Nasogastric Tube Feeding Versus Total Parenteral Nutrition in Older Dysphagic Patients with Pneumonia: Retrospective Cohort Study.

OBJECTIVES: Many older patients with pneumonia cannot intake orally after admission and may need nutritional care such as nasogastric tube feeding or total parenteral nutrition. This study sought to compare in-hospital outcomes between patients receiving nasogastric tube feeding and total parenteral nutrition. DESIGN: This is a retrospective cohort study. SETTING: A hospital-based database constructed by the Diagnosis Procedure Combination survey data comprising more than 100 acute-care hospitals. PARTICIPANTS: The study included consecutive older inpatients aged >65 years admitted to participating hospitals with a diagnosis of pneumonia from 2014 through 2017. MEASUREMENTS: We compared patients who received total parenteral nutrition and those who received nasogastric tube feeding in terms of characteristics and outcomes. RESULTS: Among the included inpatients, a total of 336 (73.2%) patients received total parenteral nutrition and 123 (26.8%) patients received nasogastric tube feeding. Patients with nasogastric tube feeding had less in-hospital mortality (13.8% vs 27.1%, p = 0.003) and a smaller number of complications (mean; 0.71 vs 1.44, p <0.001), shorter length of hospital stay (mean; 27.6 vs 48.9, p <0.001), more discharges home (72.4% vs 35.1%, p <0.001), and more discharges without oral intake (65.9% vs 45.8%, p <0.001) than patients with total parenteral nutrition. The same results were obtained in propensity score analysis. CONCLUSIONS: Older patients with pneumonia treated with total parenteral nutrition were significantly more likely to have higher in-hospital mortality than those receiving nasogastric tube feeding.

Effect of rehabilitation on mortality of patients with Guillain-Barre Syndrome: a propensity-matched analysis using nationwide database.

BACKGROUND: Rehabilitation for patients with Guillain-Barre Syndrome (GBS) is recommended as it improves the outcome of neurological deficits. Few studies focused on the effect of rehabilitation on mortality of the patients. AIM: To investigate the effect of rehabilitation on hospital mortality of patients with GBS using the Japanese Diagnosis Procedure Combination (DPC) nationwide administrative claims database. DESIGN: A retrospective observational cohort study. SETTING: Hospitals adopting the Japanese DPC system. POPULATION: Patients hospitalized with a diagnosis of GBS between July 2007 and October 2011. METHODS: Data analyzed included sex, age, Barthel index at admission, use of ventilation, immune therapy, and rehabilitation during hospitalization, comorbidity, hospital volume, type of hospital, and in-hospital death. One-to-one propensity score-matching was used to compare hospital mortality rates within 30- and 90-days after admission in rehabilitation and non-rehabilitation groups. The adjusted odds ratios of rehabilitation to hospital mortality were also estimated. RESULTS: A total of 3835 patients were identified and analyzed. Patients with advancing age, lower Barthel index at admission, comorbidities, ventilation, or immune therapy were more likely to receive rehabilitation during hospitalization. Propensity-matched analysis of 926 pairs showed that the rehabilitation group had lower hospital mortality rates within both 30- and 90-days than the non-rehabilitation group. The adjusted odds ratios of rehabilitation to hospital mortality within 30- and 90-days were 0.14 and 0.23, respectively. CONCLUSION: After matching patients' background, rehabilitation was associated with lower hospital mortality of patients with GBS. CLINICAL REHABILITATION IMPACT: Rehabilitation treatment is essential for patients with GBS to improve their survival.

ACVR1 (587T>C) mutation in a variant form of fibrodysplasia ossificans progressiva: second report.

Fibrodysplasia ossificans progressiva (FOP) is a rare, congenital disorder caused by heterozygous mutation of the bone morphogenetic protein type I receptor ACVR1. Various forms of atypical FOP have recently been identified, and a novel mutation, ACVR1 (587T>C), was reported in 2011. We report on the second patient worldwide with ACVR1 (587T>C) mutation. A 22-year-old Japanese male with no family history of heterotopic ossification did not show any malformation of the great toes and showed normal development from birth to the age of 17 years, when heterotopic ossification appeared in the lumbar area. The clinical symptoms were similar to those reported previously: the delayed onset with a slower and mild clinical course and little finger camptodactyly. Gene analysis revealed that the patient was heterozygous for ACVR1 (587T>C) mutation, the same one as reported in 2011, suggesting a correlation between the location of the mutation and the clinical symptoms. This second report of ACVR1 (587T>C) mutation worldwide is particularly meaningful in that it highlights the difference between clinical symptoms of the first reported patient with ACVR1 (587T>C) mutation and those of classic FOP.

