Megahertz repetition rate-based lock-in detection scheme for rapid data acquisition in terahertz time domain spectroscopy.

We report a fast pump modulation scheme in a terahertz time domain spectroscopy (THz-TDS) system by utilizing the intensity modulation from the megahertz repetition rate of the pump pulse for lock-in detection. In conventional THz-TDS, the modulation required for the high signal-to-noise ratio lock-in detection is achieved through the use of an optical chopper or an AC bias. Here, we propose the use of an electro-optic modulator (EOM), operated as a pulse picker, to vary the repetition rate of the pump pulse, relative to the probe pulse, allowing us to directly use the megahertz laser repetition rate as the reference modulation frequency for lock-in detection. Our proposed scheme is applicable to all types of pulsed THz emitters, including those that cannot be electronically biased. Since the maximum allowable modulation frequency is limited only by the laser repetition rate and/or by the bandwidth of the EOM, megahertz modulation rates, and, consequently, rapid data acquisition times, become possible. Using our technique, we were able to detect an oscillating signal with frequencies up to 10 kHz, using ∼1 µs integration time per point, ∼100× faster than previously reported values for THz-TDS systems.

Contrast Injection from an Intermediate Catheter Placed in an Intradural Artery is Associated with Contrast-Induced Encephalopathy following Neurointervention.

BACKGROUND AND PURPOSE: Contrast-induced encephalopathy can result from neurotoxicity of contrast medium in the affected area. The development of intermediate catheters has allowed guidance of catheters to more distal arteries. This study focused on the association between contrast-induced encephalopathy and contrast injection from an intermediate catheter guided into a distal intradural artery during neurointervention for cerebral aneurysms. MATERIALS AND METHODS: We retrospectively reviewed 420 consecutive aneurysms in 396 patients who underwent neurointervention for extracranial aneurysms and unruptured intracranial aneurysms at our institution from February 2012 to January 2023. Patients were divided into a group with contrast-induced encephalopathy and a group without. To identify risk factors for contrast-induced encephalopathy, we compared clinical, anatomic, and procedural factors between groups by multivariate logistic regression analysis and stepwise selection. RESULTS: Among the 396 patients who underwent neurointervention for cerebral aneurysms, 14 (3.5%) developed contrast-induced encephalopathy. Compared with the group without contrast-induced encephalopathy, the group with contrast-induced encephalopathy showed significantly higher rates of patients on hemodialysis, previously treated aneurysms, intradural placement of a catheter for angiography, nonionic contrast medium, and flow-diversion procedures in univariate analyses. Stepwise multivariate logistic regression analysis revealed intradural placement of a catheter for angiography (OR = 40.4; 95% CI, 8.63-189) and previously treated aneurysms (OR = 8.20; 95% CI, 2.26-29.6) as independent predictors of contrast-induced encephalopathy. CONCLUSIONS: Contrast injection from an intradural artery and retreatment of recurrent aneurysms were major risk factors for contrast-induced encephalopathy. Attention should be paid to the location of the intermediate catheter for angiography to avoid developing contrast-induced encephalopathy.

Impact of the Comprehensive Awareness Modification of Mouth, Chewing and Meal (CAMCAM) Program on the Attitude and Behavior Towards Oral Health and Eating Habits as Well as the Condition of Oral Frailty: A Pilot Study.

