The expression of the formin Fhod3 in mouse tongue striated muscle.

The sarcomere is the contractile unit of striated muscle and is composed of actin and myosin filaments. There is increasing evidence to support that actin assembly mediated by Fhod3, a member of the formin family of proteins, is critical for sarcomere formation and maintenance in cardiac muscle. Fhod3, which is abundantly expressed in the heart, localizes to the center of sarcomeres and contributes to the regulation of the cardiac function, as evidenced by the fact that mutations in Fhod3 cause cardiomyopathy. However, the role of Fhod3 in skeletal muscle, another type of striated muscle, is unclear. We herein show that Fhod3 is expressed in the tongue at both mRNA and protein levels, although in smaller amounts than in the heart. To determine the physiological role of Fhod3 expressed in the tongue, we generated embryos lacking Fhod3 in the tongue. The tongue tissue of the Fhod3-depleted embryos did not show any significant structural defects, suggesting that Fhod3 is dispensable for normal development of the mouse tongue. Unexpectedly, the immunostaining analysis revealed the absence of specific sarcomeric signals for Fhod3 in the wild-type tongue when compared to the Fhod3-depleted tongue as a negative control, despite the use of antibodies that had previously been validated by immunostaining of heart tissues. Taken together, although Fhod3 protein is expressed at a significant level in the tongue, Fhod3 in the tongue does not appear to exhibit the same sarcomeric pattern as observed in the heart, suggesting a different role for Fhod3 in the tongue muscles.Key words: actin, formin, sarcomere, striated muscle.

Comparison of Nocifensive Behavior in NaV1.7-, NaV1.8-, and NaV1.9-Channelrhodopsin-2 Mice by Selective Optogenetic Activation of Targeted Sodium Channel Subtype-Expressing Afferents.

Voltage-gated sodium channels, including NaV1.7, NaV1.8, and NaV1.9, play important roles in pain transmission and chronic pain development. However, the specific mechanisms of their action remain unclear, highlighting the need for in vivo stimulation studies of these channels. Optogenetics, a novel technique for targeting the activation or inhibition of specific neural circuits using light, offers a promising solution. In our previous study, we used optogenetics to selectively excite NaV1.7-expressing neurons in the dorsal root ganglion of mice to induce nocifensive behavior. Here, we further characterize the impact of nocifensive behavior by activation of NaV1.7, NaV1.8, or NaV1.9-expressing neurons. Using CRISPR/Cas9-mediated homologous recombination, NaV1.7-iCre, NaV1.8-iCre, or NaV1.9-iCre mice expressing iCre recombinase under the control of the endogenous NaV1.7, NaV1.8, or NaV1.9 gene promoter were produced. These mice were then bred with channelrhodopsin-2 (ChR2) Cre-reporter Ai32 mice to obtain NaV1.7-ChR2, NaV1.8-ChR2, or NaV1.9-ChR2 mice. Blue light exposure triggered paw withdrawal in all mice, with the strongest response in NaV1.8-ChR2 mice. These light sensitivity differences observed across NaV1.x-ChR2 mice may be dependent on ChR2 expression or reflect the inherent disparities in their pain transmission roles. In conclusion, we have generated noninvasive pain models, with optically activated peripheral nociceptors. We believe that studies using optogenetics will further elucidate the role of sodium channel subtypes in pain transmission.

Ten-year single-center outcomes following endovascular repair for abdominal aortic aneurysm using the INCRAFT device.

