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Identifying optimal depression screening tools for use in maternal health clinics could improve maternal and infant health. We compared four tools for diagnostic performance and epidemiologic associations. This study was nested in a cluster-randomized trial in Kenya. Women in 20 maternal health clinics were evaluated at 6 weeks postpartum with Center for Epidemiologic Studies Depression Scale (CESD-10), Edinburgh Postnatal Depression Scale (EPDS), Patient Health Questionnaire-9 and -2 (PHQ-9, PHQ-2) for moderate-to-severe depressive symptoms (MSD) [CESD-10 ≥ 10, EPDS≥13, PHQ-9 ≥ 10, or PHQ-2 ≥ 3]. We assessed area under the curve (AUC) per scale (CESD-10, EPDS) against probable major depressive disorder (MDD) using the PHQ-9 scoring algorithm. Associations between MSD and intimate partner violence (IPV) were compared between scales. Among 3605 women, median age was 24 and 10 % experienced IPV. Prevalence of MSD symptoms varied by tool: 13 % CESD-10, 9 % EPDS, 5 % PHQ-2, 3 % PHQ-9. Compared to probable MDD, the CESD-10 (AUC:0.82) had higher AUC than the EPDS (AUC:0.75). IPV was associated with MSD using all scales: EPDS (RR:2.5, 95%CI:1.7–3.7), PHQ-2 (RR:2.3, 95%CI:1.6–3.4), CESD-10 (RR:1.9, 95%CI:1.2–2.9), PHQ-9 (RR:1.8, 95%CI:0.8–3.8). Our study did not include clinical diagnosis of MDD by a specialized clinician, instead we used provisional diagnosis of probable MDD classified by the PHQ-9 algorithm as a reference standard in diagnostic performance evaluations. Depression screening tools varied in detection of postpartum MSD. The PHQ-2 would prompt fewer referrals and showed strong epidemiologic association with a cofactor. • We compared four depression scales (EPDS, PHQ-9/-2, CESD-10) in postpartum women. • Scales had differences in diagnostic yield and epidemiologic associations. • Experts speculate perinatal depression estimates differ across studies due to tools used. • We confirm this with empiric data about tool influence on depression estimates. • PHQ-2 may provide optimal features for wide-scale use in maternal child health. [ABSTRACT FROM AUTHOR]

The objectives were 1) to design and produce two novel unpadded bicycle saddles with a wide/medium width and partial nose cutout; 2) to investigate the responses on pressure distribution and perceived discomfort in female cyclists. For comparison, a standard saddle was also tested. Nineteen female cyclists pedaled on an ergometer cycle for 20 min with each saddle in a counterbalanced order. A pressure mat measured saddle interface pressure. Discomfort ratings were collected using a visual analogue scale. Total mean saddle pressure remained similar across saddles. The wide saddle increased anterior and decreased posterior mean saddle pressure as compared with the standard (p < .002) and the medium saddle (p < .001). Significantly increased ischial tuberosity discomfort was found for the novel saddles (p < .001), while crotch discomfort was not significantly different between saddles. The medium width saddle appeared to be the best compromise since increased crotch discomfort was avoided and saddle pressures were redistributed. Such design may be suggested as an alternative to traditional saddles for women reporting discomfort in the perineal region. [ABSTRACT FROM AUTHOR]

Dual amylin and calcitonin receptor agonists (DACRAs) are known to induce significant weight loss as well as improve glucose tolerance, glucose control, and insulin action in rats. However, to what extent DACRAs affect insulin sensitivity beyond that induced by weight loss and if DACRAs affect glucose turnover including tissue-specific glucose uptake is still unknown. Hyperinsulinemic glucose clamp studies were carried out in pre-diabetic ZDSD and diabetic ZDF rats treated with either the DACRA KBP or the long-acting DACRA KBP-A for 12 days. The glucose rate of disappearance was assessed using 3-3H glucose and tissue-specific glucose uptake was evaluated using 14C-2-deoxy- D -glucose (14C-2DG). In diabetic ZDF rats, KBP treatment significantly reduced fasting blood glucose and improved insulin sensitivity independent of weight loss. Furthermore, KBP increased the rate of glucose clearance, likely by increasing glucose storage, but without altering the endogenous glucose production. This was confirmed in pre-diabetic ZDSD rats. Direct assessment of tissue-specific glucose uptake showed, that both KBP and KBP-A significantly increased glucose uptake in muscles. In summary, KBP treatment significantly improved insulin sensitivity in diabetic rats and markedly increased glucose uptake in muscles. Importantly, in addition to their well-established weight loss potential, the KBPs have an insulin-sensitizing effect independent of weight loss, highlighting DACRAs as promising agents for the treatment of type 2 diabetes and obesity. [Display omitted] • KBP is a dual amylin and calcitonin receptor agonist. • KBP improves glucose control and insulin sensitivity in diabetic rats. • KBP increases glucose uptake in muscles. • KBP has insulin-sensitizing effects independent of weight loss. • KBP is a promising agent for treating type 2 diabetes and obesity. [ABSTRACT FROM AUTHOR]