OBJECTIVES: Preserving sufficient oral function and maintaining aadequate nutrition are essential for preventing physical frailty and the following long-term care. We recently developed the 6-month Comprehensive Awareness Modification of Mouth, Chewing And Meal (CAMCAM) program, in which participants gather monthly to learn about oral health and nutrition while eating a textured lunch together. This study examined whether the CAMCAM program could improve attitude and behavior towards oral health, mastication, and diet as well as ameliorate oral frailty in community-dwelling older adults. DESIGN: Single-arm pre-post comparison study. SETTING AND PARTICIPANTS: A total of 271 community-dwelling adults (72.3 ± 5.7 years of age; 159 women [58.7%]) in 4 Japanese municipalities were recruited, of which 249 participants (92%) were assessed at the final evaluation. INTERVENTION: Participants gathered once a month at community centers to learn about oral health and nutrition while eating a "munchy" textured lunch containing proper nutrition. MEASUREMENTS: Oral frailty, frailty, and eating behavior were evaluated with the Oral Frailty Index-8 (OFI-8), Kihon checklist (KCL), and CAMCAM checklist, respectively. Participants were divided into Oral frailty (OF) and Robust groups according to OFI-8 scores. The differences in KCL and CAMCAM checklist results between the OF and Robust groups were statistically tested along with changes in scores after the program. RESULTS: KCL and CAMCAM checklist scores were significantly lower in the OF group at the initial assessment. OFI-8 and KCL findings were significantly improved in the OF group after completing the program (all P <0.05). Regarding the CAMCAM checklist, awareness of chewing improved significantly in the Robust group (P=0.009), with a similar tendency in the OF group (P=0.080). CONCLUSION: The findings of this pilot study suggest that the CAMCAM program may improve both oral and systemic frailty in addition to attitudes towards chewing, oral health, and meals, especially in individuals with oral frailty. The CAMCAM program merits expansion as a community-based frailty prevention program.

High-frequency spin torque oscillation in orthogonal magnetization disks with strong biquadratic magnetic coupling.

In this study, we numerically investigate the spin transfer torque oscillation (STO) in a magnetic orthogonal configuration by introducing a strong biquadratic magnetic coupling. The orthogonal configuration consists of top and bottom layers with in-plane and perpendicular magnetic anisotropy sandwiching a nonmagnetic spacer. The advantage of an orthogonal configuration is the high efficiency of spin transfer torque leading a high STO frequency; however, maintaining the STO in a wide range of electric current is challenging. By introducing biquadratic magnetic coupling into the orthogonal structure of FePt/spacer/Co90Fe10, Ni80Fe20 or Ni, we were able to expand the electric current region in which the stable STO is realized, resulting in a relatively high STO frequency. For example, approximately 50 GHz can be achieved in an Ni layer at a current density of 5.5 × 107 A/cm2. In addition, we investigated two types of initial magnetic state: out-of-plane and in-plane magnetic saturation; this leads to a vortex and an in-plane magnetic domain structure after relaxation, respectively. The transient time before the stable STO was reduced to between 0.5 and 1.8 ns by changing the initial state from out-of-plane to in-plane.

Poor Health Behaviors among Housebound Japanese Community-Dwelling Older Adults Due to Prolonged Self-Restraint during the First COVID-19 Pandemic: A Cross-Sectional Survey.

BACKGROUND: Prolonged self-restraining behaviors induced by the coronavirus disease 2019 (COVID-19) pandemic's containment measures can limit various positive health behaviors. OBJECTIVE: We examined the decline in going-out and certain other positive health behaviors and investigated the relationship between excessive decreases in going-out frequency and declining engagement in positive health behaviors among community-dwelling older adults during the self-restraint period. DESIGN: This study employed a cross-sectional survey design. SETTING: This study was conducted in Nishi Tokyo City, Tokyo, Japan. PARTICIPANTS: The participants were 294 respondents (150 women) aged 50 years and older who lived in public housing that were permitted to be surveyed during the self-restraint period. MEASUREMENTS: Their pre-pandemic going-out frequency around February 2020 and going-out frequency during the self-restraint period starting in April 2020 were reported. We mainly assessed the existence of home health behaviors (i.e., exercise, in-person and phone conversations, and healthy diet). A self-report questionnaire was used to obtain data. RESULTS: Going-out frequency decreased in 41.2% of the 294 respondents owing to the government's request for self-restraint. In total, 13 individuals had been going out less than one time per week (housebound) before the request. Of the 281 people who were not housebound before the government's self-restraint request, 13.9% were newly housebound. Newly housebound individuals were 5.3 times less likely to exercise, had 2.1 times fewer social contacts, and 2.6 times less balanced or healthy diets than those who maintained their frequency of going out. CONCLUSIONS: Prolonged self-restraint due to the COVID-19 pandemic may lead to housebound status and poor health behaviors. Public health intervention is needed to prevent excessive self-restraint, along with new measures integrating information and communication technologies to enable older adults to live active lives.

