Reduction of thyroid hormone may participate in the modulation of cytochromes P450 2C11 and 3A2 by retinol.
Both hypothyroidism and retinol supplementation in rats induce CYP 3A2 and suppress CYP 2C11. Therefore studies were performed to evaluate the role of thyroid hormones in the modulation of P450 expression by retinol. Adult male Sprague-Dawley rats were given retinol as a single oral dose of 75 mg/kg. Rats were killed and hepatic microsomes prepared at 24, 48, 72, and 96 hr following treatment. The catalytic activity of 2C11 was reduced maximally by retinol at 48 hr (by 30%) whereas 3A2 activity was elevated maximally at 24 hr (by 30%). The serum concentration of testosterone was not altered at any time point. However, retinol produced a decline in the concentration of thyroxine by 35% and 43% at 24 and 48 hr, respectively. These data suggest that administration of large doses of retinol may alter hepatic microsomal enzyme expression by perturbation of plasma thyroid hormone levels.


Simultaneous monitoring of cytomegalovirus-specific antibody and T-cell levels in seropositive heart transplant recipients.
Human cytomegalovirus (CMV) active infection (CMV infection) poses serious risks to CMV-seropositive heart transplant recipients. We evaluated the usefulness of simultaneous assessment of CMV-specific values for parameters of the humoral (antibodies) and cellular (CD4+ and CD8+ T-cells) immune responses in the identification of heart recipients at risk of developing CMV infection after transplantation. We prospectively studied 38 CMV-seropositive heart recipients. Anti-CMV antibody titers were assessed using enzyme-linked immunosorbent assays. CD4+ and CD8+ T-cell responses to overlapping peptide pools of the CMV proteins pp65 and immediate early protein-1 (IE1) were evaluated by flow cytometry. Immunological studies were performed before transplantation and at 30 days after transplantation. Patients with CMV infection were compared with heart recipients without CMV infection. During the 6-month follow-up period, 13 (34.2%) patients developed CMV infection. At baseline, the mean anti-CMV-IgG antibody titer was lower in patients who developed CMV infection. This difference remained at 30 days after transplantation. One month after transplantation, the mean percentage of IE1-specific CD8+ T cells that are IFNg-positive (CD8/IFNg + IE1) was lower in CMV-infected patients. The predictive value of these variables at 30 days was increased when they were combined. Cox regression analysis revealed an association between the risk of developing CMV infection and the combination marker (low anti-CMV titer [<16,100] and low CD8/IFNg + IE1 percentages [<0.40%], relative hazard, 6.07; p = 0.019). The combination marker remained significant after adjustment for clinical variables. This novel approach of a simultaneous assessment of specific anti-CMV antibody titers and CD8/IFNg + IE1 percentages might help identify heart transplant recipients with an increased risk of developing CMV infection.


Parents' responses to prognostic disclosure at diagnosis of a child with a high-risk brain tumor: Analysis of clinician-parent interactions and implications for clinical practice.
Previous studies have found that parents of children with cancer desire more prognostic information than is often given even when prognosis is poor. We explored in audio-recorded consultations the kinds of information they seek. Ethnographic study including observation and audio recording of consultations at diagnosis. Consultations were transcribed and analyzed using an interactionist perspective including tools drawn from conversation and discourse analysis. Enrolled 21 parents and 12 clinicians in 13 cases of children diagnosed with a high-risk brain tumor (HRBT) over 20 months at a tertiary pediatric oncology center. Clinicians presented prognostic information in all cases. Through their questions, parents revealed what further information they desired. Clinicians made clear that no one could be absolutely certain what the future held for an individual child. Explicit communication about prognosis did not satisfy parents' desire for information about their own child. Parents tried to personalize prognostic information and to apply it to their own situation. Parents moved beyond prognostic information presented and drew conclusions, which could change over time. Parents who were present in the same consultations could form different views of their child's prognosis. Population level prognostic information left parents uncertain about their child's future. The need parents revealed was not for more such information but rather how to use the information given and how to apply it to their child in the face of such uncertainty. Further research is needed on how best to help parents deal with uncertainty and make prognostic information actionable.


Identification and Characterization of Two Novel Extracellular β-Glucanases from Chaetomium globosum against Fusarium sporotrichioides.
Chaetomium globosum can inhibit the growth of fusarium by means of their extracellular proteins. Two novel β-glucanases, designated Cgglu17A and Cgglu16B, were separated from the supernatant of C. globosum W7 and verified to have the ability to hydrolyze cell walls of Fusarium sporotrichioides MLS-19. Cgglu17A (397 amino acids) was classified as glycoside hydrolase family 17 while Cgglu16B belongs to the family16 (284 amino acids). Recombinant protein Cgglu17A was successfully expressed in Escherichia coli, and the enzymes were purified by affinity chromatography. Maximum activity of Cgglu17A appeared at the pH 5.5 and temperature 50 °C, but Cgglu16B shows the maximum activity at the pH 5.0 and temperature 50 °C. Most of heavy metal ions had inhibition effect on the two enzymes, but Cgglu17A and Cgglu16B were respectively activated by Ba2+ and Mn2+. Cgglu17A exhibited high substrate specificity, almost only catalyzing the cleavage of β-1,3-glycosidic bond, in various polysaccharose, to liberate glucose. However, Cgglu16B showed high catalytic activities to both β-1,3-glycosidic and β-1,3-1,4-glycosidic bonds. Cgglu17A was an exo-glucanase, but Cgglu16B was an endo-glucanase based on hydrolytic properties assay. Both of two enzymes showed potential antifungal activity, and the synergistic effect was observed in the germination experiment of pathogenic fungus. In conclusion, Cgglu17A (exo-1,3-β-glucanase) and Cgglu16B (endo-1,3(4)-β-glucanase) were confirmed to play a key role in the process of C. globosum controlling fusarium and have potential application value on industry and agriculture for the first time.


An experimental investigation into the effects of flooding on the ixodid tick Boophilus microplus (Canestrini).
The effect of water immersion on the non-parasitic stages of Boophilus microplus were investigated both under laboratory and field conditions. Survival of engorged female ticks was influenced by their age and the temperature of the water. Eggs and larvae were more resistant to submerison than were engorged females and their survival was increased at low temperatures and in water with high oxygen content. The persistence of this tick in areas prone to flooding was attributed to the survival of parasitic stages and to larvae on the pasture. Heavy rains produce favourable pasture conditions for tick reproduction so that a large increase in population size may be expected to follow such rain.


A simplified method to approximate a ROC curve with a Bézier curve to calculate likelihood ratios of quantitative test results.
In order to calculate likeli hood ratios (LR) values for quantitative test results, a distribution-independent algorithm based on Bézier curves is proposed. Receiver operating characteristic (ROC) analysis provides the LR as the slope of the tangent to the ROC curve at the point corresponding to the test result. • Here, we make use of cubic Bézier curves defined by Bernstein polynomials of degree 3. • A simplified method to adjust a Bézier curve to a ROC curve is presented • The crucial advantage of this procedure is that Bézier curves are constructed by tangents to the ROC curve, whose slopes immediately provide the LR of a specific point on the curve.


[Imaging cardiac hydatid cysts: 8 cases].
Early diagnosis of cardiac echinococcosis is required because this uncommon disease may lead to serious complications. We report 8 cases of cardiac hydatidosis, review the modes of diagnosis, and stress the contribution of modern imaging techniques. This retrospective study describes 8 patients with cardiac echinococcosis. All had chest radiographs and thoracic computed tomography (CT). Transthoracic sonography was performed in 6 cases and magnetic resonance imaging (MRI) in 5. Our patients ranged in age from 7 to 46 years, and the clinical features of their disease varied. Chest radiography showed the contours of the heart to be deformed in 3 cases and cardiomegaly in 3 others. Echocardiography revealed a homogeneous unilocular hydatid cyst in 5 cases. CT found homogeneous hypodense unilocular lesions in 7 cases, and a septated cyst with cardiac wall calcifications in one case. MRI showed round homogeneous lesions in 3 cases, all dark in T1-weighted sequences and bright in T2. Clinical features vary substantially, and clinical latency is not uncommon. Chest radiography generally shows mediastinal masses. Transthoracic echocardiography can locate and count cardiac hydatid cysts and identify their borders. CT can simultaneously assess any visceral extension of the disease, while MRI provides details of mediastinal extensions. Transthoracic echocardiography suggests the initial diagnosis. CT and MRI provide details of the location and extension of the cardiac hydatidosis.


Statistics for the analysis of molecular dynamics simulations: providing P values for agonist-dependent GPCR activation.
Molecular dynamics (MD) is the common computational technique for assessing efficacy of GPCR-bound ligands. Agonist efficacy measures the capability of the ligand-bound receptor of reaching the active state in comparison with the free receptor. In this respect, agonists, neutral antagonists and inverse agonists can be considered. A collection of MD simulations of both the ligand-bound and the free receptor are needed to provide reliable conclusions. Variability in the trajectories needs quantification and proper statistical tools for meaningful and non-subjective conclusions. Multiple-factor (time, ligand, lipid) ANOVA with repeated measurements on the time factor is proposed as a suitable statistical method for the analysis of agonist-dependent GPCR activation MD simulations. Inclusion of time factor in the ANOVA model is consistent with the time-dependent nature of MD. Ligand and lipid factors measure agonist and lipid influence on receptor activation. Previously reported MD simulations of adenosine A2a receptor (A2aR) are reanalyzed with this statistical method. TM6-TM3 and TM7-TM3 distances are selected as dependent variables in the ANOVA model. The ligand factor includes the presence or absence of adenosine whereas the lipid factor considers DOPC or DOPG lipids. Statistical analysis of MD simulations shows the efficacy of adenosine and the effect of the membrane lipid composition. Subsequent application of the statistical methodology to NECA A2aR agonist, with resulting P values in consistency with its pharmacological profile, suggests that the method is useful for ligand comparison and potentially for dynamic structure-based virtual screening.


