Arnis-based Exercise Program for Balance Control in Community-Dwelling Older Adults: Study Protocol for a Pilot Randomized Controlled Trial

Background: Aging causes impairment in balance and increases the prevalence of falls in older adults. Martial arts are now incorporated into exercise programs to improve balance. Arnis, a Filipino Martial Art, can improve the balance control of older adults. Objectives: This study primarily aims to determine the effects of an Arnis-based exercise program on balance control of healthy community-dwelling older adults. This study also aims to describe its effect on older adults’ concerns about falling and lower limb functional strength. Methods:This will be a single-blind, pilot randomized controlled trial. Participants will be randomly allocated to either the intervention or control group. The intervention group will perform an Arnis-based exercise program for 40-60 minutes per session thrice a week for 12 weeks. The control group will continue to do their usual activities for the duration of the study. Participants will be measured at baseline and 12 weeks after for balance, concern for falling, and lower limb strength using the Berg Balance Scale, Timed-Up and Go Test, Falls Efficacy Scale-International Filipino, and the 30-second Chair Sit-to-stand Test, respectively. Data will be analysed through independent and paired t-tests. A p-value Expected Results: Significant improvements in the balance scores in the intervention group are expected after 12 weeks of the Arnis-based exercise program, along with its effects on concerns for falling and lower extremity strength. The pilot study will provide data on the effectiveness of Arnis as a reference for future larger experimental studies

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old