Summary We estimate the impact of a Farmer Field School intervention among small-scale farmers in northern Tanzania on two main development objectives: food security and poverty. We employ a series of evaluation methodologies, including a Quasi-Difference-in-Difference setup, to account for potential selection into the project, despite lack of baseline data. We find strong positive effects on food security, but no effect on poverty. Investigating possible mechanisms for this result shows that reallocation of labor resources toward own agricultural production and improved production smoothing may have led to improved food security while poverty remained unaffected. [ABSTRACT FROM AUTHOR]

Abstract: Polyethylenimines (PEIs) are highly efficient non-viral transfectants, but can induce cell death through poorly understood necrotic and apoptotic processes as well as autophagy. Through high resolution respirometry studies in H1299 cells we demonstrate that the 25kDa branched polyethylenimine (25k-PEI-B), in a concentration and time-dependent manner, facilitates mitochondrial proton leak and inhibits the electron transport system. These events were associated with gradual reduction of the mitochondrial membrane potential and mitochondrial ATP synthesis. The intracellular ATP levels further declined as a consequence of PEI-mediated plasma membrane damage and subsequent ATP leakage to the extracellular medium. Studies with freshly isolated mouse liver mitochondria corroborated with bioenergetic findings and demonstrated parallel polycation concentration- and time-dependent changes in state 2 and state 4o oxygen flux as well as lowered ADP phosphorylation (state 3) and mitochondrial ATP synthesis. Polycation-mediated reduction of electron transport system activity was further demonstrated in ‘broken mitochondria’ (freeze-thawed mitochondrial preparations). Moreover, by using both high-resolution respirometry and spectrophotometry analysis of cytochrome c oxidase activity we were able to identify complex IV (cytochrome c oxidase) as a likely specific site of PEI mediated inhibition within the electron transport system. Unraveling the mechanisms of PEI-mediated mitochondrial energy crisis is central for combinatorial design of safer polymeric non-viral gene delivery systems. [Copyright &y& Elsevier]

Abstract: Recycling of materials from municipal solid waste is commonly considered to be superior to any other waste treatment alternative. For the material fractions with a significant energy content this might not be the case if the treatment alternative is a waste-to-energy plant with high energy recovery rates. The environmental impacts from recycling and from incineration of six material fractions in household waste have been compared through life cycle assessment assuming high-performance technologies for material recycling as well as for waste incineration. The results showed that there are environmental benefits when recycling paper, glass, steel and aluminium instead of incinerating it. For cardboard and plastic the results were more unclear, depending on the level of energy recovery at the incineration plant, the system boundaries chosen and which impact category was in focus. Further, the environmental impact potentials from collection, pre-treatment and transport was compared to the environmental benefit from recycling and this showed that with the right means of transport, recyclables can in most cases be transported long distances. However, the results also showed that recycling of some of the material fractions can only contribute marginally in improving the overall waste management system taking into consideration their limited content in average Danish household waste. [Copyright &y& Elsevier]

Abstract: The 25kDa branched polyethylenimine (PEI) is a highly efficient synthetic polycation used in transfection protocols, but also triggers mitochondrial-mediated apoptotic cell death processes where the mechanistic issues are poorly understood. We now demonstrate that PEI in a concentration- and time-dependent manner can affect functions (membrane potential, swelling and respiration) and ultrastructural integrity of freshly isolated rat liver mitochondria. The threshold concentration for detection of PEI-mediated impairment of rat liver mitochondrial functions is 3μg/mL, however, lower PEI levels still exert some effects on mitochondrial morphology and respiration, and these may be related to the inherent membrane perturbing properties of this polycation. The PEI-mediated mitochondrial swelling phase is biphasic, with a fast decaying initial period (most prominent from 4μg/mL PEI) followed by a slower, linear swelling response. The slow phase is presumably the result of a time-dependent transition permeability opening in mitochondria initially resistant to swelling/depolarization, but may further be related to PEI-induced nanoscale structural defects and/or formation of pores in the outer membrane. Respiration assessments further suggested that PEI in the presence of exogenous ADP behaves in a similar fashion to a slow-acting inhibitory compound. PEI further shows an uncoupling property that is detectable at low respiration rates. The relevance of these findings to PEI-mediated initiation of intrinsic apoptotic pathway is discussed. [Copyright &y& Elsevier]