Long-acting β2 agonists and corticosteroids restore the reduction of histone deacetylase activity and inhibit H2O2-induced mediator release from alveolar macrophages.
Treatment of COPD with a combination of long-acting β(2) agonists and corticosteroids is currently used worldwide. The mechanisms of the anti-inflammatory effects and their associations with histone deacetylase (HDAC) activity remain unclear. Human alveolar macrophages were isolated and stimulated with H(2)O(2) in the presence of varying concentrations of long-acting β(2) agonists and corticosteroids. Supernatants were collected for IL-8 and MMP-9 measurements. Cell lysates were analyzed for HDAC (mainly HDAC1/HDAC2) activity. Quantitative real-time PCR was performed to determine the levels of IL-8 and MMP-9 mRNA. Both long-acting β(2) agonists, salmeterol and formoterol, and corticosteroids, fluticasone and budesonide, showed anti-inflammatory effects to a certain extent on H(2)O(2)-induced IL-8 and MMP-9 release in alveolar macrophages. Combinations of long-acting β(2) agonists and corticosteroids exerted greater effects to suppress mediator release, and both transcription and translation of IL-8 and MMP-9 were inhibited. It seemed that the levels of IL-8 and MMP-9 after H(2)O(2) stimulation were inversely associated with the activity of HDAC. H(2)O(2) stimulation resulted in a significant decrease in HDAC activity and was associated with an increase in mediator release. In contrast, treatment with long-acting β(2) agonists, corticosteroids or theophylline restored the H(2)O(2)-induced decrease in HDAC activity and inhibited mediator release. Combinations of long-acting β(2) agonists and corticosteroids exerted greater effects on the suppression of mediator release in relation to the enhancement of HDAC activity. This supports at least in part the likely contribution of anti-inflammatory effects of long-acting β(2) agonists and corticosteroids to the clinical benefits seen in COPD patients.


Sperm lacking Bindin are infertile but are otherwise indistinguishable from wildtype sperm.
Cell-cell fusion is limited to only a few cell types in the body of most organisms and sperm and eggs are paradigmatic in this process. The specialized cellular mechanism of fertilization includes the timely exposure of gamete-specific interaction proteins by the sperm as it approaches the egg. Bindin in sea urchin sperm is one such gamete interaction protein and it enables species-specific interaction with a homotypic egg. We recently showed that Bindin is essential for fertilization by use of Cas9 targeted gene inactivation in the sea urchin, Hemicentrotus pulcherrimus. Here we show phenotypic details of Bindin-minus sperm. Sperm lacking Bindin do not bind to nor fertilize eggs at even high concentrations, yet they otherwise have wildtype morphology and function. These features include head shape, tail length and beating frequency, an acrosomal vesicle, a nuclear fossa, and they undergo an acrosomal reaction. The only phenotypic differences between wildtype and Bindin-minus sperm identified is that Bindin-minus sperm have a slightly shorter head, likely as a result of an acrosome lacking Bindin. These data, and the observation that Bindin-minus embryos develop normally and metamorphose into normal functioning adults, support the contention that Bindin functions are limited to species-specific sperm-egg interactions. We conclude that the evolutionary divergence of Bindin is not constrained by any other biological roles.


Guideline No. 435: Minimally Invasive Surgery in Fertility Therapy.
To evaluate the benefits and risks of minimally invasive procedures in the management of patients with infertility and provide guidance to gynaecologists who manage common conditions in these patients. Patients with infertility (inability to conceive after 12 months of unprotected intercourse) undergoing investigation and treatment. Minimally invasive reproductive surgery can be used to treat infertility, improve fertility treatment outcomes, or preserve fertility. All surgery has risks and associated complications. Reproductive surgery may not improve fertility outcomes and may, in some instances, damage ovarian reserve. All procedures have costs, which are borne either by the patient or their health insurance provider. We searched English-language articles from January 2010 to May 2021 in PubMed/MEDLINE, Embase, Science Direct, Scopus, and Cochrane Library (see Appendix A for MeSH search terms). The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix B (Tables B1 for definitions and B2 for interpretations of strong and conditional [weak] recommendations). Gynaecologists who manage common conditions in patients with infertility. RECOMMENDATIONS.


Electrocatalysis of molecular oxygen reduction reaction at liquid-liquid interface and DFT computational study of proton transfer from the conjugate acid of 2,2'-dipyridylamineto oxygen.
In this study, the catalytic effect of 2,2'-dipyridylamine (DPA) on the reduction of oxygen (O2) at the polarized water/1,2-dichloroethane (DCE) interface was investigated. Ferrocene (Fc) and tetrathiafulvalene (TTF) were weak electron donors used in this study. Slow reduction of O2 at the interface containing Fc and TTF was significantly accelerated upon the addition of DPA. Voltammetry and biphasic shake flask experiments revealed that DPA acts as a proton ionophore to transfer protons between the aqueous and organic phases. The PA, GB, and pKa values of all possible conjugate acids of DPA were calculated. Then, a mechanism was suggested to explain the interaction between protonated DPA and oxygen molecular. The mechanism was computationally analyzed by using density functional theory (DFT). Furthermore, DFT calculations at the B3LYP/6-31G** level of theory showed that the conjugate acid species of DPA transfer proton to O2 at the interface. The results show that DPA-H2+ and DPA-H1+ are the best species to transfer proton to molecular oxygen.


Effect of cycloheximide on temperature regulation in rats.
The effect of cycloheximide, an inhibitor of protein synthesis, on temperature regulation in afebrile rats was studied to determine whether its reported antipyretic effect might be attributable to a non-specific antimetabolic effect. Within 60 min after administration of cycloheximide (5 mg/kg IP) to female rats at ambient temperatures of 34, 25 and 15 degrees C, a significant decrease in colonic temperature was observed as compared with control rats administered saline IP. Measurements of rate of oxygen consumption showed that cycloheximide (5 mg/kg IP) significantly depressed the ability of rats to increase their heat production during a cold stress (15 degrees C). In the cold the rate of oxygen consumption increased 8.7 +/- 0.8 ml/min/kg0.75 in the control rats but only 1.8 +/- 0.9 ml/min/kg0.75 in the cycloheximide-treated rats. Since the thermoregulatory changes accompanying cold stress are similar to those observed during the genesis of fever, these data suggest that cycloheximide may have a general depressant effect on heat production rather than a specific antipyretic effect.


Impact of Gender on Child and Adolescent PTSD.
This review examines the recent literature on biological factors that influence sex differences in posttraumatic stress disorder (PTSD) during childhood and adolescence, focusing on neurobiological, hormonal, and genetic factors that may increase risk in girls. More than 60% of children and adolescents are exposed to traumatic events, and many develop PTSD. There is increasing recognition of gender differences in PTSD, with women having double the rates of the disorder compared to men. These gender differences in symptoms and their underlying neurobiology appear to emerge during adolescence, although it is still unclear which biological mechanisms may play key roles in the development of sex difference. The literature on gender effects in children and adolescents is still in the early stages, and more prospective and longitudinal work is needed; however, estrogen appears to play a key role in increasing risk for PTSD in girls, which emerges in adolescence.


A comparative study of different aspects in manipulating ratio spectra used for the analysis of cefradine in the presence of its alkaline degradation product.
Six stability-indicating UV-spectrophotometric methods manipulating ratio spectra were utilized for the analysis of cefradine in presence of its alkaline degradate. These methods are different forms of transformations; ratio difference, mean centering, derivative ratio using numerical differentiation, derivative ratio using Savitsky-Golay filter, continuous wavelet transform and derivative continuous wavelet transform. Water was used as a solvent and the linearity ranges were 6-26 μg/mL. Determination of accuracy and precision for the suggested procedures were executed. Assessment of specificity was run through analyzing laboratory prepared mixtures containing cefradine and its alkaline degradate. The suggested methods were useful for cefradine estimation in tablets. Statistically, the outputs obtained from the recommended and published methods reveal no significant differences.


The effects of a sudden salinity change on cortisol, glucose, lactate, and osmolality levels in grouper Epinephelus malabaricus.
Grouper Epinephelus malabaricus (weighing 46.37 ± 5.10 g) previously maintained in 24‰ seawater were transferred to 14, 19, 24 (control), 29, and 34‰ seawater. Serum cortisol, glucose, lactate, and osmolality levels were measured at 7 time points during 240 min. Serum cortisol and glucose levels of fish transferred to 29 and 34‰ seawater significantly increased to the highest after 10 and 20 min, respectively. No significant differences in serum cortisol and glucose levels were observed for the fish after 30 min among all treatments. Serum lactate level of fish transferred to 14, 19, 29, and 34‰ seawater was significantly lower than that of the control fish after 10-30 min. However, no significant differences in serum lactate were observed 60 min among five treatments. The serum osmolality of the fish following 240-min transfer increased directly with salinity, whereas the osmoregulatory capacity value (medium osmolality-plasma osmolality) of the fish following 240-min transfer was inversely related to salinity. It is concluded that grouper showed strong osmoregulation in 14-34‰ seawater. Serum cortisol and glucose levels of fish transferred to 29 and 34‰ seawater increased rapidly in 10-30 min, indicating an early stress response.


To evaluate and compare the compressive strength of root dentin exposed to calcium hydroxide, mixed with various vehicles for a period of 30 days - An in vitro study.
Long-term use of intracanal medicaments such as calcium hydroxide (CH) reduces the fracture resistance of dentin. This study aimed to evaluate and compare the compressive strength of root dentin exposed to CH, mixed with various vehicles after 30 days of placement. Sixty single-rooted extracted human permanent premolars were collected, and complete instrumentation was done. Samples were divided into six groups. In Group I, no medicament was placed. In Group II, Group III, and Group IV, the root canals were filled with CH powder mixed with normal saline, distilled water, and local anesthetic solution. In Group V and Group VI, the root canals were filled with Metapaste and RC-Cal. Access cavities were sealed using IRM and were stored for 30 days. Teeth sectioned to obtain a 5 mm thick dentin cylinder subjected to compressive loading to evaluate the fracture resistance using a universal testing machine. Results were analyzed using one-way ANOVA and multiple comparisons using Bonferroni test. Highest mean compressive strength was recorded in Group I followed by Group II, Group IV, Group VI, Group III, and Group V. CH when used as a root canal dressing material will reduce the compressive strength of the teeth irrespective of the form of CH and vehicle.


The inhibition of Na-dependent Ca uptake by verapamil in synaptic plasma membrane vesicles.
This study on the effect of verapamil on the Na+-dependent Ca2+ uptake system (Na+-Ca2+ exchanger) of synaptic plasma membrane (SPM) vesicles showed that verapamil inhibited the Na+-dependent Ca2+ uptake in a dose dependent manner. A 50% inhibition was obtained with 175 microM verapamil. Calcium uptake in SPM vesicles is dependent on the Na+ gradient across the membrane and on the membrane potential. Both components of the Ca2+ uptake system were inhibited by verapamil. Na+-coupled GABA uptake in SPM vesicles was also inhibited by verapamil in a similar dose-dependent fashion. It seems therefore that verapamil inhibits Na+ gradient driven processes in synaptic plasma membrane vesicles.


