SULTR2;1 Adjusts the Bolting Timing by Transporting Sulfate from Rosette Leaves to the Primary Stem.

Sulfur (S) is an essential macronutrient for plant growth and metabolism. SULTR2;1 is a low-affinity sulfate transporter facilitating the long-distance transport of sulfate in Arabidopsis. The physiological function of SULTR2;1 in the plant life cycle still needs to be determined. Therefore, we analyzed the sulfate transport, S-containing metabolites accumulation, and plant growth using Arabidopsis SULTR2;1 disruption lines, sultr2;1-1 and sultr2;1-2, from seedling to mature growth stages to clarify the metabolic and physiological roles of SULTR2;1. We observed that sulfate distribution to the stems was affected in sultr2;1 mutants resulting in decreased levels of sulfate, cysteine, glutathione (GSH), and total S in the stems, flowers, and siliques; however, the GSH levels increased in the rosette leaves. This suggested the essential role of SULTR2;1 in sulfate transport from rosette leaves to the primary stem. In addition, sultr2;1 mutants unexpectedly bolted earlier than the wild-type without affecting the plant biomass. Correlation between GSH levels in rosette leaves and the bolting timing suggested the rosette leaf GSH levels or limited sulfate transport to the early stem can trigger bolting. Overall, this study demonstrated the critical roles of SULTR2;1 in maintaining the S metabolite levels in the aerial part and transitioning from the vegetative to the reproductive growth phase.

Combination of high-flow nasal oxygen and ketamine/dexmedetomidine sedation for diagnostic catheterization in a child with pulmonary arterial hypertension: a case report.

Pulmonary hypertension is associated with significant risk of perioperative life-threatening events. We present a case of a 12-year-old child with severe pulmonary arterial hypertension who successfully underwent diagnostic cardiac catheterization under ketamine and dexmedetomidine sedation with the support of high-flow nasal oxygen. Ketamine and dexmedetomidine are reported to have minimal effect on pulmonary vasculature in children with pulmonary hypertension and can be safely used in this population along with its lack of respiratory depression. Positive pressure generated by high-flow nasal oxygen improves upper airway patency, prevents micro-atelectasis, and is shown to improve the effectiveness of ventilation and oxygenation in patients under sedation breathing spontaneously. The presented strategy may contribute to enhancing the safety and effectiveness of procedural sedation for children with life-threatening pulmonary hypertension.

Search for nutritional and inflammatory marker ratios to predict neutropenia in FEC therapy for breast cancer: A retrospective observational study.

OBJECTIVE: Nutritional and inflammatory marker ratios are known to predict response to chemotherapy in breast cancer, but whether they predict adverse effects caused by chemotherapy remains unclear. We investigated whether nutritional and inflammatory marker ratios before starting FEC therapy (5-fluorouracil, epirubicin, and cyclophosphamide) predict grade 4 neutropenia as a serious adverse effect. MATERIALS AND METHODS: 61 patients with breast cancer who started FEC therapy for the first time as preoperative or postoperative chemotherapy were studied. Relevant nutritional and inflammatory marker ratios were compared between patients who developed grade 4 neutropenia (n = 44) and those who did not (n = 17). RESULTS: In univariate analysis, occurrence of neutropenia was related significantly (p < 0.05) to pre-FEC-therapy white blood cell count, platelet count, neutrophil count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and modified Glasgow prognostic score. Analysis using cutoff values obtained from receiver operating characteristic curves showed that LMR, NLR, and PLR predicted grade 4 neutropenia. However, multivariate logistic regression analysis identified no independent factor associated with grade 4 neutropenia. A post-hoc power analysis revealed an inadequate sample size. CONCLUSION: Inflammatory marker ratios, especially PLR, may predict grade 4 neutropenia caused by FEC therapy for breast cancer. Although multivariate analysis identified no independent predictive markers in this study due to inadequate sample size, further prospective large-scale research is needed to examine the usefulness of nutritional and inflammatory marker ratios for predicting adverse effects.

Effects of wearing surgical masks on fraction of inspired oxygen in spontaneously breathing patients: improving safety for frontline healthcare professionals under pandemic situations.

