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This retrospective study aimed to determine the optimal cutoff values of the Dry Eye-Related Quality-of-Life Score (DEQS) questionnaire for diagnosing dry eye disease (DED) and classifying DED severities. Participants completed the DEQS questionnaire, the Japanese version of the Ocular Surface Disease Index (J-OSDI) questionnaire, and DED examinations. DED was diagnosed according to the 2016 Asia Dry Eye Society diagnostic criteria based on DED symptoms (J-OSDI ≥ 13 points) and tear film breakup time ≤ 5 s. Receiver operating characteristic (ROC) analysis was used to calculate the optimal cutoff values of the DEQS summary score for detecting DED and grading its severity. Among 427 patients, 296 (69.3%) and 131 (30.7%) were diagnosed with DED and non-DED, respectively. ROC analysis determined an optimal cutoff value of 15.0 points for DED diagnosis, with 83.5% sensitivity, 87.0% specificity, and an area under the curve of 0.915. The positive and negative predictive values for DEQS ≥ 15.0 points were 93.6% and 69.9%, respectively. DEQS cutoff values of 15.0, 20.0, and 26.8 points could be accepted for severity classification of DED subjective symptoms in clinical use and represent mild, moderate, and severe DED, respectively. Conclusively, the optimal cutoff values of DEQS enable DED detection and subjective symptom severity classification. [ABSTRACT FROM AUTHOR]

Bivalent ligands are composed of two pharmacophores connected by a spacer of variable size. These ligands are able to simultaneously recognize two binding sites, for example in a G protein-coupled receptor heterodimer, resulting in enhanced binding affinity. Taking advantage of previously described heterobivalent dopamine-neurotensin receptor ligands, we demonstrate specific interactions between dopamine D3 (D3R) and neurotensin receptor 1 (NTSR1), two receptors with expression in overlapping brain areas that are associated with neuropsychiatric diseases and addiction. Bivalent ligand binding to D3R-NTSR1 dimers results in picomolar binding affinity and high selectivity compared to the binding to monomeric receptors. Specificity of the ligands for the D3R-NTSR1 receptor pair over D2R-NTSR1 dimers can be achieved by a careful choice of the linker length. Bivalent ligands enhance and stabilize the receptor-receptor interaction leading to NTSR1-controlled internalization of D3R into endosomes via recruitment of β-arrestin, highlighting a potential mechanism for dimer-specific receptor trafficking and signalling. Budzinski et al use bivalent ligands, BRET assays and radioligand competition to demonstrate a specific interaction between two receptors associated with neuropsychiatric diseases and addiction, dopamine D3 (D3R) and neurotensin receptor 1. They show that the bivalent ligands promote endosomal trafficking of D3R, suggesting a potential role for dimerization in vivo. [ABSTRACT FROM AUTHOR]

Description Introduction Spontaneous esophageal rupture, also known as Boerhaave's syndrome, is an uncommon and potentially life-threatening condition that requires urgent surgical management. We report a case of spontaneous esophageal rupture that was successfully treated by primary closure and drainage laparoscopically. Case report The patient was a 49 year-old man with a history of liver cirrhosis. He experienced sudden-onset epigastric pain triggered by vomiting after drinking alcohol, and transported to our hospital. On admission, a thoracic CT scanning revealed mediastinal emphysema without pleural effusion. We diagnosed BS and performed an emergency operation. We chose laparoscopic trans-hiatal approach as it was thought to be minimally invasive compared with open thoracic surgery. Five trocars were placed in a similar way of gastric cancer surgery. We identified laceration on the left wall of the lower esophagus under assistance of intra-operative upper endoscopy, and conducted drainage and repair by primary closure with continuous barbed suture. Finally, an omental pedicle flap was applied for over sutured site. The operation time was 214 minutes and the amount of blood loss was 50 cc. In the post-operative course, intra-mediastinal abscess was observed and he required antibiotic therapy. However, the patient was discharged on the 16th post-operative day without a serious complication such as anastomotic leakage. Discussion Primary esophageal repair is the gold standard in Boerhaave's syndrome and the approach is usually left thoracotomy. However, if there is no perforation into the thoracic cavity as in our case, less invasive approach should be considered such as laparoscopic trans-hiatal approach. We could observe the lower esophagus completely under a good field of view in this approach. There are several treatments, and it should always be tailored to the patient's condition. Laparoscopic trans-hiatal approach is considered to be useful for the treatment of lower esophageal wall rupture. It is difficult to conduct a comparative study of the various methods that can be used to treat spontaneous esophageal rupture in cases that require emergent surgery, as the number of cases is limited. Therefore, the further accumulation of cases is necessary. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Description Background: As the thoracic esophageal carcinoma has a high metastatic rate of upper mediastinal lymph nodes, especially along the recurrent laryngeal nerve (RLN), it is crucial to perform complete lymph nodes dissection along the RLN without complications. Although Intraoperative neural monitoring (IONM) during thyroid and parathyroid surgery has gained widespread acceptance as the useful tool of visual nerve identification, the utilization of IONM during esophageal surgery has not become common. Here, we describe our procedures focusing on a lymphadenectomy along the RLN utilizing the IONM. Methods and Procedures: We first dissect ventral and dorsal side of the esophagus preserving the membranous structure (mesoesophagus), which contains tracheoesophageal artery, RLN and lymph nodes. We next identify the location of the RLN which runs in the mesoesophagus using IONM before visual contact. After that, we perform lymphadenectomy around the RLN preserving the nerve. To evaluate the efficacy of this method, we compared short term surgical outcome of our 36 consecutive cases (neural monitoring group; Nm) of esophagectomy in prone positioning with 56 of our historical cases (conventional method group; Cm). Results: In all 36 cases of Nm group, we could obtain the location information of the RLN before the visual contact. Although the operation time of thoracic part was significantly longer in Nm group compared to Cm group (281 min vs. 254 min each, P  = 0.005), postoperative RLN paralysis according to postoperative laryngoscopy was seen in 3 cases (8.3%) after surgical operation in Nm group, which was significantly lower than that in the Cm group (18/56, 32.1%, P  = 0.005). As a result, median postoperative hospital stay was significantly shorter in Nm group than Cm group (22 days vs. 39 days each, P  = 0.0003). Conclusion: Mesentery-oriented lymph nodes dissection using IONM has substantial advantages to perform accurate and safe thoracoscopic esophagectomy. It could decrease the RLN paralysis and postoperative hospital stay after esophagectomy. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Various gene alterations related to acute leukemia are reported to be involved in drug resistance. We investigated idarubicin (IDR) resistance using exome nuclear DNA analyses of the human acute leukemia cell line MOLT-3 and the derived IDR-resistant cell line MOLT-3/IDR. We detected mutations in MOLT-3/IDR and MOLT-3 using both Genome Analysis Toolkit (GATK) and SnpEff program. We found 8839 genes with specific mutations in MOLT-3/IDR and 1162 genes with accompanying amino acid mutations. The 1162 genes were identified by exome analysis of polymerase-related genes using Kyoto Encyclopedia of Genes and Genomes (KEGG) and, among these, we identified genes with amino acid changes. In resistant strains, LIG and helicase plurality genes showed amino-acid-related changes. An amino acid mutation was also confirmed in polymerase-associated genes. Gene ontology (GO) enrichment testing was performed, and lipid-related genes were selected from the results. Fluorescent activated cell sorting (FACS) was used to determine whether IDR permeability was significantly different in MOLT-3/IDR and MOLT-3. The results showed that an IDR concentration of 0.5 μg/mL resulted in slow permeability in MOLT-3/IDR. This slow IDR permeability may be due to the effects of amino acid changes in polymerase- and lipid-associated genes. [ABSTRACT FROM AUTHOR]