Effects of losartan/hydrochlorothiazide on serum uric acid levels and blood pressure in hypertensive patients.

The effect of a mixed formulation of 50 mg losartan (LOS) and 12.5 mg hydrochlorothiazide (HCTZ) on blood pressure and the uric acid metabolism was analyzed in 73 patients who switched to this formulation from other antihypertensive drugs. Eight patients who switched to the formulation from the regular dose of renin-angiotensin (RA) inhibitor (angiotensin receptor blocker [ARB] or angiotensin-converting enzyme [ACE] inhibitor) only showed a significant decrease in blood pressure, from 156.9 ± 14.1/88.6 ± 9.7 mmHg to 128.3 ± 16.0/76.1 ±10.7 mmHg (p = 0.007), and a significant increase in serum uric acid levels, from 5.2 ± 1.1 mg/dL to 6.8 ± 0.7 mg/dL (p = 0.02). In the other 50 patients who switched from a combination of the regular dose of RA inhibitor and calcium channel blocker (CCB), their blood pressure significantly increased, from 126.0 ± 13.8/72.0 ± 10.0 mmHg to 132.5 ± 16.4/76.5 ± 11.3 mmHg (p = 0.02), and their serum uric acid levels also significantly increased, from 5.6 ± 1.1 mg/dL to 6.1 ± 1.3 mg/dL (p = 0.0002). Considering that guidelines recommend using antihypertensive therapies that do not lead to an increase in serum uric acid levels, we conclude that using the ARB/HCTZ combination is less suitable than the regular dose of the ARB/CCB combination due to its effect on hypertension and serum uric acid levels.

Feasibility of stomach exploration with a guided capsule endoscope.

BACKGROUND AND STUDY AIMS: Video capsule endoscopy has been established in diagnosis of small-bowel disease and has been evaluated for esophageal pathology and recently for colorectal diagnostics. Gastric capsule endoscopy has not hitherto been feasible due to the stomach's large surface area and volume. We present the first application of a magnetically navigated capsule in the human stomach. PATIENTS AND METHODS: 29 volunteers and 24 patients (men 42, women 11; mean age 47.5 years) were included in a feasibility study. Low-level magnetic fields were used to maneuver the double-sensor video capsule within the human stomach with an air-water interface provided by ingestion of 1300 ml water within 1 hour before examination. Visualization of all parts of the stomach was attempted; time for visualization was recorded, and a subjective assessment of completeness of visualization was documented. RESULTS: There was technical failure in one individual; thus technical success rate was 98 %. In the 52 remaining cases, examiners assessed that the antrum, body, fundus, and cardia were fully visualized in 98 %, 96 %, 73 % and 75 %, respectively. Mean duration of examinations was 30 minutes (range 8 - 50), with a longer time (mean 37 minutes) for volunteers for study reasons. In total, 30 findings were identified: 14 were detected by both gastroscopy and capsule, 10 lesions were identified by guided capsule examination only, 6 by gastroscopy only. No significant capsule-related adverse events occurred. CONCLUSION: Magnetically navigated video capsule endoscopy appears to be feasible and sufficiently accurate for gastric examination. It may permit endoscopic examinations that are more patient-friendly and without sedation. Comparative studies are under way.

Effects of three strong statins (atorvastatin, pitavastatin, and rosuvastatin) on serum uric acid levels in dyslipidemic patients.

We have retrospectively investigated the effects of three strong statins, atorvastatin, pitavastatin, and rosuvastatin, on serum uric acid (SUA) levels. SUA levels after a few months of statin treatment were compared with those before treatment in 150 outpatients with dyslipidemia. In the atorvastatin (n = 62) and rosuvastatin (n = 45) groups, the SUA levels were reduced by 6.5% (p < 0.0001) and 3.6% (p = 0.03) respectively, but in the pitavastatin group (n = 43), the SUA level increased by 3.7% (p = 0.38). Because uric acid is considered a risk factor for cardiovascular disorders, atorvastatin or rosuvastatin treatment may be recommended when statins are used in patients at high risk for cardiovascular disorders complicated with hyperuricemia.

