A Prospective Comparison of EUS-Guided FNA Using 25-Gauge and 22-Gauge Needles

Background and Aims. There are limited data on the differences in diagnostic yield between 25-gauge and 22-gauge EUS-FNA needles. This prospective study compared the difference in diagnostic yield between a 22-gauge and a 25-gauge needle when performing EUS-FNA. Methods. Forty-three patients with intraluminal or extraluminal mass lesions and/or lymphadenopathy were enrolled prospectively. EUS-FNA was performed for each mass lesion using both 25- and 22-gauge needles. The differences in accuracy rate, scoring of needle visibility, ease of puncture and quantity of obtained specimen were evaluated. Results. The overall accuracy of 22- and 25-gauge needle was similar at 81% and 76% respectively (N.S). Likewise the visibility scores of both needles were also similar. Overall the quantity of specimen obtained higher with the 22-gauge needle (score: 1.64 vs. P < .001). However the 25-gauge needle was significantly superior to the 22-gauge needle in terms of ease of puncture (score: 1.9 vs. 1.29, P < .001) and in the quantity of specimen in the context of pancreatic mass EUS-FNA (score: 1.8 vs. 1.58, P < .05). Conclusion. The 22-gauge and 25-gauge needles have similar overall diagnostic yield. The 25-gauge needle appeared superior in the subset of patients with hard lesions and pancreatic masses

The Administration of Xultophy for Diabetic Patients on Hemodialysis

Background: Recent diabetic treatments include Insulin Degludec/ liraglutide (IDeg/Lira, Xultophy) in clinical practice. Authors have continued clinical research concerning diabetes, chronic renal failure, dialysis, and others. Subjects and Methods: Ten patients with type 2 diabetes mellitus (T2DM) undergoing hemodialysis were investigated. They showed that ages 74.5 ± 5.9 years, M/F=6/4, BMI 21.1± 3.8kg/m2, hemodialysis duration 8.1 ± 5.7 years. At the beginning, fundamental data were Cre 8.2 ± 1.9 mg/dL, HbA1c 6.5 ± 0.8%. Xultophy was started on 5-12 doses and continued for 6 months with the same or 1-4 increased doses for better glycemic variability. Results: Out of 10 subjects, the changes in HbA1c showed a decrease in 7, stable in 2, and an increase in 1. HbA1c value was 6.2 ± 0.8% in average at 6 months. There were no remarkable adverse effects by Xultophy for 6 months. Discussion and Conclusion: Xultophy was started at 5-12 doses, which were remarkably lower doses than usual doses with satisfactory efficacy. One of the reasons may be from the characteristic of the patients, who were diabetic with undergoing hemodialysis. Another factor is possibly from liraglutide, which has hepatic clearance with potential vascular protective effects. These results are expected to become reference data for future research

Carnitine for Body Composition in Hemodialysis Patients

Background: Authors and colleagues have continued clinical research for hemodialysis patients. Currently, a pilot study presents intervention of carnitine for changes of the body composition. Subjects and Methods: Subjects were six patients on hemodialysis with intervention of carnitine (group 1). Average data were 74.3 years, 65.4 kg, 22.6 in BMI. As levocarnitine, L-Cartin FF injection 1000 mg was administered three times a week for six months. Group 2 has six control patients for age-, sex-, body weight, BMI-matched (group 2). Body composition of muscle and fat tissues were measured by InBody 770 on 0 and 6 months. Results: In group 1, muscle volume and skeletal muscle showed increasing tendency without statistical significance. In contrast, there were significant decreases of body fat volume (22.3 kg vs 20.5 kg, 39.0% vs 35.8%) (p<0.05). No significant differences were found in hemoglobin, total protein, albumin and Cardio-Thoracic Ratio (CTR) of chest X-ray. Group 2 showed no significant changes. Discussion and Conclusion: Hemodialysis patients often have muscular reduction. Previous reports showed improved lean body mass by carnitine administration, which may support our result. These results from current pilot study would be expected to become useful reference data in the pathophysiological investigation in patients on hemodialysis

Investigation of Nerve Conduction in Patients with Diabetes and/or Hemodialysis

Diabetic peripheral neuropathy (DPN) has been clinically important, and nerve conduction studies (NCS) have been performed with rather complexity and high cost. By advances in technology, simple and useful DPN-Check device was developed obtaining NCS data as sural nerve conduction velocity (SNCV) and sural nerve action potential (SNAP). We enrolled 52 subjects classified into 4 groups according to the presence of hemodialysis (HD) and diabetes mellitus (DM) as follows: HD (+), DM (+) in group 1, HD (+), DM (-) in group 2, HD (-), DM (+) in group 3 and healthy controls in group 4. Average age was similar from 68 to 74 years in 4 groups. Median value of SNCV was 31, 48, 49, 54 m/sec, and median value of SNAP was 3, 9, 6, 22 μV, respectively, in 4 groups. These results might suggest some relationship between impaired states of HD and DM, and would become fundamental data for pathophysiological investigation of peripheral neuropathy of HD and/or DM in the future

Investigation of Nerve Conduction in Patients with Diabetes and/or Hemodialysis

Diabetic peripheral neuropathy (DPN) has been clinically important, and nerve conduction studies (NCS) have been performed with rather complexity and high cost. By advances in technology, simple and useful DPN-Check device was developed obtaining NCS data as sural nerve conduction velocity (SNCV) and sural nerve action potential (SNAP). We enrolled 52 subjects classified into 4 groups according to the presence of hemodialysis (HD) and diabetes mellitus (DM) as follows: HD (+), DM (+) in group 1, HD (+), DM (-) in group 2, HD (-), DM (+) in group 3 and healthy controls in group 4. Average age was similar from 68 to 74 years in 4 groups. Median value of SNCV was 31, 48, 49, 54 m/sec, and median value of SNAP was 3, 9, 6, 22 μV, respectively, in 4 groups. These results might suggest some relationship between impaired states of HD and DM, and would become fundamental data for pathophysiological investigation of peripheral neuropathy of HD and/or DM in the future