We examined the impact of 5-aminolevulinic acid (5-ALA) and sodium-ferrous-citrate supplementation on aerobic capacity and redox balance through a placebo-controlled, double-blind trial. Fourteen healthy volunteers were randomly assigned to Pla + ALA (4-week placebo followed by 4-week 5-ALA supplementation) or ALA + Pla (4-week 5-ALA supplement followed by a 4-week placebo) group and administered 5-ALA (25 mg/day) or placebo once daily. The participants underwent submaximal incremental cycling tests at weeks 0, 2, 4, 6, and 8. In the cycling test at week 0, individual load-intensity stages required for blood lactate levels >2 mmol/L (lactate threshold, LT) and 4 mmol/L (onset of blood lactate accumulation, OBLA) were determined. The heart rate (HR), blood lactate (La), and oxidative stress markers (diacron reactive oxygen metabolite, d-ROMs; biological antioxidant potential, BAP) were measured at resting, LT, and OBLA states in each cycling test. Marker values were not significantly different between the groups. HR, La, and d-ROMs at resting, LT, and OBLA states were not significantly different among the conditions. BAP and BAP/d-ROMs ratios were significantly different in the OBLA state at week 4 of the 5-ALA group compared with that of the placebo group (p < 0.05). In conclusion, 5-ALA supplementation might improve redox balance during high-intensity aerobic exercise. [ABSTRACT FROM AUTHOR]

Neurally mediated syncope (NMS) is associated with a sudden loss of consciousness. However, the diagnostic tools and measures for prognosis management are limited. To overcome these limitations, the differences in the binding energies of Giα-protein-coupled receptors to the Glu9 and Glu12 residues on the α2B-AR gene were elucidated through the analysis of α2B-AR gene polymorphism. The suppression of the activity of adenylate cyclase (AC), which is involved in vasoconstriction, may be related to the onset of NMS. The head-up tilt (HUT) test results indicated differences in systolic blood pressure (SBP) and AC activity between patients with vasodepressor (VT)-NMS and healthy volunteers. Patients with VT-NMS had increased AC activity and decreased SBP. Conversely, in healthy volunteers, no changes in AC activity or SBP were found. These findings suggest that a high SBP and elevated AC activity at rest are likely to cause syncope. A high incidence of cardiovascular events is found in patients with negative HUT test results, highlighting the importance of investigating the cause of syncope in cases where the HUT test results are negative. Overall, our results may provide a means of assessing the risk of NMS development within healthy populations and underscore the importance of subsequent treatments for NMS. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID-19) pandemic has emphasized the paucity of non-contact and non-invasive methods for the objective evaluation of dry eye disease (DED). However, robust evidence to support the implementation of mHealth- and app-based biometrics for clinical use is lacking. This study aimed to evaluate the reliability and validity of app-based maximum blink interval (MBI) measurements using DryEyeRhythm and equivalent traditional techniques in providing an accessible and convenient diagnosis. In this single-center, prospective, cross-sectional, observational study, 83 participants, including 57 with DED, had measurements recorded including slit-lamp-based, app-based, and visually confirmed MBI. Internal consistency and reliability were assessed using Cronbach's alpha and intraclass correlation coefficients. Discriminant and concurrent validity were assessed by comparing the MBIs from the DED and non-DED groups and Pearson's tests for each platform pair. Bland–Altman analysis was performed to assess the agreement between platforms. App-based MBI showed good Cronbach's alpha coefficient, intraclass correlation coefficient, and Pearson correlation coefficient values, compared with visually confirmed MBI. The DED group had significantly shorter app-based MBIs, compared with the non-DED group. Bland–Altman analysis revealed minimal biases between the app-based and visually confirmed MBIs. Our findings indicate that DryEyeRhythm is a reliable and valid tool that can be used for non-invasive and non-contact collection of MBI measurements, which can assist in accessible DED detection and management. [ABSTRACT FROM AUTHOR]

Simple Summary: Serum C-reactive protein (CRP) is an established biomarker for acute inflammation and has been identified as a prognostic indicator for hepatocellular carcinoma (HCC). It is especially important to verify the utility of CRP in HCC patients treated with lenvatinib because the benefits of lenvatinib vary greatly depending on each case. We retrospectively analyzed 125 HCC patients who received lenvatinib treatment at six centers. The low-CRP (<0.5 mg/dL) group exhibited significantly longer overall survival (OS) than the high-CRP (0.5≥ mg/dL) group (22.9 vs. 7.8 months, p < 0.001). In addition, time-to-treatment failure (TTF) was significantly longer in the low-CRP group (8.5 vs. 4.4 months, p = 0.007). In conclusion, baseline serum CRP level was identified as a useful prognostic factor in HCC patients receiving lenvatinib treatment. Background: Serum C-reactive protein (CRP) is an established biomarker for acute inflammation and has been identified as a prognostic indicator for hepatocellular carcinoma (HCC). However, the significance of the serum CRP level, specifically in HCC patients treated with lenvatinib, remains unclear. Methods: We retrospectively analyzed 125 HCC patients who received lenvatinib treatment at six centers. Clinical characteristics were assessed to identify clinical associations between serum CRP and HCC prognosis. Results: The median overall serum CRP level was 0.29 mg/dL. The cohort was divided into two groups: the low-CRP group with a serum CRP < 0.5 mg/dL and the high-CRP group with a serum CRP ≥ 0.5 mg/dL. The low-CRP group exhibited significantly longer overall survival (OS) than the high-CRP group (22.9 vs. 7.8 months, p < 0.001). No significant difference was observed for progression-free survival (PFS) between the high- and low-CRP groups (9.8 vs. 8.4 months, p = 0.411), while time-to-treatment failure (TTF) was significantly longer in the low-CRP group (8.5 vs. 4.4 months, p = 0.007). The discontinuation rate due to poor performance status was significantly higher in the high-CRP group (p < 0.001). Conclusion: A baseline serum CRP level exceeding 0.5 mg/dL was identified as an unfavorable prognostic factor in HCC patients receiving lenvatinib treatment. [ABSTRACT FROM AUTHOR]