Changes in liver tests during 1-year treatment of patients with Type 2 diabetes with pioglitazone, metformin or gliclazide.
Patients with Type 2 diabetes are at increased risk of liver damage. Therefore, it is of particular importance to investigate the hepatic effects of drugs used to treat such patients. Liver testing results performed in four 1-year, randomized, double-blind studies comparing effects of pioglitazone, metformin or a sulphonylurea, gliclazide, in the treatment of over 3700 patients with Type 2 diabetes have been analysed. Pioglitazone caused reductions in mean levels of hepatic enzymes of between 3 and 18%, whilst gliclazide caused small increases of between 3 and 13%. Metformin treatment showed either small mean increases or decreases. More patients receiving pioglitazone had liver tests within the normal range at the end of treatment (> or = 87%) compared with patients receiving metformin (> or= 80%) or gliclazide (> or = 75%). Slightly fewer patients with pioglitazone than with comparators showed a large increase (> 3 upper limit of normal) in alanine aminotransferase levels at any time during treatment (pioglitazone 0.9%, metformin 1.9%, gliclazide 1.9%). During pioglitazone treatment there is a reduction in liver enzyme levels. Although the mechanism of this effect is not clear, the results demonstrate potential beneficial effects on the liver during treatment of patients with Type 2 diabetes with pioglitazone.


Pregnancy weight gain in Iranian women attending a cross-sectional study of public health centres in Rasht.
to investigate pregnancy weight gain in a group of Iranian women who regularly attended urban public health centres for prenatal care in Rasht, Iran. an existing data study analysing routinely collected health-centre data. six randomly selected health centres in urban areas in Rasht. 704 pregnant women aged 26.1+/-5.6 years who regularly attended health centres for prenatal care and delivered between June 2002 and May 2003. data on pre-pregnancy weight, height, total pregnancy weight gain, mother's age, smoking habit, parity, baby birth weight, mother's education and working status were extracted from the health records. The women were categorised based on their pre-pregnancy body mass index (BMI) as 'underweight', 'normal weight' and 'overweight' (and obese). Participants were also grouped on the basis of their years of schooling as 'low', 'intermediate' and 'high-education'; pregnancy weight gain was compared between groups and with recommended ranges. weight gain below the lower cut-off recommended by the Institute of Medicine (IOM) were 64% and 67% in underweight and normal weight women, respectively. Baby birth weight and chance of low birth weight were negatively related to pre-pregnancy BMI and pregnancy weight gain. After controlling for the differences in parity, pre-pregnancy BMI, mothers' working status and age, highly educated women (>12 years schooling) gained more weight during pregnancy than women with an intermediate (5-12 years schooling) or lower level of education (< 5 years schooling). this study indicated that a considerable proportion of underweight and normal weight women had pregnancy weight gain below the lower cut off recommended by the IOM. These findings suggest that, in terms of pregnancy weight gain, prenatal care in the present health system is unsatisfactory. It would seem that a more effective nutritional education programme, especially for less educated pregnant women, is necessary.


Enhancement of InSe Field-Effect-Transistor Performance against Degradation of InSe Film in Air Environment.
The degradation of InSe film and its impact on field effect transistors are investigated. After the exposure to atmospheric environment, 2D InSe flakes produce irreversible degradation that cannot be stopped by the passivation layer of h-BN, causing a rapid decrease for InSe FETs performance, which is attributed to the large number of traps formed by the oxidation of 2D InSe and adsorption to impurities. The residual photoresist in lithography can cause unwanted doping to the material and reduce the performance of the device. To avoid contamination, a high-performance InSe FET is achieved by a using hard shadow mask instead of the lithography process. The high-quality channel surface is manifested by the hysteresis of the transfer characteristic curve. The hysteresis of InSe FET is less than 0.1 V at Vd of 0.2, 0.5, and 1 V. And a high on/off ratio of 1.25 × 108 is achieved, as well relative high Ion of 1.98 × 10-4 A and low SS of 70.4 mV/dec at Vd = 1 V are obtained, demonstrating the potential for InSe high-performance logic device.


Retrospective chart review of urinary glycosaminoglycan excretion and long-term clinical outcomes of enzyme replacement therapy in patients with mucopolysaccharidoses.
Mucopolysaccharidoses (MPS) are a group of rare, inherited metabolic diseases that result from a deficiency in one of several lysosomal enzymes essential for stepwise glycosaminoglycan (GAG) degradation, leading to GAG accumulation and widespread cellular pathology and clinical disease. Although disease presentation is heterogeneous, the clinical hallmarks are largely comparable across several MPS subtypes. Extensive data have shown that the level of urinary GAG (uGAG) excretion above normal is strongly correlated with disease severity and clinical outcomes in MPS diseases. Thus, change in uGAG excretion may have significant value as a potential primary endpoint in clinical trials of MPS diseases that are too rare to study using traditional clinical endpoints. A retrospective medical chart review was undertaken of patients with MPS I, II, and VI who had been treated long term with enzyme replacement therapy (ERT). The relationship between uGAG reduction and clinical outcomes relevant to the major clinical manifestations of these MPS diseases was evaluated. A multi-domain responder index (MDRI) score was calculated, measuring the following 4 domains: 6-min walk test, pulmonary function, growth rate, and Clinician Global Impression of Change. For each domain, a minimal important difference (MID) was defined based on published information of these outcome measures in MPS and other diseases. Of the 50 patients evaluated, 18 (36%) had MPS I, 23 (46%) had MPS II, and 9 (18%) had MPS VI. Forty-two were clinical practice patients and 8 had participated in clinical trials. Across all MPS subtypes, the mean (± SD) uGAG level at baseline was 66.0 ± 51.5 mg/mmol creatinine (n = 48) and there was a mean reduction of 54.6% following ERT. Analysis of the MDRI score based on the MID defined for each domain showed a greater magnitude of improvement in patients with increased uGAG reduction when compared with those patients with lower uGAG reduction for all assessed uGAG thresholds, and a trend toward a higher likelihood of positive mean MDRI score in patients with a uGAG reduction ≥40%. In this retrospective study, uGAG reduction was associated with long-term clinical outcomes as assessed by a number of approaches, supporting the use of uGAG reduction as a biomarker primary endpoint.


The relationship between eHealth literacy, social media self-efficacy and health communication intention among Chinese nursing undergraduates: A cross-sectional study.
With the popularization of the Internet, it has become possible to widely disseminate health information via social media. Medical staff's health communication through social media can improve the public's health literacy, and improving the intention of health communication among nursing undergraduates is of great significance for them to actively carry out health communication after entering clinical practice. To explore the relationship among eHealth literacy, social media self-efficacy, and health communication intention and to determine the mediating role of social media self-efficacy in the relationship between eHealth literacy and health communication intention. A cross-sectional descriptive correlation design was used in this study. Stratified cluster sampling was used to select 958 nursing students from four nursing colleges in Jiangsu Province, China, from June to July 2021. Data were collected using the eHealth Literacy Scale, the Social Media Self-efficacy Scale, and the Health Communication Intention Questionnaire. Sociodemographic data were also collected. Correlation analysis and regression analysis were used to determine the relationship between eHealth literacy, social media self-efficacy, and health communication intention. Health communication intention is positively correlated with eHealth literacy and social media self-efficacy. There is a significant positive correlation between eHealth literacy and health communication intention (β = 0.57, p < 0.001), and social media self-efficacy played a mediating role in the influence of eHealth literacy on health communication intention (the mediating effect accounted for 37.2% of the total effect). The study found that eHealth literacy and social media self-efficacy had an impact on health communication intention. Because there is a correlation between eHealth literacy and social media self-efficacy and health communication intention, in order to promote health communication intention of nursing students, it is also important to cultivate eHealth literacy and social media self-efficacy of nursing students. In view of these results, targeted educational programs must be developed to improve eHealth literacy and social media self-efficacy among nursing undergraduates, thereby promoting their health information transmission.


Validity of a new feedback method for the VEMP test.
We used a feedback method, based on a blood pressure manometer with inflatable cuff, to control the sternocleidomastoid muscle (SCM) contraction. To obtain comparable left-right VEMP responses, it is necessary (1) to determine which cuff pressures on both sides yield identical mean rectified voltage (MRV) values of the SCM contraction and (2) to apply these cuff pressures during the VEMP test. To investigate the effect of the SCM muscle contraction variability on the VEMP variables when applying the feedback method. Subjects pushed with their jaw against the hand-held inflated cuff to generate cuff pressures of subsequently 30, 40 and 50 mmHg during a MRV and VEMP measurement. When analyzing the relationship between the applied cuff pressures and the MRV values/VEMP amplitudes, we showed that (1) there was a linear relationship, (2) there was no side effect and (3) there was an interaction effect between 'side' and 'subject'. There was neither a side effect, nor an effect of the applied cuff pressure when considering the p13 latencies. As for the n23 values, there was no side effect but there was a significant difference when comparing the n23 latencies at cuff pressures of 30 vs 40 mmHg/50 mmHg.


Pain Management in Horses.
There has been great progress in the understanding of basic neurobiologic mechanisms of pain, but this body of knowledge has not yet translated into new and improved analgesics. Progress has been made regarding pain assessment in horses, but more work is needed until sensitive and accurate pain assessment tools are available for use in clinical practice. This review summarizes and updates the knowledge concerning the cornerstones of pain medicine (understand, assess, prevent, and treat). It highlights the importance of understanding pain mechanisms and expressions to enable a rational approach to pain assessment, prevention, and management in the equine patient.


Methyl (Z)-2-[(2,4-dioxothia-zolidin-3-yl)meth-yl]-3-(2-methyl-phen-yl)prop-2-enoate.
The C=C bond in the title compound, C(15)H(15)NO(4)S, has a Z configuration. The thia-zolidine ring is essentially planar [maximum deviation = 0.008 (1) Å for the N atom] and is oriented at a dihedral angle of 59.1 (1)° with respect to the benzene ring. In the crystal, pairs of C-H⋯O hydrogen bonds link centrosymmetrically related mol-ecules into dimers, generating R(2) (2)(18) ring motifs. The crystal packing is further stabilized by C-H⋯π and C-O⋯π [O⋯centroid = 3.412 (2) Å and C-O⋯centroid = 115.0 (1)°] inter-actions.


Acetylcholine receptor antibody characteristics in myasthenia gravis. Fractionation of alpha-bungarotoxin binding site antibodies and their relationship to IgG subclass.
Anti-acetylcholine receptor (anti-AChR) antibodies from two myasthenia gravis (MG) patients, known to have anti-AChR to the alpha-bungarotoxin (alpha-BuTx) binding site on the AChR (anti-alpha-BuTx site), were fractionated on an affinity column of human AChR fully saturated with alpha-BuTx. More than 80% of the anti-AChR in the pass-through fractions was directed against the alpha-BuTx site, whereas anti-AChR eluted from the column was mostly directed at other sites on the AChR. Recovery of anti-AChR was greater than 60%. Anti-alpha-BuTx site antibodies varied from 0 to 33% of the total anti-AChR antibodies in 12 MG sera. Fractionation on Sepharose-Protein A showed that anti-alpha-BuTx was only restricted to IgG3 in two patients. Anti-alpha-BuTx site antibody, which can be separated from antibodies binding to other antigenic determinants on the AChR, is variable in amount and heterogeneous in its subclass distribution. Although it may play an important pathogenic role in some patients, our results do not support the existence of an anti-alpha-BuTx site antibody common to all MG patients.


