The costs of crest induction for Daphnia carinata.
The effects of notonectid-induced crests on growth and reproduction, and resource allocation to crest construction, moult losses and eggs of Daphnia carinata were measured. An attempt was made to elucidate the mechanisms of physiological costs of crest induction for this species. The crested morph of d. carinata reached a significantly larger size than the uncrested form. Reproductive output was similar in early instars, but the crested morph produced more eggs in latter broods. Instar duration was longer for the crested morph and age at first reproduction was delayed. Survival was also lower in this form. Crest construction required significant resources (equivalent to 60 eggs over a life time) but evidence is presented that these resources were obtained primarily by re-allocation of available material rather than collection of extra resources. The crested morph allocated significantly more resources to moulting than its uncrested counter-parts. The uncrested morph produced large eggs in early instars and progressively smaller ones in later instars. The crested morph produced only small eggs. The hypothesis is presented that the crest-induction strategy of D. carinata involves at least two separate sets of responses, each with its own costs and trade-offs. The first response is production of the crest. The cost of crest production is an increased cost of moulting. D. carinata off sets this cost by increasing instar duration and thus age at reproduction. The second response is increased size. D. carinata achieves this by reducing the fraction of available resources allocated to reproduction. The cost is lower reproductive output.


Activation of Stat3 sequence-specific DNA binding and transcription by p300/CREB-binding protein-mediated acetylation.
Signal transducers and activators of transcription (Stat) belong to a family of latent cytoplasmic factors that can be activated by tyrosine phosphorylation by members of the Jak tyrosine kinase family in response to a variety of cytokines and growth factors. Activated Stats form dimers and translocate into nucleus to induce expression of critical genes essential for normal cellular events. Here we report for the first time that Stat3 can be modified by acetylation both in vivo and in vitro. A major site of Stat3 that is acetylated by its coactivator, p300/CREB-binding protein (CBP), resides in the C-terminal transcriptional activation domain at lysine 685. Furthermore, the acetylation of Stat3 can stimulate its sequence-specific DNA binding ability and transactivation activity. Inhibition of histone deacetylase activity in cells results in increased Stat3 nuclear localization. These observations clearly indicate a novel mechanism for Stat3 activation in mammalian cells.


Characteristics of START assessments completed in mental health jail diversion programs.
Many different instruments have been developed to assist in the assessment of risk for violence and other criminal behavior. However, there is limited evidence regarding how these instruments work in the 'real world'. Even less is known about how these instruments might work for assessing risk in jail diversion populations, whether in research or practice. To address these knowledge gaps, the present study examined the characteristics of risk assessments completed by program staff (n=10) on 96 mental health jail diversion clients (72 men and 24 women) using the Short-Term Assessment of Risk and Treatability (START). The findings provide preliminary support for the reliability and validity of START assessments completed in jail diversion programs, the first evidence of the transportability of START outside psychiatric settings, and further evidence regarding the reliability and validity of START assessments completed in the field. They additionally support the consideration of an eighth, general offending risk domain in START assessments.


The Mediating Roles of Hostility and Dissociation in the Relationship Between Sexual Assault and Suicidal Thinking in College Students.
Sexual assault and suicide are two serious public health concerns. Research has documented the relationship between sexual assault and suicidal thinking and attempts; however, limited research explores the more multifaceted relationships between posttraumatic stress reactions and suicidal ideation in college students through unsuccessful modulation of emotion. The authors hypothesized a mediation model where the relationship between sexual assault and suicidal ideation is mediated by dissociation and hostility. In total, 1,677 undergraduate students were administered modified versions of the Traumatic Life Events Questionnaire (TLEQ), Symptom Checklist-90-Revised (SCL-90-R), and Peritraumatic Dissociative Experiences Questionnaire (PDEQ). The results revealed both significant partial but equal mediators of hostility and dissociation. However, a portion of the direct effect between sexual assault and suicidal ideation remained unaccounted for by indirect effects. The current model supports previous work on dialectical behavior therapy that says either side of the dialectic between extreme expression and suppression of hostility increases the likelihood of suicidal thinking after sexual assault. With sexual assault survivors, practitioners should use strategies that emphasize both anger expression and healthy avoidance as a way to modulate emotion to potentially reduce suicidal thoughts. Future research should focus on different gender models, additional possible mediators such as alcohol use and guilt, and different forms of sexual assault. Limitations of the correlational, cross-sectional methodology are discussed.


Guideline implementation for breast healthcare in low- and middle-income countries: breast healthcare program resource allocation.
Breast cancer is serious public health problem in countries of all resource levels. Although major advances in the detection and treatment of the disease have occurred in higher income settings, similar progress has been slow or scarce in most low- and middle-income countries (LMCs). The poorer outcomes in LMCs may relate to the limited capability of their healthcare systems (HCS) to provide successful early detection, diagnosis, and treatment of breast cancer. Impediments to better outcomes include insufficient numbers of appropriately trained healthcare workers, limited access to screening/treatment facilities, inadequate supplies of necessary drugs, and timeliness of treatment after diagnosis. Clearly, these HCS deficiencies are broader than the scope of the Breast Health Global Initiative (BHGI) and are not unique to the issue of breast cancer. To address issues in HCS that hinder the delivery of breast health services, the BHGI Healthcare Systems and Public Policy Panel explored the HCS structures and function needed to operate a breast care program (BCP). Like with all BHGI guidelines, those proposed by this panel were expressed in terms of 4 strata of resource levels: basic, limited, enhanced, and maximal. The current report describes the issues and questions related to HCS that are important to consider when designing, implementing, and measuring the performance of a BCP. Health ministers, other policymakers, healthcare personnel, administrators, and anyone else involved in developing a BCP can use and adapt this framework to improve outcomes and ensure the more effective use of resources.


Studies on two polyherbal formulations (ZPTO and ZTO) for comparison of their antidyslipidemic, antihypertensive and endothelial modulating activities.
Cardiovascular disorders (CVDs) are the leading cause of disease burden worldwide. Apart from available synthetic drugs used in CVDs, there are many herbal formulations including POL-10 (containing 10 herbs), which have been shown to be effective in animal studies but POL-10 was found to cause tachycardia in rodents as its side effect. This study was designed to modify the composition of POL-10 for better efficacy and/or safety profile in CVDs. To assess the antidyslipidemic, antihypertensive and endothelial modulatory properties of two herbal formulations, (ZPTO and ZTO) containing Z: Zingiber officinalis, P: Piper nigrum, T: Terminalia belerica and O: Orchis mascula, different animal models including, tyloxapol and high fat diet-induced dyslipidemia and spontaneously hypertensive rats (SHR) were used. Effect on endothelial function was studied using isolated tissue bath set up coupled with PowerLab data acquisition system. The antioxidant activity was carried out using DPPH radical-scavenging assay. Based on preliminary screening of the ingredients of POL-10 in tyloxapol-induced hyperlipidemic rats, ZPTO and ZTO containing four active ingredients namely; Z, P, T and O were identified for further studies and comparison. In tyloxapol-induced hyperlipidemic rats, both ZPTO and ZTO caused significant reduction in serum triglyceride (TG) and total cholesterol (TC). In high fat diet-fed rats, ZPTO decreased TC, low-density lipoproteins cholesterol (LDL-C) and atherogenic index (AI). ZTO also showed similar effects to those of ZPTO with additional merits being more effective in reducing AI, body weight and more importantly raising high-density lipoproteins. In SHR, both formulations markedly reduced systolic blood pressure, AI and TG levels, ZTO being more potent in reversing endothelial dysfunction while was devoid of cardiac stimulatory effect. In addition, ZTO also reduced LDL-C and improved glucose levels in SHR. In DPPH radical-scavenging activity test, ZTO was also more potent than ZPTO. The modified formulation, ZTO was not only found more effective in correcting cardiovascular abnormalities than ZPTO or POL-10 but also it was free from tachycardiac side-effect, which might be observed because of the presence of Piper nigrum in ZPTO.


Panorama of reconstruction of skull base defects: from traditional open to endonasal endoscopic approaches, from free grafts to microvascular flaps.
Introduction A substantial body of literature has been devoted to the distinct characteristics and surgical options to repair the skull base. However, the skull base is an anatomically challenging location that requires a three-dimensional reconstruction approach. Furthermore, advances in endoscopic skull base surgery encompass a wide range of surgical pathology, from benign tumors to sinonasal cancer. This has resulted in the creation of wide defects that yield a new challenge in skull base reconstruction. Progress in technology and imaging has made this approach an internationally accepted method to repair these defects. Objectives Discuss historical developments and flaps available for skull base reconstruction. Data Synthesis Free grafts in skull base reconstruction are a viable option in small defects and low-flow leaks. Vascularized flaps pose a distinct advantage in large defects and high-flow leaks. When open techniques are used, free flap reconstruction techniques are often necessary to repair large entry wound defects. Conclusions Reconstruction of skull base defects requires a thorough knowledge of surgical anatomy, disease, and patient risk factors associated with high-flow cerebrospinal fluid leaks. Various reconstruction techniques are available, from free tissue grafting to vascularized flaps. Possible complications that can befall after these procedures need to be considered. Although endonasal techniques are being used with increasing frequency, open techniques are still necessary in selected cases.


Microbial consortia at steady supply.
Metagenomics has revealed hundreds of species in almost all microbiota. In a few well-studied cases, microbial communities have been observed to coordinate their metabolic fluxes. In principle, microbes can divide tasks to reap the benefits of specialization, as in human economies. However, the benefits and stability of an economy of microbial specialists are far from obvious. Here, we physically model the population dynamics of microbes that compete for steadily supplied resources. Importantly, we explicitly model the metabolic fluxes yielding cellular biomass production under the constraint of a limited enzyme budget. We find that population dynamics generally leads to the coexistence of different metabolic types. We establish that these microbial consortia act as cartels, whereby population dynamics pins down resource concentrations at values for which no other strategy can invade. Finally, we propose that at steady supply, cartels of competing strategies automatically yield maximum biomass, thereby achieving a collective optimum.