Shoseiryuto (SST) (Xiao-Qing-Long-Tang in Chinese) is an effective treatment for respiratory diseases, such as bronchial asthma and allergic rhinitis, but its effects on the bronchial tight-junction (TJ) barrier have not been clarified. This study aimed to evaluate the effect of SST on TJ-barrier function in human bronchial epithelial (16HBE) cells. The 16HBE cells were cultured in a culture medium without (control) and with SST in the absence and presence of bacterial endotoxin lipopolysaccharide (LPS) in transwell chambers. Transepithelial electrical resistance (TEER) and sodium fluorescein (Na-F) permeability of the cultured-cell monolayer were measured as TJ integrity markers. In addition, immunofluorescence staining and quantitative real-time polymerase chain reaction analysis were used to measure the expression of the TJ protein, occludin. SST increased TEER and decreased Na-F permeability of the 16HBE cell monolayers. Furthermore, SST increased both occludin mRNA and immunostained protein expressions, suggesting that SST has the effect of directly promoting epithelial TJ-barrier function. LPS decreased TEER, increased Na-F permeability, and decreased both occludin mRNA and protein expression. LPS-induced barrier dysfunction was completely blocked by pre/co- and posttreatment with SST. These results suggest that SST has protective and therapeutic effects against LPS-induced TJ-barrier damage. To our knowledge, these are the first results to demonstrate the protective and therapeutic effects conferred by TJ-barrier promoting, which may be a novel mechanism contributing to the efficacy of SST for respiratory diseases. [ABSTRACT FROM AUTHOR]

A newly developed O‐glycosylated M‐hepatitis B surface antigen (HBsAgGi) measurement system can detect hepatitis B surface antigen (HBsAg) associated with infectious particles. We investigated the association of HBsAgGi levels with clinical parameters and a history of hepatocellular carcinoma (HCC) development in a cross‐sectional cohort analysis (Study 1) as well as the quantitative changes in HBsAgGi during nucleos(t)ide analogue (NA) therapy in a longitudinal cohort analysis (Study 2). A total of 124 patients with genotype C chronic HBV infection were analysed in Study 1 to evaluate correlations of HBsAgGi with conventional HBV markers and HCC history. Among those, 36 patients receiving NA therapy were enrolled in Study 2 for quantitative comparisons between pre‐treatment baseline and 48 weeks of NA therapy. In Study 1, serum HBsAgGi was significantly associated with HBsAg (r =.5857, p <.00001) and weakly but significantly correlated with HBV DNA (r =.2936, p =.001). Although HBsAgGi (p =.111) was comparable between HCC history (+) group and HCC history (−) group, the HBsAgGi/HBsAg ratio (p =.011) was significantly higher in HCC history (+) patients. In Study 2, HBsAgGi was significantly decreased after 48 weeks of NA therapy (p <.001). HBsAg findings were similar (p =.005) along with an HBV DNA reduction (p <.001). In the baseline hepatitis B e antigen (HBeAg) (+) subgroup, HBsAgGi decreased significantly between baseline and 48 weeks of NA (p =.005), while HBsAg was comparable (p =.051). Low HBsAg and high HBsAgGi were associated with a history of HCC development. HBsAgGi decreased significantly by 48‐week NA therapy. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID-19) pandemic has emphasized the paucity of non-contact and non-invasive methods for the objective evaluation of dry eye disease (DED). However, robust evidence to support the implementation of mHealth- and app-based biometrics for clinical use is lacking. This study aimed to evaluate the reliability and validity of app-based maximum blink interval (MBI) measurements using DryEyeRhythm and equivalent traditional techniques in providing an accessible and convenient diagnosis. In this single-center, prospective, cross-sectional, observational study, 83 participants, including 57 with DED, had measurements recorded including slit-lamp-based, app-based, and visually confirmed MBI. Internal consistency and reliability were assessed using Cronbach's alpha and intraclass correlation coefficients. Discriminant and concurrent validity were assessed by comparing the MBIs from the DED and non-DED groups and Pearson's tests for each platform pair. Bland–Altman analysis was performed to assess the agreement between platforms. App-based MBI showed good Cronbach's alpha coefficient, intraclass correlation coefficient, and Pearson correlation coefficient values, compared with visually confirmed MBI. The DED group had significantly shorter app-based MBIs, compared with the non-DED group. Bland–Altman analysis revealed minimal biases between the app-based and visually confirmed MBIs. Our findings indicate that DryEyeRhythm is a reliable and valid tool that can be used for non-invasive and non-contact collection of MBI measurements, which can assist in accessible DED detection and management. [ABSTRACT FROM AUTHOR]

