Revascularization and Digestive Tract Repair in Secondary Aortoenteric Fistula Using a Single-Center in Situ Revascularization Strategy.

BACKGROUND: Information regarding optimal revascularization and digestive tract repair in secondary aortoenteric fistula (sAEF) remains unclear. Thus, reporting treatment outcomes and presenting comprehensive patient details through a structured treatment approach are necessary to establish a treatment strategy for this rare, complex, and fatal condition. METHODS: We performed a single-center retrospective review of consecutive sAEF managed based on our in situ revascularization and intestinal repair strategy. The primary endpoint of this study was all-cause mortality, and secondary endpoints were the incidence of in-hospital complications and midterm reinfections. RESULTS: Between 2007 and 2020, 16 patients with sAEF, including 13 men (81%), underwent in situ revascularization and digestive tract repair. The median follow-up duration for all participants was 36 (interquartile range, 6-62) months. Among the participants, 81% (n = 13), 13% (n = 2), and 6% (n = 1) underwent aortic reconstruction with rifampin-soaked grafts, unsoaked Dacron grafts, and femoral veins, respectively. The duodenum was the most commonly involved site in enteric pathology (88%; n = 14), and 57% (n = 8) of duodenal breaks were repaired by a simple closure. Duodenum's second part-jejunum anastomosis was performed in 43% of patients (n = 6), and 19% of the patients (n = 3) died perioperatively. In-hospital complications occurred in 88% patients (n = 14), and the most frequent complication was gastrointestinal. Finally, 81% patients (n = 13) were discharged home. Oral antibiotics were administered for a median duration of 5.7 months postoperatively; subsequently, the participants were followed up carefully. Reinfection was detected in 6% of the patients (n = 1) who underwent reoperation without any complications. The 1-year and 3-year overall survival rates of participants were 75% (n = 12) and 75% (n = 9), respectively, and no sAEF-related deaths occurred, except perioperative death. CONCLUSIONS: Surgical intervention with contemporary management based on our vascular strategy and digestive tract procedure may be a durable treatment for sAEF.

Negative chemotaxis of Ligilactobacillus agilis BKN88 against gut-derived substances.

Ligilactobacillus agilis is a motile lactic acid bacterium found in the gastrointestinal tracts of animals. The findings of our previous study suggest that the motility of L. agilis BKN88 enables gut colonization in murine models. However, the chemotactic abilities of motile lactobacilli remain unknown. This study aimed to identify the gut-derived chemoeffectors and their corresponding chemoreceptors in L. agilis BKN88. Chemotaxis assays with chemotactic and non-chemotactic (ΔcheA) L. agilis strains revealed that low pH, organic acids, and bile salts served as repellents. L. agilis BKN88 was more sensitive to bile and acid than the gut-derived non-motile lactobacilli, implying that L. agilis might utilize motility and chemotaxis instead of exhibiting stress tolerance/resistance. L. agilis BKN88 contains five putative chemoreceptor genes (mcp1-mcp5). Chemotaxis assays using a series of chemoreceptor mutants revealed that each of the five chemoreceptors could sense multiple chemoeffectors and that these chemoreceptors were functionally redundant. Mcp2 and Mcp3 sensed all tested chemoeffectors. This study provides further insights into the interactions between chemoreceptors and ligands of motile lactobacilli and the unique ecological and evolutionary features of motile lactobacilli, which may be distinct from those of non-motile lactobacilli.

Machine learning estimation of biodegradable organic matter concentrations in municipal wastewater.

