Impact of an angulated aorto-septal relationship on cardio-cerebrovascular outcomes in patients undergoing hemodialysis.

Aortic and valvular calcification are well-known risk factors for cardio-cerebrovascular events in patients undergoing hemodialysis. We investigated the clinical impact of an angulated aorto-septal angle as a result of aortic elongation due to aortic calcification on cardio-cerebrovascular outcomes in patients undergoing hemodialysis. We investigated 306 patients (mean age 65.4 years, 68% male) who underwent pre-scheduled routine echocardiography between April and September 2018. The angle between the anterior wall of the aorta and the ventricular septal surface (ASA) was quantified. We determined aortic and mitral valve calcification scores based on calcified cardiac changes; the aortic and mitral valve scores ranged between 0-9 and 0-6, respectively. The primary endpoint was a composite including cardio-cerebrovascular events and cardio-cerebrovascular death. The mean duration of dialysis among the patients in this analysis was 9.6 years. The primary endpoint was observed in 54 patients during the observational period (median 1095 days). Multivariable Cox proportional hazards analyses identified left ventricular ejection fraction (per 10% increase: hazard ratio [HR] 0.67; 95% confidential interval [CI] 0.53-0.84, P = 0.001), left ventricular mass index (per 10 g/m2 increase: HR 1.14; 95% CI 1.05-1.24, P = 0.001), ASA (per 10 degree increase: HR 0.69; 95% CI 0.54-0.88; P = 0.003), and aortic valve calcification score (HR 1.15; 95% CI 1.04-1.26, P = 0.005) as independent determinants of the primary endpoint. Kaplan-Meier analysis showed a higher incidence of the primary endpoint in patients with ASA <119.4 degrees than those with ASA ≥119.4 degrees (Log-rank P < 0.001). An angulated aorto-septal angle is an independent risk factor for cardio-cerebrovascular events and cardio-cerebrovascular death in patients undergoing hemodialysis.

Association between Serum 25-Hydroxyvitamin D Levels and Sarcopenia in Patients Undergoing Chronic Haemodialysis.

INTRODUCTION: Sarcopenia and vitamin D deficiency are highly prevalent among patients undergoing haemodialysis. Although vitamin D deficiency, assessed using serum 25-hydroxyvitamin D (25(OH)D) levels, is known to be associated with sarcopenia in the general population, whether serum 25(OH)D levels are associated with sarcopenia in patients undergoing haemodialysis with suppressed renal activation of 25(OH)D remains unclear. This study aimed to examine the association between serum 25(OH)D levels and sarcopenia in patients undergoing haemodialysis. METHODS: Serum 25(OH)D level measurements and assessment of sarcopenia using the Asian Working Group for Sarcopenia criteria were conducted in 95 stable outpatients undergoing maintenance haemodialysis therapy. RESULTS: Sarcopenia was observed in 22 (23.1%) patients. In multiple logistic regression analysis, serum 25(OH)D levels were associated with sarcopenia (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.77-0.99, p = 0.039) independent of traditional risk factors for sarcopenia. In multiple linear regression analyses, serum 25(OH)D levels were associated with parameters of skeletal muscle mass and strength (ß = 0.145, p = 0.046, and ß = 0.194, p = 0.020, respectively). The adjusted OR for sarcopenia was 5.60 (95% CI 1.52-20.57, p = 0.009) in the vitamin D deficiency group categorized based on the cut-off serum 25(OH)D level of 10 ng/mL. Regarding model discrimination, adding vitamin D deficiency to the traditional risk factors significantly improved the integrated discrimination improvement score (0.093, p = 0.007). CONCLUSION: Lower serum 25(OH)D levels were associated with sarcopenia independent of traditional risk factors in patients undergoing haemodialysis with suppressed vitamin D activation in the kidney. This finding implies that circulating 25(OH)D may have an important relationship with the skeletal muscle function of patients undergoing haemodialysis, and its measurement may be recommended to identify patients at high risk for sarcopenia among those undergoing haemodialysis.

Coexistence of Low Muscle Mass and Osteoporosis as a Predictor of Fragility Fractures in Long-Term Kidney Transplant Recipients.