Surgical treatment of migraine headaches.
This prospective study was conducted to investigate the role of removal of corrugator supercilii muscles, transection of the zygomaticotemporal branch of the trigeminal nerve, and temple soft-tissue repositioning in the treatment of migraine headaches. Using the criteria set forth by the International Headache Society, the research team's neurologist evaluated patients with moderate to severe migraine headaches, to confirm the diagnosis. Subsequently, the patients completed a comprehensive migraine headaches questionnaire and the team's plastic surgeon injected 25 units of botulinum toxin type A (Botox) into each corrugator supercilii muscle. The patients were asked to maintain an accurate diary of their migraine headaches and to complete a monthly questionnaire documenting pertinent information related to their headaches. Patients in whom the injection of Botox resulted in complete elimination of the migraine headaches then underwent resection of the corrugator supercilii muscles. Those who experienced only significant improvement underwent transection of the zygomaticotemporal branch of the trigeminal nerve with repositioning of the temple soft tissues, in addition to removal of the corrugator supercilii muscles. Once again, patients kept a detailed postoperative record of their headaches. Of the 29 patients included in the study, 24 were women and five were men, with an average age of 44.9 years (range, 24 to 63 years). Twenty-four of 29 patients (82.8 percent, p < 0.001) reported a positive response to the injection of Botox, 16 (55.2 percent, p < 0.001) observed complete elimination, eight (27.6 percent, p < 0.04) experienced significant improvement (at least 50 percent reduction in intensity or severity), and five (17.2 percent, not significant) did not notice a change in their migraine headaches. Twenty-two of the 24 patients who had a favorable response to the injection of Botox underwent surgery, and 21 (95.5 percent, p < 0.001) observed a postoperative improvement. Ten patients (45.5 percent, p < 0.01) reported elimination of migraine headaches and 11 patients (50.0 percent, p < 0.004) noted a considerable improvement. For the entire surgical group, the average intensity of the migraine headaches reduced from 8.9 to 4.1 on an analogue scale of 1 to 10, and the frequency of migraine headaches changed from an average of 5.2 per month to an average of 0.8 per month. For the group who only experienced an improvement, the intensity fell from 9.0 to 7.5 and the frequency was reduced from 5.6 to 1.0 per month. Only one patient (4.5 percent, not significant) did not notice any change. The follow-up ranged from 222 to 494 days, the average being 347 days. In conclusion, this study confirms the value of surgical treatment of migraine headaches, inasmuch as 21 of 22 patients benefited significantly from the surgery. It is also evident that injection of Botox is an extremely reliable predictor of surgical outcome.


Replacing cyclophosphamide/cytarabine/mercaptopurine with cyclophosphamide/etoposide during consolidation/delayed intensification does not improve outcome for pediatric B-cell acute lymphoblastic leukemia: a report from the COG.
With modern chemotherapy, approximately 90% of patients with pediatric acute lymphoblastic leukemia are now cured. However, subsets of patients can be identified who remain at very high risk of relapse with expected 4-year disease-free survival rates <80%; such patients are appropriate candidates for intensive therapeutic strategies designed to improve survival. The AALL1131 trial was designed to determine, in a randomized fashion, whether substitution with cyclophosphamide/etoposide (experimental arm 1) would improve the 4-year disease-free survival of children, adolescents, and young adults with very high-risk B-cell acute lymphoblastic leukemia compared to a modified Berlin-Frankfurt-Münster regimen (control arm). Patients 1-30 years of age with newly diagnosed very high-risk B-cell acute lymphoblastic leukemia were randomized after induction in a 1:2 fashion to the control arm or experimental arm 1 in which they were given cyclophosphamide (440 mg/m2 days 1-5)/etoposide (100 mg/m2 days 1-5) during part 2 of consolidation and delayed intensification. Prospective interim monitoring rules for efficacy and futility were included where futility would be determined for a one-sided P-value ≥0.7664. The study was stopped for futility as the interim monitoring boundary was crossed [hazard ratio 0.606 (95% confidence interval: 0.297 - 1.237)] and the very high-risk arm of AALL1131 was closed in February 2017. Using data current as of December 31, 2017, 4-year disease-free survival rates were 85.5±6.8% (control arm) versus 72.3±6.3% (experimental arm 1) (P-value = 0.76). There were no significant differences in grade 3/4 adverse events between the two arms. Substitution of this therapy for very high-risk B-cell acute lymphoblastic leukemia patients on the Children's Oncology Group AALL1131 trial (NCT02883049) randomized to cyclophosphamide/etoposide during part 2 of consolidation and delayed intensification did not improve disease-free survival.


Coupling alkaline pre-extraction with alkaline-oxidative post-treatment of corn stover to enhance enzymatic hydrolysis and fermentability.
A two-stage chemical pretreatment of corn stover is investigated comprising an NaOH pre-extraction followed by an alkaline hydrogen peroxide (AHP) post-treatment. We propose that conventional one-stage AHP pretreatment can be improved using alkaline pre-extraction, which requires significantly less H2O2 and NaOH. To better understand the potential of this approach, this study investigates several components of this process including alkaline pre-extraction, alkaline and alkaline-oxidative post-treatment, fermentation, and the composition of alkali extracts. Mild NaOH pre-extraction of corn stover uses less than 0.1 g NaOH per g corn stover at 80°C. The resulting substrates were highly digestible by cellulolytic enzymes at relatively low enzyme loadings and had a strong susceptibility to drying-induced hydrolysis yield losses. Alkaline pre-extraction was highly selective for lignin removal over xylan removal; xylan removal was relatively minimal (~20%). During alkaline pre-extraction, up to 0.10 g of alkali was consumed per g of corn stover. AHP post-treatment at low oxidant loading (25 mg H2O2 per g pre-extracted biomass) increased glucose hydrolysis yields by 5%, which approached near-theoretical yields. ELISA screening of alkali pre-extraction liquors and the AHP post-treatment liquors demonstrated that xyloglucan and β-glucans likely remained tightly bound in the biomass whereas the majority of the soluble polymeric xylans were glucurono (arabino) xylans and potentially homoxylans. Pectic polysaccharides were depleted in the AHP post-treatment liquor relative to the alkaline pre-extraction liquor. Because the already-low inhibitor content was further decreased in the alkaline pre-extraction, the hydrolysates generated by this two-stage pretreatment were highly fermentable by Saccharomyces cerevisiae strains that were metabolically engineered and evolved for xylose fermentation. This work demonstrates that this two-stage pretreatment process is well suited for converting lignocellulose to fermentable sugars and biofuels, such as ethanol. This approach achieved high enzymatic sugars yields from pretreated corn stover using substantially lower oxidant loadings than have been reported previously in the literature. This pretreatment approach allows for many possible process configurations involving novel alkali recovery approaches and novel uses of alkaline pre-extraction liquors. Further work is required to identify the most economical configuration, including process designs using techno-economic analysis and investigating processing strategies that economize water use.


Insulin pump therapy: impact on the lives of children/young people with diabetes mellitus and their parents.
Advances in medical technology and research documenting clinical effectiveness have led to the increased use of insulin pumps worldwide. However, their use by children in the UK is relatively limited and there is little evidence regarding their impact on patients' lives. This study aimed to examine the impact of switching from multiple daily injections to insulin pumps on the glycaemic control and daily lives of children/young people and their families. University College London Hospital, London. Face-to-face semi-structured interviews were conducted with children/young people with type 1 diabetes mellitus (5-17 years; N = 34) and their parents (N = 38), receiving insulin pump therapy and attending paediatric diabetes outpatients clinics at a major university teaching hospital in London. Glycated haemoglobin A1c values from 6 months prior to, and after pump therapy were obtained. Qualitative and quantitative approaches were undertaken for data analysis. Glycated haemoglobin A1c and the impact of the use of insulin pumps on the children and their families. The majority of parents (N = 32) and the children/young people (N = 30) reported that glycaemic control was easier to maintain within the target range with pumps compared to injections. This was supported by glycated haemoglobin A1c measures. Participants generally found the devices easy to use and more acceptable than injections. However, parents and children/young people reported many challenges in the early stages of pump therapy (e.g. 7 children/young had worse control at 6 months after starting CSII). Parents and children/young people reported an overall increase in lifestyle flexibility and an improved ability to participate in home, school and social activities whilst maintaining glycaemic control. Administration of insulin via pumps rather than injections was generally preferred. Participants reported most difficulty at the commencement of use. Pump therapy conferred benefits in terms of glycaemic control, general well-being, enabling young people to be more in control of their condition and live more normal lives, as reported by most participants. These are important goals of health policy for children/young people with long-term conditions in the UK.


An Efficient Microarray-Based Genotyping Platform for the Identification of Drug-Resistance Mutations in Majority and Minority Subpopulations of HIV-1 Quasispecies.
The response of human immunodeficiency virus type 1 (HIV-1) quasispecies to antiretroviral therapy is influenced by the ensemble of mutants that composes the evolving population. Low-abundance subpopulations within HIV-1 quasispecies may determine the viral response to the administered drug combinations. However, routine sequencing assays available to clinical laboratories do not recognize HIV-1 minority variants representing less than 25% of the population. Although several alternative and more sensitive genotyping techniques have been developed, including next-generation sequencing (NGS) methods, they are usually very time consuming, expensive and require highly trained personnel, thus becoming unrealistic approaches in daily clinical practice. Here we describe the development and testing of a HIV-1 genotyping DNA microarray that detects and quantifies, in majority and minority viral subpopulations, relevant mutations and amino acid insertions in 42 codons of the pol gene associated with drug- and multidrug-resistance to protease (PR) and reverse transcriptase (RT) inhibitors. A customized bioinformatics protocol has been implemented to analyze the microarray hybridization data by including a new normalization procedure and a stepwise filtering algorithm, which resulted in the highly accurate (96.33%) detection of positive/negative signals. This microarray has been tested with 57 subtype B HIV-1 clinical samples extracted from multi-treated patients, showing an overall identification of 95.53% and 89.24% of the queried PR and RT codons, respectively, and enough sensitivity to detect minority subpopulations representing as low as 5-10% of the total quasispecies. The developed genotyping platform represents an efficient diagnostic and prognostic tool useful to personalize antiviral treatments in clinical practice.