[The effect of dry standing time in cows with the obesity syndrome on selected indicators of metabolism and the state of their calves].
Differences in the composition of the blood (plasma) and urine of cows were evaluated in groups (n = 8) with a normal time of dry standing (50-60 days) and in cows standing dry for 80 to 124 days. Two approaches were used: repeated examination of the same animals two to three weeks before parturition and six to eight weeks after parturition, and single examination of the cows being in the same stage of reproduction cycle. A number of changes were recorded, testifying to a reduction of the function of the adrenal glands and to a decrease in the activity of the liver in the cows left to stand dry for a longer time. The calves of these cows had changes in their blood (plasma), indicating a hypofunction of the adrenal glands and a reduced phagocytic activity of the leucocytes, one of the parameters of the immunity system.


Evaluation of amonafide in disseminated malignant melanoma. A Southwest Oncology Group study.
Amonafide (AMF), NSC 308847 is an investigational anticancer drug acting as a DNA intercalating agent. This paper presents results of a phase II clinical study of AMF in disseminated malignant melanoma. Twenty patients, eleven males and nine females, with biopsy proven malignant melanoma, performance status 0-2; median age 59 (range 29-74), and no previous chemotherapy, were treated with AMF 300 mg/m2/day by 60 min i.v. infusion for five days repeated every three weeks. Fifteen patients had lung (9 patients) and/or liver (8 patients) involvement. None had known brain metastasis at entry. All 20 patients were evaluated for response and toxicity. Six patients had stable disease and fourteen had increasing disease. With 0/20 responses, the upper 95% confidence limit for the response rate was 14%. The median survival time was 5.7 months. Hematologic toxicity was dose limiting with the incidence of leucopenia 45% and thrombocytopenia 20%. The nonhematologic toxicities included nausea and vomiting (60%), alopecia (20%), headaches (15%), diarrhea (10%), and phlebitis (10%). We conclude that AMF administered at this dose and schedule is not active in the treatment of patients with malignant melanoma, previously untreated with chemotherapy.


Effects of menthol gum chewing on postoperative nausea, vomiting, and length of hospital stay in children undergoing appendectomy: A randomized controlled trıal.
This study aimed to determine the effects of menthol gum chewing on nausea, vomiting, and length of hospital stay after appendectomy in children. Postoperative nausea and vomiting (PONV) can be induced by general anesthesia. Several drugs are available to reduce the risk of PONV; however, their cost and side effects limit their clinical use. This was a randomized controlled clinical trial that included 60 children aged 7-18 years who underwent an appendectomy at the Pediatric Surgery Clinic of a tertiary hospital between April and June 2022. Data for this study were collected via the developed information form, which included participants' descriptive characteristics and bowel function parameters, and the Baxter Retching Faces (BARF) nausea scale. Children in the study group who underwent an appendectomy were given chewing gum and asked to chew it for an average of 15 min, whereas those in the control group received no intervention. The BARF nausea score measured during the menthol gum chewing period was lower in the study group, and the difference score value calculated after pretest time was higher in the study group, as expected (p < 0.001). Moreover, menthol gum chewing was found to shorten hospital stay by 1 day (p < 0.05). Menthol gum chewing reduced the severity of postoperative nausea and length of hospital stay. Chewing gum can be used as a nonpharmacological method by pediatric nurses in clinical practice to reduce the severity of postoperative nausea and length of hospital stay.


Poly(ADP-ribosyl)ation of acetyltransferase NAT10 by PARP1 is required for its nucleoplasmic translocation and function in response to DNA damage.
N-acetyltransferase 10 (NAT10), an abundant nucleolar protein with both lysine and RNA cytidine acetyltransferase activities, has been implicated in Hutchinson-Gilford progeria syndrome and human cancer. We and others recently demonstrated that NAT10 is translocated from the nucleolus to the nucleoplasm after DNA damage, but the underlying mechanism remains unexplored. The NAT10 and PARP1 knockout (KO) cell lines were generated using CRISPR-Cas9 technology. Knockdown of PARP1 was performed using specific small interfering RNAs targeting PARP1. Cells were irradiated with γ-rays using a 137Cs Gammacell-40 irradiator and subjected to clonogenic survival assays. Co-localization and interaction between NAT10 and MORC2 were examined by immunofluorescent staining and immunoprecipitation assays, respectively. PARylation of NAT10 and translocation of NAT10 were determined by in vitro PARylation assays and immunofluorescent staining, respectively. Here, we provide the first evidence that NAT10 underwent covalent PARylation modification following DNA damage, and poly (ADP-ribose) polymerase 1 (PARP1) catalyzed PARylation of NAT10 on three conserved lysine (K) residues (K1016, K1017, and K1020) within its C-terminal nucleolar localization signal motif (residues 983-1025). Notably, mutation of those three PARylation residues on NAT10, pharmacological inhibition of PARP1 activity, or depletion of PARP1 impaired NAT10 nucleoplasmic translocation after DNA damage. Knockdown or inhibition of PARP1 or expression of a PARylation-deficient mutant NAT10 (K3A) attenuated the co-localization and interaction of NAT10 with MORC family CW-type zinc finger 2 (MORC2), a newly identified chromatin-remodeling enzyme involved in DNA damage response, resulting in a decrease in DNA damage-induced MORC2 acetylation at lysine 767. Consequently, expression of a PARylation-defective mutant NAT10 resulted in enhanced cellular sensitivity to DNA damage agents. Collectively, these findings indicate that PARP1-mediated PARylation of NAT10 is key for controlling its nucleoplasmic translocation and function in response to DNA damage. Moreover, our findings provide novel mechanistic insights into the sophisticated paradigm of the posttranslational modification-driven cellular response to DNA damage. Video Abstract.


Villous adenoma of the duodenum in a patient with familial adenomatosis coli.
A case of familial adenomatosis coli with villous adenoma of the third portion of the duodenum, which falls in the category of a Gardner's syndrome, is described. The patient, who had complained of an abdominal mass which had been diagnosed as a desmoid tumor after surgical resection, had numerous adenomatous polyps throughout the colon confirmed by colonoscopy with biopsy. Endoscopic examination of the upper gastrointestinal tract revealed fundic gland polyposis in the stomach and numerous small adenomas in the duodenum. In addition, there was a pedunculated polyp in the third portion of his duodenum, measuring 30 mm in diameter, the surface of which had a cauliflowerlike appearance. The polyp was removed with the electrocautery snare and was histologically diagnosed as villous adenoma. Our case report supports the concept that villous adenoma, which possesses a high malignant potential, may occur in the upper gastrointestinal tract in patients with familial adenomatosis coli, and careful examination of the upper gastrointestinal tract including the distal duodenum seems to be necessary in the follow-up patients with this disease.


Screening putative antigens as stimulators in the Mycobacterium bovis interferon-gamma release assay for cattle.
Bovine tuberculosis (BTB) represents not only a significant economic concern, but also an important public health problem. Currently, interferon-gamma (IFN-γ) release assays (IGRAs) are widely used as an adjunct to the tuberculin test (TST) for the diagnosis of BTB. A great number of international studies have demonstrated that the sensitivity of the IFN-γ assay, which uses purified protein derivatives (PPDs) as diagnostic reagents, is superior to that of the TST. However, there are concerns about its specificity, largely because of the cross reactivity of common antigens shared by pathogenic and non-pathogenic mycobacterial species. The use of pathogen-specific antigens theoretically offers the most effective way to improve the specificity of IGRAs. In this study, we evaluated the potential utility of 13 purified recombinant putative antigens, which are highly specific to the Mycobacterium tuberculosis complex, as diagnostic reagents in IGRAs. A CFP-10-ESAT-6 fusion protein (abbreviated CE) displayed the greatest potential, whereas four region of difference 2 (RD2) antigens, especially Rv1985c were identified as potential candidate antigens, and can be included in an IGRA cocktail, together with CE as stimulators in the IFN-γ release assay for the diagnosis of BTB.


Sorting out release, uptake and processing of alpha-synuclein during prion-like spread of pathology.
Parkinson's disease is a progressive neurological disorder that is characterized by the formation of intracellular protein inclusion bodies composed primarily of a misfolded and aggregated form of the protein α-synuclein. There is growing evidence that supports the prion-like hypothesis of α-synuclein progression. This hypothesis postulates that α-synuclein is a prion-like pathological agent and is responsible for the progression of Parkinson pathology in the brain. Potential misfolding or aggregation of α-synuclein that might occur in the peripheral nervous system as a result of some insult, environmental or genetic (or more likely a combination of both) that might spread into the midbrain, eventually causing degeneration of the neurons in the substantia nigra. As the disease progresses further, it is likely that α-synuclein pathology continues to spread throughout the brain, including the cortex, leading to deterioration of cognition and higher brain functions. While it is unknown why α-synuclein initially misfolds and aggregates, a great deal has been learned about how the cell handles aberrant α-synuclein assemblies. In this review, we focus on these mechanisms and discuss them in an attempt to define the role that they might play in the propagation of misfolded α-synuclein from cell-to-cell. The prion-like hypothesis of α-synuclein pathology suggests a method for the transmission of misfolded α-synuclein from one neuron to another. This hypothesis postulates that misfolded α-synuclein becomes aggregation prone and when released and taken up by neighboring cells, seeds further misfolding and aggregation. In this review we examine the cellular mechanisms that are involved in the processing of α-synuclein and how these may contribute to the prion-like propagation of α-synuclein pathology. This article is part of a special issue on Parkinson disease.


