Depressive symptoms are associated with medication use and lower health-related quality of life in overweight women with binge eating disorder.
Depression is a most burdensome illness, with personal and societal costs surpassing those of any other illness. Furthermore, depression affects women at a much higher rate than men. The most prevalent eating disorder among adult women is binge eating disorder (BED). Depression and obesity are common in women with BED, most of whom seek treatment later in life. Depression, obesity, and age are associated with greater health care use and lower health-related quality of life (HRQOL). Hence, for women with BED estimating the effects of depression can be confounded by both age and body mass index (BMI). The current study examined the relationships between depression, HRQOL, and health care utilization among treatment seeking women with BED. Participants (n = 105) completed the Structured Clinical Interview for DSM-IV, a health care utilization and cost survey, the Personality Assessment Inventory depression scale, and the EQ-5D to measure HRQOL. On average, participants were severely obese with a mean BMI of 38.20 (SD = 6.80); 67.27% had a lifetime history of depression. Participants had higher health care costs and lower HRQOL than published age- and gender-matched norms. After controlling for age and BMI, depressive symptoms were significantly related to greater medication use (excluding antidepressants), and lower HRQOL. Results suggest that targeting depressive symptoms may reduce the economic and personal burden of BED for women.


Mechanochemically Activated Aluminosilicate Clay Soils and their Application for Defluoridation and Pathogen Removal from Groundwater.
In this study, aluminosilicate rich clay soils were prepared through mechanochemical activation. The chemical and mineralogical properties were investigated using X-Ray Fluorescence (XRF) and X-ray diffraction (XRD). The functional groups, morphology and surface area were evaluated using Fourier Transform Infra-Red (FTIR), Scanning electron microscopy (SEM) and Brunauer-Emmett-Teller (BET) analysis. Batch experiments were used to evaluate its defluoridation efficiency while antibacterial activities were assessed using well diffusion method. Maximum adsorption capacity was found to be 1.87 mg/g with 32% fluoride removal. Fluoride adsorption was found to reduce in the presence of Cl-, PO₄2- and CO₃2- while it increased in the presence of SO₄2- and NO₃-. Adsorption data fitted well to Freundlich isotherms, hence, confirming heterogeneous multilayer adsorption. Kinetic studies revealed that fluoride adsorption fitted well to pseudo-second order model. The sorption of F- onto the clays' surface followed intra-particle diffusion mode. High correlation coefficient indicates that the sorption process was greatly controlled by particle diffusion while it is minimal in pore diffusion model. Antibacterial studies revealed no zone of inhibition for all the activated clays, hence indicating that they are not active against the bacterial strains of Escherichia coli used in this study. The results showed activated clays' potential for defluoridation. Its effectiveness in pathogen removal is limited. Hence further modifications of the clays' surfaces are hereby recommended.


Physical activity and risk of vasomotor symptoms in women with and without a history of depression: results from the Harvard Study of Moods and Cycles.
To examine whether physical activity was associated with decreased risk of vasomotor symptoms in a prospective study of women transitioning through menopause. Hypotheses were evaluated in the Harvard Study of Moods and Cycles, a longitudinal study of women with and without a history of major depression (N = 523). Ordinal logistic regression models were utilized to assess the odds of vasomotor symptoms (none, mild, moderate/severe; Greene Climacteric Scale) associated with physical activity (quartiles of metabolic equivalent-hours per week) at study enrollment and over a 3- to 5-year follow-up period. No significant associations between physical activity and vasomotor symptoms were observed for the sample as a whole. However, exploratory analyses stratified by depression history revealed that among the 157 women with a lifetime history of major depression, high (odds ratio [OR] = 0.28, 95% CI: 0.09-0.83) or moderately high (OR = 0.33, 95% CI: 0.11-0.99) physical activity proximal to the vasomotor assessment, as well as consistently high (OR = 0.27, 95% CI: 0.10-0.75) or increasing (OR = 0.33, 95% CI: 0.12-0.92) physical activity over the duration of the 3- to 5-year follow-up period was associated with decreased vasomotor symptoms relative to sedentary behavior. No significant associations were observed for women without a history of depression. Physical activity may be associated with decreased risk of vasomotor symptoms among women with a history of major depression.


Kinesin family member 23 knockdown inhibits cell proliferation and epithelial-mesenchymal transition in esophageal carcinoma by inactivating the Wnt/β-catenin pathway.
Kinesin family member 23 (KIF23) serves as a tumor-promoting gene with prognostic values in various tumors. However, the role of KIF23 in esophageal carcinoma (ESCA) progression is largely unknown. The overlapping differentially expressed genes (DEGs) in GSE12452, GSE17351, and GSE20347 datasets were identified via GEO2R tool and Venn diagram software. KIF23 expression was analyzed using GSE12452, GSE17351, and GSE20347 datasets, GEPIA database, and qRT-PCR. Cell proliferation was assessed by CCK-8 and EdU incorporation assays. Gene set enrichment analysis (GSEA) analysis was performed to investigate the pathways associated with the regulatory mechanisms of KIF23 in ESCA. The expression of E-cadherin, vimentin, N-cadherin, and matrix metalloproteinase-9 (MMP-9) and alternation of Wnt/β-catenin pathway were detected by western blot analysis. We identified two overlapping upregulated DEGs, among which KIF23 was selected for subsequent experiments. KIF23 was overexpressed in ESCA samples and cells, and knockdown of KIF23 retarded cell proliferation in ESCA cells. Besides, KIF23 knockdown suppressed epithelial-mesenchymal transition (EMT) process in ESCA cells, as evidenced by the increase of E-cadherin expression and the reduction of vimentin, N-cadherin, and MMP-9 expression. GSEA analysis suggested that Wnt signaling pathway was the significant pathway related to KIF23. Moreover, we demonstrated that KIF23 silencing inhibited the Wnt/β-catenin pathway in ESCA cells. Activation of Wnt/β-catenin pathway by SKL2001 reversed the effects of KIF23 silencing on cell proliferation and EMT in ESCA cells. In conclusion, KIF23 knockdown inhibited the proliferation and EMT in ESCA cells through blockage of Wnt/β-catenin pathway.


Haloprofundus salilacus sp. nov., Haloprofundus halobius sp. nov. and Haloprofundus salinisoli sp. nov.: three extremely halophilic archaea isolated from salt lake and saline soil.
Three halophilic archaeal strains, Gai1-5T, SEDH52T and SQT7-1T were isolated from Gaize salt lake and Xiadi salt lake in Tibet, and saline soil from Xinjiang, respectively. Phylogenetic analysis based on 16S rRNA gene and rpoB' gene sequences showed that these three strains formed different branches separating them from Haloprofundus halophilus NK23T (97.7-98.3% similarities for 16S rRNA gene and 94.7-94.8% similarities for rpoB' gene, respectively) and Haloprofundus marisrubri SB9T (94.7-96.4% similarities for 16S rRNA gene and 92.3-93.2% similarities for rpoB' gene, respectively). Several phenotypic characteristics distinguish the strains Gai1-5 T, SEDH52T and SQT7-1T from Haloprofundus halophilus NK23T and Haloprofundus marisrubri SB9T. The average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values among the three strains and current Haloprofundus members were in the range of 83.3-88.3% and 27.2-35.7%, respectively, far below the species boundary threshold values. The major polar lipids of three strains were phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylglycerol sulphate (PGS), phosphatidylglycerol phosphate methyl ester (PGP-Me), sulfated mannosyl glucosyl diether (S-DGD-1), mannosyl glucosyl diether-phosphatidic acid (DGD-PA) and sulfated mannosyl glucosyl diether-phosphatidic acid (S-DGD-PA). These results showed that strains Gai1-5T (= CGMCC 1.16079T = JCM 33561T), SQT7-1T (= CGMCC 1.16063T = JCM 33553 T) and SEDH52T (= CGMCC 1.17434T) represented three novel species in the genus Haloprofundus, for which the names Haloprofundus salilacus sp. nov., Haloprofundus salinisoli sp. nov., and Haloprofundus halobius sp. nov. are proposed.


The Self Diagnosis Method. A new methodology to assess environmental management in sea ports.
A methodology has been designed to assess the performance of the environmental management in sea ports. The Self Diagnosis Method, developed by two research teams and about sixty sea ports, allows the comparison of the current environmental situation with that corresponding to previous years and the assessment of the opportunities for improvement. The main objective is to review the management activities and procedures that affect the environment and the way the port authority handles significant environmental aspects. It has been designed as a "first level" tool: it can be applied in approximately six hours by a non-expert user. It is based on the ISO 14001 vocabulary, requirements and structure, and it can be considered as a first step in the voluntary implementation of an environmental management system for port communities.


Antitumor activity of 7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, CKD602, as a potent DNA topoisomerase I inhibitor.
We developed a novel water-soluble camptothecin analogue, CKD602, and evaluated the inhibition of topoisomerase I and the antitumor activities against mammalian tumor cells and human tumor xenografts. CKD602 was a nanomolar inhibitor of the topoisomerase I enzyme in the cleavable complex assay. CKD602 was found to be 3 times and slightly more potent than topotecan and camptothecin as inhibitors of topoisomerase, respectively. In tumor cell cytotoxicity, CKD602 was more potent than topotecan in 14 out of 26 human cancer cell lines tested, while it was comparable to camptothecin. CKD602 was tested for the in vivo antitumor activity against the human tumor xenograft models. CKD602 was able to induce regression of established HT-29, WIDR and CX-1 colon tumors, LX-1 lung tumor, MX-1 breast tumor and SKOV-3 ovarian tumor as much as 80, 94, 76, 67, 87% and 88%, respectively, with comparable body weight changes to those of topotecan. Also the therapeutic margin (R/Emax: maximum tolerance dose/ED58) of CKD602 was significantly higher than that of topotecan by 4 times. Efficacy was determined at the maximal tolerated dose levels using schedule dependent i.p. administration in mice bearing L1210 leukemia. On a Q4dx4 (every 4 day for 4 doses) schedule, the maximum tolerated dose (MTD) was 25 mg/kg per administration, which caused great weight loss and lethality in < 5% tumor bearing mouse. This schedule brought significant increase in life span (ILS), 212%, with 33% of long-term survivals. The ex vivo antitumor activity of CKD602 was compared with that of topotecan and the mean antitumor index (ATI) values recorded for CKD602 were significantly higher than that noted for topotecan. From these results, CKD602 warrants further clinical investigations as a potent inhibitor of topoisomerase I.