Human leukocyte antigen (HLA)-G plays a role in various physiological immunomodulatory functions. Aberrant HLA-G expression is observed in various disease states, including tumors, autoimmune disorders, and viral infections. The present study investigated the association between HLA-G functional gene polymorphisms (rs1736933 [-486 C > A], rs1049033 [+2018 C > T], 14 bp Insertion [Ins]/Deletion [Del] [+2961 Del > Ins], and rs1063320 [+3142 C > G]) and disease susceptibility, hepatocellular carcinoma (HCC) development, and hepatitis B surface antigen (HBsAg) clearance. Allele discrimination of the 3 SNPs (-486 C > A, +2018 C > T, +3142 C > G) was determined by a TaqMan 5′ exonuclease assay, while the 14 bp Ins/Del polymorphism was typed by fragment analysis using Genetic Analyzer and GeneMapper software. The above polymorphisms were analyzed for 325 Japanese hepatitis B virus (HBV) patients, 355 Japanese healthy subjects (Controls) as healthy controls, and 799 Japanese hepatitis C virus (HCV) patients as disease controls, respectively. The 14 bp Insertion allele was significantly more frequent in HBV patients than Controls (27.1 % vs 20.6 %, odds ratio [OR] 1.43, P = 0.005) but did not differ between HCV patients and Controls. Similar results were found for the rs1063320 G allele (38.9 % vs 26.3 %, OR 1.78, P < 0.001) and the rs1736933 T allele (32.2 % vs 26.9 %, OR 1.29, P = 0.034) between HBV and Controls. The rs1049033 T allele showed a weak but significant association with HCC development in the dominant model (OR 1.95, P = 0.04). Regarding HBsAg clearance, the A allele at rs1736933 was significantly correlated in the recessive model (OR 3.23, P = 0.003). This study revealed significant associations of HLA-G gene polymorphisms with disease susceptibility, HCC development, and HBsAg clearance in HBV patients. [ABSTRACT FROM AUTHOR]

An abstract of the study "Synthesis of 2-Aminoazoles from Thioesters via α-Heterosubstituted Ketones by Copper-Mediated Cross-Coupling" by H. Kobayashi and colleagues is presented.

An abstract of the article "10-step asymmetric total synthesis and stereochemical elucidation of (+)-dragmacidin D," by J.J. Jackson and colleagues is presented.

Background: Hay fever is a common allergic disease, with an estimated worldwide prevalence of 14.4% and a variety of symptoms. This study assessed the minimal clinically important difference (MCID) of nasal symptom score (NSS), non‐nasal symptom score (NNSS), and total symptoms score (TSS) for app‐based hay‐fever monitoring. Methods: MCIDs were calculated based on the data from a previous large‐scale, crowdsourced, cross‐sectional study using AllerSearch, an in‐house smartphone application. MCIDs were determined with anchor‐based and distribution‐based methods. The face scale score of the Japanese Allergic Conjunctival Disease Standard Quality of Life Questionnaire Domain III and the daily stress level due to hay fever were used as anchors for determining MCIDs. The MCID estimates were summarized as MCID ranges. Results: A total of 7590 participants were included in the analysis (mean age: 35.3 years, 57.1% women). The anchor‐based method produced a range of MCID values (median, interquartile range) for NSS (2.0, 1.5–2.1), NNSS (1.0, 0.9–1.2), and TSS (2.9, 2.4–3.3). The distribution‐based method produced two MCIDs (based on half a standard deviation, based on a standard error of measurement) for NSS (2.0, 1.8), NNSS (1.3, 1.2), and TSS (3.0, 2.3). The final suggested MCID ranges for NSS, NNSS, and TSS were 1.8–2.1, 1.2–1.3, and 2.4–3.3, respectively. Conclusions: MCID ranges for app‐based hay‐fever symptom assessment were obtained from the data collected through a smartphone application, AllerSearch. These estimates may be useful for monitoring the subjective symptoms of Japanese patients with hay fever through mobile platforms. [ABSTRACT FROM AUTHOR]

In the past decade, various lipidomics methodologies have been developed using mass spectrometry based analytical technologies, enabling wide coverage lipid detection in a quantitative manner. Hence, lipidomics has become a widely-accepted approach for biomarker discovery and mechanism elucidation in both medical and biology research fields; however, there are still technical challenges. In this study, focusing on the sample preparation procedure, a single step deproteinization by a water-soluble organic solvent, such as methanol (MeOH), ethanol (EtOH), isopropanol (IPA) or acetonitrile (ACN), was evaluated and proved to be satisfactory for lipidomics analysis. Moreover, during this investigation ACN deproteinization was revealed to not be an effective method for lipid extraction because lipid decomposition was observed during the protein precipitation process through lipase activation, potentially due to the insufficient protein denaturation. Therefore, excluding ACN, protein precipitation by alcohol was evaluated as the lipid extraction reagent. Moreover, adding the MTBE-MeOH (mMM) method, one of the major liquid-liquid extraction methods for shotgun lipidomics, these four approaches were compared. Lipids were extracted from mouse plasma by these four methods and used for exhaustive lipid profiling by liquid chromatography mass spectrometry (LC/MS) analysis. Comparison of these four methods revealed that alcohol based protein precipitation was a useful sample preparation procedure for LC/MS based lipidomics analysis. Whereas MeOH extraction was appropriate for hydrophilic lipid species, IPA was effective for hydrophobic lipids such as triacylglycerols (TG). In practice, EtOH extraction is thought to be the best approach to cover wide range of lipid species using a simple preparation procedure. [ABSTRACT FROM AUTHOR]

Local recurrence after colorectal liver metastasis (CRLM) resection severely affects survival; however, the required surgical margin width remains controversial. This study investigated the impact of KRAS status on surgical margin width and local recurrence rate (LRR) post-CRLM resection. Overall, 146 resected CRLMs with KRAS status (wild-type KRAS (wtKRAS): 98, KRAS mutant (mKRAS): 48) were included. The LRR for each group, R1 (margin positive) and R0 (margin negative), was analyzed by KRAS status. R0 was further stratified into Ra (margin ≥ 5 mm) and Rb (margin < 5 mm). Patients with local recurrence had significantly worse 5-year overall survival than those without local recurrence (p = 0.0036). The mKRAS LRR was significantly higher than wtKRAS LRR (p = 0.0145). R1 resection resulted in significantly higher LRRs than R0 resection for both wtKRAS and mKRAS (p = 0.0068 and p = 0.0204, respectively), and while no significant difference was observed in the Ra and Rb LRR with wtKRAS, the Rb LRR with mKRAS (33.3%) was significantly higher than Ra LRR (5.9%) (p = 0.0289). Thus, R0 resection is sufficient for CRLM with wtKRAS; however, CRLM with mKRAS requires resection with a margin of at least 5 mm to prevent local recurrence. [ABSTRACT FROM AUTHOR]