Utility of 5-aminolaevulinic acid fluorescence-guided endoscopic biopsy for malignant mesothelioma in a cat and dog.

Malignant mesothelioma (MM) is uncommon in cats and dogs and can be challenging to diagnose. Adequate tissue sampling is required for superior diagnostic accuracy. Protoporphyrin IX, a metabolite of 5-aminolaevulinic acid (5-ALA), is a photosensitiser for photodynamic diagnosis (PDD). To the best of our knowledge, no study has reported the use of 5-ALA-PDD to detect MM in veterinary medicine. The present study describes the use of 5-ALA-PDD for MM diagnosis in a cat and dog, as well as the effectiveness of intracavitary chemotherapy. We evaluated the use of PDD with 5-ALA hydrochloride (5-ALA-PDD) in two cases of MM. A 12-year-old cat presented with a 1-month history of respiratory distress, and a 9-year-old dog presented with a 3-month history of mild abdominal distention. We endoscopically biopsied lesions in both the cases using 5-ALA-PDD. Histopathological examination revealed mesothelioma, and immunohistochemical staining was positive for calretinin. Both patients were treated with carboplatin. The cat died of respiratory failure. Although, the dog's condition improved 21 days after the first chemotherapeutic drug administration, the dog died on day 684 owing to cardiac-related issues. 5-ALA-PDD is thus, safe and feasible for the diagnosis of MM in veterinary medicine.

Ascending palatine branch from the lingual artery with multiple other variations of the external carotid artery.

The external carotid artery (ECA) is the major blood supply for structures in the head and neck. Typically, it has 8 separate branches; but there are many anatomical variations, making it difficult to predict surgical outcomes and complications without 3-dimensional imaging. This case study focuses on a cadaver with multiple anatomical variations in the ECA, i.e., lingual, facial, occipital, ascending pharyngeal, and posterior auricular arteries, found during routine dissection of the right cadaveric neck. We also discuss the incidences of several other anatomical variations of the ECA branches and their surgical implications and potential complications.

Enteric viruses replicate in salivary glands and infect through saliva.

Enteric viruses like norovirus, rotavirus and astrovirus have long been accepted as spreading in the population through fecal-oral transmission: viruses are shed into feces from one host and enter the oral cavity of another, bypassing salivary glands (SGs) and reaching the intestines to replicate, be shed in feces and repeat the transmission cycle1. Yet there are viruses (for example, rabies) that infect the SGs2,3, making the oral cavity one site of replication and saliva one conduit of transmission. Here we report that enteric viruses productively and persistently infect SGs, reaching titres comparable to those in the intestines. We demonstrate that enteric viruses get released into the saliva, identifying a second route of viral transmission. This is particularly significant for infected infants, whose saliva directly transmits enteric viruses to their mothers' mammary glands through backflow during suckling. This sidesteps the conventional gut-mammary axis route4 and leads to a rapid surge in maternal milk secretory IgA antibodies5,6. Lastly, we show that SG-derived spheroids7 and cell lines8 can replicate and propagate enteric viruses, generating a scalable and manageable system of production. Collectively, our research uncovers a new transmission route for enteric viruses with implications for therapeutics, diagnostics and importantly sanitation measures to prevent spread through saliva.

Social Detachment Influenced Muscle Mass and Strength during the COVID-19 Pandemic in Japanese Community-Dwelling Older Women.

