Radical chain reactions involving 9-alkyl-9-borafluorenes

The preparation of 9-alkyl-9-borafluorenes and their use as radical precursors in chain reactions were investigated. These organoboranes were found to be excellent precursors of primary and secondary alkyl radicals. Reactions were readily initiated by traces of oxygen and efficient processes involving sulfonyl-based radical traps were discovered. Due to the very high reactivity of the intermediate 9-H and 9-alkyl-9-borafluorenes, problems of reproducibility were identified.

Patient information leaflets: informing or frightening? A focus group study exploring patients' emotional reactions and subsequent behavior towards package leaflets of commonly prescribed medications in family practices.

BACKGROUND The purpose of patient information leaflets (PILs) is to inform patients about the administration, precautions and potential side effects of their prescribed medication. Despite European Commission guidelines aiming at increasing readability and comprehension of PILs little is known about the potential risk information has on patients. This article explores patients' reactions and subsequent behavior towards risk information conveyed in PILs of commonly prescribed drugs by general practitioners (GPs) for the treatment of Type 2 diabetes, hypertension or hypercholesterolemia; the most frequent cause for consultations in family practices in Germany. METHODS We conducted six focus groups comprising 35 patients which were recruited in GP practices. Transcripts were read and coded for themes; categories were created by abstracting data and further refined into a coding framework. RESULTS Three interrelated categories are presented: (i) The vast amount of side effects and drug interactions commonly described in PILs provoke various emotional reactions in patients which (ii) lead to specific patient behavior of which (iii) consulting the GP for assistance is among the most common. Findings show that current description of potential risk information caused feelings of fear and anxiety in the reader resulting in undesirable behavioral reactions. CONCLUSIONS Future PILs need to convey potential risk information in a language that is less frightening while retaining the information content required to make informed decisions about the prescribed medication. Thus, during the production process greater emphasis needs to be placed on testing the degree of emotional arousal provoked in patients when reading risk information to allow them to undertake a benefit-risk-assessment of their medication that is based on rational rather than emotional (fearful) reactions.

Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions.

OBJECTIVE To systematically review evidence on genetic risk factors for carbamazepine (CBZ)-induced hypersensitivity reactions (HSRs) and provide practice recommendations addressing the key questions: (1) Should genetic testing for HLA-B*15:02 and HLA-A*31:01 be performed in patients with an indication for CBZ therapy to reduce the occurrence of CBZ-induced HSRs? (2) Are there subgroups of patients who may benefit more from genetic testing for HLA-B*15:02 or HLA-A*31:01 compared to others? (3) How should patients with an indication for CBZ therapy be managed based on their genetic test results? METHODS A systematic literature search was performed for HLA-B*15:02 and HLA-A*31:01 and their association with CBZ-induced HSRs. Evidence was critically appraised and clinical practice recommendations were developed based on expert group consensus. RESULTS Patients carrying HLA-B*15:02 are at strongly increased risk for CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in populations where HLA-B*15:02 is common, but not CBZ-induced hypersensitivity syndrome (HSS) or maculopapular exanthema (MPE). HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported from Asian countries only, including China, Thailand, Malaysia, and India. HLA-B*15:02 is rare among Caucasians or Japanese; no HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported so far in these groups. HLA-A*31:01-positive patients are at increased risk for CBZ-induced HSS and MPE, and possibly SJS/TEN and acute generalized exanthematous pustulosis (AGEP). This association has been shown in Caucasian, Japanese, Korean, Chinese, and patients of mixed origin; however, HLA-A*31:01 is common in most ethnic groups. Not all patients carrying either risk variant develop an HSR, resulting in a relatively low positive predictive value of the genetic tests. SIGNIFICANCE This review provides the latest update on genetic markers for CBZ HSRs, clinical practice recommendations as a basis for informed decision making regarding the use of HLA-B*15:02 and HLA-A*31:01 genetic testing in patients with an indication for CBZ therapy, and identifies knowledge gaps to guide future research. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

A short, efficient synthesis of 2'-deoxypseudoisocytidine based on Heck-chemistry

A novel synthesis of 2'-deoxypseudoisocytidine as well as of its phosphoramidite building block for oligonucleotide synthesis is presented. The synthesis is based on Heck-coupling between N-protected pseudoisocytosine and a silyl protected furanoid glycal. With this procedure the corresponding phosphoramidite building block is obtained in 5 steps and an overall yield of 28%.

