Food-dependent exercise-induced anaphylaxis caused by leek and several allergens of the allium family.

Exercise-induced anaphylaxis (EIA) is a relatively rare condition but can be a diagnostic pitfall in daily practice. Leek allergy is extremely rare, and there have been no reports, to our knowledge, of leek-dependent EIA. Here, we report the first case of exercise- and leek-induced anaphylaxis. An 18-year-old woman presented with symptoms of anaphylaxis after exercise in the morning. Prick-to-prick tests for leek was 1+ and challenge test for heated leek was negative, but leek-dependent physical exertion challenge test evoked anaphylaxis. We diagnosed food-dependent EIA by some additional tests including immunoblotting assay with patient's serum. Leek allergy is an extremely rare condition, so careful interview and investigation of allergens is important to eliminate causative substances of anaphylaxis.

Is tooth conservation possible in odontogenic sinusitis? Prospective evaluation of affected teeth condition-based protocol.

BACKGROUND: Affected tooth conservation is an often-overlooked problem in odontogenic sinusitis (ODS) treatment. Treatable dental conditions are improperly managed with extractions imposing an unnecessary health burden on patients. Furthermore, no down-to-earth protocols have been proposed for the clinical management of these patients. AIM: This study aims to prospectively validate a treatment protocol for ODS based on dental mobility, an indirect sign of poor long-term tooth survival. The protocol suggests endoscopic sinus surgery (ESS) alone followed by dental treatment for immobile affected teeth, and concomitant ESS and extraction for mobile teeth. Extraction of immobile teeth is considered if inflammation persists after the treatment. MATERIAL AND METHODS: Forty cases treated with our protocol were prospectively examined about ODS cure and preservation of affected teeth. RESULTS: Among the 35 patients with immobile affected teeth, only one required extraction for complete ODS cure after ESS. All five cases with mobile teeth and one with postoperative extraction had marginal periodontitis. CONCLUSION AND SIGNIFICANCE: Ninety-seven percent of immobile affected teeth were preserved with complete ODS cure in this study. In case marginal periodontitis is present, extraction is likely to be necessary, although ESS should be prioritized over blanket extractions to preserve the teeth for patients' quality life.

Benefits of amplification for unaided speech discrimination in age-related hearing loss with flat type audiogram.

OBJECTIVE: The present study aimed to investigate whether hearing aid use can induce improvement as acclimatization effect in unaided speech perception in patients with age-related hearing loss. METHODS: Fifty ears in 41 patients (age range: 65-91 years) diagnosed as age-related hearing loss were enrolled in this study. They used hearing aids for more than 8 hours per day. Unaided speech audiometry using 67-S Japanese monosyllabic word list was performed one or two years after the commencement of hearing aid use. The changes in the unaided speech discrimination score before and after the commencement of hearing aid use were analyzed. To investigate factors for improvement, the patients' backgrounds in terms of age, sex, pure tone average, unaided maximum speech discrimination score, fitting period (one year/two years), fitting ear (bilateral/unilateral), audiogram type (flat-type/other-type), and the level of amplification were also analyzed. RESULTS: Significant improvement in the unaided speech discrimination score after hearing aid use was seen only in the flat-type audiogram group. More than half of older patients in the flat-type audiogram group improved their unaided maximum speech discrimination score 10 % or more. The analysis of aided hearing thresholds revealed that the flat-type audiogram group had significantly lower thresholds of 3kHz and 4kHz than the other-type audiogram group. The age, sex, pure tone average, fitting period, fitting ear, functional gain were not influential factors for improvement. On the other hand, unaided maximum speech discrimination score before using hearing aid and aided hearing threshold at 4kHz had a negative correlation with improvement. CONCLUSION: The findings suggested that older patients with age-related hearing loss whose audiogram is a flat type can benefit from amplification as means of improving their unaided speech perception since flat-type audiogram can be more easily adjusted to sufficiently amplify speech sound at high frequencies. It should be considered that the potential for experience-dependent plasticity is retained even in older adults.

Olfactory Preservation in Craniofacial Resection of Tumor Invading Hemianterior Skull Base: Operative Video.

