Synthesis of Fluorescent Dansyl Derivatives of Methoxyamine and Diphenylhydrazine as Free Radical Precursors.

Starting from dansyl-chloride, in reaction with 1,1-diphenylhydrazine and methoxyamine, two new fluorescent derivatives 1 and 2 were obtained and characterized by NMR, IR, UV-Vis, HR-MS, and fluorescence spectroscopy. The single-crystal X-ray structure was obtained for compound 2. Both compounds generate free radicals by oxidation, as demonstrated by ESR spectroscopy. Compound 1 generates the corresponding hydrazyl-persistent free radical, evidenced directly by ESR spectroscopy, while compound 2 generates in the first instance the methoxyaminyl short-lived free radical, which decomposes rapidly with the formation of the methoxy radical, evidenced by the ESR spin-trapping technique. By oxidation of compounds 1 and 2, their fluorescence is quenched.

Synthesis, Characterization, and Biologic Activity of New Acyl Hydrazides and 1,3,4-Oxadiazole Derivatives.

Starting from isoniazid and carboxylic acids as precursors, thirteen new hydrazides and 1,3,4-oxadiazoles of 2-(4-substituted-phenoxymethyl)-benzoic acids were synthesized and characterized by appropriate means. Their biological properties were evaluated in terms of apoptosis, cell cycle blocking, and drug metabolism gene expression on HCT-8 and HT-29 cell lines. In vitro antimicrobial tests were performed by the microplate Alamar Blue assay for the anti-mycobacterial activities and an adapted agar disk diffusion technique for other non-tubercular bacterial strains. The best antibacterial activity (anti-Mycobacterium tuberculosis effects) was proved by 9. Compounds 7, 8, and 9 determined blocking of G1 phase. Compound 7 proved to be toxic, inducing apoptosis in 54% of cells after 72 h, an effect that can be predicted by the increased expression of mRNA caspases 3 and 7 after 24 h. The influence of compounds on gene expression of enzymes implicated in drug metabolism indicates that synthesized compounds could be metabolized via other pathways than NAT2, spanning adverse effects of isoniazid. Compound 9 had the best antibacterial activity, being used as a disinfectant agent. Compounds 7, 8, and 9, seemed to have antitumor potential. Further studies on the action mechanism of these compounds on the cell cycle may bring new information regarding their biological activity.

A novel adaptive fluorescent probe for cell labelling.

In this study we describe the synthesis and characterisation of a new hydrazone-based fluorescent compound that is able to selectively label the endoplasmic reticulum (ER) in yeast and mammalian living cells. The fluorescence properties of the compound depended on the DMSO/water ratio and on the pH. NMR experiments allowed determination of the conformation adopted in various environments. Apart from the convenient synthetic procedure, our compound displays low cell toxicity and blue emission compatible with filters routinely used in fluorescence microscopy.

Sleep complaints associated with wish to die after a suicide crisis-an exploratory study.

The present study explores whether sleep concerns are associated with wish to die throughout a 1-month time interval following a suicide crisis. Sixty-eight patients admitted to the emergency department of a general or psychiatric hospital were enrolled. Sleep difficulties were assessed using the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale, self-reported satisfaction with sleep and time in bed. Suicidal ideation was assessed through the presence of a wish to die at 1 month following a suicide crisis. Co-existing psychiatric diagnoses were assessed using the French version of the Mini International Neuropsychiatric Interview (MINI). Potential covariate factors such as personal and family history of suicidal behaviours and sociodemographic variables were accounted for. We found that wish to die was associated significantly with insomnia severity, low satisfaction with sleep and sleep duration 1 month after the suicide crisis, even after controlling for covariates. This exploratory study is limited by a small sample size, and results cannot be generalized to patients with psychotic disorders or alcohol use disorders. Also, other factors related potentially to suicidal ideation, such as depression severity, stressful events or levels of family support, were not accounted for. However, overall our study supports the assessment of sleep complaints as a potential indicator of suicide risk in the weeks that follow a suicide crisis.

