An analysis of sugary endosperm in sorghum: Characterization of mutant phenotypes depending on alleles of the corresponding starch debranching enzyme.

Sorghum is the fifth most important cereal crop. Here we performed molecular genetic analyses of the 'SUGARY FETERITA' (SUF) variety, which shows typical sugary endosperm traits (e.g., wrinkled seeds, accumulation of soluble sugars, and distorted starch). Positional mapping indicated that the corresponding gene was located on the long arm of chromosome 7. Within the candidate region of 3.4 Mb, a sorghum ortholog for maize Su1 (SbSu) encoding a starch debranching enzyme ISA1 was found. Sequencing analysis of SbSu in SUF uncovered nonsynonymous single nucleotide polymorphisms (SNPs) in the coding region, containing substitutions of highly conserved amino acids. Complementation of the rice sugary-1 (osisa1) mutant line with the SbSu gene recovered the sugary endosperm phenotype. Additionally, analyzing mutants obtained from an EMS-induced mutant panel revealed novel alleles with phenotypes showing less severe wrinkles and higher Brix scores. These results suggested that SbSu was the corresponding gene for the sugary endosperm. Expression profiles of starch synthesis genes during the grain-filling stage demonstrated that a loss-of-function of SbSu affects the expression of most starch synthesis genes and revealed the fine-tuned gene regulation in the starch synthetic pathway in sorghum. Haplotype analysis using 187 diverse accessions from a sorghum panel revealed the haplotype of SUF showing severe phenotype had not been used among the landraces and modern varieties. Thus, weak alleles (showing sweet and less severe wrinkles), such as in the abovementioned EMS-induced mutants, are more valuable for grain sorghum breeding. Our study suggests that more moderate alleles (e.g. produced by genome editing) should be beneficial for improving grain sorghum.

Prevalence and associated factors of disability in patients with chronic pain: An observational study.

ABSTRACT: The primary treatment goal of patients experiencing chronic pain has shifted from pain reduction to functional status improvement. However, the prevalence of disability and its associated factors in patients with chronic pain remain unknown.Individuals aged ≥50 years who visited the Pain Center at Nara Medical University with chronic pain from June 2019 to May 2020 were eligible for enrollment. Patients were asked to complete the Japanese version of the 12-item World Health Organization Disability Assessment Schedule 2.0. Patient demographics, pain intensity, level of catastrophizing, anxiety, depression, and exercise habits were assessed. Multivariate logistic regression analysis was used to identify the factors associated with disability.Of the 551 patients with a median age of 73 years, 51.5% experienced disability. Fixed factors such as age (odds ratio [OR], 1.03; 95% confidence interval [CI] 1.01-1.06, P = .002) and lumbar and lower limb pain (OR, 3.10; 95% CI, 1.83-5.24, P < .001) and some modifiable factors, including anxiety (OR, 2.06; 95% CI, 1.06-3.98, P = .03), depression (OR, 3.62; 95% CI, 1.92-6.82, P < .001), pain catastrophizer (OR, 2.94; 95% CI, 1.88-4.61, P < .001), numeric rating scale at the most painful site (OR, 1.29; 95% CI, 1.18-1.42, P < .001), exercise habits (walking (OR, 0.52; 95% CI, 0.33-0.83, P = .006) and working out (OR, 0.58; 95% CI, 0.34-0.99, P = .046), were found to be independently associated with disability.This cross-sectional study revealed a high prevalence of disability in patients with chronic pain and identified the factors associated with disability.

The short-term effect of COVID-19 pandemic on disability, pain intensity, psychological status, and exercise habits in patients with chronic pain.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has affected the lives of people worldwide. The first declaration of a state of emergency in Japan, based on the Act on Special Measures for the Prevention and Control of the Novel Coronavirus, was issued from 16 April 2020 to 14 May 2020 to reduce person-to-person contact. Restrictions on going out, participating in community activities, and visiting hospitals were in place. This study investigates the short-term effects of the COVID-19 pandemic on patients with chronic pain. METHODS: This study included outpatients with chronic pain undergoing treatment at the Pain Center of Nara Medical University Hospital. The patients had completed questionnaires for a disability during the study period, from 1 July to 30 September 2019 (baseline), 1 October to 31 December 2019 (pre-pandemic), and 1 July to 30 September 2020 (during the pandemic). The questionnaire covered changes in disability, pain intensity, health-related quality of life (QOL), anxiety, depression, catastrophic thinking, and the presence/absence of exercise habits at baseline, pre-pandemic, and during the pandemic. RESULTS: Of the 245 eligible patients, there was no significant disability difference between baseline, pre-pandemic, and during the pandemic (p = 0.14). Similarly, pain intensity, health-related QOL, anxiety, depression, and the presence/absence of exercise habits did not significantly differ between baseline, pre-pandemic, and during the pandemic either. The current study observed significant differences in terms of catastrophic thinking (p = 0.02). CONCLUSION: The effects of the COVID-19 pandemic on patients with chronic pain were not apparent in the short-term. Clinical trail registration: UMIN000043174.

