Double-blind, placebo-controlled trial of pirfenidone in patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a fatal disorder without an effective therapy to date. In a double-blind, randomized, placebo-controlled trial, 107 patients were prospectively evaluated for efficacy of a novel compound, pirfenidone. The difference in the change in the lowest oxygen saturation by pulse oximetry (SpO2) during a 6-minute exercise test, the primary endpoint, from baseline to 6 months was not significant between the two groups (p = 0.0722). In a prespecified subset of patients who maintained a SpO2 greater than 80% during a 6-minute exercise test at baseline, the lowest SpO2 improved during a 6-minute exercise test in the pirfenidone group at 6 and 9 months (p = 0.0069 and 0.0305, respectively). Positive treatment effect was demonstrated in secondary endpoints: (1) change in VC measurements at 9 months (p = 0.0366) and (2) episodes of acute exacerbation of IPF occurring exclusively in the placebo group during the 9 months (p = 0.0031). Significant adverse events were associated with pirfenidone; however, adherence to treatment regimen was similar between pirfenidone and placebo groups. In conclusion, treatment with pirfenidone improved VC and prevented acute exacerbation of IPF during the 9 months of follow-up. Future long-term studies are needed to clarify the overall safety and efficacy of pirfenidone in IPF.     

Effect of long‐term late‐evening snack on health‐related quality of life in cirrhotic patients

Aim: In patients with liver cirrhosis, abnormal energy metabolism induces low health‐related quality of life (HRQOL) scores. However, late‐evening snack (LES) prevents morning starvation in cirrhotic patients. Our aim is to assess the effect of long‐term LES on HRQOL in cirrhotic patients, using the 36‐item Short Form (SF‐36) health survey. Methods: Thirty‐nine cirrhotic patients classified as Child–Pugh grade A were recruited. The patients were randomly divided into two groups: 24 were assigned to the non‐LES group and 15 to the LES group. SF‐36 scores, anthropometric data and serum biochemical parameters were examined in the non‐LES and LES groups at 0, 6 and 12 months. Results: Neither anthropometric data nor laboratory data showed significant differences between the non‐LES and the LES groups at 0, 6 and 12 months. The role–emotional (RE) HRQOL scores at 6 months and mental health (MH) scores at 6 and 12 months were significantly reduced from the baseline level in the non‐LES group. In contrast, these scores remained unchanged in the LES group. General health perception (GH) scores at 12 months, RE at 6 months and MH at 6 and 12 months in the LES group were significantly higher than those of the non‐LES group. Conclusion: Long‐term LES administration may be helpful in maintaining higher HRQOL in patients with cirrhosis.     

Association Between Pulse Wave Velocity and a Marker of Renal Tubular Damage (N‐Acetyl‐β‐D‐Glucosaminidase) in Patients Without Diabetes

The authors assessed the association between the ratio of urinary activity of N‐acetyl‐β‐D‐glucosaminidase (NAG) to creatinine and the brachial‐ankle pulse wave velocity (baPWV) in patients without overt diabetes mellitus (DM). This was a cross‐sectional study of 233 patients who had an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² and no history of kidney disease. Patients were divided into two groups: high NAG group (>5.8 U/g creatinine) and low NAG group (≤5.8 U/g creatinine). Mean baPWVs of the high NAG group were significantly higher than those of the low NAG group in both the eGFR ≥30 and <60 tertiles and the eGFR ≥60 and <90 tertiles. The baPWV was positively correlated with NAG in all patients (r=0.341, P<.001). Stepwise multivariate regression analysis showed that the baPWV was significantly related with NAG, age, and systolic blood pressure. Elevated NAG is related to elevated arterial stiffness in patients without DM.     

Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial

A double-blind, parallel-group, placebo-controlled trial was performed on 50- to 80-year-old Japanese men and women diagnosed with mild cognitive impairment in order to examine the efficacy of oral administration of Yamabushitake (Hericium erinaceus), an edible mushroom, for improving cognitive impairment, using a cognitive function scale based on the Revised Hasegawa Dementia Scale (HDS-R). After 2 weeks of preliminary examination, 30 subjects were randomized into two 15-person groups, one of which was given Yamabushitake and the other given a placebo. The subjects of the Yamabushitake group took four 250 mg tablets containing 96% of Yamabushitake dry powder three times a day for 16 weeks. After termination of the intake, the subjects were observed for the next 4 weeks. At weeks 8, 12 and 16 of the trial, the Yamabushitake group showed significantly increased scores on the cognitive function scale compared with the placebo group. The Yamabushitake group's scores increased with the duration of intake, but at week 4 after the termination of the 16 weeks intake, the scores decreased significantly. Laboratory tests showed no adverse effect of Yamabushitake. The results obtained in this study suggest that Yamabushitake is effective in improving mild cognitive impairment.     

Association between energy cost of walking,muscle activation,and biomechanical parameters in older female fallers and non-fallers

Objective

To determine the nervous activation, muscle strength, and biomechanical parameters that influence the cost of walking in older fallers and non-fallers.

Methods

Maximal voluntary isokinetic torque was measured for the hip, knee and ankle of older women. Oxygen consumption was measured at rest and during 8 min of walking at self-selected speed. An additional minute of walking was performed to collect kinematic variables and the electromyographic signal of trunk, hip, knee, and ankle muscles, which was analyzed by the linear envelope. Cost of walking was calculated by subtracting resting body mass-normalized oxygen consumption from walking body mass-normalized oxygen consumption. Stride time and length, and ankle and hip range of motion were calculated from kinematic data.

Findings

Older adult fallers had 28% lower knee extensor strength (p = 0.02), 47% lower internal oblique activation at heel contact (p = 0.03), and higher coactivation between tibialis anterior and gastrocnemius lateralis in each of the gait phases (p < 0.05). For fallers, a higher activation of gluteus maximus was associated with a higher cost of walking (r = 0.55, p < 0.05 and r = 0.71, p < 0.01, before and after heel contact, respectively). For non-fallers, an association between cost of walking and age (r = 0.60, p = 0.01) and cost of walking and thigh muscle coactivation (r = 0.53, p = 0.01) existed.

Interpretation

This study demonstrated that there may be links between lower-extremity muscle weakness, muscle activation patterns, altered gait, and increased cost of walking in older fallers.     

Layer-specific dilation of penetrating arteries induced by stimulation of the nucleus basalis of Meynert in the mouse frontal cortex

To clarify mechanisms through which activation of the nucleus basalis of Meynert (NBM) increases cerebral cortical blood flow, we examined whether cortical parenchymal arteries dilate during NBM stimulation in anesthetized mice. We used two-photon microscopy to measure the diameter of single penetrating arteries at different depths (∼800 μm, layers I to V) of the frontal cortex, and examined changes in the diameter during focal electrical stimulation of the NBM (0.5 ms at 30 to 50 μA and 50 Hz) and hypercapnia (3% CO₂ inhalation). Stimulation of the NBM caused diameter of penetrating arteries to increase by 9% to 13% of the prestimulus diameter throughout the different layers of the cortex, except at the cortical surface and upper part of layer V, where the diameter of penetrating arteries increased only slightly during NBM stimulation. Hypercapnia caused obvious dilation of the penetrating arteries in all cortical layers, including the surface arteries. The diameters began to increase within 1 second after the onset of NBM stimulation in the upper cortical layers, and later in lower layers. Our results indicate that activation of the NBM dilates cortical penetrating arteries in a layer-specific manner in magnitude and latency, presumably related to the density of cholinergic nerve terminals from the NBM.     

Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome

Adiponectin, also referred to as AdipoQ or ACRP30, is a plasma protein produced and secreted exclusively from adipose tissue. The protein contains a collagen-like domain and a C1q-like globular domain. A protease-generated globular segment enhances fatty acid oxidation in muscles, thereby modulating lipid and glucose metabolism. Plasma adiponectin levels are inversely correlated with the severity of insulin resistance. A recent genome-wide scan study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. Here, we screened Japanese patients with type 2 diabetes and age- and BMI-matched nondiabetic control subjects for mutations in adiponectin gene. We identified four missense mutations (R112C, I164T, R221S, and H241P) in the globular domain. Among these mutations, the frequency of I164T mutation was significantly higher in type 2 diabetic patients than in age- and BMI- matched control subjects (P < 0.01). Furthermore, plasma adiponectin concentrations of subjects carrying I164T mutation were lower than those of subjects without the mutation. All the subjects carrying I164T mutation showed some feature of metabolic syndrome, including hypertension, hyperlipidemia, diabetes, and atherosclerosis. Our findings suggest that I164T mutation is associated with low plasma adiponectin concentration and type 2 diabetes.     

Breastfeeding reduces the severity of respiratory syncytial virus infection among young infants: A multi‐center prospective study

Background: The objective of this study was to evaluate the effects of breastfeeding on the severity of respiratory syncytial virus infection in early infancy. Methods: A rapid test for respiratory syncytial virus (RSV) was administered by 16 general pediatricians from May 2002 to April 2005 in infants undergoing medical checkups for the common cold, all of whom were 100 days old or younger and had birthweights of more than 2500 g without underlying disease. Infants were divided into three groups: the Full breastfeeding group, the Partial group, and the Token group. RSV‐positive cases were followed up for 10 days after the initial diagnosis and the following three points were investigated: (i) the incidence of hospitalization; (ii) the duration of hospitalization; and (iii) the incidence of requiring oxygen therapy. Results: RSV antigen was detected in 203 of the total of 892 cases, and these were diagnosed as cases of RSV infectious disease. Although there were no significant differences in the hospitalization rate among the three groups, there were significant differences in the duration of hospitalization and the rate of requiring oxygen therapy. Multivariate logistic regression revealed that the requirement of oxygen therapy was significantly lower in the Full breastfeeding group (P= 0.032; odds ratio, 0.256; 95% confidence interval, 0.074–0.892). Conclusions: Breastfeeding reduces the severity of respiratory syncytial virus infection in early infancy.