BACKGROUND: During pandemic situations, many guidelines recommend that surgical masks be worn by both healthcare professionals and infected patients in healthcare settings. The purpose of this study was to clarify the levels and changes of oxygen concentration over time while oxygen was administered over a surgical mask. METHODS: Patients scheduled to undergo general anesthesia (n = 99) were enrolled in this study. First, patients were administered oxygen at 6 L/min via an oxygen mask over a surgical mask for 5 min. The patients removed the surgical mask and then took a 3-min break; thereafter, the same amount of oxygen was administered for another 5 min via the oxygen mask. We measured the fraction of inspired oxygen (FiO2), the end-tidal CO2 (EtCO2), and respiratory frequency every minute for 5 min, both while administering oxygen with and without a surgical mask. The FiO2 was measured at the beginning of inspiration and the EtCO2 was measured at the end of expiration. RESULTS: The FiO2 at 5 min was significantly lower when breathing with a surgical mask than that without it (mean difference: 0.08 [95% CI: 0.067-0.10]; p <  0.001). In contrast, the EtCO2 at 5 min was significantly higher when breathing with a surgical mask than that without it (mean difference: 11.9 mmHg [95% CI: 10.9-12.9]; p <  0.001). CONCLUSION: The FiO2 was lower when oxygen was administered over surgical masks than when patients did not wear surgical masks. Oxygen flow may need to be adjusted in moderately ill patients requiring oxygen administration.

Longer Bread Shelf-Life and Improved Noodle-Making Properties Imparted by a Novel Wheat Genotype Are Stable in Different Genetic Backgrounds.

A recently developed wheat variety, known as 5-5 wheat, which has inactive GBSSI-B1, GBSSI-D1, SSIIa-B1, and SSIIa-D1 isozymes, accumulates a novel type of starch, affecting bread texture and leading to reduction in bread staling. These properties are potentially useful for commercial bakery products; thus, the 5-5 genotype represents a new resource for wheat breeding. In this study, the 5-5 alleles were backcrossed into the hard wheat variety "Minaminokaori" and the soft wheat variety "Shirogane-Komugi", which are both leading Japanese wheat varieties. In comparison to their parental varieties, the two 5-5 near-isogenic lines (NILs) showed a decrease in amylose levels, an increase in the proportion of short chains of amylopectin, a lower gelatinization temperature and enthalpy change, a higher peak viscosity and breakdown viscosity as measured by a Rapid Visco Analyzer, a reduced retrogradation rate, and an increase in grain hardness. Importantly, the 5-5 NILs also showed lower bread crumb firmness and reduced hardening after storage for 2 days at either 20 °C or 7 °C. Considering the results obtained here along with those from the original line, it is clear that the 5-5 genotype can generate specific changes in starch characteristics and staling regardless of its genetic background. Thus, we renamed the 5-5 wheat lines "Slow Staling" (SS) wheat. As expected, our results indicated that the hard wheat SS NIL was more suitable for bread-making. On the other hand, we found that white salted noodle made with the SS NIL of the soft wheat variety had a relatively shorter cooking time, a softer texture, and a reduction in textural changes during storage, all of which are potentially useful for noodle manufacturers.

Hyperammonemia with impaired consciousness caused by continuous 5-fluorouracil infusion for colorectal cancer: A case report.

A 66-year-old woman was diagnosed with stage IVb sigmoid colon cancer. Modified FOLFOX-6 (mFOLFOX-6; levofolinate‒fluorouracil‒oxaliplatin) plus panitumumab was selected as the chemotherapeutic regimen, but she was administered a regimen without oxaliplatin (L-OHP) or bolus 5-fluorouracil (5-FU) because of her general condition and concern about adverse effects. The patient had impaired consciousness on day 3 of chemotherapy. Computed tomography (CT) and magnetic resonance imaging (MRI) of the brain showed no findings of hemorrhage, infarction, brain metastasis, and leukoencephalopathy. Except for high blood ammonia concentration (353 µg/dL), there were no other findings that could have caused her condition. Impaired consciousness due to hyperammonemia was diagnosed. We started an intravenous drip supplemented with branched chain amino acids for liver protection. Approximately 6 hours later, blood ammonia level improved to 88 µg/dL, which approached the reference value. Consciousness level improved over time, reaching a level of alertness on day 5 after starting chemotherapy. 5-FU was suspected to be the cause of impaired consciousness due to hyperammonemia, but the exact cause could not be identified because most of the previously reported cases were given L-OHP, bolus 5-FU, and other concomitant medications. In this case, since there were no other concomitant medications, it is highly probable that continuous infusion of 5-FU alone caused impaired consciousness due to hyperammonemia. This is an important case that indicates the need to monitor carefully for the occurrence of hyperammonemia when 5-FU is administered continuously; it also proposes future issues for investigation.

Novel quantitative trait loci for low grain cadmium concentration in common wheat (Triticum aestivum L.).