Influence of Diabetes and Hemodialysis Against Nerve Conduction Studies

Background: Diabetic peripheral neuropathy (DPN) has been prevalent and discussed, and nerve conduction studies (NCS) has been continued. We have checked NCS using recently introduced useful DPN-Check device. Subjects and Methods: The subjects were 66 patients (pts) classified into 4 groups according to existence of diabetes mellitus (DM) and hemodialysis (HD); Group1: DM (+), HD (+) in 15 pts, group 2: DM (-), HD (+) in 15 pts, group 3: DM (+), HD (-) in 20 pts, group 4: 16 healthy controls. Methods included measurements of sural nerve conduction velocity (SNCV) and sural nerve action potential (SNAP) using HDN-1000. Results: Average age in each group was 64.4 years to 72.6 years. SNCV value of 4 group in average was 37.1 m/sec, 46.3 m/sec, 49.3 m/sec, 53.2 m/sec, respectively, and value of group 1 was significantly lower than those of group 2,3,4 (p<0.01). Similarly, average SNAP was 4.1 μV, 8.7 μV, 8.0 μV, 21.6 μV, respectively, and group 1,2,3 were significantly lower than group 4 (p<0.01). There was significant correlation between SNCV and SNAP in all subjects (p<0.01). Significant correlations were shown between DM duration and SNCV, and DM duration and SNAP (p<0.01). Discussion and Conclusion: SNCV and SNAP were measured successfully and easily by HDN-1000, indicating clinical availability. Obtained data suggested that 1) SNCV is not significantly decreased due to only uremic neuropathy, 2) SNCV is significantly decreased in patients with both HD and DM, 3) SNAP is significantly decreased in patents with DM for years and 4) SNAP would be remarkably decreased when HD is in addition to DM. These results would become the basal data of future NCS for DM and HD

Arabidopsis HDA6 Regulates Locus-Directed Heterochromatin Silencing in Cooperation with MET1

Heterochromatin silencing is pivotal for genome stability in eukaryotes. In Arabidopsis, a plant-specific mechanism called RNA–directed DNA methylation (RdDM) is involved in heterochromatin silencing. Histone deacetylase HDA6 has been identified as a component of such machineries; however, its endogenous targets and the silencing mechanisms have not been analyzed globally. In this study, we investigated the silencing mechanism mediated by HDA6. Genome-wide transcript profiling revealed that the loci silenced by HDA6 carried sequences corresponding to the RDR2-dependent 24-nt siRNAs, however their transcript levels were mostly unaffected in the rdr2 mutant. Strikingly, we observed significant overlap of genes silenced by HDA6 to those by the CG DNA methyltransferase MET1. Furthermore, regardless of dependence on RdDM pathway, HDA6 deficiency resulted in loss of heterochromatic epigenetic marks and aberrant enrichment for euchromatic marks at HDA6 direct targets, along with ectopic expression of these loci. Acetylation levels increased significantly in the hda6 mutant at all of the lysine residues in the H3 and H4 N-tails, except H4K16. Interestingly, we observed two different CG methylation statuses in the hda6 mutant. CG methylation was sustained in the hda6 mutant at some HDA6 target loci that were surrounded by flanking DNA–methylated regions. In contrast, complete loss of CG methylation occurred in the hda6 mutant at the HDA6 target loci that were isolated from flanking DNA methylation. Regardless of CG methylation status, CHG and CHH methylation were lost and transcriptional derepression occurred in the hda6 mutant. Furthermore, we show that HDA6 binds only to its target loci, not the flanking methylated DNA, indicating the profound target specificity of HDA6. We propose that HDA6 regulates locus-directed heterochromatin silencing in cooperation with MET1, possibly recruiting MET1 to specific loci, thus forming the foundation of silent chromatin structure for subsequent non-CG methylation

Coexistence of Trichome Variation in a Natural Plant Population: A Combined Study Using Ecological and Candidate Gene Approaches

The coexistence of distinct phenotypes within populations has long been investigated in evolutionary ecology. Recent studies have identified the genetic basis of distinct phenotypes, but it is poorly understood how the variation in candidate loci is maintained in natural environments. In this study, we examined fitness consequences and genetic basis of variation in trichome production in a natural population of Arabidopsis halleri subsp. gemmifera. Half of the individuals in the study population produced trichomes while the other half were glabrous, and the leaf beetle Phaedon brassicae imposed intensive damage to both phenotypes. The fitness of hairy and glabrous plants showed no significant differences in the field during two years. A similar result was obtained when sibling hairy and glabrous plants were transplanted at the same field site, whereas a fitness cost of trichome production was detected under a weak herbivory condition. Thus, equivalent fitness of hairy and glabrous plants under natural herbivory allows their coexistence in the contemporary population. The pattern of polymorphism of the candidate trichome gene GLABROUS1 (GL1) showed no evidence of long-term maintenance of trichome variation within the population. Although balancing selection under fluctuating biotic environments is often proposed to explain the maintenance of defense variation, the lack of clear evidence of balancing selection in the study population suggests that other factors such as gene flow and neutral process may have played relatively large roles in shaping trichome variation at least for the single population level

Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study

IntroductionAdolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated.Material and methodsMendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese.ResultsSignificant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI.ConclusionsOur Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS