Population pharmacokinetics and pharmacodynamic target attainment analysis of cefazolin using total and unbound serum concentration in patients with prostatectomy or nephrectomy.

The aim of this study was to analyze the population pharmacokinetics of total and unbound concentrations of prophylactic cefazolin (CFZ) in patients with prostatectomy or nephrectomy. We also aimed to calculate a pharmacodynamics target unbound concentration that exceeded the minimum inhibitory concentration (MIC), to design an effective dosing regimen. Briefly, 614 total concentration and 610 unbound concentration samples from 152 individuals were evaluated, using a nonlinear mixed-effects model. The obtained pharmacodynamics index target value reflected the probability of maintaining CFZ unbound trough concentrations exceeding MIC90, 0.5 mg/L, and MIC50, and 1.0 mg/L, to account for methicillin-susceptible Staphylococcus aureus (MSSA) or Escherichia coli. Population pharmacokinetics were estimated using a two-compartment model with nonlinear protein binding. Unbound systemic clearance (CL) was significantly associated with creatinine clearance, while the maximum protein-binding constant was significantly associated with albumin levels. The probability of achieving an unbound concentration exceeding the MIC50 for E. coli or MIC90 for MSSA in a patient with normal renal function following a 1 g CFZ infusion over 15 min was above 90% at 3 h after the initial dose. Our findings indicated that population pharmacokinetic parameters are useful for determining unbound CFZ pharmacokinetics and evaluating intraoperative CFZ redosing intervals.

Role of the medial agranular cortex in unilateral spatial neglect.

Unilateral spatial neglect (USN) results from impaired attentional networks and can affect various sensory modalities, such as visual and somatosensory. The rodent medial agranular cortex (AGm), located in the medial part of the forebrain from rostral to caudal direction, is considered a region associated with spatial attention. The AGm selectively receives multisensory input with the rostral AGm receiving somatosensory input and caudal part receiving visual input. Our previous study showed slower recovery from neglect with anterior AGm lesion using the somatosensory neglect assessment. Conversely, the functional differences in spatial attention across the entire AGm locations (anterior, intermediate, and posterior parts) are unknown. Here, we investigated the relationship between the severity of neglect and various locations across the entire AGm in a mouse stroke model using a newly developed program-based analysis method that does not require human intervention. Among various positions of the lesions, the recovery from USN during recovery periods (postoperative day; POD 10-18) tended to be slower in cases with more rostral lesions in the AGm (r = - 0.302; p = 0.028). Moreover, the total number of arm entries and maximum moving speed did not significantly differ between before and after AGm infarction. According to these results, the anterior lesions may slowly recover from USN-like behavior, and there may be a weak association between the AGm infarct site and recovery rate. In addition, all unilateral focal infarctions in the AGm induced USN-like behavior without motor deficits.

Serum stratifin measurement is useful for evaluating disease severity and outcomes in patients with acute exacerbation of interstitial lung disease: a retrospective study.

BACKGROUND: Serum levels of stratifin (SFN), a member of the 14-3-3 protein family, increase in patients with drug-induced lung injury associated with diffuse alveolar damage. Therefore, we hypothesised that SFN levels would be higher in those experiencing acute exacerbation of interstitial lung disease (AE-ILD). A secondary analysis was also planned to determine whether SFN levels could discriminate survival in those with AE. METHODS: Thirty-two patients with clinically stable ILD (CS-ILD) and 22 patients with AE-ILD were examined to assess whether high serum SFN levels were associated with AE-ILD and whether SFN levels reflected disease severity or prognosis in patients with AE-ILD. RESULTS: Serum SFN levels were higher in the AE-ILD group than in the CS-ILD group (8.4 ± 7.6 vs. 1.3 ± 1.2 ng/mL, p < 0.001). The cut-off value of the serum SFN concentration for predicting 90-day and 1-year survival was 6.6 ng/mL. SFN levels were higher in patients who died within 90 days and 1 year than in patients who survived beyond these time points (13.5 ± 8.7 vs. 5.6 ± 5.3 ng/mL; p = 0.011 and 13.1 ± 7.5 vs. 3.1 ± 1.9 ng/mL; p < 0.001, respectively) in the AE-ILD group. When this cut-off value was used, the 90-day and 1-year survival rates were significantly better in the population below the cut-off value than in those above the cut-off value (p = 0.0017 vs. p < 0.0001). CONCLUSIONS: High serum SFN levels are associated with AE-ILD and can discriminate survival in patients with AE-ILD.