Levels of benzimidazole resistance in Haemonchus contortus and Trichostrongylus colubriformis recorded from an egg hatch test procedure.
A method of using commercially available benzimidazole anthelmintics in an egg hatch test, to record levels of resistance is described. The test shows that a side-resistance is present to all the benzimidazole anthelmintics tested against both Haemonchus contortus and Trichostrongylus colubriformis after selection with thiabendazole. Additional selection on the field resistant strain of H contortus with thiabendazole showed increased levels of resistance to all the compounds tested while similar selection of T colubriformis failed to change the level of resistance after 20 generations. The level of resistance recorded by the egg hatch test in vitro is greater than that recorded for adults in vivo for the CF strain of H contortus and T colubriformis. Problems associated with reading the test are mentioned as are the different levels for the threshold of activity.


Persistence of Symptoms After Total vs Supracervical Hysterectomy in Women with Histopathological Diagnosis of Adenomyosis.
To compare symptom persistence in women with adenomyosis based on retention or removal of the cervix at the time of hysterectomy. Retrospective cohort study and follow-up survey (Canadian Task Force classification xx). Tertiary care academic hospital in Boston, Massachusetts. Women (n = 1580) who underwent laparoscopic hysterectomy for benign indications between 2008 and 2012 at Brigham and Women's Faulkner Hospital and Brigham and Women's Hospital. Retrospective chart review and follow-up survey. Among the 1580 women contacted, 762 (48%) responded to the postoperative symptom resolution survey. Of these 762 women, 623 agreed to participate in the study. Menopausal women or those who had undergone bilateral salpingo-oophorectomy were excluded. Adenomyosis was identified on histopathologic evaluation of the uterus in 171 of the remaining 443 women (39%). Compared with women without adenomyosis, those with adenomyosis were older on average (mean age, 46.6 ± 6.8 years vs 45.0 ± 5.5 years; p = .009) and more likely to report that abnormal bleeding and pain led to their hysterectomy (87.7% vs 79.8%; p = .03 and 64.9% vs 51.4%; p = .009, respectively). The rates of total and supracervical hysterectomies were similar in the 2 groups. Following surgery, women with adenomyosis were less likely than those without adenomyosis to report persistent pain (adjusted odds ratio [aOR], 0.43; 95% confidence interval [CI], 0.20-0.93; p = .03). Persistent bleeding was similar in the 2 groups (aOR, 0.97; 95% CI, 0.49-1.93; p = .94). Among women with adenomyosis, multivariable logistic regression showed no difference in persistence of symptoms with cervical removal or retention at the time of hysterectomy. Compared with women without adenomyosis, those with histopathologically proven adenomyosis were less likely to report persistent pain following hysterectomy. Retention of the cervix does not appear to increase the risk of symptom persistence or postprocedure patient satisfaction.


Diastolic dysfunction and heart failure with a preserved ejection fraction: Relevance in critical illness and anaesthesia.
Epidemiological and clinical studies suggest that HF with a preserved ejection fraction will become the more common form of HF which clinicians will encounter. The spectrum of diastolic disease extends from the asymptomatic phase to fulminant cardiac failure. These patients are commonly encountered in operating rooms and critical care units. A clearer understanding of the underlying pathophysiology and clinical implications of HF with a preserved ejection fraction is fundamental to directing further research and to evaluate interventions. This review highlights the impact of diastolic dysfunction and HF with a preserved ejection fraction during the perioperative period and during critical illness.


Common dermatologic manifestations of cutaneous exposure to petroleum and its derivatives.
Crude petroleum serves as the precursor for thousands of chemicals found in a variety of commercial and industrial products. The authors present a brief background on the composition of petroleum and the production of its derivatives, a description of the common cutaneous manifestations of petroleum derivative exposure, and a review of the treatment options for these diseases.


T11TS Treatment Augments Apoptosis of Glioma Associated Brain Endothelial Cells, Hint Toward Anti-Angiogenic Action in Glioma.
Malignant glioma continues to be a clinical challenge with an urgent need for developing curative therapeutic intervention. Apoptosis induction in tumor-associated endothelial cells represent a central mechanism that counteracts angiogenesis in glioma and other solid tumors. We previously demonstrated that intraperitoneal administration of sheep erythrocyte membrane glycopeptide T11-target structure (T11TS) in rodent glioma model inhibits PI3K/Akt pathway and Raf/MEK/ERK signaling in glioma-associated brain endothelial cells. In the present study, we investigated whether T11TS treatment influence apoptosis signaling in vivo in glioma-associated brain endothelial cells. Annexin-V/PI staining showed that T11TS treatment in glioma-induced rats increases apoptosis of glioma-associated endothelial cells within glioma milieu compared to brain endothelial cells in glioma induced and control groups. Flowcytometric JC-1 assay revealed that T11TS administration triggers loss of mitochondrial membrane potential in glioma-associated brain endothelial cells. Flowcytometry, immunoblotting, and in situ immunofluoresecnt imaging were employed to investigate the effect of T11TS on apoptotic regulatory proteins in brain endothelial cells. T11TS treatment-upmodulated expression of p53, Bax, Fas, FasL, and FADD in glioma associated endothelial cells and downregulated Bcl-2 protein. T11TS therapy induced cytochrome-c release into cytosol, activated caspase -9, 8, 3, and cleaved Bid in glioma associated brain endothelial cells. The study demonstrates that T11TS induces apoptosis in glioma-associated brain endothelial cells via p53 accumulation and activation of intrinsic as well as Fas-dependent extrinsic pathway. The pro-apoptotic action of T11TS on glioma-associated endothelial cells provides crucial insight into how T11TS exerts its anti-angiogenic function in glioma. J. Cell. Physiol. 232: 526-539, 2017. © 2016 Wiley Periodicals, Inc.


Serotype distribution and antimicrobial resistance of Salmonella enterica from patients with gastroenteritis in Crete, Greece.
The aim of the present study was to determine the serotype distribution and the evolution of antimicrobial resistance among Salmonella enterica strains isolated from patients with diarrhea in Crete, Greece, during a 5-year period (2000-2004). Among the 401 S. enterica isolates recovered, serotype Enteritidis was the most prevalent (66.6%), followed by serotype Typhimurium (14.2%). The rates of resistance to ampicillin, amoxicillin-clavulanic acid, gentamicin, chloramphenicol, tetracycline, nalidixic acid and trimethoprim-sulfamethoxazole were 8.5, 7, 0.7, 5.4, 14.2, 2.7 and 2.7%, respectively. A marked decrease in resistance was observed during the study period. Resistance and multidrug resistance was most common in serotype Typhimurium. The extended-spectrum beta-lactamase production observed in one strain of S. enterica serotype Virchow and the reduced ciprofloxacin susceptibility detected in 2.7% of the isolates studied are causes of concern.


Physical Activity in Peri-Urban Communities: Testing Intentional and Implicit Processes within an Ecological Framework.
Given the substantive health inequalities in peri-urban communities and the potential for physical activity to promote health in these communities, identifying modifiable physical activity determinants in this population is important. This study explored effects of the peri-urban environment and psychological constructs on physical activity intentions and behavioural automaticity guided by an integrated theoretical framework. Peri-urban Australians (N = 271) completed self-report measures of environmental (i.e. physical/social environment, and neighbourhood selection), motivational (i.e. autonomous motivation), and social cognition (i.e. attitudes, norms, and perceived behavioural control [PBC]) constructs, past behaviour, intentions, and automaticity. A well-fitting path analytic model revealed that: autonomous motivation predicted all social cognition constructs; subjective norms and PBC, but not attitudes; autonomous motivation predicted intentions and automaticity; and subjective norms and PBC mediated effects of autonomous motivation on intentions. Of the environmental constructs, only neighbourhood selection was related to intentions, mediated by PBC. Autonomous motivation is an important correlate of physical activity intentions and automaticity, and subjective norms and PBC also related to intentions. Individuals perceiving a supportive environment were more likely to report positive PBC and intentions. Targeting change in autonomous motivation, and normative and control beliefs may help enhance physical activity intentions and automaticity in peri-urban communities.


Pharmaceutical interventions in medications prescribed for administration via enteral tubes in a teaching hospital.
to analyze the impact of guidelines regarding errors in medications prescribed for administration through enteral tubes. quantitative study, in three phases, undertaken in internal medicine, neurology and an intensive care unit in a general teaching hospital. In Phase 1, the following was undertaken: a protocol for dilution and unit-dose repackaging and administration for 294 medications via enteral tubes; a decision flowchart; operational-standard procedures for dilution and unit-dose repackaging of oral pharmaceutical forms and for administration of medications through enteral tubes. In phase 2, errors in 872 medications prescribed through enteral tubes, in 293 prescriptions for patients receiving inpatient treatment between March and June, were investigated. This was followed by training of the teams in relation to the guidelines established. In Phase 3, pharmaceutical errors and interventions in 945 medications prescribed through enteral tubes, in 292 prescriptions of patients receiving inpatient treatment between August and September, were investigated prospectively. The data collected, in a structured questionnaire, were compiled in the Microsoft Office Excel(r) program, and frequencies were calculated. 786 errors were observed, 63.9% (502) in Phase 2, and 36.1% (284) in Phase 3. In Phase 3, a reduction was ascertained in the frequency of prescription of medications delivered via enteral tubes, medications which were contraindicated, and those for which information was not available. guidelines and pharmaceutical interventions were determined in the prevention of errors involving medications delivered through enteral tubes. analisar o impacto de diretrizes sobre erros em medicamentos prescritos para administração via sondas enterais. estudo quantitativo, em três fases, realizado em clínica médica, neurologia e unidade de terapia intensiva de hospital geral universitário. Na Fase 1 elaborou-se: protocolo de diluição, unitarização - transformação e administração para 294 medicamentos via sondas enterais; fluxograma decisório; procedimentos operacionais-padrão de diluição e unitarização de formas farmacêuticas orais e de administração de medicamentos via sondas enterais. Na Fase 2 investigou-se, retrospectivamente, erros em 872 medicamentos prescritos via sondas enterais, em 293 prescrições de pacientes internados de março a junho. Seguiu-se capacitação das equipes sobre diretrizes estabelecidas. Na Fase 3 investigou-se, prospectivamente, erros e intervenções farmacêuticas em 945 medicamentos prescritos via sondas enterais, em 292 prescrições de pacientes internados de agosto a setembro. Dados coletados, em formulário estruturado, foram compilados no programa Microsoft Office Excel(r) e calculadas as frequências. foram observados 786 erros, 63,9% (502) na Fase 2 e 36,1% (284) na Fase 3. Na Fase 3 verificou-se redução na frequência de prescrição de medicamentos, via sondas enterais, contraindicados e sem informações disponíveis. diretrizes e intervenções farmacêuticas foram determinantes na prevenção dos erros de medicamentos via sondas enterais. analizar el impacto de directrices sobre errores en medicamentos prescritos para administración vía sondas enterales. estudio cuantitativo, en tres fases, realizado en una clínica médica-neurología y en unidad de terapia intensiva de un hospital general universitario. En la Fase 1 se elaboró: protocolo de dilución, reenvasado - transformación y administración para 294 medicamentos vía sondas enterales; diagrama de flujo de decisión; procedimientos operacionales estándar de dilución y reenvasado - transformación de formas farmacéuticas orales y de administración de medicamentos vía sondas enterales. En la Fase 2 se investigó, retrospectivamente, errores en 872 medicamentos prescritos vía sondas enterales, en 293 prescripciones de pacientes internados de marzo a junio. La continuación, capacitación de los equipos sobre directrices establecidas. En la Fase 3 se investigó, prospectivamente, errores e intervenciones farmacéuticas en 945 medicamentos prescritos vía sondas enterales, en 292 prescripciones de pacientes internados de agosto a septiembre. Datos fueron colectados en un formulario estructurado, compilados en el programa Microsoft Office Excel(r) y se calcularon las frecuencias. se observaron 786 errores, 63,9% (502) en la Fase 2 y 36,1% (284) en la Fase 3. En la Fase 3 se verificó una reducción en la frecuencia de prescripción de medicamentos, vía sondas enterales, contraindicados y sin informaciones disponibles. las directrices e intervenciones farmacéuticas fueron determinantes en la prevención de los errores de medicamentos vía sondas enterales.