Patients' experiences of using the Integrated Palliative care Outcome Scale for a person-centered care: A qualitative study in the specialized palliative home-care context.
The aim of this study was to explore patients' experiences of using the Integrated Palliative care Outcome Scale (IPOS) during specialized palliative home care. The study adopted a qualitative approach with an interpretive descriptive design. Interviews were performed with 10 patients, of whom a majority were diagnosed with incurable cancer. Our findings suggest that the use of IPOS as a basis for conversation promotes safe care by making the patients feel confident that the care provided was adapted to them which gives them a sense of safety. IPOS facilitated discussions between patients and nurses about care needs. The patients believed that using IPOS enabled reflection on their well-being and life situation. In conclusion, the study finds that using IPOS is beneficial and provide ways to enable person-centered care and with advantage could be used in specialized palliative home care. The results may help overcome barriers and facilitate the use of patient-reported outcome measures (PROMs). To enable the use of PROMs such as IPOS in palliative home care, nurses need education and opportunities to develop routines that enable patients' voice to be heard and thereby compose a basis for care.


Anaerobic-fed and sequencing-batch treatment of sugar-beet processing wastes: a comparative study.
The aim of this study was to compare a batch-fed continuously mixed anaerobic reactor (FCMR) with an anaerobic sequencing batch reactor (ASBR), in terms of waste stabilization and methane production treating sugar-beet processing wastewater and beet-pulp simultaneously. A reactor was operated as FCMR, which then was operated as an ASBR by changing operational conditions after the steady-state was reached. Although the hydraulic retention time value of the ASBR configuration was lower (8 days) than that of the FCMR (15 days) and the corresponding organic loading rate (OLR) was higher (0.71 to 1.33 g COD/L x d), increased biomass retention enabled a significant increase in biomethanation for the ASBR configuration. So, methane production yield of 255 +/- 11 mL/g COD-added was increased to 337 +/- 15 mL/g COD-added (32.2% increase in methane yield) when the configuration was changed from FCMR to ASBR. The experimental results indicated that the ASBR configuration, which was applied to sugar-beet processing wastes for the first time, was superior to the FCMR configuration.


Photopic, mesopic, and scotopic vision.
This paper analyzes the work relating to the visibility curve as well as to the spectral efficiency of radiation in regard to visual acuity and contrast sensitivity. Methods of calculation of the visual efficiency for various types of light sources are presented. The results of an investigation of the brightness-luminance relation are analyzed. Recommendations regarding the photometric conditions for the small luminance range are indicated. Certain physiological characteristics of the spectral sensitivity of the eye are examined.


The CCR6/CCL20 axis mediates Th17 cell migration to the ocular surface in dry eye disease.
Th17 cells are believed to be the primary effector cells in the pathogenesis of dry eye disease (DED). However, the mechanisms by which Th17 cells migrate from the lymphoid tissues to the ocular surface are unknown. The purpose of this study was to investigate the role of the C-C chemokine receptor 6/C-C chemokine ligand 20 (CCR6/CCL20) chemokine axis in mediating Th17 cell migration in DED. DED was induced by housing C57BL/6 mice in a low-humidity environment supplemented with scopolamine treatment. Th17 cell expression of CCR6 was evaluated using flow cytometry and ocular surface expression of CCL20 was measured using PCR and ELISA assays. CCL20 neutralizing antibody was administered subconjunctivally to DED mice and disease severity, including the frequency of conjunctival Th17 cells, was evaluated. CCR6 is preferentially expressed by Th17 cells in both normal and DED mice and DED significantly upregulates ocular surface expression of CCL20. Disruption of CCR6/CCL20 binding with CCL20 neutralizing antibody decreases T-cell migration in vitro and reduces Th17 cell infiltration of the conjunctiva when administered in vivo, significantly improving clinical signs of DED. These changes were accompanied by a decrease in ocular surface inflammatory cytokine levels and corneal CD11b+ cell frequencies. Treatment also significantly reduced the generation of Th17 cells. Local neutralization of CCL20 decreases Th17 cell infiltration of the ocular surface in DED, leading to improvement in clinical signs of disease. This suggests that CCR6/CCL20 interactions direct Th17 cell migration in DED and that disruption of this axis may be a novel therapeutic approach to this condition.


Romidepsin (FK228) in a Mouse Model of Lipopolysaccharide-Induced Acute Kidney Injury is Associated with Down-Regulation of the CYP2E1 Gene.
BACKGROUND Romidepsin (FK228) or depsipeptide, is a selective inhibitor of histone deacetylase 1 (HDAC1) and HDAC2. This study aimed to investigate the effects and molecular mechanisms of romidepsin (FK228) in a mouse model of acute kidney injury (AKI) induced by lipopolysaccharide (LPS). MATERIAL AND METHODS The mouse model of AKI was developed by intraperitoneal injection of LPS. The mice were also treated intraperitoneally with romidepsin (FK228) six hours following injection of LPS. Markers of renal injury were measured, including blood urea nitrogen (BUN), serum creatinine (SCR), and serum cystatin C (Cys C) were measured. Histology and transmission electron microscopy were performed to evaluate tissue injury further. Levels of HDACs were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) assays were used to investigate the regulation of CYP2E1 expression. RESULTS Treatment with romidepsin (FK228) significantly reduced the levels of BUN, SCR, and Cys C induced by LPS. Histology of the mouse kidneys showed that treatment with romidepsin (FK228) reduced the degree of renal injury. CYP2E1 significantly reduced following treatment with romidepsin (FK228) in the mouse model of AKI. Also, acetylation of H3 was upregulated following treatment with romidepsin (FK228), and binding of hepatocyte nuclear factor-1 alpha (HNF-1a) on the CYP2E1 promoter was significantly increased. CONCLUSIONS In a mouse model of LPS-induced AKI, treatment with romidepsin (FK228) downregulated the expression of CYP2E1 by inhibiting the binding if HNF-1a with the CYP2E1 promoter to reduce renal injury.


Influence of a healthy Nordic diet on serum fatty acid composition and associations with blood lipoproteins - results from the NORDIET study.
The fatty acid (FA) composition of serum lipids is related to the quality of dietary fat intake. To investigate the effects of a healthy Nordic diet (ND) on the FA composition of serum cholesterol esters (CE-FA) and assess the associations between changes in the serum CE-FA composition and blood lipoproteins during a controlled dietary intervention. The NORDIET trial was a 6-week randomised, controlled, parallel-group dietary intervention study that included 86 adults (53±8 years) with elevated low-density lipoprotein cholesterol (LDL-C). Serum CE-FA composition was measured using gas chromatography. Diet history interviews were conducted, and daily intake was assessed using checklists. Food and nutrient intake data indicated that there was a reduction in the intake of fat from dairy and meat products and an increase in the consumption of fatty fish with the ND. The levels of saturated fatty acids in cholesterol esters (CE-SFA) 14:0, 15:0, and 18:0, but not 16:0, showed a significant decrease after intake of ND compared to the control diet (p<0.01). Also, a significant increase in serum 22:6n - 3 was observed compared with the control diet (p<0.01). The changes in CE-SFA 14:0, 15:0, and 18:0 correlated positively with changes in LDL-C, HDL-C, LDL-C/HDL-C, ApoA1, and ApoB (p<0.01), respectively, whereas the changes in polyunsaturated fatty acids in cholesterol esters (CE-PUFA) 22:6n - 3 were negatively correlated with changes in the corresponding serum lipids. The decreased intake of saturated fat and increased intake of n-3 PUFA in a healthy ND is partly reflected by changes in the serum CE-FA composition, which are associated with an improved serum lipoprotein pattern.


Can the work ability model provide a useful explanatory framework to understand sustainable employability amongst general practitioners: a qualitative study.
Work ability (WA) is an indication of how well someone's health, skills and experience match current job demands. The aim of this study was to ascertain whether the work ability model can provide a useful explanatory framework to understand some elements of sustainable employability (SE) amongst GPs. A thematic analysis of 19 in-depth interviews with GPs in the Northern Rivers region of NSW, Australia, was conducted and formed the basis for a qualitative validation of the work ability model. In order to provide a more comprehensive reflection on the factors and dynamics found to underpin work ability amongst ageing GPs required the creation of specific subcategories within the WA model. Additionally, new themes relevant to general practice also emerged from the data. The analyses revealed a set of important, new factors and relationships that required additions and refinements to the original model, in order to fully explain sustainable employability in this GP sample. These new emerging themes that required model extension were 'Work-life balance and lifestyle', 'Extended social community' and 'Impact of gender'. While the WA model provides a basic explanatory framework for understanding some elements of sustainable employability amongst GPs, a revision of the current model has been proposed to sufficiently describe the factors impinging on sustainable employability in this group. The extended model can potentially be used for addressing workforce planning issues and to assist in programme design to promote sustainable employability amongst GPs and could potentially be translated to other health professional groups.


