Effect of post-operative anticoagulation management in patients who have undergone On-X mechanical heart valve replacement surgery on post-discharge warfarin therapy.

WHAT IS KNOWN AND OBJECTIVE: We evaluated the effect of the proportion of time maintained within the target international normalized ratio (INR) postoperatively in hospitalized patients who underwent On-X mechanical heart valve replacement on warfarin therapy after discharge. METHODS: Inclusion was patients who were ≥18 years, received warfarin for a minimum of 10 days without any interruptions during hospitalization and followed by the anticoagulation service (ACS) clinic after discharge between June 2006 and June 2016. Patients were excluded if they had incomplete medical records, INR goal changes, known as warfarin resistance, transferred to another facility or expired during the study. The patients were divided into 3 groups according to the proportion of time maintained within therapeutic INR range (TTR) from day 4 to 10 of warfarin initiation (low: <30%, moderate: ≥30% to <70%, and high: ≥70%). The number of days needed to reach target INR for 2 consecutive measurements after discharge and the number of ACS visits was compared among the groups. RESULTS AND DISCUSSION: Among 539 postoperative patients, 273 were included. The baseline demographics were similar among the 3 groups. The mean time needed to reach target INR for 2 consecutive measurements was 68.6 ± 106.1 days. The low group required time needed to reach target INR for 2 consecutive measurements of 94.0 ± 140.9 days compared with 44.8 ± 57.1 days in the high group (P = .007). Additionally, the low group had more ACS visits than the high group (low, 6.6 ± 5.2 vs high, 4.6 ± 3.9; P = .025). Patient compliance affected the time needed to reach target INR for 2 consecutive measurements (compliant, 42.36 ± 58.5 days vs non-compliant, 132.0 ± 157.1 days, P < .001). WHAT IS NEW AND CONCLUSION: The study implicated that high postoperative TTR would reduce the time to require post-discharge target INR and the number of ACS visits.

Sex-Dependent Adverse Drug Reactions to 5-Fluorouracil in Colorectal Cancer.

Sex-related incidence and outcomes were reported in various cancers, including colorectal cancer. 5-Fluorouracil (5-FU) is widely used as an essential chemotherapeutic agent for colorectal cancer. However, sex-based differences in 5-FU toxicity have yet to be reported in human cancer cell lines and xenograft mouse models to date. Here, we investigated, for the first time, sex-based differences in 5-FU toxicity using human colon cancer cell lines, xenograft mouse models, and Korean patients' data. Female-derived colon cancer cell lines exhibited greater 5-FU-induced cytotoxicity than male-derived colon cancer cell lines. We established two xenograft mouse models: one with a male-derived human colon cancer cell line injected into male mice (a male-xenograft model) and another involving a female-derived human colon cancer cell line injected into female mice (a female xenograft model). Treatment with 5-FU inhibited tumor growth and led to hematological toxicity in a female xenograft model more potently than in a male xenograft model. We analyzed the data obtained from Korean patients with colorectal cancer to examine sex differences in adverse drug reactions caused by 5-FU. Korean female patients with colorectal cancer who received 5-FU chemotherapy experienced more frequent adverse drug reactions including alopecia and leukopenia than male patients. Taken together, we demonstrated that female may be associated with increased risk of toxicity to 5-FU treatment in colorectal cancer based on in vitro and in vivo investigations and clinical data analysis. Our study suggests sex as an important clinical factor, which predicts induction of toxicity related to 5-FU treatment.

Bacterial Dissemination to the Brain in Sepsis.