Cadmium (Cd) is as an extremely toxic metal that can contaminate agricultural soils. To reduce the risk of Cd intake in food cereals, the development of cultivars with low grain Cd concentration (GCC) is an effective countermeasure. We analyzed quantitative trait loci (QTLs) for GCC in a doubled haploid (DH) common wheat (Triticum aestivum L.) population derived from 'Chugoku 165' (low GCC) × 'Chukei 10-22' (high GCC). We found novel loci for low GCC on the short arm of chromosome 4B and on the long arm of chromosome 6B. These QTLs accounted for 9.4%-25.4% (4B) and 9.0%-17.8% (6B) of the phenotypic variance in the DH population. An association analysis with 43 cultivars identified 3 loci at these QTLs: QCdc.4B-kita, QCdc.6B-kita1, and QCdc.6B-kita2. In contrast to durum wheat and barley, no QTL was detected on the chromosomes of homeologous group 5 for heavy metal P1B-type ATPase 3. These results will contribute to marker-assisted selection for low GCC in breeding of common wheat.

[A patient with neurosarcoidosis presenting with easy falling and dysphagia].

A 68-year-old woman was referred to our hospital for progressive dizziness, gait disturbances and weight loss for 18 months. The patient was alert and showed dysphagia and a marked tendency to fall backward. Electronystagmography showed bilateral vestibular dysfunction and audiometry showed right sensorineural hearing disturbance. Cerebrospinal fluid exam showed mononuclear pleocytosis and elevated protein levels. On 18F-FDG PET/CT, abnormal uptake was observed in the mediastinal lymph nodes, from which biopsy specimens were obtained. Histological findings showed non-caseous granuloma and a diagnosis of bilateral vestibulocochlear, glossopharyngeal and vagal nerve palsies due to neurosarcoidosis was made. Steroid therapy resulted in improvement in her clinical symptoms. Neurosarcoidosis should be included in the differential diagnosis of patients showing progressive easy falling and dysphagia.

Multifamily QTL analysis and comprehensive design of genotypes for high-quality soft wheat.

Milling properties and flour color are essential selection criteria in soft wheat breeding. However, high phenotypic screening costs restrict selection to relatively few breeding lines in late generations. To achieve marker-based selection of these traits in early generations, we performed genetic dissection of quality traits using three doubled haploid populations that shared the high-quality soft wheat variety Kitahonami as the paternal parent. An amplicon sequencing approach allowed effective construction of well-saturated linkage maps of the populations. Marker-based heritability estimates revealed that target quality traits had relatively high values, indicating the possibility of selection in early generations. Taking advantage of Chinese Spring reference sequences, joint linkage maps of the three populations were generated. Based on the maps, multifamily quantitative trait locus (QTL) analysis revealed a total of 86 QTLs for ten traits investigated. In terms of target quality traits, 12 QTLs were detected for flour yield, and 12 were detected for flour redness (a* value). Among these QTLs, six for flour yield and nine for flour a* were segregating in more than two populations. Some relationships among traits were explained by QTL collocations on chromosomes, especially group 7 chromosomes. Ten different ideotypes with various combinations of favorable alleles for the flour yield and flour a* QTLs were generated. Phenotypes of derivatives from these ideotypes were predicted to design ideal genotypes for high-quality wheat. Simulations revealed the possibility of breeding varieties with better quality than Kitahonami.

Amylose and amylopectin functionality during storage of bread prepared from flour of wheat containing unique starches.

Bread crumb firming is largely determined by the properties of gluten and starch, and the transformations they undergo during bread making and storage. Amylose (AM) and amylopectin (AP) functionality in fresh and stored bread was investigated with NMR relaxometry. Bread was prepared from flours containing normal and atypical starches, e.g., flour from wheat line 5-5, with or without the inclusion of Bacillus stearothermophilus α-amylase. Initial crumb firmness increased with higher levels of AM or shorter AM chains. Both less extended AM and gluten networks and too rigid AM networks led to low crumb resilience. AP retrogradation during storage increased when crumb contained more AP or longer AP branch chains. Shorter AP branch chains, which were present at higher levels in 5-5 than in regular bread, were less prone to retrogradation, thereby limiting gluten network dehydration due to gluten to starch moisture migration. Correspondingly, crumb firming in 5-5 bread was restricted.

[Two adult patients with acute necrotizing encephalopathy following influenza virus infection].