Plasma levels of vascular endothelial growth factor and pigment epithelium-derived factor before and after intravitreal injection of bevacizumab.

AIMS: To determine the level of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in the plasma of patients with proliferative diabetic retinopathy before and after an intravitreal injection of bevacizumab. METHODS: Eleven patients with type 2 diabetes and control of 30 non-diabetic patients were studied. The 11 eyes of 11 patients received an injection of bevacizumab (1.25 mg). Samples of blood were collected just before the injection, and after 1 day, 7 days and 1 month. The concentrations of VEGF and PEDF in the plasma were measured by ELISA. RESULTS: The VEGF concentration before the injection was 114.0 pg/ml. It was significantly reduced to 9.7 pg/ml after 1 day, to 11.7 pg/ml after 7 days and to 25.9 pg/ml even after 1 month (p<0.001, p<0.001, p<0.001, respectively). The PEDF concentration before the injection was 7.2 microg/ml. It was significantly reduced to 5.8 microg/ml after 1 day, to 5.8 microg/ml after 7 days and to 6.3 microg/ml after 1 month (p<0.001, p<0.001, p>0.05, respectively). CONCLUSIONS: The decreased levels of blood VEGF after an intravitreal injection of bevacizumab indicate that bevacizumab enters the general circulation and may also affect the PEDF levels. Thus, we should carefully examine patients for systemic changes and the fellow eye after an intravitreal injection of bevacizumab.

Association analysis between canine behavioural traits and genetic polymorphisms in the Shiba Inu breed.

The relationships between behavioural trait data and the genotype of 15 polymorphisms in eight neurotransmitter-related genes were analysed in 77 dogs of the Shiba Inu breed, an indigenous Japanese dog. The data were obtained from a 26-item questionnaire on the dog's behaviour, distributed to the dog's owners, through veterinary hospitals and the Shiba Inu breed magazine. A factor analysis of the questionnaire items extracted eight factors accounting for 66.8% of the variance. An association analysis between these factors and genetic polymorphisms indicated that the polymorphism of c.471T>C in the solute carrier family 1 (neuronal/epithelial high-affinity glutamate transporter) member 2 (SLC1A2) gene was significantly associated with Factor 1, referred to as 'aggression to strangers'. This association remained stable in separate analyses of data from surveys obtained from the hospitals and those obtained from the magazine. The results suggest that the c.471T>C polymorphism is associated with some types of aggressive behaviour in the Shiba Inu. Further studies using other dog breeds are necessary to extend these findings to dogs in general.

Transcriptional induction of SOX9 by NF-kappaB family member RelA in chondrogenic cells.

OBJECTIVE: Although SOX9 is a key molecule for chondrogenic differentiation, little is known about the upstream signal. The present study attempted to identify transcription factors to induce SOX9 expression and examined the mechanism. METHODS: Sequences of about 1 kb of 5'-end flanking regions were compared between human and mouse SOX9 genes. In vivo localization was examined by immunohistochemistry in the limb cartilage of fetal mice. Promoter activities of the SOX9, SOX6, and type II collagen (COL2A1) genes were determined in human non-chondrogenic HeLa cells and mouse chondrogenic ATDC5 cells transfected with a luciferase-reporter gene containing the promoter fragments. Protein-DNA binding was examined by electrophoretic mobility shift and chromatin immunoprecipitation assays. The chondrogenic differentiation was assessed by endogenous SOX9, SOX6, and COL2A1 mRNA levels, and by Alcian blue staining and alkaline phosphatase activity. RESULTS: Among transcription factors whose binding motifs were identified in the highly-conserved regions between human and mouse SOX9 promoters, a nuclear factor kappa B (NF-kappaB) member RelA strongly activated the promoter activity. RelA and SOX9 were co-localized in the limb cartilage. Deletion, mutagenesis, and tandem-repeat analyses identified the core region responsive to RelA at the NF-kappaB binding motif to be around -250bp of the human SOX9 promoter, and this was confirmed to show specific binding to RelA. RelA induced the chondrogenic differentiation parameters in HeLa and ATDC5 cells. CONCLUSION: We have identified RelA as a transcriptional factor for SOX9 induction and chondrogenic differentiation via binding to an NF-kappaB binding motif in the SOX9 promoter.