Social detachment due to coronavirus disease (COVID-19) has caused a decline in physical activity, leading to sarcopenia and frailty in older adults. This study aimed to compare muscle mass, strength, and function values in older women before and after the first wave of the COVID-19 pandemic (April-May 2020). Furthermore, changes in muscle measures across women who experienced different levels of impact on their social participation due to the COVID-19 pandemic were examined. Muscle mass (total, trunk, and appendicular muscle), grip strength, oral motor skills, social interactions (social network and participation), and social support were assessed in 46 Japanese community-dwelling older women (mean, 77.5 y; range 66-93 y) before and after the first wave of the COVID-19 pandemic. Trunk muscle mass significantly decreased after the first wave of the pandemic. When comparing changed values between the enhanced/maintained and reduced group during the pandemic, significant group difference was observed in trunk muscular mass, grip strength, and oral motor skills. Intriguingly, those who enhanced social participation had a positive change of grip strength values, showing that social participation might influence muscle function during the COVID-19 pandemic.

Long-term outcomes of hemostatic therapy for variceal bleeding and the challenge pending in the post-direct-acting antivirals era.

Background and study aims: This study evaluated the longterm outcomes of mainly endoscopic hemostatic therapy for gastrointestinal variceal bleeding and of the transition of hemostatic therapy. Patients and methods: Among 1,163 patients treated for gastrointestinal varices between April 2006 and June 2020, a total of 125 patients who underwent emergency hemostatic therapy were enrolled. Survival rates and secondary evaluation points were analyzed. Additionally, patients were classified into two groups: the previous and latter term. Patients' background, therapeutic method, and treatment results were compared between the groups. Results: 94.4% had cirrhosis. The average Child-Pugh score was 8.90. Successful primary hemostasis rate was 98.4%, and 5.6% died within 2 weeks, all with a Child-Pugh score ≥9. The respective 1- and 5-year survival rates for Child-Pugh grade A/B were 81.3% and 55.4%, while those for Child-Pugh grade C were 58.1% and 17.8%. Child-Pugh grade C or hepatocellular carcinoma was significantly associated with poor prognosis. In total, 21.6% experienced variceal re-bleeding; 62.9% of these cases were triggered by continued alcohol consumption. There was no significant difference in survival between patients with and without variceal re-bleeding and in post-treatment survival between the previous and latter terms. In the latter term, the number of cases caused by continued alcohol consumption significantly increased. Conclusions: Multidisciplinary treatment and continuation of proper management after hemostatic therapy for variceal bleeding are crucial. Continued alcohol consumption leads to variceal bleeding and re-bleeding; its proper management, including alcohol abstinence, is one of the major challenges left in the post-directacting antivirals era.

Structure-activity relationships of antifungal phenylpropanoid derivatives and their synergy with n-dodecanol and fluconazole.

trans-Anethole (anethole) is a phenylpropanoid; with other drugs, it exhibits synergistic activity against several fungi and is expected to be used in new therapies that cause fewer patient side effects. However, the detailed substructure(s) of the molecule responsible for this synergy has not been fully elucidated. We investigated the structure-activity relationships of phenylpropanoids and related derivatives, with particular attention on the methoxy group and the double bond of the propenyl group in anethole, as well as the length of the p-alkyl chain in p-alkylanisoles. Antifungal potency was largely related to p-alkyl chain length and the methoxy group of anethole, but not to the double bond of its propenyl group. Production of reactive oxygen species also played a role in these fungicidal activities. Inhibition of drug efflux was associated with the length of the p-alkyl chain and the double bond of the propenyl group in anethole, but not with the methoxy group. Although a desirable synergy was observed between n-dodecanol and anethole or p-alkylanisoles with a length of C2-C6 in alkyl chains, it cannot be explained away as being solely due to the inhibition of drug efflux. Similar results were obtained when phenylpropanoid derivatives were combined with fluconazole against Candida albicans.

Sensitivity analysis in a radiological impact assessment of a nuclear power plant discharge. A comparison of the Morris, Spearman and Sobol' approaches.