INTRODUCTION: Sarcopenia and osteoporosis are highly prevalent among kidney transplant recipients (KTRs). Although osteoporosis is known to increase fracture risk in KTRs, it is unclear whether sarcopenia or osteosarcopenia is associated with this increased risk. Thus, we aimed to investigate the association of the coexistence of low muscle mass (LMM) and osteoporosis with the risk of fracture in long-term KTRs. METHODS: Exactly 342 stable KTRs underwent dual-energy X-ray absorptiometry and skeletal muscle mass index (SMI) measurement using bioelectrical impedance analysis. RESULTS: LMM and osteoporosis were observed in 109 (31.9%) and 93 patients (27.2%), respectively. During a follow-up period of 5.1 years, 48 (14.0%) fractures occurred. KTRs with LMM had a higher fracture risk, but this was not significant (adjusted hazard ratio [aHR] 1.82, 95% confidence interval [CI] 0.94-3.50, p = 0.073). Similar results were obtained in KTRs with osteoporosis (aHR 1.84, 95% CI 0.96-3.47, p = 0.063). We divided the KTRs into four groups according to the presence of LMM and/or osteoporosis. The cumulative incidence rates of fractures were 13.0%, 11.1%, 10.5%, and 31.3% in the KTRs without both LMM and osteoporosis, those with LMM alone, those with osteoporosis alone, and those with both, respectively. The KTRs with both LMM and osteoporosis had a 2.92fold higher risk of fractures (95% CI 1.29-6.49; p = 0.010) than those without both LMM and osteoporosis. CONCLUSION: Long-term KTRs with the coexistence of LMM and osteoporosis had an independently higher risk of fragility fractures than those without both LMM and osteoporosis. The combination of SMI and osteoporosis definitions can be used to identify KTRs with a high fracture risk.

The Impact of Liver Chemistries on Respiratory Failure among Hemodialysis Patients with COVID-19 during the Omicron Wave.

Objective Although the coronavirus disease 2019 (COVID-19) Omicron variant causes less severe symptoms than previous variants, early indicators for respiratory failure are needed in hemodialysis patients, who have a higher mortality rate than the general population. Liver chemistries are known to reflect the severity of COVID-19 in the general population. This study explored the early indicators for worsened respiratory failure based on patient characteristics, including liver chemistries. Methods This retrospective study included 117 patients admitted for COVID-19 during the Omicron wave. Respiratory failure was defined as oxygen requirement during treatment. Information on the symptoms and clinical characteristics, including liver chemistries [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], at admission was collected. Results Thirty-five patients (29.9%) required oxygen supply during treatment. In the multivariate logistic regression analyses, AST [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.00-1.13, p=0.029], ALT (OR 1.09, 95% CI 1.02-1.18, p=0.009), and moderate COVID-19 illness (Model including AST, OR 6.95, 95% CI 2.23-23.17, p<0.001; Model including ALT, OR 7.19, 95% CI 2.21-25.22, p=0.001) were independent predictors for respiratory failure. Based on the cutoff values determined by the receiver operating characteristic curve, higher AST (≥23 IU/L) and ALT levels (≥14 IU/L) were also independently associated with respiratory failure (higher AST: 64.3% vs. 18.8%, OR 3.44, 95% CI 1.08-11.10, p=0.035; higher ALT: 48.8% vs. 19.7%, OR 4.23, 95% CI 1.34-14.52, p=0.013, respectively). Conclusion The measurement of AST and ALT levels at baseline may help predict oxygen requirement in hemodialysis patients with COVID-19.

Importance of "meal first" strategy and effective situations of supplement use in elite athletes: Japan high performance sport center position stand.