Intranasal lysine-aspirin administration decreases polyp volume in patients with aspirin-intolerant asthma.

INTRODUCTION: Nasal polyposis associated with aspirin-intolerant asthma tends to be difficult to control, with frequent recurrences. We examined the effect of intranasal lysine-aspirin administration on resistant nasal polyps of asthmatic, aspirin-intolerant patients, when used in addition to routine therapy. PATIENTS AND METHODS: Thirteen patients with asthma and intolerance to aspirin were recruited. All but one had undergone numerous polypectomies and were uncontrolled on standard therapy with intranasal corticosteroids, leukotriene receptor antagonists and nasal douching. Aspirin treatment involved one drop (100 microl) of 30 mg/ml lysine-aspirin solution to each nostril, initially daily, increased every two or three days up to a maximal of 18 drops (54 mg lysine-aspirin) a day. Nasal symptoms, nitric oxide level, nasal inspiratory peak flow rate, peak expiratory flow rate and nasendoscopic grading were assessed prior to therapy and three months later. We also compared the change in endoscopic polyp scores during three months of lysine-aspirin administration with the changes which had occurred during the three months prior to administration (during which time other therapies had been identical). RESULTS: Nasal blockage symptoms tended to decrease; other nasal symptoms were unchanged. Significant changes were seen in nasal inspiratory peak flow rate (103.3 +/- 18.9 and 140.0 +/- 16.7 l/min before and after aspirin, respectively; p = 0.014), but not in peak expiratory flow rate (438.7 +/- 33.4 and 440.0 +/- 28.4 l/min before and after aspirin, respectively; p = 0.700). Nasal nitric oxide levels rose significantly (in both sides, p = 0.028). Expired chest nitric oxide levels did not change. Nasal polyp scores on nasendoscopic examination were significantly reduced (right side, p = 0.027; left side, p = 0.018). Compared with the preceding three months, adding intranasal lysine-aspirin application had the effect on decreasing nasal polyp volume (right side, p = 0.031; left side, p = 0.016). CONCLUSION: This open study suggests that intranasal lysine-aspirin administration reduces nasal polyp volume in aspirin-intolerant patients, without any adverse affect on concomitant asthma. This was a preliminary study and should be followed by a placebo-controlled, double-blind trial.

Prevalence of hyperventilation syndrome in an allergy clinic, compared with a routine ENT clinic.

OBJECTIVES: A high prevalence of chronic hyperventilation syndrome in patients with asthma has been reported. We examined whether this phenomenon extended to allergy clinic patients in general and whether the prevalence was higher in patients attending a general allergy clinic compared with those attending a routine ENT clinic in our hospital. METHODS: We examined the prevalence of hyperventilation syndrome in unselected, consecutive patients (n = 100) seen in an allergy clinic. The validated Nijmegen questionnaire was completed by patients in the waiting room. We also administered the questionnaire to unselected, consecutive patients (n = 100) in a routine ENT clinic. RESULTS: There was no significant difference in prevalence of hyperventilation between allergy clinic and routine ENT clinic patients (25/100 vs 23/100). CONCLUSION: The result indicates a high prevalence of hyperventilation amongst hospital attendees in general. Consideration should perhaps be given to the possible role of hyperventilation in symptomatology.

Osteoarthritis development in novel experimental mouse models induced by knee joint instability.

OBJECTIVE: Although osteoarthritis (OA) is induced by accumulated mechanical stress to joints, little is known about the underlying molecular mechanism. To apply approaches from mouse genomics, this study created experimental mouse OA models by producing instability in the knee joints. METHODS: The models were of four types: severe, moderate, mild, and medial, depending on the severity and direction of instability imposed by combinations of ligament transection and menisectomy. OA development was evaluated by X-ray and histology by Safranin-O staining, and quantified using our original gradings. Expressions of type II, IX and X collagens and matrix metalloproteinase (MMP)-2, -3, -9 and -13 were further examined by immunohistochemistry and in situ hybridization (ISH). RESULTS: The severe, moderate and mild models exhibited OA development in the posterior tibial cartilage. The severe model showed cartilage destruction at 2 weeks and osteophyte formation at 4-8 weeks after surgery; however, the mild model showed only a partial cartilage destruction at 8 weeks. The grading confirmed that the OA disorders progressed depending on the severity of joint instability. In the medial model, the OA development in the medial tibial cartilage was similar to that in the posterior cartilage of the mild model. Among the collagens and MMPs, type X collagen and MMP-13 were markedly induced and colocalized in the early stage OA cartilage. CONCLUSION: We established four types of mouse models exhibiting various speeds of OA progression. By applying a mouse genomics approach to the models, molecular backgrounds in various stages of OA development can be clarified.