Influenza encephalopathy is characterized by high fever, disturbance of consciousness following influenza virus infection. We encountered 2 adult patients with influenza-associated acute necrotizing encephalopathy (Case 1, a 70-year-old woman with diabetes; Case 2, a 49-year-old woman with multiple myeloma), showing hemorrhagic lesions in the bilateral thalamus. Case 1 presented with fever and disturbance of consciousness followed by status epilepticus, and Case 2 developed fever and drowsiness as initial manifestation. Influenza type A was positive in Case 1 and influenza type B was positive in Case 2. In the acute phase, 2 patients required respiratory ventilation and were treated with anti-influenza drug, steroid and immunoglobulin. Cognitive impairment remained in the both patients in the chronic phase. When acute necrotizing encephalopathy is suspected, intensive treatment should be started as early as possible to improve clinical outcome of patients.

Perspectives on Low Temperature Tolerance and Vernalization Sensitivity in Barley: Prospects for Facultative Growth Habit.

One option to achieving greater resiliency for barley production in the face of climate change is to explore the potential of winter and facultative growth habits: for both types, low temperature tolerance (LTT) and vernalization sensitivity are key traits. Sensitivity to short-day photoperiod is a desirable attribute for facultative types. In order to broaden our understanding of the genetics of these phenotypes, we mapped quantitative trait loci (QTLs) and identified candidate genes using a genome-wide association studies (GWAS) panel composed of 882 barley accessions that was genotyped with the Illumina 9K single-nucleotide polymorphism (SNP) chip. Fifteen loci including 5 known and 10 novel QTL/genes were identified for LTT-assessed as winter survival in 10 field tests and mapped using a GWAS meta-analysis. FR-H1, FR-H2, and FR-H3 were major drivers of LTT, and candidate genes were identified for FR-H3. The principal determinants of vernalization sensitivity were VRN-H1, VRN-H2, and PPD-H1. VRN-H2 deletions conferred insensitive or intermediate sensitivity to vernalization. A subset of accessions with maximum LTT were identified as a resource for allele mining and further characterization. Facultative types comprised a small portion of the GWAS panel but may be useful for developing germplasm with this growth habit.

Successful treatment of non-HIV progressive multifocal leukoencephalopathy: case report and literature review.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a subacute onset demyelinating disease caused by JC virus and characterized by multifocal involvement of the subcortical white matter and cerebellar hemispheres or peduncles on magnetic resonance imaging (MRI). However, non-HIV PML patients with brain lesions limited to the cerebellum and brainstem have not been well characterized. METHODS: We report a 68-year-old man with systemic lupus erythematosus under treatment with immunosuppressants who developed non-HIV PML with brain lesions limited to the cerebellum and brainstem and successfully treated with a combination of mefloquine and mirtazapine. We performed a literature review to characterize patients with non-HIV PML with brain lesions limited to the cerebellum and brainstem. RESULTS: Eight cases with non-HIV brainstem/cerebellar form PML were identified including our case. All cases had compromised status related underlying diseases. Four (50%) had a good prognosis. Five cases were treated, including 3 with favourable outcomes. Between the good prognosis group (n = 4) and the poor prognosis group (n = 4), treatment status for PML and the interval between the initial manifestation and diagnosis did not differ. Among those who performed contrast-enhanced brain imaging, lesion enhancement was related to good prognosis (good prognosis group vs. poor prognosis group; 100% vs. 0%). CONCLUSION: PML should be considered in the differential diagnosis of brain lesions limited to the cerebellum and brainstem in immunocompromised patients. The presence of immune response against JC virus and inflammatory reactions may indicate good prognosis in non-HIV brainstem/cerebellar form PML.

[A male patient with adult-onset sporadic calpainopathy presenting with hypertrophy of the upper extremities].

A 33-year-old man presented with slowly progressive weakness in the lower extremities over 8 years. At the age of 16 years, the elevation of serum creatine kinase level was detected. Physical examination revealed scapular winging, exaggerated lumbar lordosis and tendoachilles contracture. Gowers sign was positive and proximal dominant limb weakness was noted. Hypertrophy was observed in the upper limbs such as the biceps brachii and forearm flexor muscles. Muscle biopsy showed distinct differences in size of muscle fibers and regenerating and necrotic muscle fibers. A histological study revealed decreased calpain3 expression. Gene analysis of CAPN3 revealed two known gene mutations, leading to a diagnosis of calpainopathy (limb girdle muscular dystrophy 2A; LGMD2A). We here report our patient to discuss findings of upper limb hypertrophy, which are frequently missed compared to the lower limb, but important clinical findings.

