Discovery of N-X anomeric amides as electrophilic halogenation reagents.

Electrophilic halogenation is a widely used tool employed by medicinal chemists to either pre-functionalize molecules for further diversity or incorporate a halogen atom into drugs or drug-like compounds to solve metabolic problems or modulate off-target effects. Current methods to increase the power of halogenation rely on either the invention of new reagents or activating commercially available reagents with various additives such as Lewis or Brønsted acids, Lewis bases and hydrogen-bonding activators. There is a high demand for new reagents that can halogenate otherwise unreactive compounds under mild conditions. Here we report the invention of a class of halogenating reagents based on anomeric amides, taking advantage of the energy stored in the pyramidalized nitrogen of N-X anomeric amides as a driving force. These robust halogenating methods are compatible with a variety of functional groups and heterocycles, as exemplified on over 50 compounds (including 13 gram-scale examples and 1 flow chemistry scale-up).

General Synthesis of N-Alkylindoles from N,N-Dialkylanilines via [4 + 1] Annulative Double C-H Functionalization.

Strategies enabling the construction of indoles and novel polycyclic heterocycles from simple building blocks streamline syntheses in synthetic and medicinal chemistry. Herein, we report a C-H functionalization approach to N-alkylindoles proceeding via a double, site-selective C(sp3)-H/C(sp2)-H [4 + 1] annulation of readily accessed N,N-dialkylanilines. This protocol features a site-selective hydrogen atom transfer by a tuned N-tBu amidyl radical and addition of a sulfonyl diazo coupling partner, which promotes highly site-selective homolytic aromatic substitution of the (hetero)aromatic core. Mild decarboxylation of the annulation product enables the overall introduction of a carbyne equivalent into the N,N-dialkylaniline scaffold. Furthermore, the site-selectivity and mild conditions of the indolization facilitate direct access to N-alkyl indole scaffolds in late-stage functionalization (LSF) settings.

Benzylic C-H Esterification with Limiting C-H Substrate Enabled by Photochemical Redox Buffering of the Cu Catalyst.

Copper-catalyzed radical-relay reactions provide a versatile strategy for selective C-H functionalization; however, reactions with peroxide-based oxidants often require excess C-H substrate. Here, we report a photochemical strategy to overcome this limitation by using a Cu/2,2'-biquinoline catalyst that supports benzylic C-H esterification with limiting C-H substrate. Mechanistic studies indicate that blue-light irradiation promotes carboxylate-to-copper charge transfer, reducing resting-state CuII to CuI, which activates the peroxide to generate an alkoxyl radical hydrogen-atom-transfer species. This "photochemical redox buffering" introduces a unique strategy to sustain the activity of Cu catalysts in radical-relay reactions.

Di(2-picolyl)amines as Modular and Robust Ligands for Nickel-Catalyzed C(sp2)-C(sp3) Cross-Electrophile Coupling.

Ni-catalyzed aryl-alkyl coupling reactions are reliant on using a limited set of commercially available bidentate nitrogenous ligands to enable the reaction, because noncommercial analogues usually entail challenging syntheses. In this work, di(2-picolyl)amines (DPAs) are explored as an alternative modular ligand class for the nickel-catalyzed aryl-alkyl cross-electrophile coupling. Novel DPA ligands were synthesized directly from inexpensive amine and pyridine building blocks in a single step. This facile synthetic route enabled the parallel synthesis of DPA ligands with varied steric and electronic properties. From this collection of ligands, a few robust ligands for C(sp2)-C(sp3) cross-electrophile coupling were identified and tested in the cross-coupling of a range of diverse molecules, including model examples for late-stage functionalization.

Factors underlying denial of and disbelief in COVID-19.