Beyond physiological hypoarousal: the role of life stress and callous-unemotional traits in incarcerated adolescent males.
The development of antisocial behavior in youth has been examined with neurobiological theories that suggest that adolescents who are less responsive to their environments are less likely to develop empathy in the absence of extant physiological arousal. However, little attention is paid to these individuals' social context. Individuals with adverse early experiences can also exhibit attenuated physiological arousal. The current investigation examines whether psychopathic symptoms or life stress exposure is associated with cortisol and its diurnal rhythm within 50 incarcerated adolescent boys (14-18years old). Ten saliva cortisol samples were collected 1-2weeks after admission to a maximum-security juvenile facility. Hierarchical Linear Modeling distinguished waking cortisol levels, the awakening response (CAR) and the diurnal rhythm. Multiple interviews and self-report measures of CU traits and stressor exposure were collected. Boys with higher levels of CU traits or greater life stress exposure had flat diurnal rhythms and a steeper awakening response in analyses with lifetime stress exposure specifically. Nonetheless, boys who were elevated on both CU traits and prior stress exposure had steeper diurnal rhythms. These results extend neurobiological theories of cortisol and illustrate that boys with the combination of severe stress with CU traits have a unique physiological profile.


Mechanisms for multiple resistances in field populations of rice stem borer, Chilo suppressalis (Lepidoptera: Crambidae) from Sichuan Province, China.
Chilo suppressalis Walker (Lepidoptera: Crambidae) is a widely destructive pest occurring in rice, particularly in the rice-growing regions of Asia. In recent years, C. suppressalis has developed resistance to several insecticides because of the extensive use of insecticides. The resistance levels to four insecticides were determined among populations from different regions of Sichuan Province, China, using a drop-method bioassay. Based on LC50 values of a laboratory susceptible strain, all field populations showed moderate level of resistance to triazophos (23.9- to 83.5-fold) and were either susceptible or had a low level of resistance to abamectin (2.1- to 5.8-fold). All field-collected populations had a low or moderate level of resistance to chlorpyrifos (1.7- to 47.1-fold) and monosultap (2.7- to 13.5-fold). The synergism experiment indicated that the resistance of the XW19 to triazophos may be associated with cytochrome P450 monooxygenases (P450s), with the highest synergistic ratio (SR) of 3.05-fold and increased ratio (IR) of 2.28-fold for piperonylbutoxide (PBO). The P450 activity of the TJ19 population was the greatest among the six field populations. Moreover, the relative expression levels of four resistance-related P450 genes were detected with qRT-PCR, and the results indicated that CYP324A12, CYP321F3 and CYP9A68 were overexpressed in the resistant population, especially in the XW19 population (by 1.2-, 3.4 -, and 18.0-fold, respectively). In addition, the relative expression levels of CYP9A68 among the CZ19 and TJ19 populations were also enhanced 10.5- and 24.9-fold, respectively. These results suggested that CYP324A12, CYP321F3 and CYP9A68 may be related to the resistance development of C. suppressalis to triazophos.


Mapping conformational ensembles of aβ oligomers in molecular dynamics simulations.
Although the oligomers formed by Aβ peptides appear to be the primary cytotoxic species in Alzheimer's disease, detailed information about their structures appears to be lacking. In this article, we use exhaustive replica exchange molecular dynamics and an implicit solvent united-atom model to study the structural properties of Aβ monomers, dimers, and tetramers. Our analysis suggests that the conformational ensembles of Aβ dimers and tetramers are very similar, but sharply distinct from those sampled by the monomers. The key conformational difference between monomers and oligomers is the formation of β-structure in the oligomers occurring together with the loss of intrapeptide interactions and helix structure. Our simulations indicate that, independent of oligomer order, the Aβ aggregation interface is largely confined to the sequence region 10-23, which forms the bulk of interpeptide interactions. We show that the fractions of β structure computed in our simulations and measured experimentally are in good agreement.


Nafamostat has anti-asthmatic effects associated with suppressed pro-inflammatory gene expression, eosinophil infiltration and airway hyperreactivity.
Asthma is characterized by an imbalance between proteases and their inhibitors. Hence, an attractive therapeutic option could be to interfere with asthma-associated proteases. Here we exploited this option by assessing the impact of nafamostat, a serine protease inhibitor known to neutralize mast cell tryptase. Nafamostat was administered in a mouse model for asthma based on sensitization by house dust mite (HDM) extract, followed by the assessment of effects on airway hyperreactivity, inflammatory parameters and gene expression. We show that nafamostat efficiently suppressed the airway hyperreactivity in HDM-sensitized mice. This was accompanied by reduced infiltration of eosinophils and lymphocytes to the airways, and by lower levels of pro-inflammatory compounds within the airway lumen. Further, nafamostat had a dampening impact on goblet cell hyperplasia and smooth muscle layer thickening in the lungs of HDM-sensitized animals. To obtain deeper insight into the underlying mechanisms, a transcriptomic analysis was conducted. This revealed, as expected, that the HDM sensitization caused an upregulated expression of numerous pro-inflammatory genes. Further, the transcriptomic analysis showed that nafamostat suppressed the levels of multiple pro-inflammatory genes, with a particular impact on genes related to asthma. Taken together, this study provides extensive insight into the ameliorating effect of nafamostat on experimental asthma, and our findings can thereby provide a basis for the further evaluation of nafamostat as a potential therapeutic agent in human asthma.


Xanthine oxidase inhibitor allopurinol improves atrial electrical remodeling in diabetic rats by inhibiting CaMKII/NCX signaling.
Atrial fibrillation (AF) is a common arrhythmia which is associated with higher risk of stroke, heart failure and all-cause mortality. Abnormal Ca2+ handling in diabetes mellitus (DM) can cause delayed depolarization involved with increased NCX activity. Complicated mechanisms are involved in atrial remodeling, of which CaMKII may be a key node signal. Therefore, we intend to explore whether CaMKII activation induces atrial electrical remodeling by regulating NCX expression in this study. Adult male SD rats were used to establish a diabetic rat model, divided into three groups: the control group, DM group and allopurinol group. Hemodynamic and ECG indicators were recorded, after which electrophysiological studies were conducted. The protein expression of CaMKII, p-CaMKII, XO, MnSOD and NCX was measured by Western blot and immunohistochemistry. H&E and Masson staining were applied for observing myocardial fibrosis. HL-1 cells were cultured for the measurement of ROS generation. The arrangement of atrial myocytes was disordered and the collagen volume fraction of the atrium tissue was elevated in the DM group compared with the control group, and improved by allopurinol. Higher incidence of inducible AF, reduced conduction velocity and higher conduction inhomogeneity were observed in diabetic rats. These electrophysiological abnormalities were accompanied by higher oxidative stress and protein expression of p-CaMKII and NCX. Allopurinol prevented the development of these abnormal changes. Allopurinol can improve atrial electrical remodeling by inhibiting CaMKII activity and protein expression of NCX. These data indicate xanthine oxidase inhibition can reduce oxidative stress and ameliorate atrial electrical remodeling.


Resolution of a gold latensification-elon ascorbic acid developer for Ilford L4 emulsion.
The electron-microscopical autoradiographical resolution of a gold latensification-elon ascorbic acid (GEA) developer for Ilford L4 emulsion was determined experimentally, using radioactive line sources of tritiated albumin (Heijnen and Geuze, 1977). For sections with a thickness of 62 nm (SD +/- 11), which were covered with a carbon layer about 5 nm thick and a slightly overlapping monolayer of L4 silver bromide crystals, the measured half-distance (HD) of resolution was 115 nm. This improvement in resolution, the high efficiency of the GEA developer for L4 emulsion (Wisse and Tates, 1968), and the excellent visibility of the cellular structures under the small silver grains, mean that the L4-GEA combination deserves preverence as a method for quantitative electron-microscopical autoradiography.


Co-curing preparation of flame retardant and smoke-suppressive epoxy resin with a novel phosphorus-containing ionic liquid.
Phosphorus-containing ionic liquid derivatives have been proven to be effective flame retardants for epoxy resin (EP). Flame retardants can accelerate the curing process and improve flame retardancy and smoke suppression of EP composites, which is challenging. In this paper, a novel phosphorus-containing ionic liquid (TPP-PF6) was synthesized and used both as a co-curing agent with 4,4'-diaminodiphenylmethane (DDM) and as a highly effective flame retardant for EP. It has been found that TPP-PF6 was conducive to improve the char formation of EP to inhibit the smoke release at high temperatures. For EP/TPP-PF6 composites, the flame-retardant performance was enhanced rapidly with the increase of TPP-PF6. With only 2 wt% of TPP-PF6, EP/2.0TPP-PF6 reached a UL-94 V-0 rating and a limiting oxygen index of 30.3%. The peak heat release rate, total heat release, and total smoke production values of EP/2.0TPP-PF6 were reduced by 36.32%, 45.81%, and 15.1% compared with those of pure EP, respectively. The thermal degradation products and flame retardant mechanism in gas and condensed phases were studied. It was found that TPP-PF6 had flame retardant effect in the barrier effect of the condensed phase and the quenching effect of the gas phase. This work explores the high-efficiency flame retardant and smoke-suppressive structures with co-curing properties for EP, thus promoting the wide application of EP materials.