Annual record on the number of general urological surgeries registered in the National Clinical Database system between April 2018 and December 2021 in Japan.

BACKGROUND: The Japanese National Clinical Database (NCD) is a large-scale, nationwide, web-based data entry system that covers the majority of surgical cases performed in Japan. An NCD specializing in urological surgery was launched based on the NCD system in 2018. METHODS: All urological surgeries performed at more than 1000 institutions were registered from 2018. We herein report the number of surgeries conducted as stipulated in the "Certified Urology Surgeon Training Curriculum" between April 2018 and December 2021. RESULTS: A total of 1 377 677 cases were registered from 1185 facilities nationwide under the initiative of the Japanese Urological Association. We examined the number of procedures performed every year for each of the 10 categories. CONCLUSIONS: The NCD system sustainably provides important information relating to the preoperative status, operational outcome, and best practice for urological surgery in Japan.

Effects of Anti-Fibrotic Drugs on Transcriptome of Peripheral Blood Mononuclear Cells in Idiopathic Pulmonary Fibrosis.

Two anti-fibrotic drugs, pirfenidone (PFD) and nintedanib (NTD), are currently used to treat idiopathic pulmonary fibrosis (IPF). Peripheral blood mononuclear cells (PBMCs) are immunocompetent cells that could orchestrate cell-cell interactions associated with IPF pathogenesis. We employed RNA sequencing to examine the transcriptome signature in the bulk PBMCs of patients with IPF and the effects of anti-fibrotic drugs on these signatures. Differentially expressed genes (DEGs) between "patients with IPF and healthy controls" and "before and after anti-fibrotic treatment" were analyzed. Enrichment analysis suggested that fatty acid elongation interferes with TGF-ß/Smad signaling and the production of oxidative stress since treatment with NTD upregulates the fatty acid elongation enzymes ELOVL6. Treatment with PFD downregulates COL1A1, which produces wound-healing collagens because activated monocyte-derived macrophages participate in the production of collagen, type I, and alpha 1 during tissue damage. Plasminogen activator inhibitor-1 (PAI-1) regulates wound healing by inhibiting plasmin-mediated matrix metalloproteinase activation, and the inhibition of PAI-1 activity attenuates lung fibrosis. DEG analysis suggested that both the PFD and NTD upregulate SERPINE1, which regulates PAI-1 activity. This study embraces a novel approach by using RNA sequencing to examine PBMCs in IPF, potentially revealing systemic biomarkers or pathways that could be targeted for therapy.

Applicability of the histidine-tryptophan-ketoglutarate solution as a machine perfusion solution for marginal liver grafts.

BACKGROUND AND AIM: There are very few reports comparing the use of the University of Wisconsin solution and histidine-tryptophan-ketoglutarate solution as machine perfusion solutions for marginal liver grafts. We aimed to clarify whether the use of the histidine-tryptophan-ketoglutarate solution in hypothermic machine perfusion improves the split-liver graft function in a large animal model. METHODS: Porcine split-liver grafts were created by 75% liver resection. Hypothermic machine perfusion experimental groups were divided as follows: Group 1, perfusate, University of Wisconsin gluconate solution (UW group; n = 5), and Group 2, perfusate, histidine-tryptophan-ketoglutarate solution (HTK group; n = 4). After 4 h of preservation, the liver function was evaluated using an isolated liver reperfusion model for 2 h. RESULTS: In the HTK group, the portal vein and hepatic artery resistance during hypothermic machine perfusion and the portal vein resistance during isolated liver reperfusion were lower than those in the UW group. In addition, the total Suzuki score for hepatic ischemia-reperfusion injury in the HTK group was significantly better than that in the UW group. The number of anti-ETS-related genes staining-positive sinusoid epithelial cell nuclei in the HTK group was higher than that in the UW group (not significant). CONCLUSIONS: The histidine-tryptophan-ketoglutarate solution can be perfused with lower vascular resistance than the University of Wisconsin solution, reducing shear stress and preventing sinusoid epithelial cell injury in marginal grafts used as split-liver grafts.

