Morphometric assessment of tibial nerve and its branches around the ankle.

It is essential to understand the considerable variations in bifurcation patterns of the tibial nerve (TN) and its peripheral nerves at the level of the tarsal tunnel to prevent iatrogenic nerve injury during surgical nerve release or nerve block. A total of 16 ankles of 8 human cadavers were dissected to investigate the branching patterns of the TN, using 2 imaginary lines passing through the tip of the medial malleolus (MM) as reference lines. Bifurcation patterns and detailed information on the relative locations of the medial plantar, lateral plantar, medial calcaneal, and inferior calcaneal nerves to the reference lines were recorded. The most common bifurcation pattern was Type 1 in 12 ankles (75%), followed by Type 2 in 2 ankles (13%). One medial calcaneal nerve (MCN) was seen in 11 (69%) specimens and 2 MCN branches were seen in 5 (31%) specimen. 88% of the MCN branches bifurcated from the TN, whereas 6% originated from both TN and lateral plantar nerve (LPN). At the level of the tip of the MM, 2 of 7 parameters showed statistically significant difference between both sexes (P < .05). There was a statistically significant difference between left and right ankles in 2 of 7 measurements (P < .05). Further morphometric analysis of the width, distance, and angle between the TN branches and the tip of MM showed a highly variable nature of the location of the peripheral nerve branches.

Risk of depression and anxiety in multiple sclerosis and neuromyelitis optica spectrum disorder: A nationwide cohort study in South Korea.

BACKGROUND: We investigated the risks of depression/anxiety in patients with multiple sclerosis (pwMS) or patients with neuromyelitis optica spectrum disorder (pwNMOSD). OBJECTIVES: MS/NMOSD cohorts were collected from Korean National Health Insurance Service, using the International Classification of Diseases-10th and information on Rare Intractable Disease program. Patients who were younger than 20 years, had a previous depression/anxiety, or died in the index year were excluded. METHODS: Hazard ratios (HRs) of depression/anxiety in pwMS and pwNMOSD from controls matched 1:5 for age, sex, hypertension, diabetes, and dyslipidemia were calculated using Cox regressions with a 1-year lag period and estimated over time. RESULTS: During a mean follow-up of 4.1 years, adjusted hazard ratios (aHR) for depression were 3.25 (95% confidence interval (CI) = 2.59-4.07) in MS and 2.17 (1.70-2.76) in NMOSD, and aHRs for anxiety were 1.83 (1.49-2.23) in MS and 1.56 (1.26-1.91) in NMOSD. The risks of anxiety/depression did not differ between MS and NMOSD and were highest in the second year after diagnosis of MS/NMOSD. The relative risk of depression was higher in younger pwMS/pwNMOSD, and the relative risk of anxiety was higher in pwMS who was male, had low income, or lived in a non-urban area. CONCLUSION: The risk of depression and anxiety was increased in pwMS/pwNMOSD.

The risk of type 2 diabetes mellitus in multiple sclerosis and neuromyelitis optica spectrum disorder: A nationwide cohort study.

BACKGROUND AND OBJECTIVES: An association has been suggested between premorbid type 2 diabetes mellitus (T2DM) and the risk of multiple sclerosis (MS). However, little is known about the risk of developing T2DM in MS and neuromyelitis optica spectrum disorder (NMOSD). This study aimed to determine the T2DM risk in patients with MS and NMSOD. METHODS: The Korean National Health Insurance Service database was analyzed, and 1,801 and 1,721 adults with MS and NMOSD, respectively, who were free of T2DM between January 2010 and December 2017, were included. Matched controls were selected based on age, sex, and the presence of hypertension and dyslipidemia. RESULTS: The risk of developing T2DM was 1.54 times higher in NMOSD than in the controls (adjusted hazard ratio [aHR], 95 % confidence interval [CI] = 1.20-1.96). However, increased T2DM risk was not observed in MS (aHR = 1.13, 95 % CI = 0.91-1.42). The T2DM risk in patients with NMOSD was higher in those who received steroid treatment (aHR = 1.77, 95 % CI = 1.36-2.30) but not in those who did not (aHR = 0.59, 95 % CI = 0.24-1.43, p for interaction = 0.02). DISCUSSION: T2DM risk was increased in NMOSD but not in MS. Administering steroid treatment to patients with NMOSD may increase their T2DM risk.