In traditional craniofacial resection of tumors invading the anterior skull base, the bilateral olfactory apparatus is resected. Recently, transnasal endoscopy has been used for olfactory preservation in resections of unilateral low-grade malignancies. However, for tumors that invade the orbita or for high-grade malignancies, the transnasal endoscopic skull base surgery has been controversial. This video demonstrates the surgical techniques of olfactory preservation during craniofacial resection of a high-grade malignancy invading the hemianterior skull base and orbita. We present the case of a 32-year-old woman with osteosarcoma in the right ethmoid sinus. The tumor invaded the ipsilateral cribriform plate, dura menta, and orbital periosteum; however, the nasal septum and crista galli were intact ( Fig. 1A, B ). Because the tumor was a high-grade malignancy and the orbita had been invaded, we performed craniofacial resection instead of endoscopic resection ( Fig. C2A ). We drilled into the right side of the crista galli, midline of the cribriform plate, and perpendicular plate of the ethmoid bone via craniotomy. As a result, we accessed the nasal cavity directly ( Fig. 2B ). To preserve the nasal septum, we detached the remaining right septal mucosa through the transfacial approach ( Fig. 2C ). Because of the high risk of cerebrospinal fluid leakage as a result of previous irradiation, we performed vascularized free flap reconstruction of the skull base instead of pericranial flap. Postoperative computed tomography revealed no evidence of tumor ( Fig. 1C, D ). The patient's sense of smell returned after 1 postoperative day, and she was discharged on the postoperative day 14. The link to the video can be found at: https://youtu.be/XzPABYwzkjs .

Opportunities for Interactive Communication in Mechanically Ventilated Critically Ill Patients: A Video-Based Observational Study.

Background: Mechanically ventilated critically ill patients need the opportunity to communicate their physical and psychosocial concerns to nurses. However, these patients face the unique problem of lacking even the opportunity to communicate. Aims: The study aimed to describe the characteristics of communication opportunities for critically ill mechanically ventilated patients. Methods: The study was designed as a video-based descriptive observational study. Participants included seven mechanically ventilated critically ill patients at the intensive care unit, coronary care unit, or high care unit who were conscious and seven registered nurses (seven pairs). Videos were recorded continuously from 8 am to 4 pm, and the footage was then descriptively analyzed. Data collection took place between July 2019 and June 2020. Results: The total recording time was 668.0 minutes. Of these 668.0 minutes, nurses stayed in the Conversation Area of the Patient for 279.6 minutes, and of these 279.6 minutes, two-way face-to-face communication between nurse and patient occurred for 78.0 minutes. Of these 78.0 minutes, communications were started by nurses for 47.2 minutes (174 scenes) and by patients for 24.2 minutes (36 scenes). The patient-started two-way communication scenes included 37 instances of Patient-Intentional-Action that triggered the start of communication. Actions using the upper limbs were observed in 20 instances and represented the most frequently used body part. The head/face, lower limbs, or trunk were also used in some of the actions. Gestures were the most commonly used action type (14 instances). Other types included lip movement, grimace, leg flex/extension, and cough. Conclusions: We found that nurses tended to start communication more frequently than patients did and that patients demonstrated Patient-Intentional-Action with a variety of actions using various body parts. Communication opportunities for patients were created when nurses took the initiative to start communication or when they noticed and responded to the Patient-Intentional-Action. Our findings demonstrate that nurses need to recognize and always respond to Patient-Intentional-Action and to take the initiative in communicating rather than waiting for the patient to do so.

Physiological and Pathological Roles of the Cytohesin Family in Neurons.

The cytohesin proteins, consisting of four closely related members (cytohesins-1, -2, -3, and -4), are a subfamily of the Sec7 domain-containing guanine nucleotide exchange factors for ADP ribosylation factors (Arfs), which are critical regulators of membrane trafficking and actin cytoskeleton remodeling. Recent advances in molecular biological techniques and the development of a specific pharmacological inhibitor for cytohesins, SecinH3, have revealed the functional involvement of the cytohesin-Arf pathway in diverse neuronal functions from the formation of axons and dendrites, axonal pathfinding, and synaptic vesicle recycling, to pathophysiological processes including chronic pain and neurotoxicity induced by proteins related to neurodegenerative disorders, such as amyotrophic lateral sclerosis and Alzheimer's disease. Here, we review the physiological and pathological roles of the cytohesin-Arf pathway in neurons and discuss the future directions of this research field.