This study investigates whether a novel estimation method based on machine learning can feasibly predict the readily biodegradable chemical oxygen demand (RB-COD) and slowly biodegradable COD (SB-COD) in municipal wastewater from the oxidation-reduction potential (ORP) data of anoxic batch experiments. Anoxic batch experiments were conducted with highly mixed liquor volatile suspended solids under different RB-COD and SB-COD conditions. As the RB-COD increased, the ORP breakpoint appeared earlier, and fermentation occurred in the interior of the activated sludge, even under anoxic conditions. Therefore, the ORP decline rates before and after the breakpoint were significantly correlated with the RB-COD and SB-COD, respectively (p < 0.05). The two biodegradable CODs were estimated separately using six machine learning models: an artificial neural network (ANN), support vector regression (SVR), an ANN-based AdaBoost, a SVR-based AdaBoost, decision tree, and random forest. Against the ORP dataset, the RB-COD and SB-COD estimation correlation coefficients of SVR-based AdaBoost were 0.96 and 0.88, respectively. To identify which ORP data are useful for estimations, the ORP decline rates before and after the breakpoint were separately input as datasets to the estimation methods. All six machine learning models successfully estimated the two biodegradable CODs simultaneously with accuracies of ≥0.80 from only ORP time-series data. Sensitivity analysis using the Shapley additive explanation method demonstrated that the ORP decline rates before and after the breakpoint obviously contributed to the estimation of RB-COD and SB-COD, respectively, indicating that acquiring the ORP data with various decline rates before and after the breakpoint improved the estimations of RB-COD and SB-COD, respectively. This novel estimation method for RB-COD and SB-COD can assist the rapid control of biological wastewater treatment when the biodegradable organic matter concentration dynamically changes in influent wastewater.

Immunogenic Modification of Ligilactobacillus agilis by Specific Amino Acid Substitution of Flagellin.

Ligilactobacillus agilis is a flagellated motile commensal microbe that resides in the gastrointestinal tract of mammals and birds. Flagellin, the major subunit protein of flagellar filament, from pathogenic bacteria is generally a proinflammatory molecule that stimulates immune cells via Toll-like receptor 5 (TLR5). Interestingly, the flagellins of L. agilis are known to be immunologically attenuated despite the fact that the structure of the proteins, including the TLR5 recognition site, is highly conserved among bacteria. The results of our previous study suggested that this is attributed to the differences in three specific amino acids within the conserved TLR5 recognition site; however, this hypothesis remains to be confirmed. In this study, a series of recombinant L. agilis flagellins, with amino acid substitutions at the TLR5 recognition site, were constructed, and their immunogenic activity was evaluated in vitro. Then, an L. agilis strain with an active immunogenic TLR5 recognition site was generated. In vitro and in vivo immunological studies revealed that the mutant L. agilis strain with the modified flagellin was more immunogenic than the wild-type strain. In conclusion, the specific amino acid residues in L. agilis flagellins likely contribute to the discrimination between pathogens and commensals by the host defense system. Additionally, the immunogenically potent L. agilis mutants may serve as a useful platform for oral vaccine delivery. IMPORTANCE The interactions between gut microbes and immune cells play an important role in the health and disease of hosts. Ligilactobacillus agilis is a flagellated commensal bacterium found in the gut of mammals and birds. However, the flagellin proteins of L. agilis are immunologically attenuated and barely induce TLR5-dependent inflammation, unlike the flagellins of several pathogenic bacteria. This study demonstrated that three specific amino acids in the flagellin protein are responsible for this low immunogenicity in L. agilis. The results obtained herein improve our understanding of the symbiosis between gut microbes and their hosts.

Prospective clinical study for claudication after endovascular aneurysm repair involving hypogastric artery embolization.

PURPOSE: This prospective study aimed to assess the prognosis of claudication after endovascular aneurysm repair (EVAR) involving hypogastric artery (HGA) embolization. METHODS: Patients who were scheduled to undergo EVAR involving bilateral or unilateral HGA embolization (BHE or UHE, respectively) between May 2017 and January 2019 were included in this study. Patients underwent the walk test preoperatively, one week postoperatively, and monthly thereafter for six months. The presence of claudication and the maximum walking distance (MWD) were recorded. A near-infrared spectroscopy monitor was placed on the buttocks, and the recovery time (RT) was determined. A walking impairment questionnaire (WIQ) was completed to determine subjective symptoms. RESULTS: Of the 13 patients who completed the protocol, 12 experienced claudication in the 6-min walk test. The MWD was significantly lower at one week postoperatively than preoperatively. The claudication prevalence was significantly higher at five and six months postoperatively after BHE than after UHE. BHE was associated with longer RTs and lower WIQ scores than UHE. CONCLUSIONS: We noted a trend in adverse effects on the gluteal circulation and subjective symptoms ameliorating within six months postoperatively, with more effects being associated with BHE than with UHE. These findings should be used to make decisions concerning management strategies for HGA reconstruction.