Evaluation of SARS-CoV-2 Vaccine-Induced Antibody Responses in Patients with Neuroimmunological Disorders: A Real-World Experience.

This study evaluates the antibody responses to SARS-CoV-2 vaccines in patients with neuroimmunological disorders (pwNID) who are receiving immunomodulating treatments, compared to healthy individuals. It included 25 pwNID with conditions such as optic neuritis, neuromyelitis optica spectrum disorder, multiple sclerosis, myasthenia gravis, and polymyositis, as well as 56 healthy controls. All participants had completed their full SARS-CoV-2 vaccination schedule, and their blood samples were collected within six months of their last dose. The concentration of anti-SARS-CoV-2 IgG antibodies was measured using an enzyme-linked immunosorbent assay. The results showed that pwNID had significantly lower antibody titers (58.4 ± 49.2 RU/mL) compared to healthy individuals (81.7 ± 47.3 RU/mL). This disparity persisted even after adjusting for age and the interval between the final vaccination and sample collection. A notable correlation was found between the use of immunomodulating treatments and reduced antibody levels, whereas mRNA vaccines were linked to higher antibody concentrations. The conclusion of this study is that immunomodulating treatments may reduce the effectiveness of SARS-CoV-2 vaccines in pwNID. This insight is crucial for healthcare providers in designing vaccination strategies and managing treatment plans for pwNID on immunomodulating therapies, highlighting the need for personalized approaches in this subgroup.

OsLRR-RLP2 Gene Regulates Immunity to Magnaporthe oryzae in Japonica Rice.

Rice is an important cereal crop worldwide, the growth of which is affected by rice blast disease, caused by the fungal pathogen Magnaporthe oryzae. As climate change increases the diversity of pathogens, the disease resistance genes (R genes) in plants must be identified. The major blast-resistance genes have been identified in indica rice varieties; therefore, japonica rice varieties with R genes now need to be identified. Because leucine-rich repeat (LRR) domain proteins possess R-gene properties, we used bioinformatics analysis to identify the rice candidate LRR domain receptor-like proteins (OsLRR-RLPs). OsLRR-RLP2, which contains six LRR domains, showed differences in the DNA sequence, containing 43 single-nucleotide polymorphisms (SNPs) in indica and japonica subpopulations. The results of the M. oryzae inoculation analysis indicated that indica varieties with partial deletion of OsLRR-RLP2 showed susceptibility, whereas japonica varieties with intact OsLRR-RLP2 showed resistance. The oslrr-rlp2 mutant, generated using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), showed increased pathogen susceptibility, whereas plants overexpressing this gene showed pathogen resistance. These results indicate that OsLRR-RLP2 confers resistance to rice, and OsLRR-RLP2 may be useful for breeding resistant cultivars.

Acceleration of wheat breeding: enhancing efficiency and practical application of the speed breeding system.

BACKGROUND: Crop breeding should be accelerated to address global warming and climate change. Wheat (Triticum aestivum L.) is a major food crop. Speed breeding (SB) and speed vernalization (SV) techniques for spring and winter wheat have recently been established. However, there are few practical examples of these strategies being used economically and efficiently in breeding programs. We aimed to establish and evaluate the performance of a breeder-friendly and energy-saving generation acceleration system by modifying the SV + SB system. RESULTS: In this study, a four-generation advancement system for wheat (regardless of its growth habits) was established and evaluated using an energy-efficient extended photoperiod treatment. A glasshouse with a 22-hour photoperiod that used 10 h of natural sunlight and 12 h of LED lights, and minimized temperature control during the winter season, was successful in accelerating generation. Even with one or two field tests, modified speed breeding (mSB) combined with a speed vernalization system (SV + mSB) reduced breeding time by more than half compared to traditional field-based methods. When compared to the existing SV + SB system, the SV + mSB system reduced energy use by 80% to maintain a 22-hour photoperiod. Significant correlations were found between the SV + mSB and field conditions in the number of days to heading (DTH) and culm length (CL). Genetic resources, recombinant inbred lines, and breeding materials that exhibited shorter DTH and CL values under SV + mSB conditions showed the same pattern in the field. CONCLUSIONS: The results of our SV + mSB model, as well as its practical application in wheat breeding programs, are expected to help breeders worldwide incorporate generation acceleration systems into their conventional breeding programs.

