Search

With improved diagnosis and treatments, a greater percentage of breast cancer patients are achieving long-term survival. Consequently, long-term cardiotoxicity secondary to chemotherapy has become more prevalent, warranting improved cardiac surveillance. We evaluated changes in left atrial (LA) strain in breast cancer patients immediately post anthracycline (AC) therapy to assess its utility as a marker of diastolic dysfunction. This was a prospective cohort study of 128 consecutive human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who underwent transthoracic echocardiography prior to and immediately post AC treatment. Traditional left ventricular (LV) systolic and diastolic parameters and LA volumes were evaluated; additionally, LV global longitudinal strain (LV GLS) and LA phasic strain were measured. All patients had normal LV ejection fraction (>53%) post AC, though LV GLS was significantly reduced. Peak E and é velocities were reduced post AC, with no change in LA volumes. LA reservoir strain (LAS RES 34.8% vs 31.5%, p<0.001) and conduit strain (LAS CD 17.2% vs 14.4%, p<0.001) were significantly lower post AC and correlated modestly with LV diastolic parameters. Reduction in LA strain post AC was evident even in patients with preserved LV systolic and diastolic function. More patients demonstrated alteration in diastolic function (≥15% reduction in LAS RES from baseline) (32%) compared to alteration in systolic function (≥15% reduction in LV GLS) (23%). LA strain is a promising marker of early diastolic dysfunction. We demonstrate its potential utility in surveillance of breast cancer patients treated with AC. [Display omitted] [ABSTRACT FROM AUTHOR]

Bone marrow transplantation (BMT) has significantly improved survival rates in various hematological malignancies. However, this has led to an increased prevalence of long-term cardiotoxicity, particularly in those with prior anthracycline (AC) therapy. To evaluate changes in left atrial (LA) volume and function, including LA strain, in BMT patients with prior AC exposure and evaluate its utility as a marker of diastolic dysfunction. This was a cross-sectional analysis of 79 BMT patients with prior AC exposure who underwent a comprehensive surveillance transthoracic echocardiogram compared to age-matched healthy volunteers. Left ventricular (LV) and LA parameters were evaluated between the 2 groups. BMT patients were stratified using traditional measures of diastolic function and additionally utilizing LA strain. LV systolic dysfunction with reduced LVEF (13/79) or global longitudinal strain (29/79) was present in BMT patients. There were no differences in LA volumes between the two groups. LA reservoir strain (30.1 ± 11.2% vs 34.1 ± 9.6%, p < 0.001) and LA conduit strain (13.6 ± 8.4% vs 17.0 ± 10.5%, p < 0.001) were reduced in the BMT group compared to controls. LA reservoir strain had modest correlation with mitral annular e′ velocity (r = 0.468, p < 0.001). Using current diastolic function guidelines, 26/79 BMT patients had evidence of diastolic dysfunction. However, utilizing LA reservoir strain, an additional 35 patients were identified. LA strain can identify early diastolic dysfunction in BMT patients with prior AC treatment. With diastolic dysfunction known to precede systolic dysfunction post AC, changes in LA reservoir strain may identify more patients with cardiac dysfunction, prompting increased surveillance and treatment. Mechanisms of Cardiotoxicity post BMT and AC. Following bone marrow transplant (BMT) and anthracycline (AC) therapy, a greater proportion of patients show evidence of diastolic dysfunction than systolic dysfunction. Using left atrial reservoir strain (LAS RES), a significantly greater proportion of patients are identified with 'subclinical' diastolic dysfunction. ASE – American Society of Echocardiography; EACVI – European Association of Cardiovascular Imaging; LVEF – left ventricular ejection fraction; LV GLS – left ventricular global longitudinal strain. [Display omitted] • Speckle-tracking echocardiography in bone marrow transplant (BMT) patients • Alterations in left atrial (LA) reservoir and conduit strain in BMT patients • LV diastolic dysfunction: LA strain versus routine diastolic parameters • LA reservoir strain in identification of 'subclinical' diastolic dysfunction [ABSTRACT FROM AUTHOR]

