One-Pot Direct Synthesis of Siloles from 1-Bromo-2-silylethynylbenzenes or 1-Bromo-4-silyl-1,3-enynes.

We propose one-pot synthesis of siloles from readily available starting materials. This methodology is practical for the preparation of multisubstituted siloles in good to excellent yields with complete regioselectivity. Sequential reactions, such as lithiation, silylation, and diisobutylaluminum-hydride-promoted cyclization, enable the preparation of the siloles. This transformation provides siloles through two efficient C-Si bond formations in one vessel.

The efficacy of deep learning models in the diagnosis of endometrial cancer using MRI: a comparison with radiologists.

PURPOSE: To compare the diagnostic performance of deep learning models using convolutional neural networks (CNN) with that of radiologists in diagnosing endometrial cancer and to verify suitable imaging conditions. METHODS: This retrospective study included patients with endometrial cancer or non-cancerous lesions who underwent MRI between 2015 and 2020. In Experiment 1, single and combined image sets of several sequences from 204 patients with cancer and 184 patients with non-cancerous lesions were used to train CNNs. Subsequently, testing was performed using 97 images from 51 patients with cancer and 46 patients with non-cancerous lesions. The test image sets were independently interpreted by three blinded radiologists. Experiment 2 investigated whether the addition of different types of images for training using the single image sets improved the diagnostic performance of CNNs. RESULTS: The AUC of the CNNs pertaining to the single and combined image sets were 0.88-0.95 and 0.87-0.93, respectively, indicating non-inferior diagnostic performance than the radiologists. The AUC of the CNNs trained with the addition of other types of single images to the single image sets was 0.88-0.95. CONCLUSION: CNNs demonstrated high diagnostic performance for the diagnosis of endometrial cancer using MRI. Although there were no significant differences, adding other types of images improved the diagnostic performance for some single image sets.

Analysis of Chaotic Dynamics by the Extended Entropic Chaos Degree.

The Lyapunov exponent is the most-well-known measure for quantifying chaos in a dynamical system. However, its computation for any time series without information regarding a dynamical system is challenging because the Jacobian matrix of the map generating the dynamical system is required. The entropic chaos degree measures the chaos of a dynamical system as an information quantity in the framework of Information Dynamics and can be directly computed for any time series even if the dynamical system is unknown. A recent study introduced the extended entropic chaos degree, which attained the same value as the total sum of the Lyapunov exponents under typical chaotic conditions. Moreover, an improved calculation formula for the extended entropic chaos degree was recently proposed to obtain appropriate numerical computation results for multidimensional chaotic maps. This study shows that all Lyapunov exponents of a chaotic map can be estimated to calculate the extended entropic chaos degree and proposes a computational algorithm for the extended entropic chaos degree; furthermore, this computational algorithm was applied to one and two-dimensional chaotic maps. The results indicate that the extended entropic chaos degree may be a viable alternative to the Lyapunov exponent for both one and two-dimensional chaotic dynamics.

An Improved Calculation Formula of the Extended Entropic Chaos Degree and Its Application to Two-Dimensional Chaotic Maps.

The Lyapunov exponent is primarily used to quantify the chaos of a dynamical system. However, it is difficult to compute the Lyapunov exponent of dynamical systems from a time series. The entropic chaos degree is a criterion for quantifying chaos in dynamical systems through information dynamics, which is directly computable for any time series. However, it requires higher values than the Lyapunov exponent for any chaotic map. Therefore, the improved entropic chaos degree for a one-dimensional chaotic map under typical chaotic conditions was introduced to reduce the difference between the Lyapunov exponent and the entropic chaos degree. Moreover, the improved entropic chaos degree was extended for a multidimensional chaotic map. Recently, the author has shown that the extended entropic chaos degree takes the same value as the total sum of the Lyapunov exponents under typical chaotic conditions. However, the author has assumed a value of infinity for some numbers, especially the number of mapping points. Nevertheless, in actual numerical computations, these numbers are treated as finite. This study proposes an improved calculation formula of the extended entropic chaos degree to obtain appropriate numerical computation results for two-dimensional chaotic maps.

Ringer's ethyl pyruvate solution attenuates hypoperfusion and renal injury after multivisceral ischemia-reperfusion in rabbits.