OBJECTIVE: This study aimed to report the long-term outcomes beyond 10 years of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms using the low-profile INCRAFT device. METHODS: This was a single-center, retrospective cohort study of all patients undergoing EVAR using the INCRAFT device as part of the regulatory trial between 2012 and 2013. Primary endpoint was aneurysm-related death. Secondary endpoints were all-cause death, reintervention, late open conversion, and aneurysm status (shrinkage, stable, and growth). RESULTS: Thirty patients with a mean age of 71.8 ± 7.7 years were included in this study. The median aneurysm diameter at EVAR was 54.5 mm (interquartile range, 53-56.8 mm). All abdominal aortic aneurysms in this study were treated following the device's instructions for use. At index EVAR, the INCRAFT device was successfully implanted in all patients using a percutaneous approach under local anesthesia. No patients experienced major adverse events or procedure-related complications 30 days after EVAR. During the median follow-up of 125 months (interquartile range, 98-131 months) with follow-up rates of 100% at 5 years and 96.7% at 10 years, aneurysm-related mortality was 0%, and freedom from all-cause mortality was 82.9% at 5 years and 75.3% at 10 years. Reintervention was required in 10 patients with 15 procedures. Sac growth was observed in 11 patients (36.7%), six of whom eventually required late open conversion; five of these patients underwent open aneurysmorrhaphy with stent graft preservation, and one underwent open surgical repair with endograft explantation. Late rupture was identified in one case, where type Ia endoleak led to rupture at 69 months, and open repair was successfully performed. Freedom from reintervention was 89.0% at 5 years but declined to 60.9% at 10 years; freedom from late open conversion was 100% at 5 years but declined to 70.8% at 10 years. CONCLUSIONS: Long-term outcomes of the INCRAFT stent graft showed no aneurysm-related deaths. However, sac growth occurred persistently throughout the follow-up period, resulting in a relatively high rate of reinterventions in the later periods, which highlights the importance of lifelong postoperative surveillance and appropriate reinterventions when indicated.

Midterm outcomes of endovascular repair for abdominal aortic aneurysm using the cuff-first technique to prevent type II endoleaks.

OBJECTIVE: The aim of this study was to evaluate the initial and midterm outcomes of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) using the cuff-first technique (CFT) to prevent type II endoleak (T2EL). METHODS: CFT involves deploying an aortic cuff inside the AAA to cover the ostium of the aortic side branch vessels before deploying the main body. We performed a retrospective review of all patients undergoing EVAR with CFT or side branch embolization (SBE) for AAAs at The Jikei University Hospital between 2016 and 2022. Primary endpoint was the rate of aneurysm sac shrinkage. Secondary endpoints were procedure time, radiation exposure, technical and clinical success rates, occurrence of T2EL, and freedom from reintervention or aneurysm-related death. RESULTS: Of 406 patients who underwent EVAR for AAAs, CFT was utilized in 56 (CFT group) and SBE in 35 (SBE group); all 91 patients were included in this study. There were no differences in patient demographics between groups, but there were differences in patency rate of the inferior mesenteric artery and absent intraluminal thrombus. The technical success rate per target vessel in the CFT and SBE group was 97.8% and 91.8%, and the clinical success rate was 91.0% and 100%, respectively. The median procedure time was shorter for CFT than for SBE: CFT, 10 (interquartile range [IQR], 6-14) minutes vs SBE, 25 (IQR, 18.5-45) minutes; P < .05), and median radiation exposure was lower for CFT than for SBE (CFT, 1455 (IQR, 840-2634) mGy vs SBE, 2353 (IQR, 1552-3586) mGy; P < .05). During the median follow-up of 25 months (IQR, 12.5-47 months), sac shrinkage occurred at similar rates in both groups (CFT, 37.5% vs SBE, 40.0%; P = .812), and there were no differences in freedom from reintervention (CFT, 96.2% and 91.4% at 12 and 36 months vs SBE, 100% and 89.5% at 12 and 36 months; log-rank P = .761) and freedom from aneurysm-related death (100% at 36 months in both groups; log-rank P = .440). The odds ratio of CFT vs SBE for sac regression was calculated by adjusting for inferior mesenteric artery patency and absent intraluminal thrombus, resulting in no statistical significance (odds ratio, 1.231; 95% confidence interval, 0.486-3.122). CONCLUSIONS: CFT is feasible with a shorter procedure time and lower radiation exposure than SBE and comparable mid-term outcomes, including sac shrinkage rate, compared with SBE. We believe that CFT, if anatomically suitable, is an alternative to SBE for the prevention of T2EL during EVAR.

Clinical impact of proximal fixation augmentation using the Najuta thoracic fenestrated stent graft during endovascular treatment for distal aortic arch aneurysm.

