Structure-Reactivity Studies of 2-Sulfonylpyrimidines Allow Selective Protein Arylation.

Protein arylation has attracted much attention for developing new classes of bioconjugates with improved properties. Here, we have evaluated 2-sulfonylpyrimidines as covalent warheads for the mild, chemoselective, and metal free cysteine S-arylation. 2-Sulfonylpyrimidines react rapidly with cysteine, resulting in stable S-heteroarylated adducts at neutral pH. Fine tuning the heterocyclic core and exocyclic leaving group allowed predictable SNAr reactivity in vitro, covering >9 orders of magnitude. Finally, we achieved fast chemo- and regiospecific arylation of a mutant p53 protein and confirmed arylation sites by protein X-ray crystallography. Hence, we report the first example of a protein site specifically S-arylated with iodo-aromatic motifs. Overall, this study provides the most comprehensive structure-reactivity relationship to date on heteroaryl sulfones and highlights 2-sulfonylpyrimidine as a synthetically tractable and protein compatible covalent motif for targeting reactive cysteines, expanding the arsenal of tunable warheads for modern covalent ligand discovery.

An Automated Computer-Vision "Bubble-Counting" Technique to Characterise CO2 Dissolution into an Acetonitrile Flow Stream in a Teflon AF-2400 Tube-in-Tube Flow Device.

Invited for this month's cover is the group of Matt O'Brien at Keele University. The cover picture shows a depiction of 'computer vision' in the context of CO2 dissolution into tube-in-tube membrane devices in continuous flow. The original manuscript is part of the Special Collection on "Automation in Chemistry and Beyond" and more information can be found in the Research Article by Matthew O'Brien and Ruxandra Moraru.

An Automated Computer-Vision "Bubble-Counting" Technique to Characterise CO2 Dissolution into an Acetonitrile Flow Stream in a Teflon AF-2400 Tube-in-Tube Flow Device.

A Teflon AF-2400 based tube-in-tube device was used to generate flow streams of CO2 in acetonitrile and a computer-vision based 'bubble counting' technique was used to estimate the amount of CO2 that had passed into solution whilst in the tube-in-tube device by quantifying the amount of CO2 that left solution (forming separate gas-phase segments) downstream of the back-pressure regulator. For both CO2 pressures used, there appeared to be a minimum residence time below which no CO2 was observed to leave solution. This was assumed to be due to residual CO2 below (or close to) the saturation concentration at atmospheric pressure and, by taking this into account, we were able to fit curves corresponding to simple gradient-driven diffusion and which closely matched previously obtained colorimetric titration data for the same system. The estimated value for the residual concentration of CO2 (0.37 M) is higher than, but in reasonable general correspondence with, saturation concentrations previously reported for CO2 in acetonitrile (0.27 M).

Validation of a Romanian version of the short form of the oral health impact profile (OHIP-14) for use in an urban adult population.

PURPOSE: To obtain a valid Romanian version of the OHIP-14 for use among Romanian adults, either in Romania or abroad. MATERIALS AND METHODS: The Romanian version of the OHIP-14 was obtained through the back translation technique and pre-tested in a pilot study. Subsequently, it was self-administered to 187 adults who also underwent a clinical examination. Cronbach alpha was used to check the internal consistency and reliability analysis and validity tests were used to determine the psychometric properties of the questionnaire. RESULTS: The Cronbach alpha coefficient obtained was 0.88. Inter-item correlation coefficients were between 0.01 and 0.74; item-total correlation values ranged between 0.25 and 0.77. There were statistically significant associations (p <= 0.001) between the respondents' self-perceived oral health (r = 0.41), the dental treatment need (r = 0.35) and the mean of the OHIP-14 total scores. Similar statistically significant associations (p <= 0.001) existed between the OHIP-14 total scores mean and the clinical data - the number of decayed (D) and of missing (M) teeth and the prosthetic treatment need - proving the construct validity of the questionnaire. The subscales 'physical pain' and 'psychological disability' have the most important impact on the overall OHIP-14 score. The subscales 'social disability' and 'handicap' seem to make the least contribution to the overall OHIP-14 score. CONCLUSION: The Romanian version of the OHIP-14 is a valid and reliable questionnaire that can be used in future studies.