Ringer's ethyl pyruvate solution (REPS) has been protective against experimental renal, intestinal, and spinal ischemia and may be useful for organ protection in major vascular surgery. The purpose of this study was to investigate whether REPS attenuates organ injury in a rabbit model of supraceliac aortic cross-clamp that simulates thoracoabdominal aortic surgery. Following the Institutional Animal Care and Use Committee's approval, 20 rabbits were undergone cross-clamping of the supraceliac thoracic aorta for 30 min, and observed for 180 min after reperfusion. Either REPS (33 mg/kg/h of ethyl pyruvate) or Ringer's lactate solution were infused throughout the study period. Arterial pressure and aortic blood flow were continuously monitored. Blood lactate concentration, serum transaminase levels, neutrophil activation, and urinary N-acetyl-beta-glucosaminidase (NAG) activity were evaluated. After reperfusion, supraceliac aortic blood flow was significantly higher, and urinary NAG was significantly lower in animals that received REPS, while the other parameters were not significantly different. In conclusion, REPS attenuated the reduction of aortic blood flow and urinary NAG elevation after the cross-clamp of supraceliac aorta.

Functions and regulation of lipocalin-2 in gut-origin sepsis: a narrative review.

Lipocalin-2 (Lcn2), an innate immune protein, has come to be recognized for its roles in iron homeostasis, infection, and inflammation. In this narrative review, we provide a comprehensive description based on currently available evidence of the clinical implications of Lcn2 and its therapeutic potency in gut-origin sepsis. Lcn2 appears to mitigate gut barrier injury via maintaining homeostasis of the microbiota and exerting antioxidant strategy, as well as by deactivating macrophages and inducing immune cell apoptosis to terminate systemic hyper-inflammation. We propose that development of a therapeutic strategy targeting lipocalin-2 could be highly promising in the management of gut-origin sepsis.

Host Range of the Conjugative Transfer System of IncP-9 Naphthalene-Catabolic Plasmid NAH7 and Characterization of Its oriT Region and Relaxase.

NAH7 and pWW0 from gammaproteobacterial Pseudomonas putida strains are IncP-9 conjugative plasmids that carry the genes for degradation of naphthalene and toluene, respectively. Although such genes on these plasmids are well-characterized, experimental investigation of their conjugation systems remains at a primitive level. To clarify these conjugation systems, in this study, we investigated the NAH7-encoded conjugation system by (i) analyzing the origin of its conjugative transfer (oriT)-containing region and its relaxase, which specifically nicks within the oriT region for initiation of transfer, and (ii) comparing the conjugation systems between NAH7 and pWW0. The NAH7 oriT (oriTN) region was located within a 430-bp fragment, and the strand-specific nicking (nic) site and its upstream sequences that were important for efficient conjugation in the oriTN region were identified. Unlike many other relaxases, the NAH7 relaxase exhibited unique features in its ability to catalyze, in a conjugation-independent manner, the site-specific intramolecular recombination between two copies of the oriTN region, between two copies of the pWW0 oriT (oriTW) region (which is clearly different from the oriTN region), and between the oriTN and oriTW regions. The pWW0 relaxase, which is also clearly different from the NAH7 relaxase, was strongly suggested to have the ability to conjugatively and efficiently mobilize the oriTN-containing plasmid. Such a plasmid was, in the presence of the NAH7Δnic derivative, conjugatively transferable to alphaproteobacterial and betaproteobacterial strains in which the NAH7 replication machinery is nonfunctional, indicating that the NAH7 conjugation system has a broader host range than its replication system. IMPORTANCE: Various studies have strongly suggested an important contribution of conjugative transfer of catabolic plasmids to the rapid and wide dissemination of the plasmid-loaded degradation genes to microbial populations. Degradation genes on such plasmids are often loaded on transposons, which can be inserted into the genomes of the recipient bacterial strains where the transferred plasmids cannot replicate. The aim was to advance detailed molecular knowledge of the determinants of host range for plasmids. This aim is expected to be easily and comprehensively achieved using an experimental strategy in which the oriT region is connected with a plasmid that has a broad host range of replication. Using such a strategy in this study, we showed that (i) the NAH7 oriT-relaxase system has unique properties that are significantly different from other well-studied systems and (ii) the host range of the NAH7 conjugation system is broader than previously thought.

