The purpose of the present investigation was to examine the relationships between the exercise history and the bone mineral density (BMD) and bone mineral content (BMC) in female Japanese young adults using dual X-ray absorptiometry (DXA). One-hundred twenty females, aged between 18 to 28 years, participated in the present investigation. The BMD at the lumbar spine (L-BMD), whole body BMD and BMC (WB-BMD and WB-BMC), lean body mass (LBM) and fat mass (FM) were measured by DXA. Using a self-administrered questionnaire, the exercise habits during preschool (4-6 years), primary school (7-12 years), junior high school (13-15 years), high school (16-18 years), and the current habits (>18 years) were eveluated. The L-BMD, WB-BMD and WB-BMC were significantly higher in the subjects with exercise habits during both the period of <18 years and >18 years compared with those in the subjects without an exercise history during all periods (p<0.05). In a separate analysis with the data stratified by the school age, the subjects with an exercise history during primary school, junior high school, or high school had significantly higher BMD and BMC values compared with the non-exercisers (each, p<0.05). In contrast, the BMD and BMC did not differ significantly according to either the exercise history during pre-school nor the current exercise status. A multiple stepwise regression analysis revealed that the body weight, LBM, FM, age of menarche, and exercise habits during high school were significant determinants of the L-BMD, WB-BMD and WB-BMC (p<0.001). The results of the present investigation show that both the exercise history during school age and the current exercise habits affect the BMD and BMC in young adults. In particular, high school females should be encouraged to participate in the regular exercise to increase their bone health. Future studies will be needed to confirm the targeted age-group(s) for participation in sports/exercise for the improvement of bone health, including an analysis of the type and intensity of exercise/sports.

Recent reports have described several cases of double muscle transfers to restore natural, symmetrical smiles in patients with long-standing facial paralysis. However, these complex procedures sometimes result in cheek bulkiness owing to the double muscle transfer. We present the case of a 67-year-old woman with long-standing facial paralysis, who underwent two-stage facial reanimation using two superficial subslips of the serratus anterior muscle innervated by the masseteric and contralateral facial nerves via a sural nerve graft. Each muscle subslip was transferred to the upper lip and oral commissures, which were oriented in different directions. Furthermore, a horizontal fascia lata graft was added at the lower lip to prevent deformities such as lower lip elongation and deviation. Voluntary contraction was noted at roughly 4 months, and a spontaneous smile without biting was noted 8 months postoperatively. At 18 months after surgery, the patient demonstrated a spontaneous symmetrical smile with adequate excursion of the lower lip, upper lip, and oral commissure, without cheek bulkiness. Dual-innervated muscle transfer using two multivector superficial subslips of the serratus anterior muscle may be a good option for long-standing facial paralysis, as it can achieve a symmetrical smile that can be performed voluntarily and spontaneously.

Recent reports have described several cases of double muscle transfers to restore natural, symmetrical smiles in patients with long-standing facial paralysis. However, these complex procedures sometimes result in cheek bulkiness owing to the double muscle transfer. We present the case of a 67-year-old woman with long-standing facial paralysis, who underwent two-stage facial reanimation using two superficial subslips of the serratus anterior muscle innervated by the masseteric and contralateral facial nerves via a sural nerve graft. Each muscle subslip was transferred to the upper lip and oral commissures, which were oriented in different directions. Furthermore, a horizontal fascia lata graft was added at the lower lip to prevent deformities such as lower lip elongation and deviation. Voluntary contraction was noted at roughly 4 months, and a spontaneous smile without biting was noted 8 months postoperatively. At 18 months after surgery, the patient demonstrated a spontaneous symmetrical smile with adequate excursion of the lower lip, upper lip, and oral commissure, without cheek bulkiness. Dual-innervated muscle transfer using two multivector superficial subslips of the serratus anterior muscle may be a good option for long-standing facial paralysis, as it can achieve a symmetrical smile that can be performed voluntarily and spontaneously.