Ribavirin aerosol in hospitalized adults with respiratory distress and COVID-19: An open-label trial.
There is an unmet medical need for effective treatments for hospitalized patients with coronavirus disease 2019 (COVID-19). Ribavirin is a broad-spectrum antiviral with demonstrated in vitro activity against multiple viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This trial evaluated the potential of ribavirin inhalation solution (ribavirin aerosol) to reduce COVID-19 disease severity in adults with confirmed SARS-CoV-2 infection and a diagnosis of respiratory distress. This phase I, multicenter, open-label, nonrandomized trial was conducted from February 2021 through August 2021. Patients received ribavirin aerosol (100 mg/ml for 30 min or 50 mg/ml for 60 min) twice daily for up to 6 days. The primary end point was change from baseline in clinical status severity, rated on a 7-point scale (1 [death]; 7 [not hospitalized; no limitations on activities]), at day 7 (or end-of-treatment/early termination) and day 30 (follow-up). Fifty-one patients were treated with ribavirin aerosol (mean age, 51.5 years; 78.4% men); mean number of doses was 9.7 (range, 1-12). Improvement of ≥1 level in clinical status severity was observed in 31.4% (16/51) and 78.4% (40/51) of patients at end-of-treatment and day 30, respectively. Of 21 patients who required a ventilator, 16 (76.2%) were able to discontinue ventilator use. Five patients (9.8%) died between end-of-treatment and day 30. Three patients (5.9%) discontinued study treatment due to adverse events. No deaths were considered related to study treatment. These data provide preliminary evidence that ribavirin aerosol may be an efficacious treatment for respiratory distress in adults with COVID-19.


Precancerous lesions of the colon and rectum.
Fourty-six cases of polyps and polypoid lesions of the colon and rectum were operated at the First Department of Surgery, Gifu University School of Medicine during the last 16 years. Polyps were classified into five groups according to their degree of atypicality and the relationship between polyps and cancer was investigated. The adenomatous polyps were prone to become malignant and it appears that the larger the polyp size, the greater the incidence of severe atypia and the greater the polyps' malignant potentiality. The malignant polyps developed more frequently in the distal colon and rectum than in other parts. Focal and invasive cancers limited to the submucosal layer were found exclusively in the sigmoid colon and rectum.


The role of optimism and pessimism in chronic pain patients adjustment.
This study analyses the relationships between patients' dispositional optimism and pessimism and the coping strategies they use. In addition, the coping strategies repercussions on adjustment to chronic pain were studied. Ninety-eight patients with heterogeneous chronic pain participated. The assessment tools were as follows: Life Orientation Test (LOT), the Vanderbilt Pain Management Inventory (VPMI), the McGill Pain Questionnaire (MPQ), Hospital Anxiety and Depression Scale (HADS), and the Impairment and Functioning Inventory for Chronic Pain Patients (IFI). The hypothetical model establishes positive relationships between optimism and the use of active coping strategies, whereas pessimism is related to the use of passive coping. Active coping is associated with low levels of pain, anxiety, depression and impairment and high levels of functioning. However, passive coping is related to high levels of pain, anxiety, depression and impairment and low levels of functioning. The hypothetical model was empirically tested using the LISREL 8.20 software package and the unweighted least squares method. The results support the hypotheses formulated regarding the relations among optimism, pessimism, coping and adjust of chronic pain patients. By analysing optimism among chronic pain patients, clinicians could make better predictions regarding coping and adjustment.


Protective effects of tranilast on oxazolone-induced rat colitis through a mast cell-dependent pathway.
Mast cells in the gut play an important role in the innate and adaptive immune responses that are relevant to human inflammatory bowel disease. However, the contribution of mast cells to the development of inflammatory bowel disease is not well understood. This study aimed to determine the role of mast cells in oxazolone-induced colitis and to explore whether the mast cell membrane stabiliser tranilast could ameliorate colonic inflammation. Wild-type rats and mast cell-deficient rats were sensitised and challenged with oxazolone, then treated with tranilast after challenge. Controls were treated with saline. Mast cell-deficient rats presented a weak response to oxazolone, while wild-type rats showed severe ulcerative colitis after stimulation with oxazolone. The mast cell-deficient rats model had a significantly lower disease activity index score than wild-type rats model (1.8±1.64 vs. 8.3±0.58 respectively; P<0.01). Tranilast could reduce the secretion of cytokines, immunoglobulins and myeloperoxidase activity in tranilast treatment groups compared with the model group. The number of mast cells in the wild-type model was higher than in the other groups. There was no significant change in mast cell-deficient rats. Mast cells play an important role in oxazolone-induced colitis. The mast cell membrane stabiliser tranilast can ameliorate oxazolone-induced colitis via a mast cell-dependent pathway.


[Clinical importance of evaluation of the effect of bicycle exercises on cardiodynamics of patients with ischemic heart disease].
An analysis of the results of polycardiographic examinations conducted during muscle work done by patients with ischaemic heart disease extends our knowledge of the functional state of the myocardium and is of certain prognostic importance; besides, such an analysis permits to make the prognosis of the effect of cardiac glycosides on the heart rhythm.


Electroencephalogram and clinical focalities in juvenile myoclonic epilepsy.
Partial seizures and asymmetric abnormalities seen on electroencephalogram (EEG) are infrequent in juvenile myoclonic epilepsy, but when present, can lead to a misdiagnosis of partial seizures. We report four patients with juvenile myoclonic epilepsy who had generalized spike or polyspike and wave discharges on EEG in addition to clinical and EEG evidence of focality. The clinical course and response to therapy was similar to that in typical juvenile myoclonic epilepsy.


Estimating the effective degrees of freedom in univariate multiple regression analysis.
The general linear model provides the most widely applied statistical framework for analyzing functional MRI (fMRI) data. With the increasing temporal resolution of recent scanning protocols, and more elaborate data preprocessing schemes, data independency is no longer a valid assumption. In this paper, we revise the statistical background of the general linear model in the presence of temporal autocorrelations. First, when detecting the activation signal, we explicitly account for the temporal autocorrelation structure, which yields a generalized F-test and the associated corrected (or effective) degrees of freedom (DOF). The proposed approach is data driven and thus independent of any specific preprocessing method. Then, for event-related protocols, we propose a new model for the temporal autocorrelations ("damped oscillator" model) and compare this model to another, previously used in the field (first-order autoregressive model, or AR(1) model). In the case of long fMRI time series, an efficient approximation for the number of effective DOF is provided for both models. Finally, the validity of our approach is assessed using simulated and real fMRI data and is compared with more conventional methods.


Serological and molecular detection of bovine leukemia virus in cattle in Iraq.
Bovine leukemia virus (BLV) is highly endemic in many countries, including Iraq, and it impacts the beef and dairy industries. The current study sought to determine the percentage of BLV infection and persistent lymphocytosis (PL) in cattle in central Iraq. Hematological, serological, and molecular observations in cross breeds and local breeds of Iraqi cattle naturally infected with BLV were conducted in the peripheral blood mononuclear cells of 400 cattle (340 cross breed and 60 local breed) using enzyme-linked immunosorbent assay and polymerase chain reaction (PCR). On the basis of the absolute number of lymphocytes, five of the 31 positive PCR cases had PL. Among these leukemic cattle, one case exhibited overt neutrophilia. Serum samples were used to detect BLV antibodies, which were observed in 28 (7%) samples. PCR detected BLV provirus in 31 samples (7.75%). All 28 of the seropositive samples and the 3 seronegative samples were positive using PCR. Associations were observed between bovine leukosis and cattle breed, age and sex. Age-specific analysis showed that the BLV percentage increased with age in both breeds. Female cattle (29 animals; 7.34%) exhibited significantly higher infectivity than male cattle (two animals; 4.34%). In conclusion, comprehensive screening for all affected animals is needed in Iraq; programs that segregate cattle can be an effective and important method to control and/or eliminate the BLV.


Benzimidazole Based 'Turn on' Fluorescent Chemodosimeter for Zinc Ions in Mixed Aqueous Medium.
Benzimidazole based compound 3 is designed and synthesized. The compound 3 is evaluated as fluorogenic sensor for metal ions in mixed aqueous solutions. Among all the metal ions tested, the compound 3 selectively senses Zn(2+) ions. The imine bond of 3 gets cleaved by Zn(2+) ions. Thus, 3 behave as 'turn on' fluorescent chemodosimeter for Zn(2+) ions with limit of detction in micromolar range. Furthurmore, we demonstated that 3 can detect Zn(2+) ions in cells of Allium cepa. Graphical Abstract Benzimidazole based ligand 3 is designed and synthesized which behave as chemodosimeter for Zn(2+) ions. We further demonstrated that 3 can detect Zn(2+) ions in cells of Allium cepa.


Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart.
Both iron overload and iron deficiency have been associated with cardiomyopathy and heart failure, but cardiac iron utilization is incompletely understood. We hypothesized that the transferrin receptor (Tfr1) might play a role in cardiac iron uptake and used gene targeting to examine the role of Tfr1 in vivo. Surprisingly, we found that decreased iron, due to inactivation of Tfr1, was associated with severe cardiac consequences. Mice lacking Tfr1 in the heart died in the second week of life and had cardiomegaly, poor cardiac function, failure of mitochondrial respiration, and ineffective mitophagy. The phenotype could only be rescued by aggressive iron therapy, but it was ameliorated by administration of nicotinamide riboside, an NAD precursor. Our findings underscore the importance of both Tfr1 and iron in the heart, and may inform therapy for patients with heart failure.


Generation of Transgenic Rodent Malaria Parasites Expressing Human Malaria Parasite Proteins.
We describe methods for the rapid generation of transgenic rodent Plasmodium berghei (Pb) parasites that express human malaria parasite (HMP) proteins, using the recently developed GIMO-based transfection methodology. Three different genetic modifications are described resulting in three types of transgenic parasites. (1) Additional Gene (AG) mutants. In these mutants the HMP gene is introduced as an "additional gene" into a silent/neutral locus of the Pb genome under the control of either a constitutive or stage-specific Pb promoter. This method uses the GIMO-transfection protocol and AG mutants are generated by replacing the positive-negative selection marker (SM) hdhfr::yfcu cassette in a neutral locus of a standard GIMO mother line with the HMP gene expression cassette, resulting in SM free transgenic parasites. (2) Double-step Replacement (DsR) mutants. In these mutants the coding sequence (CDS) of the Pb gene is replaced with the CDS of the HMP ortholog in a two-step GIMO-transfection procedure. This process involves first the replacement of the Pb CDS with the hdhfr::yfcu SM, followed by insertion of the HMP ortholog at the same locus thereby replacing hdhfr::yfcu with the HMP CDS. These steps use the GIMO-transfection protocol, which exploits both positive selection for Pb orthologous gene-deletion and negative selection for HMP gene-insertion, resulting in SM free transgenic parasites. (3) Double-step Insertion (DsI) mutants. When a Pb gene is essential for blood stage development the DsR strategy is not possible. In these mutants the HMP expression cassette is first introduced into the neutral locus in a standard GIMO mother line as described for AG mutants but under the control elements of the Pb orthologous gene; subsequently, the Pb ortholog CDS is targeted for deletion through replacement of the Pb CDS with the hdhfr::yfcu SM, resulting in transgenic parasites with a new GIMO locus permissive for additional gene-insertion modifications.The different types of transgenic parasites can be exploited to examine interactions of drugs/inhibitors or immune factors with HMP molecules in vivo. Mice either immunized with HMP-vaccines or treated with specific drugs can be infected/challenged with these transgenic mutants to evaluate drug or vaccine efficacy in vivo.