Synthesis and biological activities of some new isonicotinic acid 2-(2-hydroxy-8-substituted-tricyclo[7.3.1.0(2.7)]tridec-13-ylidene)-hydrazides.

A series of several new isoniazid derivatives, isonicotinic acid 2-(2-hydroxy-8-substituted-tricyclo[7.3.1.0(2.7)]tridec-13-ylidene)-hydrazides, were synthesized and fully characterized. These new isoniazid derivatives were studied regarding their antibacterial activity and cytotoxicity, as well as their influences on some metabolizing enzymes. The best anti-mycobacterial activity was observed in the case of compounds containing alkyl side chains in the 8 position of tricyclo[7.3.1.0(2.7)]tridec-13-ylidene group. On contrary, the antimicrobial activity of these new compounds against various non-tuberculosis strains showed the best activity to be with the phenyl side chain of compound 6. It proved also to be the most toxic, inducing apoptosis and blocking the cell cycle in G0/G1 phase. The cell cycle was blocked in G0/G1 phase also by compound 3, but this compound did not show any toxicity. All compounds induced the expression of NAT1 and NAT2 genes in HT-29 cell line, and the expression of CYP1A1 in HT-29 and HCT-8 cell lines. The expression level of CYP3A4 was increased by compounds 1, 6 and 7 in HCT-8 cells. These results indicated that the activation of other metabolizing pathways, apart from those of isoniazid, take place. It might also point out the possibility of an increased isoniazid acetylation ratio by co-administration with new compounds in slow acetylators.

A Synthetic Approach for Oxadiazole-Decorated Azobenzene Photoswitches.

This work reports the design and synthesis of novel oxadiazole-decorated azobenzenes, structural analysis of the resulting compounds and behavior under light irradiation. The synthetic strategy involved constructing amino functionalized heterocyclic key intermediates which were used either to yield electrophilic diazonium salts able to react with phenol moieties or as nucleophilic partners in Bayer-Mills reaction with nitroso-substituted derivatives. The amino-derived oxadiazole intermediates were investigated by absorption and emission spectroscopy providing blue and green emitted light. The target oxadiazole-decorated azobenzenes were structurally characterized, including solid-state structures, and subsequently used in irradiation experiments in order to take advantage of the azo group known to provide photoswitching abilities. We noticed quenching of the emissive properties in presence of the azo group; however, all compounds were very stable to repeated cycles of light irradiation. In addition, according to structural diversification we could obtain half-lives of the meta stable isomers within hours to hundreds of hours range. The experimental results were very well correlated with DFT calculations.

Synthesis and bioevaluation of some new isoniazid derivatives.

The aim of the study was to synthesize some new compounds with potential anti-tuberculosis activity, containing isoniazid and α,ß-unsaturated thiocinnamamide-like thioamides as precursors. The obtained derivatives were evaluated regarding their biological activity (antioxidant and antibacterial), as well as their influence on the eukaryotic cell cycle. The results suggested that the newly obtained derivatives of isoniazid exhibited different biological activities, depending on their structure; thus, the most active compound in terms of anti-oxidant and anti-Mycobacterium tuberculosis effects proved to be the isonicotinic acid N'-(1-amino-1-mercapto-3-phenyl-propen-1-yl)-hydrazide. This compound also increased the expression of NAT1 and NAT2 genes, which are implicated in the metabolism of the isoniazid, demonstrating that it could be rapidly metabolized, and thus well tolerated. The largest spectrum of antibacterial activity (excluding M. tuberculosis) was noticed for the isonicotinic acid N'-[1-amino-1-mercapto-3-(p-chloro-phenyl)-propen-1-yl]-hydrazide, which was also the most cytotoxic, especially at high concentrations, although not significantly affecting the cellular cycle phases. The obtained results showed that the new derivatives could represent potential candidates for the treatment of M. tuberculosis infections, but further research is needed in order to improve their pharmacological properties, by increasing their antimicrobial activity and reducing the risk of side-effects.

