Manipulation of Macrophage Uptake by Controlling the Aspect Ratio of Graft Copolymer Micelles.

Nanostructures of drug carriers play a crucial role in nanomedicine due to their ability to influence drug delivery. There is yet no clear consensus regarding the optimal size and shape (e.g., aspect ratio) of nanoparticles for minimizing macrophage uptake, given the difficulties in controlling the shape and size of nanoparticles while maintaining identical surface properties. Here, we employed graft copolymer self-assembly to prepare polymer micelles with aspect ratios ranging from 1.0 (spherical) to 10.8 (cylindrical) and closely matched interfacial properties. Notably, our findings emphasize that cylindrical micelles with an aspect ratio of 2.4 are the least susceptible to macrophage uptake compared with both their longer counterparts and spherical micelles. This reduced uptake of the short cylindrical micelles results in a 3.3-fold increase in blood circulation time compared with their spherical counterparts. Controlling the aspect ratio of nanoparticles is crucial for improving drug delivery efficacy through better nanoparticle design.

Exploring the Impact of Linkage Structure in Ferroelectric Nematic and Smectic Liquid Crystals.

The liquid crystal molecule 3-fluoro-4-(3,4,5-trifluorophenyl)phenyl 2,6-difluoro-4-(trans-5-n-propyl-1,3-dioxane-2-yl)benzoate (DIO) has attracted considerable interest owing to its unique ferroelectric nematic phase and extraordinarily high dielectric constant. To expand the DIO series, novel analogs with 1,3-dioxane units converted to ester units (EST analogs) were synthesized, and their physical properties were characterized. The EST analogs exhibited ferroelectric phases similar to those of the corresponding DIO analogs. Interestingly, an EST analogue featuring a defluorinated benzoate unit exhibited a ferroelectric smectic A phase, despite its smaller longitudinal dipole moment of 6.9 D. This result diverges from the common knowledge that the formation of large longitudinal dipoles is traditionally effective in the emergence of ferroelectric phases. Unlike the DIO series, the EST analogs can be readily obtained without the formation of undesired geometric isomers, which is advantageous for practical applications. The results of this study provide valuable insights into the design of liquid-crystalline materials expressing ferroelectric phases.

Utility of articulating instruments as an alternative to robotic devices in laparoscopic right hemicolectomy.

Laparoscopic complete mesocolic excision with central vessel ligation has been widely accepted for its oncological benefits in colon cancer surgery. However, laparoscopic right hemicolectomy involves a risk for vascular injury during dissection around the surgical trunk. This technical difficulty has been attributed to the limited movement of conventional laparoscopic forceps. Although robotic devices can overcome the restricted motion of laparoscopic devices, they are not yet widely used. The ArtiSential is an articulating laparoscopic instrument that has a two-joint end-effector that enables a wide range of motion precisely reflecting the surgeon's finger movements, and is designed to compensate for the drawbacks of conventional laparoscopic tools. The present study demonstrated the utility of articulating instruments in laparoscopic right hemicolectomy by comparing the authors' laparoscopic procedures, using articulating instruments, with robotic procedures. Articulating laparoscopic instruments can be successfully maneuvered in virtually the same manner as robotic devices and, as such, represent a viable alternative to robotic surgery. Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-024-00654-w.

A surgical case of anti-coagulant ileus mimicking small-bowel tumors: a case report.

BACKGROUND: Anti-coagulant ileus, characterized by intramural hematoma due to excessive anti-coagulant therapy, presents a diagnostic challenge. Although previously considered uncommon, recently, reporting cases of anti-coagulant ileus have become more frequent. Herein, we report a rare surgical case of anti-coagulant ileus mimicking small-bowel tumors. CASE PRESENTATION: A 79-year-old man was admitted to our hospital for fatigue. He had been administered warfarin for 5 months for atrial fibrillation. On admission, the patient exhibited mild epigastric tenderness. Laboratory test results revealed anemia (hemoglobin, 8.4 g/dL); unmeasurably prolonged prothrombin time (PT) with international normalized ratio (INR) > 8; and elevated soluble interleukin 2 receptor (sIL-2R) levels (849 IU/mL; normal range, 122-496 IU/mL). Abdominal plain computed tomography (CT) showed a circumferentially thickened intestinal wall at one site in the jejunum and two in the ileum. After hospitalization, bowel obstruction did not improve with conservative treatment. Suspecting small-bowel tumors such as lymphoma, the patient subsequently underwent open surgery on day 3 after admission. No obvious tumor mass was observed intra-operatively. However, only thickened and hemorrhagic segments were identified at the suspected sites. We performed partial jejunal and ileal resections of 12 and 27 cm, respectively. Histopathology confirmed submucosal congestion, edema, and hemorrhage in each area without tumor components, leading to the final diagnosis of intramural hematoma. The postoperative course was uneventful, and he was discharged on postoperative day 9. No recurrence occurred during the 5-year follow-up period. CONCLUSIONS: We encountered a surgical case of anti-coagulant ileus, which was difficult to differentiate from malignant lymphoma based on CT findings and high sIL-2R levels. The possibility of anti-coagulant ileus should always be considered in patients on long-term anticoagulation medication and bowel obstruction with high PT-INR values.