RATIONALE: Sepsis causes brain dysfunction and neuroinflammation. It is unknown whether neuroinflammation in sepsis is initiated by dissemination of bacteria to the brain and sustained by persistent infection, or whether neuroinflammation is a sterile process resulting solely from circulating inflammatory mediators. OBJECTIVES: To determine if gut bacteria translocate to the brain during sepsis, and are associated with neuroinflammation. METHODS: Murine sepsis was induced using cecal ligation and puncture, and sepsis survivor mice were compared with sham and unoperated control animals. Brain tissue of patients who died of sepsis was compared with patients who died of noninfectious causes. Bacterial taxa were characterized by 16S ribosomal RNA gene sequencing in both murine and human brain specimens; compared among sepsis and nonsepsis groups; and correlated with levels of S100A8, a marker of neuroinflammation using permutational multivariate ANOVA. MEASUREMENTS AND MAIN RESULTS: Viable gut-associated bacteria were enriched in the brains of mice 5 days after surviving abdominal sepsis (P < 0.01), and undetectable by 14 days. The community structure of brain-associated bacteria correlated with severity of neuroinflammation (P < 0.001). Furthermore, bacterial taxa detected in brains of humans who die of sepsis were distinct from those who died of noninfectious causes (P < 0.001) and correlated with S100A8/A9 expression (P < 0.05). CONCLUSIONS: Although bacterial translocation is associated with acute neuroinflammation in murine sepsis, bacterial translocation did not result in chronic cerebral infection. Postmortem analysis of patients who die of sepsis suggests a role for bacteria in acute brain dysfunction in sepsis. Further work is needed to determine if modifying gut-associated bacterial communities modulates brain dysfunction after sepsis.

Energy and material flows of megacities.

Understanding the drivers of energy and material flows of cities is important for addressing global environmental challenges. Accessing, sharing, and managing energy and material resources is particularly critical for megacities, which face enormous social stresses because of their sheer size and complexity. Here we quantify the energy and material flows through the world's 27 megacities with populations greater than 10 million people as of 2010. Collectively the resource flows through megacities are largely consistent with scaling laws established in the emerging science of cities. Correlations are established for electricity consumption, heating and industrial fuel use, ground transportation energy use, water consumption, waste generation, and steel production in terms of heating-degree-days, urban form, economic activity, and population growth. The results help identify megacities exhibiting high and low levels of consumption and those making efficient use of resources. The correlation between per capita electricity use and urbanized area per capita is shown to be a consequence of gross building floor area per capita, which is found to increase for lower-density cities. Many of the megacities are growing rapidly in population but are growing even faster in terms of gross domestic product (GDP) and energy use. In the decade from 2001-2011, electricity use and ground transportation fuel use in megacities grew at approximately half the rate of GDP growth.

Predicting augmented renal clearance using estimated glomerular filtration rate in critically-ill children
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AIMS: Measured glomerular filtration rate (mGFR) is often used to identify augmented renal clearance (ARC). However, in the clinical setting, estimated GFR (eGFR) is obtained more quickly and inexpensively. We aimed to determine whether eGFR can identify ARC by evaluating the correlation between the eGFR and vancomycin trough level (VTL). MATERIALS AND METHODS: We retrospectively reviewed the records of patients aged ≤ 18 years who underwent vancomycin therapeutic drug monitoring at our tertiary hospital from July 2009 to June 2014. VTL, serum creatinine concentration, eGFR, and clinical factors affecting VTL were analyzed. RESULTS: Of 101 patients, 76 (75.25%) had a subtherapeutic VTL. Patient age (p = 0.006), the daily vancomycin dose (p = 0.041) and dosing interval (p = 0.006), and eGFR (p < 0.001) affected the VTL. Multivariate analysis showed a significant relationship between eGFR and VTL (adjusted R2, 0.812; p < 0.001). An increased eGFR (odds ratio, 1.002; 95% confidence interval, 1.001 - 1.003; p = 0.001) was a risk factor for a subtherapeutic vancomycin level. The cutoff eGFR value predicting a subtherapeutic vancomycin level was 110.51 mL/min/1.73m2 (area under the curve, 0.753). CONCLUSIONS: The eGFR correlates with the VTL, and the eGFR cutoff value can predict a subtherapeutic vancomycin level. eGFR is a reliable and efficient alternative to mGFR for identifying ARC.
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The successful accomplishment of nutritional and clinical outcomes via the implementation of a multidisciplinary nutrition support team in the neonatal intensive care unit.