OBJECTIVE: Prevention of late type Ia endoleaks is the main concern in thoracic endovascular aortic aneurysm repair (TEVAR) for thoracic aortic aneurysm. Since 2017, we have performed zone 0 TEVAR with proximal fixation augmentation using a Najuta thoracic fenestrated stent graft in addition to zone 2 TEVAR for distal arch aneurysms. We report the early and midterm outcomes of TEVAR performed using this strategy. METHODS: This single-center retrospective study enrolled 386 cases of TEVAR for thoracic aortic disease between January 2013 and December 2020. Patients with thoracic aortic aneurysm treated by TEVAR landing at zone 2 was referred to as the standard group, whereas those treated by TEVAR landing at zone 0 using a Najuta fenestrated stent graft in addition to zone 2 TEVAR was referred to as the augmentation group. We retrospectively compared the clinical outcomes between the two groups. The primary end point was secondary intervention for postoperative type Ia endoleaks. Secondary end points were technical success, aneurysm-related death, and major adverse events (MAEs), including stroke, paraplegia, endoleaks, and secondary interventions. RESULTS: We performed TEVAR in 41 and 30 cases in the standard and augmentation groups, respectively. The mean aneurysm sizes in the standard and augmentation groups were 54.5 and 57.3 mm (P = .23), and the proximal neck lengths were 16.8 and 17.4 mm (P = .65), respectively. The anatomical characteristics seemed to be similar in both groups. The technical success rate in both groups was 100%. Three cases in the standard group had MAEs, including two stroke and one brachial artery pseudoaneurysm; whereas two cases had MAEs in the augmentation group, including one stroke and one paraplegia. There was no 30-day mortality or retrograde type A dissection in both groups. The mean observation periods in the standard and augmentation groups were 46 months (range, 1-123 months) and 35 months (range, 1-73 months), respectively. At 36 and 60 months after the procedure, the freedom from aneurysm-related death was 97.6% and 97.6% in the standard group, 100.0% and 100.0% in the augmentation group (P = .39); and the freedom from reintervention for type Ia endoleaks was 79.2% and 65.2% in the standard group, 100.0% and 100.0% in the augmentation group (P = .0087). A statistically significant decrease in reinterventions for type Ia endoleaks was observed in the augmentation group. CONCLUSIONS: Proximal fixation augmentation using the Najuta fenestrated stent graft during TEVAR for distal arch aneurysm is effective in preventing the postoperative late type Ia endoleaks.

Impact of osteoporosis on overall survival following endovascular repair for abdominal aortic aneurysms.

OBJECTIVE: To evaluate the impact of osteoporosis on overall survival following endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAAs). METHODS: This was a retrospective, single-center cohort study on 172 patients who had undergone primary EVAR for AAA between 2016 and 2018. Bone mineral density (BMD) was assessed by measuring the Hounsfield units (HUs) of the 11th thoracic vertebra on preoperative computed tomography; a BMD value of <110 HU was considered osteoporosis. All patients were divided into those with osteoporosis and those without osteoporosis, and long-term outcomes were compared. In addition, hazard ratios of each variable for all-cause mortality were evaluated using univariate and multivariate analysis. RESULTS: All 172 patients were divided into two groups: 72 patients (41.9%) with osteoporosis and 100 patients (58.1%) without osteoporosis. The mean age was older and the mean BMD was lower in patients with osteoporosis than patients without osteoporosis (mean, 79.2 ± 7.2 years vs 75.0 ± 8.7 years, respectively; P < .05; 78.1 ± 26.7 HU vs 155.1 ± 36.3 HU, respectively; P < .05). During the median follow-up period of 68 months, overall survival was significantly lower in patients with osteoporosis than patients without osteoporosis (osteoporosis: 63.9% and 36.7% at 5 years and 7 years; nonosteoporosis: 83.8% and 74.6% at 5 years and 7 years, respectively; log-rank P < .05); freedom from aneurysm-related mortality did not differ significantly between groups (osteoporosis: 94.3% and 89.0% at 5 years and 7 years; nonosteoporosis: 100.0% and 96.7% at 5 years and 7 years, respectively; log-rank P = .078). In a multivariate analysis for overall survival after EVAR, coexistence of osteoporosis was found to be an independent risk factor for all-cause mortality (hazard ratio, 1.76; 95% confidence interval, 1.01-3.06; P < .05), as well as variables including age, statin use, sarcopenia, and aneurysm diameter. CONCLUSIONS: Patients with osteoporosis showed a higher all-cause mortality after EVAR than patients without osteoporosis. We believe that comorbidity of osteoporosis may be useful in estimating the life expectancy of patients with AAA.

