Prospective evaluation of non-invasive saliva specimens for the diagnosis of syphilis and molecular surveillance of Treponema pallidum.

The promising diagnostic performance of molecular testing for syphilis using saliva and urine samples has been reported; however, further evaluation of its possible application for diagnosis and molecular surveillance is required. In addition, the development of a rapid and easy-to-perform molecular test for syphilis is important for its use in the clinical setting. We comprehensively evaluated the diagnostic and surveillance performance of two novel loop-mediated isothermal amplification (LAMP) assays using saliva and urine samples. Saliva, urine, and whole blood were collected from patients who underwent serological testing for syphilis at outpatient clinics. Treponema pallidum DNA in specimens was detected using quantitative PCR (qPCR), nested PCR, and novel LAMP assays. T. pallidum genotyping was conducted by multi-locus sequence typing (MLST). Of the 163 patients recruited, 98 were diagnosed with syphilis (primary: n = 35; secondary: n = 40; latent: n = 23). qPCR showed the highest sensitivity among the molecular tests performed with a sensitivity of 54.1% and 30.3% for all syphilis patients using saliva and urine samples, respectively. A novel method of LAMP combined with dry reagents and crude DNA extraction (Dry-LAMP) showed a probit detection limit of 37.4 copies/reaction within 45 min. The agreement rate between Dry-LAMP and qPCR for saliva was 95.7% (κ coefficient 0.90). The T. pallidum genotype was identified in 48 patients by MLST using saliva samples. Molecular analysis of saliva could be used as a supplementary diagnostic test for syphilis and molecular surveillance of the T. pallidum genotype. Dry-LAMP is expected to be helpful in the clinical diagnosis of syphilis.

Microstructure Morphology of Chemical and Structural Phase Separation in Thermally treated KxFe2-ySe2 Superconductor.

The iron-based KxFe2-ySe2 superconductor displays phase separation, leading to the coexisting metallic phase embedded in an antiferromagnetic matrix. The metallic character of the system is believed to arise from a percolative granular network affecting normal as well as superconducting state properties. This network can be manipulated and controlled through thermal treatments. In this study, we have used scanning X-ray micro-fluorescence to visualize morphology of the phase separation and the percolation in KxFe2-ySe2, manipulated by distinct thermal treatments, i.e., fast quenching and slow cooling. We find a differing spatial correlation between Fe and K in differently treated samples, ascribed to different Fe vacancy ordering. We have identified an intermediate phase that acts as an interface between the two phases. The high temperature quenching produces oriented clustered microstructure in which the percolation threshold is lower and hence a more effective network for the transport pathways. Instead, the slow cooling results in larger interfaces around the percolation threshold affecting the superconducting properties of the system. The results provide a quantitative characterization of microstructural morphology of differently grown KxFe2-ySe2 showing potential for the design of electronic devices based on sub-micron scale chemical phase separation, thus opening avenues for further studies of complex heterogeneous structures.

A mesocortical dopamine circuit enables the cultural transmission of vocal behaviour.

The cultural transmission of behaviour depends on the ability of the pupil to identify and emulate an appropriate tutor1-4. How the brain of the pupil detects a suitable tutor and encodes the behaviour of the tutor is largely unknown. Juvenile zebra finches readily copy the songs of the adult tutors that they interact with, but not the songs that they listen to passively through a speaker5,6, indicating that social cues generated by the tutor facilitate song imitation. Here we show that neurons in the midbrain periaqueductal grey of juvenile finches are selectively excited by a singing tutor and-by releasing dopamine in the cortical song nucleus HVC-help to encode the song representations of the tutor used for vocal copying. Blocking dopamine signalling in the HVC of the pupil during tutoring blocked copying, whereas pairing stimulation of periaqueductal grey terminals in the HVC with a song played through a speaker was sufficient to drive copying. Exposure to a singing tutor triggered the rapid emergence of responses to the tutor song in the HVC of the pupil and a rapid increase in the complexity of the song of the pupil, an early signature of song copying7,8. These findings reveal that a dopaminergic mesocortical circuit detects the presence of a tutor and helps to encode the performance of the tutor, facilitating the cultural transmission of vocal behaviour.

