N-arylsulfonyl hydrazones as inhibitors of IMP-1 metallo-beta-lactamase

Members of a family of N-arylsulfonyl hydrazones have been identified as novel inhibitors of IMP-1, a metallo-beta-lactamase of increasing prevalence. Structure-activity relationship studies have indicated a requirement for bulky aromatic substituents on each side of the sulfonyl hydrazone backbone for these compounds to serve as efficient inhibitors of IMP-1. Molecular modeling has provided insight into the structural basis for the anti-metallo-beta-lactamase activity exhibited by this class of compounds.     

A good practice guide for translating and adapting hearing-related questionnaires for different languages and cultures

Objectives: To raise awareness and propose a good practice guide for translating and adapting any hearing-related questionnaire to be used for comparisons across populations divided by language or culture, and to encourage investigators to publish detailed steps. Design: From a synthesis of existing guidelines, we propose important considerations for getting started, followed by six early steps: (1) Preparation, (2, 3) Translation steps, (4) Committee Review, (5) Field testing and (6) Reviewing and finalising the translation. Study sample: Not applicable. Results: Across these six steps, 22 different items are specified for creating a questionnaire that promotes equivalence to the original by accounting for any cultural differences. Published examples illustrate how these steps have been implemented and reported, with shared experiences from the authors, members of the International Collegium of Rehabilitative Audiology and TINnitus research NETwork. Conclusions: A checklist of the preferred reporting items is included to help researchers and clinicians make informed choices about conducting or omitting any items. We also recommend using the checklist to document these decisions in any resulting report or publication. Following this step-by-step guide would promote quality assurance in multinational trials and outcome evaluations but, to confirm functional equivalence, large-scale evaluation of psychometric properties should follow.     

Aloe vera or resveratrol supplementation in larval diet delays adult aging in the fruit fly, Drosophila melanogaster

Longevity extension in Drosophila melanogaster by feeding diet supplemented with chemicals throughout adulthood can cause harmful side effects. We tested the effect of larval diet supplementation with five different concentrations of resveratrol and one concentration of Aloe vera extract on the adult longevity of short-lived D melanogaster populations. Resveratrol and A vera extract supplementation of larval diet extended adult longevity in both the male and female flies without reducing fecundity but by efficient reactive oxygen species scavenging through increased antioxidant enzymes activity and better neuroprotection as indicated by increased locomotor activity in adult males.     

Mitigating peroxynitrite mediated mitochondrial dysfunction in aged rat brain by mitochondria-targeted antioxidant MitoQ

Although reactive oxygen species mediated oxidative stress is a well-documented mechanism of aging, recent evidences indicate involvement of nitrosative stress in the same. As mitochondrial dysfunction is considered as one of the primary features of aging, the present study was designed to understand the involvement of nitrosative stress by studying the impact of a mitochondria-targeted antioxidant MitoQ, a peroxynitrite (ONOO^?) scavenger, on mitochondrial functions. Four groups of rats were included in this study: Group I: Young—6 months (-MitoQ), Group II: Aged—22 months (??MitoQ), Group III: Young—6 months (+?MitoQ), Group IV: Aged—22 months (+?MitoQ). The rats belonging to group III and IV were treated with oral administration of MitoQ (500 μM) daily through drinking water for 5 weeks. MitoQ efficiently suppressed synaptosomal lipid peroxidation and protein oxidation accompanied by diminution of nitrite production and protein bound 3-nitrotyrosine. MitoQ normalized enhanced caspase 3 and 9 activities in aged rat brains and efficiently reversed ONOO^? mediated mitochondrial complex I and IV inhibition, restored mitochondrial ATP production and lowered mitochondrial membrane potential loss. To ascertain these findings, a mitochondrial in vitro model (iron/ascorbate) was used involving different free radical scavengers and anti-oxidants. MitoQ provided better protection compared to mercaptoethylguanidine, N-nitro-l-arginine-methyl ester and superoxide dismutase establishing the predominancy of ONOO^? in the process compared to ^?NO and O ₂ ^?? . These results clearly highlight the involvement of nitrosative stress in aging process with MitoQ having therapeutic potential to fight against ONOO^? mediated aging deficits.     

Novel 2,6-bis(4-methoxyphenyl)-1-methylpiperidin-4-one oxime esters: synthesis and a new insight into their antioxidant and antimicrobial potential

A simple and efficient protocol for the synthesis of novel 2,6-bis(4-methoxyphenyl)-1-methylpiperidin-4-one oxime esters 4(a–q) is described. Initially, p-anisaldehyde 1 was condensed (Mannich reaction) with acetone and ammonium acetate trihydrate afforded 2,6-bis(4-methoxyphenyl)piperidin-4-one 2. Then, methylation followed by oximation with hydroxylamine hydrochloride (NH₂OH?HCl) furnished a key scaffold 4. Further, to explore the enhanced biological properties of the piperidin-4-one core i.e. the key scaffold 4 was conjugated with substituted benzoyl chlorides in the presence of anhydrous K₂CO₃ as base to obtain novel 2,6-bis(4-methoxyphenyl)-1-methylpiperidin-4-one oxime esters 4(a–q) in excellent yields. The newly synthesized compounds were characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR and mass spectroscopic techniques, and screened for their in vitro antioxidant and antimicrobial activities. Most of the compounds exerted positive efficacy towards the biological assays performed. Among the synthesized analogues, compounds 4l and 4m exhibited promising antioxidant activity and on the other hand compounds 4b and 4d manifested persuasive antibacterial activity, whereas compound 4b displayed stupendous antifungal activity against A. flavus strain.     

Psychometric properties of the hearing handicap questionnaire: a Kannada (South-Indian) translation

Objective: To assess the psychometric properties of the Hearing Handicap Questionnaire (HHQ) in Kannada (a South-Indian language) among adults with hearing loss. Design: The study involved a cross-sectional survey design. Participants provided demographic details and completed the Kannada and English (original) version of the HHQ questionnaire. To evaluate test-retest reliability, ～50% of the participants completed the Kannada version for the second time after 15 days. Study sample: The sample comprised 103 adults with hearing loss recruited from local audiology clinics. Results: Exploratory factor analysis indicated a one-factor structure, which explained 71% of the variance in Kannada-HHQ scores. The internal consistency measured with Cronbach’s alpha was 0.96. The test-retest reliability correlations of the Kannada version with the English and with the same Kannada version re-administered after 15 days were 0.96 and 0.91, respectively. Convergent validity of the scale was confirmed by significant correlations with the Participation Scale and the Assessment of Quality of Life scales. Discriminant validity was found to be low as all the Kannada-HHQ questions were highly correlated with each other (r>?0.60). No floor and ceiling effects were identified. Conclusions: The psychometric properties of the Kannada-HHQ scale are considered to be adequate for clinical or research use.