Evaluation of two devices for self-measurement of blood pressure according to the international protocol: the Omron M5-I and the Omron 705IT.
Two devices for self-measurement of blood pressure at the brachial artery-the Omron M5-I and the Omron 705IT-were evaluated according to the international protocol of the European Society of Hypertension. The international validation protocol is divided into two phases: the first phase is performed on 15 selected subjects and if the device passes this phase, 18 supplementary subjects are included making a total number of 33 subjects on which the final validation is performed. For each subject, four blood pressure (BP) measurements were performed simultaneously by two trained observers using mercury sphygmomanometers alternately with three measurements by the tested device. The difference between the BP value given by the device and that obtained by the two observers (mean of the two observers) was calculated for each measure. The 99 differences were classified into categories (<or=5, <or=10, <or=15 mmHg). The number of differences in each category was compared to the number required by the international protocol. An individual analysis was then done to determine for each subject the number of comparisons <or=5 mmHg. At least 22 of the 33 subjects should have two of their three comparisons <or=5 mmHg. The two tested devices passed the first phase of the validation process. For the second phase, the average differences between the device and mercury sphygmomanometer readings were -0.9+/-5.8 and -0.8+/-4.8 mmHg for systolic blood pressure (SBP) and diastolic blood pressure (DBP) respectively for the Omron M5-I device and -0.2+/-4.5 and -2.0+/-4.8 mmHg for the Omron 705IT device. Readings for the two devices differing by less than 5, 10 and 15 mmHg for systolic and diastolic values fulfil the recommendation criteria of the international protocol as well as the individual analysis. The Omron M-5I and the Omron 705IT devices pass the validation recommendations of the international protocol.


[Bacterial meningitis and Pseudomonas aeruginosa: apropos of a case].
Meningitis caused by gram-negative bacilli increased since the 1970, with a higher incidence in small children. Within this group of infections, the meningitis caused by Pseudomonas sp is rare. The case of a 54-year-old patient with a clinical picture of meningitis is reported. Pseudomonas aeruginosa was isolated from the cerebrospinal fluid. The meningitis caused by Pseudomonas aeruginosa should be taken into consideration because of the severity of the clinical picture and the high mortality and increasing strain resistance.


Lipid targets in clinical practice: successes, failures and lessons to be learned.
Optimal risk factor control is integral to managing patients with proven coronary heart disease (CHD+) and for those at risk of coronary heart disease (CHD-). The primary aim of the study was to assess the success rate of reaching lipid risk factor targets in a multiple risk factor clinic. A retrospective audit was conducted in 488 patients (CHD+, n = 112; CHD-, n = 376) who attended the Cardiovascular Risk Factor Clinic at Tallaght Hospital, Dublin in 2009 and 2010. Risk factor targets achieved in CHD+ and CHD- patients were LDLc (54/62 %), HDLc (67/67 %), systolic blood pressure (35/38 %), diastolic blood pressure (82/75 %), smoking cessation (27/26 %), BMI ≤ 30 (39/50 %) and normal waist circumference (27/39 %). Patients not reaching LDLc targets were found to be receiving fewer lipid-lowering drugs and having higher LDL levels at the initial clinic visit than those reaching targets. This retrospective audit highlights gaps in achieving target lipid levels at a multiple risk factor clinic level. High initial LDLc levels and lack of drug titration are evident. Guideline changes, staff rotation, clinic visit frequency and multiplicity of targets may be contributory. More emphasis needs to be placed on education and algorithm-based strategies to achieve better risk factor control.


K-stimulated release of leu- and met-enkephalin from rat striatal slices: lack of effect of morphine and naloxone.
The release of leu- and met-enkephalin from rat striatal slices was determined by superfusing the slices in vitro and running the superfusates directly over columns of Amberlite XAD-2 from which the peptides were eluted with methanol and measured by radioimmunoassay. Depolarization by high K concentrations increased the release of both pentapeptides many fold; the degree of increase, however, depended in part on the length of time chosen for the stimulation period, suggesting that the stimulation effect was very short lived. The stimulated release of both peptides (but not the resting release) was at least partially dependent on Ca in the medium and was totally inhibited by high Mg concentrations. Selected concentrations of naloxone and morphine in the superfusing medium had no effect on the resting or stimulated release of the peptides. The results support the hypothesis that these peptides serve as neurotransmitters in the striatum, but autoregulation of their release by morphine and naloxone could not be demonstrated.


The vectorcardiogram in 4 children undergoing the arterial switch repair.
Four children with complete transposition (concordant atrioventricular and discordant ventriculo-arterial connections), aged 1.2 to 16.4 years, underwent a delayed repair by the arterial switch procedure from March 1985 to October 1986. Three children had undergone previous atrial diversion repairs in early childhood. Two of these children had developed right ventricular dysfunction with tricuspid incompetence as well as having recurrent and symptomatic supraventricular tachyarrhythmias. They underwent banding of the pulmonary trunk 0.7 and 1 year prior to the final repair. The third child had dynamic obstruction of the left ventricular outflow tract and prior banding was not performed. A fourth child had right ventricular dysfunction on initial assessment in early infancy and then had banding of the pulmonary trunk. Two patients survived the arterial switch operation. Vectorcardiograms were performed on these 4 children before arterial switch repair. The left maximal spatial voltage did not correlate with elevated left to right ventricular pressure ratio at cardiac catheterization before arterial switch repair nor did it relate to survival after operation. The horizontal loop was clockwise in all patients preoperatively. The vectorcardiogram in these children was not a useful indicator that the left ventricle was suitably prepared for the arterial switch repair.


Harvesting Chlorella vulgaris by magnetic flocculation using Fe₃O₄ coating with polyaluminium chloride and polyacrylamide.
The harvesting of Chlorella vulgaris was investigated by magnetic flocculation, where the natural magnetite was used as magnetic seeds and the polyaluminium chloride (PACl) and polyacrylamide (PAM) were used as the coating polymer on the Fe3O4 surface. The composite modes of PACl, PAM, and Fe3O4 and their effects on harvesting were studied. The results showed that adding the composite PACl/Fe3O4 first (at (0.625 mmol Al/L)/(10 g/L)) followed by the addition PAM (at 3mg/L) was the optimum dosing strategy. Following this strategy, 99% of cells could be harvested in less than 0.5 min, and it could overcome negative impacts from pH and algal organic matter. Compared to PACl, ζ-potentials of PACl/Fe3O4 were found to be increased substantially from -4.9-8.5 mV to 1.5-19.5 mV at pH range 2.1-12.3. The charge neutralization of PACl/Fe3O4 and sweeping of PAM play an important role in magnetic harvesting of microalgal cells.


Comparison of systematic mediastinal lymph node dissection versus systematic sampling for lung cancer staging and completeness of surgery.
This self-controlled prospective study was designed to investigate the efficacy of systematic sampling (SS), compared with systematic mediastinal lymph node dissection (SMLD), for pathologic staging and completeness of surgery. Over a period of 11 mo, 110 patients with lung cancer were enlisted and treated by pulmonary resection. Surgeons systematically sampled mediastinal lymph nodes prior to pulmonary resection, and after pulmonary resection SMLD was performed to each patient using Mountain's procedure [1]. After SMLD, pN status was classified as N0 in 57 cases, N1 in 27, and N2 in 26. SS detected 38.3% of pooled nodes and 37.6% of pooled positive nodes collected from SMLD. Pathologic diagnosis after SS was understaged in nine cases (8.2%) compared with staging after SMLD. However, surgery was incomplete in 24 cases (21.8%) if SMLD was not performed after sampling. Negative predictive value for SS was 86.8% on the right side, and 95.0% on the left. Three categories were generated according to pN status: negative nodes in SS and additional negative nodes from SMLD [S(-)D(-)], negative nodes in SS but additional positive nodes from SMLD [S(-)D(+)], and positive nodes in SS [S(+)D(+)]. cN2 (P=0.000) and CEA level (P=0.001) were correlated with pN status. There was significant overall survival difference between non-N2 group and N2 group (P=0.002). SMLD may harvest about three times of mediastinal lymph nodes compared with SS. SS is more likely to affect the completeness of surgery instead of underrating pathologic stage.


Inhibition of clathrin by pitstop 2 activates the spindle assembly checkpoint and induces cell death in dividing HeLa cancer cells.
During metaphase clathrin stabilises the mitotic spindle kinetochore (K)-fibres. Many anti-mitotic compounds target microtubule dynamics. Pitstop 2™ is the first small molecule inhibitor of clathrin terminal domain and inhibits clathrin-mediated endocytosis. We investigated its effects on a second function for clathrin in mitosis. Pitstop 2 did not impair clathrin recruitment to the spindle but disrupted its function once stationed there. Pitstop 2 trapped HeLa cells in metaphase through loss of mitotic spindle integrity and activation of the spindle assembly checkpoint, phenocopying clathrin depletion and aurora A kinase inhibition. Pitstop 2 is therefore a new tool for investigating clathrin spindle dynamics. Pitstop 2 reduced viability in dividing HeLa cells, without affecting dividing non-cancerous NIH3T3 cells, suggesting that clathrin is a possible novel anti-mitotic drug target.


Total internal reflection Raman spectroscopy of barley leaf epicuticular waxes in vivo.
The use of total internal reflection (TIR)-Raman spectroscopy to examine cuticular wax layers in vivo at the surface of barley leaves (Hordeum vulgare L. cultivar Pastoral) is demonstrated. The limited penetration depth (40 nm) of the evanescent wave compared to the thickness of the wax layer eliminates problems arising from fluorescence from underlying pigments. Epicuticular wax crystals are observed to be more crystalline than the amorphous wax layer, which is analysed after removal of the wax crystals by cellulose acetate stripping. Carotenoids are detected as trace species in the cuticular waxes.


Four hydrophobic amino acid residues in the C-terminal effector domain of the yeast Mig1p repressor are important for its in vivo activity.
The Mig1 repressor is a zinc finger protein that mediates glucose repression in yeast. Previous work in Saccharomyces cerevisiae has shown that two domains in Miglp are required for repression: the N-terminal zinc finger region and a C-terminal effector domain. Both domains are also conserved in Miglp homologs from the distantly related yeasts Kluyveromyces lactis and K. marxianus, and these Mig1 proteins can fully replace the endogenous Mig1p in S. cerevisiae. We have now made a detailed analysis of the conserved C-terminal effector domain in Mig1p from K. marxianus, using expression in S. cerevisiae to monitor its function. First, a series of small deletions were made within the effector domain. Second, an alanine scan mutagenesis was carried out across the effector domain. Third, double, triple and quadruple mutants were made that affect certain residues within the effector domain. Our results show that four conserved residues within the effector domain, three leucines and one isoleucine, are particularly important for its function in vivo. The analysis further revealed that while the C-terminal effector domain of KmMig1p mediates a seven- to nine-fold repression of the reporter gene, a five- to sixfold residual effect also exists that is independent of the C-terminal effector domain. Similar results were obtained when the corresponding mutations were made in ScMig1p. Moreover, we found that mutations in these residues affect the interaction between Mig1p and the general corepressor subunit Cyc8p (Ssn6p). Modeling of the C-terminal effector domain using a protein of known structure suggests that it may be folded into an alpha-helix.


