The role of substance use, smoking, and inflammation in risk for suicidal behavior.
Alcohol and substance use disorders are important predictors for suicidal behavior. However, the role of individual substances as proximal risk factors for suicidal behavior and the mechanisms through which substance use affect risk are not entirely clear. We examine whether the frequency of substance use and whether biological markers in the HPA axis and inflammatory pathways are associated with clinical risk factors of suicidal behavior of aggression, impulsivity, hopelessness, and poor sleep. The sample consisted of psychiatric inpatients, aged 15-30 years, admitted for suicide attempt (n = 38), suicidal ideation (n = 40); and healthy controls (n = 37). We measured hair cortisol concentrations, glucocorticoid receptor (GR) sensitivity, stimulated production of interleukin- or IL-6, C-reactive protein, and mRNA expression of GR, SKA2, FKBP5, TNF-α, and IL-1β. Smoking was associated with increased aggression [β = 2.9, 95% CI (-0.03, 6), p = 0.05], impulsivity [β = 3.1, 95% CI (1.6, 4.6), p < 0.001], and poor sleep [β = 0.5, 95% CI (0.03, 0.95), p = 0.04] even after controlling for demographics and group. Similarly, TNF-α mRNA was associated with impulsivity [β = 0.07, 95% CI (0.01, 0.1), p = 0.02] and hopelessness [β = 0.03, 95% CI (0.004, 0.05), p = 0.03]. Smoking tobacco (r = 0.32, p < 0.001) was positively associated with TNF-α mRNA. Study limitations include the cross-sectional design, retrospective assessment, and relatively small sample size. Future longitudinal studies are needed to test whether inflammatory markers mediate the relationships between smoking, clinical risk factors, and suicidal behavior; and to examine whether smoking cessation could reduce the risk for suicidal behavior in at-risk patients.


Cardiometabolic changes in treated versus never treated HIV-infected black South Africans: the PURE study.
The use of antiretroviral treatment is known to be accompanied by several negative health outcomes and may negatively affect a country such as South Africa, which is the most burdened by the human immunodeficiency virus (HIV) in the world. We aimed to determine whether receiving antiretroviral treatment changes the cardiometabolic profile of HIV-infected South Africans. In this sub-study, embedded in the Prospective Urban and Rural Epidemiology (PURE) study, we compared the cardiometabolic profile in a cohort of 66 treated and 71 never treated HIV-infected participants from the North-West province, South Africa. By using standard techniques, these participants' cardiometabolic, biochemical and lifestyle variables were assessed in 2005 and 2010, respectively. The treated group showed a higher percentage change in pulse pressure (13.3%; p = 0.004), systolic blood pressure (4.5%; p = 0.029) and CD4 cell count (9.2%; p = 0.009) levels over five years. During follow-up (2010), lipid variables were worse in the treated group. Further, antiretroviral treatment was associated with the percentage change in pulse pressure (R(2) = 0.24; β = 0.19; p = 0.020). We concluded that Africans receiving antiretroviral treatment had a greater increase in pulse pressure and systolic blood pressure, as well as an unfavourable lipid profile when compared to never treated participants. Whether, in the long term, antiretroviral treatment will lead to increased arterial stiffness and/or accelerated atherosclerosis among this HIV-infected African population remains to be seen.


Mouse Genome Informatics (MGI): Resources for Mining Mouse Genetic, Genomic, and Biological Data in Support of Primary and Translational Research.
The Mouse Genome Informatics (MGI), resource ( www.informatics.jax.org ) has existed for over 25 years, and over this time its data content, informatics infrastructure, and user interfaces and tools have undergone dramatic changes (Eppig et al., Mamm Genome 26:272-284, 2015). Change has been driven by scientific methodological advances, rapid improvements in computational software, growth in computer hardware capacity, and the ongoing collaborative nature of the mouse genomics community in building resources and sharing data. Here we present an overview of the current data content of MGI, describe its general organization, and provide examples using simple and complex searches, and tools for mining and retrieving sets of data.


Whither nursing models? The value of nursing theory in the context of evidence-based practice and multidisciplinary health care.
This paper presents a discussion of the role of nursing models and theory in the modern clinical environment. Models of nursing have had limited success in bridging the gap between theory and practice. Literature on nursing models and theory since the 1950s, from health and social care databases. Arguments against nursing theory are challenged. In the current context of multidisciplinary services and the doctrine of evidence-based practice, a unique theoretical standpoint comprising the art and science of nursing is more relevant than ever. A theoretical framework should reflect the eclectic, pragmatic practice of nursing. Nurse educators and practitioners should embrace theory-based practice as well as evidence-based practice.


Using Machine Learning Techniques to Develop Risk Prediction Models for the Risk of Incident Diabetic Retinopathy Among Patients With Type 2 Diabetes Mellitus: A Cohort Study.
To construct and validate prediction models for the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus. Patients with type 2 diabetes mellitus hospitalized over the period between January 2010 and September 2018 were retrospectively collected. Eighteen baseline demographic and clinical characteristics were used as predictors to train five machine-learning models. The model that showed favorable predictive efficacy was evaluated at annual follow-ups. Multi-point data of the patients in the test set were utilized to further evaluate the model's performance. We also assessed the relative prognostic importance of the selected risk factors for DR outcomes. Of 7943 collected patients, 1692 (21.30%) developed DR during follow-up. Among the five models, the XGBoost model achieved the highest predictive performance with an AUC, accuracy, sensitivity, and specificity of 0.803, 88.9%, 74.0%, and 81.1%, respectively. The XGBoost model's AUCs in the different follow-up periods were 0.834 to 0.966. In addition to the classical risk factors of DR, serum uric acid (SUA), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), estimated glomerular filtration rate (eGFR), and triglyceride (TG) were also identified to be important and strong predictors for the disease. Compared with the clinical diagnosis method of DR, the XGBoost model achieved an average of 2.895 years prior to the first diagnosis. The proposed model achieved high performance in predicting the risk of DR among patients with type 2 diabetes mellitus at each time point. This study established the potential of the XGBoost model to facilitate clinicians in identifying high-risk patients and making type 2 diabetes management-related decisions.


Survival strategies of the crab spider Thomisus onustus Walckenaer 1806 (Chelicerata, Arachnida, Thomisidae).
The initial energy supply of emerging spiderlings is relatively meagre, so survival without feeding on insects during a spell of bad weather is limited to a period of a few days or weeks. During our investigations, spiderlings of Thomisus onustus (Arachnida, Thomisidae) were kept on different diets. There was a significant difference in survival rate between spiderlings that were starved or fed on pollen, "nectar", or Drosophila. The results showed that pollen and nectar can be a source of energy for spiders for an extensive period. This demonstrates another way in which spiders may survive starvation when insect prey is lacking and thus ensure the survival of a whole population.


Status and potential diagnostic roles of essential trace elements in Kashin- Beck disease patients.
This updated and comprehensive meta-analysis study sought to explore the changes of seven essential trace elements, including selenium (Se), iron (Fe), zinc (Zn), manganese (Mn), fluorine (F), iodine (I) and copper (Cu) in Kashin-Beck disease (KBD) patients compared with healthy individuals. The findings of the current study will provide a valuable reference for implementation of early clinical intervention and prevention of KBD. All related articles included in this review were retrieved from the following databases: Chinese National Knowledge Infrastructure (CNKI), Wan Fang Data, China Biology Medicine disc (CBM disc), PubMed and Web of Science up to April 30, 2020. The following combination keywords were used as the search criteria: "(Kashin-Beck disease OR KBD) AND ((selenium OR iron OR zinc OR manganese OR fluorine OR iodine OR copper) OR (Se OR Fe OR Zn OR Mn OR F OR I OR Cu))". All statistical analyses were performed using RevMan 5.3 and Stata 16.0 software. A total of 55 articles were included in the current study. Meta-analysis showed that the levels of serum Se (SMD = -2.37, 95 % CI: -1.58 to -0.72, P < 0.00001), hair Se (SMD = -2.19, 95 % CI: -3.05 to -1.33, P < 0.00001), urinary Se (SMD = -2.36, 95 % CI: -3.26 to -1.46, P < 0.00001) and erythrocyte Se (SMD = -5.12, 95 % CI: -9.55 to -0.69, P = 0.02) were significantly lower in KBD patients compared with the levels in healthy controls. Then, the findings showed that the levels of serum F (SMD = -0.58, 95 % CI: -1.04 to -0.12, P = 0.01) and hair I (SMD = -0.57, 95 % CI: -1.06 to -0.08, P = 0.02) in patients were substantially lower than that in controls. Analysis showed that the levels of hair Zn (SMD = 0.26, 95 % CI: 0.04 to 0.49, P = 0.02) and hair Mn (SMD = 0.55, 95 % CI: 0.24 to 0.85, P = 0.0005) were markedly higher in patients compared with the levels in healthy controls. Notably, urinary Se (AUC = 0.7851, P = 0.0235, Sensitivity = 81.82 %, Specificity = 81.82 %) showed a good diagnostic value for KBD. The findings of the current study showed that the levels of Se, serum F and hair I were lower in patients with KBD compared with those in healthy controls, whereas the levels of hair Zn and hair Mn were higher in KBD patients compared with the levels in controls. This outcome would be further validated in our future studies. Of note, these results indicated that Se, F and I deficiencies were associated with the pathogenesis of KBD.


Cloning and sequence analysis of cDNA for rat corticotropin-releasing factor precursor.
DNA complementary to the rat hypothalamic mRNA coding for the corticotropin-releasing factor precursor (prepro-CRF) has been cloned by screening a cDNA library with a human genomic DNA probe. Nucleotide sequence analysis of the cloned cDNA has revealed that rat prepro-CRF consists of 187 amino acid residues including a putative signal peptide. The CRF and putative signal peptide regions are more highly conserved among rat, human and ovine prepro-CRF than is the cryptic portion.