It may be logical to use majority voting as a decision-making process, if and when there are only two options 'on the table'. When there are more than two options in contention, a binary procedure may not be so logical. Nevertheless, in current practice, either alternative amendments or each of several options are subjected to a majority vote. Election systems vary enormously; many are proportional, some are preferential, a few are two-tier, and so on. With the exception of a few multi-option referendums, however, most political decisions are subject to a (simple or weighted) binary ballot. Just as there are lots of electoral systems by which multi-candidate elections can be conducted, there are several though fewer voting procedures by which multi-option decisions could be taken. This article first questions current practice; next, it looks at different voting procedures and concludes that a preferential points system is the most accurate; and then it focuses on the topic which now dominates British politics: the UK's relationship with the EU. In particular, it analyses Parliament's second Brexit indicative vote in which a multi-option debate was (not) resolved in a series of majority votes; might a different methodology have been more appropriate? [ABSTRACT FROM AUTHOR]

In a democracy, decisions may be taken in a number of non-violent ways. Some are taken by everybody in referendums or, after an election, by the members of parliament; almost all of these ballots and elections of the general population, as well as decisions by elected representatives, are binding. Other, usually non-binding decisions, may be made by independent commissions or public enquiries, albeit sometimes subject to a government veto; while yet further decisions of government may be influenced by consultations, public opinion surveys, deliberative polls and focus groups. Given the ever-increasing sophistication with which some forms of deliberative democracy operate, it is time to ask whether they too should be legally binding if, that is, (a) the representative sample meets certain minimum criteria, and (b) the outcome, the social choice or ranking, has passed a pre-determined threshold of support. Accordingly, this article first examines the way a social choice or ranking can be identified; next, with frequent reference to instances from across the globe, it takes an overview of the more common means of public participation; and then, in regard to item (b) above, it advocates criteria by which the outcomes of some of these democratic instruments may be deemed to be binding. [ABSTRACT FROM AUTHOR]

In a Borda count, bc, M. de Borda suggested the last preference cast should receive 1 point, the voter's penultimate ranking should get 2 points, and so on. Today, however, points are often awarded to (first, second,..., last) preferences cast as per ( n, n−1, ..., 1) or more frequently, ( n −1, n−2,..., 0). If partial voting is allowed, and if a first preference is to be given n or n − 1 points regardless of how many preferences the voter casts, he/she will be incentivised to rank only one option/candidate. If everyone acts in this way, the bc metamorphoses into a plurality vote... which de Borda criticized at length. If all the voters submit full ballots, the outcome-social choice or ranking-will be the same under any of the above three counting procedures. In the event of one or more persons submitting a partial vote, however, outcomes may vary considerably. This preliminary paper suggests research should consider partial voting. The author examines the consequences of the various rules so far advocated and then purports that M. de Borda, in using his formula, was perhaps more astute than the science has hitherto recognised. [ABSTRACT FROM AUTHOR]

PR-STV and the Quota Borda System (QBS) are two excellent electoral systems, not least because they are both proportional and preferential. The former has been well tried in many settings; the latter has only recently been put to the test in an industrial dispute, under the commission of Mediation Northern Ireland. This article examines the two systems from both a practical and a theoretical standpoint. [ABSTRACT FROM AUTHOR]

With the help of a grant from the Joseph Rowntree Charitable Trust, the de Borda Institute and the New Economics Foundation did some research into decision making. The binary majority vote is often inadequate and inaccurate, and it was thought that perhaps a multi-option procedure of preferential voting would be more suitable for a modern, pluralist society. As part of that project, an experiment was conducted on the web, based on a Modified Borda Count. The subject of discussion was the UK controversy about how to fund the political process. After a critique of dichotomous decision making and an introduction to consensus voting, this article describes the experiment, analyses the vote and makes recommendations for any future exercise. [ABSTRACT FROM AUTHOR]

