Scanning pH-metry for Observing Reversibility in Protein Folding.

One of the main factors affecting protein structure in solution is pH. Traditionally, to study pH-dependent conformational changes in proteins, the concentration of the H+ ions is adjusted manually, complicating real-time analyses, hampering dynamic pH regulation, and consequently leading to a limited number of tested pH levels. Here, we present a programmable device, a scanning pH-meter, that can automatically generate different types of pH ramps and waveforms in a solution. A feedback loop algorithm calculates the required flow rates of the acid/base titrants, allowing one, for example, to generate periodic pH sine waveforms to study the reversibility of protein folding by fluorescence spectroscopy. Interestingly, for some proteins, the fluorescence intensity profiles recorded in such a periodically oscillating pH environment display hysteretic behavior indicating an asymmetry in the sequence of the protein unfolding/refolding events, which can most likely be attributed to their distinct kinetics. Another useful application of the scanning pH-meter concerns coupling it with an electrospray ionization mass spectrometer to observe pH-induced structural changes in proteins as revealed by their varying charge-state distributions. We anticipate a broad range of applications of the scanning pH-meter developed here, including protein folding studies, determination of the optimum pH for achieving maximum fluorescence intensity, and characterization of fluorescent dyes and other synthetic materials.

Effects of strength exercises combined with other training on physical performance in frail older adults: A systematic review and meta-analysis.

OBJECTIVES: Strength training is one of the most important protocols for frailty prevention in the older population. However, effects of adding other types of exercise to strength training in frail older adults remain unknown. Therefore, this review and meta-analysis determined the effects of strength exercise combined with other types of training on physical performance in frail older adults. METHODS: MEDLINE, PubMed, CINAHL, and Cochrane databases were searched through October 2021. In our study, we included both pre-frailty and frailty as frail older adults. The intervention was strength training combined with other exercise training, whereas the control group received usual care or light-intensity exercises. The included studies included at least one of the following outcomes: handgrip strength, knee extensor strength, gait speed, Timed Up and Go, and short physical performance battery. RESULTS: Ten articles met the inclusion criteria and were included. The results indicated that handgrip strength (SMD = 0.86, 95% CI= 0.01-1.70, p = 0.05), knee extensor strength (SMD = 0.61, 95%CI = 0.12-1.10, p = 0.01), TUG (SMD = -1.79, 95%CI = -3.16- -0.43, p=0.01), and SPPB (SMD = 0.53, 95%CI = 0.12-0.94, p = 0.01) improved significantly in the experimental group. CONCLUSIONS: Strength exercise combined with other exercise training improved muscle strength, TUG, and SPPB, but not gait velocity, in frail older adults.

Phimosis with Preputial Fissures as a Predictor of Undiagnosed Type 2 Diabetes in Adults.

Diabetes is usually asymptomatic in its early stage. Early diagnosis may improve outcomes by enabling initiation of treatment before end organ damage has progressed. The aim of this study was to determine whether the clinical sign of phimosis with preputial fissures is predictive of type 2 diabetes in patients not previously diagnosed with diabetes. Twenty-eight patients with acquired phimosis and preputial fissures were collected prospectively. Twenty-eight controls with acquired phimosis without preputial fissures were selected. Statistically significant differences were found in body mass index, random plasma glucose, glucosuria and glycosylated haemoglobin levels, but not in age, family history of diabetes, hypertension and classical hyperglycaemic symptoms. Diabetes was confirmed in all 28 patients in the preputial fissures group, but only 2 (7.1%) patients in the non-preputial fissures group (p < 0.0001). In conclusion, phimosis with preputial fissures may be a specific sign of undiagnosed diabetes mellitus.