The "meal first" strategy is traditionally recommended for athletes' conditioning. However, the importance of the "meal first" principle has not been detailly well documented in athletes' lives. Supplement use has recently become a common part of athletes' diets, but unmonitored supplement use can cause negative consequences, such as anti-doping violations and health issues. Therefore, this review summarizes how the "meal first" strategy and planned supplement use are important for enhancing athletes' health and performance. We believe that the "meal first" strategy is beneficial in terms of the following aspects: (1) consumption of multi-nutrients and other functional components simultaneously; (2) positive effects on psychological well-being; (3) contribution to athletes' health by way of mastication; and (4) less risk for anti-doping violations. Before supplement use, we recommend that athletes first verify their basic factors (e.g., diet, training, and sleep), given that the benefits of supplements are examined and demonstrated with the control of those factors. Otherwise, athletes cannot obtain maximal benefits from the supplements. In contrast, there are situations in which supplements in athletes' lives can be advantageous, such as (1) nutrient deficiency due to ongoing dietary characteristics; (2) interruption of meals due to disease; (3) inaccessibility of quality food during athletic travel; (4) difficulty preparing food due to societal restrictions associated with disasters or infection outbreaks; (5) having a meal before, during, or after exercise is difficult; and (6) achieving targeted intake of performance-enhancing ingredients is not practical. In summary, we emphasize that the "meal first" strategy is recommended for athletes' conditioning, but there are several contexts when supplement use can be more useful in athletes' lives.

Non-A Blood Type Is a Risk Factor for Poor Cardio-Cerebrovascular Outcomes in Patients Undergoing Dialysis.

The clinical impact of ABO blood type on cardio-cerebrovascular outcomes in patients undergoing dialysis has not been clarified. A total of 365 hemodialysis patients participated in the current study. The primary endpoint was defined as a composite including cardio-cerebrovascular events and cardio-cerebrovascular death. The primary endpoint was observed in 73 patients during a median follow-up period of 1182 days, including 16/149 (11%) with blood type A, 22/81 (27%) with blood type B, 26/99 (26%) with blood type O, and 9/36 (25%) with blood type AB. At baseline, no difference was found in the echocardiographic parameters. Multivariable Cox regression analyses revealed that blood type (type A vs. non-A type; hazard ratio (HR): 0.46, 95% confidence interval (95% CI): 0.26-0.81, p = 0.007), age (per 10-year increase; HR: 1.47, 95% CI: 1.18-1.84), antiplatelet or anticoagulation therapy (HR: 1.91, 95% CI: 1.07-3.41), LVEF (per 10% increase; HR: 0.78, 95% CI: 0.63-0.96), and LV mass index (per 10 g/m2 increase; HR: 1.07, 95% CI: 1.01-1.13) were the independent determinants of the primary endpoint. Kaplan-Meier curves also showed a higher incidence of the primary endpoint in the non-A type than type A (Log-rank p = 0.001). Dialysis patients with blood type A developed cardio-cerebrovascular events more frequently than non-A type patients.

Combination of anti-glycopeptidolipid-core IgA antibody and clinical features for diagnosing potential nontuberculous mycobacterium pulmonary disease in routine practice.

BACKGROUND: The anti-Mycobacterium avium complex (MAC) antibody test measures levels of IgA antibody against the glycopeptidolipid (GPL) core in the bacterial cell walls and is a useful clinical indicator of nontuberculous mycobacterium pulmonary disease (NTM-PD). However, it is not currently possible to diagnose the disease using anti-MAC antibodies alone. OBJECTIVES: The study aim was to assess the efficacy of the combination of anti-MAC antibodies and clinical findings for diagnosing potential NTM-PD. METHODS: This cross-sectional study included 938 patients tested using the anti-MAC antibody. NTM-PD was diagnosed by multiple positive cultures of the same species in sputum samples. Multivariate logistic regression models were used to identify the clinical factors related to NTM-PD. RESULTS: Overall, 19.6% (184/938) of participants were diagnosed with NTM-PD. In multivariate analysis, positive anti-MAC antibodies, low body mass index, absence of malignancy, and cavity-forming lung lesions were significantly associated with NTM-PD at diagnosis. The positive rates of the anti-MAC antibody test were 79.4% (135/170) for MAC and 55.6% (5/9) for Mycobacterium abscessus complex, respectively. CONCLUSIONS: Bronchoscopic examinations should be performed especially in certain types of individuals from whom sputum samples cannot be obtained. Anti-MAC antibodies are also positive in patients other than those harboring MAC, but the rate may be low because of the different components in GPLs.