Synthesis of pyrrolidine C-nucleosides via Heck reaction

A novel method for the synthesis of pyrrolidine C-nucleosides has been developed. The key step of the synthesis is the palladium(0)-mediated coupling of a disubstituted N-protected 2-pyrroline and 5-iodouracil. C-Nucleoside 14 and its N-methyl derivative 15 can easily be converted to the corresponding phosphoramidite building blocks for DNA synthesis

Role of phytohormones in insect-specific plant reactions

The capacity to perceive and respond is integral to biological immune systems, but to what extent can plants specifically recognize and respond to insects? Recent findings suggest that plants possess surveillance systems that are able to detect general patterns of cellular damage as well as highly specific herbivore-associated cues. The jasmonate (JA) pathway has emerged as the major signaling cassette that integrates information perceived at the plant–insect interface into broad-spectrum defense responses. Specificity can be achieved via JA-independent processes and spatio-temporal changes of JA-modulating hormones, including ethylene (ET), salicylic acid (SA), abscisic acid (ABA), auxin, cytokinins (CK), brassinosteroids (BR) and gibberellins (GB). The identification of receptors and ligands and an integrative view of hormone-mediated response systems are crucial to understand specificity in plant immunity to herbivores.

Punitive reactions to completed crimes versus accidentally uncompleted crimes

Previous studies have shown that the harm caused by crime affects punitive reactions even if differences in the degree of harm are merely accidental. However, it remains unclear whether the effect is direct or whether it is mediated by attributed responsibility or blame. Participants were 303 university students who listened to 4 case vignettes (between-subjects design). Half received information about a completed crime and half about an accidentally uncompleted crime. Crime type was either fraud or rape. The results suggest that individuals consider the actual harm to a significantly greater extent than attribution theory would predict. Moreover, the link between harm and punishment was virtually not mediated by attributed blame and not moderated by individual differences in morality. Future studies should investigate whether the harm-punishment link is a result of an automatic act of retaliation or a desire to compensate for the harm done to the victim (restorative justice).

Restoring balance within cognitive unit or deservingness evaluation? The role of attitudes and deservingness in shaping emotional reactions to others’ outcomes

Based on Heider’s theory I persumed that personal attitudes are stronger predictors of emotional responses to others’ outcomes than deservingness evaluation. I manipulated outcome, attitude and deservingness experimentally, and measured specific emotions. It appeared deservingness to play a secondary role in eliciting joy and sorrow when interpersonal attitudes were involved.

Large-scale land acquisitions in Peru: Land (re)-concentration, agrarian change and reactions from rural communities

More than 40 years after the agrarian reform, Peru is experiencing a renewed process of concentration of land ownership in the hands of large-scale investors, favoring the development of a sugar cane production cluster along the northern coast. The expansion of the agricultural frontier by means of large irrigation projects – originally developed to benefit medium- and small-scale farmers – is carried out today in order to be sold to large-scale investors for the production of export crops. In the region of Piura the increasing presence of large-scale biofuel investors puts substantial pressure on land and water resources, not only changing the use of and access to land for local communities, but also generating water shortages vis-à-vis the multiple water demands of local food producers. The changes in land relations and the agro-ecosystem, the altering food production regime as well as the increasing proletarization of smallholders, is driving many locals – even those which (initially) welcomed the investment – into resistance activities against the increasing control of land, water and other natural resources in the hands of agribusinesses. The aim of this presentation is to discuss the contemporary political, social and cultural dynamics of agrarian change along the northern Peruvian coast as well as the «reactions from below» emanating from campesino communities, landless laborers, brick producers, pastoralists as well as other marginalized groups. The different strategies, forms and practices of resistance with the goal of the «protection of the territory» shall be explored as well as the reasons for their rather scattered occurrence and the lack of alliances on the land issue. This input shall make a contribution to the on-going debate on individual and communal property rights and the question of what is best in terms of collective defense against land grabbing.

Reactions of CF3-enones with arenes under superelectrophilic activation: a pathway to trans-1,3-diaryl-1-CF3-indanes, new cannabinoid receptor ligands

4-Aryl-1,1,1-trifluorobut-3-en-2-ones ArCH[double bond, length as m-dash]CHCOCF3 (CF3-enones) react with arenes in excess of Brønsted superacids (TfOH, FSO3H) to give, stereoselectively, trans-1,3-diaryl-1-trifluoromethyl indanes in 35-85% yields. The reaction intermediates, the O-protonated ArCH[double bond, length as m-dash]CHC(OH(+))CF3 and the O,C-diprotonated ArHC(+)CH2C(OH(+))CF3 species, have been studied by means of (1)H, (13)C, (19)F NMR, and DFT calculations. Both types of the cations may participate in the reaction, depending on their electrophilicity and electron-donating properties of the arenes. The formation of CF3-indanes is a result of cascade reaction of protonated CF3-enones to form chemo-, regio- and stereoselectively three new C-C bonds. The obtained trans-1,3-diaryl-1-trifluoromethyl indanes were investigated as potential ligands for cannabinoid receptors CB1 and CB2 types. The most potent compound showed sub-micromolar affinity for both receptor subtypes with a 6-fold selectivity toward the CB2 receptor with no appreciable cytotoxicity toward SHSY5Y cells.