Increased risk of myocardial infarction in amyotrophic lateral sclerosis: A nationwide cohort study in South Korea.

BACKGROUND: The risk of myocardial infarction (MI), the major form of CVD, in amyotrophic lateral sclerosis (ALS) is currently unknown. We investigated the risk of MI in ALS and analyzed the effect of ALS-related physical disability on the risk of MI using the Korean National Health Insurance Service database. METHODS: A total of 659 ALS patients and 10,927 non-ALS participants were finally selected between January 1, 2011, and December 31, 2015. A Cox hazard regression model was used to examine the hazard ratios (HRs) for MI in ALS after adjustment for potential confounders. RESULTS: The incidence rate of MI was 26.2 per 1000 person-years, and the adjusted HR (aHR) for MI in ALS patients was 10.6 (95% confidence interval [CI] 7.2-15.4) compared with the controls. ALS patients who developed physical disability had an even higher risk of MI (aHR 18.6, 95% CI 11.5-30.0) compared with those who did not develop disability (aHR 7.4, 95% CI 4.6-11.9). The increased risk of MI was more prominent in female subjects than in male subjects (aHR 17.8, 95% CI 10.8-29.4 vs. aHR 6.9, 95% CI 4.1-11.6, P for interaction 0.006) and in obese subjects than in non-obese subjects (aHR 17.8, 95% CI 10.5-30.1 vs. aHR 7.9, 95% CI 4.9-12.8, P for interaction 0.018). CONCLUSIONS: Our findings suggest that the risk of MI is high in ALS patients compared with a control population, and the risk is more prominent in those who develop physical disability, or who are female or obese.

Clinical characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease according to their epitopes.

Background: The detection of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Ab) is essential for the diagnosis of MOG-Ab-associated disease (MOGAD). The clinical implications of different epitopes recognized by MOG-Ab are largely unknown. In this study, we established an in-house cell-based immunoassay for detecting MOG-Ab epitopes and examined the clinical characteristics of patients with MOG-Ab according to their epitopes. Methods: We conducted a retrospective review of patients with MOG-Ab-associated disease (MOGAD) in our single center registry, and collected serum samples from enrolled patients. Human MOG variants were generated to detect epitopes recognized by MOG-Ab. The differences in clinical characteristics according to the presence of reactivity to MOG Proline42 (P42) were evaluated. Results: Fifty five patients with MOGAD were enrolled. Optic neuritis was the most common presenting syndrome. The P42 position of MOG was a major epitope of MOG-Ab. The patients with a monophasic clinical course and childhood-onset patients were only observed in the group that showed reactivity to the P42 epitope. Conclusion: We developed an in-house cell-based immunoassay to analyze the epitopes of MOG-Ab. The P42 position of MOG is the primary target of MOG-Ab in Korean patients with MOGAD. Further studies are needed to determine the predictive value of MOG-Ab and its epitopes.