Clinical presentation and short-term outcome of acute coronary syndrome in native young Saudi population.
To investigate acute coronary syndromes (ACS) in the young Saudi population in Aseer Region, southwestern Saudi Arabia. We retrospectively reviewed our database between January 2006 and May 2009, 924 patients were diagnosed to have ACS. Among them 107 patients (11.6%) met our definition of young [66 (61.7%) male < 45 years, and 41 (38.3%) female < 55 years]. We compared this study population to a control group of 50 elderly patients consecutively enrolled in a contemporary period. The overall age was 42.3 ± 7.9 and 68.7 ± 10.1 years in the study population and control respectively. 100% of the population and 92% of the control group presented with chest pain. Diabetes mellitus (DM) prevalence was 46.7% in the study population (63.4% in females), and 62% in the control group. Hypertension, smoking, dyslipidemia and overweight/obesity were reported in 31.8%, 25.2%, 21.5% and 44.9% of the study population and 58%, 6%, 26% and 42% of the control group, respectively. Past history of coronary artery disease was documented in 16.8% of the study population and 38% of the control group. The discharge diagnoses were ST-segment elevation myocardial infarction (STEMI) in 41 (38.3%) (representing 4.4% of the whole ACS population) and 11 (22%) patients of the study population and control group respectively, non-ST-segment elevation myocardial infarction in 36 (33.6%) and 23 (46%) patients of the study population and control group, respectively, and unstable angina in 30 (28.0%) and 15 (30%) patients of the study population and control group, respectively. Coronary angiography was performed in 86 (80.4%) and 41 (82%) patients in the study population and control group respectively. In hospital, one young patient had acute ischemic stroke and one elderly patient died, 22.4% of the study population and 32% of control group were discharged with clinical diagnosis of heart failure or in need for diuretics. In our study, the young Saudi population with ACS had chest pain as the leading symptom. STEMI was the major final diagnosis and among one of the highest reported worldwide. There is a high prevalence of DM; however, they have favorable in hospital and short-term outcome.


Energy acquisition strategy for reproduction in a semelparous squid.
Energy demand for reproduction leads to a wide diversity of foraging and life-history strategy among wild animals, linking to a common objective to maximize reproductive success. Semelparous squid species in particular can use up to 50% of the total energy intake for reproduction. However, the energy acquisition strategy for reproduction is still a controversial issue regarding whether the squid shift in diet ontogenetically. Here we used Argentinean shortfin squid (Illex argentinus) as a case study to investigate the strategy of energy acquisition for reproduction, by analyzing energy density of the squid's reproductive tissues including ovary, nidamental glands and oviduct eggs, and stable isotopes and fatty acids of the squid's ovary. The reproductive energy (the sum of the energy accumulated in ovary, nidamental glands and oviduct eggs) increased significantly with maturation. The ovary nitrogen stable isotopes (δ15N) showed a significant increase with maturation, but the increase by maturity stage was not equal to the typical enrichment of about 3‰ per trophic level. Isotopic niche width showed an increasing trend with maturation, and isotopic niche space exhibited greater overlap at advanced maturity stages. The relative amounts of 16:0, 20:5n3 and 20:4n6 in the ovary, tracing for carnivores and top predators, increased after the onset of maturation. The overall fatty acid profiles of the ovary showed significant differences among maturity stages, but obvious overlaps were found for mature squids. Mixed-effects model results revealed that reproductive energy was positively correlated with δ15N values. The reproductive energy was also positively related to the relative amounts of 18:0 and 20:4n6, respectively tracing for herbivores and top predators. Our results validate that the squid shifts to feed on higher trophic prey for reproduction as energy demand increases once maturation commences. However, the squid does not shift feeding habits at a trophic level but instead broadens prey spectrum, coupled with increasing intake of higher trophic prey items, to meet the energy demand for reproduction. Such energy acquisition strategy may be selected by the squid to maximize reproductive success by balancing energy intake and expenditure from foraging, warranting future studies that aim to clarify such strategy for reproduction among semelparous species.


Recommendations with respect to the improvement of lubricating qualities of synovial fluid in artificial joints.
This paper gives a short description of the lubricating properties of yellow and red bone marrow taken from a femur of a cadaver. The experiments have been conducted on a 'ball-on-plate' model. The balls were made from steel 100 CR6 (German) and the plates were made from the same steel and ultra-high molecular weight polyethylene (UHMWPE, German 'Herulen'). The friction coefficients under loads of 50 and 300 N were determined with different combinations of friction components. It has been found that the lubricating properties of yellow and red marrow have advantages over synovial fluid. In the light of these results the author develops a new approach to the design of a new hip endoprosthesis.


Endomyocardial fibrosis in a white girl with sero-positive juvenile rheumatoid arthritis.
A white girl with sero-positive juvenile rheumatoid arthritis was subsequently found to have endomyocardial fibrosis. We believe that these two rare conditions were not causally related.


Oral subchronic toxicity of aqueous crude extract of Plantago australis leaves.
The toxic effects of chronic oral administration (60 days) of aqueous crude extract (AE) of Plantago australis Lam. (Plantaginaceae) in rats at doses of 850 and 1700 mg/kg on biochemical (ALT, AST, creatinine, urea, glucose, alkaline phosphatase, total proteins and albumin), hematological (complete hemogram), and histopathological (heart, lung, liver, kidney, esophagus, stomach and gut) parameters were studied. All biochemical and hematological parameters were found to be in the normal range, but ALT in animals that received AE of 850 mg/kg was higher. Histopathological analysis of organs, especially the liver did not present alterations.


Ginsenoside rich fraction of Panax ginseng C.A. Meyer improve feeding behavior following radiation-induced pica in rats.
Panax ginseng is an indigenous medicinal herb and has traditionally been used among Asian population for relief of many human ailments. We investigated the prophylactic role of Korean P. ginseng extract (KG) against X-ray irradiation-induced emesis in an acute rat pica model. Rats were treated with KG (12.5, 25, 50 mg/kg orally at -48, -24 and 0 h) prior to X-ray irradiation (6 Gy), and intake of kaolin and normal food and body weight changes examined as an index of the acute emetic stimulus. Levels of serotonin in small intestine tissue were assessed and histopathology of gastric tissue, small intestine and colon examined specific staining. Pre-treatment with KG (12.5 and 25 mg/kg) reduced X-ray irradiation-induced kaolin intake at 24h. Normal food intake was improved in rats treated with 25 mg/kg KG. The anti-emetic effect of KG was further confirmed on the basis of serotonin release, histopathological findings. Our findings collectively indicate that KG protects against X-ray irradiation-induced acute pica to a moderate extent, leading to improved feeding behavior in rats.


Plasma estradiol, free testosterone, sex hormone binding globulin binding capacity, and prolactin in benign prostatic hyperplasia and prostatic cancer.
The nature of hormonal changes with age and the possible role of these changes in the development of benign prostatic hyperplasia (BPH) and prostatic cancer (PC) were studied by assaying the plasma levels of total and free testosterone (T), estradiol (E2), prolactin, and sex hormone binding globulin binding capacity (SHBG) in 20 normal healthy men aged 40-59 years, in 30 patients with BPH aged 63-79 years, and in 30 patients with PC of similar height, weight, and age as the BPH patients. The mean E2 was highly significantly (P less than 0.0005) lower in the PC patients and in the young controls than in the BPH patients. The mean free T was significantly higher in the young controls than in the BPH patients (P less than 0.025) and PC patients (P less than 0.0005). The PC patients had a slightly lower (P less than 0.05) mean free T and mean E2/free T ratio than the BPH patients. The mean E2/free T ratio was significantly higher in the BPH patients (P less than 0.0005) and in the PC patients (P less than 0.0025) than in the young controls. It seems possible that the observed age-dependent significant increase in plasma estrogen concentration in the BPH patients may act as a protective factor against prostatic cancer.


Effectiveness of Vernonia scorpioides ethanolic extract against skin inflammatory processes.
Vernonia scorpioides (Asteraceae) is a native Brazilian medicinal plant that is commonly used to treat skin disorders. Considering the traditional use of Vernonia scorpioides and the lack of information about its pharmacological properties, we investigated the topical anti-inflammatory effect of the ethanolic extract of Vernonia scorpioides (EEVS) on acute and chronic cutaneous inflammation models in mouse. The topical anti-inflammatory effect of EEVS was evaluated against acute models (12-O-tetradecanoylphorbol acetate (TPA)- and arachidonic acid (AA)-induced mouse ear oedema) and chronic models (multiple applications of croton oil). The EEVS caused a dose-related inhibition of oedema in both the TPA- and AA-induced acute models (DI(50)=0.24 and 0.68 mg/ear with an inhibition of 80 ± 5% and 65 ± 5%, respectively, for 1mg/ear). In addition, the TPA-induced increase in myeloperoxidase activity (MPO) in the ear was reduced (77 ± 8%) by the topical application of EEVS. In the chronic model, the EEVS reduced all parameters evaluated: oedema formation (31 ± 2%), epidermal hyperproliferation (histology) and MPO (25 ± 10%). However, the topical treatment of EEVS had no effect on N-acetyl-β-d-glucosaminidase activity. The EEVS effectively interfered in the ear oedema on the delayed-type hypersensitivity reaction induced by oxazolone. The topical treatment with EEVS performed on both phases or only on the elicitation phase caused the inhibition of the ear oedema-induced by oxazolone in 42.9% and 63.4%, respectively, when compared to control animals (sensitized and challenged). The results suggest that EEVS is effective as a topical anti-inflammatory agent in acute and chronic inflammatory processes and that its action is markedly influenced by the inhibition of neutrophil migration into inflamed tissue as well as by epidermal hyperproliferation.


Up-regulation of TLR9 gene expression by LPS in mouse macrophages via activation of NF-kappaB, ERK and p38 MAPK signal pathways.
Toll-like receptors (TLR) are critical in the activation of macrophages by bacterial products. It has been shown that TLR2 and TLR4 mediate lipopolysaccharide (LPS) and lipoproteins signal transduction, respectively. Regulation of TLR2 and TLR4 expression by LPS was considered to be one of the mechanisms to control the overall responses of immune cells to bacteria. However, little is known about whether the other members of TLR family are regulated by LPS. Recently, TLR9 was demonstrated to be essential for CpG DNA signaling. Given the effective immune modulation by CpG DNA, regulation of TLR9 expression might play important role in controlling the overall responses of immune cells to bacteria. In this study, regulation of TLR9 gene expression in mouse macrophage cell line RAW264.7 by LPS was investigated. Semiquantitative RT-PCR was performed to determine gene expression of TLR9. Following LPS stimulation, TLR9 gene expression was upregulated within 1 h and reached peak level at about 3 h. LPS stimulation activated NF-kappaB, ERK and p38 MAPK signal pathways. Pretreatment of macrophages with inhibitors of NF-kappaB, ERK and p38 MAPK signal pathways inhibited LPS-induced upregulation of TLR9 mRNA expression. Our results demonstrated that LPS stimulation could upregulate gene expression of TLR9 via NF-kappaB, ERK, and p38 MAPK signal pathways in macrophages, indicating that macrophages with increased TLR9 expression induced by LPS might respond to invading bacteria more effectively.


