Gangs, displaced, and group-based aggression

Many urban areas experienced an alarming growth of gang activity and violence during the end of the 20th and the beginning of the 21st centuries. Gang members, motivated by various factors, commit a variety of different types of violent acts towards rivals and other targets. Our focus involves instances of displaced aggression, which generally refers to situations in which aggression is targeted towards individuals who have either not themselves committed an offense against the aggressor (s), or who provide an offense that is too mild to justify the aggression levels that are expressed towards them. We discuss how social–psychological mechanisms and models of two types of displaced aggression might help explain some aspects of the retaliatory behavior that is expressed by members of street gangs. We also propose general techniques that have the potential to reduce such aggressive behavior

Functional bisphosphonate synthesis for the development of new anti-resorption bone drug candidates

Herein we present the synthesis of b-mono and b-bis-substituted vinylidenebisphosphonate esters bearing a carboxylic ester moiety to be used as building blocks for further functionalizations. Reactions of these new bisphosphonate scaffolds through hydrogenation of the unsaturated CQC bond and through metal mediated addition of aryl boronic acids and indoles provide a wide range of new bisphosphonate products as potential leads to contrast osteoporosis

Organocatalytic Enantioselective Epoxidation of Some Aryl-Substituted Vinylidenebisphosphonate Esters: On the Way to Chiral Anti-Osteoporosis Drugs

The synthesis of a new class of epoxide derivatives from prochiral vinylidene bisphosphonate (VBP) precursors is reported using hydrogen peroxide as the terminal oxidant. The reaction is carried out using a series of possible organic catalysts having a basic character, the best results being observed using quinine and sparteine. These catalysts not only provide from good to excellent epoxide yields with a large variety of VBPs but also interesting enantioselectivities in the 67-96% ee range at least in the case of the Ph and m-MeO-Ph VBP derivatives opening the way to a number of chiral anti-osteoporosis potentially active pharmaceutical ingredient

Challenging synthesis of bisphosphonate derivatives with reduced steric hindrance

An alternative approach is reported for the synthesis of methyl ester protected bisphosphonate building blocks, such as methylene bisphosphonate, vinylidenebisphosphonate and aryl substituted prochiral vinylidenebisphosphonates, that cannot be obtained directly from dimethyl phosphite and dichloromethane

Highly Stereoselective Synthesis of Nitrogen Bisphosphonates: Organocatalytic Condensation on Osteoporosis Prodrugs

Thanks to their structural similarity with pyrophosphate, gem-bisphosphonates (BPs) ensure specific bone targeting and are widely employed as drugs for the treatment of bone disorders like osteoporosis whose costs, every year, were estimated in €37 billion treating, affecting about 27.5 million people in Europe.[1] New recent studies demonstrated the cellular activity of nitrogen containing BP (N-BP) bearing long alkyl chain acting as potent inhibitors of specific enzymes thus leading to inactivation of osteoclasts that are the cells deputed to bone resorption. Despite of importance of enantiopure drugs in pharmacology, there is only one example of in vitro test on an enantiopure bisphosphonic acid. [2] Herein we present a straightforward synthesis of a β-substituted isatin bisphosphonates precursor on which asymmetric ketones condensation catalyzed by natural derived organocatalysts gave new N-BPs in high yield and high enantiomeric excess. Isatin BP precursor (IsBP) was obtained in high yield and purity by a simple Michael addition of isatin to vinylidenebisphosphonate tetraethylester (VBP). Aldol condensation of acetone on the carbonyl of the IsBP moiety was investigated using a wide range of natural derived organocatalyst, resulting in good yields and moderate e.e. using synthetic quinidine-thiourea catalyst. The optimized catalytic system was applied to a wide range of linear and cyclic aliphatic as well as aromatic ketones: six membered ring aliphatic ketones showed quantitative yields with a dramatic increase in e.e. as well as with electron rich acetophenones. Use of the pseudo-enantiomer quinine-thiourea catalyst allowed to obtain both enantiomeric form of the synthesized molecules. This efficient and versatile synthesis of BPs enabled the preparation of several enantioenriched BP tetraethyl esters that were deprotected removing the ester moieties [3] forming the corresponding bisphosphonic acids

Facile Cu(II) Mediated Addition of Indoles to a New Class of Bisphosphonate Precursors