Novel index, neutrophil percentage (%) is a useful marker for disease activity in MOG antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a CNS autoimmune disease affecting the brain, spinal cord, and optic nerve. The neutrophil-to-lymphocyte ratio (NLR) is related to autoimmune disease activity. However, the clinical implication of index ratios such as the NLR is unclear in patients with MOGAD. OBJECTIVES: We investigated the relationship between index ratios such as the NLR and disease activity and disability to discover the index that best correlates with an attack in MOGAD. METHODS: Using a CNS demyelinating disease cohort, we reviewed 39 patients with MOGAD (age 37.4 ± 12.0 years; F:M = 20:19) who had 390 blood samples available for cell count analysis. We calculated the NLR, eosinophil-to-lymphocyte-ratio (ELR), platelet-to-lymphocyte-ratio (PLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and neutrophil percentage (N%) [neutrophil count (/mm3) / WBC (/mm3) x 100 (%)]. We investigated the associations between each index ratio and disease activity and disability using the receiver operating characteristic (ROC) curve, machine learning program (kNN algorithm), and generalized estimating equations (GEE) analysis. RESULTS: In patients with MOGAD, the NLR, PLR, and N% were higher and ELR was lower during an attack than in remission (all p<0.001). The areas under the ROC curve for the NLR, ELR, PLR, and N% were 0.68, 0.69, 0.61, and 0.68, respectively, with the highest sensitivity of 76.0% in the ELR and the highest specificity of 76.3% in the N%. The classification accuracy scores of the kNN machine learning algorithm were 71% for the NLR, 62% for the ELR, 63% for the PLR, and 72% for the N%. In the GEE analysis of attack samples, both the NLR and treatment-naive had positive associations with the Expanded Disability Status Scale (EDSS) score (ß=0.137, p = 0.008 and ß=1.142, p = 0.003, respectively), and the PLR was negatively associated with the EDSS score (ß=-0.004, p = 0.022). DISCUSSION: Our study suggests that the novel index, neutrophil% is the simplest and the most useful marker to differentiate between attack and remission and shows comparable reliability with NLR in MOGAD. Moreover, the NLR and PLR could be used as supportive biomarkers for disease disability during an attack in patients with MOGAD.

Epicranial headache part 1: Primary stabbing headache.

BACKGROUND/OBJECTIVE: Primary stabbing headache is a common but under-recognized primary headache disorder. The objectives of this review were to provide practical information for better understanding and identification of the disease, suggest an algorithm for differential diagnosis, and provide an insight into the pathophysiology of primary stabbing headache hypothesized from its clinical course. METHODS: This narrative review of primary stabbing headache is based on a literature search and the authors' clinical reasoning. RESULT: The phenotype of each stab is typically abrupt, ultrashort-lasting (<3 s), focal or multifocal, paroxysms of pain occurring sporadically or in clusters. The diagnosis of primary stabbing headache is clinical; fixed or migrating stabs without background pain or sensory abnormalities and the absence of features suggestive of other disorders (e.g., cranial autonomic symptoms or signs) can aid in the diagnosis of primary stabbing headache. The clinical patterns include monophasic, intermittent, and chronic primary stabbing headache, of which the first two are considered typical. The pathophysiology of primary stabbing headache has not yet been elucidated. In this review, we postulated the mechanism of stabbing headache, based on the pain phenotype and clinical course, and provide a clinical algorithm for the differential diagnosis of primary stabbing headache. CONCLUSION: Knowledge about the typical manifestations and clinical patterns of primary stabbing headache will aid in the proper diagnosis and differential diagnosis. Treatment should be tailored by considering the clinical patterns. Further research is needed to elucidate the pathophysiological mechanisms and optimal treatment of primary stabbing headache.

Increased Risk of Developing Depression in Disability after Stroke: A Korean Nationwide Study.

Stroke is a leading cause of mortality and a major cause of disability worldwide. A significant number of stroke survivors suffer from depression, impeding the activities of daily living and rehabilitation. Here, we examined the risk of depression among stroke survivors according to the severity of disabilities and compared its incidence with a matched control group. We included data from the Korean National Health Insurance Service of 207,678 stroke survivors. Cox proportional hazard models were used to calculate the risk of depression among stroke survivors. Stroke survivors had a greater risk of developing depression than the matched control group with an adjusted hazard ratio of 2.12 (95% confidence interval 2.09-2.15). Stroke survivors with more severe disabilities were associated with a higher risk of depression than those with mild disabilities. The risk of developing depression was prominently high within the first year after a stroke. Males and younger people (<65 years) were independent risk factors for depression in stroke survivors. This study demonstrated an increased risk of developing depression in stroke survivors compared to control subjects, and a higher risk of depression was associated with a more severe degree of disability. Clinicians should be aware of the risk of depression developing in stroke survivors, especially those with disabilities.