Muscle fiber composition is associated with physical performance, with endurance athletes having a high proportion of slow-twitch muscle fibers compared to power athletes. Approximately 45% of muscle fiber composition is heritable, however, single nucleotide polymorphisms (SNP) underlying inter-individual differences in muscle fiber types remain largely unknown. Based on three whole genome SNP datasets, we have shown that the rs236448 A allele located near the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene was associated with an increased proportion of slow-twitch muscle fibers in Russian (n = 151; p = 0.039), Finnish (n = 287; p = 0.03), and Japanese (n = 207; p = 0.008) cohorts (meta-analysis: p = 7.9 × 10−5. Furthermore, the frequency of the rs236448 A allele was significantly higher in Russian (p = 0.045) and Japanese (p = 0.038) elite endurance athletes compared to ethnically matched power athletes. On the contrary, the C allele was associated with a greater proportion of fast-twitch muscle fibers and a predisposition to power sports. CDKN1A participates in cell cycle regulation and is suppressed by the miR-208b, which has a prominent role in the activation of the slow myofiber gene program. Bioinformatic analysis revealed that the rs236448 C allele was associated with increased CDKN1A expression in whole blood (p = 8.5 × 10−15) and with greater appendicular lean mass (p = 1.2 × 10−5), whereas the A allele was associated with longer durations of exercise (p = 0.044) reported amongst the UK Biobank cohort. Furthermore, the expression of CDKN1A increased in response to strength (p < 0.0001) or sprint (p = 0.00035) training. Accordingly, we found that CDKN1A expression is significantly (p = 0.002) higher in the m. vastus lateralis of strength athletes compared to endurance athletes and is positively correlated with the percentage of fast-twitch muscle fibers (p = 0.018). In conclusion, our data suggest that the CDKN1A rs236448 SNP may be implicated in the determination of muscle fiber composition and may affect athletic performance. [ABSTRACT FROM AUTHOR]

Among several secreted glycoproteins belonging to the thrombospondin family, thrombospondin 2 (TSP2) is involved in various functions, including collagen/fibrin formation. Liver/serum TSP2 levels have been correlated to liver fibrosis stage and disease activity in nonalcoholic fatty liver disease. This study investigated whether serum TSP2 was associated with clinicopathological features in hepatitis C virus (HCV)-infected patients as well. A total of 350 patients with HCV who had undergone liver biopsy were retrospectively enrolled and divided into a discovery cohort (n = 270) and a validation cohort (n = 80). In the discovery cohort, serum TSP2 levels were moderately correlated with both liver fibrosis stage (r = 0.426, P < 0.0001) and activity grade (r = 0.435, P < 0.0001). The area under the receiver operating characteristic curve of TSP2 for predicting severe fibrosis (≥ F3) was 0.78 and comparable to or better than those of autotaxin (0.78), FIB-4 index (0.78), and APRI (0.76). The discovery cohort findings were closely replicated in the validation cohort. Moreover, comprehensive liver genetic analysis of HCV-infected patients confirmed that the expression of the THBS2 gene encoding TSP2 was significantly higher in severely fibrotic F4 than in F1 patients. Circulating TSP2 levels may reflect the severity of hepatic fibrosis/inflammation in HCV-infected patients. [ABSTRACT FROM AUTHOR]

We investigated and characterized the prevalence of dry eye disease (DED) in Parkinson's disease (PD). PubMed and EMBASE databases were searched for relevant studies between January 1, 1979 and March 10, 2022. Quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Study-specific estimates were combined using the DerSimonian–Laird random-effects model. Prevalence of subjective DED symptoms in patients with PD and mean differences in blink rate, corneal thickness, tear film breakup time, and tear secretion volume on Schirmer test I were compared to those in controls. Of 383 studies, 13 (1519 patients with PD) and 12 were included in qualitative and quantitative syntheses, respectively. Meta-analysis revealed a 61.1% prevalence of subjective DED symptoms in PD and that, compared with controls, patients with PD had significantly lower blink rate, thinner corneal thickness, shorter tear film breakup time, and lower tear secretion volumes on Schirmer test I, without and with anesthesia. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in response to a research about serum adhesion molecule profiles in children with progressive renal disorders.

Inchinkoto (ICKT), a traditional herbal medicine that is often used as a hepatoprotective drug in Japan, has pharmacological properties that include antioxidant, anti-inflammatory, and choleretic actions. Genipin is a metabolite of geniposide and the most abundant ingredient of ICKT; furthermore, it is considered to be the active substance responsible for its pharmacological properties in the liver. Drugs with such pharmacological characteristics are expected to prevent intestinal barrier dysfunction, which causes inflammatory bowel diseases (IBDs). However, no studies have investigated the effects of ICKT on the intestinal epithelial barrier. Therefore, we investigated the activity of ICKT in intestinal tight junctions by using cultured Caco-2 cell monolayers. The action of the compound on tight junctions was examined by measuring transepithelial electrical resistance (TEER) and sodium fluorescein (Na-F) permeability in the presence or absence of lipopolysaccharide (LPS). Moreover, the expression of the tight junction protein claudin-1 was assessed by using immunofluorescent staining. ICKT and genipin increased TEER and decreased Na-F permeability, which was suggestive of enhanced intestinal epithelial barrier function. Moreover, they prevented the LPS-induced destruction of the barrier, i.e., a decrease in TEER and an increase in Na-F permeability. Immunofluorescence staining revealed a high claudin-1 expression level on the cell surface, whereas exposure to LPS downregulated claudin-1. In turn, ICKT and genipin prevented the LPS-mediated reduction of claudin-1. These results suggest that ICKT enhances intestinal epithelial barrier function by upregulating claudin-1. Furthermore, genipin contributed to these effects. ICKT may be a promising medicine for the prevention and treatment of diseases associated with intestinal barrier disruption, such as IBD, obesity, and metabolic disorders. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle fiber type distribution has implications for human health, muscle function, and performance. This knowledge has been gathered using labor-intensive and costly methodology that limited these studies. Here, we present a method based on muscle tissue RNA sequencing data (totRNAseq) to estimate the distribution of skeletal muscle fiber types from frozen human samples, allowing for a larger number of individuals to be tested. Methods: By using single-nuclei RNA sequencing (snRNAseq) data as a reference, cluster expression signatures were produced by averaging gene expression of cluster gene markers and then applying these to totRNAseq data and inferring muscle fiber nuclei type via linear matrix decomposition. This estimate was then compared with fiber type distribution measured by ATPase staining or myosin heavy chain protein isoform distribution of 62 muscle samples in two independent cohorts (n = 39 and 22). Results: The correlation between the sequencing-based method and the other two were rATPas = 0.44 [0.13–0.67], [95% CI], and rmyosin = 0.83 [0.61–0.93], with p = 5.70 × 10–3 and 2.00 × 10–6, respectively. The deconvolution inference of fiber type composition was accurate even for very low totRNAseq sequencing depths, i.e., down to an average of ~ 10,000 paired-end reads. Conclusions: This new method (https://github.com/OlaHanssonLab/PredictFiberType) consequently allows for measurement of fiber type distribution of a larger number of samples using totRNAseq in a cost and labor-efficient way. It is now feasible to study the association between fiber type distribution and e.g. health outcomes in large well-powered studies. [ABSTRACT FROM AUTHOR]