Thanks to their structural similarity with pyrophosphate, gem-bisphosphonates (BPs) ensure specific bone targeting and are widely employed as drugs for the treatment of bone disorders like osteoporosis, Paget disease and cancer . New recent studies demonstrated the cellular activity of nitrogen containing BP (N-BP) bearing long alkyl chain acting as potent inhibitors of specific enzymes thus leading to inactivation of osteoclasts that are the cells deputed to bone resorption. Herein we present a straightforward synthesis of a new class of β-substituted alkylidene bisphosphates precursors on wich Cu(II) mediated conjugate addition of indoles gave new N-BPs bearing different indolyl derivatives. A modified Knoevenagel condensation of oxalates and aril -ketoesters with methylen-bisphosphate (MBP) was carried out in the presence of TiCl4. The present system provided a facile access to a new class of mono and bi-substituted BP precursors in high yields endowed with an ester moiety. While Cu(II)-catalyzed addition of indoles to the new bis-substituted BP precursors could not be performed, addition to the mono ester substituted BP proceeded readily providing the desired compounds in good yields. It is worth noting that the same reaction on aryl substituted prochiral BPs could not be possible and this further underlines the importance of the newly discovered class of prochiral BPs. The effect of the length of the alkyl chain in the ester moiety was investigated as well. This efficient and versatile synthesis of BPs allowed the preparation of several BP tetraethyl esters that were deprotected removing the ester moieties forming the corresponding bisphosphonic acids that are currently under investigation to assess their activity in the inhibition of the osteoclast activity

ESTRATÉGIAS DE ENFRENTAMENTO DE ESTRESSE EM JOVENS UNIVERSITÁRIOS: UMA REVISÃO SISTEMÁTICA DA LITERATURA

É preocupante como o estresse vem acometendo os estudantes universitários, e que nem todos sabem como enfrentar a situação. Objetivo: Este estudo analisou as características teóricas e metodológicas de estudos empíricos sobre os efeitos adversos do estresse na saúde física e mental de estudantes universitários e suas estratégias de enfrentamento, também identificando os estudos com intervenção para o manejo do estresse nessa população. Metodologia: Foi realizada uma revisão sistemática da literatura com a pergunta norteadora: “Quais são os estressores e as estratégias de enfrentamento que os estudantes apresentam no contexto universitário segundo estudos publicados em língua portuguesa e inglesa nos últimos cinco anos?”. A busca foi feita nas bases eletrônicas dos PERIÓDICOS/CAPES, EBSCO Information Services e da Scientific Library Eletronic Online (SciELO), com os descritores em português e inglês: “estratégias de enfrentamento”, “estudantes universitários” e “estresse”, processados no software Rayyan. Retornaram 224 estudos. Após a aplicação dos critérios de inclusão e exclusão, foram lidos na íntegra 26 artigos diretamente relacionados aos temas: coping, estresse, resiliência, ansiedade e depressão. Resultados: A maior parte das publicações ocorreram entre 2017 e 2019, realizadas por pesquisadores americanos e chineses. O delineamento predominante foi quantitativo (n = 13), com amostras de 100-200 participantes de diversos cursos e 57,69% abordavam diretamente o estresse, indicando estressores mais frequentes o estresse acadêmico, pobreza, preconceito, discriminação e as barreiras linguísticas encontradas por estudantes intercambistas. Diferenças de sexo e a associação entre coping mal adaptativo e ansiedade ou depressão reforçam a importância do tema e trazem dados relevantes para estudos com intervenção. Dois estudos apresentaram projetos de intervenção com os alunos, visando promover estratégias de enfrentamento por meio do gerenciamento de estresse e identificação dos sentimentos e pensamentos negativos. Conclusão: O estresse acomete grande parte da população universitária, tornando indispensável propostas de intervenção para promover estratégias de enfrentamento mais adaptativas

Diketopyrrolopyrrole Bisphosphonate Conjugate: A New Fluorescent Probe for in Vitro Bone Imaging

We report the synthesis of a conjugate molecule between an unusual red fluorescent diketopyrrolopyrrole (DPP) unit and a bisphosphonate (BP) precursor using the "Click Chemistry" strategy to target bone tissue and monitor the interaction. After deep investigation, conjugation through a triazole unit between \u3b3-azido rather than \u3b2-azido BP and an alkyne functionalized DPP fluorophore group turned out to be the winning strategy. Visualization of the DPP-BP conjugate on osteoclasts as well as the specific anti-resorption activity was successfully demonstrated

Low toxicity and unprecedented anti-osteoclast activity of a simple sulfur-containing gem-bisphosphonate: A comparative study

Bisphosphonates (BPs) are key drugs for the treatment of bone resorption diseases like osteoporosis, Paget's disease and some forms of tumors. Recent findings underlined the importance of lipophilic N-containing BPs to ensure high biological activity. Herein we present some unprecedented results concerning the low toxicity and good anti-osteoclast activity of low molecular weight hydrophilic S-containing BPs. A series of S and N-containing BPs bearing aromatic and aliphatic substitution were prepared through Michael addition reaction between vinylidenebisphosphonate tetraethyl ester and the proper nucleophile under basic catalysis. S-containing BPs showed a generally low toxicity, determined with the neutral-red assay using the L929 cell line, and, in particular for an aliphatic one, a good biological activity assessed on primary cultures of human osteoclast