The role of Gata3 in renin cell identity.
Renin cells are precursors for other cell types in the kidney and show high plasticity in postnatal life in response to challenges to homeostasis. Our previous single-cell RNA-sequencing studies revealed that the dual zinc-finger transcription factor Gata3, which is important for cell lineage commitment and differentiation, is expressed in mouse renin cells under normal conditions and homeostatic threats. We identified a potential Gata3-binding site upstream of the renin gene leading us to hypothesize that Gata3 is essential for renin cell identity. We studied adult mice with conditional deletion of Gata3 in renin cells: Gata3fl/fl;Ren1dCre/+ (Gata3-cKO) and control Gata3fl/fl;Ren1d+/+ counterparts. Gata3 immunostaining revealed that Gata3-cKO mice had significantly reduced Gata3 expression in juxtaglomerular, mesangial, and smooth muscle cells, indicating a high degree of deletion of Gata3 in renin lineage cells. Gata3-cKO mice exhibited a significant increase in blood urea nitrogen, suggesting hypovolemia and/or compromised renal function. By immunostaining, renin-expressing cells appeared very thin compared with their normal plump shape in control mice. Renin cells were ectopically localized to Bowman's capsule in some glomeruli, and there was aberrant expression of actin-α2 signals in the mesangium, interstitium, and Bowman's capsule in Gata3-cKO mice. Distal tubules showed dilated morphology with visible intraluminal casts. Under physiological threat, Gata3-cKO mice exhibited a lower increase in mRNA levels than controls. Hematoxylin-eosin, periodic acid-Schiff, and Masson's trichrome staining showed increased glomerular fusion, absent cubical epithelial cells in Bowman's capsule, intraglomerular aneurysms, and tubular dilation. In conclusion, our results indicate that Gata3 is crucial to the identity of cells of the renin lineage.NEW & NOTEWORTHY Gata3, a dual zinc-finger transcription factor, is responsible for the identity and localization of renin cells in the kidney. Mice with a conditional deletion of Gata3 in renin lineage cells have abnormal kidneys with juxtaglomerular cells that lose their characteristic location and are misplaced outside and around arterioles and glomeruli. The fundamental role of Gata3 in renin cell development offers a new model to understand how transcription factors control cell location, function, and pathology.


Oxytocin treatment for core symptoms in children with autism spectrum disorder: a systematic review and meta-analysis.
The purpose of this article is to examine the efficacy of oxytocin in treating core symptoms of autism spectrum disorder (ASD) with children. A systematic literature search was conducted to identify randomized controlled trials (RCTs) of oxytocin for the treatment of core symptoms in children with ASD. The search included studies published between January 1, 1999 and March 15, 2023, that were randomized, single or double-blinded, and included a placebo control group. Standard screening rules were applied to select relevant studies, resulting in the inclusion of five RCTs involving 486 children with ASD. Ultimately, a total of five RCTs, involving 486 children with ASD, were included in the review using standard screening rules.One of the included studies demonstrated a statistically significant improvement in Social Responsiveness Scale (SRS) and Repetitive Behavior Scale-Revised (RBS) scores when children with ASD were treated with oxytocin (24 IU/2 days for 6 weeks). The improvement in core symptoms persisted at the 6-month follow-up. The meta-analysis findings suggested that oxytocin might have a moderate effect in improving the core symptom of narrow interests and repetitive stereotyped behaviors in children with ASD. While the therapeutic value of oxytocin in treating core symptoms of ASD in children is not fully established, the results of this meta-analysis indicate a potential moderate effect. However, further studies with larger sample sizes and more robust RCTs are needed to directly demonstrate the efficacy of oxytocin. Future research should also focus on effect size and outcome evaluation accuracy while minimizing bias in RCT experiments.


Exposure of patients to low doses of X-radiation during neuro-interventional imaging and procedures: Dose estimation and analysis of γ-H2AX foci and gene expression in blood lymphocytes.
Radiation has widespread applications in medicine. However, despite the benefits of medical radiation exposures, adverse long-term health effects are cause for concern. Protein and gene biomarkers are early indicators of cellular response after low-dose exposure. We examined DNA damage by quantifying γ-H2AX foci and expression of twelve candidate genes in the blood lymphocytes of patients exposed to low doses of X-radiation during neuro-interventional procedures. Entrance surface dose (ESD; 10.92-1062.55 mGy) was measured by thermoluminescence dosimetry (TLD). Absorbed dose was estimated using γ-H2AX focus frequency and gene expression, with in vitro dose-response curves generated for the same biomarkers. γ-H2AX foci in post-exposure samples were significantly higher than in pre-exposure samples. Among the genes analysed, FDXR, ATM, BCL2, MDM2, TNFSF9, and PCNA showed increased expression; CDKN1A, DDB2, SESN1, BAX, and TNFRSF10B showed unchanged or decreased expression. Absorbed dose, estimated based on γ-H2AX focus frequency and gene expression changes, did not show any correlation with measured ESD. Patients undergoing interventional procedures receive considerable radiation doses, resulting in DNA damage and altered gene expression. Medical procedures should be carried out using the lowest radiation doses possible without compromising treatment.


Associations between school-related factors and mental health among transgender and gender diverse youth.
Transgender and gender diverse youth (TGD) report high rates of mental health concerns. However, there is reason to expect that among TGD youth there is variation in mental health experiences related to specific aspects of gender identity. Furthermore, although certain school characteristics are related to improved mental health for sexual minority youth, it is unclear whether the same school characteristics are associated with improved mental health for TGD youth and whether gender identity moderates the associations between school characteristics and mental health. Using baseline data from Project AVANT, a longitudinal study of TGD youth ages 14-18 years in the United States (N = 252), we report on several mental health outcomes (i.e., depression, anxiety, nonsuicidal self-injury, and PTSD), with attention to differences by gender identity. Secondly, we examined associations of three protective school-related factors (i.e., school-connectedness, presence of a Gay-Straight or Gender-Sexuality Alliance [GSA], and state mandated protections for sexual and gender minority students) with TGD youth mental health. TGD youth reported elevated levels of anxious and depressive symptoms, with nonbinary youth assigned female at birth reporting higher mean depressive symptoms relative to transgender females. Among the aggregate sample of TGD youth, 69.9% reported clinically significant anxiety, 57.9% reported clinically significant depression, 56.7% reported nonsuicidal self-injury, and 46.4% met screening criteria for posttraumatic stress disorder. Despite a small effect size, greater school-connectedness was significantly associated with fewer mental health concerns and gender identity moderated the association between school-connectedness and number of anxiety symptoms. Gender identity also moderated the association between presence of a GSA and number of anxious symptoms, depressive symptoms, and clinically significant depression, respectively. No significant associations of state-level protections and mental health outcomes were detected. Findings highlight the importance of improving mental health and fostering GSA-engagement and school-connectedness among TGD youth. Implications for school psychologists are discussed.


Pharmacokinetics of atenolol in patients with renal impairment.
The pharmacokinetics of atenolol, a new cardioselective beta-adrenoceptor blocking agent, were determined following both acute and chronic dosing in 33 hypertensive patients with widely differing levels of renal impairment. In patients with normal renal function the atenolol half-life was calculated to be about six hours following single 100 mg oral doses. This value increased markedly in patients with renal insufficiency and the blood clearance of atenolol was found to have a significant correlation with the glomerular filtration rate. This demonstrated the importance of the kidneys in the elimination of the drug. After 8 weeks oral treatment with atenolol (100 mg twice daily) a significant decrease in blood pressure, heart rate and plasma renin activity was observed, but no correlation was established between the blood levels of atenolol and any of its pharmacodynamic effects. A positive correlation was found however between the anti-hypertensive action of atenolol and the pretreatment value of the plasma renin activity.


Thioredoxin upregulation by 5-aminolaevulinic acid-based photodynamic therapy in human skin squamous cell carcinoma cell line.
5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT) is widely performed in the clinical setting for superficial skin cancers, giving favorable results, but residual tumor and recurrence occur occasionally. Thioredoxin is a common antioxidant that suppresses apoptosis and facilitates cell growth. We investigated the expression of thioredoxin following ALA-PDT in human skin squamous cell carcinoma cell line, HSC-5. ALA-PDT was performed in HSC-5 cells using low-dose (5 J/cm(2), 100 mW/cm(2)) or high-dose (30 J/cm(2), 100 mW/cm(2)) irradiation, and the expression of thioredoxin was measured by Western blotting. An MTT assay was used to assess cell growth following a low dose of multiple irradiations. Cell death was examined by Western blotting for caspase-3 and PARP. Immunofluorescence double staining using annexin V and propidium iodine was also performed. Expression of thioredoxin was only observed following low-dose exposure ALA-PDT. Multiple low-dose exposure ALA-PDT significantly proliferated cell growth. With high-dose exposure ALA-PDT, caspase-3 and PARP expression were seen, and cell death due to apoptosis and/or necrosis was observed, but thioredoxin was barely detected. Low-dose exposure ALA-PDT increased the expression of thioredoxin and facilitated the growth of HSC-5 cells.


Gaseous carbon dioxide and methane, as well as dissolved organic carbon losses from a small temperate wetland under a changing climate.
Temperate forests can contain large numbers of wetlands located in areas of low relief and poor drainage. These wetlands can make a large contribution to the dissolved organic carbon (DOC) load of streams and rivers draining the forests, as well as the exchange of methane (CH4) and carbon dioxide (CO2) with the atmosphere. We studied the carbon budget of a small wetland, located in Kejimkujik National Park, Nova Scotia, Canada. The study wetland was the Pine Marten Brook site, a poor fen draining a mixed hardwood-softwood forest. We studied the loss of DOC from the wetland via the outlet stream from 1990 to 1999 and related this to climatic and hydrologic variables. We added the DOC export information to information from a previously published model describing CH4 and CO2 fluxes from the wetland as a function of precipitation and temperature, and generated a new synthesis of the major C losses from the wetland. We show that current annual C losses from this wetland amount to 0.6% of its total C mass. We then predicted that under climate changes caused by a doubling of atmospheric CO2 expected between 2040 and 2050, total C loss from the wetland will almost double to 1.1% of total biomass. This may convert this wetland from what we assume is currently a passive C storage area to an active source of greenhouse gases.