OBJECTIVE: To investigate factors that influence or promote disbelief and negative attitudes toward COVID-19. METHODS: This was cross-sectional study involving 544 males and females ≥ 18 years of age in Greece between December of 2020 and January of 2021. All participants were informed about the purpose of the study, protection of anonymity, and volunteer participation. Participants completed an online anonymous 40-item questionnaire. Analysis of data included the identification of correlations and use of t-tests and ANOVA. RESULTS: The level of knowledge regarding COVID-19 transmission routes, manifestations, and prevention was high in our sample. Women appeared to have a more positive attitude toward COVID-19 prevention and management than did men (p = 0.032 and p = 0.018, respectively). Younger people (18-30 years of age) seemed to deny the validity of scientific data and mass media reports about ways to deal with the pandemic more commonly than did those > 30 years of age (p = 0.003 and p = 0.001, respectively). People who resided in cities more commonly believed in scientific announcements than did those living in villages (p = 0.029). CONCLUSIONS: In order to minimize cases of denial of and disbelief in COVID-19 and to promote vaccination, a series of actions are required. Governments should implement a series of measures to contain the disease, taking into consideration the psychological and social aspects of those policies.

Investigation of Healthcare Satisfaction of Roma Living in Camps or Urban Complex of Central Greece.

Background: Roma in Greece face multiple discrimination, particularly in the areas of housing, education, employment and health. Objective: The aim of this study is to explore the perceptions and beliefs of Greek Roma living both in camps and in urban neighborhoods for public health structures as well as to assess their satisfaction with health care services. Methods: The study sample consisted of 185 subjects (94 females and 91 males) with a mean age of 39.8 years (SD = 15.7). Of the people involved in the study, 80 come from the settlement of Larissa and 105 from the camp of Tyrnavos. A special survey questionnaire, "The scale of attitudes, feelings and satisfaction of Roma health services", was used for collecting the data. The statistical analysis was carried out using the SPSS statistical program. Results: The statistical indicators of the sample, taken together, indicate a moderate trend towards a negative escalation of attitudes, feelings and satisfaction of health services. Based on the t-test results for independent samples, the average score on the Roma satisfaction scale of the Larissa settlement (M = -0,41, SD = 0,74) was not found to differ, statistically significantly, from the Roma population of the Tyrnavos camp (M = -0,61, SD = 0,94), t (182) = 1,680 (p = 0,095). Conclusion: The results of this study, despite its reasonable limitations, lead to a redefinition of some views regarding the attitude of the Roma towards the public health and care system, as well as the needs created.

Factors underlying denial of and disbelief in COVID-19 / Fatores subjacentes à negação e descrença em relação à COVID-19

ABSTRACT Objective: To investigate factors that influence or promote disbelief and negative attitudes toward COVID-19. Methods: This was cross-sectional study involving 544 males and females ≥ 18 years of age in Greece between December of 2020 and January of 2021. All participants were informed about the purpose of the study, protection of anonymity, and volunteer participation. Participants completed an online anonymous 40-item questionnaire. Analysis of data included the identification of correlations and use of t-tests and ANOVA. Results: The level of knowledge regarding COVID-19 transmission routes, manifestations, and prevention was high in our sample. Women appeared to have a more positive attitude toward COVID-19 prevention and management than did men (p = 0.032 and p = 0.018, respectively). Younger people (18-30 years of age) seemed to deny the validity of scientific data and mass media reports about ways to deal with the pandemic more commonly than did those > 30 years of age (p = 0.003 and p = 0.001, respectively). People who resided in cities more commonly believed in scientific announcements than did those living in villages (p = 0.029). Conclusions: In order to minimize cases of denial of and disbelief in COVID-19 and to promote vaccination, a series of actions are required. Governments should implement a series of measures to contain the disease, taking into consideration the psychological and social aspects of those policies.

