Scoping review of indicators and methods of measurement used to evaluate the impact of dog population management interventions

Background: Dogs are ubiquitous in human society and attempts to manage their populations are common to most countries. Managing dog populations is achieved through a range of interventions to suit the dog population dynamics and dog ownership characteristics of the location, with a number of potential impacts or goals in mind. Impact assessment provides the opportunity for interventions to identify areas of inefficiencies for improvement and build evidence of positive change. Methods: This scoping review collates 26 studies that have assessed the impacts of dog population management interventions. Results: It reports the use of 29 indicators of change under 8 categories of impact and describes variation in the methods used to measure these indicators. Conclusion: The relatively few published examples of impact assessment in dog population management suggest this field is in its infancy; however this review highlights those notable exceptions. By describing those indicators and methods of measurement that have been reported thus far, and apparent barriers to efficient assessment, this review aims to support and direct future impact assessment

Platinum-group element (PGE) geochemistry of Mesoarchean ultramafic–mafic cumulate rocks and chromitites from the Nuasahi Massif, Singhbhum Craton (India)

The Mesoarchean Nuasahi Massif in eastern India comprises a lower ultramafic and an upper gabbro unit. The lower unit consists of orthopyroxenite, harzburgite, dunite and three chromitite bands. All these rocks are characterized by adcumulate textures. The upper unit consists of gabbro with magnetite layers. At the contact between the eastern orthopyroxenite and the lower part of the upper gabbro, a sulfide-rich breccia zone with platinum-group-element (PGE) mineralization is present. Detailed studies of major-, trace- and PGE abundances suggest that the ultramafic-mafic cumulate rocks, chromitites and breccias are genetically linked. The chondrite-normalized U-shaped rare earth element (REE) patterns of the harzburgite resemble those of Phanerozoic boninite. The overall U-shaped REE patterns of the ultramafic rocks indicate derivation of the parental magma from a metasomatized depleted mantle source. The upper gabbros have higher relative abundances of trace elements than the lower ultramafic rocks, due to crystallization from a fractionated magma. Whole-rock geochemistry suggests that the lower ultramafic cumulate rocks with chromitites crystallized from a boninitic parental magma, whereas the upper gabbros with magnetite bands may be formed from residual boninitic magma that was contaminated by more tholeiitic-like magmas. The boninitic parental magma that crystallized to form the lower ultramafic unit was most likely generated by second-stage melting of a depleted metasomatized mantle source in a supra-subduction zone (SSZ) setting and emplaced into crustal sequences. The PGE abundances in the Nuasahi rocks provide additional constraints on their geochemical evolution during the Mesoarchean. Primitive-mantle-normalized PGE diagrams show (1) Ru enrichment in chromitites (Pd/Ru = 0.17 - 0.64), (2) Pd/Pt fractionation in both chromitites (Pd/Pt = 3.1) and ultramafic rocks (Pd/Pt = 0.62), (3) marked Ir depletion in ultramafic rocks (Pd/Ir = 6.3) and (4) overall PGE enrichment in chromitites (PGEtotal = 142 – 502 ppb). The large Ir depletion in the ultramafic rocks, and the overall Ir-depleted character of other rocks from the Nuasahi Massif, may be related to multiple episodes of melt extraction from the mantle source, giving it a subchondritic character

Shedding light on designing potential meprin β inhibitors through ligand-based robust validated computational approaches: A proposal to chemists!