Multi-omics analysis reveals the genetic basis of rice fragrance mediated by betaine aldehyde dehydrogenase 2.

INTRODUCTION: Fragrance is an important economic and quality trait in rice. The trait is controlled by the recessive gene betaine aldehyde dehydrogenase 2 (BADH2) via the production of 2-acetyl-1-pyrroline (2AP). OBJECTIVES: Variation in BADH2 was evaluated at the population, genetic, transcriptional, and metabolic levels to obtain insights into fragrance regulation in rice. METHODS: Whole-genome resequencing of the Korean World Rice Collection of 475 rice accessions, including 421 breeding lines and 54 wild accessions, was performed. Transcriptome analyses of a subset of 279 accessions, proteome analyses of 64 accessions, and volatile profiling of 421 breeding lines were also performed. RESULTS: We identified over 3.1 million high-quality single nucleotide polymorphisms (SNPs) in Korean rice collection. Most SNPs were present in intergenic regions (79%), and 190,148 SNPs (6%) were located in the coding sequence, of which 53% were nonsynonymous. In total, 38 haplotypes were identified in the BADH2 coding region, including four novel haplotypes (one in cultivated and three in wild accessions). Tajima's D values suggested that BADH2 was under balancing selection in japonica rice. Furthermore, we identified 316 expression quantitative trait loci (eQTL), including 185 cis-eQTLs and 131 trans-eQTLs, involved in BADH2 regulation. A protein quantitative trait loci (pQTL) analysis revealed the presence of trans-pQTLs; 13 pQTLs were mapped 1 Mbp from the BADH2 region. Based on variable importance in projection (VIP) scores, 15 volatile compounds, including 2AP, discriminated haplotypes and were potential biomarkers for rice fragrance. CONCLUSION: We generated a catalog of haplotypes based on a resequencing analysis of a large number of rice accessions. eQTLs and pQTLs associated with BADH2 gene expression and protein accumulation are likely involved in the regulation of 2AP variation in fragrant rice. These data improve our understanding of fragrance and provide valuable information for rice breeding.

Mutations in OsDET1, OsCOP10, and OsDDB1 confer embryonic lethality and alter flavonoid accumulation in Rice (Oryza sativa L.) seed.

Morphological and biochemical changes accompanying embryogenesis and seed development are crucial for plant survival and crop productivity. Here, we identified a novel yellowish-pericarp embryo lethal (yel) mutant of the japonica rice cultivar Sindongjin (Oryza sativa L.), namely, yel-sdj. Seeds of the yel-sdj mutant showed a yellowish pericarp and black embryo, and were embryonic lethal. Compared with wild-type seeds, the yel-sdj mutant seeds exhibited significantly reduced grain size, grain weight, and embryo weight, and a remarkably lower rate of embryo retention in kernels subjected to milling. However, the volume of air space between embryo and endosperm, density of embryo, and total phenolic content (TPC) and antioxidant activity of mature grains were significantly higher in the yel-sdj mutant than in the wild type. Genetic analysis and mapping revealed that the yel-sdj mutant was non-allelic to the oscop1 null mutants yel-hc, yel-cc, and yel-sk, and its phenotype was controlled by a single recessive gene, LOC_Os01g01484, an ortholog of Arabidopsis thaliana DE-ETIOLATED 1 (DET1). The yel-sdj mutant carried a 7 bp deletion in the second exon of OsDET1. Seeds of the osdet1 knockout mutant, generated via CRISPR/Cas9-based gene editing, displayed the yel mutant phenotype. Consistent with the fact that OsDET1 interacts with CONSTITUTIVE PHOTOMORPHOGENIC 10 (OsCOP10) and UV-DAMAGED DNA BINDING PROTEIN 1 (OsDDB1) to form the COP10-DET1-DDB1 (CDD), seeds of oscop10 and osddb1 knockout mutants also showed the yel phenotype. These findings will enhance our understanding of the functional roles of OsDET1 and the CDD complex in embryogenesis and flavonoid biosynthesis in rice seeds.