Sarcopenia Aneurysm Scoring System Predicts Early and Midterm Mortality After Endovascular Repair for Abdominal Aortic Aneurysm.

OBJECTIVE: The objective of the study was to develop a better model of prediction after EVAR using the psoas muscle index (PMI). SUMMARY BACKGROUND DATA: The Glasgow Aneurysm Score (GAS), the modified Leiden Score (mLS), the Comorbidity Severity Score (CSS), and the Euro Score (ES) are known prognostic scoring after EVAR. Similarly, sarcopenia measured by PMI has been reported to be an important predictor. This study investigated a new scoring system using PMI predicting short and midterm overall mortality after EVAR. METHODS: Three hundred ten patients were retrospectively evaluated. The primary endpoint was all-cause death. One hundred three patients were assigned to the derivation cohort and 207 patients to the validation cohort. RESULTS: The all-cause mortality rates were 8.8% at 1 year, 23.5% at 3 years, and 32.8% at 5 years. In a multivariate analysis, age, aneurysm diameter, eGFR, and PMI were associated with all-cause mortality in the derivation cohort. The SAS system was defined as the sum of the following factors: elderly (75 years), large aneurysm (65 mm), low eGFR (30 mL/min/1.73m 2 ), and low PMI (males: 48.2 cm 2 /m 2 , females: 36.8 cm 2 /m 2 ). We compared the SAS with the other prognostic scoring for 5-year mortality evaluating the area under the receiver operating characteristic curves in the validation cohort (GAS: 0.731, mLS: 0. 718, CSS: 0. 646, ES: 0.661, and SAS: 0.785, P = 0.013). CONCLUSION: We developed the SAS to predict all-cause mortality after elective EVAR and this scoring showed excellent predictive performance.

The masseter muscle thickness is a predictive marker for postoperative pneumonia after endovascular aneurysm repair.

PURPOSE: Oral frailty is characterized by a decrease in the oral and swallowing function and is a risk factor for pneumonia. In the current study, we analyzed the association between the masseter muscle thickness (MMT) and postoperative pneumonia and mortality after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm. METHODS: Overall, 247 patients were retrospectively evaluated. The primary end point was postoperative pneumonia. The MMT was measured as the maximum thickness of the masseter muscle 2 cm caudal to the zygomatic arch using computed tomography images obtained within 3 months before EVAR. Pneumonia was defined as the presence of progressive infiltrates, consolidation, or cavitation on imaging and a fever or leukocytosis. RESULTS: Twenty (8.1%) cases of postoperative pneumonia occurred within 1 year after EVAR. We found that patients with a low MMT (≤ 30th percentile: males, 10.4 mm; females: 8.8 mm) had a significantly higher risk of developing postoperative pneumonia within 1 year after elective EVAR than those with a high value. A comparison of the utility of the MMT and psoas muscle index (PMI) for predicting the 1-, 3-, and 5-year all-cause mortality revealed that the MMT had superior predictive performance. CONCLUSION: The MMT before elective EVAR predicted postoperative pneumonia and life expectancy, and its predictive performance was superior to that of the PMI.

Frequency of the requirement of inappropriate uncuffed tracheal tube size for pediatric patients: a retrospective observational analysis.