We examined the intracellular metabolic fate of plasma glucose during a hyperglycemic clamp in impaired glucose-tolerant (IGT; n = 21) and normal glucose-tolerant subjects (n = 10) using a combination of [3-3H]glucose infusion with measurement of [3H]water formation and indirect calorimetry. IGT was associated with ∼35% reduced first-phase insulin responses, normal second-phase insulin response, and 25-30% reduced insulin sensitivity, resulting in ∼35% reduced plasma glucose disposal. This was coupled with ∼55% reduced storage of plasma glucose (P < 0.01) and ∼15-20% reduced glycolysis of plasma glucose (P < 0.03), accounting for ∼75 and 25% of the reduction in glucose disposal, respectively. Decreased glucose oxidation accounted for virtually all the decrease in glycolysis. Therefore, nonoxidative glycolysis of plasma glucose in IGT was similar to that in NGT (P > 0.9) and accounted for an increased proportion of systemic glucose disposal (P < 0.05). We conclude that, in IGT, decreased disposal of plasma glucose involves mainly decreased glycogen synthesis and to a lesser extent decreased glycolysis, which is accounted for by decreased glucose oxidation. An increased proportion of plasma glucose hence undergoes nonoxidative glycolysis, representing a novel early abnormality in the pathogenesis of T2DM. [ABSTRACT FROM AUTHOR]

Abstract: Six new 4-amino-5-cyano-2,6-diarylpyrimidines 5a–h has been synthesized in a facile manner by reacting the appropriate arylamidines 4a–d with bisnitriles 3a–e. Reduction of the nitro group of 5a–e using Pd in ethyl acetate furnished 6a–e in good yields. Reaction of 6a–e individually with phthalic anhydride yielded 7a–e in good to excellent yields. The newly synthesized heterocycles were characterized by IR, 1H-NMR and mass spectral data. Compounds 5f–h and 7a–e were also evaluated against inflammation. Pyrimidines 5g, h exhibited better antiinflammatory activity when compared with acetylsalicylic acid (ASA). Phthalimide derivatives 7a–e also presented antiinflammatory activity, and three of them, viz., 7a–c have been found to be twice more active than aspirin. Cytotoxical evaluations of compounds 7a–e using neoplastic cells (NCI-H292 and Hep-2) presented 41% of growth inhibition of neoplastic cells NCI-H292. [Copyright &y& Elsevier]

Examines the prevention of thromboembolism after myocardial infarction. Effects of low-dose heparin or smoking on the development of leg vein thrombosis; Association of cigarette smoking with a decreased incidence of leg vein thrombosis after myocardial infarction; Efficacy of low-dose heparin prophylaxis.

Chagas' disease affects approximately eight million people throughout the world, especially the poorest individuals. The protozoan that causes this disease–Trypanosoma cruzi–has the enzyme cruzipain, which is the main therapeutic target. As no available medications have satisfactory effectiveness and safety, it is of fundamental importance to design and synthesize novel analogues that are more active and selective. In the present study, molecular docking and the in silico prediction of ADMET properties were used as strategies to optimize the trypanocidal activity of the pyrimidine compound ZN3F based on interactions with the target site in cruzipain. From the computational results, eight 4‐amino‐5‐carbonitrile‐pyrimidine analogues were proposed, synthesized (5a‐f and 7g‐h) and, tested in vitro on the trypomastigote form of the Tulahuen strain of T. cruzi. The in silico study showed that the designed analogues bond favorably to important amino acid residues of the active site in cruzipain. An in vitro evaluation of cytotoxicity was performed on L929 mammal cell lines. All derivatives inhibited the Tulahuen strain of T. cruzi and also exhibited lower toxicity to L929 cells. The 5e product, in particular, proved to be a potent, selective (IC50 = 2.79 ± 0.00 μM, selectivity index = 31.3) inhibitor of T. cruzi. The present results indicated the effectiveness of drugs based on the structure of the receptor, revealing the potential trypanocidal of pyrimidines. This study also provides information on molecular aspects for the inhibition of cruzipain. [ABSTRACT FROM AUTHOR]

Examines the awareness on generativity versus stagnation on the developmental stage of life. Implications on the need for individual affirmation of love for oneself; Prevalence of individual performance for better self-assessment; Indication on the context of generativity on the care to geriatrics.