Cone beam computed tomography as a method of quantitative and qualitative analysis of alveolar crest in the frontal mandibular area.

UNLABELLED: New radiographic maxillofacial techniques, cone beam computerized tomography (CBCT) are a necessity in the assessment of jaw bone offer to effectively evaluate the treatment. AIM: To quantitatively and qualitatively evaluate anterior mandibular area on CBCT comparing to orthopantomography (OPG). MATERIAL AND METHODS: Fifty-one dental patients, aged between 20 and 77 years, were quantitatively analyzed and 81 dental patients, aged between 20 and 79 years, were qualitatively analyzed. ANOVA and Mann-Whitney tests were used for statistical analyses. RESULTS: Strong statistical significant differences were recorded between CBCT and OPG assessments for all groups of teeth (p<0.001), when evaluation was performed on distances to mandibular base. When assessing the distance to the incisive canal, the differences were recorded only for the left canine zone. Mean densities of central incisor, lateral incisor and canine regions, were 1,400-1,425 HU, 1,212-1,224 HU, and 1,150-1,175 HU, respectively. There was a marginal statistical evidence that bone density was lower in canine zone comparing to central incisor area (p=0.08). CONCLUSIONS: Measurements on CBCT are more accurate when compared with OPG. Bone density of central incisor region is higher. Therefore, CBCT permits the clinician to have all necessary information when planning dental implants.

Perceptions of intimidation and bullying in dental schools: a multi-national study.

OBJECTIVES: To determine first year dental students' perceptions of intimidation by instructors and bullying by fellow students. METHODS: Data were collected through a cross-sectional survey of first year dental students from seven dental schools representing five countries; one each from Romania, South Africa, Australia and the U.S.A., and three from Malaysia. Self-report questionnaires were administered to participants at least six months after they had commenced their dental degree course during 2005-6. RESULTS: Over a third (34.6%) reported that they had been intimidated or badly treated by their tutors/instructors and 17% reported that they had been bullied or badly treated by their fellow students in the recent past. There were statistically significant differences in reports of intimidation by instructors between the different dental schools. Intimidation by instructors was associated with a history of medication use for stress, anxiety and depression, and perceived stress in the past month. There were no statistically significant variations in reports of bullying by fellow students between different dental schools. Bullying by fellow students was associated with dieting to lose weight, self-reported general health and perceived stress. CONCLUSIONS: This multi-national study highlights that intimidation and bullying is prevalent within dental teaching and training environments. Future research is needed to explore their impact on students' wellbeing and academic progress as well as on patient care. CLINICAL IMPLICATIONS: Dentists are the best recruiters for the profession. If the dental school experience is a negative one it can have significant impact on the future of the profession

Emotional intelligence and perceived stress in dental undergraduates: a multinational survey.

This multinational survey investigated the relationship between emotional intelligence (EI) and perceived stress (PS) in seven countries. First-year dental undergraduates attending a dental school in England, Greece, Romania, South Africa, Australia, and the United States and three schools in Malaysia were invited to complete a set of questionnaires on age, gender, academic background, satisfaction with career choice, EI, and PS. Of 860 questionnaires distributed, 596 were fully completed--a response rate of 69.3 percent. Mean EI score was 123.8 (95 percent CI 122.7-124.9), and mean PS score was 19.1 (95 percent CI 18.6-19.7). Significant differences in EI and PS scores were detected between different countries. Females (p<0.05), younger students (p<0.001), those without a previous higher education qualification (p<0.001), and those not satisfied with their decision to study dentistry (p<0.001) were more likely to report PS when compared to their counterparts. A significant inverse relationship (coefficient=-0.29, p=0.001) between EI and PS was detected. Independent significant predictors of PS identified were gender (beta=0.22, t=5.71, p=0.001), previous higher education qualification (beta=-0.14, t=-2.42, p=0.010), satisfaction with decision to study dentistry (beta=-0.20, t=-5.11, p=0.001), and EI (beta=-0.24, t=-6.09, p=0.001), with the latter being relatively the most important predictor. In conclusion, the inverse relationship between EI and PS has been confirmed in this heterogeneous sample representing diverse sociocultural and academic contexts of dental undergraduates.