Ultra-high-density mapping for safe and effective typical atrioventricular nodal reentrant tachycardia ablation.

Ultra-high-density mapping was used for potential-guided radiofrequency ablation for typical atrioventricular nodal reentrant tachycardia. The mapping detailed the spread of activation in the Koch's triangle and identified target potentials and tachycardia circuits. This mapping provides additional information to the slow pathway conventionally used for safe and effective ablation.

Widespread spontaneous spinal epidural hematoma treated with a combined technique using a flexible neuroendoscope after hemilaminectomy: A case report.

Background: One-third of spinal epidural hematomas occur spontaneously, and these may be associated with the acute onset of severe paralysis. Here, we present a case of T4-L4 symptomatic spontaneous spinal epidural hematoma which was successfully removed using a flexible neuroendoscope after hemilaminectomy. Case Description: Using flexible neuroendoscopy, we successfully treated a T4-L4 spinal epidural hematoma in an 89-year-old Japanese female who spontaneously developed back pain and paraparesis. The hematoma was removed utilizing a hemilaminectomy at three vertebral levels (T11, T12, and L1), while the remaining hematoma debris was completely evacuated with flexible neuroendoscopy. Neurological improvement was observed immediately postsurgery. Conclusion: Flexible neuroendoscopy provided a less extensive surgical method for removing a T4-L4 spontaneous epidural hematoma.

A Case of Bilateral Vertebral Artery Dissecting Aneurysm Treated With Multimodality Therapy Under Superficial Temporal Artery Assistance-Posterior Cerebral Artery Bypass.

A ruptured bilateral vertebral artery dissecting aneurysm (BVDA) is a challenging vascular disorder. Trapping surgery with bypass assistance could be a potential treatment; however, there is a risk of ischemic complications. Recently, endovascular treatment has been reported, but its long-term outcomes remain uncertain. The patient was a 57-year-old male who presented with subarachnoid hemorrhage. Digital subtraction angiography showed a dilated dominant left vertebral artery (VA) and a narrowed right VA, suggesting a BVDA. First, we performed a right superficial temporal artery-superior cerebellar artery (STA-SCA) insurance bypass. We then performed proximal clipping of the left vertebral VA. The pulsation of the STA-SCA bypass disappeared on day 6. Three-dimensional computed tomography angiography (3DCTA) showed the emergence of a fusiform aneurysm and proximal stenosis of the contralateral VA. On day 31, we performed a superficial temporal artery-posterior cerebral artery (STA-PCA) insurance bypass. Stent-assisted coil embolization was planned for two days after the STA-PCA bypass. However, preoperative angiography showed progression of right proximal VA stenosis, and stenting appeared impossible. There was no change in somatosensory evoked potential (SEP), and angiography showed sufficient retrograde blood flow to the posterior circulation during the right VA balloon occlusion test (BOT). Therefore, internal trapping of the right VA was performed. Postoperative angiography showed perfect patency of the left STA-PCA bypass and retrograde blood flow to the posterior circulation. There was no additional neurological deficit after endovascular treatment. Multimodality therapy could be a potential treatment for bilateral VA dissection.

Ruptured proximal middle cerebral artery traumatic pseudoaneurysm treated with bypass-assisted trapping surgery: A case report.