Factors Affecting the Implementation of Continuous Quality Improvement in Health Facilities in Southern Nation and Nationalities Peoples Region (SNNPR), Ethiopia.
Continuous quality improvement (CQI) has become an important aspect of healthcare organizations. The objective of this study was to identify contributing factors for implementing continuous quality improvement projects in health facilities for the better delivery of healthcare service in the region of South Nation and Nationalities Peoples Region (SNNPR), Ethiopia. A cross-sectional study was conducted from April to May 2018 in health facilities within two districts (woredas) located in SNNPR. Descriptive, bivariate, and multivariate analyses were used. During the analysis, a P-value less than 0.05 and 95% confidence interval (CI) were used to assess the significance of the associations. A total of 144 health professionals participated in the study. The majority of the respondents (75%) were male and 35% reported that their respective health facilities have implemented continuous quality improvement projects. More than half of the leaders (51.4%) were not receptive to new ideas and the majority of leaders were not encouraging learning (62.5%) or engaged in the quality improvement project implementation process (66%). Multivariate logistic regression analysis revealed that 84% of the health facilities were implementing a continuous quality improvement project (AOR=0.138 (0.029-0.652)). Similarly, client satisfaction was 90% (AOR=0.101 (0.019-0.522)) and the percentage of staff who believe that the quality improvement project contributed to the improvement of work at their respective health facility was 80% (AOR=0.181 (0.047-0.696)). The following variables, "Leaders receptiveness to new ideas", "Leaders share information/data about health facility service delivery status", "Health facility has a quality improvement project plan", "Staff know using indicators to tell progress about service delivery", and "Health facility assess client satisfaction level" were found to be independent predictors of continuous quality improvement (CQI) project implementation.


Pharmacotherapies for lipid modification: beyond the statins.
The widespread clinical use of statins has contributed to significant reductions in the rate of cardiovascular morbidity and mortality over the past 3 decades, and statins are considered first-line therapy for the prevention and treatment of atherosclerotic vascular disease. Nevertheless, various other lipid-lowering agents can provide clinical benefit by supplementing or augmenting statin therapy in patients with severe hypercholesterolaemia or mixed dyslipidaemia, or by providing an alternative for patients who are intolerant to statins. Bile acid resins and niacin were prescribed for lipid modification for years before the introduction of the statins, and new data continue to emerge regarding their use in different patient groups and for specific conditions. Ezetimibe can be appropriate for patients whose primary lipid abnormality is an elevated LDL-cholesterol level, whereas the fibrates seem to be most beneficial in patients with low levels of HDL cholesterol and elevated triglycerides. At the end of 2012 and the beginning of 2013, the first microsomal triglyceride transfer protein inhibitor, lomitapide, and the first antisense therapy to target apolipoprotein B, mipomersen, were approved for the treatment of individuals with extremely elevated LDL-cholesterol levels caused by homozygous familial hypercholesterolaemia. Although two agents in the experimental class of cholesteryl ester transfer protein inhibitors have failed to show a benefit in clinical trials, newer drugs in this class could provide an additional strategy to address residual cardiovascular risk in patients treated with statins.


Methaemoglobinaemia secondary to topical lignocaine/ prilocaine in a circumcised neonate.
The use of topical lignocaine/prilocaine (EMLA, Astra Pharmaceuticals, North Ryde, NSW, Australia) for pain relief for neonatal circumcision is becoming more prevalent. Because of immaturity of the methaemoglobin reductase pathway, the neonate is vulnerable to methaemoglobinaemia which is a recognized complication of prilocaine therapy. This is the second report of methaemoglobinaemia due to the use of EMLA in association with circumcision during the newborn period.


Drugs, sex and AIDS: sexual relationships among injecting drug users and their sexual partners in Vietnam.
HIV transmission in Vietnam is strongly linked to drug injection, but there is the potential for an epidemic driven by sexual behaviour. HIV-education programmes to date focus largely on personal responsibility and fail to address adequately other aspects of HIV-related risks in social contexts. Based on ethnographic fieldwork conducted in 2002, this paper examines the association between HIV-related risks (unsafe drug use and unsafe sex) and gender relations among injecting drug users. Three patterns of relationships are analysed: between injecting drug users and their injecting partners; between injecting drug users and their smoking partners; and between injecting drug users and their non-using partners. Data shows that intimate relations play an important role in managing HIV-related risks among injecting drug users. HIV prevention must pay due attention to the specific contexts of injecting drug users' lives. Some implications of these findings are discussed and relevant recommendations are proposed.


A comparison of induction with vaginal prostaglandin E2 versus spontaneous of labor in grand multiparous women.
To compare the outcome of labor in grand multiparous women (para 6 or more) who had induction of labor with vaginal prostaglandin E2 with grand multiparous women in spontaneous labor. A retrospective case-control study was performed, 202 grand multiparous women were induced labor with vaginal prostaglandin E2 and compared with outcomes with grand multiparous women who entered in spontaneous labor and delivered during the same study period and served as control group. There were no statistically significant differences in the duration of labor, fetal birth weight, use of oxytocin augmentation, and Apgar scores in the two groups. Fourteen women (6.9%) in the induction group delivered by cesarean section compared to six woman (3.0%) in the control group. This was a statistically significant difference (P = 0.01). In the induction group, the mean duration of the hospital stay was longer (P = 0.003) and there was one neonatal fetal death and one uterus rupture. Induction of labor with vaginal prostaglandin E2 in grand multiparous women is still relatively safe.


Improved stability of highly fluorinated phospholipid-based vesicles in the presence of bile salts.
The stability of fluorinated phospholipid-based vesicles in terms of detergent-induced release of encapsulated carboxyfluorescein has been evaluated. The fluorinated liposomes are substantially more resistant towards the lytic action of sodium taurocholate than conventional DSPC or even DSPC/CH 1/1 liposomes. Concerning structure/permeability relationships, the larger the fluorination degree of the membrane, the higher the resistance of the fluorinated liposomes to their destruction by the detergent. These results show that fluorinated liposomes have a promising potential as drug carrier and delivery systems for oral administration.


Controllable synthesis of hierarchical MoS2 nanotubes with ultra-uniform and superior storage potassium properties.
Molybdenum disulfide (MoS2) is a promising nanomaterial which has been extensively investigated in photo-/electro-catalysis, sensors, and batteries due to its excellent physical/chemical properties. In this manuscript, MoS2 hierarchical nanotubes with hollow nanostructure are successfully synthesized via a facile hydrothermal method. SEM indicates that such MoS2 nanotubes have perfect uniformity while TEM demonstrates the hollow structure. Specifically, the ratio of MoS2 to the randomly produced polysulfide in the synthesized MoS2 nanotubes is 4.29 which confirms that the synthesized MoS2 nanotubes have quite high quality. Compared with the previous studies, our MoS2 nanotubes show superior rate capability and cyclability (127 mAh g-1 at 200 mA g-1 after 100 cycles) in the potassium ion battery.


Effects of temperature manipulation on gamete development and reproductive activity in the farmed catfish Lophiosilurus alexandri.
Temperature is a critical factor for fish management, especially during breeding season. This study evaluated gametogenesis and gonadal maturation in the catfish Lophiosilurus alexandri under farming conditions in two temperatures. The fish were divided in the following experimental groups: (S0) control group, before starting the experiment, (S1) 30 days at 23 °C, (S2) 70 days at 23 °C, (S3) 30 days at 27 °C, and (S4) 70 days at 27 °C. Gonad, liver, and blood samples were obtained to analyze reproductive and health parameters. In females, increased gonadosomatic index (GSI) was associated with a decreased proportion of perinucleolar follicles and increased diameter of vitellogenic follicles in S4. Postovulatory follicles were found only in fish kept at 27 °C, whereas atretic follicles were more frequent at 23 °C. In S4, females had higher hepatic levels of vitellogenin and lower levels of zona radiata proteins. In males, a lower proportion of spermatogonia was found at 27 °C (S4), whereas GSI and proportions of spermatocytes, spermatids, and spermatozoa were similar among the groups. Levels of cortisol were higher in females of group S3. Plasma 17β-estradiol, 11-ketotestosterone and 17α-hydroxyprogesterone were significantly higher in S4. Hematocrit, erythrocytes, and glucose were higher at 27 °C. Together, the present study indicate that exposure of L. alexandri to 27 °C provides suitable conditions for germ cell development and gonadal maturation in captivity, promotes increase of sex steroids, follicular growth, and oocyte maturation, with onset of ovulation occurring at 30 days. At 23 °C, spermatogonia proliferation is favored in males, but it cannot be recommended for stimulating female maturation of L. alexandri in fish farming.


An inhibition effect in the temporal constrains of attentional selection: the Backward Blink.
The study aims at investigating the dynamics of visual information processing during sequential control of attentional selection. By combining two different traditional paradigms we show for the first time that during rapid selection of visual targets, encoding of a new target stimulus is facilitated by suppression of the preceding relevant stimulus category (Backward Blink; BB). Such inhibition would operate to reduce interference from previously stored information, in order to facilitate the instantiation of a new attentional episode. Results suggest that the same underlying inhibitory mechanism might contribute to two different attentional effects, specifically, the switch cost and the Attentional Blink, suggesting a general inhibitory mechanism of attentional control, with broad implications for understanding how the brain perceives any task-relevant stimulus.


Predictive factors for complete response of chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma.
To identify clinical and imaging features associated with complete response (CR) to first session of transarterial chemoembolization (TACE) with drug-eluting beads (DEB) in patients with hepatocellular carcinoma. In this prospective historical cohort, 172 patients with 315 tumours who received at least one DEB-TACE from 2007 to 2013 were studied. Imaging response was evaluated according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST). Age, gender, aetiology of cirrhosis, Child and BCLC scores, particles size, location in the liver, size of the tumour, presence of a capsule, hypervascularisation on DSA and CT/MRI scans, and blush extinction were analysed. After one session of treatment, CR was observed in 36 % of the 315 tumours treated. Nodule size, location in the liver, and complete blush extinction on DSA was statistically correlated to complete response, whereas capsule aspect on imaging and demographic criteria were not. In multivariate analysis only, location in the liver and nodule size were significant features. Tumour location in the segments 1 and 4 is a pejorative factor for CR, whereas tumour size <5 cm is a positive predictive factor. These criteria could, therefore, be taken into consideration to improve the selection of patients for DEB-TACE. • Literature on predictive factors of complete response after DEB-TACE is under-studied. • Tumour size <5 cm is associated with complete response. • Location in segments 1 or 4 is a pejorative factor for response. • No demographic parameter influences complete response.