BACKGROUND: Nutritional support is critical for preterm infants in the neonatal intensive care unit (NICU). A multidisciplinary nutritional support team (NST) that focuses on providing optimal and individualized nutrition care could be helpful. We conducted a thorough evaluation of clinical and nutritional outcomes in a tertiary NICU following the implementation of an NST. METHODS: This study used a retrospective approach with historical comparisons. Preterm neonates < 30 weeks gestational age or weighing < 1250 g were enrolled. Clinical and nutritional outcomes were compared before and after the establishment of the NST. Medical records were reviewed, and clinical and nutritional outcomes were compared between the two groups. RESULTS: In total, 107 patients from the pre-NST period and 122 patients from the post-NST period were included. The cumulative energy delivery during the first week of life improved during the post-NST period (350.17 vs. 408.62 kcal/kg, p < 0.001). The cumulative protein and lipid deliveries also significantly increased. The time required to reach full enteric feedings decreased during the post-NST period (6.4 ± 5.8 vs. 4.7 ± 5.1 days, p = 0.016). Changes of Z-score in weight from admission to discharge exhibited more favorable results in the post-NST period (-1.13 ± 0.99 vs.-0.91 ± 0.74, p = 0.055), and the length of ICU stay significantly decreased in the post-NST period (81.7 ± 36.6 vs. 72.2 ± 32.9 days, p = 0.040). CONCLUSIONS: NST intervention in the NICU resulted in significant improvements in the provision of nutrition to preterm infants in the first week of life. There were also favorable clinical outcomes, such as increased weight gain and reduced length of ICU stay. Evaluable data remain sparse in the NICU setting with premature neonatal populations; therefore, the successful outcomes identified in this study may provide support for NST practices.

Epigenetic Modulation of Human Induced Pluripotent Stem Cell Differentiation to Oligodendrocytes.

Pluripotent stem cells provide an invaluable tool for generating human, disease-relevant cells. Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system, characterized by myelin damage. Oligodendrocytes are the myelinating cells of the central nervous system (CNS); they differentiate from progenitor cells, and their membranes ensheath axons, providing trophic support and allowing fast conduction velocity. The current understanding of oligodendrocyte biology was founded by rodent studies, where the establishment of repressive epigenetic marks on histone proteins, followed by activation of myelin genes, leads to lineage progression. To assess whether this epigenetic regulation is conserved across species, we differentiated human embryonic and induced pluripotent stem cells to oligodendrocytes and asked whether similar histone marks and relative enzymatic activities could be detected. The transcriptional levels of enzymes responsible for methylation and acetylation of histone marks were analyzed during oligodendrocyte differentiation, and the post-translational modifications on histones were detected using immunofluorescence. These studies showed that also in human cells, differentiation along the oligodendrocyte lineage is characterized by the acquisition of multiple repressive histone marks, including deacetylation of lysine residues on histone H3 and trimethylation of residues K9 and K27. These data suggest that the epigenetic modulation of oligodendrocyte identity is highly conserved across species.

Awareness of the adverse effects associated with prophylactic corticosteroid use during docetaxel therapy.

PURPOSE: Weekly or tri-weekly docetaxel treatment mandates the use of dexamethasone to prevent toxicity. However, the adverse effects of prophylactic steroid use are often overlooked. We investigated the incidence of corticosteroid-associated adverse effects during docetaxel therapy, focusing on hyperglycemia and infection as well as the identification of possible risk factors. METHODS: This study was conducted through retrospective chart review of 632 patients who started docetaxel-based chemotherapy between July 2011 and June 2012 at Seoul National University Hospital. Hyperglycemia was defined as more than two random glucose levels >200 mg/dL. All documented episodes of infection that required treatment with antibiotics were regarded as infectious episodes. RESULTS: The incidences of hyperglycemia in overall patients and in patients without previous diabetes mellitus were 13.7 and 10.9%, respectively. Infectious episodes greater than grade 2 and grade 3 developed in 29.6 and 19.9% of patients, respectively. Multivariable logistic regression analysis showed that body mass index and previous diabetes mellitus were independent risk factors for hyperglycemia, whereas corticosteroid dose was not. Treatment duration and frequency of high blood glucose levels over 200 mg/dL were independent risk factors for infection. CONCLUSIONS: Due to the significant difference in patient and treatment characteristics, we could not obtain meaningful comparisons between weekly and tri-weekly docetaxel administration regimens. This study suggests that adverse effects associated with prophylactic steroid use need to be recognized and optimally managed during docetaxel therapy.