Comparison of two total body irradiation fractionation regimens with respect to acute and late pulmonary toxicity.
Total body irradiation (TBI) is commonly used with autologous bone marrow transplantation (BMT) for treatment of hematologic malignancies. Pulmonary complications of TBI can cause long-term morbidity and mortality. The authors have compared the pulmonary toxicity and efficacy of two different TBI fractionation regimens in otherwise identical autologous BMT protocols. Between 1990 and 1997 patients younger than 60 years of age with low-grade lymphoma at high risk of treatment failure were enrolled on one of two sequential protocols for autologous BMT differing only in their TBI regimens. The preoperative chemotherapy regimens were identical and consisted of intravenous etoposide (1500 mg/m(2)) for 1 day, intravenous cyclophosphamide (60 mg/kg) for 2 days, and mesna (10 mg/kg). The TBI used in protocol A consisted of twice-daily fractions of 1.7 grays (Gy) for 3 days to a total of 10.2 Gy through lateral fields, with no lung shielding. In protocol B, the TBI consisted of 3 Gy once daily for 4 days to a total of 12 Gy through anteroposterior fields, with lung shielding (5 half-value layers) during the third dose. Fifty-eight patients were treated on protocol A and 24 on protocol B. The groups were equivalent with regard to age, performance status (PS) and gender. Lung function was assessed objectively by pulmonary function tests (PFTs) before and at intervals after TBI. The pulmonary function parameters assessed included forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)), forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75)), diffusing capacity for carbon monoxide (DL(CO)), and total lung capacity (TLC). Each patient's post-TBI PFTs were normalized to the corresponding pre-TBI values and analyzed using a random effects model. Clinical pulmonary function status was scored according to Radiation Therapy Oncology Group criteria for acute and late lung toxicity. All clinical pulmonary toxicities such as pneumonitis, pneumonia, and diffuse alveolar hemorrhage, whether specifically related to TBI or not, were scored. Toxicity was classified as either acute (i.e., occurring within 90 days of TBI) or late (i.e., occurring more than 90 days after TBI). The endpoints of analysis were overall survival (OS), freedom from progression, and chronic pulmonary toxicity. Survival, progression, and complication free survival were computed using the method of Kaplan and Meier. Three-year actuarial OS rates were 66% and 67% for protocols A and B, respectively. Patients 50 years of age or older had a hazard ratio of death 3.5 times higher than younger patients. Freedom from progression was significantly different for the 2 TBI regimens (P < 0.001; log-rank test): 31% at 3 years in the protocol A group compared with 82% in protocol B group. Patients on protocol A had a rate of progression 4.7 times higher than patients on protocol B. The TBI protocols did not differ significantly in their effects on FVC, FEV(1), FEF(25-75), DL(CO), and TLC. Patients 45 years of age or older had lower average posttransplant values of FEV(1), FVC, and DL(CO) than younger patients. There was no significant difference in acute or late toxicity rates between patients on the two protocols. Seven of the 57 patients in the twice-daily TBI (protocol A) group had acute pulmonary events (Grade 3 or greater), compared with 6 of the 24 patients in the once-daily (protocol B) group (P = 0.19). The 3-year freedom from late complications rate was 80% in the protocol A group and 70% in the protocol B group (P = 0.45). Patients with a PS of 1 had a hazard ratio of late complications 3.2 times greater than patients with a PS of 0 (P < 0.001). It is possible to intensify TBI from a total dose of 10.2 Gy delivered in 6 twice-daily fractions to 12 Gy delivered in 4 once-daily fractions without significantly increasing the risk of pulmonary toxicity. The increased dose may contribute to a decrease in the recurrence rate in these patients. (c) 2001 American Cancer Society.


Approach to a Child with Congestive Heart Failure.
Pediatric heart failure (PHF) is an important cause of mortality and morbidity. Whereas ischemic heart disease is the most important cause of heart failure in adults, congenital heart diseases (CHD) and cardiomyopathies are important etiologies of PHF. Management of PHF also differs from that of adults. Here authors have reviewed the literature on PHF with respect to etiology, symptoms, investigations and treatment strategies.


The Role of Genomic Techniques in Predicting Response to Radiation Therapy.
The understanding of the relationship between genetic variation and an individual patient's response to radiation therapy (RT) has gained significant ground over the past several years. Genetic markers have been identified that could ultimately serve as the foundation for predictive models in clinical practice, and that hold the potential to revolutionize the delivery of precision medicine in oncology. Single nucleotide polymorphisms, single genes, and/or gene signatures could ultimately serve as the basis for patient stratification in prospective clinical trials. Currently, molecular markers relevant to breast, lung, and head and neck cancers have been integrated into clinical practice and serve as predictive tools to guide systemic therapy. In the future, the use of predictive models based on genomic determinants may become standard practice in radiation oncology, offering the potential to further personalize the delivery of RT and optimize the therapeutic ratio.


The role of cue-target translation in backward inhibition of attentional set.
Backward inhibition (BI) refers to a reaction time cost incurred when returning to a recently abandoned task compared to returning to a task not recently performed. The effect has been proposed to reflect an inhibitory mechanism that aids transition from one task to another. The question arises as to precisely what aspects of a task may be inhibited and when the process takes place. Recent work has suggested a crucial role for response-related components of the task, which occur late in the typical trial structure (cue-target-response). In contrast to this suggestion, the authors present evidence that the way in which the task is cued can also modulate BI. Specifically, they find that the less transparent the cue-target relationship, the greater the level of BI. This also demonstrates that BI can be triggered at early stages of the trial structure, specifically during task preparation and prior to response processes. The authors conclude that BI is not tied to any particular component of the task structure but arises from whatever component generates the greatest intertrial conflict.


Induction of apoptosis by zerumbone isolated from Zingiber zerumbet (L.) Smith in protozoan parasite Leishmania donovani due to oxidative stress.
In the present context of emergence of resistance aligned with the conventional anti-leishmanial drugs and occasional treatment failure compelled us to continue the search for replaceable therapeutic leads against Leishmania infection. Various ginger spices of the Zingiberaceae family are widely used as spices, flavouring agents, and medicines in Southeast Asia because of their unique flavour as well as due to their medicinal properties. Zerumbone, a natural component of Zingiber zerumbet (L.) Smith, has been studied for its pharmacological potential as antiulcer, antioxidant, anticancer, and antimicrobial. In this study, we have shown that zerumbone could induce ROS mediated apoptosis in Leishmania donovani promastigotes and also found effective in reducing intracellular amastigotes in infected-macrophages. We emphasized the potential of zerumbone to be employed in the development of new therapeutic drugs against L. donovani infection and provided the basis for future research on the application of transitional medicinal plants.


Controlling contagion processes in activity driven networks.
The vast majority of strategies aimed at controlling contagion processes on networks consider the connectivity pattern of the system either quenched or annealed. However, in the real world, many networks are highly dynamical and evolve, in time, concurrently with the contagion process. Here, we derive an analytical framework for the study of control strategies specifically devised for a class of time-varying networks, namely activity-driven networks. We develop a block variable mean-field approach that allows the derivation of the equations describing the coevolution of the contagion process and the network dynamic. We derive the critical immunization threshold and assess the effectiveness of three different control strategies. Finally, we validate the theoretical picture by simulating numerically the spreading process and control strategies in both synthetic networks and a large-scale, real-world, mobile telephone call data set.


Nonfloral sources of chemicals that attract male euglossine bees (Apidae: Euglossini).
We present chemical analysis of four rotten or fungus-infected logs that attracted fragrance-collecting male euglossine bees. Eight of the 10 volatile compounds detected have never been found in the fragrances of orchids pollinated by male euglossine bees. Nonfloral sources of chemicals such as rotting wood may constitute an important fragrance resource for male bees. Since rotten logs produce large quantities of chemicals over long periods of time, such nonfloral sources might be more important than flowers as a source of certain fragrances for some euglossine bee species. Fragrance collecting in euglossine bees might have evolved originally in relation with rotting wood rather than flowers.


BioCreAtIvE task 1A: gene mention finding evaluation.
The biological research literature is a major repository of knowledge. As the amount of literature increases, it will get harder to find the information of interest on a particular topic. There has been an increasing amount of work on text mining this literature, but comparing this work is hard because of a lack of standards for making comparisons. To address this, we worked with colleagues at the Protein Design Group, CNB-CSIC, Madrid to develop BioCreAtIvE (Critical Assessment for Information Extraction in Biology), an open common evaluation of systems on a number of biological text mining tasks. We report here on task 1A, which deals with finding mentions of genes and related entities in text. "Finding mentions" is a basic task, which can be used as a building block for other text mining tasks. The task makes use of data and evaluation software provided by the (US) National Center for Biotechnology Information (NCBI). 15 teams took part in task 1A. A number of teams achieved scores over 80% F-measure (balanced precision and recall). The teams that tried to use their task 1A systems to help on other BioCreAtIvE tasks reported mixed results. The 80% plus F-measure results are good, but still somewhat lag the best scores achieved in some other domains such as newswire, due in part to the complexity and length of gene names, compared to person or organization names in newswire.


Pleurisy.
Pleuritic chest pain is a common presenting symptom and has many causes, which range from life-threatening to benign, self-limited conditions. Pulmonary embolism is the most common potentially life-threatening cause, found in 5 to 20 percent of patients who present to the emergency department with pleuritic pain. Other clinically significant conditions that may cause pleuritic pain include pericarditis, pneumonia, myocardial infarction, and pneumothorax. Patients should be evaluated appropriately for these conditions before an alternative diagnosis is made. History, physical examination, and chest radiography are recommended for all patients with pleuritic chest pain. Electrocardiography is helpful, especially if there is clinical suspicion of myocardial infarction, pulmonary embolism, or pericarditis. When these other significant causes of pleuritic pain have been excluded, the diagnosis of pleurisy can be made. There are numerous causes of pleurisy, with viral pleurisy among the most common. Other etiologies may be evaluated through additional diagnostic testing in selected patients. Treatment of pleurisy typically consists of pain management with nonsteroidal anti-inflammatory drugs, as well as specific treatments targeted at the underlying cause.


Correlation between KCNQ1 and KCNJ11 gene polymorphisms and type 2 and post-transplant diabetes mellitus in the Asian Indian population.
Type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) share a common pathophysiology. However, diabetes mellitus is a complex disease, and T2DM and PTDM have different etiologies. T2DM is a metabolic disorder, characterized by persistent hyperglycemia, whereas PTDM is a condition of abnormal glucose tolerance, with variable onset after organ transplant. The KCNQ1 and KCNJ11 gene encode potassium channels, which mediate insulin secretion from pancreatic β-cells, and KCN gene mutations are correlated with the development of diabetes. However, no studies have been carried out to establish an association between KCNQ1 and KCNJ11 gene polymorphisms and T2DM and PTDM. Therefore, our study was aimed at the identification of the role of KCNQ1 and KCNJ11 gene polymorphisms associated with T2DM and the risk of developing PTDM in the Asian Indian population. We have carried out a case-control study including 250 patients with T2DM, 250 control subjects, 42 patients with PTDM and 98 subjects with non-PTDM. PCR-RFLP analysis was carried out following the isolation of genomic DNA from EDTA-blood samples. The results of the present study reveal that two single nucleotide polymorphisms (rs2283228 and rs5210, of the KCNQ1 and KCNJ11 genes, respectively) are associated with both T2DM and PTDM. The results of our study suggest a role of KCNQ1 and KCNJ11 gene variants in the increased risk of T2DM and PTDM in the Asian Indian population.