Background: Traumatic pseudoaneurysms are rare but have a high mortality rate; therefore, immediate diagnosis is vital. Most pseudoaneurysms are in the internal carotid artery or peripheral arteries, while proximal middle cerebral artery pseudoaneurysms have rarely been reported. We present a case of ruptured traumatic pseudoaneurysm located at the M1-M2 bifurcation. Case Description: A 42-year-old man was injured in a motorcycle accident and his Glasgow coma scale score on admission was 7 (Eye opening1, Verbal response2, Motor response4 [E1V2M4]). Head computed tomography (CT) showed thick subarachnoid hemorrhage (SAH). We suspected a ruptured aneurysm, but three-dimensional CT angiography (3D-CTA) did not detect any vascular defects. Head magnetic resonance angiography showed progressive right M1 stenosis suggesting arterial dissection. 3D-CTA on day 20 showed a small aneurysm in the proximal portion of the M2. Although surgery was scheduled for day 26, suddenly left hemiparesis appeared on day 24. Head CT detected fresh SAH and emergency surgery was performed on day 25. We dissected around the ruptured point under M1 temporary occlusion with superficial temporal artery-M2 assist bypass. Contrary to our expectations, there was only a small laceration in the right M2 superior trunk. We trapped the laceration and the proximal portion of the M2 superior trunk while preserving antegrade blood flow from the M1 to the M2 inferior trunk. On the 5-month follow-up, the patient was able to walk independently. Conclusion: Unreasonably thick traumatic SAH or spastic stenosis after head injury may indicate a traumatic pseudoaneurysm and require repeated neurovascular evaluation. If a pseudoaneurysm is detected, immediate surgical intervention is mandatory.

Cell death and wing reduction during the metamorphosis of sex-specific flightless morphs in winter geometrid moths.

Winter geometrid moths show striking sexual dimorphism by having female-specific flightless morphs. The evolutionary grades of wing reduction in winter geometrid moths vary and range from having short wings, vestigial wings, to being wingless. Although the ontogenetic processes underlying the development of the wingless or short-wing morphs in Lepidoptera has been well studied, the mechanisms underlying the development of vestigial wing morphs in winter geometrid moths during metamorphosis are poorly understood. In the winter geometrid moth Sebastosema bubonaria Warren, 1896, the males have functional wings, but the females have vestigial wings. Here, we studied the ontogenetic processes affecting wing reduction in the winter geometrid moth S. bubonaria using light microscopy and transmission electron microscopy, and compared the ontogenetic process of wing reduction in this species with that in another species of the wingless-female winter moth that we investigated previously. Our results showed that, in the vestigial-wing morphs, the loss of pupal wing epithelium was terminated in the middle of the wing degeneration process, whereas in the wingless morph, the pupal wing epithelium disappeared almost completely and the final appearance of the wings differed slightly among flightless morphs. We propose that the extent and location of cell death in the pupal wing play an important role in the various patterns of reduced wings that are observed in flightless moths.

Efficacy and safety of atrial fibrillation ablation in heart failure patients with left ventricular ejection fraction less than 50.

INTRODUCTION: The efficacy of catheter ablation in patients with low cardiac function has been previously reported; however, only a few studies have included mid-range ejection fraction (mrEF). This study aimed to evaluate the efficacy and safety of atrial fibrillation (AF) ablation in patients with left ventricular ejection fraction (LVEF) < 50%. METHODS: This study retrospectively analyzed 79 patients (reduced ejection fraction [rEF]/mrEF, 38/41; paroxysmal/persistent, 37/42; heart failure hospitalizations within one year before ablation, 36 [45.6%]) who underwent the first ablation procedure at our hospital from April 2017 to December 2021. Radiofrequency ablation and cryoablation were performed for 69 and 10 patients, respectively. RESULTS: Complications included pacemaker implantation for postoperative sick sinus syndrome in one patient and inguinal hematoma in one patient. Regarding efficacy, there were significant postoperative improvements in echocardiographic data, blood test values, and diuretic use. After a mean follow-up of 60 months, 86.1% patients had no AF recurrence. There were 9 heart failure hospitalizations (11.4%) and 5 all-cause deaths (6.3%); no significant differences were found between the rEF and mrEF groups. No significant predictors of AF recurrence were found in preoperative patient characteristics. CONCLUSION: AF ablation in patients with LVEF <50% significantly improved cardiac and renal functions with few complications, resulting in a high non-recurrence rate and reduced heart failure.

A case of middle cerebral artery large circumferential aneurysm treated with bypass-assisted trapping surgery.