The relationship between distribution of body fat mass and carotid artery intima-media thickness in Korean older adults.

[Purpose] The aim of this study was to examine the relationships between the amount and distribution of body fat and the carotid intima-media thickness to explore whether coronary artery disease risk may be mediated through effects on the amount of fat mass in older adults. [Subjects and Methods] A total of 200 elderly females was participated. The percentage of body fat mass was measured by the bioelectrical impedance analysis method, and the carotid intima-media thickness was measured by B-mode ultrasound. Analysis of covariance was performed to assess independent associations between the four categories of percentage of body fat mass and the carotid intima-media thickness after multivariate adjustment. Logistic regression analyses were utilized to calculate odds ratios and 95% confidence intervals for examining independent associations between percentage of body fat mass and the estimated risk of coronary artery disease. [Results] Analysis of covariance showed that the carotid intima-media thickness was significantly thick in both obesity and overweight groups. When multivariate-adjusted OR for the estimated risk of coronary artery disease, the odds ratios for the obesity and overweight groups were 3.0 (95% confidence interval, 1.1 to 8.7) and 2.5 (95% confidence interval, 1.0 to 6.1), respectively. [Conclusion] This study demonstrates that elderly females with a high body fat mass are more likely to have the estimated risk of CAD than who fit body fat mass in elderly female.

Cardiac Damage Biomarkers Following a Triathlon in Elite and Non-elite Triathletes.

The purpose of the present study was to investigate cardiac damage biomarkers after a triathlon race in elite and non-elite athlete groups. Fifteen healthy men participated in the study. Based on performance, they were divided into elite athlete group (EG: n=7) and non-elite athlete group (NEG: n=8). Participants' blood samples were obtained during four periods: before, immediately, 2 hours and 7 days after finishing the race. creatine kinase (CK), creatine kinase-myoglobin (CK-MB), myoglobin, and lactate dehydrogenase (LDH) were significantly increased in both groups immediately after, and 2 hours after finishing the race (p<.05). CK, CK-MB, and myoglobin were completely recovered after 7 days (p<.05). Hematocrit (Hct) was significantly decreased in both groups (p<.05) 7 days after the race. LDH was significantly decreased in the EG (p<.05) only 7 days after the race. Homoglobin (Hb) was significantly decreased in the NEG (p<.05) only 2 hours after the race. Although cardiac troponin T (cTnT) was significantly increased in the EG but not in the NEG 2hours after the race (p<.05), there was no group-by-time interaction. cTnT was completely recovered in both groups 7 days after the race. In conclusion, cardiac damage occurs during a triathlon race and, is greater in elite than in non-elite. However, all cardiac damage markers return to normal range within 1 week.

The Effects of 12 Weeks Regular Aerobic Exercise on Brain-derived Neurotrophic Factor and Inflammatory Factors in Juvenile Obesity and Type 2 Diabetes Mellitus.

