Thermostability and catechol-O-methyltransferase inhibitory activity of acylated anthocyanins from purple yam.

The thermostability of purple yam was investigated to be used as natural colorants. In addition, the inhibitory properties of purple yam and its isolated anthocyanins toward human catechol-O-methyltransferase (COMT), a key neurotransmitter involved in Parkinson's disease and depression, were also investigated. The thermostability of purple yam was higher than that of the reference samples (purple sweet potato and purple potato). Quantitative HPLC analysis revealed that alatanin A (2) contributed to the thermostability of purple yam. Methanol extracts of purple yam exhibited the highest COMT inhibitory activity of the tested samples. Alatanin D (1) showed the highest inhibitory activity of the anthocyanins in purple yam (IC50 19 µM). This study revealed the thermostability and COMT inhibitory activity of purple yam and may lead to its use not only as a thermostable natural source of colorants, but also for the prevention and treatment of Parkinson's disease and depression.

Developmental changes in the balance of glycolytic ATP production and oxidative phosphorylation in ventricular cells: A simulation study.

The developmental program of the heart requires accurate regulation to ensure continuous circulation and simultaneous cardiac morphogenesis, because any functional abnormalities may progress to congenital heart malformation. Notably, energy metabolism in fetal ventricular cells is regulated in a manner that differs from adult ventricular cells: fetal cardiomyocytes generally have immature mitochondria and fetal ventricular cells show greater dependence on glycolytic ATP production. However, although various characteristics of energy metabolism in fetal ventricular cells have been reported, to our knowledge, a quantitative description of the contributions of these factors to fetal ventricular cell functions has not yet been established. Here, we constructed a mathematical model to integrate various characteristics of fetal ventricular cells and predicted the contribution of each characteristic to the maintenance of intracellular ATP concentration and sarcomere contraction under anoxic conditions. Our simulation results demonstrated that higher glycogen content, higher hexokinase activity, and lower creatine concentration helped prolong the time for which ventricular cell contraction was maintained under anoxic conditions. The integrated model also enabled us to quantitatively assess the contributions of factors related to energy metabolism in ventricular cells. Because fetal cardiomyocytes exhibit similar energy metabolic profiles to stem cell-derived cardiomyocytes and those in the failing heart, an improved understanding of these fetal ventricular cells will contribute to a better comprehension of the processes in stem cell-derived cardiomyocytes or under pathological conditions.

Which cleansing care is better, foot bath or shower? Analysis of 236 limb ulcers.

Foot baths and showering are two widely used methods to cleanse limb ulcers. However, some clinicians warn that foot baths may contribute to the spread of infection at the ulcer site. This study aimed to retrospectively investigate the relationship between cleansing methods and the limb prognoses of 236 patients with chronic limb ulcers. These patients were divided into two groups according to the method used to cleanse their ulcers, foot bath and showering. Limb prognosis, including loss of all toes and major amputation, was retrospectively analysed. The rates of loss of all toes and major amputation were 53·0% and 30% in the foot bath group, and 35·3% and 18·4% in the showering group, respectively. The rates of loss of all toes (adjusted odds ratios = 2·07; P = 0·0066; 95% confidence intervals, 1·22-3·50) and major amputation (adjusted odds ratio = 1·90; P = 0·037; 95% confidence intervals, 1·03-3·50) were significantly higher in the foot bath group than those in the showering group. Our results demonstrate that showering is preferable to foot baths for the cleansing of chronic limb ulcers. Clinicians should be cautious that inappropriate cleansing may cause ulcer infections to spread.

Involvement of nitric oxide in the wound bed microcirculatory change during negative pressure wound therapy.

This study investigated the role of nitric oxide (NO) in the mechanism of blood flow increase in the wound bed during negative pressure wound therapy (NPWT). We developed an improved experimental model that allowed visualisation of the wound bed microcirculation under NPWT. Wounds were created on the mouse ear, taking care to preserve the subdermal vascular plexus, because the wound bed microcirculation was visualised using an intravital microscope system. We investigated whether application of a NO synthase inhibitor (N(G) -nitro-l-arginine methyl ester: L-NAME) might diminish the effect of the NPWT in increasing the wound blood flow. The experimental animals were divided into a negative pressure group (negative pressure of -125 mmHg applied to the wound for 5 minutes; n = 8), and a negative pressure plus L-NAME group (administration of L-NAME prior to application of the negative pressure; n = 8). In the negative pressure group, significant increase of blood flow was observed at 1 minute after the negative pressure application, which was sustained until 5 minutes. On the contrary, in the negative pressure plus L-NAME group, no significant changes were observed throughout the period of observation. These findings suggest that NO synthesis is involved in the wound bed microcirculatory change induced by NPWT.