Effects of bone turnover status on the efficacy and safety of denosumab among haemodialysis patients.

Denosumab is reported to increase bone mineral density (BMD) among haemodialysis patients; however, hypocalcaemia is a serious adverse effect among chronic kidney disease (CKD) patients. Identifying which patients will show greater improvement in BMD is important. We enrolled 84 haemodialysis patients with osteoporosis in our study. 28 patients initiated denosumab treatment between October 2019 and October 2020. We assessed BMD changes and investigated the association between baseline bone turnover marker (BTM) levels and 6-month changes in BMD after denosumab treatment. BMD was increased at 6 months in denosumab-treated patients compared with patients not treated with denosumab (lumbar spine: 5.34% vs. - 0.49%; total hip: 2.43% vs. - 0.47%). Bone-specific alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase-5b (TRACP-5b) at baseline were independently associated with increased BMD in the total hip (BAP: ß = 0.472, p value = 0.004; TRACP-5b: ß = 0.433, p value = 0.008) and lumbar spine (BAP: ß = 0.591, p value = 0.001; TRACP-5b: ß = 0.613, p value = 0.0008). BAP and TRACP-5b were also independent predictors of hypocalcaemic events (OR [95% CI] 1.747 [1.084-4.604] and 1.006 [1.000-1.015], respectively). BTMs may be associated with increased BMD and hypocalcaemic events after denosumab treatment. BTM measurement may be useful for assessing the effect of denosumab on BMD; however, careful monitoring of serum calcium levels is needed.

A case series of favorable vessel dilatation using a nitinol scoring element-equipped helical balloon catheter (AngioSculpt®).

OBJECTIVE: Although percutaneous transluminal angioplasty is an effective therapy against vascular access failure in hemodialysis patients, recurrent stenosis imposes enormous burden for hemodialysis patients. A nitinol scoring element-equipped helical balloon catheter (AngioSculpt®) has been altered the landscape for treating several vascular diseases. It is not, however, fully elucidated whether AngioSculpt for advanced vascular access stenosis, difficult to expand by conventional balloons, successfully provides bailout angioplasty. Here, we report our cases whose intradialytic venous pressure significantly improved after percutaneous transluminal angioplasty without any serious adverse complications using AngioSculpt. PATIENTS AND METHODS: Among patients undergoing hemodialysis in Masuko Memorial Hospital, 16 cases with resistant and recurrent vascular access stenosis underwent AngioSculpt (diameter 6 mm, total length 4 cm) angioplasty. We simultaneously measured the average venous pressures during hemodialysis before and after percutaneous transluminal angioplasty. RESULTS: The average outflow vessel stenosis rate was 73.0 ± 11.3% before AngioSculpt intervention. Fully enlarged vessels were observed by expanding vessels at maximum pressure of 14 atm in all cases without any complications including vascular ruptures. Their intradialytic venous pressures decreased from 181.8 ± 39.2 mmHg to 150.5 ± 39.3 mmHg ( p < 0.0001). CONCLUSION: AngioSculpt may provide a promising option for treating hemodialysis patients with severely advanced vascular access stenosis, who would otherwise need repeated vascular access surgeries and/or conventional percutaneous transluminal angioplasties.

Post-Exercise Whole Body Cryotherapy (-140 °C) Increases Energy Intake in Athletes.

PURPOSE: The purpose of the present study was to investigate the effect of whole-body cryotherapy (WBC) treatment after exercise on appetite regulation and energy intake. METHODS: Twelve male athletes participated in two trials on different days. In both trials, participants performed high-intensity intermittent exercise. After 10 min following the completion of the exercise, they were exposed to a 3-min WBC treatment (-140 °C, WBC trial) or underwent a rest period (CON trial). Blood samples were collected to assess plasma acylated ghrelin, serum leptin, and other metabolic hormone concentrations. Respiratory gas parameters, skin temperature, and ratings of subjective variables were also measured after exercise. At 30 min post-exercise, energy and macronutrient intake were evaluated during an ad libitum buffet meal test. RESULTS: Although appetite-regulating hormones (acylated ghrelin and leptin) significantly changed with exercise (p = 0.047 for acylated ghrelin and p < 0.001 for leptin), no significant differences were observed between the trials. Energy intake during the buffet meal test was significantly higher in the WBC trial (1371 ± 481 kcal) than the CON trial (1106 ± 452 kcal, p = 0.007). CONCLUSION: Cold exposure using WBC following strenuous exercise increased energy intake in male athletes.