Deep anesthesia worsens outcome of rats with inflammatory responses.

OBJECTIVE: We tested the hypothesis that deep anesthesia with sevoflurane, known as a potent immunomodulator, for 4 h would worsen the 24-h outcomes of rats through modulation of the inflammatory responses. METHODS: Forty-nine male Wistar rats, administered low dose of lipopolysaccharide (0.5 mg/kg) intravenously to elicit moderate inflammatory responses mimicked mild surgical stress, underwent one minimum alveolar concentration (MAC) or 2 MAC sevoflurane anesthesia for 4 h. The 24-h survival rate, arterial blood gases, plasma interleukin (IL)-6 and tumor necrosis factor (TNF)-α concentrations, and rate of T lymphocyte apoptosis in spleen were evaluated. We further examined the effects of hypotension and TNF-α discharge on the survival rate. RESULTS: The survival rate in 2 MAC group was significantly lower accompanied with decreased base excess and increased level of cytokines (IL-6, TNF-α) compared to 1 MAC group. The apoptosis rate did not differ between the two groups. Neither norepinephrine infusion to restore hypotension nor administration of anti-TNF-α antibody improved the outcome in the 2 MAC group. CONCLUSIONS: Deep anesthesia with sevoflurane even for a short-term period augments the release of inflammatory cytokines evoked by inflammatory insults like surgical stress, impairs the acid-base balance, and subsequently deteriorates the outcomes.

Neutrophil gelatinase-associated lipocalin regulates gut microbiota of mice.

BACKGROUND AND AIM: Because neutrophil gelatinase-associated lipocalin (NGAL) is known to provide significant bacteriostatic effects during infectious conditions, we tested the hypothesis that this protein is up-regulated and secreted into the intraluminal cavity of the gut under critically ill conditions and is thus responsible for the regulation of bacterial overgrowth. METHODS: With our institutional approval, male C57BL/6J mouse (6-7 weeks) were enrolled and applied for lipopolysaccharide or peritonitis model compared with naïve control. We assessed NGAL protein concentrations in intestinal lumen and up-regulation of NGAL expression in intestinal tissues in in vivo as well as ex vivo settings. Simultaneously, we examined the effects of NGAL protein administration on the growth of Escherichia coli (E. coli) in in vivo and in vitro experimental settings. The localization of NGAL in intestinal tissues and lumen was also assessed by immunohistological approach using NGAL antibody. RESULTS: Both lipopolysaccharide and peritonitis insults evoked the marked up-regulation of NGAL mRNA and protein levels in gut tissues such as crypt cells. In addition, the administration of NGAL protein significantly inhibited the outgrowth of enteric E. coli under both in vitro and in vivo conditions, accompanied by histological evidence. CONCLUSION: Neutrophil gelatinase-associated lipocalin protein accompanied by apparent bacteriostatic action accumulated in the intestinal wall and streamed into the mucosal layer during critically ill state, thereby possibly shaping microbiota homeostasis in the gut.

The effects of epidural anesthesia on growth of Escherichia coli at pseudosurgical site: the roles of the lipocalin-2 pathway.

BACKGROUND: Neutrophil-derived lipocalin-2 exerts bacteriostatic effects through retardation of iron uptake by the Gram-negative organisms like Escherichia coli. We tested the hypothesis that the expression of lipocalin-2, a bacteriostatic protein, was upregulated by induction of surgical site infection (SSI) with E coli in healthy and diseased rats and that epidural anesthesia modulated its expression. METHODS: Male Wistar rats were randomized into a healthy or disease group, the latter of which was administered lipopolysaccharide. Both groups were further divided into 3 subgroups, the control, saline, and lidocaine groups: group healthy control (n = 10), healthy saline (n = 10), and healthy lidocaine (n = 10) versus group disease control (n = 15), disease saline (n = 18), and disease lidocaine (n = 19), respectively. While saline was epidurally administered to the control and saline groups, lidocaine was administered to the lidocaine groups. Except for the control groups, E coli was injected to the pseudosurgical site to mimic SSI after abdominal surgery. Plasma concentrations of inflammatory cytokine and lipocalin-2 were measured. At 72 hours, the surgical site tissues were obtained to evaluate mRNA expression of lipocalin-2 and E coli DNA expression. RESULTS: All disease subgroups showed markedly increased plasma inflammatory cytokines versus the healthy subgroups. Among the disease subgroups, plasma concentrations of lipocalin-2 and tissue mRNA expression of lipocalin-2 were significantly increased in group disease lidocaine versus the others. Concurrently, E coli DNA expression in the tissue specimens was also significantly lower in group disease lidocaine as compared with group disease saline. CONCLUSIONS: Epidural anesthesia was associated with an increase in the expression lipocalin-2 and a decrease in the expression of E coli DNA at pseudosurgical sites in sick but not healthy rats. These observations suggest a potential mechanism by which epidural anesthesia could reduce the risk of SSI.