Surgical technique for superselective neck dissection under local anesthesia in recurrent head and neck cancer.

The aim of this paper is to describe a safe and effective surgical technique for neck dissection under local anesthesia. An increasing number of patients cannot undergo general anesthesia due to systemic complication arising from old age. Moreover, the long-term survival of patients with recurrent or metastatic cancer due to advances in chemotherapy has increased the necessity of neck dissection under local anesthesia. Appropriate pain control and selection of medical devices are important factors for success of the surgery under local anesthesia. In addition to the usual subcutaneous infiltration anesthesia for pain control, nerve blocks for each cervical nerve encountered during surgery are extremely effective. Since muscle relaxants are not available, sharp devices such as knife or scissors, instead of electric scalpel, should be used to prevent unexpected muscle contractions caused by electric current. This video presents well-proven techniques and technical tips for superselective neck dissection under local anesthesia.

[The Safety of Bladder Irrigation with Solution G Prepared with Tap Water].

This study investigated the safety of bladder irrigation in patients with indwelling bladder catheter using Solution G prepared with tap water. Solution G was prepared using tap water and stored in a refrigerator for 1 week. The bacterial count range in the solution was estimated to be between 0 and 10 colony forming units/ml. The values were within the reference range in the Water Supply Act of Japan. Subsequently, bladder irrigation was performed with the prepared Solution G in six patients. The number of bacteria, leukocytes, and bacterial flora were evaluated before and 1 and 3 months after bladder irrigation. The results indicated no significant change in the values during this period. Therefore, bladder irrigation with Solution G prepared with tap water is safe.

A Case of Acquired Factor V Inhibitor Following Nivolumab Administration.

Acquired factor V inhibitor (AFVI) is a very rare disease. We presented herein a case of hypopharyngeal cancer in which AFVI developed after nivolumab administration. Blood test findings two weeks after the first dose of nivolumab showed a significant prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT), indicating a marked abnormality in the coagulation function. Factor V activity had decreased significantly and was below the detection limit (<3%), and the factor V inhibitor level was as high as 16 Bethesda units (BU)/mL. His underlying illness was a malignant tumor, but we considered that nivolumab administration was the cause of AFVI, considering the time when coagulation abnormality developed. No significant bleeding tendency was observed in the subsequent course, and the AFVI was followed up without treatment. To the best of our knowledge, the present study is the first to report AFVI occurrence after immune checkpoint inhibitor administration.

Patch testing with the Japanese baseline series 2015: A 4-year experience.

BACKGROUND: The Japanese baseline series (JBS), established in 1994, was updated in 2008 and 2015. The JBS 2015 is a modification of the thin-layer rapid-use epicutaneous (TRUE) test (SmartPractice Denmark, Hillerød, Denmark). No nationwide studies concerning the TRUE test have previously been reported. OBJECTIVES: To determine the prevalence of sensitizations to JBS 2015 allergens from 2015 to 2018. METHODS: We investigated JBS 2015 patch test results using the web-registered Skin Safety Care Information Network (SSCI-Net) from April 2015 to March 2019. RESULTS: Patch test results of 5865 patients were registered from 63 facilities. The five allergens with the highest positivity rates were gold sodium thiosulfate (GST; 25.7%), nickel sulfate (24.5%), urushiol (9.1%), p-phenylenediamine (PPD; 8.9%), and cobalt chloride (8.4%). The five allergens with the lowest positivity rates were mercaptobenzothiazole (0.8%), formaldehyde (0.9%), paraben mix (1.1%), mercapto mix (1.1%), and PPD black rubber mix (1.4%). CONCLUSIONS: Nickel sulfate and GST had the highest positivity rates. The JBS 2015, including a modified TRUE test, is suitable for baseline series patch testing.

The relationship between dental metal allergy, periodontitis, and palmoplantar pustulosis: An observational study.