Residual cardiovascular risk and failure of high density lipoprotein cholesterol raising treatment have refocused interest on targeting hypertriglyceridemia. Hypertriglyceridemia, triglyceride-rich lipoproteins, and remnant cholesterol have demonstrated to be important risk factors for cardiovascular disease; this has been demonstrated in experimental, genetic, and epidemiological studies. Fibrates can reduce cardiovascular event rates with or without statins. High dose omega-3 fatty acids continue to be evaluated and new specialized targeting treatment modulating triglyceride pathways, such as inhibition of apolipoprotein C-III and angiopoietin-like proteins, are being tested with regard to their effects on lipid profiles and cardiovascular outcomes. In this review, we will discuss the role of hypertriglyceridemia, triglyceride-rich lipoproteins and remnant cholesterol on cardiovascular disease, and the potential implications for treatment stargeting hypertriglyceridemia.
Apolipoprotein C-III ; Cardiovascular Diseases* ; Cholesterol ; Cholesterol, HDL ; Epidemiologic Studies ; Fatty Acids, Omega-3 ; Fibric Acids ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypertriglyceridemia* ; Lipoproteins ; Risk Factors ; Triglycerides

No abstract available.
*Angiotensin-Converting Enzyme Inhibitors ; Humans

Hypercholesterolemia and hypertension are among the most important risk factors for cardiovascular (CV) disease. They are also important contributors to metabolic diseases including diabetes that further increase CV risk. Updated guidelines emphasize targeted reduction of overall CV risks but do not explicitly incorporate potential adverse metabolic outcomes that also influence CV health. Hypercholesterolemia and hypertension have synergistic deleterious effects on interrelated insulin resistance and endothelial dysfunction. Dysregulation of the renin-angiotensin system is an important pathophysiological mechanism linking insulin resistance and endothelial dysfunction to atherogenesis. Statins are the reference standard treatment to prevent CV disease in patients with hypercholesterolemia. Statins work best for secondary CV prevention. Unfortunately, most statin therapies dose-dependently cause insulin resistance, increase new onset diabetes risk and exacerbate existing type 2 diabetes mellitus. Pravastatin is often too weak to achieve target low-density lipoprotein cholesterol levels despite having beneficial metabolic actions. Renin-angiotensin system inhibitors improve both endothelial dysfunction and insulin resistance in addition to controlling blood pressure. In this regard, combined statin-based and renin-angiotensin system (RAS) inhibitor therapies demonstrate additive/synergistic beneficial effects on endothelial dysfunction, insulin resistance, and other metabolic parameters in addition to lowering both cholesterol levels and blood pressure. This combined therapy simultaneously reduces CV events when compared to either drug type used as monotherapy. This is mediated by both separate and interrelated mechanisms. Therefore, statin-based therapy combined with RAS inhibitors is important for developing optimal management strategies in patients with hypertension, hypercholesterolemia, diabetes, metabolic syndrome, or obesity. This combined therapy can help prevent or treat CV disease while minimizing adverse metabolic consequences.
Atherosclerosis ; Blood Pressure ; Cardiovascular Diseases ; Cholesterol ; Diabetes Mellitus, Type 2 ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Hypercholesterolemia ; Hypertension ; Insulin Resistance ; Lipoproteins ; Metabolic Diseases ; Obesity ; Pravastatin ; Renin-Angiotensin System ; Risk Factors

Genome-wide association studies have identified various genetic variants associated with complex disorders. However, these studies have commonly been conducted in a cross-sectional manner. Therefore, we performed a longitudinal exome-wide association study (EWAS) in a Japanese cohort. We aimed to identify genetic variants that confer susceptibility to hypertension using ~244 000 single-nucleotide variants (SNVs) and physiological data from 6026 Japanese individuals who underwent annual health check-ups for several years. After quality control, the association of hypertension with SNVs was tested using a generalized estimating equation model. Finally, our longitudinal EWAS detected seven hypertension-related SNVs that passed strict criteria. Among these variants, six SNVs were densely located at 12q24.1, and an East Asian-specific motif (haplotype) ‘CAAAA’ comprising five derived alleles was identified. Statistical analyses showed that the prevalence of hypertension in individuals with the East Asian-specific haplotype was significantly lower than that in individuals with the common haplotype ‘TGGGT’. Furthermore, individuals with the East Asian haplotype may be less susceptible to the adverse effects of smoking on hypertension. The longitudinal EWAS for the recessive model showed that a novel SNV, rs11917356 of COL6A5, was significantly associated with systolic blood pressure, and the derived allele at the SNV may have spread throughout East Asia in recent evolutionary time.