Pulmonary function at 1 year of age in survivors of neonatal respiratory distress: a multivariate analysis of factors associated with sequelae.
We studied pulmonary function 1 year after neonatal respiratory distress (RD) in 54 infants who had been treated at birth in the same neonatal intensive care unit. RD was related to hyaline membrane disease in 36 cases (group I) and to other causes in 18 cases (group II). Compared with predicted values, dynamic lung compliance (CL) was lower (less than -2 SD) and total pulmonary resistance (RL) was higher (+2 SD) in 18 (33%) and 12 (22%) infants, respectively. The relationships between these functional abnormalities at 1 year of age and the characteristics of the neonatal respiratory disease were assessed using a multifactorial analysis (multiple correspondences analysis). We found that elevated RL (greater than +2 SD) at 1 year of age was very significantly related with hyaline membrane disease, involving both high rate of positive pressure ventilation and prolonged intubation, and with the presence of both tachypnea and abnormal chest X rays at the time of discharge. Compared with elevated RL, the relationships between low CL (less than -2 SD) and the same neonatal characteristics were less significant; in particular, there was no strong link between low CL and hyaline membrane disease. Finally, birth before 30 weeks gestation was an index of severity.


Conformational equilibria in the gamma chain COOH terminus of human fibrinogen.
The conformations of the gamma chain COOH terminus of intact fibrinogen and various fragments containing this region have been compared by an immunochemical analysis. Location of a major epitope in the sequence gamma 391-405 was successfully predicted from a hydrophobicity profile. An antibody population specific for the native epitope within the gamma 391-405 segment was isolated by immunoadsorption. Between 19.2 and 22.8% of antibodies were obtained from three different antisera, indicating that this region represents one of the major epitopes of native fibrinogen. Anti-gamma 391-405(N) antibodies were used to determine the value of Kconf, the equilibrium constant for the interconversion of the non-native and native conformations of this epitope. The measurements were done using native fibrinogen, fragments D1 and DD, gamma chain, and gamma 391-405. In addition, the effect of 5 M guanidine HCl on the conformation of fragments D1 and DD, which is known to abolish their antipolymerizing activity, was studied. Radioiodinated fibrinogen was used in the determination of Kconf, CI50%, and CIs (quantitative analytical parameters calculated from competitive inhibition radioimmunoassays) by measuring the competition between 125I-fibrinogen and the fibrinogen derivatives under study for binding to the immunochemically purified antibody. The measurements indicated that the epitope is unperturbed by iodination of fibrinogen and that 38.5% of fragment D1, 8.9% of fragment DD, 3.6% of the gamma chain, and less than 0.008% of the gamma 391-405 molecules adopt in aqueous solution the native conformation within the epitope. Denaturation of fragment D1 with 5 M guanidine HCl affected only slightly the conformation of this gamma chain determinant. More significant changes in the conformation were observed when fragment DD was denatured. The results suggest that long-range interactions are necessary for the stabilization of the native structure in the region of fibrinogen that interacts with the antibody and which is in close vicinity to the polymerization site, cross-linking site, and platelet recognition site.


Evaluation of water quality for agricultural suitability in the Benslimane region, Morocco.
Morocco is basically a semiarid country with limited rainfall reducing the opportunities for rainfed agriculture. For feeding its ever growing population, irrigation is required. This study aims to evaluate the groundwater quality for irrigation in the Benslimane region by studying the main influencing chemical elements and characteristics. The main purpose is to provide the farmers and agricultural developers with a clear comprehension of the groundwater status. We focused on the determination and statistical analysis of physicochemical parameters and major elements (electrical conductivity, pH, Na+, K+,Ca2+, Mg2+, Cl-, SO42-, CO32-, and HCO3-) for 120 samples and the derivation of water quality indices like SAR, %Na, RSC, PI, KR, and MAR, along with graphical approaches such as Wilcox's and Richards's diagrams. Factors affecting groundwater hydrochemistry and quality were also discussed. The results show generally alkaline and shallow waters, with the majority of the samples belonging to the Na-Cl facies. Rock alteration, dissolution, ion exchange, evaporation, and anthropogenic activity are the main factors controlling water chemistry. Most prospected wells indicate high salinity problems due to salt water intrusion. With regard to the suitability of groundwater for irrigation, the majority of wells is of medium to poor quality and is therefore unsuitable. These types of water are found throughout the area, with a significant dominance on the coastal zone. The long-term use of this groundwater would therefore have negative impacts on soil quality and the sustainability of agricultural production. Therefore, we recommend proper agricultural management and irrigation practices in the Benslimane region, in order to increase agricultural production while preserving water and soil resources.


Diurnal regulation of milk lipid production and milk secretion in the rat: effect of dietary protein and energy restriction.
Lactating rats consuming a control diet (20% casein) ad libitum and kept on a 12-h light-dark cycle produced milk during the dark phase at a rate 50% greater than that during the light period. Diurnal variations in the food consumptions of these animals, maternal live weights and litter weight gains were also observed. This diurnal variation with respect to milk production and food consumption appears to be abolished by feeding a low protein (10% casein) diet. However, the variation was amplified when the amount of the control diet was restricted to 25 g/d and made available at the middark period; this was probably related to the meal-feeding behavior of these rats because they consumed all their food within 6 h after it was made available. The rates of fatty acid synthesis in the mammary glands, livers and adipose tissue measured in vivo from [3H]H2O incorporation also varied diurnally with maximal rates at the middark period. Similar rates were obtained for the rats receiving restricted amounts of the control diet measured in the feeding period, whereas the values for the rats fed the low protein diet in the dark period tended to be significantly lower. The milk fatty acids were also analyzed, and whereas no diurnal differences were detected in the samples taken from control rats, a marked reduction in the proportion of the medium-chain acids was observed in the samples from rats receiving restricted amounts of the control diet taken immediately before the normal feeding period.


Genetic and non-genetic tailoring of microalgae for the enhanced production of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) - A review.
The myriad health benefits associated with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) laid the path for their application in the functional foods and nutraceutical industries. Fish being primarily exploited for extraction of EPA and DHA are unsustainable sources; thus, oleaginous microalgae turn out to be an alternative sustainable source. This review paper aims to provide the recent developments in the context of enhancing EPA and DHA production by utilising non-genetic tailoring and genetic tailoring methods. We have also summarized the legislation, public perception, and possible risks associated with the usage of genetically modified microalgae focusing on EPA and DHA production.


Reactive oxygen species-dependent HSP90 protein cleavage participates in arsenical As(+3)- and MMA(+3)-induced apoptosis through inhibition of telomerase activity via JNK activation.
The effects of six arsenic compounds including As(+3), MMA(+3), DMA(+3), As(+5), MMA(+5), and DMA(+5) on the viability of NIH3T3 cells were examined. As(+3) and MMA(+3), but not the others, exhibited significant cytotoxic effects in NIH3T3 cells through apoptosis induction. The apoptotic events such as DNA fragmentation and chromosome condensation induced by As(+3) and MMA(+3) were prevented by the addition of NAC and CAT, and induction of HO-1 gene expression in accordance with cleavage of the HSP90 protein, and suppression of telomerase activity were observed in NIH3T3 cells under As(+3) and MMA(+3) treatments. An increase in the intracellular peroxide level was examined in As(+3)- and MMA(+3)-treated NIH3T3 cells, and As(+3)- and MMA(+3)-induced apoptotic events were blocked by NAC, CAT, and DPI addition. HSP90 inhibitors, GA and RD, significantly attenuated the telomerase activity in NIH3T3 cells with an enhancement of As(+3)- and MMA(+3)-induced cytotoxicity. Suppression of JNKs significantly inhibited As(+3)- and MMA(+3)-induced apoptosis by blocking HSP90 protein cleavage and telomerase reduction in NIH3T3 cells. Furthermore, Hb, SnPP, and dexferosamine showed no effect against As(+3)- and MMA(+3)-induced apoptosis, and overexpression of HO-1 protein or inhibition of HO-1 protein expression did not affect the apoptosis induced by As(+3) or MMA(+3). These data provide the first evidence to indicate that apoptosis induced by As(+3) and MMA(+3) is mediated by an ROS-dependent degradation of HSP90 protein and reduction of telomerase via JNK activation, and HO-1 induction might not be involved.


A tumor microenvironment-activatable nanoplatform with phycocyanin-assisted in-situ nanoagent generation for synergistic treatment of colorectal cancer.
The in-situ generation of therapeutic agents in targeted lesions is promising for revolutionizing oncotherapy but is limited by the low production efficiency. Given the specific tumor microenvironment (TME) of colorectal cancer (CRC), i.e., mild acidity, overexpressed H2O2, glutathione (GSH) and H2S, we develop phycocyanin (PC) encapsulated PZTC/SS/HA nanocapsules (NCs) for TME-responsive, protein-assisted "turn-on'' therapy of CRC. The NCs are prepared by sequentially assembling Cu2+-tannic acid (TA) coordination shell, disulfide bond-bearing cross-linker, and hyaluronic acid (HA) on the sacrificial template ZIF-8, thus achieving pH-, GSH-responsiveness, and tumor targeting capability, respectively. Once reaching the CRC sites, the NCs can quickly disintegrate and release Cu2+ and PC, accompanied by subsequent endogenous H2S-triggered generation of copper sulfide (CuS). Significantly, the intracellular sulfidation process can be accelerated by PC, thereby enabling efficient photothermal therapy (PTT) under NIR-Ⅱ laser. Besides, Cu2+-associated chemodynamic therapy (CDT) can be simultaneously activated and enhanced by PTT-induced local hyperthermia and disulfide bond-induced GSH consumption. This CRC-targeted and TME-activated synergistic PTT/CDT strategy displays high therapeutic efficacy both in vitro and in vivo, which can open up a new avenue for biomolecule-assisted in-situ nanoagent generation and effective TME-responsive synergistic treatment of CRC.