PURPOSE: This study aimed to investigate the relationship between dental metal allergy, periodontitis, and palmoplantar pustulosis among patients from a dental metal allergy clinic over a period of 8 years. METHODS: This study included 436 patients who visited our dental metal allergy clinic between April 1, 2009 and March 31, 2016. Diagnoses of skin diseases, periodontal records, dental metal series patch test results, and electron probe microanalysis (EPMA) data were obtained from medical records. Relative risk (RR) values were estimated from these data. RESULTS: Of the 359 patients who underwent the patch test, 241 showed a positive reaction. Of the 187 patients who underwent EPMA, 113 had allergenic metals in their dental prostheses. These patients were suspected to have a dental metal allergy. Furthermore, 150 of the 436 patients were diagnosed with palmoplantar pustulosis (PPP). The RR of metal allergy between patients with PPP and healthy subjects was 3.88. The RR of periodontal disease between patients with PPP and PPP-negative patients in the national average was 2.54. CONCLUSION: In this study, both dental metal allergy and periodontitis showed a high RR for PPP.

Effect of universal varicella vaccination and behavioral changes against coronavirus disease 2019 pandemic on the incidence of herpes zoster.

BACKGROUND: Since 2014, universal varicella vaccination has reduced the varicella and herpes zoster (HZ) incidence in vaccine recipients and increased the incidence in the child-rearing generation until 2017. OBJECTIVE: This study aimed to understand the future epidemiologic trends of HZ after the disappearance of varicella epidemics and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: The Miyazaki Dermatologist Society has been monitoring and analyzing the incidence of HZ patients after universal vaccination since 1997. RESULTS: The HZ incidence in Oka varicella vaccine recipients aged 0-4 years decreased with the reduction in chickenpox incidence. The HZ incidence among those aged 5-9 years increased between 2015 and 2017 and decreased thereafter. From 2014-2020, the HZ incidence continued to increase to 36.6%, 51.3%, 70.2%, 56.7%, and 27.3% among those aged 10-19, 20-29, 30-39, 40-49, and 50-59 years, respectively. The HZ incidence in patients aged ≥ 60 years increased by 2.3% annually from 2014 to 2020, corresponding to an annual 2% increase since 1997, and was unaffected by varicella epidemics. COVID-19 infection control measures, lifestyle changes and the resulting stress did not affect the HZ incidence in 2020. CONCLUSION: Universal varicella vaccination eliminated varicella epidemics, and HZ was reduced in vaccine recipients. The HZ incidence for those aged 10-59 years increased from 2014 to 2020, in contrast to those aged ≥ 60 years, which is attributable to booster immunity expiration due to varicella contact in this age group.

Carotid artery ligation via sternotomy as a palliative surgery: Case report of advanced intramediastinal malignant soft tissue tumor.

Under extreme conditions and in palliative settings, shared decision making with the patient is vital; narrative decisions beyond evidence could be considered. If there is a chance of symptom palliation, extended surgery should not be avoided merely because of the limited life expectancy.

Cytohesin-2 mediates group I metabotropic glutamate receptor-dependent mechanical allodynia through the activation of ADP ribosylation factor 6 in the spinal cord.

Group I metabotropic glutamate receptors (mGluRs), mGluR1 and mGluR5, in the spinal cord are implicated in nociceptive transmission and plasticity through G protein-mediated second messenger cascades leading to the activation of various protein kinases such as extracellular signal-regulated kinase (ERK). In this study, we demonstrated that cytohesin-2, a guanine nucleotide exchange factor for ADP ribosylation factors (Arfs), is abundantly expressed in subsets of excitatory interneurons and projection neurons in the superficial dorsal horn. Cytohesin-2 is enriched in the perisynapse on the postsynaptic membrane of dorsal horn neurons and forms a protein complex with mGluR5 in the spinal cord. Central nervous system-specific cytohesin-2 conditional knockout mice exhibited reduced mechanical allodynia in inflammatory and neuropathic pain models. Pharmacological blockade of cytohesin catalytic activity with SecinH3 similarly reduced mechanical allodynia and inhibited the spinal activation of Arf6, but not Arf1, in both pain models. Furthermore, cytohesin-2 conditional knockout mice exhibited reduced mechanical allodynia and ERK1/2 activation following the pharmacological activation of spinal mGluR1/5 with 3,5-dihydroxylphenylglycine (DHPG). The present study suggests that cytothesin-2 is functionally associated with mGluR5 during the development of mechanical allodynia through the activation of Arf6 in spinal dorsal horn neurons.