Effect of mechanical forces on finger nail curvature: an analysis of the effect of occupation on finger nails.

BACKGROUND: We studied the relationship between mechanical force and nail curvature. METHODS: The effect of different frequencies and strengths of mechanical force on nail curvature was assessed. In Study 1, 63 carpenters and 63 office workers were enrolled, and the configurations of their thumb nails were assessed by measuring the curve index (defined as nail height/width) and pinch strength. In Study 2, nail curvature and pinch strength of jazz bassists, who characteristically do not use the right fourth and fifth fingers but use the left fifth finger a lot, were compared. In Study 3, the thumb nail curvature and pinch strength of the dominant and nondominant sides of the 126 participants from Study 1 were compared. RESULTS: Study 1: Carpenters had a significantly lower mean thumb nail curve index and higher mean pinch strength. Study 2: The nails of the unused right fourth and fifth fingers were much more curved than the nails of the frequently used left fourth and fifth fingers. The pinch strength of the right fifth finger was much weaker than the pinch strength of the left fifth finger. Study 3: The dominant side had a significantly lower nail curve index and higher pinch strength. CONCLUSION: The frequency and strength of mechanical forces on finger nails significantly affect nail appearance.

Elective use of an uncuffed small-bore cricothyrotomy tube with balloon occlusion of the subglottic airway.

PURPOSE: To conduct a qualitative observational study on positive pressure ventilation through a percutaneous uncuffed small-bore cricothyrotomy tube with balloon occlusion of the subglottic airway to minimize supraglottic leak. CLINICAL FEATURES: Ten consecutive procedures were performed in the nine men enrolled in this study. The demographics of the participants were: aged 50-73 yr, weight 48-87 kg, American Society of Anesthesiologists class I-II, and scheduled for endoscopic submucosal dissection via flexible endoscopy for en bloc resection of superficial meso- and hypopharyngeal cancer. The airway was initially secured with a supraglottic airway (SGA) under sevoflurane-based anesthesia, and a cricothyrotomy was then performed using a Portex(®) Minitrach II uncuffed cricothyrotomy tube (4-mm internal diameter). Following SGA removal, a Coopdech(®) bronchial blocker was orally or nasally inserted, and the balloon was inflated to occlude the trachea immediately beneath the glottis. The ventilator setting was initially based on observation of chest motion and end-tidal carbon dioxide tension and then readjusted according to arterial blood gas levels. All procedures were completed within a median time of 149 min. Effective ventilation was achieved in all patients despite mild hypercapnia (PaCO2 of 58 mmHg at maximum) in some patients. SpO2 levels were maintained at ≥ 98%. CONCLUSION: This technique provides effective intraoperative ventilation and easy endoscopic access, and it countermeasures against the likely complication of postoperative laryngeal edema. Moreover, there is no need for conventional tracheostomy or prolonged intubation. This approach establishes a curative and less invasive pharyngeal cancer therapy. Certain adverse outcomes can be avoided, including impaired speech and swallowing, possible delayed closure of the stoma, or a compromised cosmetic outcome.

[Determination of the critical time point for efficacy of L-arginine infusion therapy in a case of MELAS with frequent stroke-like episodes].

MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) is the most representative subtype of mitochondrial diseases. Administration of L-arginine (L-Arg) or a precursor of nitric oxide (NO) has been proposed as a promising medication for MELAS because one of the pathophysiological mechanisms is supposedly a decreased capacity for NO-dependent vasodilation. We experienced a girl with MELAS and frequent stroke-like episodes who was treated with L-Arg infusion. We evaluated the efficacy of L-Arg infusion therapy based on whether her headache and nausea were disappeared and neurological symptoms were improved within 24 hours of L-Arg administration. L-Arg infusions were effective in all four episodes when the treatment was started within 4 hours of the onset of stroke-like episodes. On the other hand, the infusion was effective in only one out of five episodes when the medication was delayed by more than 4 hours after the onset. Furthermore, the early administration of L-Arg resulted in better outcomes regarding new lesions determined by brain MRI. Our data suggest that L-Arg infusion may be most effective when it is started within 4 hours of the onset of neurological symptoms in the acute phase of MELAS. The study of a large number of episodes in many patients will be needed to determine the critical time point of L-Arg administration after the onset of the acute phase of MELAS.