A case of a shrunken multilocular mediastinal cyst that developed into thymic carcinoma with lung metastases 13 years later.

Multilocular thymic cysts (MTC) are acquired multilocular cysts caused by inflammation. The rarity of such lesions and a lack of recognition make diagnosis and treatment difficult. Herein, we present our experience with a multilocular mediastinal cyst that resulted in the development of thymic cancer with metastasis over a period of 13 years. Computed tomography findings revealed an anterior mediastinal mass that was suspected to be an MTC in a 49-year-old man. The mass shrank gradually over a period of 7 years; however, growth was observed at 10 years after initial detection. At 13 years after detection, thymic carcinoma with multiple lung metastases was diagnosed. Resection was recommended during the follow-up period, but the patient refused treatment. A multilocular wall and location are factors that indicate MTC. However, even if a definitive diagnosis is not made, resection of multilocular anterior mediastinal cysts should be considered as determining the preoperative diagnosis is difficult. Nevertheless, our case suggests that the coexistence of tumors with cysts is possible, and the potential for malignant tumor development exists.

[Regional anesthesia and cancer immunology].

Regional anesthesia has been widely applied as an excellent method for perioperative analgesia. Recent studies suggested that regional anesthesia is a promising approach to minimize the risk of surgical site infection and postoperative cancer recurrence, subsequently providing the benefits to the long-term outcome. In particular, it is of great interest that regional anesthesia might be able to reduce cancer recurrence. In cancer patients, innate immunity against cancer could be depressed, resulting in the predisposition to evoke metastasis. Besides, during the perioperative periods, tumor immunity is significantly depressed due to surgical pain, activation of sympathetic nervous system, inflammatory responses, and others. In this review article, we discuss the tumor immunity during the perioperative period, with focus on the alterations of tumor immunity and regional anesthesia.

A case of Pseudo-Meigs' syndrome due to Brenner tumor.

A 65-year-old woman with suspected ascites-associated abdominal distention had elevated CA125 levels. Contrast-enhanced computed tomography to search for the cause of the ascites showed bilateral pleural effusions, ascites, and an ovarian tumor. On magnetic resonance imaging the tumor exhibited a lobulated structure and markedly low signal intensity on both T1- and T2-weighted imaging, with no restrictions on diffusion-weighted images. Progressive enhancement was observed at tumor margins. Meigs syndrome due to fibroma was suspected, and total hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy were performed. Postoperatively, the pleural effusion and ascites resolved promptly without specific treatment. On pathological examination, the ovarian tumor was diagnosed as a benign Brenner tumor with scattered nests of transitional epithelium within a large amount of stroma. Based on the clinical course, the patient was diagnosed with pseudo-Meigs' syndrome due to a Brenner tumor.

Survival outcomes among patients with multiple myeloma in the era of novel agents: exploratory assessment using an electronic medical record database in Japan.