Medical students' self-evaluations of their patient-centered cultural sensitivity: implications for cultural sensitivity/competence training.

The goals of this study were to (1) empirically assess the need for training in patient-centered culturally sensitive health care among medical students and (2) determine if training in such care needs to be customized to some degree based on individual or subgroup differences. Two hundred seventeen advanced (third- and fourth-year) medical students from 4 medical schools participated. Participants self-reported their current levels of engagement in patient-centered culturally sensitive health care using an online version of the Tucker-Culturally Sensitive Health Care Inventory Provider Form. Results indicated that participating advanced medical students gave self-ratings of engagement in patient-centered culturally sensitive health care that indicate high engagement in some but not all of the behaviors and attitudes that indicate this care. Additionally, their self-ratings differed in association with their gender, race/ethnicity, being fluent in a language other than English, and prior experience providing health care to racial/ethnic minority patients. Conclusions include that some medical students need training in patient-centered culturally sensitive health care, and this training ideally should be assessment-based and customized to address areas where there are low self-ratings of engagement in patient-centered culturally sensitive health care.

Exploring Arylazo-3,5-Bis(trifluoromethyl)pyrazole Switches.

Arylazopyrazoles stand out among the azoheteroarene photoswitches due to their excellent properties in terms of stability of the least stable isomer and conversion between isomers, leading to their use in several interesting applications. We report herein the synthesis of arylazo-trifluoromethyl-substituted pyrazoles and their switching behavior under light irradiation. UV-vis and NMR experiments showed that arylazo-1H-3,5-bis(trifluoromethyl)pyrazoles displayed very long half-lives in DMSO (days), along with reasonable values of other parameters that characterize a photoswitch. Inclusion of naphthyl moieties as aryl counterparts of the arylazopyrazoles is beneficial only in combination with trifluoromethyl groups, while extending the conjugation by grafting the pyrazole moiety with electron-donating or -withdrawing substituents positively affects the photoswitching behavior, in terms of isomerization yield and half-lives of the least stable isomer. The experimental values were correlated with theoretical calculations indicating the valuable influence of the trifluoromethyl groups onto the photoswitching behavior.

Validation of a provider self-report inventory for measuring patient-centered cultural sensitivity in health care using a sample of medical students.

The paper describes the construction and initial evaluation of the new Tucker-Culturally Sensitive Health Care Inventory (T-CSHCI) Provider Form, which was developed to address the shortcomings of existing similar measures. Two hundred seventeen (217) 3rd and 4th year medical students completed the T-CSHCI-Provider Form. Factor analysis was used to identify non-overlapping items. The final solution produced five factors: patient-centeredness, interpersonal skills, disrespect/disempowerment, competence, and cultural knowledge/responsiveness. The five T-CSHCI-Provider Form factors/subscales proved to be reliable and were associated with related constructs as hypothesized. This study provides initial evidence that the T-CSHCI-Provider Form measures independent dimensions of patient-centered culturally sensitive health care as perceived by medical students. Recommendations for ways in which the T-CSHCI Provider Form can be used to guide culturally sensitive health care training are provided.

A polycarboxylic chelating ligand for efficient resin purification of His-tagged proteins expressed in mammalian systems.

We describe the synthesis of a novel polyamino polycarboxylic ligand, its ability to coordinate metal-ions and attachment to a solid support designed for protein purification through Immobilised Metal-ion Affinity Chromatography (IMAC). The resin was found to be highly efficient for purification of His-tagged HCV E2 glycoproteins expressed in 293T mammalian cells.

A novel profluorescent paramagnetic diaza-crown ether: synthesis, characterization and alkaline metal-ion complexation.

