A preliminary study of the original TIBSIT and its cultural adaptation in Malaysia.

BACKGROUND: A simple and self-administered 'scratch & sniff' test kit like the TIBSIT smell kit based on the Taiwan Smell Identification Test (TWSIT), provides a safe and quick assessment of olfaction. The original TIBSIT has been validated for use in Taiwan with age specific scores for different age groups and diagnosis. The main aim of this study is to examine if TIBSIT can be applicable for the Malaysian population and perform cultural adaptation as necessary to allow a more accurate assessment using this tool. METHOD AND MATERIAL: A preliminary study of the original TIBSIT (Phase 1) followed by cultural adaption (Phase 2) were carried out on volunteers from various neighbourhoods in Klang Valley, Malaysia comprising of age group 16-80 years. A total of 150 test subjects and 50 test subjects were recruited for Phase 1 and Phase 2 respectively. Cultural adaptation was done with changes to the distractors that were found to be confusing. In addition, modifications included added language translation and visual reinforcement with images of the odour's substance of origin. RESULTS: 109 out of the 150 responses were accepted for Phase 1. A detection rate of less than 75% was found in three of the odours with the remaining showing an average rate of 87.2% to 97.7%. These three odours were culturally adapted for Phase 2. All 50 responses for Phase 2 were accepted; two of the odours' detection rates improved to 98% but the plum odour was only detected 53% of the time. CONCLUSION: TIBSIT provides a quick office-based olfaction testing. The culturally adapted test kit is a potentially useful screening test for the Malaysian population. It is also safe and excludes the need of the clinician to carry out the test. This becomes especially useful in testing any dysosmia (hyposmia/anosmia) cases suspected of SARS-COV-2 virus infection (COVID-19).

Reconstructing folding energy landscape profiles from nonequilibrium pulling curves with an inverse Weierstrass integral transform.

The energy landscapes that drive structure formation in biopolymers are difficult to measure. Here we validate experimentally a novel method to reconstruct landscape profiles from single-molecule pulling curves using an inverse Weierstrass transform (IWT) of the Jarzysnki free-energy integral. The method was applied to unfolding measurements of a DNA hairpin, replicating the results found by the more-established weighted histogram (WHAM) and inverse Boltzmann methods. Applying both WHAM and IWT methods to reconstruct the folding landscape for a RNA pseudoknot having a stiff energy barrier, we found that landscape features with sharper curvature than the force probe stiffness could not be recovered with the IWT method. The IWT method is thus best for analyzing data from stiff force probes such as atomic force microscopes.

Determining intrachain diffusion coefficients for biopolymer dynamics from single-molecule force spectroscopy measurements.

The conformational diffusion coefficient for intrachain motions in biopolymers, D, sets the timescale for structural dynamics. Recently, force spectroscopy has been applied to determine D both for unfolded proteins and for the folding transitions in proteins and nucleic acids. However, interpretation of the results remains unsettled. We investigated how instrumental effects arising from the force probes used in the measurement can affect the value of D recovered via force spectroscopy. We compared estimates of D for the folding of DNA hairpins found from measurements of rates and energy landscapes made using optical tweezers with estimates obtained from the same single-molecule trajectories via the transition path time. The apparent D obtained from the rates was much lower than the result found from the same data using transition time analysis, reflecting the effects of the mechanical properties of the force probe. Deconvolution of the finite compliance effects on the measurement allowed the intrinsic value to be recovered. These results were supported by Brownian dynamics simulations of the effects of force-probe compliance and bead size.