The dominance model for heterosis explains culm length genetics in a hybrid sorghum variety.

Heterosis helps increase the biomass of many crops; however, while models for its mechanisms have been proposed, it is not yet fully understood. Here, we use a QTL analysis of the progeny of a high-biomass sorghum F1 hybrid to examine heterosis. Five QTLs were identified for culm length and were explained using the dominance model. Five resultant homozygous dominant alleles were used to develop pyramided lines, which produced biomasses like the original F1 line. Cloning of one of the uncharacterised genes (Dw7a) revealed that it encoded a MYB transcription factor, that was not yet proactively used in modern breeding, suggesting that combining classic dw1or dw3, and new (dw7a) genes is an important breeding strategy. In conclusion, heterosis is explained in this situation by the dominance model and a combination of genes that balance the shortness and early flowering of the parents, to produce F1 seed yields.

Transforaminal vs Interlaminar Epidural Steroid Injection for Acute-Phase Shingles: A Randomized, Prospective Trial.

BACKGROUND: The acute phase of shingles is characterized by severe pain, and one of the complications of shingles known as postherpetic neuralgia (PHN) is associated with prolonged pain. Although factors predicting the development of PHN, as well as its preventative measures, have been investigated, there is no single treatment effective for PHN. Some studies showed effectiveness of epidural injection to alleviate pain associated with acute-phase shingles. In these studies, epidural injection was performed by interlaminar (IL) approach. However, transforaminal (TF) approach may be more effective as it enables injection of steroids and local anesthetics closer to the dorsal root ganglion where inflammation primarily occurs. There have not been any studies comparing the analgesic effects of epidural injection approaches for pain associated with acute-phase shingles. OBJECTIVE: We compared the analgesic effects of IL and TF epidural injection approaches for pain associated with acute-phase shingles. STUDY DESIGN: We conducted a randomized prospective trial. SETTING: Nara Medical University Hospital, Department of Anesthesiology. METHODS: Forty patients with acute-phase shingles were randomly assigned to receive epidural steroid injections by TF or IL approaches. Patients were evaluated at the baseline, as well as at 1 month and 3 months after the treatment using the VAS and SF-36 scores. Patients with VAS score of over 40 at the 3-month follow-up were considered as having PHN, and the number of patients with PHN was compared between the IL and TF groups. RESULTS: Except the mental component of the SF-36 score and severity of skin rash, patient characteristics were not significantly different between the groups. VAS scores at 1 and 3-month follow-up were significantly lower than those at the baseline, and there was no difference between the groups. All SF-36 scores were not significantly different between groups at 1- and 3-month. There was no significant difference in the occurrence of PHN between the groups. LIMITATIONS: We had a small sample size that did not reach the number of patients needed by the power analysis in the study. Then, our follow-up period of 3 months was relatively short. CONCLUSIONS: VAS scores, the SF-36 RCS and MCS scores improved in both groups, however, there was no difference in the analgesic effects of the IL and TF epidural steroid injections at 1 and 3 months for acute-phase shingles patients. KEY WORDS: Shingles epidural steroid injection interlaminar approach; transforaminal approach, fluoroscopic, postherpetic neuralgia, VAS, SF-36.

Sorghum DW1 positively regulates brassinosteroid signaling by inhibiting the nuclear localization of BRASSINOSTEROID INSENSITIVE 2.