Starting from Kryptofix 22 two different branches were covalently attached through the nitrogen atoms, one containing a fluorescent moiety and the other the stable free radical TEMPO. The novel derivative exhibits fluorescence and paramagnetic properties, while the diaza-crown part ensures the affinity for alkaline metal-ions.

Assessments for measuring patient-centered cultural sensitivity in community-based primary care clinics.

OBJECTIVE: To develop and test the reliability of three race/ethnicity-specific forms of the pilot Tucker-Culturally Sensitive Health Care Inventory (T-CUSHCI) for use by patients at community-based primary care centers to evaluate the level of patient-centered cultural sensitivity perceived in the health care that they experience. METHODS: This research involved two studies using independent samples of primary care patients. In study 1, mostly low-income African-American, Hispanic and non-Hispanic white American patients (N=221) rated the importance of specific provider and office staff behaviors and attitudes, and center policies and physical environment characteristics that were earlier identified in previous focus groups as characteristics of patient-centered culturally sensitive healthcare. In study 2, three pilot race/ethnicity-specific T-CUSHCI patient forms were constructed from the items rated as at least important in study 1. Mostly low-income African-American and non-Hispanic white American patients (N=180) provided data to determine the reliability of the T-CUSHCI patient form for their racial/ethnic group. RESULTS: The pilot T-CUSHCI-African-American patient form and the pilot T-CUSHCI-non-Hispanic white American patient form were found to have Cronbach's alpha coefficients ranging from 0.71-0.96 and six-month test-retest and split-half reliabilities ranging from 0.92-0.99. CONCLUSION: The pilot T-CUSHCI patient forms (one each for African Americans, Hispanics and non-Hispanic whites) should be further tested using a national sample of patients. In the interim, these inventory forms can be used as clinical tools to obtain patient feedback for providing "individualized" patient-centered culturally sensitive healthcare.

Long-lived states detect interactions between small molecules and diamagnetic metal ions.

Long-lived states of nuclear spin order were used for the first time to probe interactions between molecules and diamagnetic metal ions. Proton spin states with lifetimes twice as long as the spin-lattice relaxation time constants of the same nuclei were promoted on the methoxyphenyl and tolyl substituents of a 1,3,4-oxadiazole derivative. The transient interaction of this oxadiazole derivative with silver(I) ions significantly speeds up the relaxation rate constants of proton long-lived states. The interactions between silver and organic compounds lead to the formation of coordination polymers that can be used for the preparation of bio-compatible materials.

Family interaction patterns and their association with family support among women with breast cancer.

BACKGROUND: Family support often plays a major role in helping women accept, cope with, and recover from breast cancer, and yet its association with specific family interaction patterns among racially diverse women facing breast cancer has been insufficiently examined. OBJECTIVE: The aim of the study was to examine what specific family interaction patterns exist among diverse women with breast cancer and determine if these family interaction patterns are significantly associated with levels of perceived family support and family support satisfaction reported by these women. METHODS: Participants were 73 white women and 18 African American women with breast cancer. RESULTS: Three different family interaction patterns were identified (ie, cohesive-expressive, conflictual, and nonexpressive). Also, (a) the African American women in cohesive-expressive families versus conflictual families were more satisfied with their emotional family support, (b) the non-Hispanic white women in conflictual families versus nonexpressive families perceived that they received significantly more tangible family support, and (c) the non-Hispanic white women in cohesive-expressive families and those in conflictual families perceived that they received significantly more emotional support from their family members than did non-Hispanic white women in nonexpressive families. CONCLUSIONS: Three main family interaction patterns were found among African American and non-Hispanic white women with breast cancer, which were associated with levels of satisfaction with family support or perceived family support. IMPLICATIONS FOR PRACTICE: Findings from this study can be used to (a) more accurately assess the levels of satisfaction with family support experienced by diverse women with breast cancer and (b) implement family interventions to increase family support for these women.