Despite recent advances in the range of therapies available for the treatment of multiple myeloma (MM), there are limited data surrounding survival outcomes and baseline characteristics influencing survival in general clinical practice in Japan. The aim of this study was to use electronic medical records (EMRs) to examine overall survival (OS) and prognostic factors in Japanese patients with MM. We extracted EMRs in the Real World Data (RWD) database of patients with a confirmed diagnosis of MM and treatment history with bortezomib, thalidomide, and/or lenalidomide. OS and prognostic factors for OS were analyzed using a univariate analysis and decision tree model. Of the 6509 patients in the database with a diagnosis of MM, 1565 were eligible. Patients had a median (range) age of 72 (23-92) years, a median OS of 53.5 months, and a 5-year OS rate of 45.6%. In alignment with previous studies, International Staging System stage and age were prognostic of OS. In addition, platelet and erythrocyte counts, chloride, total protein, C-reactive protein, and lactate dehydrogenase levels were identified as important prognostic factors for OS and were used to pilot a simple prognostic tool. In conclusion, we found that the survival outcomes extracted from EMRs in the RWD of Japanese patients with MM aligned with a previous retrospective study from Japan. Baseline laboratory parameters prognostic for OS were explored with additional factors to International Staging System and age identified. These might be used to optimize treatment selection, although further investigation using additional data sources is required.

ParI, an orphan ParA family protein from Pseudomonas putida KT2440-specific genomic island, interferes with the partition system of IncP-7 plasmids.

Pseudomonas putida KT2440 is an ideal soil bacterium for expanding the range of degradable compounds via the recruitment of various catabolic plasmids. In the course of our investigation of the host range of IncP-7 catabolic plasmids pCAR1, pDK1 and pWW53, we found that the IncP-7 miniplasmids composed of replication and partition loci were exceptionally unstable in KT2440, which is the authentic host of the archetypal IncP-9 plasmid pWW0. This study identified ParI, a homologue of ParA family of plasmid partitioning proteins encoded on the KT2440-specific cryptic genomic island, as a negative host factor for the maintenance of IncP-7 plasmids. The miniplasmids were destabilized by ectopic expression of ParI, and the loss rate correlated with the copy number of ParB binding sites in the centromeric parS region. Mutations in the conserved ATPase domains of ParI abolished destabilization of miniplasmids. Furthermore, ParI destabilized miniplasmid derivatives carrying the partition-deficient parA mutations but failed to impact the stability of miniplasmid derivatives with parB mutations in the putative arginine finger. Altogether, these results indicate that ParI interferes with the IncP-7 plasmid partition system. This study extends canonical partition-mediated incompatibility of plasmids beyond heterogeneous mobile genetic elements, namely incompatibility between plasmid and genomic island.

A comparison of bone conductivity on titanium screws inserted into the vertebra using different surface processing.

PURPOSE: Antibacterial iodine-supported titanium has an anodized oxide layer; thus, it can be expected to have a higher osteoconductivity than untreated titanium. This study aimed to compare the osteoconductivity between untreated titanium (Ti), anodically oxidized titanium (AO-Ti), and iodine-supported titanium (I-Ti) screws. METHODS: The screws were inserted into the vertebral bodies of 30 dogs (12 for the biomechanical, and 18 for the histological examination). The vertebral bodies were analyzed at 4 or 8 weeks after screw insertion. Biomechanically, rotational torque of the screw was measured. Histologically, bone formation index (ratio of the length of the part where the bone directly contacts with the length of the screw) and bone volume density (ratio of the area of the bone tissue to the area between the threads of the screw) were measured. RESULT: At 4 weeks, the torque value was significantly higher in the AO-Ti (0.59 ± 0.16 Nm) and I-Ti (0.72 ± 0.14 Nm) groups than in the Ti group (0.39 ± 0.12 Nm), with the AO-Ti and I-Ti groups showing no significant difference. Bone formation index was significantly higher in the AO-Ti (72.5% ± 0.8%) and I-Ti (73.4% ± 1.5%) groups than in the Ti group (64.6% ±1.7%), with the AO-Ti and I-Ti groups showing no significant difference. Bone volume density did not show a significant difference. At 8 weeks, the results were similar to those at 4 weeks. CONCLUSIONS: I-Ti had a higher osteoconductivity than Ti, indicating that iodine coating did not adversely affect osteoconductivity.

Beta-Blocker Therapy Preserves Normal Splenic T-Lymphocyte Numbers Reduced in Proportion to Sepsis Severity in a Sepsis Model.