Semi-dwarf traits have been widely introgressed into cereal crops to improve lodging resistance. In sorghum (Sorghum bicolor L. Moench), four major unlinked dwarfing genes, Dw1-Dw4, have been introduced to reduce plant height, and among them, Dw3 and Dw1 have been cloned. Dw3 encodes a gene involved in auxin transport, whereas, Dw1 was recently isolated and identified as a gene encoding a protein of unknown function. In this study, we show that DW1 is a novel component of brassinosteroid (BR) signaling. Sorghum possessing the mutated allele of Dw1 (dw1), showed similar phenotypes to rice BR-deficient mutants, such as reduced lamina joint bending, attenuated skotomorphogenesis, and insensitivity against feedback regulation of BR-related genes. Furthermore, DW1 interacted with a negative regulator of BR signaling, BRASSINOSTEROID INSENSITIVE 2 (BIN2), and inhibited its nuclear localization, indicating that DW1 positively regulates BR signaling by inhibiting the function of BIN2. In contrast to rice and wheat breeding which used gibberellin (GA) deficiency to reduce plant height, sorghum breeding modified auxin and BR signaling. This difference may result from GA deficiency in rice and wheat does not cause deleterious side effects on plant morphology, whereas in sorghum it leads to abnormal culm bending.

Immunostimulatory effect of dried bonito extract on mouse macrophage cell lines and mouse primary peritoneal macrophages.

Dried bonito is a preserved food used in Japan, which contains abundant flavor ingredients and functional substances. We focused on the immunostimulatory effect of dried bonito extract (DBE) on mouse macrophage-like J774.1 cells, RAW264.7 cells, and mouse primary peritoneal macrophages. DBE significantly stimulated the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by both J774.1 cells and peritoneal macrophages by enhancing the cytokine gene expression levels. In addition, DBE stimulated nitric oxide production by enhancing the expression of inducible nitric oxide synthase in RAW264.7 cells. DBE also increased the phagocytosis activity of J774.1 cells. Immunoblot analysis revealed that DBE has an immunostimulatory effect on macrophages through activation of mitogen-activated protein kinase and nuclear factor-κB cascades. TNF-α production enhanced by DBE was partially inhibited by treatment with TLR4 inhibitor TAK-242, whereas IL-6 production enhanced by DBE was almost inhibited. These results suggested that DBE is thought to strongly stimulate the TLR4 signaling pathway for macrophage activation, and its activation is also involved in other signaling. Finally, the phagocytosis activity of peritoneal macrophages from DBE-administered BALB/c mice increased significantly, suggesting that DBE has the potential to stimulate macrophage activity in vivo. In conclusion, these data indicated that DBE contributes to activating host defense against pathogens by activating innate immunity.

Transforaminal epidural blood patch for intractable spontaneous cerebrospinal fluid leak: a case report.

BACKGROUND: Epidural blood patch (EBP) is a recognized treatment for spontaneous cerebrospinal fluid leak (SCFL) and is typically administered by the interlaminar approach. Here, we report a case of a patient in whom SCFL failed to resolve after three applications of interlaminar EBPs before finally being successfully treated with transforaminal EBP. CASE PRESENTATION: We report a case of a 41-year-old female with a definitive diagnosis of SCFL according to computed tomography (CT) myelography. A fluoroscopy-guided interlaminar EBP was applied three times without resolution of her orthostatic headache. A second myelography was therefore performed demonstrating a leak point on the ventral side of the dura mater. To close the ruptured ventral dura mater, it was necessary to fill the ventral epidural space with blood. Therefore, transforaminal EBP was performed. On spinal CT performed immediately after treatment, the ventral epidural space was observed to be filled with injected blood. Her headache improved the following day, and her symptoms completely subsided after 5 days. CONCLUSION: Transforaminal epidural blood patch is appropriate for patients with intractable cerebrospinal fluid leak. Patients with cerebrospinal fluid leakage due to rupture of the ventral side of the dura mater may be particularly good candidates for this procedure.

Bite Force and Masticatory Performance Using Implant-supported Overdentures After Treatment of Mandibular Cancer.

AIM: To evaluate overdentures with regard to artificial restoration of oral function following mandibular cancer. MATERIALS AND METHODS: We examined 32 patients who had undergone mandibular bone resection as treatment for malignancy and were using implant-supported overdentures. The patients were aged 55-87 years (mean=68.6) with a male to female ratio of 23:9. Marginal resection was performed in 29 patients and segmentectomy in 3. RESULTS: Before and after using the attachment for overdenture, oral function differed significantly. After the setting of implant-retained overdentures, maximum bite force increased on average by 362% (average, from 16.2 N to 58.8 N; p<0.01). Xylitol gum examination showed a 363% increase in masticatory performance (average, 3.1 to 8.0 points; p<0.01). CONCLUSION: Implant-retained overdenture resulted in improved oral function, that was lost after treatment for mandibular cancer.