Transplantation of pancreatic islets in dogs.
Dispersed pancreatic islet tissue, prepared by collagenase digestion without separation of exocrine and endocrine components, was transplanted into the splenic pulp of 12 dogs made diabetic by total pancreatectomy. Four dogs (group 1) were given autotransplants, and all became euglycemic 4.5 +/- 1.5 days (mean +/- SE) after the transplantation was done. Three of these dogs remained euglycemic until splenectomized 60 days after transplantation was done. Four dogs (group 2) given allogeneic transplants from histocompatible littermates within the same group were administered cyclosporine (40 mg/kg of body weight/day; starting 2 days before transplantation was done until dogs were splenectomized), and 3 of these dogs became euglycemic 8.0 +/- 2.0 days after the transplant was done. Two of the 3 dogs that became euglycemic remained so until splenectomized 60 days after transplantation was done, and the 3rd was euglycemic until 31 days after transplantation. Four dogs (group 3) given allogeneic islet transplants from nonrelated histocompatible donors within the same group were given cyclosporine (40 mg/kg/day; as described for group 2), and none became euglycemic.


Proteogenomic Analysis Greatly Expands the Identification of Proteins Related to Reproduction in the Apogamous Fern Dryopteris affinis ssp. affinis.
Performing proteomic studies on non-model organisms with little or no genomic information is still difficult. However, many specific processes and biochemical pathways occur only in species that are poorly characterized at the genomic level. For example, many plants can reproduce both sexually and asexually, the first one allowing the generation of new genotypes and the latter their fixation. Thus, both modes of reproduction are of great agronomic value. However, the molecular basis of asexual reproduction is not well understood in any plant. In ferns, it combines the production of unreduced spores (diplospory) and the formation of sporophytes from somatic cells (apogamy). To set the basis to study these processes, we performed transcriptomics by next-generation sequencing (NGS) and shotgun proteomics by tandem mass spectrometry in the apogamous fern D. affinis ssp. affinis. For protein identification we used the public viridiplantae database (VPDB) to identify orthologous proteins from other plant species and new transcriptomics data to generate a "species-specific transcriptome database" (SSTDB). In total 1,397 protein clusters with 5,865 unique peptide sequences were identified (13 decoy proteins out of 1,410, protFDR 0.93% on protein cluster level). We show that using the SSTDB for protein identification increases the number of identified peptides almost four times compared to using only the publically available VPDB. We identified homologs of proteins involved in reproduction of higher plants, including proteins with a potential role in apogamy. With the increasing availability of genomic data from non-model species, similar proteogenomics approaches will improve the sensitivity in protein identification for species only distantly related to models.


Enactive Approach and Dual-Tasks for the Treatment of Severe Behavioral and Cognitive Impairment in a Person with Acquired Brain Injury: A Case Study.
One of the most important sequela in persons who suffer from acquired brain injury is a behavioral disorder. To date, the primary approaches for the rehabilitation of this sequela are Applied Behavior Analysis, Cognitive-Behavior Therapy, and Comprehensive-Holistic Rehabilitation Programs. Despite this theoretical plurality, none of these approaches focuses on rehabilitating behavioral disorders considering the relation between affordance and environmental adaptation. To introduce this therapeutic view to neurorehabilitation, we apply the theoretical tenets of the enactive paradigm to the rehabilitation of a woman with severe behavioral and cognitive impairment. Over seventeen sessions, her behavioral and cognitive performance was assessed in relation to two seated affordances (seated on a chair and seated on a ball 65 cm in diameter) and the environmental adaptation while she was working on various cognitive tasks. These two seated affordances allowed to incorporate the theoretical assumptions of the enactive approach and to know how the behavior and the cognition were modified based on these two postural settings and the environmental adaptation. The findings indicate that the subject exhibited better behavioral (physical and verbal) and cognitive (matching success and complex task) performances when the woman worked on the therapeutic ball than when the woman was on the chair. The enactive paradigm applied in neurorehabilitation introduces a level of treatment that precedes behavior and cognition. This theoretical consideration allowed the discovery of a better relation between a seated affordance and the environmental adaptation for the improvement behavioral and cognitive performance in our case study.


Obesity under affluence varies by welfare regimes: the effect of fast food, insecurity, and inequality.
Among affluent countries, those with market-liberal welfare regimes (which are also English-speaking) tend to have the highest prevalence of obesity. The impact of cheap, accessible high-energy food is often invoked in explanation. An alternative approach is that overeating is a response to stress, and that competition, uncertainty, and inequality make market-liberal societies more stressful. This ecological regression meta-study pools 96 body-weight surveys from 11 countries c. 1994-2004. The fast-food 'shock' impact is found to work most strongly in market-liberal countries. Economic insecurity, measured in several different ways, was almost twice as powerful, while the impact of inequality was weak, and went in the opposite direction.


New host cell system for regulated simian virus 40 DNA replication.
Transformed monkey cell lines (CMT and BMT) that inducible express simian virus 40 (SV40) T antigen from the metallothionein promoter have been isolated and characterized. Immunoprecipitation of pulse-labeled T antigen demonstrates a 5- to 12-fold increase in the rate of synthesis on addition of heavy-metal inducers to the culture medium. Radioimmunoassay of cell extracts indicates the accumulation of three- to fourfold more total T antigen after 2 days of induction by comparison with uninduced controls. A direct correlation was found between the level of T-antigen synthesis and the extent of SV40 DNA replication in inducible cells. Inducible BMT cells expressing a low basal level of T antigen were efficiently transformed by a vector carrying the neomycin resistance marker and an SV40 origin of replication. These vector sequences were maintained in an episomal form in most G418-resistant cell lines examined and persisted even in the absence of biochemical selection. Extensive rearrangements were observed only if the vector contained bacterial plasmid sequences. Expression of a protein product under the control of the SV40 late promoter in such vectors was increased after heavy-metal-dependent amplification of the template. These results demonstrate the ability of BMT cells to maintain a cloned eucaryotic gene in an amplifiable episomal state.


Organization of actin in the leading edge of cultured cells: influence of osmium tetroxide and dehydration on the ultrastructure of actin meshworks.
The ordered structure of the leading edge (lamellipodium) of cultured fibroblasts is readily revealed in cells extracted briefly in Triton X-100-glutaraldehyde mixtures, fixed further in glutaraldehyde, and then negatively stained for electron microscopy. By this procedure, the leading edge regions show a highly organised, three-dimensional network of actin filaments together with variable numbers of radiating actin filament bundles or microspikes. The use of Phalloidin after glutaraldehyde fixation resulted in a marginal improvement in filament order. Processing of the cytoskeletons though the additional steps generally employed for conventional electron microscopy resulted in a marked deterioration or complete disruption of the order of the actin filament networks. In contrast, the actin filaments of the stress fiber bundles were essentially unaffected. Thus, postfixation in osmium tetroxide (1% for 7 min at room temperature) transformed the networks to a reticulum of kinked fibers, resembling those produced by the exposure of muscle F-actin to OsO4 in vitro (P. Maupin-Szamier and T. D. Pollard. 1978. J. Cell Biol. 77:837--852). While limited exposure to OsO4 (0.2+ for 20 min at 0 degrees C) obviated this destruction, dehydration in acetone or ethanol, with or without post-osmication, caused a further and unavoidable disordering and aggregation of the meshwork filaments. The meshwork regions of the leading edge then showed a striking resemblance to the networks hitherto described in critical point-dried preparations of cultured cells. I conclude that much of the "microtrabecular lattice" described by Wolosewick and Porter (1979. J. Cell Biol. 82:114--139) in the latter preparations constitutes actin meshworks and actin filament arrays, with their associated components, that have been distorted and aggregated by the preparative procedures employed.


Tele-ICU: experience to date.
Tele-intensive care unit (ICU) is a care provided to critically ill patients by off-site clinicians using audio, video, and electronic links to leverage technical, informational, and clinical resources. Providing care includes the ability to detect patient's instability or laboratory abnormalities in real-time, collect additional clinical information from or about the patient, order diagnostic testing, make diagnoses, implement treatment, render other forms of intensive care such as managing life-support devices, and communicate with patients and bedside providers. This review summarizes how tele-ICU services are delivered, the alternative approaches that have been used, and summarizes published reports of its effects on patient-focused outcomes. Tele-ICU is thought to have great promise to support critically ill adults.


Binding specificity of Escherichia coli single-stranded DNA binding protein for the chi subunit of DNA pol III holoenzyme and PriA helicase.
The Escherichia coli single-stranded DNA binding protein (SSB) plays a central role in DNA metabolism through its high affinity interactions with ssDNA, as well as its interactions with numerous other proteins via its unstructured C-termini. Although SSB interacts with at least 14 other proteins, it is not understood how SSB might recruit one protein over another for a particular metabolic role. To probe the specificity of these interactions, we have used isothermal titration calorimetry to examine the thermodynamics of binding of SSB to two E. coli proteins important for DNA replication, the chi subunit of DNA polymerase III holoenzyme and the PriA helicase. We find that an SSB tetramer can bind up to four molecules of either protein primarily via interactions with the last approximately 9 amino acids in the conserved SSB C-terminal tails (SSB-Ct). We observe intrinsic specificity for the binding of an isolated SSB-Ct peptide to PriA over chi due primarily to a more favorable enthalpic component. PriA and chi also bind with weaker affinity to SSB (in the absence of ssDNA) than to isolated SSB-Ct peptides, indicating an inhibitory effect of the SSB protein core. Although the binding affinity of SSB for both chi and PriA is enhanced if SSB is prebound to ssDNA, this effect is larger with PriA indicating a further enhancement of SSB specificity for PriA. These results also suggest that DNA binding proteins such as PriA, which also interact with SSB, could use this interaction to gain access to ssDNA by first interacting with the SSB C-termini.