[Purpose] The purpose of this study was to investigate the effects of 12 weeks regular aerobic exercise on brain-derived neurotrophic factor (BDNF) and inflammatory factors in juvenile obesity and type 2 diabetes mellitus (T2DM). Obesity and T2DM, typically common among adults, have recently become more prevalent in the Korean juvenile population, affecting not only their lipid profiles and oxidant stress levels, but also their BDNF and inflammatory factor levels. [Subjects] This study enrolled 26 juveniles (boys = 15, girls = 9) who were assigned to a control group (CG, n = 11), obesity group (OG, n = 8), or T2DM group (TG, n = 7). [Methods] The outcome of a 40-60-minute aerobic exercise session that took place three times per week for 12 weeks at a maximum oxygen intake (VO2max) of 50~60% was investigated. [Results] The exercise resulted in a significant reduction in the resting serum BDNF and TrkB levels (baseline) among juveniles in the OG and TG as compared to those in the CG. Additionally, the 12 weeks of regular aerobic exercise led to significant reductions in body weight, body fat percentage, and body mass index in the OG and a significant increase of VO2max in the OG and TG. However, no significant differences in serum NGF or inflammatory factors were found among the three groups. There was a significant increase in resting serum BDNF levels following the 12 weeks regular exercise only in the OG. [Conclusion] While 12 weeks of regular aerobic exercise had a positive effect on body composition, and increased BDNF levels of juveniles in the OG, it did not affect the inflammatory factor levels and had no effect on the TG.

Comparative dose effectiveness of intravenous and intrathecal AAV9.CB7.hIDS, RGX-121, in mucopolysaccharidosis type II mice.

Mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal disease caused by iduronate-2-sulfatase (IDS) deficiency, leading to accumulation of glycosaminoglycans (GAGs) and the emergence of progressive disease. Enzyme replacement therapy is the only currently approved treatment, but it leaves neurological disease unaddressed. Cerebrospinal fluid (CSF)-directed administration of AAV9.CB7.hIDS (RGX-121) is an alternative treatment strategy, but it is unknown if this approach will affect both neurologic and systemic manifestations. We compared the effectiveness of intrathecal (i.t.) and intravenous (i.v.) routes of administration (ROAs) at a range of vector doses in a mouse model of MPS II. While lower doses were completely ineffective, a total dose of 1 × 109 gc resulted in appreciable IDS activity levels in plasma but not tissues. Total doses of 1 × 1010 and 1 × 1011 gc by either ROA resulted in supraphysiological plasma IDS activity, substantial IDS activity levels and GAG reduction in nearly all tissues, and normalized zygomatic arch diameter. In the brain, a dose of 1 × 1011 gc i.t. achieved the highest IDS activity levels and the greatest reduction in GAG content, and it prevented neurocognitive deficiency. We conclude that a dose of 1 × 1010 gc normalized metabolic and skeletal outcomes, while neurologic improvement required a dose of 1 × 1011 gc, thereby suggesting the prospect of a similar direct benefit in humans.

Opposing diet, microbiome, and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host.

Inflammatory bowel diseases (IBDs) are chronic conditions characterized by periods of spontaneous intestinal inflammation and are increasing in industrialized populations. Combined with host genetics, diet and gut bacteria are thought to contribute prominently to IBDs, but mechanisms are still emerging. In mice lacking the IBD-associated cytokine, interleukin-10, we show that a fiber-deprived gut microbiota promotes the deterioration of colonic mucus, leading to lethal colitis. Inflammation starts with the expansion of natural killer cells and altered immunoglobulin-A coating of some bacteria. Lethal colitis is then driven by Th1 immune responses to increased activities of mucin-degrading bacteria that cause inflammation first in regions with thinner mucus. A fiber-free exclusive enteral nutrition diet also induces mucus erosion but inhibits inflammation by simultaneously increasing an anti-inflammatory bacterial metabolite, isobutyrate. Our findings underscore the importance of focusing on microbial functions-not taxa-contributing to IBDs and that some diet-mediated functions can oppose those that promote disease.

Exercise training improves leptin sensitivity in peripheral tissue of obese rats.