M1 large circumferential aneurysms are clinically challenging because they cannot be treated by simple neck clipping and they may involve the lenticulostriate arteries (LSAs). Although some reports have described endovascular and direct surgical treatment of these aneurysms, the optimal treatment approach remains uncertain. We report a case involving a ruptured large M1 circumferential aneurysm that was treated with bypass-assisted trapping surgery and showed favorable outcomes. The patient was a 47-year-old man presenting with subarachnoid hemorrhage. Digital subtraction angiography revealed a large circumferential aneurysm in the right middle cerebral artery M1 segment with involvement of the lateral and medial LSAs. We successfully performed trapping surgery with the assistance of a superficial temporal artery (STA)-M2 bypass while preserving the medial and lateral LSAs. Although left hemiparesis caused by medial LSA thrombosis appeared in the early postoperative period, the patient showed good recovery from symptoms with rehabilitation and could independently perform daily activities at the five-month follow-up. The treatment of M1 large circumferential aneurysms should involve considerations for prevention of rebleeding, blood supply to the distal area, and preservation of perforating arteries. The treatment strategy for this challenging aneurysm should be planned based on the patient's condition and individual anatomy.

A Turn-On Quinazolinone-Based Fluorescence Probe for Selective Detection of Carbon Monoxide.

Carbon monoxide (CO) is a toxic, hazardous gas that has a colorless and odorless nature. On the other hand, CO possesses some physiological roles as a signaling molecule that regulates neurotransmitters in addition to its hazardous effects. Because of the dual nature of CO, there is a need to develop a sensitive, selective, and rapid method for its detection. Herein, we designed and synthesized a turn-on fluorescence probe, 2-(2'-nitrophenyl)-4(3H)-quinazolinone (NPQ), for the detection of CO. NPQ provided a turn-on fluorescence response to CO and the fluorescence intensity at 500 nm was increased with increasing the concentration of CO. This fluorescence enhancement could be attributed to the conversion of the nitro group of NPQ to an amino group by the reducing ability of CO. The fluorescence assay for CO using NPQ as a reagent was confirmed to have a good linear relationship in the range of 1.0 to 50 µM with an excellent correlation coefficient (r) of 0.997 and good sensitivity down to a limit of detection at 0.73 µM (20 ppb) defined as mean blank+3SD. Finally, we successfully applied NPQ to the preparation of a test paper that can detect CO generated from charcoal combustion.

Catastrophic Propeller Brain Injury with Large Scalp Defect Treated with Omental Flap.

In this study, we report a case of catastrophic propeller brain injury with large scalp defect treated with omental flap reconstruction. A 62-year-old man was accidentally caught in a powered paraglider propeller during maintenance. The rotor blades impacted the left part of his head. On arrival at the hospital, he presented with a Glasgow Coma Scale score of E4V1M4. On some areas on his head, skin was noticeably cut off, and the brain tissue out-slipped through an open skull fracture. Continuous bleeding from the superior sagittal sinus (SSS) and the brain surface was observed during emergency surgery. Massive bleeding from the SSS was controlled using a number of tenting sutures and hemostatic agents. We evacuated the crushed brain tissue and coagulated the severed middle cerebral arteries. Dural plasty using the deep fascia of the thigh was performed. The skin defect was closed using an artificial dermis. The administration of high-dose antibiotics has failed to prevent meningitis. Moreover, the severed skin edges and fasciae were necrotic. Plastic surgeons performed debridement and vacuum-assisted closure therapy to promote wound healing. Follow-up head computed tomography revealed hydrocephalus. Lumbar drainage was performed; however, sinking skin flap syndrome was observed. After removing the lumbar drainage, cerebrospinal fluid leakage occurred. We then performed cranioplasty with a titanium mesh and omental flap on day 31. After the surgery, perfect wound healing and infection control were achieved; however, severe disturbance of consciousness remained. The patient was transferred to a nursing home. Primary hemostasis and infection control are mandatory. An omental flap has been determined to be effective in controlling infection by covering the exposed brain tissue.

Hepatoprotective Principles from the Rhizomes of Picrorhiza kurroa.