Effect of an acute blood donation on oxygen uptake kinetics in moderate and heavy domains over a period of 96 hours.
Studies determining the effects of blood donation (BD) on oxygen uptake kinetics are limited. This study aims to ascertain the effects of BD (~470 mL) over a period of 96 hours on oxygen uptake kinetics in moderate and heavy exercise domains. Twelve participants (nine males and three females; 31.1 ± 11.7 years, mass 79.9 ± 12.8 kg, height 175.5 ± 7.5 cm) completed four consecutive days (24-96 hours) of moderate and heavy V˙O2 on-kinetics trials pre BD and post BD. Visit one (0 hour), pre BD established hematological levels, V˙O2max and Gas Exchange Threshold (GET). Subsequent visits comprised two 6-minute moderate (∆ 50% rest-GET) and 1 heavy (∆ 20% GET-V˙O2max ) trial. Post BD 0 hour the participants donated blood post hematological testing only. Despite non-significances for V˙O2 amplitude, time constant-2 (tau2 ) for V˙O2 showed significant decreases at 24 and 48 hours, and tau3 showed significant increases at 72 and 96 hours pre to post BD (P < .05). Hemoglobin (Hb) values reduced (P < .05) pre (14.48 ± 0.16 g·dL-1 ) to post BD (13.47 ± 0.66 g·dL- 1). Hb significantly decreased at 24, 48, 72, and 96 hours compared to 0 hour post BD (P < .05). BD has no effect on V˙O2 amplitude, but time-based components show sensitivity to reduced circulating O2 ; with a decreased PO2 a slower O2 exchange across the blood myocyte barrier could result in altering O2 kinetics.


Experimental analyses of competition between two species of bumble bees (Hymenoptera: apidae).
Dynamical aspects of flower usage and forager body size in sympatric and experimentally-induced allopatric populations of Bombus flaviforns and Bombus rufocinctus were studied in 10 discrete subalpine meadows and over the last half of one summer. Results indicate that there is a high degree of asymmetry in the competitive effects and that B. flavifrons is the clear competitive and numerical dominant. When occurring alone, B. rufocinctus used the same spectrum of flowers in similar frequencies to that of B. flavifrons whose flower use was invariant over all meadows and treatments. When sympatric with B. flavifrons, B. rufocinctus was relegated to secondary, less preferred flowers. Shifts in flower use by B. rufocinctus were accompanied by changes in forager body-size: body weights were greater in allopatric populations of B. rufocinctus and smaller in those sympatric with B. flavifrons. Competitive dominance may be related to differences in species phenologies. Bombus flavifrons initiated colonies in the spring three weeks before B. rufocinctus and maintained higher densities over the summer; by virtue of greater numbers of foragers, it may control exploitation of the most profitable flowers.


A retrospective comparison of cumulative time spent in remission during treatment with olanzapine or risperidone among patients with schizophrenia.
Available studies suggest comparable efficacy of olanzapine and risperidone for the treatment of schizophrenia over the short term. This retrospective analysis of data from a 28-week, double-blind, schizophrenia trial compared the cumulative amount of time that patients met severity criteria for remission during olanzapine (10-20 mg/day) or risperidone (4-12 mg/day) treatment. The percentage cumulative time spent in remission was 40% for olanzapine- and 31% for risperidone-treated patients (P = 0.03) using Definition 1 (PANSS items P1, P2, P3, N1, N4, N6, G5, G9 < or = 3), and 18% and 11% (P = 0.01), respectively, using Definition 2 (BPRS Total reduced 50%, BPRS psychosis items < or = 3, CGI-severity < or = 3). During 28 weeks of treatment, olanzapine-treated patients spent more cumulative time in remission than risperidone-treated patients.


A measure for assessment of beneficial and harmful fortitude: development and initial validation of the Sisu Scale.
Sisu is a Finnish cultural concept that denotes determination and resoluteness in the face of adversity. We propose that sisu will supplement the English-language based research on mental fortitude traits. Sisu has not been the focus of systematic research until very recently. We created a new questionnaire measuring sisu (the Sisu Scale), sought to validate the sisu construct and its sub-factor structure as postulated in a recent qualitative study. We investigated associations of sisu with other measures of mental fortitude and well-being. More generally we aimed to enrichen the cross-cultural understanding of human experience of overcoming adversity across life's challenges. We describe and validate a questionnaire that effectively measures both beneficial and harmful sisu, each comprising three sub-factors. Beneficial sisu was associated with other measures of fortitude, but less with personality dimensions. We also confirmed the existence of an independent harmful sisu factor. Beneficial sisu was associated with higher well-being and lower depressive symptoms, and harmful sisu with lower well-being and higher levels of general stress, work stress and depressive symptoms. Together the two factors were superior compared to pre-existing measures when predicting well-being-related variables. Results suggest that the new Sisu Scale we developed may provide a valuable addition to research on mental fortitude, resilience and their consequences for well-being.


High-level expression and characterization of the recombinant enzyme, and tissue distribution of human succinic semialdehyde dehydrogenase.
The succinic semialdehyde dehydrogenase gene (SSADH; EC 188.8.131.52) from human brain was cloned and overexpressed in Escherichia coli. Based on SDS-PAGE, the apparent molecular mass of subunit was 54 kDa, in good agreement with the theoretical size. The purified SSADH appears to be a tetramer of identical subunits. The specific activity of the recombinant protein was 1.82 micromol NADH formedmin(-1)mg(-1) and the optimal pH was found to be 8.5. The Michaelis constants K(m) for succinic semialdehyde and NAD(+) were 6.3 and 125 microM, respectively. Initial velocity studies show NADH to be a competitive inhibitor with respect to NAD(+), but to be non-competitive inhibitor with respect to succinic semialdehyde. The overexpression of SSADH in E. coli and one-step purification of the highly active SSADH will facilitate further biochemical studies on this enzyme. In addition, an mRNA master dot-blot for multiple human tissues provided a complete map of the tissue distribution for SSADH. The major sites of SSADH expression are liver, skeletal muscle, kidney, and brain. The data indicate that mRNA expression of SSADH is ubiquitous, but highly regulated at the level of transcription in a tissue-specific manner.


The future of the human connectome.
The opportunity to explore the human connectome using cutting-edge neuroimaging methods has elicited widespread interest. How far will the field be able to progress in deciphering long-distance connectivity patterns and in relating differences in connectivity to phenotypic characteristics in health and disease? We discuss the daunting nature of this challenge in relation to specific complexities of brain circuitry and known limitations of in vivo imaging methods. We also discuss the excellent prospects for continuing improvements in data acquisition and analysis. Accordingly, we are optimistic that major insights will emerge from human connectomics in the coming decade.


Construct validity of the Menopause Rating Scale in Indonesia.
Objective: This study assessed the construct validity of the Menopause Rating Scale (MRS) in Indonesia. Methods: The study included 240 women aged over 45 years in Indonesia. The MRS measures psychological, somatic-vegetative, and urogenital symptoms using 11 items obtained from participants' daily symptom records. The intraclass correlation coefficient (ICC) and Cronbach's alpha coefficient were measured to examine the test-retest reliability and internal consistency reliability. The test-retest reliability was evaluated by an extra 30 participants twice at 2-week intervals. For construct validity, exploratory factor analysis (EFA) was employed to assess factor structure and confirmatory factor analysis (CFA) was used to evaluate the structural model fit of the MRS. Results: The ICC for the test-retest reliability ranged between 0.90 and 0.95. The Cronbach alpha coefficients in the somatic-vegetative, psychological, and urogenital dimensions were 0.92, 0.93, and 0.95, respectively. The Kaiser-Meyer-Olkin value was 0.96, and the Bartlett's test of sphericity was statistically significant and adequate for EFA. CFA was tested using the second-order model with three first-order factors and yielded an excellent model fit. Conclusion: Results indicated that the brief questionnaire of the MRS possesses acceptable construct validity for evaluating menopause symptoms in Indonesian women.


Control of the human cell cycle by a bacterial protein, gapstatin.
The oral gram-negative bacterium Actinobacillus actinomycetemcomitans is a major pathogen in human periodontal disease. Saline extraction releases a range of surface-associated components from this bacterium, including one which exhibits potent anti-proliferative activity as assessed by its capacity to inhibit DNA synthesis by human and other mammalian cells. Cultures incubated with this bacterial fraction for a prolonged period comprise a high proportion of cells containing a 4n level of DNA. Studies using hydroxyurea-synchronized cultures showed that cells treated with the surface-associated fraction were arrested in the G2 phase of the cell cycle and did not enter mitosis. This G2/M blockade was observed only when the bacterial fraction was added to the cells during early S phase. Our data also suggest that the active bacterial component binds to surface receptors expressed by the human cells and may act by a novel mechanism which involves down-regulation of cyclin B1 expression. The anti-proliferative activity of the bacterial fraction, purified by a combination of ammonium sulphate precipitation, HPLC anion exchange and gel filtration, has been shown to be an 8 kDa protein, which we have called gapstatin. Purified gapstatin was shown to be responsible for the the inhibitory effects of the surface-associated fraction on mammalian cells.


Organization of diencephalic and brainstem afferent projections to the lateral septum in the rat.
Ascending diencephalic and brainstem afferents to the lateral septal column were studied by retrograde transport of horseradish peroxidase following microiontophoretic injections in the various subdivisions of the lateral septal area. Predominantly ipsilateral cells, of which several coincide with reported monoaminergic cell groups, appeared in the preoptic area, several hypothalamic nuclei, periventricular nuclei, raphe nuclei, pontine area and medulla oblongata. It is concluded that there is a heterogeneous monoaminergic input to the lateral septal area organized in a complicated pattern along the longitudinal axis of the lateral septum.


Scoping review of percutaneous mechanical aspiration for valvular and cardiac implantable electronic device infective endocarditis.
Percutaneous mechanical aspiration (PMA) of intravascular vegetations is a novel strategy for management of patients with infective endocarditis (IE) who are at high risk of poor outcomes with conventional cardiac surgery. However, clear indications for its use as well as patient outcomes are largely unknown. To conduct a scoping review of the literature to summarize patient characteristics and outcomes of those undergoing PMA for management of IE. Two independent reviewers screened abstracts and full text for inclusion and independently extracted data. MEDLINE, Embase, and Web of Science. Studies published until February 21, 2023, describing the use of PMA for management of patients with cardiac implantable electronic device (CIED) or valvular IE were included. As this was a scoping review, risk of bias assessment was not performed. Descriptive data was reported. We identified 2252 titles, of which 1442 abstracts were screened, and 125 full text articles were reviewed for inclusion. Fifty-one studies, describing a total of 294 patients who underwent PMA for IE were included in our review. Over 50% (152/294) of patients underwent PMA to debulk cardiac implantable electronic device lead vegetations prior to extraction (152/294), and 38.8% (114/294) of patients had a history of drug use. Patient outcomes were inconsistently reported, but few had procedural complications, and all-cause in-hospital mortality was 6.5% (19/294). While PMA is a promising advance in the care of patients with IE, higher quality data regarding patient outcomes are needed to better inform the use of this procedure.