Prevention of Buttock Claudication by Preserving Antegrade Bilateral Superior Gluteal Arterial Blood Flow in EVAR for Aorto-Iliac Aneurysm Accompanied by Bilateral Internal Iliac Artery Aneurysms.

Buttock claudication (BC) is a complication of surgery for aorto-iliac aneurysms (AIAs) caused by sacrificing blood flow in the internal iliac artery (IIA). However, the preservation of antegrade blood flow of IIAs is often challenging when performing both open surgery and endovascular aneurysm repair (EVAR) for AIAs accompanied by IIA aneurysms. We performed EVAR and successfully preserved the antegrade blood flow of bilateral superior gluteal arteries using the GORE EXCLUDER iliac branch endoprosthesis with the VIABAHN endograft. BC did not occur, both subjectively and objectively, after surgery. This approach can be minimally invasive yet an effective procedure to prevent BC.

Xenopus laevis il11ra.L is an experimentally proven interleukin-11 receptor component that is required for tadpole tail regeneration.

Xenopus laevis tadpoles possess high regenerative ability and can regenerate functional tails after amputation. An early event in regeneration is the induction of undifferentiated cells that form the regenerated tail. We previously reported that interleukin-11 (il11) is upregulated immediately after tail amputation to induce undifferentiated cells of different cell lineages, indicating a key role of il11 in initiating tail regeneration. As Il11 is a secretory factor, Il11 receptor-expressing cells are thought to mediate its function. X. laevis has a gene annotated as interleukin 11 receptor subunit alpha on chromosome 1L (il11ra.L), a putative subunit of the Il11 receptor complex, but its function has not been investigated. Here, we show that nuclear localization of phosphorylated Stat3 induced by Il11 is abolished in il11ra.L knocked-out culture cells, strongly suggesting that il11ra.L encodes an Il11 receptor component. Moreover, knockdown of il11ra.L impaired tadpole tail regeneration, suggesting its indispensable role in tail regeneration. We also provide a model showing that Il11 functions via il11ra.L-expressing cells in a non-cell autonomous manner. These results highlight the importance of il11ra.L-expressing cells in tail regeneration.

Anticoagulation Therapy for Pregnancy-Associated Thrombosis: A Retrospective Observational Study.

Objectives: Pregnancy-associated deep vein thrombosis (DVT) is a rare disease, and data on anticoagulation therapy are lacking. The present study examined the treatment outcome with unfractionated heparin (UFH) subcutaneous injection in patients with pregnancy-associated DVT. Methods: This single-center, retrospective, observational study enrolled 15 patients with pregnancy-associated DVT treated from January 2014 to April 2021. Results: The median age was 35 years. The median gestation week at onset was 10 (interquartile range is 8-11). All patients presented with painful symptoms with edema. All patients had proximal DVT. Anticoagulation therapy using UFH was performed in 14 patients. The median continuous dose of heparin was 18,750 U/day, and the median subcutaneous dose was 20,000 U/day. During the outpatient period, the values of activated partial thromboplastin time fluctuated wildly, but the fibrin monomer complex level remained consistently low. There were two mild bleeding complications, but neither prevented the continuation of anticoagulation therapy. During delivery, thrombi were not detected in 10 of 13 patients (77%), whereas three patients (23%) exhibited regression without resolution of the thrombus. Conclusion: Anticoagulation using UFH subcutaneous injection was safely performed in patients with pregnancy-associated DVT without serious complications or progression of thrombosis.

Comparison of Edoxaban and Warfarin for the Treatment of Cancer-Associated Venous Thromboembolism　- A Retrospective Observational Study.