Sudden onset of sleep caused by hypothalamic infarction: a case report.

BACKGROUND: Hypothalamic lesions, such as tumors and demyelinating diseases, reportedly cause abnormal sleepiness. However, stroke involving the hypothalamus has rarely been described. Here, we report a patient with infarction restricted to the hypothalamus who presented with sudden onset of sleep. CASE PRESENTATION: A 42-year-old woman with a history of migraine without aura presented with irresistible sleepiness and developed several episodes of sudden onset of sleep. Neurological examinations were unremarkable except for partial left Horner syndrome. Brain magnetic resonance imaging (MRI) revealed a high-intensity lesion restricted to the left hypothalamus on diffusion-weighted and fluid-attenuated inversion recovery MRI images. Cerebrospinal fluid (CSF) orexin-A levels obtained on hospital day 3 after her sleepiness had resolved were normal (337 pg/mL; normal > 200 pg/mL). Serum anti-nuclear and anti-aquaporin 4 (AQP4) antibodies and CSF myelin basic protein and oligoclonal band were negative. A small hypothalamic infarction was suspected, and the patient was treated with intravenous edaravone and argatroban, as well as oral clopidogrel. Three months later, there had been no clinical relapse, and the hypothalamic lesion had almost disappeared on follow-up MRI. No new lesion suggestive of demyelinating disease or tumor was observed. CONCLUSION: Hypothalamic stroke should be considered a cause of sudden onset of sleep.

Amylose and amylopectin functionality during baking and cooling of bread prepared from flour of wheat containing unusual starches: A temperature-controlled time domain 1H NMR study.

Amylose (AM) and amylopectin (AP) functionality during bread making was unravelled with a temperature-controlled time domain proton nuclear magnetic resonance (TD 1H NMR) toolbox. Fermented doughs from wheat flour containing starches with atypical AP chain length distribution and/or AM to AP ratio, or supplemented with Bacillus stearothermophilus α-amylase (BStA) were analyzed in situ during baking and cooling. The gelatinization temperature of starch logically depended on AP crystal stability. It was lower when starch contained a higher portion of short AP branches and higher when starch had higher AP content. During cooling, the onset temperature and extent of AM crystallization were positively related to starch AM content. BStA use resulted in slightly weakened starch networks and increased the starch polymers' mobility at the end of baking. That proton distributions evolved in a way corresponding to starch characteristics supports the suggested interpretation of NMR profiles during baking and cooling.

[Genetic Creutzfeldt-Jakob disease with a glutamate-to-lysine substitution at codon 219 (E219K) in the presence of the E200K mutation presenting with rapid progressive dementia following slowly progressive clinical course].

A 57-year-old man developed rapidly progressive dementia and a gait disturbance over 4 months. The patient had a slowly progressive executive dysfunction and speech problems for 4 years and was previously monitored in our outpatient clinic following a diagnosis of frontotemporal dementia. Diffusion-weighted MRI revealed high signal intensities in the right caudate nucleus and the bilateral cortices. Cerebrospinal fluid analysis showed increased levels of the 14-3-3 and total tau proteins. Periodic synchronous discharge was not evident on an electroencephalogram. Prion protein gene analysis identified a glutamate-to-lysine substitution at codon 219 (E219K) in the presence of the E200K mutation, leading to a genetic diagnosis of genetic Creutzfeldt-Jakob disease (CJD). The E219K polymorphism found on the allele of the E200K mutation may have influenced the characteristic clinical course of our patient that differed from that of typical E200K genetic CJD.

[Increased frequency and spread of restlessness as the early manifestation of Parkinson's disease in a woman with restless legs syndrome].

A 57-year-old woman had been suffered from insomnia due to restlessness and abnormal sensation of the left side of the body for 33 years. Since the preceding year of the first visit frequency of the symptoms increased, and the abnormal sensation was spread to the right leg. Her daughter had restless legs syndrome (RLS) since age 20. Neurological examination showed no abnormality. Laboratory test results showed normal ferritin levels. There was no renal dysfunction or anemia. A diagnosis of RLS was made, and her symptoms responded well to pramipexole treatment. However, the patient developed right shoulder pain and right-hand tremor one year and one and a half year after the first visit, respectively. Based on clinical findings and the findings of dopamine transporter scan and cardiac 123I-MIBG scintigraphy, the patient was diagnosed with Parkinson's disease (PD). Careful observation of changes in RLS symptoms is required as an increased frequency and spread of symptoms of RLS could be the early manifestation of PD.