The new duty hour (DH) limit for doctors in Japan will begin in 2024, setting the maximum DHs for postgraduate residents at approximately 80 h weekly. To set appropriate limits, understanding the association between DHs and psychological health is necessary. Thus, we assessed the relationship between residents' psychological health and DHs. We conducted a cross-sectional study involving examinees of the General Medicine In-training Examination 2020. Mental health outcomes were measured dichotomously using the Patient Health Questionnaire-2 for depression and Mini-Z 2.0, for burnout, stress, and satisfaction. Weekly DHs were measured in seven categories at 10-h intervals. The prevalence ratios (PRs) between the DH categories were estimated for each outcome. Of the 6045 residents who provided data on DHs and psychological outcomes, 37.3% showed signs of depression, 21.6% experienced burn out, and 39.2% were highly stressed. In contrast, 62.3% were highly satisfied with their training. Proportions of burnout were higher among residents in Category 6 (≥ 90 and < 100 h; PR 1.36; 95% CI 1.11–1.66) and Category 7 (≥ 100 h; PR 1.36; 95% CI 1.10–1.68) compared with residents in Category 3 (≥ 60 and < 70 h; reference). The results partially support the weekly 80-h DH limit in terms of resident well-being. [ABSTRACT FROM AUTHOR]

Tokyo Electric Power Company's Fukushima Dai-ichi nuclear power plant released radioactive cesium (Cs) into the environment after the Great East Japan Earthquake of March 11, 2011. After radioactive Cs fell onto agricultural fields, radioactive nuclide levels in some buckwheat ( Fagopyrum esculentum Moench) grain subsequently exceeded new standard limits for radioactive materials, including that for radioactive Cs (100 Bq kg −1 ) established by the Japanese government in 2012. A survey of soils and buckwheat grain from 68 farmers’ fields in 2012 revealed that soil exchangeable potassium (K) concentration was significantly and negatively correlated with radioactive Cs concentration in the grain. The effect of K application on the reduction of radioactive Cs concentration in the grain was confirmed by pot and field experiments conducted respectively in 2012 and 2013. This effect might result from the similarity of ion forms of K and Cs and/or the lower exchangeable Cs concentrations at higher exchangeable K concentrations in soil. Based on these results, farmers were recommended to establish a soil exchangeable K concentration of 250 mg kg −1 (300 mg kg −1 in K 2 O) before applying basal fertilizer. After this recommendation, the soil K concentrations of farmers’ fields increased, causing an overall decrease in radioactive Cs concentrations of buckwheat grain produced in 2013. Consequently, no grain sample from this year exceeded the standard limits for radioactive Cs level across the affected area in Japan. These efforts contributed greatly to the rehabilitation and reconstruction of agriculture in the area contaminated with radioactive Cs. [ABSTRACT FROM AUTHOR]

Simple Summary: We performed mutation analysis of ribonucleic acid sequencing (RNA-seq) and whole mitochondrial genome data from tissues collected from metastatic lesions of a male patient in his 60s with metastatic renal cell carcinoma. We confirmed the common mutation sites of a mitochondrial gene containing the T3394Y, R11,807G, and G15,438R sites. Pathway analysis, using RNA-seq data, confirmed the common mutant pathway between renal cell carcinoma and metastatic adrenal carcinoma as cytokine–cytokine receptor (CCR) interaction. However, no common nuclear gene mutations were identified. The two similar sequences suggest that mtDNA-mutation-driven metastasis to the adrenal gland may affect CCR interactions and cause cancer cells to thrive. This study aimed to clarify whether genetic mutations participate in renal cell carcinoma (RCC) metastasis to the adrenal gland (AG). Our study analyzed whole mitochondrial gene and ribonucleic acid sequencing (RNA-seq) data from a male patient in his 60s with metastatic RCC. We confirmed common mutation sites in the mitochondrial gene and carried out Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using RNA-seq data for RCC and adrenal carcinoma. Furthermore, we confirmed the common mutation sites of mitochondrial genes in which the T3394Y (p.H30Y) site transitioned from histidine (His.; H) to tyrosine (Tyr.; Y) in the NADH dehydrogenase subunit 1 (ND1) gene. The R11,807G (p.T350A) site transitioned from threonine (Thr.; T) to alanine (Ala.; A). Additionally, the G15,438R or A (p.G231D) site transitioned from glycine (Gly.; G) to aspartic acid (Asp.; D) in cytochrome b (CYTB). Furthermore, pathway analysis, using RNA-seq, confirmed the common mutant pathway between RCC and adrenal carcinoma as cytokine–cytokine receptor (CCR) interaction. Confirmation of the original mutation sites suggests that transfer to AG may be related to the CCR interaction. Thus, during metastasis to the AG, mitochondria DNA mutation may represent the initial origin of the metastasis, followed by the likely mutation of the nuclear genes. [ABSTRACT FROM AUTHOR]

The halogen bond has been widely used as an important supramolecular tool in various research areas. However, there are relatively few studies on halogen bonding related to molecular chirality. 3-(2-Halophenyl)quinazoline-4-thione derivatives have stable atropisomeric structures due to the rotational restriction around an N-C single bond. In X-ray single crystal structures of the racemic and optically pure N-C axially chiral quinazoline-4-thiones, we found that different types of intermolecular halogen bonds (C=S⋯X) are formed. That is, in the racemic crystals, the intermolecular halogen bond between the ortho-halogen atom and sulfur atom was found to be oriented in a periplanar conformation toward the thiocarbonyl plane, leading to a syndiotactic zig-zag array. On the other hand, the halogen bond in the enantiomerically pure crystals was oriented orthogonally toward the thiocarbonyl plane, resulting in the formation of a homochiral dimer. These results indicate that the corresponding racemic and optically pure forms in chiral molecules are expected to display different halogen bonding properties, respectively, and should be separately studied as different chemical entities. [ABSTRACT FROM AUTHOR]

