Piceatannol Upregulates SIRT1 Expression in Skeletal Muscle Cells and in Human Whole Blood: In Vitro Assay and a Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Trial.

Piceatannol (PIC), a polyphenol abundant in passion fruit seeds, is reported to promote fat metabolism. This study investigated whether PIC affects sirtuin 1 (SIRT1) expression and metabolic factors in C2C12 skeletal muscle cells. C2C12 myotubes were stimulated with PIC, and alterations in gene expression, protein levels, mitochondrial DNA content, and fatty acid levels were assessed using real-time PCR, Western blotting, and Nile red staining. Furthermore, we examined changes in SIRT1 expression following the consumption of a test food containing 100 mg PIC for 2 weeks among adults with varying age and body mass index ranges. Both PIC and passion fruit seed extract induced SIRT1 expression in C2C12 myotubes to a greater extent than resveratrol. PIC also increased the expression of genes associated with mitochondrial biogenesis and fatty acid utilization, increased mitochondrial DNA content, and suppressed oleic acid-induced fat accumulation. Moreover, participants who consumed PIC exhibited significantly higher SIRT1 mRNA expression in whole blood compared to those in the placebo group. These findings suggest that PIC induces SIRT1 expression both in vitro and in the human body, which may promote mitochondrial biosynthesis and fat metabolism.

Ultrasound-guided central venous catheterization around the neck: Systematic review and network meta-analysis.

BACKGROUND: Ultrasound-guided central venous catheterization (CVC) has become the standard of care. However, providers use a variety of approaches, encompassing the internal jugular vein (IJV), supraclavicular subclavian vein (SupraSCV), infraclavicular subclavian vein (InfraSCV), proximal axillary vein (ProxiAV), distal axillary vein (DistalAV), and femoral vein. OBJECTIVE: This review aimed to compare the first-pass success rate and arterial puncture rate for different approaches to ultrasound-guided CVC above the diaphragm. METHODS: In May 2023, Embase, MEDLINE, CENTRAL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform were searched for randomized controlled trials (RCTs) comparing the 5 CVC approaches. The Confidence in Network Meta-Analysis tool was used to assess confidence. Thirteen RCTs (4418 participants and 13 comparisons) were included in this review. RESULTS: The SupraSCV approach likely increased the proportion of first-attempt successes compared to the other 4 approaches. The SupraSCV first-attempt success demonstrated risk ratios (RRs) > 1.21 with a lower 95% confidence interval (CI) exceeding 1. Compared to the IJV, the SupraSCV approach likely increased the first-attempt success proportion (RR 1.22; 95% confidence interval [CI] 1.06-1.40, moderate confidence), whereas the DistalAV approach reduced it (RR 0.72; 95% CI 0.59-0.87, high confidence). Artery puncture had little to no difference across all approaches (low to high confidence). CONCLUSION: Considering first-attempt success and mechanical complications, the SupraSCV may emerge as the preferred approach, while DistalAV might be the least preferable approach. Nevertheless, head-to-head studies comparing the approaches with the greatest first attempt success should be undertaken.

A case report of undetected cardiac arrest in a patient with an insertable cardiac monitor.

Insertable cardiac monitors (ICMs) are small electrocardiographs implanted subcutaneously to automatically record electrocardiograms when arrhythmia is detected in patients with syncope. If the ICM misses a significant arrhythmia, it may delay the diagnosis of arrhythmogenic syncope and put the patient at risk. Herein, we describe a case of undetected cardiac arrest in a patient with ICM. An 87-year-old man with syncope was admitted to the hospital. After 8 days of monitoring, the cause could not be determined, and an ICM was implanted. Nine hours after implantation, the patient experienced cardiopulmonary arrest. Despite a body surface electrocardiogram showing ventricular flatline and fibrillation, the ICM failed to record. The cause of failure to record was considered to be the fluctuation in the R-wave amplitude of the ICM and noise oversensing. In conclusion, albeit infrequently, ICMs might overlook life-threatening arrhythmias. Even in cases where the ICM fails to detect an arrhythmia matching the symptoms, it may not be feasible to entirely rule out the presence of arrhythmias. Learning objective: Insertable cardiac monitors (ICMs) are used to diagnose arrhythmogenic syncope. However, extremely infrequently, ICM may fail to record life-threatening arrhythmias. Failure to capture arrhythmias can happen due to an unfortunate combination of factors such as a low amplitude of the recorded R wave and noise. Even in cases where the ICM does not detect an arrhythmia that matches the symptoms, it may not be feasible to completely exclude the presence of arrhythmias.