BACKGROUND: The insertion of inappropriately sized uncuffed endotracheal tubes (ETTs) with a tight seal or presence of air leakage may be necessary in children. This study aimed to analyze the frequency of the requirement of inappropriately sized uncuffed ETT insertion, air leakage after the ETT was replaced with one of a larger size, and factors associated with air leakage after ETT replacement. METHODS: Patients under 2 years of age who underwent oral surgery under general anesthesia with uncuffed ETTs between December 2013 and May 2015 were enrolled. The ETT size was selected at the discretion of the attending anesthesiologists. A leak test was performed after intubation. The ETT was replaced when considered necessary. Data regarding the leak pressure (PLeak) and inspiratory and expiratory tidal volumes were extracted from anesthesia records. We considered a PLeak of 10 < PLeak ≤ 30 cmH2O to be appropriate. The frequencies of the requirement of inappropriately sized ETTs, absence of leakage after ETT replacement, ETT size difference, and leak rate were calculated. A logistic regression was performed, with PLeak, leak rate, and size difference included as explanatory variables and presence of leakage after replacement as the outcome variable. RESULTS: Out of the 156 patients enrolled, 109 underwent ETT replacement, with the requirement of inappropriately sized ETTs being observed in 25 patients (23%). ETT replacement was performed in patients with PLeak ≤ 10 cmH2O; leakage was absent after replacement (PLeak < 30 cmH2O) in 52% of patients (25/48). In the multivariate logistic model, the leak rate before ETT replacement was significantly associated with the presence of leakage after replacement (p = 0.021). CONCLUSIONS: Inappropriately sized ETTs were inserted in approximately 23% of the patients. The leak rate may be useful to guide ETT replacement.

Effect of short- and long-term heat exposure on brain monoamines and emotional behavior in mice and rats.

Heat exposure affects several physiological, neuronal, and emotional functions. Notably, monoaminergic neurotransmitters in the brain such as noradrenaline, dopamine, and serotonin, which regulate several basic physiological functions, such as thermoregulation, food intake, and energy balance, are affected by heat exposure and heat acclimation. Furthermore, cognition and emotional states are also affected by heat exposure and changes in brain monoamine levels. Short-term heat exposure has been reported to increase anxiety in some behavioral tests. In contrast, there is a possibility that long-term heat exposure decreases anxiety due to heat acclimation. These changes might be due to adaptation of the core body temperature and/or brain monoamine levels by heat exposure. In this review, we first outline the changes in brain monoamine levels and thereafter focus on changes in emotional behavior due to heat exposure and heat acclimation. Finally, we describe the relationships between emotional behavior and brain monoamine levels during heat acclimation.

Aortic Wall Enhancement Detected by Contrast Computed Tomography Scan Predicts Aortic Remodeling after Conservative Therapy for Acute Uncomplicated Type B Dissection.

BACKGROUND: The Investigation of Stent Grafts in Aortic Dissection with extended length of follow-up trial showed that pre-emptive thoracic endovascular aneurysm repair (TEVAR) for the uncomplicated type B dissection (TBAD) in the subacute phase promotes aortic remodeling and avoids aortic-related death 5 years after onset. However, there are some patients with complete aortic remodeling (CAR) with optimal medical treatment (OMT) and severe complications after TEVAR such as retrograde type A dissection. Therefore, which patients should undergo pre-emptive TEVAR and optimal surgical timing are still under debate. We reported that aortic wall enhancement (AWE) after endovascular aneurysm repair for abdominal aortic aneurysm was associated with sac shrinkage. However, there is no report about the relationship between AWE and aortic dissection. Herein, we evaluated the relationship between AWE and acute TBAD. METHODS: From March 2012 to May 2018, consecutive patients with acute TBAD were retrospectively collected. We retrospectively analyzed 35 patients with acute TBAD who were treated with OMT and without pre-emptive TEVAR in the subacute phase. AWE was defined as an increase of more than 20 Hounsfield units in mean computed tomography (CT) values, comparing images in delayed contrast-enhanced scans with those in plain scans evaluated within 3 months from onset. The measurement points were all slices including the wall of the false lumen. The patients with traumatic dissection, type A dissection, acute complicated type B dissection, chronic (>12 weeks) dissection, and those lost to follow-up within 3 months from onset were excluded. The primary end point was spontaneous CAR under OMT, as determined by the latest contrast-enhanced CT scan. RESULTS: The median follow-up period from onset was 86 weeks and there were 25 cases (71.4%) with AWE. Under OMT, CAR was observed in 20 patients (57.1%); this was significantly associated with abdominal branch dissection (6/15 [40%] vs. 2/20 [10%], P = 0.050), number of tears more than 2 at onset (11/15 [73%] vs. 4/20 [20%], P = 0.003), multiple tears at 1 month after onset (9/15 [60%] vs. 4/20 [20%], P = 0.020), maximal false lumen diameter at 1 month after onset (14 vs. 8 mm, P = 0.025), and AWE within 3 months of onset (7/15 [47%] vs. 18/20 [90%], P = 0.010). Multivariate analysis demonstrated a significant difference with multiple tears at onset (P = 0.014) and AWE within 3 months of onset (P = 0.047). CONCLUSIONS: AWE was associated with CAR under OMT for acute TBAD which is out of indication of pre-emptive TEVAR. Presence of AWE may be useful in predicting prognosis of TBAD.