Inorganic pyrophosphate in plasma in normal persons and in patients with hypophosphatasia, osteogenesis imperfecta, and other disorders of bone.
An isotope dilution method, using (32)P-labeled pyrophosphate, has been developed for the measurement of inorganic pyrophosphate (PP(1)) in human plasma. The specificity of the method was better than 90% as assessed by elution patterns during ion-exchange chromatography, by paper chromatography, and by incubation with inorganic pyrophosphatase. The 99% confidence limits for a single estimation of plasma PP(1) was +/-13%. There were no differences in plasma PP(1) between men and women, but the values in young people (0-15 yr) were slightly higher than in older people. The mean concentration (+/-SE) of PP(1) in the plasma of 73 men and women was 3.50 +/-0.11 mumoles/liter (0.217 +/-0.007 mug P/ml) and the normal range (99% limits) was 1.19-5.65 mumoles/liter (0.074-0.350 mug P/ml). It has been suggested that PP(1) may be important in calcium metabolism because PP(1) can prevent the precipitation of calcium phosphates in vitro and in vivo, and can slow the rates at which hydroxyapatite crystals grow and dissolve. Plasma PP(1) was therefore measured in several disorders of bone. Normal values were found in osteogenesis imperfecta, osteopetrosis, "acute" osteoporosis, and primary hyperparathyroidism. Plasma PP(1) was invariably raised in hypophosphatasia. The excess of PP(1) in plasma might be the cause of the defective mineralization in hypophosphatasia and the function of alkaline phosphatase in bone may be to act as a pyrophosphatase at sites of calcium deposition.


EEG-Based Emotion Classification for Alzheimer's Disease Patients Using Conventional Machine Learning and Recurrent Neural Network Models.
As the number of patients with Alzheimer's disease (AD) increases, the effort needed to care for these patients increases as well. At the same time, advances in information and sensor technologies have reduced caring costs, providing a potential pathway for developing healthcare services for AD patients. For instance, if a virtual reality (VR) system can provide emotion-adaptive content, the time that AD patients spend interacting with VR content is expected to be extended, allowing caregivers to focus on other tasks. As the first step towards this goal, in this study, we develop a classification model that detects AD patients' emotions (e.g., happy, peaceful, or bored). We first collected electroencephalography (EEG) data from 30 Korean female AD patients who watched emotion-evoking videos at a medical rehabilitation center. We applied conventional machine learning algorithms, such as a multilayer perceptron (MLP) and support vector machine, along with deep learning models of recurrent neural network (RNN) architectures. The best performance was obtained from MLP, which achieved an average accuracy of 70.97%; the RNN model's accuracy reached only 48.18%. Our study results open a new stream of research in the field of EEG-based emotion detection for patients with neurological disorders.


CD6 attenuates early and late signaling events, setting thresholds for T-cell activation.
The T lineage glycoprotein CD6 is generally considered to be a costimulator of T-cell activation. Here, we demonstrate that CD6 significantly reduces early and late T-cell responses upon superantigen stimulation or TCR triggering by Abs. Measuring calcium mobilization in single cells responding to superantigen, we found that human T cells expressing rat CD6 react significantly less well compared with T cells not expressing the exogenous receptor. When the cytoplasmic domain of rat CD6 was removed, calcium responses were recovered, indicating that the inhibitory properties of CD6 are attributable to its cytoplasmic domain. Calcium responses, and also late indicators of T-cell activation such as IL-2 release, were also diminished in TCR-activated Jurkat cells expressing human CD6, compared with CD6-deficient cells or cells expressing a cytoplasmic deletion mutant of human CD6. Similarly, calcium signals triggered by anti-CD3 were enhanced in human T lymphocytes following morpholino-mediated suppression of CD6 expression. Finally, the proliferation of T lymphocytes was increased when the CD6-CD166 interaction was blocked with anti-CD166 Abs, but inhibited when anti-CD6 Abs were used. Our data suggest that CD6 is a signaling attenuator whose expression alone, i.e. in the absence of ligand engagement, is sufficient to restrain signaling in T cells.


Molecular MRI for sensitive and specific detection of lung metastases.
Early and specific detection of metastatic cancer cells in the lung (the most common organ targeted by metastases) could significantly improve cancer treatment outcomes. However, the most widespread lung imaging methods use ionizing radiation and have low sensitivity and/or low specificity for cancer cells. Here we address this problem with an imaging method to detect submillimeter-sized metastases with molecular specificity. Cancer cells are targeted by iron oxide nanoparticles functionalized with cancer-binding ligands, then imaged by high-resolution hyperpolarized (3)He MRI. We demonstrate in vivo detection of pulmonary micrometastates in mice injected with breast adenocarcinoma cells. The method not only holds promise for cancer imaging but more generally suggests a fundamentally unique approach to molecular imaging in the lungs.


Primary biliary cirrhosis.
Primary biliary cirrhosis is a chronic cholestatic liver disease characterised by destruction of small intrahepatic bile ducts, leading to fibrosis and potential cirrhosis through resulting complications. The serological hallmark of primary biliary cirrhosis is the antimitochondrial antibody, a highly disease-specific antibody identified in about 95% of patients with primary biliary cirrhosis. These patients usually have fatigue and pruritus, both of which occur independently of disease severity. The typical course of primary biliary cirrhosis has changed substantially with the introduöction of ursodeoxycholic acid (UDCA). Several randomised placebo-controlled studies have shown that UDCA improves transplant-free survival in primary biliary cirrhosis. However, about 40% of patients do not have a biochemical response to UDCA and would benefit from new therapies. Liver transplantation is a life-saving surgery with excellent outcomes for those with decompensated cirrhosis. Meanwhile, research on nuclear receptor hormones has led to the development of exciting new potential treatments. This Seminar will review the current understanding of the epidemiology, pathogenesis, and natural history of primary biliary cirrhosis, discuss management of the disease and its sequelae, and introduce research on new therapeutic options.


Winning the arms race: host-parasite shared evolutionary history reduces infection risks in fish final hosts.
Parasite manipulation of intermediate hosts evolves to increase parasite trophic transmission to final hosts, yet counter selection should act on the final host to reduce infection risk and costs. However, determining who wins this arms race and to what extent is challenging. Here, for the first time, comparative functional response analysis quantified final host consumption patterns with respect to intermediate host parasite status. Experiments used two evolutionarily experienced fish hosts and two naive hosts, and their amphipod intermediate hosts of the acanthocephalan parasite Pomphorhynchus tereticollis The two experienced fish consumed significantly fewer infected than non-infected prey, with lower attack rates and higher handling times towards the former. Conversely, the two naive fish consumed similar numbers of infected and non-infected prey at most densities, with similar attack rates and handling times towards both. Thus, evolutionarily experienced final hosts can reduce their infection risks and costs via reduced intermediate host consumption, with this not apparent in naive hosts.


The Effect of Lightweight Concrete Cores on the Thermal Performance of Vacuum Insulation Panels.
The performance of vacuum insulation panels (VIPs) is strongly affected by several factors, such as panel thickness, design, quality of vacuum, and material type. In particular, the core materials inside VIPs significantly influence their overall performance. Despite their superior insulation performance, VIPs are limited in their widespread use as structural materials, because of their low material strength and the relatively expensive core materials. As an alternative core material that can compensate these limitations, foamed concrete, a type of lightweight concrete with very low density, can be used. In this study, two different types of foamed concrete were used as VIP core materials, with their effects on the thermal behavior of the VIPs having been evaluated using experimental and numerical methods. To confirm and generate numerical models for VIP analysis, micro-computed tomography (micro-CT) was utilized. The obtained results show that insulation effects increase effectively when panels with lightweight concrete are in a vacuum, and both foamed concrete types can be effectively used as VIP core materials.


Speciation by reinforcement: a model derived from studies of Drosophila.
Reinforcement is an increase in premating reproductive isolation between taxa resulting from selection against hybrids. We present a model of reinforcement with a novel type of selection on female mating behavior. Previous models of reinforcement have focused on the divergence of female mating preferences between nascent species. We suggest that an increase in the level of female mating discrimination can yield reinforcement without further divergence of either male characters or female preferences. This model indicates that selection on mating discrimination is a viable mechanism for reinforcement and may allow speciation under less stringent conditions than selection on female preference. This model also incorporates empirical results from genetic studies of hybrid fitness determination in Drosophila species. We find that the details of inheritance, which include sex-linked transmission, sex-limited fertility reduction, and X-autosome epistasis, have important effects on the likelihood of reinforcement. In particular, X-autosome epistasis for hybrid fitness determination facilitates reinforcement when hybrid fertility reduction occurs in males, but hinders the process when it occurs in females. HALDANE's rule indicates that hybrid sterility will generally evolve in males prior to females within nascent species. Thus, HALDANE's rule and X-autosome epistasis provide conditions that are surprisingly favorable for reinforcement in Drosophila.


Intramedullary nailing with reaming to treat non-union of the tibia.
The records of fifty-one patients who were treated by intramedullary nailing with reaming for non-union of the tibia were retrospectively reviewed. The fractures had been treated initially by closed reduction and immobilization in a cast, external fixation followed by immobilization in a cast, fixation by pins incorporated in a plaster cast, minimum internal fixation and immobilization in a cast, dynamic compression plating, or intramedullary nailing with or without reaming. After the initial treatment had failed, intramedullary nailing with reaming was done to gain union. Although closed nailing of the tibia was preferred, in thirty-three patients, the site of the non-union was opened to improve alignment by performing an osteotomy or to remove failed hardware. Bone grafts from the iliac crest were used in ten patients, and a fibular ostectomy or osteotomy was done in thirty-three. Of thirty-four open fractures (fourteen grade I, seven grade II, and thirteen grade III), eight were infected at the time of intramedullary nailing. The average time of the diagnosis of a non-union was 9.6 months; the average length of follow-up after nailing was twenty months. In forty-nine (96 per cent) of the fifty-one patients, tibial union occurred at an average of seven months postoperatively. Complications included persistent infection (three patients), acquired infection after intramedullary nailing with reaming (three patients), fracture of the nail that necessitated an additional operation (two patients), shortening of more than one centimeter (two patients), malrotation of more than 15 degrees (one patient), peroneal palsy (one patient), and amputation (one patient). When used to treat non-union of the tibia, intramedullary nailing with reaming can produce union as effectively as other alternatives, while enabling the patient to function more normally without external immobilization or walking aids.