BACKGROUND: Because anticoagulant drugs for ambulatory patients with cancer-associated venous thromboembolism (CAT) are limited to warfarin and direct oral anticoagulants (DOACs) in Japan, it is important to assess the outcomes of both drugs.Methods and Results:We retrospectively assessed the outcomes of CAT patients who were treated with warfarin or edoxaban between 2011 and 2017. The assessment was limited to the duration of anticoagulant administration. CAT patients who did not receive anticoagulation therapy were also compared with the warfarin and edoxaban groups. We enrolled 111 CAT patients treated with warfarin (n=58, mean age 62.6 years, mean time in therapeutic range [TTR] % 61.1) or edoxaban (n=53, mean age 64.6 years). Although venous thromboembolism (VTE) recurred in 2 warfarin-treated patients, the 2 treatment groups were not significantly different (P=0.18). Bleeding during anticoagulation therapy occurred in 6 warfarin-treated patients (2 with major bleeding) and in 5 edoxaban-treated patients (no major bleeding) (P=1.0). The non-anticoagulation group (n=37) showed a high recurrence rate (P<0.01) compared with the anticoagulant group. CONCLUSIONS: This study showed that warfarin and edoxaban are equally effective in preventing VTE recurrence and bleeding. However, warfarin control in CAT patients presented some difficulties. This study also demonstrated the efficacy of anticoagulant drugs, compared with no anticoagulation, for CAT patients to prevent VTE recurrence.

Ligilactobacillus agilis BKN88 possesses thermo-/acid-stable heteropolymeric flagellar filaments.

Many flagellated bacteria possess multiple flagellins, but the roles and the compositions of each flagellin are diverse and poorly understood. In Ligilactobacillus agilis BKN88, there are two active flagellin gene paralogues but their function and composition in its flagellar filaments have not been described. The aim of this study is to find the function and composition of the flagellins by employing mutant strains each of which expresses a single flagellin or a modified flagellin. Two single flagellin-expressing strains were both flagellated while the number of flagella per cell in the single flagellin-expressing derivatives was lower than that in the wild type. Nonetheless, these derivative strains were apparently equally motile as the wild type. This indicates that either flagellin is sufficient for cell motility. The immunological activity via Toll-like receptor 5 of the single flagellin-expressing strains or purified single flagellins was readily detectable but mostly variably weaker than that of the wild type. The flagellar filaments of wild type L. agilis BKN88 were more acid-/thermo-stable than those of single flagellin-expressing derivatives. Using a combination of immunoprecipitation and flagellin-specific staining, wild type BKN88 appeared to possess heteropolymeric flagellar filaments consisting of both flagellins and each flagellin appeared to be equally distributed throughout the filaments. The results of this study suggest that the two flagellins together form a more robust filament than either alone and are thus functionally complementary.

Discovery of a CNS penetrant small molecule SMN2 splicing modulator with improved tolerability for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a motor neuron disease, typically resulting from loss-of-function mutations in the survival motor neuron 1 (SMN1) gene. Nusinersen/SPINRAZA, a splice-switching oligonucleotide that modulates SMN2 (a paralog of SMN1) splicing and consequently increases SMN protein levels, has a therapeutic effect for SMA. Previously reported small-molecule SMN2 splicing modulators such as risdiplam/EVRYSDI and its analog SMN-C3 modulate not only the splicing of SMN2 but also that of secondary splice targets, including forkhead box protein M1 (FOXM1). Through screening SMA patient-derived fibroblasts, a novel small molecule, designated TEC-1, was identified that selectively modulates SMN2 splicing over three secondary splice targets. TEC-1 did not strongly affect the splicing of FOXM1, and unlike risdiplam, did not induce micronucleus formation. In addition, TEC-1 showed higher selectively on galactosylceramidase and huntingtin gene expression compared to previously reported compounds (e.g., SMN-C3) due to off-target effects on cryptic exon inclusion and nonsense-mediated mRNA decay. Moreover, TEC-1 significantly ameliorated the disease phenotype in an SMA murine model in vivo. Thus, TEC-1 may have promising therapeutic potential for SMA, and our study demonstrates the feasibility of RNA-targeting small-molecule drug development with an improved tolerability profile.