Serum Growth Differentiation Factor 15 Levels Predict the Incidence of Frailty among Patients with Cardiometabolic Diseases.

INTRODUCTION: Frailty is a crucial health issue among older adults. Growth differentiation factor 15 (GDF15) is associated with inflammation, oxidative stress, insulin resistance, and mitochondrial dysfunction, which are possible pathogeneses of frailty. However, few longitudinal studies have investigated the association between GDF15 and the incidence of frailty. Therefore, we investigated whether high serum GDF15 levels are associated with the incidence of frailty. METHODS: A total of 175 older adults (mean age: 77 ± 6 years; 63% women) with cardiometabolic diseases and no frailty out of the two criteria at baseline participated. Individuals with severe renal impairment or severe cognitive impairment were excluded. Serum GDF15 levels were measured at baseline. Patients were asked to assess frailty status at baseline and annually during follow-up using the modified version of the Cardiovascular Health Study (mCHS) and the Kihon Checklist (KCL). We examined the association between GDF15 tertiles and each frailty measure during follow-up (median 38-39 months). In the multivariate Cox regression analysis, with the GDF15 tertile groups as the explanatory variables, hazard ratios (HRs) and 95% confidence intervals (CIs) for incident frailty were calculated after adjusting for covariates and using the lowest tertile group as the reference. RESULTS: During the follow-up period, 25.6% and 34.0% of patients developed frailty, as defined by the mCHS and KCL, respectively. The highest GDF15 tertile group had a significantly higher incidence of mCHS- or KCL-defined frailty than the lowest GDF15 tertile group. Multivariate Cox regression analysis revealed that the adjusted HRs for incident mCHS- and KCL-defined frailty in the highest GDF15 tertile group were 3.9 (95% CI: 1.3-12.0) and 2.7 (95% CI: 1.1-6.9), respectively. CONCLUSION: High serum GDF15 levels predicted the incidence of frailty among older adults with cardiometabolic diseases and could be an effective marker of the risk for frailty in interventions aimed at preventing frailty, such as exercise and nutrition.

A mitochondria-specific mutational signature of aging: increased rate of A > G substitutions on the heavy strand.

The mutational spectrum of the mitochondrial DNA (mtDNA) does not resemble any of the known mutational signatures of the nuclear genome and variation in mtDNA mutational spectra between different organisms is still incomprehensible. Since mitochondria are responsible for aerobic respiration, it is expected that mtDNA mutational spectrum is affected by oxidative damage. Assuming that oxidative damage increases with age, we analyse mtDNA mutagenesis of different species in regards to their generation length. Analysing, (i) dozens of thousands of somatic mtDNA mutations in samples of different ages (ii) 70053 polymorphic synonymous mtDNA substitutions reconstructed in 424 mammalian species with different generation lengths and (iii) synonymous nucleotide content of 650 complete mitochondrial genomes of mammalian species we observed that the frequency of AH > GH substitutions (H: heavy strand notation) is twice bigger in species with high versus low generation length making their mtDNA more AH poor and GH rich. Considering that AH > GH substitutions are also sensitive to the time spent single-stranded (TSSS) during asynchronous mtDNA replication we demonstrated that AH > GH substitution rate is a function of both species-specific generation length and position-specific TSSS. We propose that AH > GH is a mitochondria-specific signature of oxidative damage associated with both aging and TSSS.

Secondary structure of the human mitochondrial genome affects formation of deletions.