RESUMO Objetivo: Investigar fatores que influenciam ou promovem a descrença e atitudes negativas em relação à COVID-19. Métodos: Estudo transversal envolvendo 544 homens e mulheres com ≥ 18 anos de idade na Grécia entre dezembro de 2020 e janeiro de 2021. Todos os participantes foram informados sobre o objetivo do estudo, proteção do anonimato e participação voluntária. Os participantes responderam a um questionário on-line anônimo com 40 itens. A análise dos dados incluiu a identificação de correlações e o uso de testes t e ANOVA. Resultados: O nível de conhecimento sobre as vias de transmissão, manifestações e prevenção da COVID-19 foi alto em nossa amostra. As mulheres pareceram ter uma atitude mais positiva em relação à prevenção e manejo da COVID-19 do que os homens (p = 0,032 e p = 0,018, respectivamente). As pessoas mais jovens (18-30 anos de idade) pareceram negar mais a validade dos dados científicos e reportagens da mídia sobre as formas de lidar com a pandemia do que aquelas com > 30 anos de idade (p = 0,003 e p = 0,001, respectivamente). As pessoas que residiam em cidades grandes acreditavam mais nos pronunciamentos científicos do que as que residiam em vilas (p = 0,029). Conclusões: Para minimizar o número de casos de negação e descrença em relação à COVID-19 e promover a vacinação, é necessária uma série de ações. Os governos devem implementar uma série de medidas para conter a doença, levando em consideração os aspectos psicológicos e sociais dessas políticas.

C(sp3)-H methylation enabled by peroxide photosensitization and Ni-mediated radical coupling.

The "magic methyl" effect describes the change in potency, selectivity, and/or metabolic stability of a drug candidate associated with addition of a single methyl group. We report a synthetic method that enables direct methylation of C(sp3)-H bonds in diverse drug-like molecules and pharmaceutical building blocks. Visible light-initiated triplet energy transfer promotes homolysis of the O-O bond in di-tert-butyl or dicumyl peroxide under mild conditions. The resulting alkoxyl radicals undergo divergent reactivity, either hydrogen-atom transfer from a substrate C-H bond or generation of a methyl radical via ß-methyl scission. The relative rates of these steps may be tuned by varying the reaction conditions or peroxide substituents to optimize the yield of methylated product arising from nickel-mediated cross-coupling of substrate and methyl radicals.

Copper-Catalyzed Functionalization of Benzylic C-H Bonds with N-Fluorobenzenesulfonimide: Switch from C-N to C-F Bond Formation Promoted by a Redox Buffer and Brønsted Base.

A copper catalyst in combination with N-fluorobenzenesulfonimide (NFSI) has been reported to functionalize benzylic C-H bonds to the corresponding benzylic sulfonimides via C-N coupling. Here, we reported a closely related Cu-catalyzed method with NFSI that instead leads to C-F coupling. This switch in selectivity arises from changes to the reaction conditions (Cu/ligand ratio, temperature, addition of base) and further benefits from inclusion of MeB(OH)2 in the reaction. MeB(OH)2 is shown to serve as a "redox buffer" in the reaction, responsible for rescuing inactive Cu(II) for continued promotion of fluorination reactivity.

Copper-Catalyzed C-H Fluorination/Functionalization Sequence Enabling Benzylic C-H Cross Coupling with Diverse Nucleophiles.

Site-selective transformation of benzylic C-H bonds into diverse functional groups is achieved via Cu-catalyzed C-H fluorination with N-fluorobenzenesulfonimide (NFSI), followed by substitution of the resulting fluoride with various nucleophiles. The benzyl fluorides generated in these reactions are reactive electrophiles in the presence of hydrogen-bond donors or Lewis acids, allowing them to be used without isolation in C-O, C-N, and C-C coupling reactions.

Oxidative Amide Coupling from Functionally Diverse Alcohols and Amines Using Aerobic Copper/Nitroxyl Catalysis.

The aerobic Cu/ABNO catalyzed oxidative coupling of alcohols and amines is highlighted in the synthesis of amide bonds in diverse drug-like molecules (ABNO=9-azabicyclo[3.3.1]nonane N-oxyl). The robust method leverages the privileged reactivity of alcohols bearing electronegative hetero- atoms (O, F, N, Cl) in the ß-position. The reaction tolerates over 20 unique functional groups and is demonstrated on a 15 mmol scale under air. Steric constraints of the catalyst allow for chemoselective amidation of primary amines in the presence of secondary amines. All catalyst components are commercially available, and the reaction proceeds under mild conditions with retention of stereocenters in both reaction partners, while producing only water as a by-product.

Knowledge and attitudes of nurses in a major public hospital in Cyprus towards pressure ulcer prevention.