Effectiveness of management protocol for insulin balls in diabetics: a scoping review.

Aim: In order to achieve good glycemic control, the prevention and management of insulin balls is important for diabetic patients during insulin therapy. However, insulin balls still occur within the clinical setting. This review evaluated the effectiveness of programs designed to manage insulin balls. Methods: A scoping review was conducted based on the Japanese and English literature available from a systematic literature search conducted from January 1964 to March 2022. Three databases were searched: PubMed, CINAHL, and Ichushi-Web. Results: A total of 33 articles met the inclusion criteria, which consisted of 3 for prevention management of insulin balls and 30 for management after the occurrence of insulin balls. Findings for prevention management suggested that the insulin injection technique education (avoidance of repeated injections to the same site) and providing knowledge (about insulin balls) prevented the appearance of insulin balls. As for post-occurrence management, insulin injection technique education (avoidance of injections to the insulin ball, avoidance of repeated injections to the same site, and switching the injection site) improved blood glucose control. Hypoglycemia was observed in all studies that included an assessment of hypoglycemia. None of the studies evaluated long-term effects of either preventive or post-occurrence management. Conclusions: Providing insulin injection technique education is an effective management protocol for insulin balls. Moreover, education about hypoglycemia is important for patients with insulin balls. Further studies to investigate the long-term effects in the management of insulin balls are needed.

[Introduction of a joint academic project between the Japan Academy of Nursing Science and the Japanese Pharmacological Society: a scoping review on assessment and preventive care of insulin balls].

Japanese Academy of Nursing Science (JANS) and the Japanese Pharmacological Society (JPS) have been conducting human interaction at each other's scientific meeting symposia in a home-and-away fashion since 2018. JANS and JPS have been working on a joint scientific project, "Scoping Review: Insulin Balls" since 2021. At the 95th Annual Meeting of the JPS held in 2022, we reported from a nursing perspective on the theme of "Assessment and preventive care of insulin balls from a scoping review". Subcutaneous injection into insulin balls has been reported to cause poor blood glucose control. Therefore, it is important to prevent insulin balls. In this study, we had the research questions, "What methods are available for assessment of the insulin injection site?" and "What is the care to prevent induration and how effective is it?" and conducted a scoping review. Regarding methods of injection site assessment, most of the literature identified the injection site by palpation, visual examination, and ultrasonography. About the preventive care, there were some reports of insulin balls occurring because patients have been injecting insulin at the same site, even though healthcare professionals instructed them to avoid the same site. Some of the literature had specific teaching methods such as hand site rotation and calendar injection method, and they were reported effective. In the future, we plan to proceed with the review including care after the development of insulin balls.

Crossover trial of the effects of a far-infrared heater that heats the feet with ceramic balls on autonomic nervous activity and mood states.