Abstract: CO2-loads from combustible waste are important inputs for national CO2 inventories and life-cycle assessments (LCA). CO2 emissions from waste incinerators are often expressed by emission factors in kg fossil CO2 emitted per GJ energy content of the waste. Various studies have shown considerable variations between emission factors for different incinerators, but the background for these variations has not been thoroughly examined. One important reason may be variations in collection of recyclable materials as source separation alters the composition of the residual waste incinerated. The objective of this study was to quantify the importance of source separation for determination of emission factors for incineration of residual household waste. This was done by mimicking various source separation scenarios and based on waste composition data calculating resulting emission factors for residual waste routed to incineration. Emission factors ranged from 27 to 40kg CO2/GJ. The results appeared most sensitive towards variations in waste composition and water content. Recycling rates and lower heating values could not be used as simple indicators of the resulting emission factors for residual household waste; however the fossil carbon ratio of the waste after source separation was found to be appropriately correlated with the emission factor. Based on the results, it is recommended to carefully evaluate the source separation and collection systems behind reported literature values when comparing different studies and when using the values for environmental assessment purposes. [Copyright &y& Elsevier]

Abstract: Background: It has been assumed that a new health technology, automated dose-dispensing (ADD), would result in benefits for medication users, including increased compliance, enhanced medication understanding, and improved safety. However, it was legislators and health professionals who pinpointed the assumed user benefits. Neither Danish nor international studies dealt with users'' perspective on ADD in general or with respect to the pinpointed benefits, and thus exploration was needed. Objectives: The objective of this article is to respond to the following research question: How does ADD affect users'' handling and consumption of medication in terms of compliance behavior, and how does the assumption of user benefits made by health professionals and legislators measure up to users'' experiences with ADD? Methods: The results built on a secondary analysis of 9 qualitative interviews with a varied selection of Danish ADD users. Decontexualizing and recontextualizing provided the framework for data analysis. Compliance behavior was framed by a theory classifying noncompliance as either conscious or unconscious. Results: Most interviewees were noncompliant in various ways, with conscious noncompliance being the more frequent type of behavior. After switching to ADD, most users experienced no change in understanding of their medications. ADD did not lead to automatic removal of old medications in users'' homes; in fact for some users, ADD led to even larger medication stockpiles. Overall, reports from patients do not show evidence of the positive implications of switching to ADD assumed by health professionals and legislators before implementation. Conclusions: As a technical aid to simplify complex medication regimes, ADD alone does not appear to eliminate noncompliance or provide a better medication understanding, nor does it automatically eliminate stockpiles of old medication in users'' homes. The gap between the perspectives of users and health professionals makes a compelling case for considering users'' voices in the development and implementation of future health technologies. [Copyright &y& Elsevier]

A new class of selective α1 adrenoceptor antagonists derived from the antipsychotic drug sertindole is described. The most potent and selective compound 1-(2-{4-[5-aminomethyl-1-(4-fluorophenyl)-1H-indol-3-yl]-1-piperidinyl}ethyl)-2-imidazolidinone (11) binds with 0.50 nM affinity for α1 adrenergic receptors and with more than 44 times lower affinity for dopamine D2,D3, D4 and serotonin 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptors. The molecular features providing high affinity for adrenergic α1 receptors and high selectivity towards dopamine D2 and serotonin 5-HT2A and 5-HT2C receptors are discussed. [Copyright &y& Elsevier]