STUDY AIM: The main aim of the study was to identify the knowledge and attitudes of nurses towards pressure ulcer prevention in a major public hospital in Cyprus. MATERIAL AND METHODS: A descriptive and cross-sectional study design was used to collect the data between December 2014 and February 2015, the sample consisted of n = 102 nurses employed in a major public hospital in Cyprus. Customised and standardised Pressure Ulcer Knowledge Test and an attitudes Likert questionnaire was used to investigate both parameters. Descriptive and inferential statistics, parametric (t-test), non-parametric tests (Mann-Whitney U) and Pearson test was applied. Statistical significance was set at p = 0.05. RESULTS: The majority of the participants (44.1%) n = 45 were employed in the intensive care unit, were female (61.8%) n = 63, registered nurses (93.1%) n = 95, had more than 5 years of experience (59.4%) n = 32 and 10.8% (n = 11) had a postgraduate title. The mean value regarding the knowledge questionnaire was 16.16, IQR: 17(15-18) correct answers 77%. In the attitudes questionnaire the median value was 41.82, IQR: 43 (40-46). Knowledge and attitudes correlated positively and statistically significantly (Pearson's R = 0,223, p = 0,019). CONCLUSION: The result suggests that nurses had relatively inadequate knowledge levels and positive attitudes, attitudes and knowledges correlated statistically significantly and positively. It is proposed that through the development of educational programs and the frequent measurement of the two parameters further improvement can be achieved.

Evaluation of the Validity and Reliability of the Waterlow Pressure Ulcer Risk Assessment Scale.

INTRODUCTION: Prevention is the ideal strategy to tackle the problem of pressure ulcers. Pressure ulcer risk assessment scales are one of the most pivotal measures applied to tackle the problem, much criticisms has been developed regarding the validity and reliability of these scales. OBJECTIVE: To investigate the validity and reliability of the Waterlow pressure ulcer risk assessment scale. METHOD: The methodology used is a narrative literature review, the bibliography was reviewed through Cinahl, Pubmed, EBSCO, Medline and Google scholar, 26 scientific articles where identified. The articles where chosen due to their direct correlation with the objective under study and their scientific relevance. RESULTS: The construct and face validity of the Waterlow appears adequate, but with regards to content validity changes in the category age and gender can be beneficial. The concurrent validity cannot be assessed. The predictive validity of the Waterlow is characterized by high specificity and low sensitivity. The inter-rater reliability has been demonstrated to be inadequate, this may be due to lack of clear definitions within the categories and differentiating level of knowledge between the users. CONCLUSION: Due to the limitations presented regarding the validity and reliability of the Waterlow pressure ulcer risk assessment scale, the scale should be used in conjunction with clinical assessment to provide optimum results.

Feedstocks to Pharmacophores: Cu-Catalyzed Oxidative Arylation of Inexpensive Alkylarenes Enabling Direct Access to Diarylalkanes.

A Cu-catalyzed method has been identified for selective oxidative arylation of benzylic C-H bonds with arylboronic esters. The resulting 1,1-diarylalkanes are accessed directly from inexpensive alkylarenes containing primary and secondary benzylic C-H bonds, such as toluene or ethylbenzene. All catalyst components are commercially available at low cost, and the arylboronic esters are either commercially available or easily accessible from the commercially available boronic acids. The potential utility of these methods in medicinal chemistry applications is highlighted.

Juvenile (age 13-18) smoking incidence determinants in Greece.

Smoking is a form of medical addiction, usually adopted during adolescence. The aim was to determine the prevalence of smoking in adolescents, aged 13-18 years old, to investigate their attitudes towards smoking and determine the contribution of social influences to onset and continuation of smoking. An anonymous self-report questionnaire was filled in by 873 high school students of Central Greece. Smoking incidence was 19.2%, with a 13.7% of regular smokers. The presence of a smoker in the family and a smoker friend were correlated with increased smoking rates. School grades were correlated negatively with smoking attitude and positively with allowance. Age was correlated negatively with social influence. Social influence appears stronger on younger ages and is a main determinant of smoking behavior. A more susceptible attitude towards smoking is formed during late adolescence. Certain social predictive factors for attitude towards smoking are proposed.