In 2012, brown bullhead (Ameiurus nebulosus) with large, raised, black growths were first reported from multiple areas within the Vermont portion of Lake Memphremagog. Subsequent surveys conducted from 2014 to 2017 at two sites within the lake indicated a prevalence of 30% in adult brown bullhead 200 mm and above total length. These lesions ranged from slightly raised smooth black areas to large nodular areas on the body surface and fins and within the oral cavity. Microscopically, these lesions were determined to be malignant melanoma with invasion into surrounding hypodermis, skeletal muscle and bone as well as metastases to gill, ovary and intestine. Liver neoplasms were also observed in 8% of the bullhead collected from Lake Memphremagog in 2015. Neither skin nor liver neoplasms were noted in Ticklenaked Pond, a site used for comparison. [ABSTRACT FROM AUTHOR]

• Ramalina aspera exhibits toxicity against B. glabrata embryos and adult snails. • Quantitative and morphological changes were observed in hemocytes of B. glabrata. • Ramalina aspera showed lethal effects against cercariae of Schistosoma mansoni. • Ramalina aspera was non-toxic to Artemia salina at low concentrations. In this study, the molluscicidal activities against Biomphalaria glabrata and cercaricidal activities against Schistosoma mansoni of the ether extract of Ramalina aspera were evaluated. Additionally, toxicity parameters were evaluated at sublethal doses in terms of the influence of the extract on the fertility and fecundity of snails, as well as morphological alterations and quantification of their immunological cells. A test with Artemia salina was also carried out, in order to verify the environmental toxicity of the compound. The ether extract of R. aspera , in which divaricatic acid was identified as the major compound, demonstrated molluscicidal activity at low concentrations against both embryos (LC 90 of 22.78, 24.23, 16.63 and 16.03 μg mL−1 for the gastrula, blastula, trochophore and veliger, respectively) and against adult snails (LC 90 of 8.66 μg mL−1), after 24 h of exposure. At the sublethal doses, it was possible to observe a decrease in fecundity and quantitative and morphological changes in the defense cells of the exposed snails. In addition, the extract of R. aspera showed a cercaricidal effect on S. mansoni from the concentration of 5.0 μg mL−1, while showing low toxicity to Artemia salina. The ether extract of R. aspera demonstrated effective molluscicidal activity on embryos and adult snails of the species B. glabrata , cercariae of S. mansoni , and presenting low toxicity on Artemia salina. In this way, it could be considered a promising compound in the development of future molluscicidal and cercaricidal agents, thus helping to combat schistosomiasis. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the cytotoxicity of organic extracts of P. moniliformis in vitro and identify the acute toxicity and genotoxicity in vivo. The leaves were extracted using three organic solvents (cyclohexane [EP1], ethyl acetate [EP2], and methanol [EP3]). Phytochemical qualitative analysis was performed by thin layer chromatography (TLC). Cytotoxicity tests were performed on human embryonic kidney (HEK) cells and J774 murine macrophages. Acute toxicity in mice was measured after intraperitoneal (ip) administration of 2000 mg/kg, while evaluation of genotoxicity and mutagenicity were assessed using the comet assay and the micronucleus (MN) test, respectively. The TLC analysis of the extracts revealed the presence of flavonoids, triterpenes, steroids, and saponins. In the cytotoxicity assay, extracts EP1 and EP3 altered proliferation of HEK cells, and all organic extracts increased the viability of J774 cells. In the toxicity tests, no deaths or behavioral alterations were observed in mice exposed to the acute dose of the extracts. Although some extracts led to changes in hematological and histological parameters, these results did not indicate physiological changes. In relation to the MN test and comet assay, no significant changes were detected in the DNA of the animals tested with the extracts EP1, EP2, and EP3. Thus, extracts of P. moniliformis were not considered to be toxic and did not induce formation of MN or damage to cellular DNA in the genotoxicity tests. [ABSTRACT FROM AUTHOR]