<p>Human meprin (EC 3.4.24.18) is a member of the metzincin superfamily. It correlates with matrix metalloproteinases and ADAMs (a disintegrin and metalloproteinase). Overexpression of meprin β is implicated in fibrosis, inflammatory diseases and cancers. However, selective meprin β inhibition is crucial to reduce cancer metastasis and adverse effects in inflammation. It also plays critical roles in modulating several interleukins and growth factors. Moreover, meprin β cleaves amyloid precursor protein, thought to be involved in the progression of Alzheimer’s disease. Therefore, meprin β inhibitors are considered to be emerging therapeutics with paramount importance in the treatment of kidney failure, fibrosis, inflammatory bowel diseases and cancer. Despite its crucial implication in several diseases, no meprin β inhibitors are available as drug candidates till date. Therefore, it is an urgent need to identify new potential meprin β inhibitors as prospective therapeutics. In this article, a series of meprin β inhibitors has been analysed through multiple molecular modelling studies as the first initiative to get an idea about their structural, physicochemical and pharmacophoric requirements for higher activity. All <i>in silico</i> approaches performed here are statistically validated and subsequently adjudicated each other. Compounds with <i>p</i>-carboxylic acid substituted arylsulphonamide moiety attached with <i>m</i>-carboxylic acid substituted benzyl group along with a methylene hydroxamate function may be crucial for imparting potential meprin β inhibition. Depending on the results obtained, 14 molecules have been proposed by QSAR model that predicted a minimum of 4-fold higher activity compared to these compounds of the current study.</p

Designing potential HDAC3 inhibitors to improve memory and learning

<p>The work presented here explores the structural and physicochemical features important for benzamide-based HDAC3 inhibitors to get an idea about the design aspect of potential inhibitors. A number of molecular modeling studies (3D-QSAR CoMFA and CoMSIA, Bayesian classification modeling) were performed on 113 diverse set of benzamide-based HDAC3 inhibitors. All these models developed are statistically reliable and correlate the SAR observations. Electron withdrawing substitution is favorable but the bulky hydrophobic group at the cap region reduces HDAC3 inhibition. Hydrophobicity and steric feature of the aryl linker function favor the activity. Aryl group substituted benzamide functionality is not favorable for HDAC3 inhibition. The amide function of the benzamide moiety is essential for Zn²⁺ chelation and the carboxylic acid function may serve as a hydrogen bond acceptor (HBA) feature. Moreover, electron withdrawing substituent at the benzamide moiety influences activity whereas steric and hydrophobic substituents reduce HDAC3 inhibition. Overall, this study may provide a valuable insight on the design of better active HDAC3 inhibitors in future.</p> <p>Communicated by Ramaswamy H. Sarma</p

Characterization of contryphans from Conus loroisii and Conus amadis that target calcium channels

Distinctly different effects of two closely related contryphans have been demonstrated on voltage-activated $Ca^{2+}$ channels. The peptides Lo959 and Am975 were isolated from Conus loroisii, a vermivorous marine snail and Conus amadis, a molluscivore, respectively. The sequences of Lo959 and Am975 were deduced by mass spectrometric sequencing (MALDI-MS/MS) and confirmed by chemical synthesis. The sequences of Lo959, $GCP^D WDPWC-NH_2$ and Am975, $GCO^D WDPWC-NH_2$ (O: 4-trans-hydroxyproline: Hyp), differ only at residue 3; Pro in Lo959, Hyp in Am975, which is identical to contryphan-P, previously isolated from Conus purpurascens, a piscivore; while Lo959 is a novel peptide. Both Lo959 and Am975 undergo slow conformational interconversion under reverse-phase chromatographic conditions, a characteristic feature of all contryphans reported thus far. Electrophysiological studies performed using dorsal root ganglion neurons reveal that both peptides target high voltage-activated $Ca^{2+}$ channels. While Lo959 increases the $Ca^{2+}$ current, Am975 causes inhibition. The results establish that subtle sequence effects, which accompany post-translational modifications in Conus peptides, can have dramatic effects on target ion channels

Assessment of independent predictors for long-term mortality between women and men after coronary artery bypass grafting: Are women different from men?