PCR-based screening, isolation, and partial characterization of motile lactobacilli from various animal feces.

BACKGROUND: Most lactobacilli found in animal intestines are generally non-motile, but there are few exceptions. Our previous work showed that Lactobacillus agilis BKN88, which is a highly motile strain originating from a chicken, takes advantage of motility in gut colonization in murine models, and thus motile lactobacilli likely have unique ecological characteristics conferred by motility. However, the ecology and habitat of gut-derived motile lactobacilli are still rarely understood. In addition, the limited availability of motile Lactobacillus isolates is one of the major obstacles for further studies. To gain insight into the ecology and habitat of the motile lactobacilli, we established a routinely applicable detection method for motile lactobacilli using PCR and subsequent selective isolation in semi-solid MRS medium for the collection of additional motile lactobacilli from animal feces. RESULTS: We applied the PCR detection using motile lactobacilli-specific primers, based on the motor switch protein gene (fliG) of flagella, to 120 animal feces, followed by selective isolation performed using 45 animal feces. As a result, motile lactobacilli were detected in 44 animal feces. In the selective isolation, 29 isolates of L. agilis and 2 isolates of L. ruminis were obtained from 8 animal species. CONCLUSIONS: These results indicated that motile lactobacilli are distributed in different animal species. Moreover, phylogenetic analysis of the L. agilis isolates suggests co-evolution with the host, and adaptation to a particular environmental niche.

Midaortic Syndrome due to Takayasu Arteritis in a Child with Acute Decompensated Cardiac Failure Managed by an Emergency Axillo-External Iliac Artery Bypass: A Follow-Up Case Report of Long-Term Outcomes.

Midaortic syndrome (MAS) is characterized by a diffuse narrowing of the distal thoracic or abdominal aorta and is concomitant with various etiologies. The common symptoms of MAS include severe hypertension or arterial insufficiency distal to the stenosis. This includes lower extremity claudication and heart failure due to afterload mismatch. We present the case of an 8-year-old girl who developed acute decompensated cardiac, respiratory, and renal failures because of the occlusion of the descending aorta secondary to Takayasu arteritis (TA). Although thoracoabdominal-aortic bypass is usually performed for patients with MAS, the procedure was considered too invasive, given the patient's condition. Therefore, we performed an emergency axillo-external iliac artery bypass for revascularization. Subsequently, organ failure improved and she was discharged. At postoperative 10 years, an asymptomatic pseudoaneurysm was detected at the distal anastomosis, for which revision surgery was performed. Overall, the long-term prognosis was satisfactory, suggesting that this procedure is less invasive and effective for treatment of MAS due to TA, in emergencies.

Long-Term Outcomes of Acute Limb Ischemia: A Retrospective Analysis of 93 Consecutive Limbs.

Objective: To examine the medium- to long-term outcomes of acute limb ischemia (ALI), which are unclear at present. Methods: We analyzed 93 consecutive limbs in 77 patients with ALI between January 2005 and December 2015 treated at our vascular center. We categorized the cases into four groups according to etiology (embolism, thrombosis, graft thrombosis, and dissection groups) to assess survival, limb salvage, and freedom from re-intervention rates. Results: The mean age at onset was 72±15 years. The median follow-up length was 2.90 years. The Rutherford categories I, IIa, IIb, and III included 1, 38, 51, and 3 cases, respectively. Thromboembolectomy was performed in all patients in the embolism and thrombosis groups. In addition, endovascular treatment was performed in 25 (37.3%) patients, especially in the thrombosis group (81.3%). A major amputation could not be avoided in 10 patients. The 5-year limb salvage rates for categories IIa and IIb were 97.1% and 83.1%, respectively. The 5-year freedom from re-intervention rate was 89.2%. The survival rates at 1, 3, and 5 years were 87.9%, 75.2%, and 60.6%, respectively. Conclusion: The 5-year survival rates of patients with ALI were equivalent to those with chronic limb threatening ischemia (CLTI). The intervention and long-term outcomes were distinguishable according to etiology.