This paper compares the Morris, Spearman and Sobol' methods of sensitivity analysis in radiological risk assessment. The determination of the most influential parameters on model with regards to the propagation of their uncertainties to output variables, is of greatest interest. This study aims to determine the relative importance of parameters uncertainties on the dose calculation uncertainty in the framework of a scenario of routine discharges discussed in the context of an IAEA working group. The scenario considers atmospheric and liquid discharges of three different types of radionuclides (14C, tritium as HTO and 110mAg) from a nuclear power plant located by the side of a river. It is concluded that the most reliable and practical method according to the ability of ranking influential parameters and the easiness of its application is the Spearman method. As key result, the three first influential variables for annual total dose for all pathways and all radionuclides were the water dissolved inorganic carbon concentration, the volatilisation rate constant and the soil layer solid liquid distribution in 14C.

Mass Equilibration and Fluctuations in the Angular Momentum Dependent Dynamics of Heavy Element Synthesis Reactions.

Mass and angle distributions for the ^{52}Cr+^{198}Pt and ^{54}Cr+^{196}Pt reactions (both forming ^{250}No) were measured and subtracted, giving new information on fast quasifission mass evolution, and the first direct determination of the dependence of sticking times on angular momentum. TDHF calculations showed good agreement with average experimental values, but experimental mass distributions unexpectedly extended to symmetric splits while the peak yield remained close to the initial masses. This implies a strong role of fluctuations in mass division early in the collision, giving insights into the transition from fast energy dissipative deep-inelastic collisions to quasifission.

Enarodustat to treat anemia in chronic kidney disease.

Anemia is a common complication in patients with chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs) are the standard therapy for anemia in CKD. It has been expected that hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibition may have the potential to provide therapeutic benefits over pre-existing ESAs for anemia in CKD. Enarodustat (JTZ-951) is an oral HIF-PH inhibitor. In preclinical studies, enarodustat has been found to increase HIF-alpha proteins, erythropoietin production and erythropoiesis. Enarodustat also shows efficient iron utilization in iron-related parameters during erythropoiesis. Clinical trials have shown that enarodustat improved anemia both in non-dialysis-dependent CKD patients and dialysis patients. The safety results in clinical trials demonstrate that enarodustat is generally well tolerated. On the basis of these results, enarodustat was approved in September 2020 in Japan for the treatment of anemia associated with CKD. This manuscript will review enarodustat, its pharmacological characteristics in preclinical studies, and its efficacy and safety in clinical trials with anemic patients in CKD.

Effects of H3 and H4 histones acetylation and bindings of CREB binding protein and p300 at the promoter on hepatic expression of gamma-glutamyltransferase gene in a streptozotocin-induced moderate hypoinsulinemic rat model.

Gamma-glutamyltransferase (GGT), a marker of liver disease, has been shown to be associated with increased risk of diabetes and relative insulin secretion deficiency. However, the mechanism of hepatic Ggt regulation has not been explored fully. In this study, we made a concerted effort to understand the mechanism by investigating the effects of acetylation of histones H3 and H4, and bindings of histone acetyltransferases, CREB binding protein (CBP) and p300, at the Ggt promoter on the regulation of the expression of Ggt gene in the livers of streptozotocin (STZ)-induced moderate hypoinsulinemia rat model. The rats treated with STZ showed remarkably higher serum GGT level and hepatic Ggt/GGT expression than the untreated control rats. Furthermore, the acetylation of histones H3 and H4, and the binding of CBP not p300 at the Ggt promoter regions were significantly higher in the livers of STZ rats than those of the control rats. These results suggest that an enhanced hepatic expression of Ggt is associated with increased acetylation of histones H3 and H4 and CBP binding at the Ggt promoter in STZ-induced moderate hypoinsulinemic rats.

Classification of the colonic splenic flexure based on three-dimensional CT analysis.