TMT-based quantitative membrane proteomics identified PRRs potentially involved in the perception of MSP1 in rice leaves.

Pathogen-associated molecular patterns (PAMPs) play a key role in triggering PAMPs triggered immunity (PTI) in plants. In the case of the rice-Magnaporthe oryzae pathosystem, fewer PAMPs and their pattern recognition receptors (PRRs) have been characterized. Recently, a M. oryzae snodprot1 homolog protein (MSP1) has been identified that functions as PAMP and triggering the PTI responses in rice. However, the molecular mechanism underlying MSP1-induced PTI is currently elusive. Therefore, we generated MSP1 overexpressed transgenic lines of rice, and a tandem mass tag (TMT)-based quantitative membrane proteomic analysis was employed to decipher the potential MSP1-induced signaling in rice using total cytosolic as well as membrane protein fractions. This approach led to the identification of 8033 proteins of which 1826 were differentially modulated in response to overexpression of MSP1 and/or exogenous jasmonic acid treatment. Of these, 20 plasma membrane-localized receptor-like kinases (RLKs) showed increased abundance in MSP1 overexpression lines. Moreover, activation of proteins related to the protein degradation and modification, calcium signaling, redox, and MAPK signaling was observed in transgenic lines expressing MSP1 in the apoplast. Taken together, our results identified potential PRR candidates involved in MSP1 recognition and suggested the overview mechanism of the MSP1-induced PTI signaling in rice leaves. SIGNIFICANCE: In plants, recognition of pathogen pathogen-derived molecules, such as PAMPs, by plant plant-derived PRRs has an essential role for in the activation of PTI against pathogen invasion. Typically, PAMPs are recognized by plasma membrane (PM) localized PRRs, however, identifying the PM-localized PRR proteins is challenging due to their low abundance. In this study, we performed an integrated membrane protein enrichment by microsomal membrane extraction (MME) method and subsequent TMT-labeling-based quantitative proteomic analysis using MSP1 overexpressed rice. Based on these results, we successfully identified various intracellular and membrane membrane-localized proteins that participated in the MSP1-induced immune response and characterized the potential PM-localized PRR candidates in rice.

Risk of Parkinson's disease in multiple sclerosis and neuromyelitis optica spectrum disorder: a nationwide cohort study in South Korea.

BACKGROUND: Neurodegeneration is associated with pathogenesis of both multiple sclerosis (MS) and neuromyelitis optica (NMOSD). Parkinson's disease (PD) is a representative neurodegenerative disease, however, whether MS or NMOSD is associated with risk of PD is not known. METHODS: MS and NMOSD cohorts were collected from the Korean National Health Insurance Service between 1 January 2010 and 31 December 2017, using International Classification of Diseases 10th revision diagnosis codes and information in the Rare Intractable Disease management programme. The PD incidence rate that occurred after a 1-year lag period was calculated and compared with that of a control cohort matched for age, sex, hypertension, diabetes and dyslipidaemia in a 1:5 ratio. RESULTS: The incidence rates of PD in patients with MS and NMOSD were 3.38 and 1.27 per 1000 person-years, respectively, and were higher than that of their matched control groups. The adjusted HR of PD was 7.73 (95% CI, 3.87 to 15.47) in patients with MS and 2.61 (95% CI, 1.13 to 6.02) in patients with NMOSD compared with matched controls. In both patients with MS and NMOSD, there were no significant differences in relative risk when stratified by sex, age, diabetes, hypertension and dyslipidaemia. CONCLUSION: The PD risk was higher in patients with MS and NMOSD compared with healthy controls and was particularly high in patients with MS. Further investigations should be performed to determine the pathophysiology and occurrence of PD in patients with MS and NMOSD.