Objective: The long-term mortality of coronary artery bypass grafting in women in not certain. The purpose of this study was to determine and compare risk factors for long-term mortality in women and men undergoing coronary artery bypass grafting. Methods: Between 1992 and 2002, 3760 consecutive patients (2598 men and 1162 women) underwent isolated coronary artery bypass grafting. Long-term survival data were obtained from the National Death Index (mean follow-up, 5.1 +/- 3.2 years). Multivariable Cox regression analysis was performed, including 64 preoperative, intraoperative, and postoperative factors separately in women and men. Results: There were no differences in in-hospital mortality (2.7% in men vs 2.9% in women, P =.639) and 5-year survival (82.0% +/- 0.8% in men vs 81.1% +/- 1.3% in women, P =.293). After adjustment for all independent predictors of long-term mortality, female sex was an independent predictor of improved 5-year survival (hazard ratio, 0.82; 95% confidence interval, 0.71-0.96; P =.014). Twenty-one independent predictors for long-term mortality were determined in men, whereas only 12 were determined in women. There were 9 common risk factors (age, ejection fraction, diabetes mellitus, &gt;= 2 arterial grafts, postoperative myocardial infarction, deep sternal wound infection, sepsis and/or endocarditis, gastrointestinal complications, and respiratory failure); however, their weights were different between women and men. Malignant ventricular arrhythmias, calcified aorta, and preoperative renal failure were independent predictors only in women. Emergency operation, previous cardiac operation, peripheral vascular disease, left ventricular hypertrophy, current and past congestive heart failure, chronic obstructive pulmonary disease, body mass index of greater than 29, preoperative dialysis, thrombolysis within 7 days before coronary artery bypass grafting, intraoperative stroke, and postoperative renal failure were independent predictors only in men. Conclusions: Despite equality between sexes in early outcome and superiority of female sex in long-term survival, there were 3 independent predictors for long-term 1 mortality after coronary artery bypass grafting unique for women compared with 12 for men. Clinical decision making and follow-up should not be influenced by stereotypes but by specific findings

Preoperative prediction of long-term survival after coronary artery bypass grafting in patients with low left ventricular ejection fraction

Objective: We aimed to develop multivariable models of preoperative risk factors that predict long-term survival after coronary artery bypass grafting in patients with b ejection fraction 25% or less. Methods: We retrospectively evaluated 544 consecutive patients with ejection fraction 25% or less who underwent coronary artery bypass grafting from 1992 to 2002 at a single institution. Long-term survival data (mean follow-up 4.1 years) were obtained from the National Death Index. Multivariable Cox regression analysis was performed to construct a predictive score for long-term mortality. A split-sample approach was also used building a model on a training group (n = 360); this model was then tested on a separate validation group (n = 184). Results: From the entire database, the predictive score was calculated according to the following equation: 0.430 (if past congestive heart failure) + 0.049 (age in years) + 0.507(if peripheral vascular disease) + 0.580 (if emergency operation) + 0.366 (if chronic obstructive pulmonary disease). The 5-year survivals of the predictive score quartiles were 82.3%, 78.2%, 65.5%, and 45.5% (P &lt; .0001). The model based on the training group had four independent predictors for long-term mortality (the same as the listed equation except for past congestive heart failure). The 5-year survival rates of the quartiles were 90.1%, 75.4%, 64.3%, and 49.2% in the training group (P &lt; .0001) and 77.4%, 71.2%, 65.8%, and 45.5% in the validation group (P = .0001). Conclusion: Coronary artery bypass grafting in patients with severe ischemic cardiomyopathy achieves satisfactory midterm and long-term survival in selected patients. This new score, which is based on long-term data from a large number of patients, may aid clinicians in selecting therapeutic interventions for patients with ischemic cardiornyopathy

Sodium channel modulating activity in a delta-conotoxin from an Indian marine snail

A 26 residue peptide (Am 2766) with the sequence CKQAGESCDIFSQNCCVG-TCAFICIE-NH2 has been isolated and purified from the venom of the molluscivorous snail, Conus amadis, collected off the southeastern coast of India. Chemical modification and mass spectrometric studies establish that Am 2766 has three disulfide bridges. C-terminal amidation has been demonstrated by mass measurements on the C-terminal fragments obtained by proteolysis. Sequence alignments establish that Am 2766 belongs to the delta-conotoxin family. Am 2766 inhibits the decay of the sodium current in brain rNav1.2a voltage-gated Na+ channel, stably expressed in Chinese hamster ovary cells. Unlike delta-conotoxins have previously been isolated from molluscivorous snails, Am 2766 inhibits inactivation of mammalian sodium channels