Effect of heat acclimation on anxiety-like behavior of rats in an open field.

To mitigate the impacts of heat exposure, animals can take some actions to maintain their core body temperature, such as heat acclimation; however, the effect of heat acclimation on anxiety-like behavior in an open field is still not understood. The purpose of this study was to examine the anxiety-like behavior of heat acclimated rats in a temperate or heated open field. After being raised in a 23 °C environment for one week, male Wistar rats were exposed to a heated environment (32 °C) for 3 h (3H), 14 days (14D), or 28 days (28D), with free access to food and water, and compared with rats reared in a temperate environment (23 °C; Cont). After heat exposure, behavioral changes were monitored using an open field test (OFT) in a heated (32 °C) or temperate environment (23 °C). Compared with those in the Cont group, the body weights of rats in the 14D and 28D groups were lower. The OFT in the heated environment showed that grooming time was longer in 3H and 14D rats. In the temperate environment, grooming time was longer in all the heated groups. Rats from the 3H and 28D groups spent longer time in the center square when tested in the temperate environment. Rearing activity increased in 28D rats in the temperate environment, while the number of line crossings did not differ significantly between the heated groups and the two open fields. These results suggest that heat acclimation affected not only the physiological index such as core body temperature but also the anxiety-like behavior, mainly in the temperate open field. These changes might be beneficial when rats are faced with an open field.

Concomitant Coil Embolization for Gutter Leak during Endovascular Aortic Repair with the Snorkel Technique.

Snorkel endovascular aortic repair (SEVAR) is reported to be effective for the treatment of pararenal or juxtarenal aortic aneurysms. SEVAR can be performed with an off-the-self device, which is applied for emergency cases. However, there is a concern that SEVAR lead to gutter leak due to insertion of multiple stents. Previously, we performed 2-staged treatment for gutter leak after SEVAR. However, the gutter leaks can also occur late, and it is often difficult to close. Therefore, if a significant gutter leak is identified intraoperatively, performing concomitant gutter coil embolization at the time of the initial surgery may be reasonable.

Changes of brain monoamine levels and physiological indexes during heat acclimation in rats.

Brain monoamines, such as noradrenaline (NA), dopamine (DA), and serotonin (5-HT), regulate many important physiological functions including thermoregulation. The purpose of this study was to clarify changes in NA, DA, and 5-HT levels in several brain regions in response to heat acclimation while also recording body temperature (Tb), heart rate (HR), and locomotor activity (Act). Rats were exposed to a heated environment (32°C) for 3h (3H), 1 day (1D), 7 days, 14 days (14D), 21 days, or 28 days (28D). After heat exposure, each of the following brain regions were immediately extracted and homogenized: the caudate putamen (CPu), preoptic area (PO), dorsomedial hypothalamus (DMH), frontal cortex (FC), and hippocampus (Hip). NA, DA, and 5-HT levels in the extract were measured by high performance liquid chromatography. Although Tb increased immediately after heat exposure, it decreased about 14D later. HR was maintained at a low level throughout heat exposure, and Act tended to increase near the end of heat exposure. After 3H, we observed a marked increase in NA level in the CPu. Although this response vanished after 1D, the level increased again after 28D. DA level in the CPu decreased significantly from 1D to 28D. 5-HT level in the PO and DMH decreased from 1D to 14D. It returned to control levels after 28D with increment of DA level. 5-HT level in the FC decreased at the start of heat exposure, but recovered after 28D; a time point at which DA level also increased. Monoamine levels in the Hip were unchanged after early heat exposure, but both 5-HT and DA levels increased after 28D. These results provide definitive evidence of changes in monoamines in individual brain regions involved in thermoregulation and behavioral, cognitive, and memory function during both acute and chronic heat exposure.

Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein-Barr virus-associated T cell and natural killer cell lymphoma.

The ubiquitous Epstein-Barr virus (EBV) infects not only B cells but also T cells and natural killer (NK) cells and is associated with various lymphoid malignancies. Recent studies have reported that histone deacetylase (HDAC) inhibitors exert anticancer effects against various tumor cells. In the present study, we have evaluated both the in vitro and in vivo effects of suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor, on EBV-positive and EBV-negative T and NK lymphoma cells. Several EBV-positive and EBV-negative T and NK cell lines were treated with various concentrations of SAHA. SAHA suppressed the proliferation of T and NK cell lines, although no significant difference was observed between EBV-positive and EBV-negative cell lines. SAHA induced apoptosis and/or cell cycle arrest in several T and NK cell lines. In addition, SAHA increased the expression of EBV-lytic genes and decreased the expression of EBV-latent genes. Next, EBV-positive NK cell lymphoma cells were subcutaneously inoculated into severely immunodeficient NOD/Shi-scid/IL-2Rγnull mice, and then SAHA was administered intraperitoneally. SAHA inhibited tumor progression and metastasis in the murine xenograft model. SAHA displayed a marked suppressive effect against EBV-associated T and NK cell lymphomas through either induction of apoptosis or cell cycle arrest, and may represent an alternative treatment option.

Fenestrated Thoracic Endovascular Repair for Acute Type B Aortic Dissection with Isolated Left Vertebral Artery: A Case Report.

Thoracic endovascular aortic repair (TEVAR) of acute uncomplicated type B aortic dissection (uTBAD) has been discussed for its potential to prevent future aortic events. We present a fenestrated TEVAR in the case of an 86-year-old man with acute uTBAD with an isolated left vertebral artery (ILVA). The ILVA originated from the distal side of the left subclavian artery, the left subclavian artery, and the intramural hematoma with an ulcer-like projection extended close to the left subclavian artery. We selected a fenestrated stent graft to achieve a proximal healthy landing. This case demonstrates that a fenestrated stent graft for acute uTBAD is useful for preserving arch vessels.

Regional and temporal genotype profiling of Clostridioides difficile in a multi-institutional study in Japan.

Clostridioides difficile, a cause of healthcare-associated infections, poses a significant global health threat. This multi-institutional retrospective study focuses on epidemic dynamics, emphasizing minor and toxin-negative clinical isolates through high-resolution genotyping. The genotype of the C. difficile clinical isolates during 2005 to 2022 was gathered from 14 hospitals across Japan (N = 982). The total number of unique genotypes was 294. Some genotypes were identified in every hospital (cross-regional genotypes), while others were unique to a specific hospital or those in close geographic proximity (region-specific genotypes). Notably, a hospital located in a sparsely populated prefecture exhibited the highest prevalence of region-specific genotypes. The isolation rate of cross-regional genotypes positively correlated with the human mobility flow. A 6-month interval analysis at a university hospital from 2019 to 2021 revealed a temporal transition of the genotype dominance. The frequent isolation of identical genotypes over a brief timeframe did not always align with the current criteria for defining nosocomial outbreaks. This study highlights the presence of diverse indigenous C. difficile strains in regional environments. The cross-regional strains may have a higher competency to spread in the human community. The longitudinal analysis underscores the need for further investigation into potential nosocomial spread.

Preemptive fenestrated endovascular repair aimed at perfusion of cervical branches in acute type B aortic dissection.