Comparative analysis of immunological properties of S-layer proteins isolated from Lactobacillus strains.

Previous studies have suggested that some Lactobacillus S-layer proteins could modulate immune responses. Primary structures of the S-layer proteins are variable, and their immunological differences are poorly understood. In this study, we evaluated the immunological properties of eight distinct S-layer proteins from different Lactobacillus species. We found that removal of the S-layer proteins from the cell surface reduced the immunological activities of Lactobacillus cells in THP-1 cells. Furthermore, the purified S-layer proteins induced the production of IL-12 p40, although their immunological activities varied between the different S-layer proteins. The production of IL-12 p40 was notably induced by the S-layer protein SLP(aly) from Lactobacillus amylolyticus NRIC 0558T. Multiple sequence alignment revealed that the percent identity of the S-layer proteins of the eight strains vary from 10 to 90 %. In particular, N-terminal regions showed high levels of diversity. To obtain more information about their structure and the immunogenicity, truncated and chimeric S-layer proteins were constructed in recombinant E. coli. Profiling of cytokine production in THP-1 cells by truncated and chimeric S-layer proteins suggested that the intact conformation of the N-terminal region of SLP(aly) contributes to high immunogenicity.

Long-Term Outcomes of Surgical Treatment by In Situ Graft Reconstruction for Infected Abdominal Aortic Aneurysm.

Objectives: The optimal surgical management for primary infected abdominal aortic aneurysm (IAAA) is controversial. Here, we report the early and long-term results of surgical treatments with the resection of the IAAA and in situ graft reconstruction with pedicled omental coverage that was performed at out hospital. Methods: Between 2010 and 2017, 27 consecutive patients (26 males, 1 female, median age 69 years) with IAAA were surgically treated with the resection of the IAAA, in situ graft reconstruction and covered with a pedicled omental flap. Perioperative and long-term outcomes were reviewed retrospectively by medical records. Results: Clinical manifestations, including pyrexia, fever and abdominal pain, were observed during the treatment of the patients. Aneurysm excision and in situ graft reconstruction with omental coverage were performed for all cases. In 13 cases (48.1%), tissue culture was positive. The antibiotic was administered intravenously for 9 to 47 days (median 18 days) postoperatively, and after confirming the reduction of the inflammatory response, it was administered as oral agents for 24 to 443 days (median 169 days).There was no perioperative death or re-infection. Perioperative complications were found in 8 cases (29.6%) of minor spinal cord infarction, ileus, chylous ascites, and cholangitis due to choledochlithiasis. During the observation period of median 1,147 days, there was no recurrence of infection, graft infection, or disease-related death. There were six deaths due to other diseases. And the overall survival rate was 76.2%. Conclusion: According to our study, the long-term outcomes of surgical treatment with in situ graft reconstruction for IAAA were considered satisfactory. (This is a translation of Jpn J Vasc Surg 2019; 28: 35-40.).

The impact of motility on the localization of Lactobacillus agilis in the murine gastrointestinal tract.

BACKGROUND: While the overall composition of the mammalian gut microbiota has been intensively studied, the characteristics and ecologies of individual gut species are incompletely understood. Lactobacilli are considered beneficial commensals in the gastrointestinal mucosa and are relatively well-studied except for the uncommon species which exhibit motility. In this study, we evaluate the importance of motility on gut colonization by comparing motile and non-motile strains of Lactobacillus agilis in mice models. RESULTS: A flagellated but non-motile L. agilis strain was constructed by mutation of the motB gene. Colonization of the wild type and the mutant strain was assessed in both antibiotic-treated female Balb/c mice and gnotobiotic mice. The results suggest that the motile strain is better able to persist and/or localize in the gut mucosa. Chemotaxis assays indicated that the motile L. agilis strain is attracted by mucin, which is a major component of the intestinal mucus layer in animal guts. CONCLUSIONS: Motility and chemotactic ability likely confer advantages in gut colonization to L. agilis. These findings suggest that the motile lactobacilli have unique ecologies compared to non-motile commensals of the lactic acid bacteria.