BACKGROUND: Aging in postmitotic tissues is associated with clonal expansion of somatic mitochondrial deletions, the origin of which is not well understood. Such deletions are often flanked by direct nucleotide repeats, but this alone does not fully explain their distribution. Here, we hypothesized that the close proximity of direct repeats on single-stranded mitochondrial DNA (mtDNA) might play a role in the formation of deletions. RESULTS: By analyzing human mtDNA deletions in the major arc of mtDNA, which is single-stranded during replication and is characterized by a high number of deletions, we found a non-uniform distribution with a "hot spot" where one deletion breakpoint occurred within the region of 6-9 kb and another within 13-16 kb of the mtDNA. This distribution was not explained by the presence of direct repeats, suggesting that other factors, such as the spatial proximity of these two regions, can be the cause. In silico analyses revealed that the single-stranded major arc may be organized as a large-scale hairpin-like loop with a center close to 11 kb and contacting regions between 6-9 kb and 13-16 kb, which would explain the high deletion activity in this contact zone. The direct repeats located within the contact zone, such as the well-known common repeat with a first arm at 8470-8482 bp (base pair) and a second arm at 13,447-13,459 bp, are three times more likely to cause deletions compared to direct repeats located outside of the contact zone. A comparison of age- and disease-associated deletions demonstrated that the contact zone plays a crucial role in explaining the age-associated deletions, emphasizing its importance in the rate of healthy aging. CONCLUSIONS: Overall, we provide topological insights into the mechanism of age-associated deletion formation in human mtDNA, which could be used to predict somatic deletion burden and maximum lifespan in different human haplogroups and mammalian species.

A Case of Aortopulmonary Fistula with Post-Operative Aortic Pseudoaneurysm Diagnosed by Transesophageal Echocardiography.

Tracheobronchial or esophageal fistula after aortic surgery has been reported sporadically in the literature, however, reports of an aortopulmonary fistula associated with a post-operative aortic pseudoaneurysm are rare. We experienced a case of refractory heart failure due to an aortopulmonary fistula associated with a post-operative aortic pseudoaneurysm. A 60-year-old man who had undergone aortic surgery 2 years earlier was hospitalized for congestive heart failure. He was diagnosed with refractory heart failure after 10 days of diuretic therapy failed to improve his condition. He underwent a contrast-enhanced computed tomography (CT) scan and was suspected to have pulmonary artery perforation of an aortic pseudoaneurysm at the anastomotic site of the ascending aortic surgery. Transesophageal echocardiography showed shunt blood flow from the aortic aneurysm into the right pulmonary artery, leading to a definitive diagnosis of aortopulmonary fistula with post-operative aortic pseudoaneurysm. Computed tomography angiography is commonly used to diagnose an aortic fistula; however, diagnosis is often difficult because of the subtle imaging findings. We highlight the usefulness of transesophageal echocardiography in providing a definitive diagnosis and detailed morphologic information on this pathophysiology.

Japan should initiate the discussion on voluntary assisted dying legislation now.

BACKGROUND: No laws or official guidelines govern voluntary assisted dying (VAD) in Japan. A legislative bill on the termination of life-sustaining measures has yet to be sent to deliberations for legislation, due to strong opposition that has prevented it from being submitted to the Diet. However, Japan has recently witnessed several cases involving VAD. MAIN TEXT: Against this backdrop, we argue that Japan should begin discussion on VAD legislation, referring to the Voluntary Assisted Dying Act 2017 (VADA2017), which was established in 2017 in Victoria, Australia. VADA2017 puts in place a wide range of stringent safeguards and is considered worldwide to be the safest and most conservative policy on a physician offering assisted dying based on the patient's premeditated request. We consider what opposing opinions from society would arise in response to the VADA2017. Among these will include arguments against VAD itself, those against the validation of this act, and opinions that oppose even the initiation of the dialogue on VAD. CONCLUSIONS: We conclude that to protect the right to life among those placed in vulnerable positions and, at the same time, to respect decision-making of those who wish for immediate death due to unbearable suffering, the dialogue must immediately begin with that on introducing a policy more conservative than that of the VADA2017, which solidly considers arguments against VAD.

Intraoperative Type B Aortic Dissection during Total Arch Replacement.

BACKGROUND: Intraoperative aortic dissection is an extremely serious complication that should be prevented whenever possible. When it does occur, it requires urgent clinical management. CASE PRESENTATION: We report the case of a 78-year-old man with Marfan syndrome who developed an intraoperative complicated type B aortic dissection with a distal anastomosis entry site during total arch replacement for a chronic dissection. CONCLUSION: Performing immediate thoracic endovascular aortic repair, we were able to improve malperfusion to the lower extremities occurred during total arch replacement.