Cotton-made cellulose support for anti-allergic pajamas.
The cotton used to produce an interlock knitted fabric is alkaline boiled, bleached and after drying, it is grafted with monochlorotriazinyl-beta-cyclodextrin (MCT-β-CD) as a support of an inclusion compound (IC) with natural anti-allergic active principles, in order to improve the curative properties and the comfort. Are used: extract of Viola tricolor Herb (VtH), solution of propolis (P) and of menthol (M), as well as the pharmacologic products: advantan (AD), hydrocortisone (HYD) and pimechrolimus (PI). The dimensions of the active compound molecules were established with software. The textile material grafted with MCT-β-CD and with active principles absorbed in the cyclodextrin cavity is investigated by EDX. The anti-microbial activity of VtH, P and M was tested. Tactile determinations of softness were performed with human appraisers. By assembling the anti-allergic knitted fabric with untreated fabric, therapeutic pajamas were obtained. The manner to process and manufacture the pajamas for patients with contact and atopic (DA) dermatitis (DC) is presented.


Influence of ciliate protozoa on biochemical changes and hydrolytic enzyme profile in the rumen ecosystem.
To assess the effect of presence or absence of rumen protozoa on fermentation characteristics and enzyme profile in growing lambs. Weaner lambs (G1, G2, G3, G4, G5 and G6 groups) were defaunated by oral administration of sodium laurel sulphate (at 8 g 100 kg(-1) body weight). The lambs of G4, G5 and G6 groups were refaunated. The roughage and concentrate ratio in the diet of G1 and G4, G2 and G5, and G3 and G6 were 50:50 (R1), 65:35 (R2) and 80:20 (R3), respectively. Daily dry matter intake was similar in defaunated and faunated lambs. However, digestibility of organic matter (OM), cellulose and gross energy were lower in defaunated lambs while crude protein (CP) digestibility was similar in both defaunated and faunated lambs. The rumen pH and NH3-N were lower (P < 0.01) while TVFA, total-N and TCA-ppt-N were higher (P < 0.01), in defaunated lambs. Ruminal activity of carboxymethyl cellulase was lower (P < 0.01) in defaunated lambs and amylase, xylanase, protease and urease were similar in faunated and defaunated lambs. Nutrient utilization, rumen metabolites and ciliate protozoal count were higher, whereas digestibility of fibre fractions was lower in high rather than low concentrate fed lambs. The rumen protozoa present before defaunation were B-type and the protozoa which re-established on refaunation were also B-type. Absence of ciliate protozoa decreased nutrient digestibility and increased ruminal TVFA and total-N with lower NH3-N concentration, indicating better energy and protein utilization in defaunated lambs. Defaunation improved energy and protein utilization in lambs.


First-trimester preeclampsia screening and prevention: impact on patient satisfaction and anxiety.
Preeclampsia affects between 2% and 5% of pregnant people in North America. First-trimester preeclampsia screening based on the Fetal Medicine Foundation risk calculation algorithm combined with treatment of high-risk patients with aspirin effectively reduces the incidence of preterm preeclampsia more than the currently used risk factor-based screening. However, the impact of such screening on patient satisfaction and maternal anxiety is unknown. This study aimed to assess the impact of first-trimester prediction and prevention of preterm preeclampsia on patient satisfaction and anxiety. Consenting pregnant patients participating in a local first-trimester (11-13+6 weeks) preterm preeclampsia screening and prevention implementation study1 were contacted 6 weeks postpartum to complete an online patient satisfaction survey, designed to assess their satisfaction with the screening program and their levels of trait anxiety (using an abbreviated version of the State-Trait Anxiety Inventory [STAIT-5]). In addition to assessing overall patient satisfaction, the level of patient satisfaction was stratified and compared according to levels of patient risk for preterm preeclampsia. Between June 2021 and December 2021, surveys were emailed to 765 participants. The response rate was 47.80% (358/765). Overall, 93% of participants reported high levels of satisfaction with preterm preeclampsia screening (70%-100%), and 98% stated that they would recommend the screening to all pregnant patients. With respect to levels of satisfaction with the program's support in reducing feelings of worry and anxiety, 87.9% of the total sample reported high satisfaction (70%-100%). The level of clinically significant symptoms of anxiety did not differ significantly between low- and high-risk groups (8% vs 10.8%, respectively). Overall, first-trimester preeclampsia screening was associated with high patient satisfaction and did not lead to differences in patient anxiety between those with high- and low-risk screen results.


The influence of positive experiences on depression and quality of life in persons with multiple sclerosis.
This correlational study determined the extent to which positive, rather than negative, experiences influence depressive symptoms and quality of life in persons with multiple sclerosis (MS). Data collected during the 7th year of an ongoing longitudinal study of quality of life in community-dwelling persons with MS were used for this analysis. Higher number of positive experiences was associated with fewer depressive symptoms, less functional limitations, and better quality of life. Using hierarchical multiple regression, age, education, functional limitations, and positive experiences accounted for 21.7% of the variance in depressive symptoms, and functional limitations, positive experiences, and depressive symptoms explained 58% of the variance in quality of life. Higher number of positive experiences predicted lower levels of depressive symptoms, even while taking disease-related functional limitations into account. Incorporating positive experiences into daily life may improve quality of life, even when battling depression and substantial limitations in functioning.


Effectiveness of cognitive behavioural therapy for chronic obstructive pulmonary disease patients: A systematic review and meta-analysis.
and purpose: Cognitive behavioural therapy (CBT) has gained increasing attention for the treatment of psychological disorders. This study aims to establish the effectiveness of CBT on psychological and physical outcomes in patients with chronic obstructive pulmonary disease (COPD). Two waves of electronic searches of the PubMed, Cochrane library, EMBASE, Web of Science and China National Knowledge Infrastructure databases were conducted. Statistical analyses were performed using Revman Manager 5.3 and Stata 12.0 software. Sixteen randomized controlled trials were eligible. There were significant improvements in anxiety (SMD = -0.23; 95% CI: -0.42 to -0.04; P = 0.02), depression (SMD = -0.29, 95% CI: -0.40 to -0.19, P < 0.01), quality of life (MD = -5.21; 95% CI: -10.25 to -0.17; P = 0.04), and mean visits to emergency departments in the CBT groups. No statistically significant differences were observed in fatigue (SMD = 0.88, 95% CI: -0.58 to 2.35, P = 0.24), exercise capacity (MD = 28.75, 95% CI: -28.30 to 85.80, P = 0.32), self-efficacy (SMD = 0.15, 95% CI: -0.05 to 0.34, P = 0.14), or sleep quality (MD = 1.21, 95% CI: -0.65 to 3.06, P = 0.20). This meta-analysis suggests that CBT can serve as a complementary therapy to improve anxiety, depression, and quality of life in COPD patients and deserves more widespread application in clinical practice.


Transoral Laser Microsurgery With Neck Dissection Versus Radiotherapy for T2N0 Supraglottic Cancer.
To compare overall survival outcomes associated with transoral laser microsurgery (TLM) with neck dissection versus definitive radiotherapy in the management of T2N0 supraglottic squamous cell carcinoma. Data were extracted from the National Cancer Database concerning patients with cT2N0M0 supraglottic cancer treated with either TLM and neck dissection with minimum lymph node yield of 10 or definitive radiotherapy. Predictors of overall survival were assessed via Cox proportional hazards regression. Seventy-six cT2N0 supraglottic squamous cell carcinoma patients who underwent TLM with neck dissection (+/- adjuvant therapy) versus 991 patients who underwent radiotherapy. TLM was associated with an overall survival benefit (OR = 0.574; 95% CI 0.383-0.860) compared with radiotherapy. There was no difference in survival between TLM patients receiving adjuvant treatment and those receiving definitive radiotherapy. An up-front, TLM-based surgical approach to cT2N0 supraglottic cancer may offer an overall survival benefit compared with definitive radiotherapy, and should receive more frequent consideration as a primary approach to this disease process. 3 Laryngoscope, 133:601-606, 2023.


A gene transfer system for the glycopeptide producer Nonomuraea sp. ATCC39727.
The filamentous actinomycete Nonomuraea sp. ATCC39727 produces the industrially important glycopeptide antibiotic A40926. We developed a gene transfer system based on intergeneric conjugation from Escherichia coli. Analysis of the ex-conjugants revealed that the incoming plasmid pSET152 had integrated at two sites in the Nonomuraea genome. One of these was characterized and found to be highly related to other PhiC31 attB sites described in Streptomyces spp., including the core TTS sequence, where crossover occurs. Surprisingly, pSET152 was also found in episomic form in the Nonomuraea ex-conjugants.


Atomic Force Microscopy Imaging and Nanomechanical Properties of Six Tau Isoform Assemblies.
The amyloid fibrillar form of the protein Tau is involved in a number of neurodegenerative diseases, also known as tauopathies. In this work, six different fibrillar Tau isoforms were assembled in vitro. The morphological and nanomechanical properties of these isoforms were studied using atomic force microscopy at high resolution in air and buffer. Our results demonstrate that all Tau isoform fibrils exhibit paired-helical-filament-like structures consisting of two protofibrils separated by a shallow groove. Interestingly, whereas the N-terminal inserts do not contribute to any morphological or mechanical difference between the isoforms with the same carboxyl-terminal microtubule-binding domain repeats, isoforms with four microtubule repeats (4R) exhibited a persistence length ranging from 2.0 to 2.8 μm, almost twofold higher than those with three repeats (3R). In addition, the axial Young's modulus values derived from the persistence lengths, as well as their radial ones determined via nanoindentation experiments, were very low compared to amyloid fibrils made of other proteins. This sheds light on the weak intermolecular interaction acting between the paired β-sheets within Tau fibrils. This may play an important role in their association into high molecular weight assemblies, their dynamics, their persistence, their clearance in cells, and their propagation.


Intraspinal transplants of serotonergic neurons in the adult rat.
Adult male Sprague-Dawley rats were made paraplegic by a complete transection of the spinal cord at lower thoracic level. One week later they were transplanted, below the level of the section, with a cell suspension prepared from the raphe region of 14-day embryos. After survival periods of 10 days to 1 year, the animals were sacrificed and the spinal cord processed for the immunocytochemical detection of 5-HT. Axons from grafted cells grew extensively into the grey matter of the host, and established axosomatic and axodendritic synapses in the anterior horn and intermediolateral column, similar to those of the intact animal. In addition, a group of transplanted animals was tested for sexual reflexes which are under the control of serotonin. It was found that ejaculation reflexes, which are absent in paraplegic rats, are restored in transplanted animals.