Prevention of rotavirus gastroenteritis in infants and children: rotavirus vaccine safety, efficacy, and potential impact of vaccines.
Rotavirus infection is the most common cause of severe gastroenteritis globally, with greater than 86% of deaths occurring in low-income and middle-income countries. There are two rotavirus vaccines currently licensed in the United States and prequalified by the World Health Organization. RV1 is a monovalent attenuated human rotavirus strain, given orally in two doses. RV5 is a pentavalent human-bovine reassortant rotavirus vaccine, given orally in three doses. A third rotavirus vaccine, LLV, is a lamb rotavirus strain given orally as a single dose, which is currently available only in China. RV1 and RV5 have been shown to be highly efficacious in developed countries, and initial results from trials in Africa and Asia are promising as well. At least three other vaccines are in development, which are being developed by manufacturers of developing countries. Further studies are needed to clarify issues including administration of oral rotavirus vaccines with breastfeeding and other oral vaccines, and alterations in dosing schedule. Using new data on global diarrheal burden, rotavirus is estimated to cause 390,000 deaths in children younger than 5 years. Should rotavirus vaccines be introduced in the routine immunization programs of all countries, a potential of 170,000 deaths could be prevented annually. The largest impact on mortality would be seen in low-income and middle-income countries, despite poor immunization coverage and lower efficacy. Therefore, international efforts are needed to ensure that rotavirus vaccines reach the populations with highest burden of rotavirus disease.


Crack smokers' intention to use condoms with loved partners: intervention development using the theory of reasoned action, condom beliefs, and processes of change.
Prevalence rates of HIV infection acquired through heterosexual contacts have risen steadily since 1982. Crack cocaine smokers are at particular risk of HIV infection due to heterosexual exposure. HIV risk reduction interventions seeking to increase condom use among drug users have met with minimal success, and there is a need for interventions to be strongly grounded in psychosocial models of behaviour change. This study presents the results of an investigation of predictors of intention to use condoms and related therapy processes among heterosexual drug users. Data were analyzed from 586 crack smokers recruited in Washington, DC, Miami, Florida, and Collier County, Florida who reported having both primary and casual sex partners. Participants responded to items derived from the theory of reasoned action, the theory of planned behaviour and the transtheoretical model of change. Condom use beliefs and therapy processes used to initiate and maintain condom use were assessed. Outcome expectancies and normative beliefs were the strongest predictors of intention to use condoms with a primary sexual partner. In turn, beliefs that condoms inhibit sexual romance and decrease sexual pleasure strongly predicted outcome expectancies. Therapy processes found to be associated with these constructs included: self-liberation, counter conditioning and stimulus control/reinforcement. Results suggest that HIV risk reduction interventions using a group format and targeting condom beliefs related to sexual romance and pleasure will decrease negative outcome expectancies about condom use. Also, reinforcing attempts to use condoms with intimate partners should increase positive outcome expectancies and intention to initiate or maintain condoms with a primary sexual partner.


Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells.
Resistance to targeted cancer therapies is an important clinical problem. The discovery of anti-resistance drug combinations is challenging as resistance can arise by diverse escape mechanisms. To address this challenge, we improved and applied the experimental-computational perturbation biology method. Using statistical inference, we build network models from high-throughput measurements of molecular and phenotypic responses to combinatorial targeted perturbations. The models are computationally executed to predict the effects of thousands of untested perturbations. In RAF-inhibitor resistant melanoma cells, we measured 143 proteomic/phenotypic entities under 89 perturbation conditions and predicted c-Myc as an effective therapeutic co-target with BRAF or MEK. Experiments using the BET bromodomain inhibitor JQ1 affecting the level of c-Myc protein and protein kinase inhibitors targeting the ERK pathway confirmed the prediction. In conclusion, we propose an anti-cancer strategy of co-targeting a specific upstream alteration and a general downstream point of vulnerability to prevent or overcome resistance to targeted drugs.


Aztec cannibalism: an ecological necessity?
It has been proposed that Aztec human sacrifice and cannibalism can best be explained as a response to population pressure and famine. The greatest amount of cannibalism, however, coincided with times of harvest, not with periods of scarcity, and is better explained as a thanksgiving. Tenochtitlan recevied large quantities of food tribute and engaged in intensive (chinampa) agriculture. These two sources alone would have provided enough to feed practically the entire population of the city. The Aztecs also consumed various animals and insects that were good protein sources. The amount of protein available from human sacrifice would not have made a significant contribution to the diet. Cannibalism was not motivated by starvation but by a belief that this was a way to commune with the gods.


Cancer invasion and micrometastasis visualized in live tissue by green fluorescent protein expression.
We report the establishment of stable, high-level green fluorescent protein (GFP)-expressing cell lines in vitro that permit the detection and visualization of distant micrometastases when they are implanted orthotopically in nude mice. Chinese hamster ovary cells were transfected with the dicistronic expression vector containing the humanized GFP cDNA. A stable GFP-expressing clone was selected in 1.5 microM methotrexate in vitro and injected s.c. in nude mice. Stable high-level expression of GFP was maintained in the s.c. growing tumors. To use GFP expression for metastasis studies, fragments of s.c. growing tumor, which are comprised of GFP-expressing cells, were implanted by surgical orthotopic implantation in the ovary of nude mice. Subsequent micrometastases were detected in systemic organs and could be visualized by GFP fluorescence in the lung, liver, and other organs down to the single-cell level. With this fluorescent tool, we detected and visualized for the first time tumor cells at the microscopic level in fresh viable tissue in their normal host organ. Confocal microscopy further enabled us to study physiologically relevant patterns of invasion and micrometastasis.


Swearing as a response to pain-effect of daily swearing frequency.
Previously we showed that swearing produces a pain lessening (hypoalgesic) effect for many people.(20) This paper assesses whether habituation to swearing occurs such that people who swear more frequently in daily life show a lesser pain tolerance effect of swearing, compared with people who swear less frequently. Pain outcomes were assessed in participants asked to repeat a swear word versus a nonswear word. Additionally, sex differences and the roles of pain catastrophizing, fear of pain, and daily swearing frequency were explored. Swearing increased pain tolerance and heart rate compared with not swearing. Moreover, the higher the daily swearing frequency, the less was the benefit for pain tolerance when swearing, compared with when not swearing. This paper shows apparent habituation related to daily swearing frequency, consistent with our theory that the underlying mechanism by which swearing increases pain tolerance is the provocation of an emotional response. This article presents further evidence that, for many people, swearing (cursing) provides readily available and effective relief from pain. However, overuse of swearing in everyday situations lessens its effectiveness as a short-term intervention to reduce pain.


Neuromuscular function following prolonged intense self-paced exercise in hot climatic conditions.
Muscle weakness following constant load exercise under heat stress has been associated with hyperthermia-induced central fatigue. However, evidence of central fatigue influencing intense self-paced exercise in the heat is lacking. The purpose of this investigation was to evaluate force production capacity and central nervous system drive in skeletal muscle pre- and post-cycle ergometer exercise in hot and cool conditions. Nine trained male cyclists performed a 20-s maximal voluntary isometric contraction (MVC) prior to (control) and following a 40-km time trial in hot (35°C) and cool (20°C) conditions. MVC force production and voluntary activation of the knee extensors was evaluated via percutaneous tetanic stimulation. In the cool condition, rectal temperature increased to 39.0°C and reached 39.8°C in the heat (P < 0.01). Following exercise in the hot and cool conditions, peak force declined by ~90 and ~99 N, respectively, compared with control (P < 0.01). Mean force decreased by 15% (hot) and 14% (cool) (P < 0.01 vs. control). Voluntary activation during the post-exercise MVC declined to 93.7% (hot) and 93.9% (cool) (P < 0.05 vs. control). The post-exercise decline in voluntary activation represented ~20% of the decrease in mean force production in both conditions. Therefore, the additional increase in rectal temperature did not exacerbate the loss of force production following self-paced exercise in the heat. The impairment in force production indicates that the fatigue exhibited by the quadriceps is mainly of peripheral origin and a consequence of the prolonged contractile activity associated with exercise.


Racial Disparities in School Belonging and Prospective Associations With Diabetes and Metabolic Syndrome.
School belonging has important implications for academic, psychological, and health outcomes, but the associations between racial disparities in school belonging and health have not been explored to date. To examine associations between school-level racial disparities in belonging and cardiometabolic health into adulthood in a national sample of Black and White children, adolescents, and young adults. Prospective cohort study of a US national sample of 4830 Black and White students (National Longitudinal Study of Adolescent Health) followed up for 13 years. The study was conducted from 1994 to 1995 for wave 1 and in 2008 for wave 4. Data were analyzed from June 14 to August 13, 2021. School-level racial disparities in belonging at baseline were calculated as the mean level of school belonging for Black students minus the mean level of school belonging for White students at the school that they attended when they were aged 12 to 20 years. Diabetes and metabolic syndrome were measured as outcomes for these same participants at 24 to 32 years of age. The study included 4830 students. For wave 1, mean (SD) age was 16.1 (1.7) years, and for wave 4, 29.0 (1.7) years. A total of 2614 (54.1%) were female, 2219 were non-Hispanic Black (45.9%), and 2611 were non-Hispanic White (54.1%). Among Black students, attending a school with a greater Black-White disparity in school belonging (more negative scores) was associated with an increased risk for diabetes (odds ratio, 0.66 [95% CI, 0.46-0.95]) and more risk factors for metabolic syndrome (rate ratio, 0.95 [95% CI, 0.90-1.00]) in adulthood 13 years later. These associations persisted above individual-level controls (age, sex, and body mass index) and school-level controls (school size, percentage of Black students, and percentage of Black teachers) and were not explained by either an individual's own perception of school belonging or the mean level of belonging across the whole school. In this prospective cohort study of US students, racial disparities in school belonging were associated with risks for diabetes and metabolic syndrome in Black students. Among students, fostering a more equal sense of school belonging across racial groups may have implications for health disparities in the cardiometabolic domain into adulthood.