The present study examined the change to the effect of the leptin sensitivity by leptin resistance-induced leptin receptor (ObRb) and leptin-related suppressor of cytokine signaling 3 (SOCS3) mRNA levels in hypothalamic, liver, muscle and leptin protein levels in blood after eight 8 weeks of exercise training and/or dietary control of high fat induced obese rats. After 2 weeks of adaptation maintenance, four-week-old male SD rats (n=42) were randomly divided into control (CO) (n=8) and high-fat diet (HF) (n=32) groups. The HF group randomly divided into HF, HF+exercise training (HFT), changed to normal diet (HFND) and changed to normal diet and exercise training (HFNDT) groups. 13 weeks of HF group average body weight significantly increased in comparison to the CO group (p<0.05). Plasma leptin levels of the HFT, HFND and HFNDT group were significantly decreased in comparison to the HF group (p<0.05). The mRNA expression of ObRb and SOCS3 in the liver and muscle of the HF group was significantly decreased comparison to that of the HFT, HFND and HFNDT group after 8 weeks intervention (p<0.05). In addition, the mRNA expression of ObRb and SOCS3 in the hypothalamus of the HF group was significantly increased comparison to that of the HFT, HFND and HFNDT group (p<0.05). HFND group also was significantly reduced comparison to of the HFT and HFNDT group (p<0.05). These findings suggest that the effect of leptin sensitivity in peripheral may primarily the more relate to combined dietary control and exercise training more than effect of dietary control.

Identification of KCNN2 as a susceptibility locus for coronary artery aneurysms in Kawasaki disease using genome-wide association analysis.

Kawasaki disease (KD) is often complicated by coronary artery lesions (CALs), including aneurysms. Because of the complications associated with KD, this disorder is the leading cause of acquired heart disease in children from developed countries. To identify genetic loci that confer a higher risk of developing CALs, we performed a case-control association study using previous genome-wide association study data for samples from KD cases only (n=186) by grouping KD patients without CALs (control: n=123) vs KD patients with extremely large aneurysms (diameter>5 mm) (case: n=17). Twelve loci with one or more sequence variants were found to be significantly associated with CALs (P<1 × 10(-5)). Of these, an SNP (rs17136627) in the potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2 (KCNN2) at 5q22.3 was validated in 32 KD patients with large aneurysms (diameter>5 mm) and 191 KD patients without CALs (odds ratio (OR)=12.6, P(combined)=1.96 × 10(-8)). This result indicates that the KCNN2 gene can have an important role in the development of coronary artery aneurysms in KD.

Alterations of Muscular Strength and Left and Right Limb Balance in Weightlifters after an 8-week Balance Training Program.

[Purpose] Balance is generally defined as the ability to maintain the body's center of gravity within its base of support and may be categorized by either static or dynamic balance. The purpose of the present study was to evaluate the effect of 8 weeks of balance training on strength, and the functional balance ability of elite weightlifters. [Subjects] Thirty-two elite weightlifters were recruited for the present study. They were divided into exercise groups (8 high school students, 8 middle school students) and control groups (8 high school students, 8 middle school students). [Methods] Body compositions were measured by the electrical impedance method, and a Helmas system was used to measure basic physical capacities. The muscular function test was conducted using a Cybex 770. [Results] There were no significant changes in body composition after the training. In contrast, significant changes were found in the number of push-ups, one-leg standing time with eyes closed, and upper body back extension. Interestingly, only the left arm external rotation value after the exercise training program showed a statistically significant difference from the baseline value. [Conclusion] The peak torque values of shoulder internal rotation and knee extension were significantly changed compared to the baseline values, which mean subjects showed balance of their muscular power. Therefore, the results of the present study suggest that an 8-week balance-training program would positively affect elite weightlifters' balance ability and flexibility. We think that well-balanced muscular functionality may enhance athletes' sport performance.

Unravelling specific diet and gut microbial contributions to inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic condition characterized by periods of spontaneous intestinal inflammation and is increasing in industrialized populations. Combined with host genetic predisposition, diet and gut bacteria are thought to be prominent features contributing to IBD, but little is known about the precise mechanisms involved. Here, we show that low dietary fiber promotes bacterial erosion of protective colonic mucus, leading to lethal colitis in mice lacking the IBD-associated cytokine, interleukin-10. Diet-induced inflammation is driven by mucin-degrading bacteria-mediated Th1 immune responses and is preceded by expansion of natural killer T cells and reduced immunoglobulin A coating of some bacteria. Surprisingly, an exclusive enteral nutrition diet, also lacking dietary fiber, reduced disease by increasing bacterial production of isobutyrate, which is dependent on the presence of a specific bacterial species, Eubacterium rectale. Our results illuminate a mechanistic framework using gnotobiotic mice to unravel the complex web of diet, host and microbial factors that influence IBD.