INTRODUCTION: The accumulation of fatigue and stress creates problems, including reductions in quality of life and productivity. OBJECTIVES: To investigate the effects of a far-infrared heater that heats the feet with ceramic balls on autonomic nervous activity and mood states. METHODS: This study was performed as a crossover trial. Participants comprised 20 women. On different days, each participant underwent 15 min of foot warming with the far-infrared heater (far-infrared group) or remained seated for 15 min (control group). Autonomic nervous activity (low-frequency component/high-frequency component, high-frequency) and mood states scales (Profile of Mood States Second Edition and Two-Dimensional Mood Scale for Self-monitoring and Self-regulation of Momentary Mood States) during the study intervention were measured and compared between groups. RESULTS: Low-frequency/high-frequency was significantly higher in the control group 10 min after the start of intervention than at baseline (P = .033). Low-frequency/high-frequency was significantly lower in the far-infrared group than in the control group at 5 min (P = .027), 10 min (P = .011), and 15 min (P = .015). High-frequency was significantly higher in the far-infrared group at 5 min (P = .008), 10 min (P = .004), and 15 min (P = .015) than at baseline. High-frequency 5 min after the start of intervention was significantly higher in the far-infrared group than in the control group (P = .033). POMS2 scores improved significantly more in the far-infrared group than in the control group, including in fatigue-inertia (P = .019), tension-anxiety (P = .025), and total mood disturbance (P = .019). Finally, the far-infrared group showed greater improvements in Two-Dimensional Mood Scale-Short Term scores such as stability (P = .002) and pleasure (P = .013). CONCLUSION: Using the far-infrared heater to heat the feet with ceramic balls stabilized and improved mood, reduced Fatigue-Inertia and Tension-Anxiety, and alleviated total mood disturbance. Parasympathetic nervous system activation was observed from 5 min after the start of heating, suggesting that short-duration heat stimulation of the feet is effective.

Development of a novel peptide inhibitor of subtilisin BPN'.

Proteinaceous protease inhibitors can strongly and specifically inhibit cognate proteases, but their use as pharmaceuticals is limited by their size. As such, the development of effective protease peptide inhibitors would be beneficial for biochemical studies and drug discovery. In this study, we applied a phage display system to select subtilisin BPN'-binding peptides and evaluated their inhibitory activities against subtilisin BPN'. A 12mer peptide with an intramolecular disulfide bond inhibited subtilisin BPN' (Ki value of 13.0 nm). Further mutational analyses of the peptide resulted in the development of a short peptide inhibitor against subtilisin BPN' that showed high inhibitory activity and binding affinity (Ki value of 0.30 nm). This activity was found to be derived from the conformational rigidity caused by the intramolecular disulfide bond and the small residue at the P1' site and from the interaction of the P4 and P6' residues with subtilisin BPN'.

Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing.

Perineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice. We first confirmed that aged mice (20-months) showed memory and plasticity deficits. They were able to retain or regain their cognitive ability when CSs were digested or PNNs were attenuated. We then explored the role of C6S in memory and neuroplasticity. Transgenic deletion of chondroitin 6-sulfotransferase (chst3) led to a reduction of permissive C6S, simulating aged brains. These animals showed very early memory loss at 11 weeks old. Importantly, restoring C6S levels in aged animals rescued the memory deficits and restored cortical long-term potentiation, suggesting a strategy to improve age-related memory impairment.

Baseline low-density lipoprotein cholesterol predicts the benefit of adding ezetimibe on statin in statin-naïve acute coronary syndrome.

We aimed to evaluate the effect of baseline low-density lipoprotein cholesterol (LDL-C) on the outcomes of patients with the acute coronary syndrome (ACS) receiving pitavastatin monotherapy or the combination of pitavastatin + ezetimibe. In the HIJ-PROPER study, 1734 ACS patients with dyslipidemia were randomly assigned to receive pitavastatin or pitavastatin + ezetimibe therapy. Statin-naïve participants (n = 1429) were divided into two groups based on the median LDL-C level (131 mg/dL) at enrollment. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina, and ischemia-driven coronary revascularization. The median follow-up was 3.2 years. In the < 131 mg/dL group (n = 686), LDL-C changes were - 34.0% and - 49.8% in the pitavastatin monotherapy and pitavastatin + ezetimibe-treated groups (P < 0.0001), respectively; in the ≥ 131 mg/dL group (n = 743), LDL-C changes were - 42.9% and - 56.4% (P < 0.0001, respectively. Kaplan-Meier analyses revealed that the primary endpoint was not significantly different between the treatment groups for the < 131 mg/dL group, however, it was significantly lower in patients treated with pitavastatin + ezetimibe in the ≥ 131 mg/dL group (Hazard ratio = 0.72, 95% confidence interval = 0.56-0.91, P = 0.007, P value for interaction = 0.012). Statin-naïve ACS patients with baseline LDL-C < 131 mg/dL did not clinically benefit from pitavastatin + ezetimibe, while patients with baseline LDL-C ≥ 131 mg/dL treated with pitavastatin + ezetimibe showed better clinical results than those treated with pitavastatin monotherapy.Clinical Trial Registration: Original HIJ PROPER study; URL: http://www.umin.ac.jp/ctr . Unique Identifier; UMIN000002742, registered as an International Standard Randomized Controlled Trial.

