The role of metabolism in cardiac development.

Metabolism is the fundamental process that sustains life. The heart, in particular, is an organ of high energy demand, and its energy substrates have been studied for more than a century. In recent years, there has been a growing interest in understanding the role of metabolism in the early differentiation of pluripotent stem cells and in cancer research. Studies have revealed that metabolic intermediates from glycolysis and the tricarboxylic acid cycle act as co-factors for intracellular signal transduction, playing crucial roles in regulating cell behaviors. Mitochondria, as the central hub of metabolism, are also under intensive investigation regarding the regulation of their dynamics. The metabolic environment of the fetus is intricately linked to the maternal metabolic status, and the impact of the mother's nutrition and metabolic health on fetal development is significant. For instance, it is well known that maternal diabetes increases the risk of cardiac and nervous system malformations in the fetus. Another notable example is the decrease in the risk of neural tube defects when pregnant women are supplemented with folic acid. These examples highlight the profound influence of the maternal metabolic environment on the fetal organ development program. Therefore, gaining insights into the metabolic environment within developing fetal organs is critical for deepening our understanding of normal organ development. This review aims to summarize recent findings that build upon the historical recognition of the environmental and metabolic factors involved in the developing embryo.

Long-term safety of desmopressin orally disintegrating tablets in men with nocturia due to nocturnal polyuria: Interim results of a specified drug use-results survey in Japan.

OBJECTIVES: This interim report presents the 12-week results of a post-marketing surveillance evaluating the safety of desmopressin orally disintegrating tablets 25 and 50 µg in Japanese men with nocturia due to nocturnal polyuria. METHODS: Of the planned study population of 1000 Japanese men receiving desmopressin for the first time for nocturia due to nocturnal polyuria, 971 cases were enrolled. In this interim analysis, 9 cases, including 6 registry violations and 3 cases of unconfirmed desmopressin dosing, were excluded from the 354 case report forms collected and fixed by the end of December 2021, and data up to 12 weeks after administration in 345 cases were defined as the safety analysis set. RESULTS: The mean age was 74.5 ± 9.9 years and 88.7% of the survey participants were aged ≥65 years. Desmopressin was started at a dose of 25 µg in 153 cases (44.3%). There were 102 adverse drug reactions (ADRs) reported in 71 cases, including 6 serious ADRs in 3 cases (0.9%). The most common ADR was hyponatremia occurring in 29 cases (8.4%). Eight of the hyponatremic cases were asymptomatic. Symptoms were resolved or slightly improved within 4 weeks of onset in 13 of 29 cases of hyponatremia. In addition, hyponatremia occurred in 11 of 217 cases (5.1%), with a serum sodium level before the administration of desmopressin of ≥140 mmol/L, and in 13 of 87 cases (14.9%), with a level of 135-139 mmol/L, and was not measured in 5 hyponatremia cases. Patient characteristics that showed significant differences in the occurrence of hyponatremia included body weight, body mass index, renal function, and pretreatment serum sodium level. Regular monitoring of serum sodium is necessary for early detection of hyponatremia. CONCLUSIONS: Hyponatremia was the most common ADR when desmopressin orally disintegrating tablets were used to treat nocturia due to nocturnal polyuria over a 12-week period.

Greater cervical kyphosis during flexion increases the risk of kyphotic deformity after laminoplasty in patients with cervical spondylotic myelopathy.

Kyphotic deformity following the loss of cervical lordosis can lead to unfavourable neurological recovery after cervical laminoplasty (CLP); therefore, it is essential to identify its risk factors. Recent studies have demonstrated that the dynamic parameters of the cervical spine, based on baseline flexion/extension radiographs, are highly useful to estimate the loss of cervical lordosis after CLP. However, it remains unclear whether such dynamic parameters can predict kyphotic deformity development after CLP. Hence, the present study aimed to investigate whether the dynamic parameters could predict kyphotic deformity in patients with cervical spondylotic myelopathy (CSM) after CLP. This retrospective study included 165 patients, consisting of 10 and 155 patients with and without cervical kyphosis of C2-C7 angle ≤ -10° at the final follow-up period, respectively. Among the static and dynamic parameters of the cervical spine, greater cervical kyphosis during flexion (fC2-C7 angle) demonstrated the best discrimination between these two cohorts, with an optimal cutoff value of -27.5°. Meanwhile, greater gap range of motion (gROM = flexion ROM - extension ROM ) had the highest ability to predict a loss of ≥ 10° in C2-C7 angle after CLP, with an optimal cutoff value of 28.5°. This study suggests that in patients with CSM, fC2-C7 angle ≤ -25° on baseline radiographs is a potential risk for kyphotic deformity after CLP. In clinical practice, the patients with this criterion (fC2-C7 angle ≤ -25°) along with gROM ≥ 30° are at high risk of developing significant kyphotic deformity after CLP.

Ultrasonographic Evaluation of Upper Esophageal Sphincter for Dysphagia During the Acute Postoperative Phase of Anterior Cervical Surgery.

STUDY DESIGN: A retrospective study. OBJECTIVE: To verify the pathophysiology of dysphagia during the acute postoperative phase of anterior cervical surgery and to identify its predictive features, using ultrasonographic (US) examination for upper esophageal sphincter (UES). SUMMARY OF BACKGROUND DATA: There are no clinical studies investigating dysphagia after anterior cervical surgery, using US examination for UES. MATERIALS AND METHODS: We enrolled patients who underwent anterior cervical spine surgery between August 2018 and March 2022. Dysphagia was evaluated using the Eating Assessment Tool-10 (EAT-10) questionnaires. The US examination was performed preoperatively and 2 weeks postoperatively. Three US parameters for morphologic measurements (outer diameter, inner diameter, and muscle thickness) and 4 for functional measurements (displacement, time to relax, passing duration, and time to contract) were assessed. To verify the pathophysiology of postoperative dysphagia, we examined the change in the ratios of US parameters (=US parameter 2 weeks postoperatively /US parameter at baseline ) and the existence of significant correlations with change in the EAT-10 score (=EAT-10 2 weeks postoperatively -EAT-10 at baseline ). To identify the predictive features, the baseline US parameters were compared between dysphagia (+) and dysphagia (-) groups. RESULTS: A total of 46 patients (mean age, 61.3 y; 78.3% male) were included for analysis. A greater increase of the EAT-10 score after surgery was positively correlated with change ratios of the muscle thickness and time to contract and negatively with change ratio of the inner diameter. The dysphagia (+) group exhibited significantly greater inner diameter and smaller muscle thickness at baseline than the dysphagia (-) group. CONCLUSION: Dysphagia during the acute postoperative phase of anterior cervical surgery is caused by the physical narrowing of the inner lumen due to muscle thickening of the UES and sphincter contractile dysfunction. In addition, a baseline UES morphology characterized by a greater inner diameter and a thinner muscle layer is predictive of postoperative dysphagia.