Optic nerve compression by normal carotid artery in patients with normal tension glaucoma.

AIM: To determine whether compression of the optic nerve by the intracranial carotid artery (ICA) can be a causative factor of normal tension glaucoma (NTG). METHODS: The medical records of 103 eyes of 54 Japanese patients with NTG and 104 eyes of 52 age matched control patients were reviewed. The neuroradiological findings of magnetic resonance images (MRI) were evaluated to determine the relation between the optic nerve and ICA. The clinical characteristics and general medical conditions, such as diabetes and systemic hypertension, were also compared between the two groups. RESULTS: The prevalence of optic nerve compression by the ICA in patients with NTG was 49.5%, which was significantly higher than that in control group with 34.6% (p = 0.035). Bilateral compression of the optic nerve was detected in 22 patients with NTG (40.7%), and this was also significantly higher (p = 0.029) than that in the control group (11 patients, 21.2%). In the NTG group, eyes with cup/disc ratio (C/D ratio) > or =0.7 showed a higher percentage of compression (52.6%) compared with eyes with C/D ratio of <0.7 (12.5%; p = 0. 042). The presence of diabetes and hypertension did not affect the incidence of optic nerve compression by ICA significantly. CONCLUSIONS: The significantly higher percentage of NTG patients who had optic nerve compression by the ICA suggests that compression of the optic nerve by ICA may be a possible causative factor or a risk factor for optic nerve damage in some patients with NTG.

Expression of pigment epithelium derived factor and vascular endothelial growth factor in choroidal neovascular membranes and polypoidal choroidal vasculopathy.

AIMS: To determine whether pigment epithelium derived factor (PEDF), a protein that inhibits angiogenesis, is expressed in human choroidal neovascular membranes (CNVMs) and in tissues from an eye with polypoidal choroidal vasculopathy (PCV). In addition, to compare the expression of PEDF with that of vascular endothelial growth factor (VEGF), a known stimulator of angiogenesis, in these tissues. METHODS: CNVMs, associated with age related macular degeneration (AMD), angioid streaks, and PCV, were obtained during surgery. The expression of PEDF and VEGF in the excised subretinal fibrovascular membranes was determined by immunohistochemistry. RESULTS: PEDF and VEGF were strongly expressed in the vascular endothelial cells and retinal pigment epithelial (RPE) cells in the CNVMs where numerous new vessels were prominent (clinically active CNVMs). On the other hand, immunoreactivity for PEDF and VEGF was weak in the new vessels where fibrosis was prominent (clinically quiescent CNVMs). However, the RPE cells were still positive for PEDF and VEGF. The specimens from the eye with PCV also showed strong expression of PEDF and VEGF in the vascular endothelial cells and the RPE cells. CONCLUSION: Because PEDF is an inhibitor of ocular angiogenesis and an inhibitor of ocular cell proliferation, our results suggest that PEDF along with VEGF may modulate the formation of subfoveal fibrovascular membranes.

The effects of a herbal medicine (Mao-to) in patients with chronic hepatitis C after injection of IFN-beta.

We found that a herbal medicine (Mao-to) relieves the side effects of interferon (IFN)-beta and the combination therapy improves the biochemical response rate. However, the exact mechanism by which Mao-to is effective remains to be established. We conducted a controlled trial to clarify the effects of Mao-to. The study was carried out in 18 patients with chronic hepatitis C, and we examined subjective symptoms, body temperature and cytokines such as interleukin (IL)-beta, IL-1receptor antagonist (ra), IL-6 and TNF-alpha. Each patient received 6 million units of IFN-beta intravenously. Mao-to was given orally just before, just after, and 1 hour after IFN administration. The control study was carried out 6 months after the combination therapy of Mao-to and IFN-beta. The scores for general malaise, arthralgia and discomfort were significantly lower in the combination group than in control group. Body temperature did not significantly differ between the two groups. Plasma IL-6 level and IL-1ra were significantly elevated in the combination group compared to control (P = 0.0057 and 0.0003, respectively). Mao-to did not affect plasma concentrations of IL-1beta and TNF-alpha. We considered the increment of IL-1ra caused by Mao-to is to be one of the key factors involved in reducing the flu-like symptoms accompanying IFN-beta and improving the biochemical response rate.