Constituent Characteristics and Functional Properties of Passion Fruit Seed Extract.

The genus Passiflora L. is widely cultivated in tropical and subtropical regions. The major species, Passiflora edulis Sims, is known as 'passion fruit' and is widely used in processed foods as well as eaten raw. P. edulis fruits are eaten for their pulp together with the seeds; however, the seeds are often discarded when used in processed foods. P. edulis seeds contain a variety of nutrients and functional components, and their industrial use is desirable from the perspective of waste reduction. Previous studies have analyzed the constituents of P. edulis and their physiological functions. P. edulis seeds contain various types of polyphenols, especially those rich in stilbenes (e.g., piceatannol). P. edulis seed extracts and isolated compounds from seeds have been reported to exhibit various physiological functions, such as antioxidant effects, improvement of skin condition, fat-burning promotion effects, and hypoglycemic effects. This review summarizes the nutritional characteristics, polyphenol content, and physiological functions of P. edulis seeds.

Semi-urgent pulmonary vein isolation using cryoballoon for haemodynamically unstable atrial fibrillation storm in a patient with low cardiac output syndrome: a case report.

BACKGROUND: Atrial fibrillation and heart failure are common coexisting conditions requiring hospitalisation for heart failure and death. Pulmonary vein isolation is a well-established option for symptomatic atrial fibrillation and for atrial fibrillation concomitant with heart failure with reduced left ventricular ejection fraction. Recently, pulmonary vein isolation using cryoballoon showed non-inferiority to radiofrequency ablation with respect to the treatment of patients with drug-refractory paroxysmal atrial fibrillation. However, the effectiveness of acute-phase rhythm control by semi-urgent pulmonary vein isolation using cryoballoon in patients with haemodynamically unstable atrial fibrillation storm accompanied with low cardiac output syndrome is unclear. Herein, we present a case in which semi-urgent pulmonary vein isolation using cryoballoon was effective for acute-phase rhythm control against drug-resistant and haemodynamically unstable repetitive atrial fibrillation tachycardia accompanied with low cardiac output syndrome. CASE PRESENTATION: A 57-year-old man was hospitalised for New York Heart Association functional class 4 heart failure with atrial fibrillation tachycardia and reduced left ventricular ejection fraction of 20% accompanied with low cardiac output syndrome-induced liver damage. The haemodynamics collapsed during atrial fibrillation tachycardia, which had become resistant to intravenous amiodarone and repeated electrical cardioversions. In addition to atrial fibrillation, atrial tachycardia and common-type atrial flutter appeared on day 3. Multiple organ failure progressed gradually due to haemodynamically unstable atrial fibrillation tachycardia storm accompanied with low cardiac output syndrome. On day 4, to focus on treatment of heart failure and multiple organ failure, semi-urgent rescue pulmonary vein isolation using cryoballoon to atrial fibrillation and cavotricuspid isthmus ablation to common-type atrial flutter were performed for acute-phase rhythm control. Soon after the ablation procedure, atrial fibrillation and common-type atrial flutter were lessened, and sinus rhythm was restored. A stable haemodynamics was successfully achieved with the improvement of hepatorenal function. The patient was discharged on day 77 without complications. CONCLUSIONS: This case demonstrates that acute-phase rhythm control by semi-urgent pulmonary vein isolation using cryoballoon could be a treatment option in patients with haemodynamically unstable atrial fibrillation tachycardia storm accompanied with low cardiac output syndrome, which is refractory to cardioversion and drug therapy.