Neurofibromatosis-Noonan Syndrome: A Possible Paradigm of the Combination of Genetic and Epigenetic Factors.
Neurofibromatosis-Noonan syndrome (NFNS) is a clinical entity possessing traits of autosomal dominant disorders neurofibromatosis type 1 (NF1) and Noonan syndrome (NS). Germline mutations that disrupt the RAS/MAPK pathway are involved in the pathogenesis of both NS and NF1. In light of a studied Greek family, a new theory for etiological pathogenesis of NFNS is suggested. The NFNS phenotype may be the final result of a combination of a genetic factor (a mutation in the NF1 gene) and an environmental factor with the epigenetic effects of muscle hypotonia (such as hydantoin in the reported Greek family), causing hypoplasia of the face and micrognathia.


Comparative assessment of the roughness, hardness, and wear resistance of aesthetic bracket materials.
The purpose of this study was to assess critical properties of orthodontic aesthetic bracket materials. Samples of polycarbonate, poly(oxy)methylene, ultra high molecular weight polyethylene (UHMWPE), and polycrystalline alumina raw material used from bracket manufacturing were subjected to: (a) profilometry for the determination of Ra, Rq, Rmax and Rz roughness parameters; (b) Vickers hardness (HV50) testing; and (c) wear resistance determined by the scratch test. The results were analyzed with one-way ANOVA and Tukey multiple comparisons test at alpha=0.05 level of significance. The UHMWP and alumina specimens showed the highest roughness values for all parameters. The highest hardness, amongst the polymeric raw materials, was obtained from the poly(oxy)methylene appliances. Differences were also noted between the polycarbonate raw material of different manufacturers implying an effect from the manufacturing process. With the exception of alumina, the highest wear resistance was found for the poly(oxy)methylene specimens. The results of this study reveal the variability among aesthetic plastic bracket raw materials, their reduced hardness and wear resistance relative to alumina as well as the inappropriateness of UHMWPE as alternative bracket material.


Agents causing occupational asthma.
The workplace is a significant contributor to the burden of asthma. Although the majority of cases probably represent what is labeled work-exacerbated asthma, in a significant number of subjects, asthma is actually caused by 1 or more agents present in the workplace; this is occupational asthma. Two types of occupational asthma are distinguished, according to whether the asthma appears after a latency period. This article discusses (1) two types of agents causing asthma with a latency period and acting through an apparently immunologic mechanism (high-molecular-weight agents and low-molecular-weight agents) and (2) agents causing asthma without a latency period.


Loss of heterozygosity on chromosome 11 in esophageal squamous cell carcinomas.
Esophageal cancer (ESC) is an important cancer worldwide. Chromosome 11 plays an important role in the development of several human cancers. In this study, 19 polymorphic microsatellite markers spanning the whole chromosome 11 were used to screen for loss of heterozygosity (LOH) in 38 primary esophageal squamous cell carcinomas. Thirty-three of 38 samples (86.8%) showed LOH at one or more loci. High frequencies (51.9-61.1%) of allelic loss were observed at D11S1338, D11S2000, D11S1990, and D11S1647 loci, in two chromosomal regions, 11p15.5 and 11q22.3. The results of this study suggest the presence of putative tumor suppressor genes in these two regions on chromosome 11 related to ESC.


Acute muscular and cardiovascular responses to high load training with pre-exercise blood flow restriction.
The purpose of this study is to examine the acute muscular and cardiovascular responses to applying blood flow restriction (BFR) before high-load training. Forty trained individuals visited the lab on three occasions. On Visit 1, participants completed paperwork and performed strength assessments. During Visits 2 and 3, participants completed four exercise conditions (one in each arm during each visit) as follows: (1) traditional resistance training (TRAD), (2) low load training with BFR (LLBFR), (3) low repetition high load training with pre-exercise BFR (PreBFR), and (4) low repetition traditional training (LRTRAD). Blood pressure, muscle thickness (MT), and isometric strength (ISO) were measured before and after exercise. Data are displayed as means (SD). Immediately following exercise, MT in TRAD was greater compared with PreBFR (mean difference = 0.18[0.30] cm, p < 0.001) and LRTRAD (mean difference = 0.28[0.30] cm, p < 0.001). In addition, LLBFR demonstrated greater MT compared with PreBFR (mean difference = 0.24[0.30] cm, p < 0.001]. Immediately following exercise, ISO was lower in TRAD compared with PreBFR (mean difference = 33.8[46.9]N, p < 0.001) and the LRTRAD condition (mean difference = 32.8[50.4]N, p < 0.001). In addition, ISO was lower in LLBFR compared with PreBFR (mean difference = 43.9 [47.4]N, p < 0.001) and LRTRAD (mean difference = 42.9 [43.8]N, p < 0.001). Immediately following exercise, systolic blood pressure was greater in TRAD compared with PreBFR and LRTRAD. The application of BFR before engaging in high-load training does not seem to augment the muscular responses to exercise when compared with traditional high loads alone; however, it may pose less demand on the cardiovascular system.


Distinct Immune Reconstitution Profiles Captured by Immune Functional Assays at 6 Months Post Allogeneic Hematopoietic Stem Cell Transplantation.
Immune reconstitution after allogeneic-hematopoietic-stem-cell transplantation (allo-HSCT) is a complex and individual process. In this cross-sectional study, whole-blood (WB) immune functional assay (IFA) was used to characterize immune function by assessing immune-related gene/pathway alterations. The usefulness of this tool in the context of infection, 6 months after transplantation, was evaluated. Sixty allo-HSCT recipients at 6 months after transplantation and 10 healthy volunteers (HV) were included. WB was stimulated in standardized TruCulture tubes using lipopolysaccharides and Staphylococcal enterotoxin B. Gene expression was quantified using a custom 144-gene panel using NanoString nCounter technology and analyzed using Ingenuity Pathway Analysis. The relationships between immune function and clinical characteristics, immune cell counts, and post-transplantation infections were assessed. Allo-HSCT recipients were able to activate similar networks of the innate and adaptive immune response compared to HV, with, nevertheless, a lower intensity. A reduced number and a lower expression of genes associated with immunoregulatory and inflammatory processes were observed in allo-HSCT recipients. The use of immunosuppressive treatments was associated with a protracted immune reconstitution revealed by transcriptomic immunoprofiling. No difference in immune cell counts was observed among patients receiving or not receiving immunosuppressive treatments using a large immunophenotyping panel. Moreover, the expression of a set of genes, including CCL3/CCL4, was significantly lower in patients with Herpesviridae reactivation (32%, 19/60), which once again was not identified using classical immune cell counts. Transcriptional IFA revealed the heterogeneity among allo-HSCT recipients with a reduced immune function, a result that could not be captured by circulating immune cell counts. This highlights the potential added value of this tool for the personalized care of immunocompromised patients.


Biomarker Characterization by MALDI-TOF/MS.
Mass spectrometric techniques frequently used in clinical diagnosis, such as gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, ambient ionization mass spectrometry, and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry (MALDI-TOF/MS), are discussed. Due to its ability to rapidly detect large biomolecules in trace amounts, MALDI-TOF/MS is an ideal tool for characterizing disease biomarkers in biologic samples. Clinical applications of MS for the identification and characterization of microorganisms, DNA fragments, tissues, and biofluids are introduced. Approaches for using MALDI-TOF/MS to detect various disease biomarkers including peptides, proteins, and lipids in biological fluids are further discussed. Finally, various sample pretreatment methods which improve the detection efficiency of disease biomarkers are introduced.


Chlamydia trachomatis trends in the United States among persons 14 to 39 years of age, 1999-2008.
We report the first population-based assessment of national trends in chlamydia prevalence in the United States. We investigated trends in chlamydia prevalence in representative samples of the U.S. population aged 14 to 39 years using data from five 2-year survey cycles of the National Health and Nutrition Examination Survey from 1999 to 2008. Prevalence estimates and 95% confidence intervals (CI) are reported stratified by age, gender, and race/ethnicity. Percent change in prevalence over this time period was estimated from regression models. In the 2007-2008 cycle, chlamydia prevalence among participants aged 14 to 39 years was 1.6% (95% CI: 1.1%-2.4%). Prevalence was higher among females (2.2%, 95% CI: 1.4%-3.4%) than males (1.1%, 95% CI: 0.7%-1.7%). Prevalence among non-Hispanic black persons was 6.7% (95% CI: 4.6%-9.9%) and was 2.5% (95% CI: 1.6%-3.8%) among adolescents aged 14 to 19 years. Over the five 2-year cycles, there was an estimated 40% reduction (95% CI: 8%-61%) in prevalence among participants aged 14 to 39 years. Decreases in prevalence were notable in men (53% reduction, 95% CI: 19%-72%), adolescents aged 14 to 19 years (48% reduction, 95% CI: 11%-70%), and adolescent non-Hispanic black persons (45%, reduction, 95% CI: 4%-70%). There was no change in prevalence among females aged 14 to 25 years, the population targeted for routine annual screening. On the basis of population estimates of chlamydia prevalence, the overall chlamydia burden in the United States decreased from 1999 to 2008. However, there remains a need to reduce prevalence in populations most at risk and to reduce racial disparities.


Skin tuberculosis in children: learning from India.
Cutaneous tuberculosis in children is a major health problem in India. It accounts for about 1.5% of all the cases of extrapulmonary tuberculosis. Scrofuloderma and lupus vulgaris are the two most common forms of tuberculosis. However, the trend in the pattern of cutaneous tuberculosis is changing, as the tuberculid, lichen scrofulosorum, has become more common in recent years. Overall, the clinical patterns are comparable with adults. However, children can have widespread and severe involvement because many unusual and uncommon patterns are known to occur in children. Underlying systemic involvement is more common in children, compared with adults.