Speed vernalization to accelerate generation advance in winter cereal crops.

There are many challenges facing the development of high-yielding, nutritious crops for future environments. One limiting factor is generation time, which prolongs research and plant breeding timelines. Recent advances in speed breeding protocols have dramatically reduced generation time for many short-day and long-day species by optimizing light and temperature conditions during plant growth. However, winter crops with a vernalization requirement still require up to 6-10 weeks in low-temperature conditions before the transition to reproductive development. Here, we tested a suite of environmental conditions and protocols to investigate whether the vernalization process can be accelerated. We identified a vernalization method consisting of exposing seeds at the soil surface to an extended photoperiod of 22 h day:2 h night at 10°C with transfer to speed breeding conditions that dramatically reduces generation time in both winter wheat (Triticum aestivum) and winter barley (Hordeum vulgare). Implementation of the speed vernalization protocol followed by speed breeding allowed the completion of up to five generations per year for winter wheat or barley, whereas only two generations can be typically completed under standard vernalization and plant growth conditions. The speed vernalization protocol developed in this study has great potential to accelerate biological research and breeding outcomes for winter crops.

Generalised autonomic failure as a prognostic factor in systemic light-chain (AL) amyloidosis.

BACKGROUND: In the present study, it was investigated whether autonomic dysfunction could predict prognosis in light-chain (AL) amyloidosis patients. PATIENTS AND METHODS: Seventy-two patients with biopsy-proven AL amyloidosis were included and underwent an autonomic function test (AFT) between January 2016 and June 2019. Autonomic failure was evaluated using the Composite Autonomic Severity Score (CASS). Survival curves and the three-year overall survival (OS) rate were estimated using the Kaplan-Meier curve, and the Cox proportional hazards regression method was used to evaluate the variables that influenced survival. RESULTS: Autonomic dysfunction was observed in 69 (96%) patients with AL amyloidosis, and the three-year OS rate was 67%. Generalised autonomic failure (GAF) was observed in 31 (43%) patients. In the Kaplan-Meier curve, the three-year OS rates in patients with sudomotor dysfunction or GAF were lower than that in control patients (35 vs. 84%, and 33 vs. 81%, respectively). In Cox proportional hazards regression model, female, bone marrow plasma cell percentage, left ventricular systolic dysfunction, and GAF were significant independent variables associated with survival. CONCLUSION: The results of this study indicate that GAF on the AFT is an independent adverse prognostic factor for survival in AL amyloidosis patients.

Cytokinin increases vegetative growth period by suppressing florigen expression in rice and maize.

Increasing the vegetative growth period of crops can increase biomass and grain yield. In rice (Oryza sativa), the concentration of trans -zeatin, an active cytokinin, was high in the leaves during vegetative growth and decreased rapidly upon induction of florigen expression, suggesting that this hormone is involved in the regulation of the vegetative phase. To elucidate whether exogenous cytokinin application influences the length of the vegetative phase, we applied 6-benzylaminopurine (BAP) to rice plants at various developmental stages. Our treatment delayed flowering time by 8-9 days when compared with mock-treated rice plants, but only at the transition stage when the flowering signals were produced. Our observations also showed that flowering in the paddy field is delayed by thidiazuron, a stable chemical that mimics the effects of cytokinin. The transcript levels of florigen genes Heading date 3a (Hd3a) and Rice Flowering locus T1 (RFT1) were significantly reduced by the treatment, but the expression of Early heading date 1 (Ehd1), a gene found directly upstream of the florigen genes, was not altered. In maize (Zea mays), similarly, BAP treatment increased the vegetative phage by inhibiting the expression of ZCN8, an ortholog of Hd3a. We showed that cytokinin treatment induced the expression of two type-A response regulators (OsRR1 and OsRR2) which interacted with Ehd1, a type-B response regulator. We also observed that cytokinin did not affect flowering time in ehd1 knockout mutants. Our study indicates that cytokinin application increases the duration of the vegetative phase by delaying the expression of florigen genes in rice and maize by inhibiting Ehd1.