[Case of delayed awakening after remifentanil leakage out of a vein].

We report a case of delayed awakening with characteristic repeated loss of consciousness after remifentanil infusion complicated by leakage from an intravenous catheter. A 30-year-old male underwent microlaryngeal surgery for a vocal cord polyp. During anesthetic induction, infiltration from an intravenous (IV) line in the left forearm was observed 10 min after initiating a continuous infusion of remifentanil 0.5 microg x kg-1 x min -1. A second peripheral IV catheter was placed in the right forearm and general anesthesia was induced with remifentanil infusion at 0.3 microg x kg-1 x min- 1, propofol 120mg, fentanyl 100 microg, and rocuronium 70 mg. Anesthesia was maintained with remifentanil 0.05-0.3 microg x kg-1 x min -1and sevoflurane (1.5% in oxygen) for the 4 min of surgery. A few minutes after tracheal extubation, the patient developed respiratory arrest and loss of consciousness. We immediately ventilated him with a bag-valve-mask and administered naloxone 0.04 mg. Thereafter, he repeatedly awoke and was drowsy three times over the next 5hr. It was followed by an uneventful postoperative period. No remarkable deficit was observed in the patient. Blood gases, electrolytes, glucose values, and body temperature were within normal ranges throughout the perioperative period. Brain computed tomography, mag- netic resonance imaging, and electroencephalography showed no abnormalities. It was considered that the incidental subcutaneous remifentanil accumulation may have caused the respiratory suppression and delayed awakening.

[Sibling cases of severe infantile form of nemaline myopathy with ACTA1-gene mutation].

Severe infantile form of nemaline myopathy is clinically characterized by marked muscle hypotonia and weakness with respiratory and feeding difficulties since infancy. Recently, mutations in the skeletal muscle alpha-actine gene (ACTA1) have been identified in many patients with the nemaline myopathy. We experienced two cases of severe infantile form of nemaline myopathy with ACTA1 mutation (missence heterozygous mutation;c.553C>T, p.R185C) in siblings presenting with different clinical symptoms and courses. The elder brother was a typical "floppy infant" at birth. Because he could not suck and swallow at all, he was fed completely through a nasogastric tube. At 2 months of age, he developed respiratory insufficiency and was placed on a respirator all day. He was diagnosed with having nemaline myopathy from his muscle biopsy, which revealed marked variation in muscle fiber size with large numbers of nemaline bodies on Gomori-trichrome stain. In contrast, the younger brother presented with mild muscular hypotonia and feeding difficulty during the neonatal stage;therefore, he was partly fed through a nasogastric tube. At 2 months of age, he was admitted to our hospital because of respiratory distress, and he required nasal continuous positive airway pressure with oxygen followed by noninvasive positive pressure ventilation intermittently, mainly at night. He was followed at his home by parents with no serious problems;however he unexpectedly died at the age of 15 months. Although most cases of severe infantile form of nemaline myopathy caused by ACTA1 mutations are sporadic and have no family history, we emphasize that clinical symptoms are variable in siblings with the same mutation.

Posterior reversible encephalopathy syndrome associated with mild COVID-19 infection in a 9-year-old child: A case report and literature review.

The neurologic complications associated with the coronavirus disease 2019 (COVID-19) is becoming more prevalent in children after the appearance of the Omicron strain. An association between COVID-19 and posterior reversible encephalopathy (PRES) has been consistently reported in adults, but little information is available in the pediatric age group. There are only few case reports of COVID-19-related PRES in children, and all of these patients were either on some type of immunomodulatory medications or whose general condition was severe. The present case, a 9-year-old Japanese boy, who had no fever but vomited several times from days 1-4 of a COVID-19 infection had an afebrile seizure on the 8th day of his illness. The patient had no history of hypertension, and had not previously been administered any immunosuppressive drugs before or during the period of his COVID-19 infection. On admission, his physical findings were unremarkable, except for a high blood pressure. The results obtained by brain computed tomography and magnetic resonance imaging were consistent with PRES. The patient recovered with no sequelae after treatment with antihypertensive drugs. Further investigations did not suggest any underlying disease that could have caused the transient hypertension. Although PRES is relatively rare in children, pediatricians should keep in mind that this syndrome can be complicated, even in children with mild COVID-19 infections.