BACKGROUND: Mobilization of the splenic flexure can be a challenging surgical step in colorectal surgery. This study aimed to classify the splenic flexure based on the three-dimensional (3D) coordinates of the splenic hilum and left renal hilum. This classification was used to compare splenic flexure mobilization during colorectal resection. METHODS: CT images of patients with colorectal cancer treated between April 2018 and December 2019 were analysed retrospectively. 3D mutual positioning of the splenic flexure from the ligament of Treitz to the splenic hilum or the left renal hilum was used to classify patients into three groups using cluster analysis. The difference in the procedure time between groups was also analysed in a subset of patients undergoing laparoscopic colectomy with complete splenic flexure mobilization. RESULTS: Of 515 patients reviewed, 319 with colorectal cancers were included in the study and categorized based on the 3D coordinates of the splenic hilum and left renal hilum as caudal (100 patients), cranial (118) and lateral (101) positions. Male sex (P < 0.001), older age (P = 0.004) and increased bodyweight (P = 0.043) were independent characteristics of the lateral group in multiple logistic regression analysis. Thirty-four patients underwent complete splenic flexure mobilization during the study period; this took significantly longer (mean 78.7 min) in the lateral group than in the caudal and cranial groups (41.8 and 43.2 min respectively; P = 0.006). CONCLUSION: Locating the splenic flexure using 3D coordinates could be helpful in predicting a longer duration for mobilization of the splenic flexure.

Caprylic acid enhances hydroxyhexylitaconic acid production in Aspergillus niger S17-5.

AIM: Aspergillus niger S17-5 produces two alkylitaconic acids, 9-hydroxyhexylitaconic acid (9-HHIA) and 10-hydroxyhexylitaconic acid (10-HHIA), which have cytotoxic and polymer building block properties. In this study, we characterized the production of 9-HHIA and 10-HHIA by addition of their expected precursor, caprylic acid, to a culture of A. niger S17-5, and demonstrated batch fermentation of 9-HHIA and 10-HHIA in a jar fermenter with DO-stat. METHODS AND RESULTS: Production titres of 9-HHIA and 10-HHIA from 3% glucose in a flask after 25 days cultivation were 0·35 and 1·01 g l-1 respectively. Addition of 0·22 g l-1 of caprylic acid to a suspension of resting cells of A. niger S17-5 led to 32% enhancement of total 9-HHIA and 10-HHIA production compared to no addition. No enhancement of the production of 9-HHIA or 10-HHIA by the addition of oxaloacetic acid was observed. Addition of caprylic acid to the culture at mid-growth phase was more suitable for 9-HHIA and 10-HHIA production due to less cell growth inhibition by caprylic acid. DO-stat batch fermentation with 3% glucose and 14·4 g l-1 of caprylic acid in a 1·5 l jar fermenter resulted in the production titres of 9-HHIA and 10-HHIA being 0·48 and 1·54 g l-1 respectively after 10 days of cultivation. CONCLUSIONS: Addition of caprylic acid to the culture of A. niger S17-5 enhances 9-HHIA and 10-HHIA production. SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that 9-HHIA and 10-HHIA are synthesized with octanoyl-CoA derived from caprylic acid, and that the supply of octanoyl-CoA is a rate-limiting step in 9-HHIA and 10-HHIA production. To the best of our knowledge, this is the first report regarding the fermentation of naturally occurring itaconic acid derivatives in a jar fermenter.

Enhancing the fungicidal activity of amphotericin B via vacuole disruption by benzyl isothiocyanate, a cruciferous plant constituent.

Amphotericin B (AmB), a typical polyene macrolide antifungal agent, is widely used to treat systemic mycoses. In the present study, we show that the fungicidal activity of AmB was enhanced by benzyl isothiocyanate (BITC), a cruciferous plant-derived compound, in the budding yeast, Saccharomyces cerevisiae. In addition to forming a molecular complex with ergosterol present in fungal cell membranes to form K+ -permeable ion channels, AmB has been recognized to mediate vacuolar membrane disruption resulting in lethal effects. BITC showed no effect on AmB-induced plasma membrane permeability; however, it amplified AmB-induced vacuolar membrane disruption in S. cerevisiae. Furthermore, the BITC-enhanced fungicidal effects of AmB significantly decreased cell viability due to the disruption of vacuoles in the pathogenic fungus Candida albicans. The application of the combinatorial antifungal effect of AmB and BITC may aid in dose reduction of AmB in clinical antifungal therapy and consequently decrease side effects in patients. These results also have significant implications for the development of vacuole-targeting chemotherapy against fungal infections.