OBJECTIVE: Most of the entry tears of uncomplicated type B aortic dissection are located in the distal arch and extends in a retrograde manner to the level of the left subclavian artery. Our objective was to evaluate feasibility and effectiveness using fenestrated sent graft with complete neck vessel preservation to treat uncomplicated type B aortic dissection. SUBJECTS AND METHODS: We retrospectively reviewed the record of patients with uncomplicated type B aortic dissection who underwent fenestrated thoracic endovascular aortic repair in subacute phase (15-90 days) between August 2016 and April 2020. The Najuta fenestrated stent graft was placed proximally beyond he left subclavian artery (zone 0-2) in an attempt to seal the entry while preserving the neck vessels. RESULTS: We evaluated 9 cases (male: 7, female: 2; median age 70 years). The median distance from the LSA to the proximal entry was 37 mm. The landing zones of the proximal end of the Najuta were zone 0: 3, zone 1: 2, and zone 2: 4 cases. Technical success was 100% with no 30-day death. None of the patients had a stroke, paraplegia or retrograde dissection, and no endoleak was observed. Complete aortic remodeling with false lumen resolution was obtained in all cases while each fenestrated vessels remained patent during the follow-up period. CONCLUSION: Preemptive thoracic endovascular aortic repair aimed at perfusion of cervical branches using the Najuta fenestrated stent is safe and effective and may be considered as a reasonable treatment option for the treatment is a safe and an effective treatment.

Initial loading of dexmedetomidine and continuous propofol sedation for prevention of delayed recovery: A randomized controlled trial.

BACKGROUND: Sedation with continuous dexmedetomidine and bolus midazolam administration provides a lower incidence of unacceptable patient movement during procedures but requires a longer recovery time. The authors aimed to compare recovery time and unacceptable patient movement during sedation with initial loading of dexmedetomidine followed by continuous propofol infusion with those during sedation with continuous dexmedetomidine and bolus midazolam administration. METHODS: In this prospective randomized controlled trial, 54 patients undergoing dental surgery and requiring intravenous sedation were assigned to either the dexmedetomidine and propofol group (n = 27, dexmedetomidine administered at 6 µg/kg/h for 5 minutes, followed by continuous propofol infusion using a target-controlled infusion) or the dexmedetomidine and midazolam group (n = 27, dexmedetomidine administered at 0.2-0.7 µg/kg/h continuously after the same initial loading dose with bolus midazolam). A bispectral index of 70 through 80 was maintained during the procedure. Patient movement that interfered with the procedure and time from the end of sedation to achieving a negative Romberg sign were assessed. RESULTS: Times from the end of sedation to achieving a negative Romberg sign in the dexmedetomidine and propofol group (median, 14 minutes [interquartile range, 12-15 minutes]) were significantly shorter (P < .001) than in the dexmedetomidine and midazolam group (median, 22 minutes [interquartile range, 17.5-30.5 minutes]). The incidence of unacceptable patient movement was comparable between groups (n = 3 in the dexmedetomidine and propofol group, n = 4 in the dexmedetomidine and midazolam group; P = .999). CONCLUSIONS: Sedation with a single loading dose of dexmedetomidine followed by continuous propofol infusion can prevent delayed recovery without increasing unacceptable patient movement. PRACTICAL IMPLICATIONS: The combination of dexmedetomidine and propofol may provide high-quality sedation for ambulatory dental practice. This clinical trial was registered in the University Hospital Medical Information Network Clinical Trials Registry. The registration number is UMIN000039668.

Impact of Bifidobacterium adolescentis in patients with abdominal aortic aneurysm: a cross-sectional study.

The relationships between various diseases and the human gut microbiota (GM) have been revealed. However, the relationships between the human abdominal aortic aneurysm (AAA) and GM remains unknown. The aim of this cross-sectional study was to clarify the association between the human AAA and GM. Stool samples from 30 consecutive patients with AAA before aneurysm repair and those of 30 controls without vascular diseases were analyzed by 16S rRNA gene (V3-4) sequencing using an Illumina MiSeq system and QIIME 2. There was no significant difference in age (75 vs. 75 years) or gender (80% vs. 87% males) between the groups. No significant difference in GM composition was observed in principal coordinate analysis between the two groups, whereas the AAA group showed a significantly lower abundance of Bifidobacterium adolescentis (p<0.01) at the species level than the controls. This study demonstrated that the abundance of B. adolescentis decreased in patients with AAA. This is the first study to show the characteristics of the GM in patients with AAA. Studies are needed to reveal if causal relationships exists between the human AAA and GM.