Preoperative Sarcopenia Assessment Using Pectoralis Muscle Mass Indicated Poor Mid-term Cardiac Surgery Prognosis.

BACKGROUND: Many studies have defined sarcopenia based on psoas muscle mass using abdominal computed tomography (CT). We hypothesized that sarcopenia can be assessed by measuring pectoralis muscle mass on chest CT and aimed to examine its relationship with the postoperative prognosis of cardiac surgery. METHODS: This retrospective study included 189 patients who underwent cardiac surgery via median sternotomy between July 2020 and June 2022. We excluded patients <70 years old, urgent/emergent cases, no chest CT within 90 days before surgery, and cases in which evaluation of the pectoralis muscle was impossible with CT. The pectoralis muscle area (PMA) was measured using a preoperative chest CT. The sarcopenia cut-off value was defined as the lowest sex-specific tertile in PMA at the level of the 4th thoracic vertebrae. RESULTS: Eighty patients were included. The lower tertile were classified as the sarcopenia group (SG) (n = 26) and the rest as the non-sarcopenia group (NSG) (n = 54). In the SG, 1-year survival was significantly worse than that in NSG (NSG: 92.7% vs. SG: 54.9%, p < 0.0001). In the multivariate model, sarcopenia was an independent risk factor for mid-term all-cause death (hazard ratio, 4.89; 95% confidence interval: 1.14-21.0, p = 0.033). CONCLUSION: Preoperative sarcopenia defined using PMA was associated with poor mid-term survival after elective cardiac surgery via median sternotomy. The pectoralis muscle mass observed through a chest CT could be used for preoperative risk scoring in older patients undergoing cardiac surgery.

Pleiotropic neuroprotective effects of taxifolin in cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) results from amyloid-ß deposition in the cerebrovasculature. It is frequently accompanied by Alzheimer's disease and causes dementia. We recently demonstrated that in a mouse model of CAA, taxifolin improved cerebral blood flow, promoted amyloid-ß removal from the brain, and prevented cognitive dysfunction when administered orally. Here we showed that taxifolin inhibited the intracerebral production of amyloid-ß through suppressing the ApoE-ERK1/2-amyloid-ß precursor protein axis, despite the low permeability of the blood-brain barrier to taxifolin. Higher expression levels of triggering receptor expressed on myeloid cell 2 (TREM2) were associated with the exacerbation of inflammation in the brain. Taxifolin suppressed inflammation, alleviating the accumulation of TREM2-expressing cells in the brain. It also mitigated glutamate levels and oxidative tissue damage and reduced brain levels of active caspases, indicative of apoptotic cell death. Thus, the oral administration of taxifolin had intracerebral pleiotropic neuroprotective effects on CAA through suppressing amyloid-ß production and beneficially modulating proinflammatory microglial phenotypes.

An increased prothrombin time-international normalized ratio in patients with acute type A aortic dissection: contributing factors and their influence on outcomes.

PURPOSE: We investigated factors contributing to coagulopathy in patients with acute type A aortic dissection (ATAAD) and coagulopathy's influence on patient outcomes. METHODS: We grouped 420 patients who underwent ATAAD repair-none under anticoagulation therapy or with liver disease-by the prothrombin time-international normalized ratio (PT-INR) at admission: < 1.2 (no coagulopathy, n = 371), 1.2-1.49 (mild coagulopathy, n = 33), or ≥ 1.5 (severe coagulopathy, n = 16). We then compared the clinical presentation, dissection morphology, and outcomes among the groups. We assessed the PT-INR in relation to the preoperative hemodynamics and searched for factors predictive of a PT-INR ≥ 1.2. RESULTS: The transfusion volume and operation time were increased among patients with coagulopathy (P < 0.05). The in-hospital mortality (15.2-37.5% vs. 5.1%, P < 0.001) and 5-year survival (61.1-74.4% vs. 87.6%) were relatively poor for these patients. The median PT-INR was 1.03 (0.97-1.1) for patients with stable hemodynamics (n = 318), 1.11 (1.02-1.21) for those in shock (blood pressure < 80 mmHg) not given cardiopulmonary resuscitation (CPR) (n = 81), and 1.1 (1.0-1.54) for those in shock given CPR (n = 21) (P < 0.001). A multivariable analysis identified shock (P < 0.001), a partially thrombosed false lumen (P = 0.006), and mesenteric malperfusion (P = 0.016) as predictive variables. CONCLUSIONS: Shock, a partially thrombosed false lumen, and mesenteric malperfusion appear to be predictive of dissection-related coagulopathy, which influences outcomes negatively.