Quantitative evaluation of pediatric umbilical loop stomas: 2 decades of experience from a single institution.

PURPOSE: Since pediatric stomas are often temporary, their creation, management, and closure should be simple, with minimal complications and excellent cosmetic results. We began employing umbilical stomas in 2000. This study aimed to characterize the ingenuity and utility of umbilical stomas and provide a quantitative evaluation of their cosmetic outcomes. METHODS: We examined cases of stoma construction and closure surgery performed in our department from January 2000 to December 2022. The umbilical and non-umbilical stoma groups included 54 and 42 cases, respectively, and the findings for both groups were compared and analyzed. RESULTS: The two groups showed no significant differences in the incidence of complications. The Manchester Scar Scale score for the umbilical stoma group (8.42 ± 1.85) was significantly better than that for the non-umbilical stoma group (16.31 ± 2.96; P < 0.01). Likewise, in Patient and Observer Scar Assessment Scale assessments, the umbilical stoma group showed significantly better scores in both the observer scale (9.48 ± 2.50 vs. 21.78 ± 7.26; P < 0.01) and the patient scale (10.5 ± 1.39 vs. 22.40 ± 7.35; P < 0.01). CONCLUSIONS: Umbilical stomas are easy to manage and yield an inconspicuous closure incision with excellent cosmetic outcomes. Although patient selection is important, pediatric umbilical stomas are a valuable option that can be actively employed.

Different Transcriptome Features of Peripheral Blood Mononuclear Cells in Non-Emphysematous Chronic Obstructive Pulmonary Disease.

Non-emphysematous chronic obstructive pulmonary disease (COPD), which is defined based on chest computed tomography findings, presented different transcriptome features of peripheral blood mononuclear cells (PBMCs) compared with emphysematous COPD. Enrichment analysis of transcriptomic data in COPD demonstrated that the "Hematopoietic cell lineage" pathway in Kyoto Encyclopedia of Genes and Genomes pathway analysis was highly upregulated, suggesting that cellular dynamic dysregulation in COPD lungs is affected by pathologically modified PBMCs. The differentially expressed genes (DEGs) upregulated in PBMCs reflected the disease state of non-emphysematous COPD. Upregulated DEGs such as XCL1, PRKCZ, TMEM102, CD200R1, and AQP1 activate T lymphocytes and eosinophils. Upregulating keratan sulfate biosynthesis and metabolic processes is associated with protection against the destruction of the distal airways. ITGA3 upregulation augments interactions with extracellular matrix proteins, and COL6A1 augments the profibrotic mast cell phenotype during alveolar collagen VI deposition. Upregulating HSPG2, PDGFRB, and PAK4 contributes to the thickening of the airway wall, and upregulating SERPINF1 expression explains the better-preserved vascular bed. Therefore, gene expression and pathway analysis in PBMCs in patients with non-emphysematous COPD represented type 2 immune responses and airway remodeling features. Therefore, these patients have asthmatic potential despite no clinical signs of asthma, in contrast to those with emphysematous COPD.

Effects of short-term upper limb immobilization on sensory information processing and corticospinal excitability.