Usefulness of troglitazone administration to obese hyperglycaemic patients with near-normoglycaemia.

AIMS: We assessed the effectiveness of 400 mg/day of troglitazone administered to hyperglycaemic patients with near-normoglycaemia who were obese and who had hyperinsulinaemia. RESULTS: The area under the plasma glucose curve in oral glucose tolerance tests (OGTT) significantly decreased from 39.8 +/- 19.4-20.5 +/- 10.2 mg/dL. h and the area under the insulin-response curve from 31.8 +/- 22.5-12.2 +/- 5.7 microU/ml x h 4 months after the start of treatment. The level of HbA1c significantly improved from 6.6 +/- 0.2 to 6.3 +/- 0.2% (p < 0.05) by 1 month after administration, and that of serum 1,5-anhydroglucitol (1,5-AG) from 12.6 +/- 1.1-18.3 +/- 2.5 micro/ml (p < 0.05). In some cases, recovery of the first-phase insulin secretion was observed. CONCLUSIONS: These findings suggest that the administration of this insulin sensitizer is useful in the treatment of obese Japanese subjects with borderline or mild diabetics accompanied by hyperinsulinaemia.

The efficacy of a herbal medicine (Mao-to) in combination with intravenous natural interferon-beta for patients with chronic hepatitis C, genotype 1b and high viral load: a pilot study.

Patients with chronic hepatitis C, with a high serum viral load (> or = 1 Meq/ml) and genotype 1b seem to be resistant to interferon (IFN) therapy. To evaluate the efficacy of a herbal medicine (Mao-to) in combination with natural IFN-beta for the treatment of these patients, eighteen Japanese patients were enrolled in this study. Every patient received 6 million units (MU) of IFN-beta intravenously daily for 8 weeks. Mao-to was given orally 3-4 times a day during the IFN-beta administration, Sixteen of the 18 patients (89%) became negative for serum HCV RNA at the end of treatment, but only 2 of them (11%) remained negative for the virus RNA at 6 months of follow-up. Serum ALT levels normalized in 17 patients (94%) at 2 weeks of follow-up after the cessation of therapy, and 11 patients (61%) retained normal ALT levels for more than 6 months of follow-up. This rate of biochemical response was high as compared with that of therapy with IFN-beta alone (19%) in the largest IFN-beta trial in Japan. Serum hyaluronic acid levels were decreased significantly from 147.0 +/- 110.5 ng/ml to 77.4 +/- 67.4 ng/ml in the sustained biochemical response group (P = 0.003). None of the patients needed to interrupt therapy because of side effects of IFN-beta. Thus, Mao-to administration together with IFN-beta treatment could increase the sustained biochemical response rate, and reduce liver fibrosis.

Association of klotho gene polymorphism with bone density and spondylosis of the lumbar spine in postmenopausal women.

Based on the fact that the klotho-deficient mouse exhibits multiple aging phenotypes, including osteopenia and subchondral sclerosis of joints, we explored the possibility of whether human klotho gene polymorphism is associated with two major age-related skeletal disorders: osteoporosis and spondylosis. Analysis of the CA repeat sequence downstream of the final exon of the klotho gene identified ten types of alleles in Japanese postmenopausal women (n = 377). We investigated the association of this microsatellite polymorphism with bone density and spondylosis score of the lumbar spine. None of the genotypes was associated with bone density in the overall population (n = 377; 754 alleles) nor in the subpopulation at not more than 10 years after menopause (20 years after menopause (n = 102; 204 alleles, p = 0.024). The type 7 allele was associated with high bone density in women more than 20 years after menopause (p = 0.042). The association study with spondylosis of postmenopausal women (n = 221) revealed that another distinct allele, type 8, was significantly associated with low spondylosis score at L-4/5 (p = 0.019) and L-5/S-1 (p = 0.048) levels in the subpopulation equal to or younger than the average age (