Effect of terbutaline sulphate on ovarian, uterine and maternal placental blood flow in the anesthetized guinea pig.
The effect of terbutaline sulphage, a beta-adrenergic agonist, on uteroplacental blood flow was studied in the guinea pig during late pregnancy. Organ blood flows and cardiac output were assessed by the radioactive microsphere technique. Infusion of terbutaline at a rate of 2nmol min-1 kg-1 body weight caused a significant increase in cardiac output and in the perfusion of the uterus and ovaries, but there was no significant alteration in maternal placental blood flow. When the infusion rate was increased tenfold, there was also a significant rise in the blood supply to the bronchi, urinary bladder, kidneys, and adrenal glands. Maternal placental blood flow was not adversely affected even by this large dose of the drug, although there was a significant reduction in the placental share of the cardiac output.


Causal effect of early life adiposity on gestational diabetes mellitus and mediating roles of lipidomic biomarkers.
The causal relationship between early life adiposity and gestational diabetes mellitus (GDM) and the underlying mechanisms remains unclear. This study aimed to investigate the independent causal association between early life adiposity and GDM and identify potential metabolic mediators and their mediating effects on this relationship. Using genome-wide association study (GWAS) summary statistics from the publicly available database of early life adiposity (5,530 cases and 8,318 controls) and GDM (11,279 cases and 179,600 controls), a two-step, two-sample Mendelian randomization (MR) was conducted to estimate the causal mediation effects of lipidomic biomarkers including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, apolipoprotein A-Ι, and apolipoprotein B on the relationship between early life adiposity and GDM. Genetically predicted childhood adiposity was positively associated with risk of GDM (OR: 1.21, 95%CI: 1.09-1.34, p = 4.58 × 10-4). This causal relationship remained after accounting for adult adiposity traits in the multivariable MR analyses. Two-step MR identified three candidate mediators that partially mediated the effect of early life adiposity on GDM, including HDL-C (5.81, 95%CI: 3.05-8.57%), apolipoprotein A-Ι (4.16, 95%CI: 1.64-6.69%), and triglyceride (2.20, 95%CI: 0.48-3.92%). This MR study demonstrated that the causal effect of childhood obesity on future GDM risk was independent of adult adiposity. We identified three mediators, including HDL-C, apolipoprotein A-Ι, and triglyceride, in this association pathway. Our results provide insights into the pathogenesis of GDM and suggest additional prevention and treatment targets for GDM related to early life adiposity.


Size-selective predation by roach (Rutilus rutilus) on zebra mussel (Dreissena polymorpha): field stuides.
Studies of predation by roach (Rutilus rutilus) on zebra mussel (Dreissena polymorpha) in a large, eutrophic lake showed that there was a clearly marked size threshold (∼ 160 mm SL) above which roach began to feed on mussels. Roach preying on various sizes of mussels selected them in proportions different from their abundance and accessibility in the habitat. The mean size of mussels ingested by roach of 220 mm and larger, which fed predominantly on Dreissena, closely followed the pattern expected for a constant ratio of mean prey size to mean predator mouth size = 0.59. To explain the size selection we applied an optimal foraging approach, based on the ability of different-sized fish to crush (cost) mussels of different sizes, and hence crushing resistance, and energy contents ('benefit'). We found that fish smaller than 160 mm, which showed no inclination to eat Dreissena, would only be able to take small mussels with a very high cost/benefit ratio. The real switch to Dreissena would be expected in fish of 230-240 mm that could take most of their prey from highly profitable, numerous, and easily accessible size classes while keeping the mean prey size at the optimal level relative to mean predator mouth size.


Bacillus velezensis strain B26 modulates the inflorescence and root architecture of Brachypodium distachyon via hormone homeostasis.
Plant growth-promoting rhizobacteria (PGPR) influence plant health. However, the genotypic variations in host organisms affect their response to PGPR. To understand the genotypic effect, we screened four diverse B. distachyon genotypes at varying growth stages for their ability to be colonized by B. velezensis strain B26. We reasoned that B26 may have an impact on the phenological growth stages of B. distachyon genotypes. Phenotypic data suggested the role of B26 in increasing the number of awns and root weight in wild type genotypes and overexpressing transgenic lines. Thus, we characterized the expression patterns of flowering pathway genes in inoculated plants and found that strain B26 modulates the transcript abundance of flowering genes. An increased root volume of inoculated plants was estimated by CT-scanning which suggests the role of B26 in altering the root architecture. B26 also modulated plant hormone homeostasis. A differential response was observed in the transcript abundance of auxin and gibberellins biosynthesis genes in inoculated roots. Our results reveal that B. distachyon plant genotype is an essential determinant of whether a PGPR provides benefit or harm to the host and shed new insight into the involvement of B. velezensis in the expression of flowering genes.


Defined and unknown roles of conductive nanoparticles for the enhancement of microbial current generation: A review.
The ability of various bacteria to make use of solid substrates through extracellular electron transfer (EET) or extracellular electron uptake (EEU) has enabled the development of valuable biotechnologies such as microbial fuel cells (MFCs) and microbial electrosynthesis (MES). It is common practice to use metallic and semiconductive nanoparticles (NPs) for microbial current enhancement. However, the effect of NPs is highly variable between systems, and there is no clear guideline for effectively increasing the current generation. In the present review, the proposed mechanisms for enhancing current production in MFCs and MES are summarized, and the critical factors for NPs to enhance microbial current generation are discussed. Implications for microbially induced iron corrosion, where iron sulfide NPs are proposed to enhance the rate of EEU, photochemically driven MES, and several future research directions to further enhance microbial current generation, are also discussed.


The effect of Malus doumeri leaf flavonoids on oxidative stress injury induced by hydrogen peroxide (H2O2) in human embryonic kidney 293 T cells.
In this study, Malus doumeri leaf flavonoids (MDLF) were used as the research object to observe their in vitro antioxidant stress ability. Hydrogen peroxide (H2O2) was used to induce oxidative stress in 293 T cells. MTT, flow cytometry, and qPCR were used to verify the effect of MDLF. In vitro cell experiments showed that at a concentration of 0-160 μg/mL, MDLF did not affect the normal proliferation of human embryonic kidney 293 T cells (HEK 293 T cells), and MDLF had no cytotoxic effect in this concentration range. It was found that MDLF could maintain the survival of HEK 293 T cells (82.6%) at a high concentration (160 μg/mL). Morphological observation also found that MDLF can inhibit the cell structure imperfection caused by H2O2. It was also observed that MDLF could significantly increase the levels of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) and reduce the level of malondialdehyde (MDA). The results of quantitative polymerase chain reaction (qPCR) showed that MDLF could significantly up-regulate the mRNA expression levels of CAT, SOD, GSH, GSH-Px, B-cell lymphoma-2 (Bcl-2) and downregulate the expression levels of B-cell lymphoma-2 associated x protein (Bax), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-B (NF-κB) in oxidative stress-injured cells. The HPLC analysis showed that MDLF contained hyperin, isoquercetin, quercitrin, hesperidin, myricetin, baicalin and quercetin. From the experimental results, it was observed that MDLF has a strong anti-oxidation ability in vitro, and it can interfere with the oxidative stress damage caused by H2O2 in 293 T cells. Therefore, MDLF is a type of natural substance with good anti-oxidant effect, and it has the potential to interfere with many diseases.


Microspore Embryogenesis Through Anther Culture in Citrus clementina Hort. ex Tan.
Anther culture is a biotechnological method that allows to obtain, in one step, homozygous plants, very important to plant breeding, due to their numerous applications in mutation research, selection, genome sequencing, genetic analysis, and transformation. To induce the microspores, i.e., the immature male gametes, to switch from the normal gametophytic pathway to the sporophytic one, it is necessary to submit them to a type of stress, such as high or low temperature, starvation, or magnetic field. Stress can be applied to the donor plants and/or the floral buds or the anthers or the isolated microspores, before or during the culture. In this chapter, the protocol to induce gametic embryogenesis from anther culture of several cultivars of Citrus clementina Hort. ex Tan. is reported.


Chemopreventive Properties of Genipin on AGS Cell Line via Induction of JNK/Nrf2/ARE Signaling Pathway.
Roles of dietary phytochemicals in cancer chemoprevention via induction of nuclear factor-erythroid-2-related factor 2 (Nrf2)-mediated antioxidant enzymes have been well established in a number of studies. In this study, FACS analysis was used to reveal that the intracellular reactive oxygen species level decreased at 0-25 μM of genipin treatment. Furthermore, immunofluorescence analysis and Western blotting were used to demonstrate that genipin treatment resulted in the upregulation and nuclear translocation of Nrf2, as well as upregulation of gastrointestinal glutathione peroxidase. Finally, we found that C-Jun-NH2-kinase (JNK) was also dose-dependently activated, where depleting JNK by using a biochemical inhibitor indicated that JNK was upstream of Nrf2. Interestingly, the antioxidant effects were limited to the treatment in the lower dosage of genipin, where higher dosage of genipin treatment resulted in the increased reactive oxygen species level and cytotoxicity. Thus, this study demonstrates for the first time that lower dosage of genipin results in the induction of JNK/Nrf2/ARE signaling pathway and protection from cell death.


Choline chloride vs choline ionic liquids for starch thermoplasticization.
Native starch containing 12% water was melt processed in presence of 23% of various plasticizers at 120°C, either by simple compression molding or by extrusion using a laboratory scale microcompounder. Glycerol, a typical starch plasticizer, was used as a reference and compared to three choline salts: raw choline chloride (which is a solid in dry state with a melting point above 300°C), and two ionic liquids synthesized from this precursor (choline acetate and choline lactate, liquids below 100°C). These ionic plasticizers were shown to allow a more efficient melting of native starch in both processes. The investigation of macromolecular structure changes during processing shows that this efficiency can be ascribed to a starch chain scission mechanism, resulting in lower specific mechanical energy input need for starch thermoplasticization compared to glycerol plasticized starch. Compared to the synthesized ionic liquids, raw commercial choline chloride leads to a good compromise between limited chain scission, and final water uptake and thermomechanical properties.