Several studies have reported the effects of short-term immobilization of the upper limb on the excitability of the primary motor cortex. In a report examining the effects of upper limb immobilization on somatosensory information processing using somatosensory-evoked potentials (SEPs), short-term upper limb immobilization reduced the amplitude and increased the latency of the P45 component recorded over the contralateral sensorimotor cortex of SEPs. However, the effects of upper limb immobilization on other regions involved in somatosensory information processing are unknown. Therefore, we investigated the effects of short-term right upper limb immobilization on sensory information processing, particularly in motor-related areas, by measuring the cortical components of SEPs. We also evaluated the excitability of the primary motor cortex and corticospinal tract as well as motor performance (visual simple reaction time and pinch force) related to these areas. All subjects were divided into two groups: the SEP group, in which the effects of upper limb immobilization on the excitability of somatosensory processing were investigated, and the transcranial magnetic stimulation (TMS) group, in which the effects of upper limb immobilization on the excitability of the corticospinal tract and primary motor cortex were investigated. Motor performance was evaluated in all subjects. We showed that 10-h right upper limb immobilization increased the cortical component of SEPs (N30) in the SEP group and decreased the excitability of the corticospinal tract, but not of the primary motor cortex, in the TMS group. The pinch force decreased after upper limb immobilization. However, the visual simple reaction time did not change between pre- and post-immobilization. The supplementary motor area and premotor cortex are believed to be the source of the N30. Therefore, these results suggest that upper limb immobilization affected somatosensory information processing in motor-related areas. Moreover, 10-h right upper limb immobilization reduced the excitability of corticospinal tracts but not that of the primary motor cortex, suggesting that circuits outside the M1, such as the intra- and inter-hemispheric inhibitory and facilitatory circuits rather than circuits within the M1, may be responsible for the reduced excitability of the central nervous system after restraint.

Changes in spike protein antibody titer over 90 days after the second dose of SARS-CoV-2 vaccine in Japanese dialysis patients.

OBJECTIVES: There is no report on antibody titers after vaccination against SARS-CoV-2 in Japanese dialysis patients. As dialysis is different between Japan and other countries, changes in antibody titers were examined. METHODS: Baseline characteristics and anti-spike protein antibody titers (Roche) over 90 days after administration of the BNT162b2 messenger RNA vaccine were investigated in dialysis patients. RESULTS: The maximum anti-spike protein antibody titer after the second dose was 738 (327 to 1143) U/mL and was reached at 19 (17 to 24) days after the second dose. Antibody titers decreased over time, with titers of 770 (316 to 1089) U/mL at 15 days, 385 (203 to 690) U/mL at 30 days, 254 (138 to 423) U/mL at 60 days, and 208 (107 to 375) U/mL at 90 days after the second dose. When an antibody titer of 137 U/mL was assumed to be a measure related to breakthrough infection, the proportion of subjects with antibody titers exceeding this level was 90.1% at 15 days, 85.3% at 30 days, 75.0% at 60 days, and 65.4% at 90 days after the second dose. When a decrease in antibody titers below the assumed breakthrough level was defined as an event, subjects with a pre-dialysis albumin ≥ 3.5 g/dL were significantly less likely to experience an event than subjects with a pre-dialysis albumin < 3.5 g/dL. CONCLUSIONS: The presence of anti-spike protein levels ≥ 313 U/mL at 30 days after the second vaccine dose might be a factor in maintaining enough antibody titers at 90 days after. Whether an additional vaccine dose is needed should be determined based on indicators serving as factors in maintaining antibody titers as well as the status of the spread of infection.

Decreased GM3 correlates with proteinuria in minimal change nephrotic syndrome and focal segmental glomerulosclerosis.

BACKGROUND: Glycolipids on cell membrane rafts play various roles by interacting with glycoproteins. Recently, it was reported that the glycolipid GM3 is expressed in podocytes and may play a role in podocyte protection. In this report, we describe the correlation between changes in GM3 expression in glomeruli and proteinuria in minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) patients. METHODS: We performed a case-control study of the correlation between nephrin/GM3 expression levels and proteinuria in MCNS and FSGS patients who underwent renal biopsy at our institution between 2009 and 2014. Normal renal tissue sites were used from patients who had undergone nephrectomy at our institution and gave informed consent. RESULTS: Both MCNS and FSGS had decreased GM3 and Nephrin expression compared with the normal (normal vs. MCNS, FSGS; all p < 0.01). Furthermore, in both MCNS and FSGS, GM3 expression was negatively correlated with proteinuria (MCNS: r = - 0.61, p < 0.01, FSGS: r = - 0.56, p < 0.05). However, nephrin expression had a trend to correlate with proteinuria in FSGS (MCNS: r = 0.19, p = 0.58, FSGS: r = - 0.48, p = 0.06). Furthermore, in a simple linear regression analysis, GM3 expression also correlated with proteinuric change after 12 months of treatment (MCNS: r = 0.40, p = 0.38, FSGS: r = 0. 68, p < 0.05). CONCLUSION: We showed for the first time that decreased GM3 expression correlates with proteinuria in MCNS and FSGS patients. Further studies are needed on the podocyte-protective effects of GM3.