Lymphocyte cell death contributes to sepsis-induced immunosuppression, leading to poor prognosis. This study examined whether sepsis severity and beta-blocker therapy could affect the degree of T-lymphocyte cell death in a mouse model of sepsis. In the first control study, 20 animals were allocated to 4 groups: control group with sham operation (group C, n = 5) and 3 groups with cecum ligation and puncture (CLP) performed at 3 different sites: proximal, middle, and distal cecum (groups CLP-P, CLP-M, and CLP-D, respectively; n = 5 in each group). Their spleens were resected under general anesthesia 24 hours after CLP, and the total number of normal splenic T lymphocytes per mouse and the percentage of apoptotic T lymphocytes were evaluated using flow cytometry. In the second experimental study, the effect of the beta-blocker esmolol was examined in CLP-P (group CLP-PE vs. CLP-P; n = 5 in each group). The total normal splenic T-lymphocyte numbers per mouse significantly decreased in proportion to CLP severity (group C, 18.6 × 106 (15 × 106-23.6 × 106); CLP-D, 9.2 × 106 (8.8 × 106-9.8 × 106); CLP-M, 6.7 × 106 (6.3 × 106-7.0 × 106); and CLP-P, 5.3 × 106 (5.1 × 106-6.8 × 106)). Beta-blocker therapy restored T-lymphocyte numbers (group CLP-PE vs. CLP-P; 6.94 ± 1.52 × 106 vs. 4.18 ± 1.71 × 106; p=0.027) without affecting apoptosis percentage. Beta-blocker therapy might improve sepsis-induced immunosuppression via normal splenic T-lymphocyte preservation.

Cesarean hysterectomy in a hybrid operating room for placenta percreta: a report of three cases.

BACKGROUND: Placenta percreta is the most severe abnormality in invasive placenta and often treated with cesarean hysterectomy. Endovascular embolization for placental abnormality is known to reduce bleeding from the placental bed and from the abnormal neovasculature surrounding the uterus. We describe three cases of placenta percreta treated with uninterrupted cesarean hysterectomy and embolization performed using a hybrid operating room (HOR). CASE DESCRIPTION: Cases were two placenta previa percretas and an impending uterine rupture with placenta percreta, treated with elective cesarean hysterectomy in HOR. Planned conversion of spinal to general anesthesia was performed after the fetal delivery. Immediate embolic devascularization of abnormal neovasculature was directly observed and facilitated adhesiolysis. Surgical blood losses were 1850 g, 2500 g, and 1180 g, respectively. CONCLUSION: Cesarean hysterectomy combined with endovascular embolization in the HOR for placenta percreta is an advantageous option to enhance patient safety by multidisciplinary approach without patient transfer.

A histological examination of spinal reconstruction using a frozen bone autograft.

Our aim was to compare the process of bone formation after reconstruction of the vertebral body using a titanium cage with either a liquid nitrogen-treated (frozen) bone autograft or non-treated fresh bone autograft. Twelve canine beagles underwent anterior reconstruction of the 5th lumbar vertebrae using a titanium cage and bone autograft. Bone formation was compared across four experimental groups: fresh bone autograft groups, with animals sacrificed at either 8 or 16 weeks post-reconstruction, and liquid nitrogen-treated (frozen) bone autograft groups, with animals again sacrificed at either 8 or 16 weeks post-reconstruction. Bone formation was evaluated histologically by calculating the proportion of 'reaction' and 'mature bone' regions at the ends of the cage, its center, and ventral/dorsal sides. The reaction region contained osteocytes with a nucleus and osteoblasts accumulated on the surface of an osteoid, while a laminar structure was visible for mature bone regions. For fresh bone autografts, the reaction and mature bone regions significantly increased from 8 to 16 weeks post-reconstruction. By comparison, for frozen autografts, the reaction bone region did not significantly increase from 8 to 16 weeks post-reconstruction, while the mature bone region did increase over this time period. The proportion of reaction bone was higher at the ends and dorsal side of the cage at 8 weeks, for both graft types, with greater bone formation at the center of the cage at 16 weeks only for the fresh bone autograft. Therefore, bone formation in the anterior spinal reconstruction site tended to be delayed when using a frozen bone autograft compared to a fresh bone autograft. The bone formation process, however, was similar for both groups, beginning at the ends and dorsal side of the cage adjacent to the surrounding vertebral bone.