Background: Fibrates have renal toxicity limiting their use in subjects with chronic kidney disease (CKD). However, pemafibrate has fewer toxic effects on renal function. In the present analysis, we evaluated the effects of pemafibrate on the renal function of diabetic subjects with or without CKD in a real-world clinical setting. Methods: We performed a sub-analysis of data collected during a multi-center, prospective, observational study of the effects of pemafibrate on lipid metabolism in subjects with type 2 diabetes mellitus complicated by hypertriglyceridemia (the PARM-T2D study). The participants were allocated to add pemafibrate to their existing regimen (ADD-ON), switch from their existing fibrate to pemafibrate (SWITCH), or continue conventional therapy (CTRL). The changes in estimated glomerular filtration rate (eGFR) over 52 weeks were compared among these groups as well as among subgroups created according to CKD status. Results: Data for 520 participants (ADD-ON, n=166; SWITCH, n=96; CTRL, n=258) were analyzed. Of them, 56.7% had CKD. The eGFR increased only in the SWITCH group, and this trend was also present in the CKD subgroup (P<0.001). On the other hand, eGFR was not affected by switching in participants with severe renal dysfunction (G3b or G4) and/or macroalbuminuria. Multivariate analysis showed that being older and a switch from fenofibrate were associated with elevation in eGFR (both P<0.05). Conclusion A switch to pemafibrate may be associated with an elevation in eGFR, but to a lesser extent in patients with poor renal function.

Background: Fibrates have renal toxicity limiting their use in subjects with chronic kidney disease (CKD). However, pemafibrate has fewer toxic effects on renal function. In the present analysis, we evaluated the effects of pemafibrate on the renal function of diabetic subjects with or without CKD in a real-world clinical setting. Methods: We performed a sub-analysis of data collected during a multi-center, prospective, observational study of the effects of pemafibrate on lipid metabolism in subjects with type 2 diabetes mellitus complicated by hypertriglyceridemia (the PARM-T2D study). The participants were allocated to add pemafibrate to their existing regimen (ADD-ON), switch from their existing fibrate to pemafibrate (SWITCH), or continue conventional therapy (CTRL). The changes in estimated glomerular filtration rate (eGFR) over 52 weeks were compared among these groups as well as among subgroups created according to CKD status. Results: Data for 520 participants (ADD-ON, n=166; SWITCH, n=96; CTRL, n=258) were analyzed. Of them, 56.7% had CKD. The eGFR increased only in the SWITCH group, and this trend was also present in the CKD subgroup (P<0.001). On the other hand, eGFR was not affected by switching in participants with severe renal dysfunction (G3b or G4) and/or macroalbuminuria. Multivariate analysis showed that being older and a switch from fenofibrate were associated with elevation in eGFR (both P<0.05). Conclusion A switch to pemafibrate may be associated with an elevation in eGFR, but to a lesser extent in patients with poor renal function.

Background: Fibrates have renal toxicity limiting their use in subjects with chronic kidney disease (CKD). However, pemafibrate has fewer toxic effects on renal function. In the present analysis, we evaluated the effects of pemafibrate on the renal function of diabetic subjects with or without CKD in a real-world clinical setting. Methods: We performed a sub-analysis of data collected during a multi-center, prospective, observational study of the effects of pemafibrate on lipid metabolism in subjects with type 2 diabetes mellitus complicated by hypertriglyceridemia (the PARM-T2D study). The participants were allocated to add pemafibrate to their existing regimen (ADD-ON), switch from their existing fibrate to pemafibrate (SWITCH), or continue conventional therapy (CTRL). The changes in estimated glomerular filtration rate (eGFR) over 52 weeks were compared among these groups as well as among subgroups created according to CKD status. Results: Data for 520 participants (ADD-ON, n=166; SWITCH, n=96; CTRL, n=258) were analyzed. Of them, 56.7% had CKD. The eGFR increased only in the SWITCH group, and this trend was also present in the CKD subgroup (P<0.001). On the other hand, eGFR was not affected by switching in participants with severe renal dysfunction (G3b or G4) and/or macroalbuminuria. Multivariate analysis showed that being older and a switch from fenofibrate were associated with elevation in eGFR (both P<0.05). Conclusion A switch to pemafibrate may be associated with an elevation in eGFR, but to a lesser extent in patients with poor renal function.