A Case of Thoracic Aortic Endovascular Repair of a Ruptured Mycotic Aortic Aneurysm Due to Pasteurella Multocida.

An 81-year-old man was admitted for general fatigue of one month's duration. Two sets of blood cultures revealed bacteremia, due to Pasteurella multocida, while computed tomography (CT) revealed a 47-mm descending aortic saccular aneurysm. After transfer to our hospital, the saccular aneurysm rapidly grew to 54 mm. An emergency thoracic endovascular aortic repair was performed, due to the aneurysm immediately rupturing after the CT scan. The patient was discharged on postoperative day 28.

Amyloid-ß: Structure, Function, and Pathophysiological Significance in Neurodegenerative Diseases.

The rate of dementia continues to increase worldwide; however, there currently exist no therapeutic strategies for this condition [...].

Exophytic cavernous hemangioma arising from the right ventricle: Report of a rare case.

Cardiac hemangioma is relatively rare, accounting for approximately 1-3% of all primary heart tumors. This benign tumor may be an incidental lesion, but can also cause arrhythmias, pericardial effusion, congestive heart failure or outflow obstruction. We report a rare case with exophytic cardiac hemangioma arising from the right ventricle. Echocardiography showed an approximately 40 mm round protruding mass on the anterior wall of the right ventricle. Cardiovascular magnetic resonance demonstrated isointense and hyperintense signals on T1- and T2-weighted images, respectively. These imaging studies suggested a pericardial cyst. Perioperative findings indicated a globular, exophytic mass, vascular in nature, arising from the right ventricle. The lesion was resected directly, and the space left by defect in the right ventricular wall was covered with a bovine pericardial patch. Cardiac hemangiomas are generally endoluminal tumors, but we must keep in mind that the differential diagnoses include various pericardial lesions by medical images.

Polymorphic SERPINA3-R124C reduces pathogenesis of its wild type by shortening the lifetime of oligomeric Aß.

Amyloid beta (Aß) 42 peptide accumulated in Alzheimer disease (AD) patients' brain, often colocalized with serine protease inhibitor family A member 3 (SERPINA3). Being a chaperon, SERPINA3 accelerated Aß42 fibrillization. While analyzing chaperon activity of human SERPINA3 polymorphisms, we found SERPINA3-R124C played a role in protecting cells from Aß42 cytotoxicity. SH-SY5Y cells exposed to Aß42 preincubated with wild-type SERPINA3 (SERPINA3-WT) resulted in extended toxicity leading cell death whereas Aß42 with SERPINA3-R124C resulted in less cytotoxicity. Transmission electron microscope and thioflavin T assay revealed that SERPINA3-R124C shortened lifetime of small soluble oligomer and maintained ß-sheet rich protofibril-like aggregates for longer time compared to that of with SERPINA3-WT. Western blot assay confirmed that SERPINA3-R124C converted Aß42 mostly into high molecular aggregates. Here, we demonstrate first time that polymorphic SERPINA3 acts as a benign chaperon by modulating the transition states of Aß42, which may contribute to the reduction of AD risk.

Suturing Fenestration of the Left Subclavian Artery Orifice in Frozen Elephant Trunk Procedure.

The frozen elephant trunk (FET) procedure enables easier replacement of the entire aortic arch because it does not require reaching the distal part of the left subclavian artery (LSCA). However, it requires additional management for reconstruction of the LSCA, which is associated with bleeding events. However, the fenestrated FET technique confers a risk of endoleakage from the fenestration site. We report our unique novel technique in which the proximal side of the hybrid stent graft is cut into V-shape around the subclavian artery and sutured continuously around the orifice of the subclavian artery during aortic stump fixation.