Correcting anemia and native vitamin D supplementation in kidney transplant recipients: a multicenter, 2 × 2 factorial, open-label, randomized clinical trial.

Anemia and vitamin D deficiency are associated with allograft failure, and hence, are potential therapeutic targets among kidney transplant recipients (KTRs). We conducted a multicenter, two-by-two factorial, open-label, randomized clinical trial to examine the effects of anemia correction and vitamin D supplementation on 2-year change in eGFR among KTRs (CANDLE-KIT). We enrolled 153 patients with anemia and >1-year history of transplantation across 23 facilities in Japan, and randomly assigned them to either a high or low hemoglobin target (>12.5 vs. <10.5 g/dl) and to either cholecalciferol 1000 IU/day or control. This trial was terminated early based on the planned interim intention-to-treat analyses (α = 0.034). Among 125 patients who completed the study, 2-year decline in eGFR was smaller in the high vs. low hemoglobin group (i.e., -1.6 ± 4.5 vs. -4.0 ± 6.9 ml/min/1.73 m2 ; P = 0.021), but did not differ between the cholecalciferol and control groups. These findings were supported by the fully adjusted mixed effects model evaluating the rate of eGFR decline among all 153 participants. There were no significant between-group differences in all-cause death or the renal composite outcome in either arm. In conclusion, aggressive anemia correction showed a potential to preserve allograft kidney function.

Risk factors for recurrent gastroesophageal reflux disease after Thal fundoplication.

PURPOSE: The recurrence rate of gastroesophageal reflux disease (GERD) after fundoplication has been reported to be 7-25%. We investigated the risk factors for recurrence of GERD after Thal fundoplication (TF) in our department with the aim of further reducing the recurrence rate of GERD. METHODS: We retrospectively analyzed 276 patients who underwent TF for GERD at our hospital between 2000 and 2019. Retrospectively considered variables were obtained from the medical records of patients. The variables included patient characteristics, GERD severity, surgery-related factors and postoperative course. RESULTS: The postoperative GERD recurrence rate was 5.8%. In the univariate analysis, the presence of convulsive seizures (12/4 vs. 110/150, p = 0.046) and the absence of a tracheostomy (0/16 vs. 53/207, p = 0.048) at the time of TF were significantly associated with recurrence. In the multivariate analysis, the presence of convulsive seizures at the time of TF was the only factor significantly associated with recurrence. CONCLUSION: The presence of convulsive seizures and the absence of a tracheostomy at the time of TF were significantly associated with GERD recurrence after TF. Active control of seizures and consideration of surgical indications, including assessment of respiratory status, are important in preventing the recurrence of GERD after TF.

Preferential performance of Thal fundoplication for gastroesophageal reflux disease: a single institution experience.

PURPOSE: Nissen fundoplication (NF) is the most commonly used surgical treatment for persistent gastroesophageal reflux disease (GERD). We introduced to the alternative Thal fundoplication (TF) (partial anterior wrapping) in 1998. The purpose of this paper is to review and report on the effectiveness of TF in our department. METHODS: We retrospectively analyzed cases of 281 patients who underwent TF for GERD at our hospital from 1998 to 2019. RESULTS: Average age, 16.3 ± 18.1 years; average body weight, 21.0 ± 16.0 kg; average operative time, 89.1 ± 43.0 min; average volume of bleeding, 11.6 ± 29.2 g; enteral feeding commenced after an average of 3.4 ± 1.3 postoperative days (PODs), and average postoperative full enteral feeding was 6.3 ± 1.4 PODs. Five patients (1.8%) had Clavien-Dindo classification III or higher; average hospital stay duration was 10.3 ± 6.0 days, with symptom recurrence affecting 17 patients (6.1%). CONCLUSION: TF may be an effective and simple treatment for GERD that has few recurrences and avoids complications common to NF, but further studies to compare it with other techniques are needed.