Treatment of the complex 1 Cp*Ru(NO)(OTf) 2 (OTf = OSO 2 CF 3 , Cp* = η 5 -C(CH 3 ) 5 ) with neat 2-propanol results in the rapid quantitative formation of the Ru(0) complex [Cp*Ru(μ-NO)] 2 and (CH 3 ) 2 C O. Formation of H 2 and CHDCl 2 is detected when the reaction between 1 and 2-propanol occurs in CDCl 3 , indicating possible formation of a short-lived metal hydride species. Similar results are observed upon treatment of 1 with ethanol and methanol, with formation of acetaldehyde and formaldehyde, respectively. The kinetics of the oxidation of 2-propanol by complex 1 is studied by 1 H NMR spectroscopy in CH 2 Cl 2 at variable temperatures and the reaction is found to be first-order in complex 1 and in 2-propanol. The kinetic isotope effect for the reaction of 1 with (CD 3 ) 2 CD-OD at −11 °C is determined to be k H / k D = 2.0 (3). A mechanism for alcohol oxidation by electrophilic ruthenium (II) complexes via a β-hydrogen elimination step is proposed. The pre-equilibrium exchange step between complex Cp*Ru(NO)(OTf) 2 ( 1 ) and alcohol-coordinated species is examined by 19 F and 1 H NMR spectroscopy in CH 2 Cl 2 solution, where triflate substitution is found to be exothermic and entropically unfavorable. The synthesis and solid state structure of the chelate-stabilized complex diol salt [Cp*Ru(NO)(HO–CH 2 CH 2 –OH)][2OTf] are discussed. [ABSTRACT FROM AUTHOR]

Polyethylenimines (PEIs) are among the most efficient polycationic non-viral transfectants. PEI architecture and size not only modulate transfection efficiency, but also cytotoxicity. However, the underlying mechanisms of PEI-induced multifaceted cell damage and death are largely unknown. Here, we demonstrate that the central mechanisms of PEI architecture- and size-dependent perturbations of integrated cellular metabolomics involve destabilization of plasma membrane and mitochondrial membranes with consequences on mitochondrial oxidative phosphorylation (OXPHOS), glycolytic flux and redox homeostasis that ultimately modulate cell death. In comparison to linear PEI, the branched architectures induced greater plasma membrane destabilization and were more detrimental to glycolytic activity and OXPHOS capacity as well as being a more potent inhibitor of the cytochrome c oxidase. Accordingly, the branched architectures caused a greater lactate dehydrogenase (LDH) and ATP depletion, activated AMP kinase (AMPK) and disturbed redox homeostasis through diminished availability of nicotinamide adenine dinucleotide phosphate (NADPH), reduced antioxidant capacity of glutathione (GSH) and increased burden of reactive oxygen species (ROS). The differences in metabolic and redox imprints were further reflected in the transfection performance of the polycations, but co-treatment with the GSH precursor N -acetyl-cysteine (NAC) counteracted redox dysregulation and increased the number of viable transfected cells. Integrated biomembrane integrity and metabolomic analysis provides a rapid approach for mechanistic understanding of multifactorial polycation-mediated cytotoxicity, and could form the basis for combinatorial throughput platforms for improved design and selection of safer polymeric vectors. [ABSTRACT FROM AUTHOR]

Abstract: The present study describes the pharmacological profile of the putative antipsychotic drug Lu 35-138 ((+)-(S)-3-{1-[2-(1-acetyl-2,3-dihydro-1H-indol-3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl}-6-chloro-1H-indole). The in vitro receptor profile of Lu 35-138 revealed high affinity (K i =5 nM) and competitive antagonism (K b =8 nM) at dopamine D4 receptors combined with potent 5-HT uptake inhibition (IC50 =3.2 nM) and moderate α1-adrenoceptor affinity (K i =45 nM). In vivo, Lu 35-138 selectively counteracted hyperlocomotion induced by d-amphetamine (0.5 mg/kg; ED50 =4.0 mg/kg, s.c.) in rats and phencyclidine (PCP; 2.5 mg/kg; ED50 =13 mg/kg, s.c.) in mice. Lu 35-138 was unable to affect hyperlocomotion induced by a high dose of d-amphetamine (2.0 mg/kg), which indicates a preferential action on limbic versus striatal structures. A similar limbic selectivity of Lu 35-138 was indicated in voltammetric measure of dopamine output in the core and shell subdivisions of the nucleus accumbens in rats. Furthermore, a relatively large dose of Lu 35-138 (18 mg/kg, s.c.) counteracted d-amphetamine-induced disruption of pre-pulse inhibition in rats and repeated administration of Lu 35-138 (0.31 or 1.25 mg/kg, p.o. once daily for 3 weeks) reduced the number of spontaneously active dopamine neurones in the ventral tegmental area, underlining its antipsychotic-like profile. Lu 35-138 failed to induce catalepsy in rats or dystonia in Cebus apella monkeys and did not deteriorate spatial memory in rats as assessed by water maze performance. Collectively, these results suggest that Lu 35-138 possesses antipsychotic activity combined with a low extrapyramidal and cognitive side effect liability. [Copyright &y& Elsevier]