Metformin reduces androgen receptor and upregulates homeobox A10 expression in uterine endometrium in women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) causes anovulation and is associated with a reduced clinical pregnancy rate. Metformin, which is widely used for treating PCOS, can lead to successful pregnancy by restoring the ovulation cycle and possibly improving endometrial abnormality during the implantation period. However, the mechanism by which metformin improves endometrial abnormality remains unknown. Women with PCOS have an aberrant expression of steroid hormone receptors and homeobox A10 (HOXA10), which is essential for embryo implantation in the endometrium. METHODS: In this study, we examined whether metformin affects androgen receptor (AR) and HOXA10 expression in PCOS endometrium in vivo and in human endometrial cell lines in vitro. Expression of AR and HOXA10 was evaluated by immunohistochemistry, fluorescent immunocytochemistry, and western blot analysis. RESULTS: AR expression was localized in both epithelial and stromal cells; however, HOXA10 expression was limited to only stromal cells in this study. In women with PCOS, 3 months after metformin treatment, the expression of AR was reduced in epithelial and stromal cells in comparison to their levels before treatment. In contrast, HOXA10 expression in the stromal cells with metformin treatment increased in comparison to its level before treatment. Further, we showed that metformin counteracted the testosterone-induced AR expression in both Ishikawa cells and human endometrial stromal cells (HESCs); whereas, metformin partly restored the testosterone-reduced HOXA10 expression in HESCs in vitro. CONCLUSIONS: Our results suggest that metformin may have a direct effect on the abnormal endometrial environment of androgen excess in women with PCOS. TRIAL REGISTRATION: The study was approved by the Ethical Committee of Fukushima Medical University (approval no. 504, approval date. July 6, 2006), and written informed consent was obtained from all patients. https://www.fmu.ac.jp/univ/sangaku/rinri.html.

Rhododendrol-induced leukoderma update II: Pathophysiology, mechanisms, risk evaluation, and possible mechanism-based treatments in comparison with vitiligo.

A small proportion of individuals utilizing cosmetics containing rhododendrol developed leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol-induced leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism-based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol-induced leukoderma helps not only elucidate the mechanisms of non-segmental vitiligo onset and progression, but also suggests prevention and treatment.

Multicenter 1-month follow-up study of the patch-test reaction to the gold sodium thiosulfate of the TRUE Test and its association with piercings and dental metal history.

BACKGROUND: There is controversy over late and long-lasting reactions to gold sodium thiosulfate (GST). OBJECTIVES: To study the GST patch-test reaction by observing the application site after 1 month, and to clarify the relevance of GST sensitization by piercings and dental metals. PATIENTS: A retrospective analysis was performed on 746 patients (143 male; 603 female) who were patch tested using GST of the TRUE Test. We conducted a questionnaire on the presence of piercings or dental metals in these patients. RESULTS: The GST positive rate was 27.9% at day (D)3 and/or D7 and 40.3% up to the 1-month reading. The positive rate was significantly higher in female patients and increased with age. Sixty-two percent of cases with a positive reaction at D7 continued to show a positive reaction after 1 month. Eleven percent of cases with a negative reaction at D3 and D7 showed a late reaction. Both piercings and dental metals were related to gold sensitization. CONCLUSIONS: The GST of the TRUE Test had a high positive and low false-negative rate. The 1-month reading after the patch test was important for identifying late reactions. Piercing history and dental metal were associated with gold sensitization.

Rhododendrol-induced leukoderma update I: Clinical findings and treatment.

Individuals who used skin-whitening cosmetics (quasi-drugs) containing 2% rhododendrol-containing agents, developed leukoderma at a higher frequency than those who have used other skin-whitening cosmetics. The Rhododenol Research Team (RD-Team) was formed and commissioned by Kanebo Cosmetics Inc. to conduct research in treatments of rhododendrol-induced leukoderma (RDL), to evaluate effective treatment options from a medical standpoint, and provide information to a wide range of people. In this study, we evaluated the efficacy of various treatments for RDL from a medical perspective, based on the information published in the literature as original or review articles. We searched the PubMed (international) and the Igaku Chuo Zasshi (ICHUSHI) (Japanese) databases using the keywords "Rhododenol" and "rhododendrol", for articles published between July 2013 and November 2020. We discuss the main clinical findings and treatments (topical, oral, phototherapy, and surgical) of this condition based on the literature review. We found that ultraviolet light therapy is the most effective treatment for RDL. We have also summarized reports of the efficacy of oral vitamin D3 in RDL. A topical prostaglandin derivative has been reported in a new study to be effective. We have provided guidance for patients using self-tanning and skin-whitening agents to improve their quality of life. Finally, we have highlighted the importance of providing patients with information on contact dermatitis and instructing them to discontinue product use immediately if they develop any symptoms of contact dermatitis while using skin-whitening agents.