Aim: Accurate detection of the hepatic fibrosis stage is essential to estimate the outcome of patients with non‐alcoholic fatty liver disease (NAFLD). Many formulas, biomarkers, and imaging tests are being developed to predict advanced liver fibrosis without performing a liver biopsy. However, these tests do not have high efficiency in detecting early‐stage hepatic fibrosis. Therefore, we aimed to detect the presence of hepatic fibrosis (≥F1) merely by using only standard clinical markers. Methods: A total of 436 patients with NAFLD who underwent liver biopsy were retrospectively enrolled as the discovery cohort (316 patients) and the validation cohort (120 patients). Liver biopsy and laboratory data were matched to extract simple parameters for identifying ≥F1. Results: We developed a novel simplified ≥F1 detecting system, designated as 2‐Step PLT16‐AST44 method, where (1) PLT of 16 × 104/μl or less, or (2) PLT greater than 16 × 104/μl and AST greater than 44 U/L is determined as having ≥F1 fibrosis. The 2‐Step PLT16‐AST44 method had a sensitivity of 68%, a specificity of 90%, a positive predictive value (PPV) of 97%, a negative predictive value (NPV) of 40%, and an accuracy of 72% to detect ≥F1 fibrosis in the discovery cohort. Validation studies further supported these results. Despite its simplicity, the 2‐Step PLT16‐AST44 method's power to detect ≥F1 fibrosis in total NAFLD patients was comparable to hyaluronic acid, type 4 collagen 7S, FIB‐4, and APRI. Conclusions: We propose the 2‐Step PLT16‐AST44 method as a simple and beneficial early‐stage hepatic fibrosis detection system. [ABSTRACT FROM AUTHOR]

The relationship between duty hours (DH) and the performance of postgraduate residents is needed to establish appropriate DH limits. This study explores their relationship using the General Medicine In-training Examination (GM-ITE). In this cross-sectional study, GM-ITE examinees of 2019 had participated. We analyzed data from the examination and questionnaire, including DH per week (eight categories). We examined the association between DH and GM-ITE score, using random-intercept linear models with and without adjustments. Five thousand five hundred and ninety-three participants (50.7% PGY-1, 31.6% female, 10.0% university hospitals) were included. Mean GM-ITE scores were lower among residents in Category 2 (45–50 h; mean score difference, −1.05; p < 0.001) and Category 4 (55–60 h; −0.63; p = 0.008) compared with residents in Category 5 (60–65 h; Reference). PGY-2 residents in Categories 2–4 had lower GM-ITE scores compared to those in Category 5. University residents in Category 1 and Category 5 showed a large mean difference (−3.43; p = 0.01). DH <60–65 h per week was independently associated with lower resident performance, but more DH did not improve performance. DH of 60–65 h per week may be the optimal balance for a resident's education and well-being. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy for high-grade meningioma (HGM) is one of the essential treatment options for disease control. However, appropriate irradiation timing remains under debate. The object of this study is to discern which prognostic factors impact recurrence in HGM patients and to propose a risk-stratification system for the application of postoperative radiotherapy. Methods: We retrospectively reviewed 55 adult patients who were diagnosed with Grade II and III intracranial meningioma. Cox regression models were applied to the analysis for impact on early recurrence in HGM patients without postoperative radiotherapy. Results: Grade III malignancy (P = 0.0073) and transformed histology (P = 0.047) proved to be significantly poor prognostic factors of early recurrence by multivariate analysis. The other candidates for recurrence factors were Simpson Grade 3–5 resection, preoperative Karnofsky Performance status < = 70%, and MIB-1 labeling index > = 15%. According to these prognostic factors, postoperative HGM patients could be stratified into three recurrence-risk groups. The prognoses were significantly different between each group, as the 3-year actual recurrence-free rates were 90% in low-risk group, 31% in intermediate-risk group, and 15% in high-risk group. Conclusion: We propose recurrence-risk stratification for postoperative HGM patients using clinically available factors. Our results suggest that the prognosis for patients with high-risk HGMs is dismal, whereas HGM patients belonging to the low-risk group could have favorable prognoses. This stratification provides us with the criteria necessary to determine whether to apply adjuvant radiotherapy to postoperative HGM patients, and to also help identify potentially curable HGMs without adjuvant radiotherapy. [ABSTRACT FROM AUTHOR]

Background: The association between salt intake and clinical outcomes in hemodialysis patients has been controversial. This study aimed to clarify the association between salt intake and mortality in hemodialysis patients. Method: The present study included patients who underwent hemodialysis from June 1st 2016 to May 31st 2020. Corrected salt intake by ideal body weight was the main predictor of outcomes. Ideal body weight was calculated assuming that the ideal body mass index is 22 kg/m2 for the Japanese population. The multivariate Cox proportional hazards model was used to determine the association between corrected salt intake and mortality, adjusting for potential confounders. The outcomes considered were all-cause mortality and cumulative incidence of cardiovascular events at year 4. Result: A total of 492 adult patients were enrolled in the study. The mean daily salt intake and corrected salt intake at baseline were 9.5 g/day and 0.17 g/kg/day, respectively. The low corrected salt intake group (< 0.13 g/kg/day) demonstrated the highest 4-year all-cause mortality. No association was observed between corrected salt intake and the cumulative incidence of cardiovascular events. In multivariate Cox proportional hazards analysis, only the group with corrected salt intake of 0.16–0.20 g/kg/day was associated with a decreased hazard risk for all-cause death compared with the low corrected salt intake group. Conclusion: The present study found that a low salt intake was associated with high all-cause mortality in hemodialysis patients. Reduced long-term survival may be attributed to malnutrition resulting from excessive salt restriction. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) exacerbation is relatively rare as compared with hepatitis B virus reactivation in patients treated with immunosuppressive or anticancer drugs. We herein present the first reported case of acute exacerbation of chronic hepatitis in a patient with HCV persistent infection caused by combination treatment with daratumumab (DARA), bortezomib, and dexamethasone (DVd therapy). A 79-year-old woman diagnosed as having chronic HCV infection 11 years prior without successful viral elimination was referred to our hospital for the treatment of acute liver injury. Multiple myeloma (MM; IgG-κ type) was diagnosed two years before referral and subjected to several treatments. She had commenced DVd therapy four months prior to admission. Since her liver enzymes did not normalize with drug discontinuation and hepatoprotective therapy, we suspected HCV exacerbation and began direct-acting antiviral (DAA) treatment with glecaprevir/pibrentasvir (GLE/PIB). Soon afterwards, her liver enzymes normalized, and she achieved a sustained virological response after 8 weeks of treatment. Clinicians should bear in mind HCV exacerbation when encountering chronic HCV with acute liver injury under MM treatment including a DARA-based regimen. In such cases, DAA therapy is an option when other urgent treatments are needed. [ABSTRACT FROM AUTHOR]