Effect of CYP1A inhibition on the biotransformation of benzo[a]pyrene in two populations of Fundulus heteroclitus with different exposure histories.
Sediment contaminated with polycyclic aromatic hydrocarbons (PAHs) from a Superfund site on the Elizabeth River (ER) in Portsmouth, VA, is teratogenic to embryonic killifish (Fundulus heteroclitus) from reference sites. However, embryos born to a population of ER killifish are resistant to PAH-induced teratogenicity. Mechanisms underlying the resistance are unclear; however, ER killifish are refractory to induction of metabolic enzyme cytochrome P4501A (CYP1A), at the level of mRNA, protein and activity. The contaminated ER sediment comprises a complex mixture of PAHs with different mechanisms of toxicity. While many are inducers of metabolic enzymes involved in both phase I and phase II of biotransformation, some PAHs can also inhibit phase I enzymatic activity. Previous research has shown that co-exposure to PAHs with different modes of action can result in synergistic embryotoxicity (Billiard, S.M., Meyer, J.N.D., Wassenberg, M., Hodson, P.V., Di Giulio, R.T., 2008. Nonadditive effects of PAHs on early vertebrate development: mechanisms and implications for risk assessment. Toxicological Sciences 105, 5-23). Two of the abundant PAHs at the ER are fluoranthene (FL), a CYP1A inhibitor, and benzo[a]pyrene (BaP), a CYP1A inducer. Based on the ER resistant phenotype and the PAH mixture in the ER sediment, we hypothesized that the inhibition of CYP1A activity affects the teratogenicity of PAHs through a biotransformation-mediated mechanism. To examine this hypothesis, we compared the responses of killifish embryos born to parents from the ER and from a reference site (King's Creek (KC), VA) after a water-borne exposure to BaP (0-400 microg/L) in the presence or absence of FL (0-500 microg/L). Embryos were dosed from 24 to 120 h post-fertilization (hpf) and were analyzed for induction of CYP1 enzymatic activity as measured by the ethoxyresorufin-O-deethylase (EROD) assay, cardiac deformities, and BaP metabolic profile. KC embryos showed significant induction of CYP1 protein activity at all BaP concentrations examined. Co-exposure to 500 microg/L of FL significantly decreased CYP1 activity and increased cardiac deformities. ER embryos showed no change in CYP1 activity or cardiac deformities for any treatment. Significantly greater concentrations of BaP and BaP 9,10-dihydrodiol were recovered from ER embryos compared to those from KC. Co-exposure with FL did not significantly alter the amount of BaP or the metabolites recovered in either population. These findings suggest that the teratogenicity observed by co-exposure to BaP and FL cannot fully be explained by alteration in BaP metabolism. This study also indicates that the metabolic adaptation observed in the ER killifish cannot be explained simply by the refractory CYP1 phenotype.


Biological markers of asexuality: Handedness, birth order, and finger length ratios in self-identified asexual men and women.
Human asexuality is defined as a lack of sexual attraction to anyone or anything and it has been suggested that it may be best conceptualized as a sexual orientation. Non-right-handedness, fraternal birth order, and finger length ratio (2D:4D) are early neurodevelopmental markers associated with sexual orientation. We conducted an Internet study investigating the relationship between self-identification as asexual, handedness, number of older siblings, and self-measured finger-lengths in comparison to individuals of other sexual orientation groups. A total of 325 asexuals (60 men and 265 women; M age, 24.8 years), 690 heterosexuals (190 men and 500 women; M age, 23.5 years), and 268 non-heterosexuals (homosexual and bisexual; 64 men and 204 women; M age, 29.0 years) completed online questionnaires. Asexual men and women were 2.4 and 2.5 times, respectively, more likely to be non-right-handed than their heterosexual counterparts and there were significant differences between sexual orientation groups in number of older brothers and older sisters, and this depended on handedness. Asexual and non-heterosexual men were more likely to be later-born than heterosexual men, and asexual women were more likely to be earlier-born than non-heterosexual women. We found no significant differences between sexual orientation groups on measurements of 2D:4D ratio. This is one of the first studies to test and provide preliminary empirical support for an underlying neurodevelopmental basis to account for the lack of sexual attraction characteristic of asexuality.


The hippocampal region of rats and mice after a single i.p. dose of clioquinol: loss of synaptic zinc, cell death and c-Fos induction.
Clioquinol (CQ) is able to chelate synaptic zinc, which can modulate excitatory and inhibitory neurotransmission. In humans, CQ was associated with cases of transient global amnesia (TGA) and with the neurodegenerative syndrome subacute myelo-optico-neuropathy (SMON). We examined the CQ induced loss of synaptic zinc, cell death and c-Fos induction in rats and mice. In rats, we found a strong reduction of histochemically reactive synaptic zinc no later than 4 h after the injection of the lowest dose of CQ (50 mg/kg) and, for all doses used, a return to control levels after 48 h. There was no evidence of cell death for any dose and up to 1 week after CQ injections. Only a slight induction of c-Fos was seen in the hippocampus for the higher doses used (100-200 mg/kg). In mice injected with 100 mg/kg, CQ also resulted in a fast loss of synaptic zinc. c-Fos was induced after 4 h in cell populations of the hippocampal region and other parts of the telencephalon, and substantially increased after 24 h. One day after the injection we found a pattern of cell loss (hilus, parts of CA3, CA1 and layer III of the medial entorhinal cortex) reminiscent of that seen in models of temporal lobe epilepsy. In conjunction with published data on the behavioral effects of zinc chelation and the modulatory effects of zinc in excitatory neurotransmission, our results indicate that the loss of synaptic zinc may have been involved in TGA and the neuropathology associated with SMON.


Participatory environmental governance of infrastructure projects affecting reindeer husbandry in the Arctic.
Several infrastructure projects are under development or already operational across the Arctic region. Often the deployment of such projects creates benefits at the national, regional, or global scales. However, local communities can experience negative impacts due to the requirements for extensive land areas, which cause pressure on traditional land use. Public participation in environmental planning such as Environmental Impact Assessment (EIA) enables local communities to provide feedback on the environmental, social, and economic challenges of infrastructure projects. Ideally, participation can improve the means of social learning for all involved parties and help to co-develop sustainable solutions. The subject of our research is reindeer herders' participation in EIA procedures of mines and wind farms in Finland because these types of projects affect reindeer husbandry. We study empirically how stakeholders involved in the EIAs perceive the participation of reindeer herders in the planning and implementation of infrastructure projects, and how these differ from the perceptions of the reindeer herders who are affected by the infrastructure projects. Our qualitative data is based on in-depth semi-structured interviews (N = 31) with members of the industry sector, consultants, governmental authorities, and representatives of local communities; in this study, the reindeer herders. The results show that herders' level of participation in the EIAs and the benefits and challenges of participation are perceived differently. Furthermore, the regulatory framework does not adequately ensure that the developer carries social and environmental responsibilities throughout the infrastructure project's lifetime, and that regular communication with herders will also be maintained after the EIAs. Herders' expertise should be used throughout the project lifetime. For example, more attention should be paid to both negotiating possible options for compensation and monitoring mechanisms when the infrastructure projects are pre-screened for the EIAs, as well as to co-designing the different project alternatives with herders for the EIAs.


Religious struggle as a predictor of subsequent mental and physical well-being in advanced heart failure patients.
Patients with congestive heart failure (CHF) often report high levels of religiousness, which may mitigate the stressfulness of their condition. However, religious struggle, reflecting negative attitudes toward God and a strained meaning system, may be detrimental to well-being. Little is known about religious struggle in those with CHF, particularly in relation to physical health and well-being over time. We examined associations of religious struggle and subsequent mental and physical well-being in 101 endstage CHF patients who completed questionnaires twice over 3 months. Religious struggle predicted higher number of nights subsequently hospitalized, higher depression, and marginally lower life satisfaction. When controlling for baseline levels of well-being, effectively assessing change in those outcomes, religious struggle remained a significant predictor of hospitalization and also emerged as a marginally significant predictor of lower physical functioning. Struggle was unrelated to health-related quality of life. Post-hoc analyses suggest that these effects were particularly strong for those endorsing greater religious identification. Religious struggle appears to have a potentially negative impact on well-being in advanced CHF; therefore, helping patients to address issues of struggle may meaningfully lessen the personal and societal costs of CHF.


Therapist-delivered and self-help interventions for gambling problems: A review of contents.
Background and aims To date, no systematic approach to identifying the content and characteristics of psychological interventions used to reduce gambling or problem gambling has been developed. This study aimed to develop a reliable classification system capable of identifying intervention characteristics that could, potentially, account for greater or lesser effectiveness. Methods Intervention descriptions were content analyzed to identify common and differentiating characteristics. A coder manual was developed and applied by three independent coders to identify the presence or absence of defined characteristics in 46 psychological and self-help gambling interventions. Results The final classification taxonomy, entitled Gambling Intervention System of CharacTerization (GIST), included 35 categories of intervention characteristics. These were assigned to four groups: (a) types of change techniques (18 categories; e.g., cognitive restructuring and relapse prevention), (b) participant and study characteristics (6 categories; e.g., recruitment strategy and remuneration policy), and (c) characteristics of the delivery and conduct of interventions (11 categories; e.g., modality of delivery and therapist involvement), and (d) evaluation characteristics (e.g., type of control group). Interrater reliability of identification of defined characteristics was high (κ = 0.80-1.00). Discussion This research provides a tool that allows systematic identification of intervention characteristics, thereby enabling consideration, not only of whether interventions are effective or not, but also of which domain-relevant characteristics account for greater or lesser effectiveness. The taxonomy also facilitates standardized description of intervention content in a field in which many diverse interventions have been evaluated. Conclusion Application of this coding tool has the potential to accelerate the development of more efficient and effective therapist-delivered and self-directed interventions to reduce gambling problems.


Narrow spectral response schottky photodiodes.
Spicer's absorption diffusion model is extended to analyze Schottky photodiodes which possess special characteristics. The model describes the generation of minority carriers by optical absorption in the bulk of a semiconductor material. The magnitude and shape of the spectral response for a minimally depleted device is found to depend on the rate of variation of the absorption coefficient with wavelength on the thickness of the absorbing region T and on the minority carrier's diffusion length l. Narrow spectral response can exist in this device only in the wavelength region wherein the absorption coefficient alpha is rapidly changing. A combination of high quantum efficiency with sharp tuning is found to exist.