A Digital Platform for the Self-Management of Knee Arthritis: MyArthritisRx.com.
MyArthritisRx.com (MARx) is an online digital platform with resources to effectively manage osteoarthritis and directs patients to the appropriate information and tools to manage their disease. The key to self-management is a self-evaluation and staging program powered by an algorithm based on 150,000 arthritis patients. Outcome data (PROMs), comorbidities, demographics, and personalized characteristics are used to provide a personalized self-evaluation and staging assessment which characterizes disease severity and risk of progression. The initial 6-week program was completed by 100 pilot patients with 92% reporting some improvement. MARx offers evidence of efficacy with promise of cost savings and improved arthritis care.


Population pharmacokinetics of methotrexate in Mexican pediatric patients with acute lymphoblastic leukemia.
To develop and validate a population pharmacokinetic model of Methotrexate (MTX) in Mexican children with acute lymphoblastic leukemia (ALL) for the design of personalized dosage regimens based on the anthropometric and physiological characteristics of each patient. A prospective study was developed in 50 children (1-15 years old) with ALL diagnosis attended at Pediatric Hemato-Oncology Service from Hospital Central "Dr. Ignacio Morones Prieto" and under treatment with high doses of MTX administered in 24-h continuous intravenous infusion. Plasma concentrations of MTX were determined in blood samples collected at 24, 36, 42 or 48 h post-infusion, by means of the CMIA immunoassay. The development of the population pharmacokinetic model was performed using the NONMEM® software evaluating the covariates that influence in clearance (CL), intercompartmental clearance (Q), central (Vc) and peripheral (Vp) volume of distribution of MTX. A two-compartment open model was selected to describe concentration-time data and body surface area (BSA) was the covariate that influences on MTX total CL. The population pharmacokinetic model obtained was: CL (L/h) = 6.5 × BSA0.62, Vc (L) = 0.36 × Weight, Q (L/h) = 0.41 and Vp (L) = 3.2. Internal validation was performed by bootstrap and visual predictive check. Predictive performance of final model was evaluated by external validation in a different group of patients. Initial MTX dosing regimens were established by stochastic simulation with final population pharmacokinetic model. The establishment of MTX dosing criteria in children with ALL should be adjusted based on the BSA of each patient to optimize oncological therapy and reduce the development of adverse effects. Therapeutic drug monitoring is an essential tool to individualize MTX doses to reduce toxicity and improve patients' outcomes.


Focus on emotion and disorders of emotion.
Regulation of emotion is becoming better understood, but despite the societal costs of disorders like depression and anxiety, their causes remain unclear. Five review articles in this issue provide perspective on this literature.


Effect of 5,7-dihydroxytryptamine on the food-aversive conditioning in the snail Helix lucorum L.
The effects of 5,7-dihydroxytryptamine (5,7-DHT), a drug which selectively ablates serotonergic terminals, were examined on acquisition of food-aversive conditioned reflex in the snail Helix lucorum. The percent of feeding reactions decreased from 80 to 15% in the conditioned group of animals after 5-8 pairings of food and electric shock. The behavioral performance of 5,7-DHT-injected animals after the same training session coincided with the data received from the unpaired control group: the percent of feeding reactions remained the same as before the training. Conditioning was carried out on the semi-intact 'lip-CNS' preparations as well. Intracellular recordings from the neurons responding to the withdrawal reaction confirmed the results of the behavioral experiments. Elaboration of associative changes was effective on preparations made from normal snails, whereas no changes were noted in 5,7-DHT-treated and pseudoconditioned animals. In 5,7-DHT-treated animals some components of the feeding behavior and withdrawal reaction changed as well. The appetitive phase duration of feeding lengthened significantly, moreover the sensitization of the withdrawal reaction evoked by rhythmic tactile stimulation disappeared in preparations made from drug-treated snails.


Long-term Outcomes in Primary CNS Lymphoma After R-MVP and High-Dose Chemotherapy With Autologous Hematopoietic Stem Cell Transplant.
Primary CNS lymphoma (PCNSL), a rare CNS malignancy, is usually treated with high-dose methotrexate in the first-line setting, typically followed by consolidation therapy. Due to the broad range of currently available treatments for PCNSL, comparability in long-term follow-up studies is limited, and data are scattered across small studies. In this study, we report the long-term survival of patients with newly diagnosed immunocompetent PCNSL, enrolled in a phase II trial from June 2005 to September 2011. Patients were treated using rituximab, methotrexate, vincristine, and procarbazine (R-MVP) chemotherapy followed by high-dose chemotherapy (HDC) and autologous stem cell transplant (ASCT) in those with partial or complete response to R-MVP. In a post hoc analysis, clinical and imaging features were evaluated in those still alive. 26 of 32 patients underwent HDC-ASCT consolidation. Of them, 3 patients died of treatment-related toxicity and 2 due to disease progression within 1 year of ASCT. None of the remaining 21 patients had disease progression with a median follow-up of 12.1 years and were included in the analysis. Compared with the post-HDC-ASCT assessment, at the last follow-up, there was no significant difference in the median Karnofsky Performance Status (80 [range: 60-100] vs 90 [range: 70-100]), the median Neurologic Assessment in Neuro-Oncology score (1 [range: 0-4] vs 1 [range: 0-5]), and leukoencephalopathy score (1 [range: 0-3] vs 1 [range: 1-4]). Long-term follow-up demonstrated that treatment was well tolerated in most patients enrolled in this study, with stable leukoencephalopathy on imaging and stable clinical performance status. Disease recurrence was not observed beyond 2 years after HDC-ASCT consolidation.


The phagocytosis-associated chemotaxis of human mononuclear leucocytes from peripheral blood is not antitubulin-sensitive.
Lymphoprep-isolated and glass-adherent mononuclear leucocytes (L-MNs) from the peripheral blood of healthy donors appeared to display directional locomotion towards sparsely distributed yeast cells during continuous observation in coverslip preparations and during observations by means of time-lapse filming in Rose chambers. The phagocytosis-associated L-MN chemotaxis was not inhibited by antitubulin concentrations which were antichemotactic thesis that a direct antitubulin-insensitive chemotaxis exists in L-MNs, besides the antitubulin-inhibited L-MN chemoataxis reported in a previous study.


Neuromuscular blockade in infants following intramuscular succinylcholine in two or five per cent concentration.
This study determined the characteristics of the neuromuscular block which followed intramuscular succinylcholine 4 mg . kg-1 in 20 infants during halothane anaesthesia. The infants were divided into two groups of ten; the first received succinylcholine in two percent solution and the second in five per cent solution. The mean maximum depression of the first twitch of the train-of-four (T1) was 89.7 +/- 5.0 per cent in 4.0 +/- 0.6 min, and the mean full recovery of T1 occurred in 15.6 +/- 0.9 min after injection. The maximum block achieved and the onset and recovery times were not affected by the concentration used. Depolarizing block, with equal depression of all twitches of the train-of-four was observed during the onset of neuromuscular blockade. During recovery, phase II block, as determined by a train-of-four ratio (T4/T1) of 0.5 or less, occurred frequently at T1 recovery of 25-50 per cent, but was not associated with prolonged paralysis. It is concluded that the onset time of 4 min for intramuscular succinylcholine 4 mg . kg-1 may be too long for emergency use in infants, and no improvement is obtained by increasing the concentration of injected succinylcholine from two to five per cent.


Examining the influence of pain and fatigue on neurocognitive functioning in adolescents and young adults with sickle cell disease.
Pain and fatigue are among the most common and impactful complications of sickle cell disease (SCD). Individuals with SCD are also more likely to have neurocognitive deficits. Previous studies have suggested that pain and fatigue might influence neurocognitive functioning in patients with SCD. However, these studies are limited by small sample sizes and inadequate measurement of cognitive performance. The present study aimed to investigate the relationship between pain and fatigue with neurocognitive functioning using performance-based measures of neurocognition. Pain and fatigue were not associated with neurocognitive performance. Implications and directions for future research are discussed.


Role of trisaccharides in larval secretion of Lycaeides argyrognomon butterfly on ant attendance.
Several myrmecophilous insects participate in symbiotic relationships with ants that receive sugar-rich food rewards. For instance, certain aphid species secrete honeydew containing high concentration of melezitose, which acts as a potent feeding-stimulant and attractant for ants. Lycaenid butterfly larvae possess dorsal nectary glands that secrete sugar-rich droplets for tending ants. However, the roles of sugar components in ant foraging and larva-tending activities are unknown. Lycaeides (Plebejus) argyrognomon are larvae that are frequently and facultatively attended by various ant species, including Formica japonica, on the host plant Indigofera pseudotinctoria. The larval secretions of this insect contained small amounts of trisaccharides, melezitose and maltotriose, which were not detected in the host plant's flower nectar, and larval secretions of two sympatric and myrmecophilous lycaenids, Zizeeria maha and Everes argiades. Melezitose and maltotriose, along with sucrose, were preferred by the worker ants. Of the four sugar mixture samples that mimicked I. pseudotinctoria floral nectar and the larval secretions of three lycaenids, respectively, the L. argyrognomon mimic was the most preferred by F. japonica ants. Moreover, the removal of trisaccharides from this mimic significantly reduced its stimulatory activity to ant feedings. These results indicated that the sugar composition of L. argyrognomon larval secretions is suited to the feeding preference of F. japonica ants, and that the trisaccharide components play a key role in increasing their preference. However, only half of the ants responded to the L. argyrognomon mimic even at the concentration corresponding to the maximum total sugar concentration in the collected larval secretions. The fact that the secretions of all L. argyrognomon larvae did not have sufficient sugar levels to stimulate ant feedings suggests that the production of sugar-rich secretions and trisaccharide components is metabolically costly for the larvae and that components other than sugars may be involved in ant attendance.


Synthesis and Antimicrobial Properties of Novel Phosphonium Salts Bearing 1,4-Dihydroxyaryl Fragment.
A versatile two-step pathway to the synthesis of triaryl(2,5-dihydroxy-6-methyl-3-(propan-2-yl)phenyl)- and triaryl(1,4-dihydroxynaphthyl)phosphonium salts from triarylphosphonium trifluoroacetates was developed. The reaction proceeds under mild conditions (20 °C, CH2 Cl2 ) with high yields (88-95 %). Some representatives of this series possess low hemolytic and high bactericidal activity against Gram-positive bacteria.