Cross-sectional survey of surrogate decision-making in Japanese medical practice.

BACKGROUND: Instances of surrogate decision-making are expected to increase with the rise in hospitalised older adults in Japan. Few large-scale studies have comprehensively examined the entire surrogate decision-making process. This study aimed to gather information to assess the current state of surrogate decision-making in Japan. METHODS: A cross-sectional survey was conducted using online questionnaires. A total of 1000 surrogate decision-makers responded to the questionnaire. We examined the characteristics of surrogate decision-makers and patients, content of surrogate decision-making meeting regarding life-sustaining treatment between the doctors and surrogate decision-makers, extent of involvement of the various parties in the surrogate decision-making process, judgement grounds for surrogate decision-making, and frequency of involvement in the surrogate decision-making process. RESULTS: Of the participants, 70.5% were male and 48.3% were eldest sons. Only 7.6% of the patients had left a written record of their preferences and 48.8% of the surrogates reported no knowledge of the patient having expressed their prior intentions regarding medical care in any form. Respondents indicated that their family meetings with healthcare professionals mostly included the information recommended by guidelines in a surrogate decision-making meeting in Japan. Most participants reported a good understanding of the meeting content. Although many participants based their decisions on multiple grounds, surrogates' considerations may not adequately reflect respect for patient autonomy in Japan. Specifically, the eldest son considered his own preference more frequently than that of the other surrogate decision-makers. In 26.1% of the cases, either zero or one family meeting with healthcare professionals was held. In these cases, significantly fewer decisions involved the participation of healthcare professionals other than the doctor compared to cases with multiple meetings. CONCLUSIONS: Surrogate decisions in Japan are most commonly made by eldest sons and may not frequently consider the perspectives of other surrogates. The finding that patient preferences were rarely known suggests a role for increased advance care planning.

Grounds for surrogate decision-making in Japanese clinical practice: a qualitative survey.

BACKGROUND: In the coming years, surrogate decision-making is expected to become highly prevalent in Japanese clinical practice. Further, there has been a recent increase in activities promoting advance care planning, which potentially affects the manner in which judgements are made by surrogate decision-makers. This study aims to clarify the grounds on which surrogate decision-makers in Japan base their judgements. METHODS: In this qualitative study, semi-structured interviews were conducted to examine the judgement grounds in surrogate decision-making for critical life-sustaining treatment choices in acute care hospitals. RESULTS: A total of 228 participants satisfied the inclusion criteria, and 15 were selected for interviews. We qualitatively analysed the content of 14 interview transcripts, excluding one that did not meet the inclusion criteria. Based on this analysis, we extracted 4 core categories, 17 categories, 35 subcategories, and 55 codes regarding judgement grounds in surrogate decision-making. The four core categories were as follows: patient preference-oriented factor (Type 1), patient interest-oriented factor (Type 2), family preference-oriented factor (Type 3), and balanced patient/family preference-oriented factor (Type 4). The Type 4 core category represented attempts to balance the preferences of the patient with those of the surrogate decision-maker. CONCLUSIONS: Surrogate decision-makers based their decisions on important aspects related to a patient's life, and they considered not only the patient's preferences and best interests but also their own preferences. As the need for surrogate decisions will increase in the future, decision-makers will need to consider judgement grounds from a more diverse perspective.

A case of right ventricular infarction due to acute type A aortic dissection with anomalous aortic origin of the right coronary artery from the left sinus of Valsalva.

Anomalous aortic origin of a coronary artery from the opposite sinus is a rare congenital condition that can cause sudden death in young people. When it is associated with acute aortic dissection, acute myocardial infarction can occur due to enlargement of the sinus of Valsalva. We report the case of a 71-year-old man with anomalous origin of the right coronary artery from the left sinus of Valsalva, who developed right ventricular infarction due to the compression of the right coronary artery between the aorta and pulmonary artery trunk.