[Survey on the Efficacy of Two Types of Medication Administration-assisting Food for Hospitalized Children].

The purpose of this study was to investigate the efficacy of two types of medication administration-assisting food. The subjects were 30 caregivers of children from one to eight years old hospitalized in the pediatrics unit of a university hospital, and 30 nurses caring for them. The caregivers gave medications to their children using two types of administration-assisting food, "chocolate" and "jelly". A questionnaire was prepared to investigate the efficacy of the administration-assisting food, and the caregivers and nurses responded to the questionnaire after the medication was given. The questionnaire data included many positive responses regarding the administration-assisting food, demonstrating its efficacy. The caregivers of children aged ≥4 years responded that the "chocolate" type was more effective than the "jelly" type in administering medications. There also tended to be a positive opinion of the "chocolate" among the nurses of children aged ≥4 years. However, the opinion of the "chocolate" and "jelly" were equivalent among the nurses of children aged <4 years. The reasons for these results were thought to be that the children were at an age when their sense of taste was developing and changing, plus correlations with past experience of the food and differences in the properties of the administration-assisting food. Easiness of swallowing of administration-assisting foods may be important for children whose taste is underdeveloped. However, the taste of administration-assisting foods may be important for children with taste development. Selecting administration-assisting foods based on these factors may be useful for the smooth administration of medication.

Effects of Intravenous Landiolol on Heart Rate and Outcomes in Patients with Atrial Tachyarrhythmias and Acute Decompensated Heart Failure: A Single-Center Experience.

OBJECTIVE: Atrial tachyarrhythmias (ATAs) lead to clinical deterioration and worsening heart failure (HF) in patients with acute decompensated HF (ADHF). We evaluated the effects of the ultrashort-acting intravenous ß1-blocker landiolol on the heart rate, hemodynamics, and outcome in patients with ATAs and ADHF. METHODS: A total of 67 consecutive hospitalized patients with ATAs and ADHF who were treated with landiolol (36 males, 67 ± 12 years) were included in this single-center retrospective study. The primary endpoints were changes in heart rate and systolic blood pressure from baseline during intravenous landiolol administration. The secondary endpoints included restoration of sinus rhythm and outcomes. RESULTS: The median maintenance dose of intravenous landiolol was 3.0 (range 1.0-12.0) µg/kg/min and the median treatment duration was 5 (range 1-24) days. Intravenous landiolol reduced heart rate (141 ± 17 beats/min at baseline to 99 ± 20 beats/min at 6 h, P < 0.001) without a marked reduction in blood pressure or deterioration of HF. During landiolol treatment, 15 (22%) patients had spontaneously restored sinus rhythm. Eight patients experienced in-hospital death, and 41 (69%) were discharged with sinus rhythm. During the follow-up of 16 ± 12 months, patients with sinus rhythm showed a lower frequency of rehospitalization due to worsening HF than patients with ATAs (5/41 vs. 7/18, P = 0.019). CONCLUSIONS: Our results showed that intravenous landiolol reduces the heart rate without markedly decreasing blood pressure in patients with ATAs and ADHF. Approximately 70% of the discharged patients were in sinus rhythm, and these patients showed a lower frequency of rehospitalization due to worsening HF (UMIN-CTR no. UMIN000033650).

Short-term outcome of percutaneous coronary intervention with directional coronary atherectomy followed by drug-coated balloon: a preliminary report.