Effect of nonsurgical periodontal therapy on salivary melatonin levels in patients with periodontal disease.
Periodontitis is an inflammatory disease in which periodontal tissues are damaged as a result of an imbalance in the oxidant/antioxidant systems. Melatonin is one hormone that controls circadian rhythms and is also an antioxidant and immune modulator. The present study was aimed to evaluate the effect of scaling and root planing (SRP) on salivary melatonin levels (SM) in patients with periodontal disease. A single-center clinical trial was conducted to evaluate the effect of SRP on SM levels in patients with periodontal disease. Forty-five participants of age 30-60 years were equally divided into three groups: 15 healthy participants, 15 participants with gingivitis, and 15 participants with periodontitis. Unstimulated salivary samples were collected from all the participants at baseline and 1 month after SRP from participants of gingivitis and periodontitis group and SM levels were determined by commercially available ELISA kit. Group comparisons were made using t-test. The level of significance was set at a P < 0.05 for all tests. SM levels were significantly lower in the chronic periodontitis group. There was a significant improvement in clinical parameters and SM levels in both chronic periodontitis and gingivitis groups after SRP. This study determined that there is a negative correlation between SM levels and the severity of periodontal disease and showed a significant increase in SM levels after SRP, suggesting that melatonin might have a protective role against periodontal disease and can be considered as an effective biomarker.


Intersection of the Gut Microbiome and Circadian Rhythms in Metabolism.
The gut microbiome and circadian rhythms (CRs) both exhibit unique influence on mammalian hosts and have been implicated in the context of many diseases, particularly metabolic disorders. It has become increasingly apparent that these systems also interact closely to alter host physiology and metabolism. However, the mechanisms that underlie these observations remain largely unknown. Recent findings have implicated microbially derived mediators as potential signals between the gut microbiome and host circadian clocks; two specific mediators are discussed in this review: short-chain fatty acids (SCFAs) and bile acids (BAs). Key gaps in knowledge and major challenges that remain in the circadian and microbiome fields are also discussed, including animal versus human models and the need for precise timed sample collection.


Mitochondrial DNA repair: a novel therapeutic target for heart failure.
Mitochondria play a crucial role in a variety of cellular processes ranging from energy metabolism, generation of reactive oxygen species (ROS) and Ca(2+) handling to stress responses, cell survival and death. Malfunction of the organelle may contribute to the pathogenesis of neuromuscular, cancer, premature aging and cardiovascular diseases (CVD), including myocardial ischemia, cardiomyopathy and heart failure (HF). Mitochondria contain their own genome organized into DNA-protein complexes, called "mitochondrial nucleoids," along with multiprotein machineries, which promote mitochondrial DNA (mtDNA) replication, transcription and repair. Although the mammalian organelle possesses almost all known nuclear DNA repair pathways, including base excision repair, mismatch repair and recombinational repair, the proximity of mtDNA to the main sites of ROS production and the lack of protective histones may result in increased susceptibility to various types of mtDNA damage. These include accumulation of mtDNA point mutations and/or deletions and decreased mtDNA copy number, which will impair mitochondrial function and finally, may lead to CVD including HF.


Patterns of biomass allocation to male and female functions in plants with different mating systems.
Using dry weight biomass we examined the patterns of investment in male and female functions (prezygotic cost) in plants with different mating systems. All the flower parts of both xenogamous and facultatively xenogamous species were heavier, i.e., larger, than those of facultatively autogamous species. Likewise, the dry weights of all the flower parts of xenogamous species exceeded those of facultatively xenogamous species. On a relative basis, xenogamous species invested less in calyces and more in corollas compared to species with the other mating systems. Facultatively autogamous species invested relatively more in pistils. Xenogamous species invested relatively more in stamens than do facultatively autogamous species. The ratios of dry weight stamens to dry weight pistils were equivalent in xenogamous and facultatively xenogamous species.The available data from xenogamous species suggest a pattern of resource allocation that is independent of sexual system (perfect-flowered, monoecious, or dioecious) and pollen vector. The cost of mating (prezygotic cost) was male biased and frequently exceeded by parental investment (postzygotic cost). These results are not consistent with models that predict equal allocation of resources to male and female sexual function but are consistent with those that predict unequal allocation of resources to those functions in outbreeding hermaphroditic angiosperms. Two additional lines of evidence are inconsistent with the expectations of sex allocation theory. First, resource allocation to sexual function was not equal in wind-pollinated species. Second, relative amounts of the resources allocated to male vis-à-vis female function did not decrease between xenogamy and facultative xenogamy i.e., with an increase in the selfing rate.


An individualized approach to the management of Cushing disease.
Cushing disease caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary corticotroph adenoma leads to hypercortisolaemia with high mortality due to metabolic, cardiovascular, immunological, neurocognitive, haematological and infectious conditions. The disorder is challenging to diagnose because of its common and heterogenous presenting features and the biochemical pitfalls of testing levels of hormones in the hypothalamic-pituitary-adrenal axis. Several late-night salivary cortisol and 24-h urinary free cortisol tests are usually required as well as serum levels of cortisol after a dexamethasone suppression test. MRI might only identify an adenoma in 60-75% of patients and many adenomas are small. Therefore, inferior petrosal sinus sampling remains the gold standard for confirmation of ACTH secretion from a pituitary source. Initial treatment is usually transsphenoidal adenoma resection, but preoperative medical therapy is increasingly being used in some countries and regions. Other management approaches are required if Cushing disease persists or recurs following surgery, including medications to modulate ACTH or block cortisol secretion or actions, pituitary radiation, and/or bilateral adrenalectomy. All patients require lifelong surveillance for persistent comorbidities, clinical and biochemical recurrence, and treatment-related adverse effects (including development of treatment-associated hypopituitarism). In this Review, we discuss challenges in the management of Cushing disease in adults and provide information to guide clinicians when planning an integrated and individualized approach for each patient.


Sex-specific variation in brown-headed cowbird immunity following acute stress: a mechanistic approach.
There is some discrepancy in the literature regarding whether acute stress is immunostimulatory or immunosuppressive. Studies of domesticated (laboratory and food) animals and humans typically indicate that acute stress is immunostimulatory, whereas studies of non-domesticated species document both immunostimulatory and immunosuppressive results. Few studies have examined the mechanisms responsible for changes in immune activity in species other than those classically used in laboratory research. We examined the effect of both acute stress and exogenous corticosterone (CORT) on the bactericidal capacity (BC) of blood plasma from captive, wild-caught brown-headed cowbirds (Molothrus ater) to determine if CORT is responsible for changes in levels of immune activity. We conducted "stress tests" in which we handled birds to elicit a stress response and then measured the birds' total CORT and BC at 30 or 90 min post-stressor. We also conducted non-invasive tests in which we administered exogenous CORT by injecting it into mealworms that were fed to the cowbirds remotely. Total, free, and bound CORT levels, corticosteroid binding globulins (CBGs), and BC at 7 or 90 min post-mealworm ingestion were measured. Both males and females exhibited significant increases in total CORT following handling stress and the administration of exogenous CORT. Experimental males and females also exhibited a significant increase in CBG capacity at 7 min post-mealworm ingestion compared to controls. Male cowbirds exhibited a significant decline in their BC following both handling stress and the administration of exogenous CORT whereas female cowbirds exhibited no decline under either condition. Female CBG levels were not different than those of males, suggesting that differences in BC could be due to differences between the sexes in the number of corticosteroid receptors which, along with CBGs, regulate the stress response. Female cowbirds may modulate their stress response as an adaptive life-history strategy for maximizing current reproduction.


Effects of hexachlorobenzene on antioxidant status of liver and brain of common carp (Cyprinus carpio).
Hexachlorobenzene (HCB)-induced oxidative damages have been published in rats while the effects have not yet been reported in fishes. Juvenile common carps (Cyprinus carpio) were exposed to waterborne HCB from 2 to 200 microg l-1 for 5, 10 or 20 days. Liver and brain were analyzed for various parameters of oxidative stress. There were no significant changes of glutathione (GSH) content and superoxide dismutase (SOD) activity in liver after 5 or 10 days exposure, whereas obvious drops were observed at higher concentrations after 20 days exposure. Significant decreases of GSH content and SOD activity in brain were found during all the exposure days. In brain, HCB also significantly elevated the contents of reactive oxygen species (ROS), thiobarbituric acid- reactive substances (TBARS, as an indicator of lipid peroxidation products), glutathione disulfide (GSSG), and activities of nitric oxide synthase (NOS), glutathione peroxidase (GPx), and glutathione reductase (GR), and inhibited activities of acetylcholinesterase (AchE) and glutathione S-transferase (GST). The results clearly demonstrated that environmentally possible level of HCB could result in oxidative stress in fish and brain was a sensitive target organ of HCB toxicity.


Mass spectrometric quantification of glycogen to assess primary substrate accumulation in the Pompe mouse.
Glycogen storage in the α-glucosidase knockout((6neo/6neo)) mouse recapitulates the biochemical defect that occurs in the human condition; as such, this mouse serves as a model for the inherited metabolic deficiency of lysosomal acid α-glucosidase known as Pompe disease. Although this model has been widely used for the assessment of therapies, the time course of glycogen accumulation that occurs as untreated Pompe mice age has not been reported. To address this, we developed a quantitative method involving amyloglucosidase digestion of glycogen and quantification of the resulting free glucose by liquid chromatography/electrospray ionization-tandem mass spectrometry. The method was sensitive enough to measure as little as 0.1 μg of glycogen in tissue extracts with intra- and interassay coefficients of variation of less than 12%. Quantification of glycogen in tissues from Pompe mice from birth to 26 weeks of age showed that, in addition to the accumulation of glycogen in the heart and skeletal muscle, glycogen also progressively accumulated in the brain, diaphragm, and skin. Glycogen storage was also evident at birth in these tissues. This method may be particularly useful for longitudinal assessment of glycogen reduction in response to experimental therapies being trialed in this model.


Protein C and fibrinolysis: a link between coagulation and fibrinolysis.
The effect of purified human activated protein C (APC) on fibrinolysis was studied by using in vitro clot lysis techniques. Clots were formed from citrated blood or plasma (supplemented with 125I-labeled fibrinogen) by adding thrombin and Ca(2+)-ions; lysis of the clots was achieved by the addition of tissue-type plasminogen activator before clot formation. The gradual release of labeled fibrin degradation products from the clot into the supernatant was taken as a measure for the lysis rate. It was demonstrated that the acceleration of clot lysis by APC added before clot formation depends on the presence of Protein S, Ca(2+)-ions and phospholipids. These observations suggest a role of APC as anticoagulant in clot lysis, since the cofactors for the expression of its anticoagulant and profibrinolytic effect are very similar. Indeed, we could demonstrate that the profibrinolytic effect of APC in vitro is associated with reduction of thrombin generation through the coagulation cascade by inactivation of factor VIIIa and factor Va. For instance, APC did not accelerate the lysis of factor X deficient blood clots. More generally, thrombin generation was associated with retarded fibrinolysis in vitro. Consequently anticoagulants such as APC or Heparin are profibrinolytic, whereas pro-coagulants such as phospholipids (in cell-free plasma) inhibit fibrinolysis through the generation of thrombin. Thrombin thus plays a crucial role as a link between coagulation and fibrinolysis. As thrombin is able to inhibit the lysis of blood and plasma clots, and not of purified fibrin clots, we hypothesize that thrombin inhibits lysis through an as yet unidentified mediator in plasma.