Background and Purpose: We previously reported that pre-ischaemic i.v. miglitol reduces myocardial infarct size through the inhibition of glycogenolysis during ischaemia. Oral administration of miglitol has been reported to produce glucagon-like peptide 1 (GLP-1). We hypothesized that p.o. administration of miglitol, an absorbable antidiabetic drug, reduces myocardial infarct size by stimulating GLP-1 receptors and inhibiting glycogenolysis in the myocardium.Experimental Approach: The effects of p.o. and i.v. administration of miglitol on myocardial infarct size were compared in a rabbit model of ischaemia induced by 30 min of coronary occlusion and 48 h of reperfusion. The levels of phospho(p)-PI3kinase and p-Akt were measured in cardiac tissue by use of Western blot analysis.Results: Both p.o. and i.v. administration of miglitol reduced the infarct size, and this effect was greater after p.o. than after i.v. administration under similar plasma miglitol concentrations. The reduction in infarct size induced by p.o. miglitol but not that induced by i.v. miglitol was partially inhibited by treatment with exendin(9-39), a GLP-1 receptor blocker. Both p.o. and i.v. miglitol improved ejection fraction and ±dP/dt after myocardial infarction. Miglitol administered p.o. but not i.v. up-regulated the myocardial expression of phospho(p)-PI3kinase and p-Akt following myocardial infarction; an effect that was inhibited by exendin(9-39).Conclusions and Implications: Administration of miglitol p.o. reduces myocardial infarct size through stimulation of GLP-1 receptors and activation of PI3kinase-Akt pathway in addition to the inhibition of glycogenolysis. These findings may have clinical implications for the p.o. administration of miglitol for the treatment of patients with diabetes mellitus combined with coronary artery disease. [ABSTRACT FROM AUTHOR]

Abstract: Individuals with schizophrenia demonstrate deficits in divergent thinking. This ability is indispensable for generating creative solutions and navigating the complexities of social interactions. In a pilot study, seventeen stable schizophrenia outpatients were randomly assigned to a training program for divergent thinking or a control program on convergent thinking. After eight weeks of training, participants in the divergent thinking program had significantly greater improvements on measures of idea fluency, negative symptoms, and interpersonal relations than did participants receiving the control program. These preliminary results suggest that interventions for divergent thinking in schizophrenia may lead to improvements in patients'' social functioning. [Copyright &y& Elsevier]

Atypical teratoid/rhabdoid tumor (AT/RT) occurring in the central nervous system is a high-grade malignant tumor, and its prognosis is poor for patients younger than 3 years of age. In this article, we present a case of infant AT/RT in the cervical spine and its successful treatment by intensive chemotherapy. The patient, a 1.75-year-old girl, developed an acute, progressive tetraparesis. MRI revealed a large, intradural mass in the cervical spine.Total surgical resection was performed, and the specimen was diagnosed as AT/RT. Continuously, she received intensive chemotherapy using thiotepa with autologous bone marrow transplantation. At the age of nearly 3 years, she received radiation therapy to the local tumor bed and craniospinal axis. She is now 4 years old and has been maintained in complete remission with a good clinical course and no neurological deficit. The success of this treatment for the patient was that we could prevent tumor recurrence until she was able to receive radiotherapy. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The effects of grain boundary- and triple junction-character on intergranular fatigue crack nucleation were studied in coarse-grained polycrystalline aluminum specimens whose grain boundary microstructures were analyzed by SEM-EBSD/OIM technique. Fatigue crack nucleation occurred mainly along grain boundaries and depended strongly on both the grain boundary character and grain boundary configuration with respect to the persistent slip bands. However, it was little dependent on the geometrical arrangements between the grain boundary plane and the stress axis. Particularly, random boundaries become preferential sites for fatigue crack nucleation. The fatigue cracks were also observed at CSL boundaries when the grain-boundary trace on the specimen surface was parallel to persistent slip bands. On the other hand, no intergranular fatigue cracks were observed at low-angle boundaries. The fatigue cracks were observed at triple junctions as well as grain boundaries. Their nucleation considerably occurred at triple junctions where random boundaries were interconnected. The grain boundary engineering for improvement in fatigue property was discussed on the basis of the results of the structure-dependent intergranular and triple junction fatigue crack nucleation. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to identify the relationship between duration of untreated psychosis (DUP), premorbid functioning, and cognitive dysfunction and the outcome of first-episode schizophrenia. Method: Thirty-four neuroleptic-naive patients who consulted hospitals in Tokyo and who were treated by psychiatrists for the first time were evaluated with regard to DUP, premorbid functioning, psychiatric symptoms, and global functioning. The neuropsychological test battery consisted of the Letter Cancellation Test, Trail-Making Test, Digit Span and Verbal Fluency Test. One year later, 24 of the subjects were reassessed for psychiatric symptoms, global functioning, and social functioning, and the relationships between DUP, premorbid functioning, and cognitive performance and the outcome was investigated. Results: Short DUP, good premorbid functioning, and good Letter Cancellation Test, Digit Span and Verbal Fluency Test scores were significantly associated with good outcome. Conclusions: The present results in a Japanese sample are consistent with previous international evidence that delay of initial treatment, premorbid functioning, and cognitive deficits are associated with outcome. A major limitation of the present study was the small size of the subject group. But because the subjects were relatively homogeneous and not influenced by psychoactive substances, the results reflect the essence of the disorder. [ABSTRACT FROM AUTHOR]

Abstract: Expression of brain-derived neurotrophic factor (BDNF) mRNA is increased in the dorsal root ganglion (DRG) in response to peripheral inflammation. Nerve growth factor (NGF) from inflammatory tissue is thought to induce expression of BDNF. Recently, it was reported that the BDNF gene has eight non-coding exons that are transcribed independently into several splice variants. Expression of these splice variants in DRG neurons stimulated with NGF has not been studied. We examined changes in expression of BDNF splice variants in a rat model of peripheral inflammation and in cultured DRG neurons exposed to NGF. Total BDNF mRNA was increased by inflammation in vivo and by NGF in vitro. Among all splice variants, exon 1-9 showed the greatest increase in expression in both experiments. Our results indicate that exon 1-9 contributes to changes in total BDNF levels and may play an important role in the acute response of DRG to NGF. [Copyright &y& Elsevier]