Directional coronary atherectomy (DCA) is a unique technique used in percutaneous coronary intervention (PCI) which involves the removal of plaque from the coronary artery. Treatment with a drug-coated balloon (DCB) appears to be effective, especially when a predilatation of the lesion is performed appropriately. We hypothesize that the combination therapy of DCA with DCB is an effective strategy in PCI. PCI with DCA followed by DCB was performed for 23 patients from December 2014 to April 2017. All DCA procedures were performed under the guidance of intravascular ultrasound (IVUS) findings and all procedures were successfully performed without incurring major complications such as a coronary perforation. Plaque area (PA) was reduced from 77.3 ± 10.4% at baseline to 50.9 ± 9.2% after DCA and luminal cross-sectional area (CSA) after PCI was enlarged from 3.6 ± 1.8 to 9.3 ± 3.3 mm2. Follow-up coronary angiography (CAG) performed at 6-10 months showed no cases having incurred restenosis. Plaque area at follow-up CAG was 52.0 ± 8.5% and luminal CSA was 9.5 ± 2.1 mm2. There were no cases undergoing target vessel revascularization (TVR) and target lesion revascularization (TLR) during the follow-up periods. PCI with DCA followed by DCB might be an effective strategy for de novo lesions.

Author Correction: Evolution of host adaptation in the Salmonella typhoid toxin.

The original version of this Letter has been modified in the abstract and main text to better reflect the distribution of Neu5Ac sialoglycans in humans. Additionally, co-author Lingquan Deng's present address has been further clarified.

Evaluation of the Predictive Validity of Thermography in Identifying Extravasation With Intravenous Chemotherapy Infusions.

Early detection of extravasation is important, but conventional methods of detection lack objectivity and reliability. This study evaluated the predictive validity of thermography for identifying extravasation during intravenous antineoplastic therapy. Of 257 patients who received chemotherapy through peripheral veins, extravasation was identified in 26. Thermography was performed every 15 to 30 minutes during the infusions. Sensitivity, specificity, positive predictive value, and negative predictive value using thermography were 84.6%, 94.8%, 64.7%, and 98.2%, respectively. This study showed that thermography offers an accurate prediction of extravasation.

Evolution of host adaptation in the Salmonella typhoid toxin.

The evolution of virulence traits is central for the emergence or re-emergence of microbial pathogens and for their adaptation to a specific host 1-5 . Typhoid toxin is an essential virulence factor of the human-adapted bacterial pathogen Salmonella Typhi 6,7 , the cause of typhoid fever in humans 8-12 . Typhoid toxin has a unique A2B5 architecture with two covalently linked enzymatic 'A' subunits, PltA and CdtB, associated with a homopentameric 'B' subunit made up of PltB, which has binding specificity for the N-acetylneuraminic acid (Neu5Ac) sialoglycans 6,13 prominently present in humans 14 . Here, we examine the functional and structural relationship between typhoid toxin and ArtAB, an evolutionarily related AB5 toxin encoded by the broad-host Salmonella Typhimurium 15 . We find that ArtA and ArtB, homologues of PltA and PltB, can form a functional complex with the typhoid toxin CdtB subunit after substitution of a single amino acid in ArtA, while ArtB can form a functional complex with wild-type PltA and CdtB. We also found that, after addition of a single-terminal Cys residue, a CdtB homologue from cytolethal distending toxin can form a functional complex with ArtA and ArtB. In line with the broad host specificity of S. Typhimurium, we found that ArtB binds human glycans, terminated in N-acetylneuraminic acid, as well as glycans terminated in N-glycolylneuraminic acid (Neu5Gc), which are expressed in most other mammals 14 . The atomic structure of ArtB bound to its receptor shows the presence of an additional glycan-binding site, which broadens its binding specificity. Despite equivalent toxicity in vitro, we found that the ArtB/PltA/CdtB chimaeric toxin exhibits reduced lethality in an animal model, indicating that the host specialization of typhoid toxin has optimized its targeting mechanisms to the human host. This is a remarkable example of a toxin evolving to broaden its enzymatic activities and adapt to a specific host.