Multifunctional biocatalyst for conjugate reduction and reductive amination.
Chiral amine diastereomers are ubiquitous in pharmaceuticals and agrochemicals1, yet their preparation often relies on low-efficiency multi-step synthesis2. These valuable compounds must be manufactured asymmetrically, as their biochemical properties can differ based on the chirality of the molecule. Herein we characterize a multifunctional biocatalyst for amine synthesis, which operates using a mechanism that is, to our knowledge, previously unreported. This enzyme (EneIRED), identified within a metagenomic imine reductase (IRED) collection3 and originating from an unclassified Pseudomonas species, possesses an unusual active site architecture that facilitates amine-activated conjugate alkene reduction followed by reductive amination. This enzyme can couple a broad selection of α,β-unsaturated carbonyls with amines for the efficient preparation of chiral amine diastereomers bearing up to three stereocentres. Mechanistic and structural studies have been carried out to delineate the order of individual steps catalysed by EneIRED, which have led to a proposal for the overall catalytic cycle. This work shows that the IRED family can serve as a platform for facilitating the discovery of further enzymatic activities for application in synthetic biology and organic synthesis.


Morphological and biological characterization of cell line developed from bovine Echinococcus granulosus.
The taeniid tapeworm Echinococcus granulosus is the causative agent of echinococcal disease, a major zoonosis with worldwide distribution. Several efforts to establish an in vitro model of E. granulosus have been undertaken; however, many of them have been designed for Echinococcus multilocularis. In the present study, we have described and characterized a stable cell line obtained from E. granulosus bovine protoscoleces maintained 3 yr in vitro. Growth characterization, morphology by light, fluorescent and electronic microscopy, and karyotyping were carried out. Cell culture origin was confirmed by immunofluorescent detection of AgB4 antigen and by PCR for the mitochondrial cytochrome c-oxidase subunit 1 (DCO1) gene. Cells seeded in agarose biphasic culture resembled a cystic structure, similar to the one formed in secondary hosts. This cell line could be a useful tool to research equinococcal behavior, allowing additional physiological and pharmacological studies, such as the effect of growth factors, nutrients, and antiparasitic drugs on cell viability and growth and on cyst formation.


Defining the nasal transcriptome in granulomatosis with polyangiitis (Wegener's).
To determine whether disease processes related to granulomatosis with polyangiitis (Wegener's) (GPA) are reflected in gene expression profiles of the nasal mucosa. Nasal brushings of the inferior turbinate were obtained from 32 patients with GPA (10 with active nasal disease, 13 with prior nasal disease, and 9 with no history of nasal disease) and a composite comparator group with and without inflammatory nasal disease (12 healthy people, 15 with sarcoidosis, and 8 with allergic rhinitis). Differential gene expression was assessed between subgroups of GPA and comparators. A total of 339 genes were differentially expressed between the GPA and comparator groups (absolute fold change >1.5; false discovery rate <0.05). Top canonical pathways up-regulated in nasal brushings from patients with GPA included granulocyte adhesion and diapedesis (P = 8.6(-22) ), agranulocyte adhesion and diapedesis (P = 1.3(-14) ), IL10 signaling (P = 3.0(-11) ), LXR/RXR activation (P = 4.3(-11) ), and TREM1 signaling (P = 9.0(-11) ). A set of genes differentially expressed in GPA independently of nasal disease activity status included genes related to epithelial barrier integrity (fibronectin 1, desmosomal proteins) and several matricellular proteins (e.g., osteonectin, osteopontin). Significant overlap of differentially expressed genes was observed between active and prior nasal disease GPA subgroups. Peripheral blood neutrophil and mononuclear gene expression levels associated with GPA were similarly altered in the nasal gene expression profiles of patients with active or prior nasal disease. Profiling the nasal transcriptome in GPA reveals gene expression signatures related to innate immunity, inflammatory cell chemotaxis, extracellular matrix composition, and epithelial barrier integrity. Thus, airway-based expression profiling is feasible and informative in GPA.


75Se-release: a short and long term assay system for cellular cytoxicity.
The gamma-emitting aminoacid 75Se-selenomethionine (75SeM) was examined as a target cell label in cytotoxic assays. It was efficiently taken up by activated, intensively metabolizing cells of various types but hardly at all by resting or low-metabolizing cells. Culturing activated cells in methionine-deficient medium with 3--5 mu Ci75SeM/ml for 18--22 h usually resulted in an uptake of 3--20 cpm/cell which was 3--200 times that of 51Cr marked cells. 75SeM-labelled cells kept in medium at ambient temperature or at 37 degrees C, maintained a high radioactivity per cell and a viability above 85% for at least 72 h without significant increase in spontaneous isotope release or loss in sensitivity in subsequent cytotoxic tests. 75Se-labelled material released from target cells was not reutilized by unlabelled lymphoid cells. Provided the cells were carefully washed after labelling and kept in optimal culture conditions, the reasonably low baseline release (usually 0.6--1.8% of input/h) in the medium control allowed performance of long-term assays of up to 54 h. However, strong cytotoxic reactions (e.g. ADCC) could cause over 50% specific 75Se-release within 5 h. With constant amounts of effector cells (3.6 x 10(3) up to 3 x 10(5)/well) identical or even higher, specific releases were obtained on 6 x 10(2) targets as compared to 1 x 10(4) targets/well. Thus, the 75Se-release assay offers a single monitoring system suitable for short (3--6 h) and long term (usually up to 44 h) cytotoxic reactions on a microscale, using 1 x 10(3) or less targets/well. Its sensitivity permits evaluation of strong and weak reactions as well as early and delayed onset cytotoxicity. In addition, with a gamma-spectrometer the radioactivity of 75Se can easily be distinguished from that of 51Cr. Due to this, and an improved method for 51Cr labelling of cells (10 mu Ci 51Cr/ml medium for 18--22 h), a double gamma-labelling of cellular proteins is available which provides new possibilities for monitoring cellular interactions in short and long term tests.


The c-SRC1 gene visualized by in situ hybridization on Xenopus laevis chromosomes.
Fluorescent in situ hybridization followed by tyramide signal amplification was used to map the site of the c-SRC1 gene on XENOPUS LAEVIS chromosomes. Positive results were obtained with a cDNA probe of about 1 kb. The c-SRC1 gene is located in the subcentromeric region in the long arm of one of the acrocentric chromosomes of the G category (classified according to Graf and Kobel, 1991). The c-SRC1 gene and the XENOPUS major histocompatibility complex (MHC) 1b locus, which consists of 20 tandemly arranged gene copies, are situated on different chromosomes of the G category.


Donor-acceptor-type polymers based on dithieno[2,3-b;7,6-b]carbazole unit for photovoltaic applications.
Dithieno[2,3-b;7,6-b]carbazole (TCZT), a type of heteropentacene with nitrogen and sulfur atoms, was synthesized with a focus on the unique reactivity of carbazole via double intramolecular Friedel-Crafts acylation. A donor-acceptor-type polymer (PTCZTBT) was also synthesized, and its physicochemical properties are reported.


Research progress on bird eggshell quality defects: a review.
The eggshell quality declined with extending of chicken laying cycles. Eggshell quality is a crucial feature that not only affects consumer preference, but also influences producers' economic profitability. The eggshell ultrastructure consists of mammillary, palisade, and vertical crystal layers. Any defect in shell structure results in a reduction in eggshell quality. Speckled, translucent, pimpled, and soft eggshells are common defects that cause significant financial losses for farmers and food security concerns for consumers. Therefore, reducing the faulty eggshells is critical for poultry production. Defective eggshell quality has been attributed to hereditary factors and external environmental stimuli. As such, improvements can be carried out through selective breeding and environmental control of components such as temperature, moisture, and diet formula balance. In this review, the molecular mechanisms of the main eggshell quality defects (speckled, translucent, pimpled, broken, and soft-shell eggs) and the relevant improvement methods are detailed. We hope this review will serve as a useful resource for poultry production management and effectively increasing eggshell quality.


Effects of BIM-22015, an analog of ACTH4-10, on functional recovery after frontal cortex injury.
Male rats, 90-100 days old, with frontal cortex lesions were given either subcutaneous sterile water (SW) as a vehicle control or 1, 10, or 100 micrograms of BIM-22015 every other day for 20 days. Brain-injured subjects tested in the Morris water maze with either 10 micrograms BIM-22015 or SW took significantly more trials than sham-operated rats to locate a submerged platform eight consecutive times within 60 s. The animals given 1 or 100 micrograms BIM-22015 took significantly fewer trials to reach criterion than brain-injured animals in the other drug treatment groups. On a percentage of savings, measured 8 days after reaching criterion, the brain-injured subjects given 1, 10, or 100 micrograms BIM-22015 did not differ from sham-operated rats. In contrast, the brain-injured animals given SW took longer to find the submerged platform than they did during the initial training. To assess long-term effects of the ACTH analog treatment, rats were trained on a delayed spatial alternation task 30 days after receiving the last injection. On this task, brain-injured rats treated with the 10-micrograms dose performed significantly better than those given sterile water. Acetylcholinesterase (AChE)-labeled neurons counted in the nucleus basalis magnocellularis indicated that rats with frontal cortex damage given the 10-micrograms treatment did not differ from the sham controls and had significantly more AChE-positive neurons than injured counterparts treated with SW or 100 micrograms.


Emergency Department Management of Suicidal Ideation: Challenges, Misperceptions, and Hope.
Behavioral crises continue to escalate across the United States. Our country has one of the highest suicide rates amongst developed nations. More than 45,000 U.S. citizens are dying annually now from suicide. Many with suicidal ideation seek care in Emergency Departments in hospital systems under resourced to handle this growing public health crisis. Evidenced-based screening, risk stratification, and treatment continues to evolve and is not standardized. Improved suicide education needs to be more broadly applied across healthcare and society. Missouri as a state is making concentrated efforts to improve resources and care for those with suicidal ideation. Many challenges need to be overcome and time will tell if new statewide initiatives will reduce Missouri's high rate of suicide.