Assessment of factors associated with prominent changes in blood pressure during an early mobilization protocol for patients with acute ischemic stroke after mechanical thrombectomy.

OBJECTIVE: To assess factors associated with changes in blood pressure during early mobilization protocol for patients with acute ischemic stroke who were treated with mechanical thrombectomy. DESIGN: Retrospective observational study. METHOD: We analyzed patients with acute ischemic stroke who were treated with mechanical thrombectomy (MT group, n=60) and patients who received conservative medical management (control group, n=60) matched by age and National Institute Health of Stroke Score at admission from April 2009 to July 2014. The proportion of patients with prominent blood pressure change during an early mobilization protocol was compared between the MT group and control group. Factors associated with prominent blood pressure change were also analyzed using multivariable logistic regression analysis. RESULT: The deviation in blood pressure response was much more significant in the MT than control group (13.3 vs. 1.7%, p<0.016). Logistic regression analysis showed the interval from admission to being able to sit in a wheelchair associated with prominent changes in blood pressure (odds ratio, 1.604; 95% confidence interval, 1.196-2.150; p<0.002). CONCLUSION: Our results showed that prominent changes in blood pressure during an early mobilization protocol can occur easily in patients with acute ischemic stroke after mechanical thrombectomy.

High-wattage pulsed irradiation of linearly polarized near-infrared light to stellate ganglion area for burning mouth syndrome.

The purpose of this study was to apply high-wattage pulsed irradiation of linearly polarized near-infrared light to the stellate ganglion area for burning mouth syndrome (BMS) and to assess the efficacy of the stellate ganglion area irradiation (SGR) on BMS using differential time-/frequency-domain parameters (D parameters). Three patients with BMS received high-wattage pulsed SGR; the response to SGR was evaluated by visual analogue scale (VAS) representing the intensity of glossalgia and D parameters used in heart rate variability analysis. High-wattage pulsed SGR significantly decreased the mean value of VAS in all cases without any adverse event such as thermal injury. D parameters mostly correlated with clinical condition of BMS. High-wattage pulsed SGR was safe and effective for the treatment of BMS; D parameters are useful for assessing efficacy of SGR on BMS.

Whole brain-pituitary in vitro preparation of the transgenic medaka (Oryzias latipes) as a tool for analyzing the differential regulatory mechanisms of LH and FSH release.

Two types of gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), are important pituitary hormones for sexual maturation and reproduction, and both of them are centrally regulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus. In mammals, these two gonadotropins are secreted from a single type of gonadotrope. The mechanisms of differential regulation by GnRH of the release of two types of gonadotropins with different secretory profiles are still unknown. In teleosts, however, LH and FSH are secreted from separate cellular populations, unlike in mammals. This feature makes them useful for studying the regulatory mechanisms of LH and FSH secretions independently. Here, we generated transgenic medaka lines that express Ca(2+) indicator protein, inverse-pericam, specifically in the LH or FSH cells. We performed cell-type-specific Ca(2+) imaging of LH and FSH cells, respectively, using the whole brain-pituitary preparations of these transgenic fish in which all neural circuits and GnRH neuronal projection to the pituitary are kept intact. LH and FSH cells showed different Ca(2+) responses to GnRH. The results suggest differential regulation mechanisms for LH and FSH release by GnRH. Moreover, we also succeeded in detecting the effect on LH cells of endogenous GnRH peptide, which was released by electrical stimulation of the axons of GnRH1 neurons. Thus, our newly developed experimental model system using the whole brain-pituitary in vitro preparation of the transgenic medaka is a powerful tool for analyzing the differential regulatory mechanisms of the release of LH and FSH by multisynaptic neural inputs to the pituitary.

