The Effect of Manual Therapy Plus Exercise in Patients with Lateral Ankle Sprains: A Critically Appraised Topic with a Meta-Analysis

A high percentage of patients with lateral ankle sprains report poor outcomes and persistent neuromuscular impairment leading to chronic ankle instability and re-injury. Several interventions have been proposed and investigated, but the evidence on manual therapy combined with therapeutic exercise for pain reduction and functional improvement is still uncertain. The purpose was to study the effectiveness of adding manual therapy to therapeutic exercise in patients with lateral ankle sprains through a critically appraised topic. The literature search was performed in PubMed, PEDro, EMBASE and CINAHL databases, and only randomized clinical trials were included according to following criteria: (1) subjects with acute episodes of lateral ankle sprains, (2) administered manual therapy plus therapeutic exercise, (3) comparisons with therapeutic exercise alone and (4) reported outcomes for pain and function. Three randomized clinical trials (for a total of 180 patients) were included in the research. Meta-analyses revealed that manual therapy plus exercise was more effective than only exercises in improving dorsal (MD = 8.79, 95% CI: 6.81, 10.77) and plantar flexion (MD = 8.85, 95% CI 7.07, 10.63), lower limb function (MD = 1.20, 95% CI 0.63, 1.77) and pain (MD = -1.23; 95% IC -1.73, -0.72). Manual therapy can be used with therapeutic exercise to improve clinical outcome in patients with lateral ankle sprains

Exome-wide association study of plasma lipids in >300,000 individuals.

We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD