diabetic retinopathy.