The Aedes aegypti mosquito is the main vector of the arboviruses that cause Zika, Yellow Fever, Dengue, and Chikungunya, incapacitating diseases that may even be fatal. There are still no vaccines for any of these viruses. Therefore, the only way to contain outbreaks is to control the vector that transmits them. In the present study, we investigated the larvicidal activity of lichen extracts (Ramalina complanata (Sw.) Ach., 1810 and Cladonia verticillaris (Raddi) Fr.), isolating components that were used against larvae of the mosquito A. aegypti. The ether extract from R. complanata exhibited an LC 50 = 5.9 µg.ml−1, while a compound isolated from this species, divaricatic acid, had an LC 50 = 27.1 µg.ml−1. The acetone extract of C. verticilaris exhibited an LC 50 = 17.4 µg.ml−1 and the isolated compound fumarprotocetraric acid (FUM) had an LC 50 = 13.6 µg.ml−1. These results demonstrate that extracts and isolated compounds from the two lichen species have strong larvicidal activities. FUM is the most active compound in our investigation. The molecular docking studies of divaricatic acid and FUM demonstrated that they bind to the active site of Aa AChE1 in an energetically favorable manner. The TRP286 residue may have contributed to the more pronounced activity of fumarprotocetraric acid compared to divaricatic acid. Other aspects related to the more pronounced activity of fumarprotocetraric acid are its molecular weight and higher solubility. Our results provide evidence of the importance of studying lichen secondary metabolites as natural sources of insecticides and investigating possible interactions with Aa AChE1. ● Ramalina complanata and Cladonia verticillaris extracts showed larvicidal activity. ● Fumarprotocetraric acid was a better larvicidal as Divaricatic acid. ● The TRP286 residue may have contributed to the very good activity of FUM. [ABSTRACT FROM AUTHOR]

This study evaluated the biological activity of an ether extract and barbatic acid (BAR) from Cladia aggregata on embryos and adult mollusks of Biomphalaria glabrata, cercariae of Schistosoma mansoni and the microcrustacean Artemia salina. The ether extract and BAR were obtained by successive extractions with diethyl ether. The obtained extracts were analyzed using thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), proton nuclear magnetic resonance (1H-NMR) and infrared (IR) spectroscopy. The results demonstrated that the ether extract exerted embryotoxic effects at 50 and 100 μg/mL and molluscicidal effects at 20 and 25 μg/mL. BAR exhibited no embryotoxicity, and its molluscicidal concentration was equal to that of the ether extract. However, after 60 min of exposure, 1 μg/mL BAR presented cercaricidal activity against the parasite S. mansoni at the second larval stage. Neither substance induced toxicity against A. salina. These results indicate the potential molluscicidal activities of the ether extract and BAR against B. glabrata and S. mansoni cercariae. In addition to these effects, there was a lack of toxicity against the aquatic environment and no damage to the biota, indicating the potential of these products for large-scale control and/or eradication of schistosomiasis. [ABSTRACT FROM AUTHOR]

This article describes an efficient and facile synthesis of 11 2,4,6-trisubstituted 5-cyanopyrimidines starting frommeta-andpara-substituted 2-cyanocinnamonitriles and arylamidines. The synthesized heterocycles,3a–k,were characterized by infrared (IR),1H NMR,13C NMR, and mass spectral data. The probable mechanism of formation of the title compounds employing 2-cyanocinnamonitriles and arylamidines in the presence of a base was clarified. A preliminary screening of the antibacterial tests clearly showed that 4 out of 11 pyrimidines,3a, 3e, 3f,and3k,were effective against bacteriaStaphyloccus aureus, Bacillus subtillis,andPseudomonas aeruginosa.Further, the minimum inhibitory concentration (MIC) against the bacteria has been determined. [ABSTRACT FROM PUBLISHER]