Selective autophagy regulates insertional mutagenesis by the Ty1 retrotransposon in Saccharomyces cerevisiae.

Macroautophagy (autophagy) is a bulk degradation system for cytoplasmic components and is ubiquitously found in eukaryotic cells. Autophagy is induced under starvation conditions and plays a cytoprotective role by degrading unwanted cytoplasmic materials. The Ty1 transposon, a member of the Ty1/copia superfamily, is the most abundant retrotransposon in the yeast Saccharomyces cerevisiae and acts to introduce mutations in the host genome via Ty1 virus-like particles (VLPs) localized in the cytoplasm. Here we show that selective autophagy downregulates Ty1 transposition by eliminating Ty1 VLPs from the cytoplasm under nutrient-limited conditions. Ty1 VLPs are targeted to autophagosomes by an interaction with Atg19. We propose that selective autophagy safeguards genome integrity against excessive insertional mutagenesis caused during nutrient starvation by transposable elements in eukaryotic cells.

Selective transport of alpha-mannosidase by autophagic pathways: identification of a novel receptor, Atg34p.

In Saccharomyces cerevisiae, aminopeptidase I (Ape1p) and α-mannosidase (Ams1p) are known cargoes of selective autophagy. Atg19p has been identified as an Ape1p receptor and targets Ape1p to the preautophagosomal structure (PAS). Under nutrient-rich conditions, transport of Ams1p to the vacuole largely depends on Atg19p. Here, we show that Atg34p (Yol083wp), a homolog of Atg19p, is a receptor for Ams1p transport during autophagy. Atg34p interacted with Ams1p, Atg11p, and Atg8p using distinct domains. Homo-oligomerized Ams1p bound to the Ams1-binding domain of Atg34p; this binding was important for the formation of a higher order complex named the Ams1 complex. In the absence of the interaction of Atg34p with Atg8p, the Ams1 complex was targeted to the preautophagosomal structure but failed to transit to the vacuole, indicating that the interaction of Atg34p with Atg8p is crucial for the Ams1 complex to be enclosed by autophagosomes. Atg34p and Atg19p have similar domain structures and are important for Ams1p transport during autophagy.

Tor directly controls the Atg1 kinase complex to regulate autophagy.

Autophagy is a bulk proteolytic process that is indispensable for cell survival during starvation. Autophagy is induced by nutrient deprivation via inactivation of the rapamycin-sensitive Tor complex1 (TORC1), a protein kinase complex regulating cell growth in response to nutrient conditions. However, the mechanism by which TORC1 controls autophagy and the direct target of TORC1 activity remain unclear. Atg13 is an essential regulatory component of autophagy upstream of the Atg1 kinase complex, and here we show that yeast TORC1 directly phosphorylates Atg13 at multiple Ser residues. Additionally, expression of an unphosphorylatable Atg13 mutant bypasses the TORC1 pathway to induce autophagy through activation of Atg1 in cells growing under nutrient-rich conditions. Our findings suggest that the direct control of the Atg1 complex by TORC1 induces autophagy.

The yeast Tor signaling pathway is involved in G2/M transition via polo-kinase.

The target of rapamycin (Tor) protein plays central roles in cell growth. Rapamycin inhibits cell growth and promotes cell cycle arrest at G1 (G0). However, little is known about whether Tor is involved in other stages of the cell division cycle. Here we report that the rapamycin-sensitive Tor complex 1 (TORC1) is involved in G2/M transition in S. cerevisiae. Strains carrying a temperature-sensitive allele of KOG1 (kog1-105) encoding an essential component of TORC1, as well as yeast cell treated with rapamycin show mitotic delay with prolonged G2. Overexpression of Cdc5, the yeast polo-like kinase, rescues the growth defect of kog1-105, and in turn, Cdc5 activity is attenuated in kog1-105 cells. The TORC1-Type2A phosphatase pathway mediates nucleocytoplasmic transport of Cdc5, which is prerequisite for its proper localization and function. The C-terminal polo-box domain of Cdc5 has an inhibitory role in nuclear translocation. Taken together, our results indicate a novel function of Tor in the regulation of cell cycle and proliferation.