Nicotinamide mononucleotide (NMN) alleviates the poly(I:C)-induced inflammatory response in human primary cell cultures.

NMN is the direct precursor of nicotinamide adenine dinucleotide (NAD+) and is considered as a key factor for increasing NAD+ levels and mitochondrial activity in cells. In this study, based on transcriptome analysis, we showed that NMN alleviates the poly(I:C)-induced inflammatory response in cultures of two types of human primary cells, human pulmonary microvascular endothelial cells (HPMECs) and human coronary artery endothelial cells (HCAECs). Major inflammatory mediators, including IL6 and PARP family members, were grouped into coexpressed gene modules and significantly downregulated under NMN exposure in poly(I:C)-activated conditions in both cell types. The Bayesian network analysis of module hub genes predicted common genes, including eukaryotic translation initiation factor 4B (EIF4B), and distinct genes, such as platelet-derived growth factor binding molecules, in HCAECs, which potentially regulate the identified inflammation modules. These results suggest a robust regulatory mechanism by which NMN alleviates inflammatory pathway activation, which may open up the possibility of a new role for NMN replenishment in the treatment of chronic or acute inflammation.

Influence of mechanical forces as a part of nail configuration.

BACKGROUND: Clinicians encounter pincer nails at a high incidence among bedridden cases who are free from weight bearing. The mechanical force transmitted by walking and loading may affect the nail configuration. This study was aimed at evaluating the influence of mechanical forces on the nail configuration. METHODS: Study 1 was conducted on a sample size of 318 great toenails, with the subjects classified into the following 3 groups: healthy volunteers, participants who were bedridden for less than 3 months, and participants who were bedridden for more than 3 months. Study 2 was conducted in 12 subjects with unilateral loading. ASSESSMENTS: The configuration of the great toenails, in terms of the curve index (defined as the nail height/nail width), was compared. RESULTS: In study 1, the curve index increased significantly as the duration of the bedridden state became longer (17.5 ± 4.75, 28.9 ± 11.0, 36.4 ± 9.58, respectively). In study 2, the curve index on the nonloaded side was significantly higher than that on the loaded side (40.0 ± 8.63 vs. 27.0 ± 8.39). CONCLUSION: Our results suggest that mechanical forces may affect the nail configuration and be involved in the pathophysiology of nail deformities.

Erratic and blood vessel-guided migration of astrocyte progenitors in the cerebral cortex.

Astrocytes are one of the most abundant cell types in the mammalian brain. They play essential roles in synapse formation, maturation, and elimination. However, how astrocytes migrate into the gray matter to accomplish these processes is poorly understood. Here, we show that, by combinational analyses of in vitro and in vivo time-lapse observations and lineage traces, astrocyte progenitors move rapidly and irregularly within the developing cortex, which we call erratic migration. Astrocyte progenitors also adopt blood vessel-guided migration. These highly motile progenitors are generated in the restricted prenatal stages and differentiate into protoplasmic astrocytes in the gray matter, whereas postnatally generated progenitors do not move extensively and differentiate into fibrous astrocytes in the white matter. We found Cxcr4/7, and integrin ß1 regulate the blood vessel-guided migration, and their functional blocking disrupts their positioning. This study provides insight into astrocyte development and may contribute to understanding the pathogenesis caused by their defects.

Acrodysostosis and pseudohypoparathyroidism (PHP): adaptation of Japanese patients with a newly proposed classification and expanding the phenotypic spectrum of variants.