Relationship Between Motor Function, DTI, and Neurophysiological Parameters in Patients with Stroke in the Recovery Rehabilitation unit.

OBJECTIVES: We investigated the relationship between pyramidal tract evaluation indexes (i.e., diffusion tensor imaging, transcranial magnetic stimulation (TMS)-induced motor-evoked potential (MEP), and central motor conduction time (CMCT) on admission to the recovery rehabilitation unit) and motor functions at discharge in patients with ischemic or hemorrhagic stroke. MATERIALS AND METHODS: Seventeen patients were recruited (12 men; 57.9 ± 10.3 years). The mean fractional anisotropy (FA) values of the right and left posterior limbs of the internal capsule were estimated using a computer-automated method. We determined the ratios of FA values in the affected and unaffected hemispheres (rFA), TMS-induced MEP, and the ratios of CMCT in the affected and unaffected hemispheres (rCMCT) and examined their association with motor functions (Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT)) at discharge. RESULTS: Higher rFA values of the posterior limb of the internal capsule on admission to the recovery rehabilitation unit led to a better recovery of upper limb function (FMA: r = 0.78, p < 0.001; ARAT: r = 0.74, p = 0.001). Patients without MEP had poorer recovery of upper limb function than those with MEP (FMA: p < 0.001; ARAT: p = 0.001). The higher the rCMCT, the poorer the recovery of upper limb function (ARAT: r = -0.93, p < 0.001). However, no association was observed between the pyramidal tract evaluation indexes and recovery of lower limb motor function. CONCLUSIONS: Evaluating the pyramidal tract is useful for predicting upper limb function prognosis, but not for lower limb function prognosis.

Renal functional outcome after laparoscopic partial nephrectomy using dynamic renal scintigraphy.

INTRODUCTION To explore postoperative operation-side renal functional outcome after laparoscopic partial nephrectomy (LPN) using dynamic renal scintigraphy. MATERIALS AND METHODS: Between July 2006 and December 2014, 62 patients with localized renal tumor received ischemic LPN at our institution. Preoperative, 6 months postoperative, and 12 months postoperative split renal functions were evaluated by dynamic renal scintigraphy using radionuclide technetium-99m-mercaptoacetyltriglycine. Postoperative operation-side renal function was calculated. To assess the significant factors affecting postoperative operation-side renal functional decrease, simple regression and multiple regression analyses were carried out. RESULTS: Postoperative operation-side renal functions were significantly decreased to 86.6% at 6 months and 86.9% at 12 months postoperatively (p < 0.0001). Simple regression analyses revealed that postoperative operation-side renal functions were significantly decreased with prolonged warm ischemia time at 6 months and 12 months postoperatively (p = 0.0058 and 0.0032, respectively). Multiple regression analysis identified warm ischemia time as an independent predictive factor for operation-side renal functional decreases at 6 months and 12 months postoperatively (p = 0.0158 and 0.0109, respectively). CONCLUSIONS: Irreversible renal damage using dynamic renal scintigraphy after LPN was observed. With prolongation of warm ischemia time during LPN, postoperative operation-side renal function was significantly decreased.

Efficacy of Exercise Therapy Initiated in the Early Phase After Kidney Transplantation: A Pilot Study.