Inferior paralabral ganglion cyst of the shoulder with labral tear -- a rare cause of shoulder pain.
Paralabral ganglion cysts of the shoulder are rare, and their pathogenesis is similar to that of meniscal cysts. The paralabral cysts are most frequently reported along the posterior, superior, and anterior aspects of the glenohumeral joint and are uncommon inferiorly to the joint. These cysts rarely become evident clinically, unless they cause compression of surrounding structures, i.e. nerve. We report a retrospective series of five patients with inferior paralabral ganglion cysts of the shoulder without compression of the surrounding nerve which were treated during the period from March 2007 to December 2009. All these patients presented with only chronic shoulder pain as their chief complaint, and preoperative MRI showed the cyst over the inferior aspect of a torn glenoid labrum. All patients were treated by arthroscopic cystic decompression with labrum repair. All patients were re-evaluated with MRI performed at an average of 15 months postoperatively. The clinical outcome, including the Constant score, was assessed for all patients at a median of 16 months postoperatively. All the five patients had remission of pain and were satisfied with the shoulder function. The postoperative MRI in all patients showed no labral cyst recurrence. The median Constant score improved from a preoperative level of 81.5 points to 98.0 points at last follow-up. This study demonstrates that, in the absence of any nerve compression symptoms around the shoulder joint, inferior paralabral cysts with labral tear also be considered in the differential diagnosis of chronic shoulder pain. Arthroscopic repair of the cyst with repair of the labrum can lead to the disappearance of symptoms. Knowledge of this clinical condition and its imaging features is critical for a correct diagnosis of this uncommon cause of chronic shoulder pain. Level IV. Retrospective therapeutic study.


Cyclin K-containing kinase complexes maintain self-renewal in murine embryonic stem cells.
Protein phosphorylation plays an important role in the regulation of self-renewal and differentiation of embryonic stem cells. However, the responsible intracellular kinases are not well characterized. Here, we discovered that cyclin K protein was highly expressed in pluripotent embryonic stem cells but low in their differentiated derivatives or tissue-specific stem cells. Upon cell differentiation, the level of cyclin K protein was decreased. Furthermore, knockdown of cyclin K led to cell differentiation, which could be rescued by an expression construct resistant to RNA interference. Surprisingly, cyclin K did not interact with CDK9 protein in cells as thought previously. Instead, it associated with CrkRS (also known as CDK12) and CDC2L5 (also known as CDK13). Similar to cyclin K, both CDK12 and CDK13 proteins were highly expressed in murine embryonic stem cells and were decreased upon cell differentiation. Importantly, knockdown of either kinase resulted in differentiation. Thus, our studies have uncovered two novel protein kinase complexes that maintain self-renewal in embryonic stem cells.


Long-term biodegradation of crude oil in high-arctic backshore sediments: The Baffin Island Oil Spill (BIOS) after nearly four decades.
With an on-going disproportional warming of the Arctic Ocean and the reduction of the sea ice cover, the risk of an accidental oil spill from ships or future oil exploration is increasing. It is hence important to know how crude oil weathers in this environment and what factors affect oil biodegradation in the Arctic. However, this topic is currently poorly studied. In the 1980s, the Baffin Island Oil Spill (BIOS) project carried out a series of simulated oil spills in the backshore zone of beaches located on Baffin Island in the Canadian High Arctic. In this study two BIOS sites were re-visited, offering the unique opportunity to study the long-term weathering of crude oil under Arctic conditions. Here we show that residual oil remains present at these sites even after almost four decades since the original oiling. Oil at both BIOS sites appears to have attenuated very slowly with estimated loss rates of 1.8-2.7% per year. The presence of residual oil continues to significantly affect sediment microbial communities at the sites as manifested by a significantly decreased diversity, differences in the abundance of microorganisms and an enrichment of putative oil-degrading bacteria in oiled sediments. Reconstructed genomes of putative oil degraders suggest that only a subset is specifically adapted for growth under psychrothermic conditions, further reducing the time for biodegradation during the already short Arctic summers. Altogether, this study shows that crude oil spilled in the Arctic can persist and significantly affect the Arctic ecosystem for a long time, in the order of several decades.


TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome.
BCR-ABL1 gene is a key molecular marker of chronic myeloid leukemia (CML), but it is still unclear which molecular factors may influence CML risk or lead to variable responses to tyrosine kinase inhibitors (TKIs). The aim of this study was to investigate the impact of TP53 c.213 G>C(Arg72Pro; rs1042522) polymorphism on CML risk and its correlation with clinical outcome. Peripheral blood samples from 141 treated CML patients and 141 sex- and age-matched healthy individuals were genotyped by PCR-RFLP. Standard genetic models for disease penetrance were evaluated by logistic regression analysis and Kaplan-Meier method was performed to estimate survival curves. Our study suggests that TP53 c.213 G>C polymorphism may be involved in CML development considering a recessive model (p=0.01; OR: 0.19; CI: 0.06-0.68). In addition, a non-homogenous distribution was found for this polymorphism in males and patients youngers than 50years (p=0.02). According to clinical response, TP53-GG genotype was associated with higher levels of BCR-ABL1 transcripts (p=0.04) and shorter event free survival (p=0.04). Moreover, a trend toward significance was found for failure free survival (p=0.06) and time to imatinib failure (p=0.08). In conclusion, our data suggest that a;TP53 c.213 G>C may be a potential biomarker of CML susceptibility and clinical outcome.


Superpixel-based deep convolutional neural networks and active contour model for automatic prostate segmentation on 3D MRI scans.
Automatic and reliable prostate segmentation is an essential prerequisite for assisting the diagnosis and treatment, such as guiding biopsy procedure and radiation therapy. Nonetheless, automatic segmentation is challenging due to the lack of clear prostate boundaries owing to the similar appearance of prostate and surrounding tissues and the wide variation in size and shape among different patients ascribed to pathological changes or different resolutions of images. In this regard, the state-of-the-art includes methods based on a probabilistic atlas, active contour models, and deep learning techniques. However, these techniques have limitations that need to be addressed, such as MRI scans with the same spatial resolution, initialization of the prostate region with well-defined contours and a set of hyperparameters of deep learning techniques determined manually, respectively. Therefore, this paper proposes an automatic and novel coarse-to-fine segmentation method for prostate 3D MRI scans. The coarse segmentation step combines local texture and spatial information using the Intrinsic Manifold Simple Linear Iterative Clustering algorithm and probabilistic atlas in a deep convolutional neural networks model jointly with the particle swarm optimization algorithm to classify prostate and non-prostate tissues. Then, the fine segmentation uses the 3D Chan-Vese active contour model to obtain the final prostate surface. The proposed method has been evaluated on the Prostate 3T and PROMISE12 databases presenting a dice similarity coefficient of 84.86%, relative volume difference of 14.53%, sensitivity of 90.73%, specificity of 99.46%, and accuracy of 99.11%. Experimental results demonstrate the high performance potential of the proposed method compared to those previously published.


Identification of CRG-2. An interferon-inducible mRNA predicted to encode a murine monokine.
In order to identify novel proteins produced by activated macrophages, a cDNA library was made from cultures of the mouse macrophage-like cell line RAW 264.7 that had been treated with conditioned medium from mitogen-stimulated spleen cells, and the library was screened by differential plaque hybridization. A cDNA clone was isolated that detected a 1.4-kilobase mRNA that accumulated dramatically in response to the spleen cell conditioned medium. The 1.4-kilobase mRNA encodes a predicted protein of 98 amino acids, designated CRG-2, molecular weight (Mr) 10,781, with a 21-residue signal peptide. The amino acid sequence indicates that CRG-2 is a member of the platelet factor 4 family (PF4) of cytokines. The CRG-2 mRNA was induced by alpha-, beta-, and gamma-interferons (IFNs) and by lipopolysaccharide. In response to IFN-gamma, the CRG-2 mRNA level reached a peak between 3 and 6 h. The accumulation of CRG-2 mRNA was not blocked by cycloheximide. Among the known members of the PF4 family, CRG-2 is most closely related to the interferon-inducible human protein IP-10. The 5'-flanking region of the crg-2 gene was isolated, and comparisons between crg-2 and IP-10 genes, mRNAs, and proteins reveal conserved features of possible functional importance. CRG-2 may play a role in host defense, particularly in the response to viral infection.


"There are risks to be taken and some just push it too far": how farmers perceive quad-bike incident risk.
To qualitatively explore how farmers perceive personal risk of an occupational quad-bike incident and develop a model of the factors that modify this perception. Grounded theory methods were used to inform data collection and analysis. Semi-structured interviews were undertaken with eight New Zealand livestock farmers. Interviews were inductively analysed to derive categories that helped explain the processes involved in quad-bike incident risk perception. Farmers perceived personal risk of experiencing a quad-bike incident could be modelled on a sliding scale from low to high. Four core categories encapsulated risk perception: the impact of previous quad-bike incidents; personal attributes; getting the job done; and being familiar with the performance of the quad bike, the terrain and task(s) being undertaken. An exploratory model was developed to elucidate the temporal gap between farmers' reflections on their perceived risk and reported real-time risk management. These findings have implications for planning quad-bike safety interventions, which may benefit from incorporating both 'reflective' contemplation of risks and skills for coping with things suddenly going wrong 'in the moment'.


Met and unmet needs for surgery in Sierra Leone: A comprehensive, retrospective, countrywide survey from all health care facilities performing operations in 2012.
Understanding a country's baseline operative actors and capacity is critical to improving the quality of services and outcomes. The aim of this study was to describe all operative providers and national operative production, to evaluate district and nationwide population rates for operations, and to estimate unmet operative need in Sierra Leone. A nationwide, exhaustive, retrospective, facility-based study of operative actors and surgical procedures was performed in Sierra Leone. Between January and May 2013, 4 teams of 12 medical students collected data on the characteristics of the institutions and of the operations performed in 2012. Data were retrieved from the log books of operations, anesthesia, and delivery. A total of 24,152 operative procedures were identified, equal to a national rate of 400 operative procedures per 100,000 inhabitants (district range 32-909/100,000, interquartile range 95-502/100,000). Hernia repair was the most common operative procedure at 86.1 per 100,000 inhabitants (22.4% of the total national volume) followed by cesarean delivery at 80.6 per 100,000 (21.0% of the total). Private, nonprofit facilities performed 54.0% of the operations, compared with 39.6% by governmental and 6.4% by private for-profit facilities. More than 90% of the estimated operative need in Sierra Leone was unmet in 2012. The unmet operative need in Sierra Leone is very high. The 30-fold difference in operative output between districts also is very high. As the main training institution, operative services within the governmental sector need to be strengthened. An understanding of the existing operative platform is a good start for expanding operative services.