Objective: This study aimed to report on 15 Japanese patients with acrodysostosis and pseudohypoparathyroidism (PHP) and analyze them using the newly proposed classification of the EuroPHP network to determine whether this classification system is suitable for Japanese patients. Design: We divided the patients into three groups based on hormone resistance, the number of fingers with short metacarpals, the existence of cone-shaped epiphyses and gene defects. Methods: We carried out clinical, radiological and genetic evaluations of two patients in group A (iPPSD5), six patients in group B (iPPDS4) and seven patients in group C (iPPSD2). Results: Group A consisted of two siblings without hormone resistance who had the most severe bone and physical developmental delays. PDE4D gene defects were detected in both cases. Group B consisted of six patients who showed hormone resistance without hypocalcemia. Short metacarpal bones with corn-shaped epiphyses were observed in all patients. In two cases, PRKAR1A gene defects were detected; however, their clinical and radiological features were not identical. The facial dysmorphism and developmental delay were less severe and PRKAR1A gene defects were detected in case B-3. Severe facial dysmorphism and deformity of metacarpal bones were observed, but no gene defect was detected in case B-1. Group C consisted of seven patients with PHP1a, four of whom had maternally inherited heterozygous inactivating mutations in one of the GNAS genes. The clinical and radiological features of the patients in group C were not identical either. Conclusions: The newly proposed classification is suitable for Japanese patients; however, heterogeneities still existed within groups B and C.

Efficacy of sodium-glucose cotransporter 2 inhibitor with glucagon-like peptide-1 receptor agonist for the glycemic control of a patient with Prader-Willi syndrome: a case report.

Prader-Willi syndrome (PWS) is often related to severe obesity and diabetes mellitus (DM). Clinical findings suggesting the benefits of glucagon-like peptide-1 (GLP-1) receptor agonists for glycemic control of DM in PWS have been recently increasing. However, there are only a few reports describing the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors for PWS. We present a diabetic female with PWS, whose glycemic control was deteriorated at the age of 19 but improved to a certain extent by introducing the GLP-1 analog liraglutide. At the age of 20, the SGLT2 inhibitor empagliflozin was administered. Subsequently, her HbA1c level and body weight markedly decreased. Improvement in both insulin resistance and secretion was observed during the subsequent six months. In addition to GLP-1 receptor agonists, SGLT2 inhibitors may be a potential approach for the management of DM in PWS, especially in young patients whose pancreatic insulin secretion capabilities are still preserved.

Noncontact Phased-Array Ultrasound Facilitates Acute Wound Healing in Mice.

BACKGROUND: The authors developed a noncontact low-frequency ultrasound device that delivers high-intensity mechanical force based on phased-array technology. It may aid wound healing because it is likely to be associated with lower risks of infection and heat-induced pain compared with conventional ultrasound methods. The authors hypothesized that the microdeformation it induces accelerates wound epithelialization. Its effects on key wound-healing processes (angiogenesis, collagen accumulation, and angiogenesis-related gene transcription) were also examined. METHODS: Immediately after wounding, bilateral acute wounds in C57BL/6J mice were noncontact low-frequency ultrasound- and sham-stimulated for 1 hour/day for 3 consecutive days (10 Hz/90.6 Pa). Wound closure (epithelialization) was recorded every 2 days as the percentage change in wound area relative to baseline. Wound tissue was procured on days 2, 5, 7, and 14 (five to six per time point) and subjected to histopathology with hematoxylin and eosin and Masson trichrome staining, CD31 immunohistochemistry, and quantitative polymerase-chain reaction analysis. RESULTS: Compared to sham-treated wounds, ultrasound/phased-array-treated wounds exhibited significantly accelerated epithelialization (65 ± 27 percent versus 30 ± 33 percent closure), angiogenesis (4.6 ± 1.7 percent versus 2.2 ± 1.0 percent CD31 area), and collagen deposition (44 ± 14 percent versus 28 ± 13 percent collagen density) on days 5, 2, and 5, respectively (all p < 0.05). The expression of Notch ligand delta-like 1 protein (Dll1) and Notch1, which participate in angiogenesis, was transiently enhanced by treatment on days 2 and 5, respectively. CONCLUSIONS: The authors' noncontact low-frequency ultrasound phased-array device improved the wound-healing rate. It was associated with increased early neovascularization that was followed by high levels of collagen-matrix production and epithelialization. The device may expand the mechanotherapeutic proangiogenesis field, thereby helping stimulate a revolution in infected wound care.