Full-coverage TP53 deep sequencing of recurrent head and neck squamous cell carcinoma facilitates prognostic assessment after recurrence.

OBJECTIVES: This study aims to evaluate whether the accumulation of TP53 mutations is associated with clinical outcome by comparing full-coverage TP53 deep sequencing of the initial and recurrent head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Medical records and surgical specimens of 400 patients with HNSCC surgically treated with curative intent, of which 95 patients developed local or locoregional recurrence, were reviewed. Of these patients, 63 were eligible for genomic analysis. Full-coverage TP53 deep sequencing of 126 paired initial and recurrent tumor samples was examined using next-generation sequencing (NGS). Temporal changes in the mutation status, molecular characterization, and clinical outcome were compared. Fisher's exact test, Kaplan-Meier method, log-rank test, and Cox regression models were used for statistical analysis. RESULTS: Of the recurrent tumors, 22% harbored accumulation of TP53 mutations, and 16% lost the original mutation. The accumulation of TP53 mutations was significantly more frequent in oral cancer than in pharyngeal or laryngeal cancer (33% vs. 7%, p = 0.016). Two-year post-recurrence survival (PRS) was associated with TP53 status for recurrent tumors, but not for initial tumors. The TP53 status for recurrent tumors was an independent risk factor in multivariate analysis (hazard ratio, 5.76; 95% confidence interval, 1.86-17.8; p = 0.0023). CONCLUSION: Approximately one-third of the recurrent HNSCC cases showed a different TP53 status from the initial tumor. Temporal changes in the mutation status differed by primary site. Full-coverage TP53 deep sequencing of recurrent tumors was useful in predicting post-recurrence prognosis.

How Is Global Warming Affecting Fruit Tree Blooming? "Flowering (Dormancy) Disorder" in Japanese Pear (Pyrus pyrifolia) as a Case Study.

Recent climate change has resulted in warmer temperatures. Warmer temperatures from autumn to spring has negatively affected dormancy progression, cold (de)acclimation, and cold tolerance in various temperate fruit trees. In Japan, a physiological disorder known as flowering disorder, which is an erratic flowering and bud break disorder, has recently emerged as a serious problem in the production of the pome fruit tree, Japanese (Asian) pear (Pyrus pyrifolia Nakai). Due to global warming, the annual temperature in Japan has risen markedly since the 1990s. Surveys of flowering disorder in field-grown and greenhouse-grown Japanese pear trees over several years have indicated that flowering disorder occurs in warmer years and cultivation conditions, and the risk of flowering disorder occurrence is higher at lower latitudes than at higher latitudes. Susceptibility to flowering disorder is linked to changes in the transcript levels of putative dormancy/flowering regulators such as DORMANCY-ASSOCIATED MADS-box (DAM) and FLOWERING LOCUS T (FT). On the basis of published studies, we conclude that autumn-winter warm temperatures cause flowering disorder through affecting cold acclimation, dormancy progression, and floral bud maturation. Additionally, warm conditions also decrease carbohydrate accumulation in shoots, leading to reduced tree vigor. We propose that all these physiological and metabolic changes due to the lack of chilling during the dormancy phase interact to cause flowering disorder in the spring. We also propose that the process of chilling exposure rather than the total amount of chilling may be important for the precise control of dormancy progression and robust blooming, which in turn suggests the necessity of re-evaluation of the characteristics of cultivar-dependent chilling requirement trait. A full understanding of the molecular and metabolic regulatory mechanisms of both dormancy completion (floral bud maturation) and dormancy break (release from the repression of bud break) will help to clarify the physiological basis of dormancy-related physiological disorder and also provide useful strategies to mitigate or overcome it under global warming.