The influence of proline on diet selection: sex-specific feeding preferences by the grasshoppers Ageneotettix deorum and Phoetaliotes nebrascensis (Orthoptera: Acrididae).
Diet selection based on the level of proline in an insect's host plant has been observed for a number of phytophagous insects, but few studies have examined potential differences in feeding preferences between males and females. The level of proline among an insect's host plants, particularly in drought-stressed plants, can be highly variable and often is positively correlated with soluble nitrogen levels. Additionally, proline is known to participate in a number of physiological functions in insects. We tested the effect of proline as a feeding stimulant in reproductively active grasshoppers using the graminivorous Ageneotettix deorum and the generalist, but mostly graminivorous, Phoetaliotes nebrascensis. Feeding preference tests using diets with representative free amino acid and sucrose levels but varying proline levels (zero, normal and 3 x normal) were examined. The feeding preference exhibited by both species was sex-specific, although the sex-specific response was more pronounced in P. nebrascensis than in A. deorum. Females of both species displayed preferences for diets high in proline. Males of neither species exhibited a preference for proline when responses were averaged over all treatment levels. However, within specific treatment combinations, male A. deorum preferred diets with high proline over diets with zero proline. These results suggest that diet selection for specific nutrients may vary between males and females because of differences in their physiological status and, possibly, differences in the nutritional requirements associated with reproduction. These results also suggest that subtle shifts in the concentration of individual nutrients within an insect's host plant may greatly influence insect feeding patterns.


The Impact of Advanced Patient Age on Mortality after Allogeneic Hematopoietic Cell Transplantation for Non-Hodgkin Lymphoma: A Retrospective Study by the European Society for Blood and Marrow Transplantation Lymphoma Working Party.
More than 60% of patients with non-Hodgkin lymphoma (NHL) are age >60 years at presentation. The purpose of this study was to compare the potential risks and benefits of allogeneic hematopoietic cell transplantation (alloHCT) in elderly patients with NHL with younger patients in a large sample, also taking into account comorbidity information. All patients age ≥18 years who had undergone alloHCT from a matched sibling or unrelated donor for NHL between 2003 and 2013 and were registered with the European Society for Blood and Marrow Transplantation were eligible for the study. The primary study endpoint was 1-year nonrelapse mortality (NRM). A total of 3919 patients were eligible and were categorized by age: young (Y), 18 to 50 y (n = 1772); middle age (MA), 51 to 65 y (n = 1967); or old (O), 66 to 77 y (n = 180). Follicular lymphoma was present in 37% of the patients; diffuse large B cell lymphoma, in 30%; mantle cell lymphoma, in 21%, and peripheral T cell lymphoma, in 11%. At the time of alloHCT, 85% of the patients were chemosensitive and 15% were chemorefractory. With a median follow-up of 4.5 years in survivors, NRM at 1 year was 13% for the Y group. 20% for the MA group, and 33% for the O group (P <.001), whereas relapse incidence and overall survival (OS) at 3 years in the 3 groups were 30%, 31%, and 28% (P = .355) and 60%, 54%, and 38% (P <.001), respectively. Multivariable adjustment for confounders, including sex, NHL subset, time from diagnosis, chemosensitivity, donor, and conditioning, confirmed older age as a significant predictor for NRM and OS, but not for relapse risk. Although comorbidity was a significant predictor of NRM in a subset analysis restricted to the 979 patients with comorbidity information available, age retained its significant impact on NRM. In conclusion, our data show that alloHCT in patients age >65 y provides similar NHL control as seen in younger patients but is associated with a higher NRM that is not fully explained by comorbidity. Thus, although alloHCT is feasible and effective in very old patients, the increased NRM risk must be taken into account when assessing the indication for alloHCT for NHL in this age group.


Adjuvant treatment of colorectal cancer. Current status and concepts.
Colorectal cancer is the second leading cause of cancer mortality in the United States, causing approximately 50,000 deaths per year. The overall prognosis and results of treatment have not changed impressively over the last three decades. Half of all the patients who undergo curative surgery finally succumb to locoregional or metastatic recurrence of their disease. Recent clinical research has been aimed at adjuvant therapeutic measures to improve survival after curative surgical resection. For rectal cancer, combined postoperative chemotherapy and radiation therapy have been shown to reduce the overall relapse rate and improve disease-free survival. Further studies of adjuvant treatment for rectal cancer are needed to evaluate the optimal radiation schedule and limit the side-effects of the treatment. Adjuvant treatment of colon cancer must still be regarded as unsettled. Since liver metastases are the most common unfavorable outcome of colon cancer, ongoing trials using liver-directed treatment (perfusion, irradiation) should be followed with interest. The lack of proven efficacy and the side-effects of these treatments strongly favor the inclusion of an observation-only control group in trials for adjuvant treatment of colon cancer. Unfortunately, there is as yet no proven significant benefit from immunotherapy as an adjuvant therapy for colorectal cancer, but further basic and clinical studies will be of great interest in this field.


Interplay between positive and negative activities that influence the role of Bicoid in transcription.
The Drosophila mophogenetic protein Bicoid (Bcd) can activate transcription in a concentration-dependent manner in embryos. It contains a self-inhibitory domain that can interact with the co-repressor Sin3A. In this report, we study a Bcd mutant, Bcd(A57-61), which has a strengthened self-inhibitory function and is unable to activate the hb-CAT reporter in Drosophila cells, to analyze the role of co-factors in regulating Bcd function. We show that increased concentrations of the co-activator dCBP in cells can switch this protein from its inactive state to an active state on the hb-CAT reporter. The C-terminal portion of Bcd(A57-61) is required to mediate such activity-rescuing function of dCBP. Although capable of binding to DNA in vitro, Bcd(A57-61) is unable to access the hb enhancer element in cells, suggesting that its DNA binding defect is only manifested in a cellular context. Increased concentrations of dCBP restore not only the ability of Bcd(A57-61) to access the hb enhancer element in cells but also the occupancy of the general transcription factors TBP and TFIIB at the reporter promoter. These and other results suggest that an activator can undergo switches between its active and inactive states through sensing the opposing actions of positive and negative co-factors.


Genomic analysis of Paenibacillus sp. MDMC362 from the Merzouga desert leads to the identification of a potentially thermostable catalase.
Microorganisms in hot deserts face heat and other environmental conditions, such as desiccation, UV radiation, or low nutrient availability. Therefore, this hostile environment harbour microorganisms with acquired characteristics related to survival in their habitat, which can be exploited in biotechnology. In this work, the genome of Paenibacillus sp. MDMC362 isolated from the Merzouga desert in Morocco was sequenced to understand its survival strategy's genetic basis; and to evaluate the thermostability of a catalase extracted from genomic annotation files using molecular dynamics. Paenibacillus sp. MDMC362 genome was rich in genetic elements involved in the fight against different stresses, notably temperature stress, UV radiations, osmotic stress, carbon starvation, and oxidative stress. Indeed, we could identify genes of the operons groES-groEL and hrcA-grpE-dnaK and those involved in the different stages of sporulation, which can help the bacteria to survive the high temperatures imposed by a desertic environment. We also observed the genetic components of the UvrABC system and additional mechanisms involved in DNA repair, which help overcome UV radiation damage. Other genes have been identified in the genome, like those coding for ectoine and proline, that aids fight osmotic stress and desiccation. Catalase thermostability investigation using molecular dynamics showed that the protein reached stability and conserved its compactness at temperatures up to 373.15 K. These results suggest a potential thermostability of the enzyme. Since the studied protein is a core protein, thermostability could be conserved among Paenibacillus sp. MDMC362 closely related strains; however, bacteria from harsh environments may have a slight advantage regarding protein stability.


Genetic polymorphisms in the CD40 ligand gene and Kawasaki disease.
Although some previous studies have reported that genetic and immunological factors play important roles in the pathogenesis of Kawasaki disease (KD), the etiological factors of this enigmatical pediatric disease are still poorly understood. This study aims to investigate whether polymorphisms of the CD40 ligand (CD40L) gene are associated with KD and the development of coronary artery lesions (CAL) in the Taiwanese children. The CD40L -3459 A/G and IVS4+121 A/G single nucleotide polymorphisms (SNPs) were genotyped in 167 children with KD and 1,010 ethnically matched healthy controls by TaqMan assay. None of the CD40L polymorphisms was associated with susceptibility or CAL development of KD, and this finding was supported by the haplotype analysis. In summary, these results provide little support for specific CD40L SNPs in the susceptibility or CAL development of KD in Taiwanese children. However, it will be necessary to validate or replicate this association in other independent large-size ethnic groups.


Characterization of hydrogenosomes and their role in glucose metabolism of Neocallimastix sp. L2.
In the anaerobic fungus Neocallimastix sp. L2 fermentation of glucose proceeds via the Embden-Meyerhof-Parnas pathway. Enzyme activities leading to the formation of succinate, lactate, ethanol, and formate are associated with the cytoplasmic fraction. The enzymes 'malic enzyme,' NAD(P)H:ferredoxin oxidoreductase, pyruvate:ferredoxin oxidoreductase, hydrogenase, acetate:succinate CoA transferase and succinate thiokinase leading to the formation of H2,CO2, acetate, and ATP are localized in microbodies. Thus, these organelles are identified as hydrogenosomes. In addition, the microbodies contain the O2-scavenging enzymes NADH- and NADPH oxidase, while NAD(P)H peroxidase, catalase, or superoxide dismutase could not be detected. In cell-free extracts from zoospores of Neocallimastix sp. L2 the specific activities of hydrogenosomal enzymes as well as the quantities of these proteins are 2- to 6-fold higher than in mycelium extracts. These findings suggest that hydrogenosomes perform an important role--especially in zoospores--as H2-evolving, ATP-generating and O2-scavenging organelles.


Glucocorticoid-regulated human serotonin transporter (5-HTT) expression is modulated by the 5-HTT gene-promotor-linked polymorphic region.
Mood, emotion and cognition are modulated by serotonergic neurotransmission, while the physiological function of serotonergic synapses depends on serotonin reuptake, which is mediated by the serotonin transporter (5-HTT). Allelic variation of 5-HTT expression in humans is caused by a functional gene-promoter polymorphism with two predominant variant alleles, which are associated with variations in anxiety measures as previously reported. Here we report that administration of dexamethasone, a potent glucocorticosteroid hormone, results in an increase in 5-HTT expression in immortalized human B-lymphoblastoid cells, which express the human 5-HTT. Functional reporter gene assays as well as 5-HT uptake and inhibitor binding measures revealed a genotype-dependent dose-response to glucocorticosteroid administration, which was antagonized by RU 38486, a non-specific glucocorticosteroid hormone antagonist. The allele-specific differences after administration of dexamethasone depended on the repetitive GC-rich sequence located approximately 1.4 kb upstream of the 5-HTT gene transcription site because of absence of a significant steroid effect after transfecting a deletional mutant reporter gene construct, which lacks this repetitive promoter sequence. Our findings may contribute to explain the vulnerability to stress-related disorders in susceptible individuals, in whom further clinical studies should follow up on these in vitro findings.