[The Mirizzi syndrome. Analysis of an unknown complication of the gallstones].
Mirizzi syndrome is one possible complication of the gallstones. The incidence in patients treated with cholecystectomy is 0.7-1.1%. We have analyzed on 4123 colecistectomie conduct in Unit of General Surgery and Organ Transplantation of the University of Parma from January 1992 to October 2006, 46 cases of syndrome of Mirizzi (1.1%) with age comprised between 29-82 years (medium 67.8 years) were 28 women (60.9%) and 18 men (39.1%). We have considered the symptomatology, the diagnostic and therapeutic way, the comorbidity. In 19 cases (41.3%) there were the signs of acute cholecystitis; in 28 cases (60.9%) the clinical picture was characterized from repeated biliary pain. The jaundice was present in 29 cases (63%) with hyperpyrexia (>38 degrees) in 27 cases (58.7%). In 14 cases (30.4%) was a Mirizzi type I, in 32 cases (69.6%) a Mirizzi of type II. The Mirizzi syndrome is a diagnosis frequently conduct intraoperatively. The surgical therapy is characterized by the acknowledgment of the biliary structures, the complete removal of the stones, the surgical therapy of the leaks.


Orphans and Vulnerable Children Affected by Human Immunodeficiency Virus in Sub-Saharan Africa.
In Sub-Saharan Africa, 15.1 million children have been orphaned because of human immunodeficiency virus (HIV). They face significant vulnerabilities, including stigma and discrimination, trauma and stress, illness, food insecurity, poverty, and difficulty accessing education. Millions of additional children who have living parents are vulnerable because their parents or other relatives are infected. This article reviews the current situation of orphans and vulnerable children, explores the underlying determinants of vulnerability and resilience, describes the response by the global community, and highlights the challenges as the HIV pandemic progresses through its fourth decade.


Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited autosomal dominant condition characterized by migrane, recurrent stroke, subcortical dementia, and pseudobulbar palsy. It begins with migraine with aura in -33% of patients. CADASIL is commonly overlooked or misdiagnosed owing to its recent identification. The pathological hallmark of angiopathy is the presence of multiple, small, deep cerebral infarcts, leucoencephalopathy, and nonatherorosclerotic, nonamyloid angiopathy involving mainly small, deep perforating cerebral arteries. Changes also are present in vascular smooth muscle cells and consist in the presence of granular osmiophilic material (GOM). The defective gene in CADASIL is Notch 3, which encodes a large transmembrane receptor. Magnetic resonance imaging shows high intensity signal lesions, often confluent, and areas of cystic degeneration of subcortical white matter and basal ganglia. Diagnostic strategies in CADASIL are matter of discussions because the electron microscopic demonstration of GOM was reported in 100% of symptomatic patients of French authors, but only in 45% of a British study. GOMs are not present in presymptomatic patients.


Measurement of D-dimer in cerebrospinal fluid using a luminescent oxygen channeling immunoassay.
Measurement of D-dimer in cerebrospinal fluid (CSF) allows insight into coagulation system activation in the central nervous system and can be utilized to monitor intracranial hemorrhage as well as acute phase processes beyond hemostasis in inflammatory and neoplastic diseases. So far, the measurability of D-dimer in low and very low concentrations in CSF was limited in conventional immunoassays. Novel high-sensitivity chemiluminescent immunoassays such as the luminescent oxygen channeling immunoassay (LOCI®) are getting increasingly available but have not been validated in CSF. The aim of this study was to investigate the accuracy and linearity of the LOCI® in assessing D-dimer in CSF. INNOVANCE LOCI hs D-dimer reagent cartridge was used for the measurement of D-dimer in CSF of patients with different neurological diseases. For the evaluation of linearity, dilution series were performed in a pooled CSF sample with the determination of intra-assay precision (CV, coefficient of variation) in 3 individual samples with 20 replicates. Furthermore, D-dimer concentrations measured by LOCI® were compared with the respective results of a routinely available clinical latex-enhanced immunoassay (HemosiIL D-Dimer HS 500). Linear regression analysis of the LOCI® method revealed a r 2 of 1.00 (p < 0.001) with a regression coefficient B of 1.012 ± 0.003 (CI: 1.005-1.019, p < 0.001) and an intercept of -1.475 ± 1.309 (CI: -4.493 to 1.543); the median intra-assay CV was 0.69% (range: 0.68-0.75). In total, 185 CSF samples were measured by LOCI® technology, showing a mean concentration of 204.84 ± 2,214.93 ng/ml. D-dimer concentration between LOCI and latex-enhanced immunoassay differed by a factor of 10.6 ± 13.6 on average with a maximum deviation by a factor of 61.3; the maximum deviation was found at low concentrations. D-dimer in CSF of patients with neurological disease can be reliably measured by the LOCI® method with high linearity and accuracy at low concentrations.


Chromosome lesions in amniotic fluid cell cultures.
The frequencies of chromosome lesions were determined on 3537 mitoses in samples of varying sizes from cultures of 25 amniotic fluid specimens taken from patients at cytogenetic risk. The average percentage values of aberrant cells, including and excluding gaps, were 12.5 and 4.9, respectively. The corresponding values for fibroblasts and peripheral blood lymphocytes from normal adult donors, calculated under the same laboratory conditions, were 5.0 (including gaps) and 2.4 (excluding gaps) and 2.4 (including gaps) and 1.0 (excluding gaps), respectively. The hypothesis of a correlation between the increased incidence of chromosome lesions and the occurrence of abnormal karyotypes in amniotic fluid cell cultures is discussed.


Can we improve the cytologic examination of malignant pleural effusions using molecular analysis?
Currently, 40% of patients remain undiagnosed after routine cytologic examination for malignant pleural effusions. Deoxyribonucleic acid (DNA) methylation is a robust strategy for detecting cancer early in tissue. We hypothesized that DNA methylation would be more sensitive in diagnosing patients with malignant pleural effusions than cytology. We conducted a prospective cohort study of 31 inpatients with pleural effusions (24 malignant pleural effusions metastatic from 10 different organs and 7 benign) over 18 months. Aspirated pleural fluid underwent cytologic examination and DNA extraction for nested methylation-specific polymerase chain reaction (PCR). We assayed for promoter hypermethylation in 8 genes known to be methylated in many cancers. Pleural fluid was considered positive if 2 or more genes were methylated by methylation-specific PCR. Cytology alone confirmed malignant pleural effusions in 15 of 24 patients (sensitivity 63%), whereas methylation alone positively identified 16 of 24 patients (sensitivity 67%). Both tests had 100% specificity in predicting benign effusions. If cytology and methylation were considered together, they exhibited 88% sensitivity and 100% specificity in discriminating benign and malignant effusions. Combined, the two assays were more sensitive than either test alone. Although the positive predictive value of each test was 100%, the negative predictive value of cytology and methylation combined was 78%, better than 47% and 44% for methylation and cytology alone, respectively. Epigenetic analysis of pleural fluid can detect malignant DNA from a variety of neoplasms, provide complementarity with cytology, and improve the diagnostic yield of the current standard examination of pleural fluid.


End product inhibition of hepatic 25-hydroxyvitamin D production in the rat: specificity and kinetics.
The role of vitamin D metabolites in the regulation of hepatic 25-hydroxyvitamin D production was investigated by examining the effects of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D on the synthesis of [25-3H]hydroxyvitamin D by rachitic rat liver homogenates. Production of [25-3H]hydroxyvitamin D was inhibited by 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, but not by 24,25-dihydroxyvitamin D. 25-Hydroxyvitamin D increased the Km of the vitamin D-25-hydroxylase enzyme(s), while 1,25-dihydroxyvitamin D decreased the Vmax with a Ki of 88.7 ng/ml. Inhibition of hepatic 25-hydroxyvitamin D production by 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D may be another control mechanism to regulate circulating vitamin D levels.


The Singaporean foodscape - Convenience, choice, entertainment, and sociality for young workers.
Singapore is famous for its diverse, affordable, and exciting foodscape. This paper focuses on understanding the multifaceted role that the Singaporean food environment plays in working young adults' lives, and how young adults interact with this environment to make food choices. Using a focused ethnographic approach, including 33 semi-structured interviews and participant-observation, we explore the ways in which busy working young adults interact with the foodscape. The food environment provides young adults, who eat out frequently, with highly accessible food options that cater to their budgets and palates. They often dine at hawker centres and similar food establishments with colleagues, friends and family. These establishments offer accessible, affordable, and appealing food. Overall, the foodscape provides a source of popular entertainment through the exploration of diverse cuisines and novel shared social experiences. Young adults are heavy users of social media to maintain social networks and to explore the food environment. Capitalizing on this, food marketing on social media targets this group with the promotion of food-related experiences. While it may not always promote healthy eating, the Singaporean foodscape offers convenience, choice, entertainment, and sociality. In the process, it facilitates the formation of cultural and national identity and the protection of mental well-being through the maintenance and development of relationships, and a sense of belonging.


Predictors of the incident metabolic syndrome in healthy obese subjects: a decade of follow-up from the Tehran Lipid and Glucose Study.
There is limited data from long-term prospective studies on the natural course of metabolic syndrome (MetS) incidence in healthy obese phenotypes. The aim of this study was to determine the incidence and predictors of the MetS in healthy obese subjects without the MetS at baseline after a decade of follow-up. In this prospective cohort study, 438 obese subjects free from MetS at baseline, aged ≥20 years, were selected from among the participants of the Tehran Lipid and Glucose Study and followed up for 10 years for development of MetS. Based on national data, central obesity was defined as waist circumference cutoff point of 89 cm for men and 91 cm for women. Initially, subjects had a mean age of 41.1 ± 11.8 years and a body mass index of 32.7 ± 2.7 kg/m(2). At the end of follow-up, the cumulative incidence (95% confidence interval) of MetS was 44.0 (36.8-51.1)%. In the multivariable analysis, the adjusted odds ratios of hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C) and insulin resistance for the development of MetS were 3.08 (1.39-6.79), 2.84 (1.26-6.42), 6.49 (3.18-13.25) and 2.87 (1.55-5.32), respectively. The area under receiver operating characteristic curve of all the components was significantly higher than various combinations of MetS components, except for the two models including combinations of three components, that is, triglycerides (TGs), HDL-C and fasting blood sugar, as well as, TGs, HDL-C and systolic blood pressure. Our findings demonstrate that MetS developed in nearly half of the individuals during the 10 years of follow-up. Predictors of MetS in healthy obese subjects may differ from the general population, and waist circumference does not have an independent role.


Validity of nutritional screening and assessment tools.
The aim of this paper is to address the design and analysis of validity studies for evaluating the performance of a nutritional screening or assessment tool. Statistical aspects of validity are discussed with the non-statistician in mind. Particular emphasis is placed on construct and criterion validity. Design issues are considered in relation to numbers of subjects and assessments. Appropriate methods of analysis are considered, as is interpretation of results. Practical suggestions regarding the implementation of validity studies in the field of nutrition risk assessment are proposed. Guidelines for the standardization of the design, analysis, and publication of results are presented.