Abstract: The lichen Cladonia verticillaris produces bioactive secondary metabolites, such as fumarprotocetraric (FUM) and protocetraric acids. Species of the genus Cladonia demonstrate anti-tumor, anti-inflammatory and antipyretic activities and have been used in folk medicine to treat respiratory diseases (throat irritation, cough, asthma and tuberculosis). The aim of the present study was to evaluate the expectorant and mucolytic activities of fumarprotocetraric acid in albino Swiss mice. FUM was extracted and purified from an acetone extract of C. verticillaris. The phenol red quantification method was used on the bronchoalveolar lavage fluid following the administration of FUM (25, 50 or 100 mg/kg orally or intraduodenally and 12.5, 25 or 50 mg/kg, intraperitoneally) for the evaluation of expectorant activity. Control groups received either saline solution (7.5 mL/kg) or ambroxol (1 mg/kg) through the same administration routes. Antioxidant activity was evaluated using the thiobarbituric acid reactive species assay in mouse lung tissue treated with the FUM at 25, 50 or 100 mg/kg orally, followed by a lipopolysaccharide solution at 1 mg/kg intrapleurally. The same protocol was used for the control groups using either saline solution (7.5 mL/kg, orally) or N-acetylcysteine (20 mg/kg, orally). Results: Orally administered FUM at doses of 25 and 50 mg/kg promoted significantly greater dose-dependent phenol red activity in the bronchoalveolar lavage and expectorant activity in comparison to the controls (p < 0.05). Lipid peroxidation (malondialdehyde equivalent) was reduced by 50% in the lung tissue. Conclusion: The results confirm the expectorant and antioxidant properties of fumarprotocetraric acid produced by the lichen C. verticillaris. [Copyright &y& Elsevier]

Evidence indicates that in type 2 diabetes (T2DM) plasma epinephrine concentrations may increase when plasma glucose concentrations are lowered into the normoglycemic range even if glycemia is generally well controlled. Moreover, in T2DM with advanced beta-cell failure, counterregulatory glucagon responses are impaired so that epinephrine responses may be critical. These findings suggest that beta-adrenergic blockade may enhance the hypoglycemic actions of insulin at normoglycemia and impair glucose counterregulation in advanced T2DM. To test these hypotheses, we studied 9 T2DM subjects (HbA1c 7.7 ± 0.3%) with advanced beta-cell failure (confirmed by requiring insulin and low plasma C-peptide responses to arginine) on 2 separate occasions by 4-hour hyperinsulinemic (∼600 pM) euglycemic (∼5.2 mM)-hypoglycemic (∼2.7 mM) clamps with [6-3H] glucose infusion for measurements of plasma glucose fluxes: on one occasion the beta-adrenergic antagonist propranolol was infused throughout the clamp, on the other occasion normal saline was infused. On both occasions, fasting plasma glucose concentrations were rendered near-normoglycemic by a variable infusion of insulin overnight, and plasma glucose concentrations during the clamp were virtually identical. Compared to normal saline, propranolol infusion increased the glucose infusion rate required to maintain the euglycemic clamp by ∼25% (P < 0.02). This was associated with increased plasma glucose disposal (P < 0.02) but no significant change in endogenous glucose release. In contrast to the euglycemic clamp, propranolol infusion did not significantly change the glucose infusion rates required to maintain the hypoglycemic clamp nor did it alter plasma glucose fluxes during hypoglycemia. We conclude that in advanced T2DM, beta-adrenergic antagonists may increase the risk of hypoglycemia by enhancing the hypoglycemic actions of insulin at normoglycemia but does not impair hypoglycemia counterregulation. ADA-Funded Research [ABSTRACT FROM AUTHOR]

Reports developments related to medicine as of November 1986. Usefulness of the non-mydriatic fundus photography in detecting diabetic retinopathy; Efficacy of a computer aided diagnosis of acute abdominal pain; Use of serum cotinine to assess the accuracy of self-reported non-smoking.

Discusses a case of cranial manipulation with possible neurovascular contact injury at the cerebello-pontine angle. Case history; Treatment options.

A diagram of the chemical equation for the 4-Amino-2,6-diaryl-5-cyanopyrimidines derivatives synthesis, as an antimicrobial agents is presented.