Oral Steroid Use and Abdominal Aortic Aneurysm Expansion　- Positive Association.

BACKGROUND: The maximum axial diameter (MAD) of a fusiform abdominal aortic aneurysm (AAA) is an indicator of the risk of expansion or rupture. Apart from smoking and MAD itself, few expansion risk factors have been reported. In this study, we investigated expansion risk factors for AAA.Methods and Results:This retrospective cohort study included 176 patients who attended Tohoku University Hospital with infrarenal fusiform AAA. AAA expansion rate was determined on multidetector computed tomography, and the correlations between expansion rate and the clinical data were analyzed. The median expansion rate was 2.405 mm/year. On univariate analysis, a significant positive correlation with expansion rate was observed for the initial MAD (P<0.001) and significant negative correlations for oral angiotensin receptor blocker usage (P=0.025), height (P=0.005), body weight (P=0.017), total cholesterol (P=0.007), low-density lipoprotein cholesterol (P=0.004), and HbA1c (P=0.037). On logistic regression analysis, significant positive associations with expansion rate were observed for initial MAD (P<0.001) and oral steroid usage (P=0.029) and a negative association for height (P=0.041). CONCLUSIONS: Oral steroid usage is an important risk factor for AAA expansion, independent of other risk factors of atherosclerosis and MAD.

Natural History and Chronological Growth Rate of Renal Artery Aneurysms.

Objective: Renal artery aneurysm (RAA) is an uncommon disease, the natural course of which is still not well known. The objective of this study is to define factors that affect the growth rate of RAAs. Materials and Methods: We retrospectively reviewed 32 aneurysms in 26 patients at our institute between January 2010 and March 2016. Basal demographics, comorbidities, reason for diagnosis, and details of the aneurysms and interventions were recorded. The chronological changes in the diameter of the RAA using multiplanar reconstructions of computed tomography images were measured and analyzed. Results: The baseline mean diameter was 20.1±8.4 mm (range: 9.9-41). The mean follow-up period was 3.13±2.1 y (range: 0.5-7.1). The median growth rate was 0.35 mm/y (interquartile range: 0.05, 0.62). The growth rate was slower when the initial diameter was <20 mm than when it was >20 mm (p=0.036). Also, whole-completed calcification was a significant factor for slower growth (p=0.016). We performed ex-vivo surgery in two cases and coil packing with stenting in one. No ruptures occurred during the study period. Conclusion: Our results suggest that cases with an RAA diameter <20 mm do not require intervention. The interval period can be longer in whole-completed calcification types.

Brain testosterone deficiency leads to down-regulation of mitochondrial gene expression in rat hippocampus accompanied by a decline in peroxisome proliferator-activated receptor-γ coactivator 1α expression.

Age-related decrease of testosterone levels in blood and brain is believed to be associated with neurodegenerative diseases such as Alzheimer's disease. However, the effect of testosterone on brain function is not well understood. Therefore, we investigated the impact of testosterone deprivation on mitochondrial gene expression in the brain of male gonadectomized (GDX) rats. We found that peripheral castration led to testosterone deficiency in the brain and caused a significant reduction in protein and mRNA expression of genes encoded by mitochondrial DNA, namely NADPH dehydrogenase subunit 1, subunit 4, cytochrome b, and cytochrome c oxidase subunit 1 and subunit 3 in the hippocampus. In addition, gene expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), which is a master regulator of mitochondrial biogenesis, and its downstream transcriptional factors, nuclear respiratory factors 1 and 2 and mitochondrial transcription factors A and B2, were also decreased in the hippocampus of GDX rats. These reductions in the expression of mitochondrial gene and transcriptional coactivators and factors were recovered by androgen replacement. These findings indicate that androgen plays an important role in mitochondrial gene expression in the hippocampus.