Sorghum Dw1, an agronomically important gene for lodging resistance, encodes a novel protein involved in cell proliferation.

Semi-dwarfing genes have contributed to enhanced lodging resistance, resulting in increased crop productivity. In the history of grain sorghum breeding, the spontaneous mutation, dw1 found in Memphis in 1905, was the first widely used semi-dwarfing gene. Here, we report the identification and characterization of Dw1. We performed quantitative trait locus (QTL) analysis and cloning, and revealed that Dw1 encodes a novel uncharacterized protein. Knockdown or T-DNA insertion lines of orthologous genes in rice and Arabidopsis also showed semi-dwarfism similar to that of a nearly isogenic line (NIL) carrying dw1 (NIL-dw1) of sorghum. A histological analysis of the NIL-dw1 revealed that the longitudinal parenchymal cell lengths of the internode were almost the same between NIL-dw1 and wildtype, while the number of cells per internode was significantly reduced in NIL-dw1. NIL-dw1dw3, carrying both dw1 and dw3 (involved in auxin transport), showed a synergistic phenotype. These observations demonstrate that the dw1 reduced the cell proliferation activity in the internodes, and the synergistic effect of dw1 and dw3 contributes to improved lodging resistance and mechanical harvesting.

Objective validity of an implant-retained overdenture with a ball attachment system after marginal mandibulectomy.

Implant-retained overdentures are known to improve oral function, but the clinical impact on patients who have had mandibular resections is still debatable. We have treated 16 patients who had such resections for oral cancer and consequent loss of the alveolar ridge, with overdentures supported by osseointegrated implants and ball attachments. To quantify their functional improvement, we evaluated their maximum bite force and masticatory performance. Their function improved significantly, (from 77.5N - 365N, 371% increase in maximum bite force, p<0.001) and masticatory performance increased (from 2.5 - 7.7, 208%, p<0.0001) after the overdentures had been inserted. While individual changes in maximum bite force showed no significant correlation, those in masticatory performance correlated significantly, which suggests that the subjects with poor masticatory function are likely to benefit from retention of an implant. These results indicate that implant-retained overdentures are an effective way to rehabilitate patients after marginal mandibular resection.

Gibberellin deficiency pleiotropically induces culm bending in sorghum: an insight into sorghum semi-dwarf breeding.

Regulation of symmetrical cell growth in the culm is important for proper culm development. So far, the involvement of gibberellin (GA) in this process has not yet been demonstrated in sorghum. Here, we show that GA deficiency resulting from any loss-of-function mutation in four genes (SbCPS1, SbKS1, SbKO1, SbKAO1) involved in the early steps of GA biosynthesis, not only results in severe dwarfism but also in abnormal culm bending. Histological analysis of the bent culm revealed that the intrinsic bending was due to an uneven cell proliferation between the lower and upper sides of culm internodes. GA treatment alleviated the bending and dwarfism in mutants, whereas the GA biosynthesis inhibitor, uniconazole, induced such phenotypes in wild-type plants--both in a concentration-dependent manner, indicating an important role of GA in controlling erectness of the sorghum culm. Finally, we propose that because of the tight relationship between GA deficiency-induced dwarfism and culm bending in sorghum, GA-related mutations have unlikely been selected in the history of sorghum breeding, as could be inferred from previous QTL and association studies on sorghum plant height that did not pinpoint GA-related genes.

[Perioperative fibrinogen concentrations in cardiac surgery with cardiopulmonary bypass].

BACKGROUND: Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) need many blood products due to deficiency of coagulation factors. Blood transfusion therapy in patients with excessive bleeding after CPB is generally empiric. We checked and studied the fibrinogen concentration and transfusion, as well as bleeding amount in the perioperative period. METHODS: The study was approved by our institutional ethics committee. Thirty patients were studied. Blood samples were obtained at the induction of anesthesia (before CPB), at the end of CPB, at the end of operation, and on the next morning, or before the patient was given fresh frozen plasma in the intensive care unit. RESULTS: For all cases, fibrinogen concentration and platelet concentration were lowest at the end of CPB. Fibrinogen concentration rose up to before CPB level on the next morning. The group in which fibrinogen concentration was less than 150 mg x dl(-1) at the end of CPB consumed more blood products than the group with fibrinogen concentration of over 150 mg x dl(-1). CONCLUSIONS: Blood transfusion therapy based on fibrinogen concentration is needed to maintain adequacy of the perioperative blood transfusion and blood conservation in cardiac surgery.