Assessment of risk factors for Korean children with Kawasaki disease.

Kawasaki disease (KD) is the most common cause of acquired heart disease in children. Intravenous immunoglobulin (IVIG) is the standard therapy for KD, but more than 10% of KD patients do not respond to IVIG and are at high risk for the development of coronary artery lesions (CALs). To identify clinical and genetic risk factors associated with CAL development and IVIG nonresponsiveness, this study analyzed the clinical data for 478 Korean KD patients. Multivariate logistic regression analysis showed that incomplete KD, IVIG nonresponse, fever duration of 7 days or longer, and the CC/AC genotypes of the rs7604693 single nucleotide polymorphism (SNP) in the PELI1 gene were significantly associated with the development of CALs, with odds ratios (ORs) ranging from 2.06 to 3.04. The risk of CAL formation was synergistically increased by the addition of individual risk factors, particularly the genetic variant in the PELI1 gene. Multivariate analysis also showed that a serum albumin level of 3.6 g/dl or lower was significantly associated with nonresponsiveness to IVIG [OR, 2.76; 95% confidence interval (CI), 1.34-5.68; P = 0.006]. Conclusively, incomplete KD, IVIG nonresponsiveness, long febrile days, and the rs7604693 genetic variant in the PELI1 gene are major risk factors for the development of CALs, whereas low serum albumin concentration is an independent risk factor for IVIG nonresponsiveness.

Square-Stepping Exercise Program Effects on Fall-Related Fitness and BDNF Levels in Older Adults in Korea: A Randomized Controlled Trial.

The risk of dementia increases with age. To mitigate this risk, we examined the effect of a square-stepping exercise (SSE) program on fall-related fitness and brain-derived neurotrophic factor (BDNF) levels. Twenty older adults in Korea were randomly assigned to either the experimental or control group (each group n = 10). Participants performed SSE for 70 min per session, twice a week, for 12 weeks with a certified instructor. The average age of the participants was 74.80 ± 6.763 years in the exercise group and 72.50 ± 6.519 years in the control group. The experiment group showed significant improvement (p < 0.01) in the lower muscle strength post-intervention. The paired t-test revealed a significant improvement (p < 0.01) in the experimental group and a significant difference in the interaction effect (p < 0.01) in the BDNF levels. There was a significant improvement (p < 0.05) in the BDNF levels in the experimental group and a significant decrease (p < 0.05) in the control group. The SSE program had a positive effect on fall-related fitness and BDNF levels.

Characterization of AAV-mediated dorsal root ganglionopathy.

Recent studies in non-human primates administered recombinant adeno-associated viruses (rAAVs) have shown lesions in the dorsal root ganglia (DRG) of unknown pathogenesis. In this study, rAAV9s manufactured using different purification methods alongside a non-expressing Null AAV9 vector was administered to groups of cynomolgus monkeys followed by neuropathological evaluation after 4 weeks. Lesions, including neuronal degeneration, increased cellularity, and nerve fiber degeneration, were observed in the DRG, regardless of purification methods. Animals did not develop any neurological signs throughout the study, and there was no loss of function observed in neuro-electrophysiological endpoints or clear effects on intraepidermal nerve fiber density. However, magnetic resonance imaging (MRI) of animals with axonopathy showed an increase in short tau inversion recovery (STIR) intensity and decrease in fractional anisotropy. In animals administered the Null AAV9 vector, DRG lesions were not observed despite vector DNA being detected in the DRG at levels equivalent to or greater than rAAV9-treated animals. This study further supports that DRG toxicity is associated with transgene overexpression in DRGs, with particular sensitivity at the lumbar and lumbosacral level. The data from this study also showed that the nerve fiber degeneration did not correlate with any functional effect on nerve conduction but was detectable by MRI.