OBJECTIVE: In patients with kidney transplant (KT), frailty is a predictor of adverse outcomes. Outcomes of exercise therapy in patients with KT, particularly the efficacy of early exercise after KT, have not been evaluated. We investigated the effect of exercise intervention beginning early after KT on physical performance, physical activity, quality of life, and kidney function in patients with KT. METHODS: KT recipients who underwent surgery with usual care plus exercise training from a prospective cohort (exercise group; n = 10) and those with usual care alone from a historical cohort (control group; n = 14) were included in this study. Early exercise comprised supervised aerobic training and physical activity instruction from day 6 to 2 months after KT. The following outcomes were measured: 6-minute walking distance, isometric knee extensor strength, gait speed, physical activity, quality of life, and estimated glomerular filtration rate. RESULTS: Analyses of covariance, adjusted for baseline values, revealed significant mean differences between exercise and control groups at 2 months after KT in 6-minute walking distance (+44.4 m, P = .03) and isometric knee extensor strength (+8.1%body weight, P = .03). No significant between-group differences were found in gait speed, physical activity, and quality of life. The analysis of variance for comparison of the area under the recovery curves of estimated glomerular filtration rate after KT revealed no significant difference between groups. CONCLUSION: Supervised aerobic training and physical activity instruction initiated in the early phase after KT can improve physical performance without adversely affecting kidney function.

A Short-Duration Combined Exercise and Education Program to Improve Physical Function and Social Engagement in Community-Dwelling Elderly Adults.

Exercise is a key intervention for improving older adults' physical function and life expectancy. Here, we investigated a short-term intervention program designed to improve the physical functioning of elderly adults in a community-dwelling setting. We examined the effect of a 5-week combined exercise and education program on the physical function, social engagement, mobility performance, and fear of falling in 42 subjects older than 65 years. Eleven subjects dropped out. There was significant improvement in the 30-second chair stand test (p < .001) and timed up-and-go test (p < .001) between the baseline and the last session. At the end of the intervention, the subjects' social engagement was significantly higher than at baseline (p = .022), but this improvement was not maintained in the follow-up assessment. These results suggest that a combined exercise and education program can improve the physical function and social engagement of elderly individuals living in a community dwelling.

Paternal methyl donor deficient diets during development affect male offspring behavior and memory-related gene expression in mice.

It has become increasingly evident that the methylation of DNA, known as an epigenetic marker, affects behavior in animals. In our previous study, a methyl-donors (folate, methionine, and choline)-deficient (FMCD) diet during the juvenile period could be shown to affect anxiety-like behavior and fear memory, accompanied by alteration in some gene expression and their methylations in the hippocampus. One question is whether the fear memory of a parent affects the fear responses of offspring. To explore this question in the present study, C57BL/6 J male (F0) mice were given a FMCD diet from 3 to 12 weeks of age. After confirming the effect of the FMCD diet on the behavior and gene expression of F0 mice, their male offspring (F1-FMCD mice) were examined using the same behavioral batteries and genetic analysis. F0 diet-based differences in F1 behavior were observed, accompanied by the differences in the expression of memory-related genes (Camk2α and PP1) and promoter methylation of the PP1 gene in the hippocampus. Our results add evidence that behavior and gene expression of the F1 generation could be altered due to differences in the father's intake of methyl-donor nutrients.

Spontaneous recovery of fear differs among early - late adolescent and adult male mice.

Adolescence is a vulnerable period for developing anxiety-related mental disorders such as post-traumatic stress disorder (PTSD), which requires a long-term course of therapy when a traumatic event has been experienced during childhood. However, the biological mechanism underlying these age-dependent characteristics remains unclear. In the present study, we used early adolescent, late adolescent and adult (4-, 8-, and 15-week old) male mice to examine age differences in fear memory, fear extinction, and spontaneous recovery of fear. We also measured the activation of extracellular signal-regulated kinase (ERK) 2 in the dorsal hippocampus (dHip) and the basolateral amygdala (BLA) following a spontaneous recovery test. Our major findings were as follows: (1) early adolescent and adult mice did not recover the fear response; only late adolescent mice recovered the fear response. (2) The ERK2 in the dHip was more activated after the spontaneous recovery test in late adolescent mice than in adult mice, and the ERK2 in the BLA was more activated after the spontaneous recovery test in adult mice than in late adolescent mice. These results suggest that there exists a unique period in which spontaneous recovery occurs and that these late adolescent behavioral signatures may be related to alteration in the ERK2 phosphorylation in the dHip and BLA.