A methanol extract of rhizomes of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae) showed hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. We had previously isolated 46 compounds, including several types of iridoid glycosides, phenylethanoid glycosides, and aromatics, etc., from the extract. Among them, picroside II, androsin, and 4-hydroxy-3-methoxyacetophenone exhibited active hepatoprotective effects at doses of 50-100 mg/kg, per os (p.o.) To characterize the mechanisms of action of these isolates and to clarify the structural requirements of phenylethanoid glycosides for their hepatoprotective effects, their effects were assessed in in vitro studies on (i) D-GalN-induced cytotoxicity in mouse primary hepatocytes, (ii) LPS-induced nitric oxide (NO) production in mouse peritoneal macrophages, and (iii) tumor necrosis factor-α (TNF-α)-induced cytotoxicity in L929 cells. These isolates decreased the cytotoxicity caused by D-GalN without inhibiting LPS-induced macrophage activation and also reduced the sensitivity of hepatocytes to TNF-α. In addition, the structural requirements of phenylethanoids for the protective effects of D-GalN-induced cytotoxicity in mouse primary hepatocytes were evaluated.

Differential involvement of LUBAC-mediated linear ubiquitination in intestinal epithelial cells and macrophages during intestinal inflammation.

Disruption of the intestinal epithelial barrier and dysregulation of macrophages are major factors contributing to the pathogenesis of inflammatory bowel diseases (IBDs). Activation of NF-κB and cell death are involved in maintaining intestinal homeostasis in a cell type-dependent manner. Although both are regulated by linear ubiquitin chain assembly complex (LUBAC)-mediated linear ubiquitination, the physiological relevance of linear ubiquitination to intestinal inflammation remains unexplored. Here, we used two experimental mouse models of IBD (intraperitoneal LPS and oral dextran sodium sulfate [DSS] administration) to examine the role of linear ubiquitination in intestinal epithelial cells (IECs) and macrophages during intestinal inflammation. We did this by deleting the linear ubiquitination activity of LUBAC specifically from IECs or macrophages. Upon LPS administration, loss of ligase activity in IECs induced mucosal inflammation and augmented IEC death. LPS-mediated death of LUBAC-defective IECs was triggered by TNF. IEC death was rescued by an anti-TNF antibody, and TNF (but not LPS) induced apoptosis of organoids derived from LUBAC-defective IECs. However, augmented TNF-mediated IEC death did not overtly affect the severity of colitis after DSS administration. By contrast, defective LUBAC ligase activity in macrophages ameliorated DSS-induced colitis by attenuating both infiltration of macrophages and expression of inflammatory cytokines. Decreased production of macrophage chemoattractant MCP-1/CCL2, as well as pro-inflammatory IL-6 and TNF, occurred through impaired activation of NF-κB and ERK via loss of ligase activity in macrophages. Taken together, these results indicate that both intraperitoneal LPS and oral DSS administrations are beneficial for evaluating epithelial integrity under inflammatory conditions, as well as macrophage functions in the event of an epithelial barrier breach. The data clarify the cell-specific roles of linear ubiquitination as a critical regulator of TNF-mediated epithelial integrity and macrophage pro-inflammatory responses during intestinal inflammation. © 2022 The Pathological Society of Great Britain and Ireland.

A case of symptomatic carotid artery occlusion after aortic arch replacement treated with carotid-carotid crossover bypass.

Background: Symptomatic common carotid artery (CCA) occlusion is rare and its treatment remains unestablished. Although cases of subclavian-to-carotid bypass have been reported, very few cases of carotid-tocarotid crossover bypass have been reported, despite its advantages. We report a case of Riles type 1A symptomatic CCA occlusion after aortic arch replacement that was treated with carotid-to-carotid crossover bypass with favorable outcomes. Case Description: A 65-year-old woman with a history of hypertension, hyperlipidemia, diabetes, and total arch replacement for thoracic aortic aneurysm was admitted to our hospital with a complaint of the right hemiparesis and motor aphasia. Head magnetic resonance imaging revealed a fresh infarction in the left cerebral hemisphere. Cervical computed tomography (CT) angiography revealed left CCA occlusion. Thoracic CT angiography showed severe stenosis of the left subclavian artery. SPECT showed a general decrease in blood flow in the left cerebral hemisphere. We performed a carotid-to-carotid crossover bypass with a synthetic graft that was passed through the subcutaneous tunnel. First, the right carotid artery-synthetic graft end-to-side anastomosis was performed. Subsequently, we performed synthetic graft-left CCA end-to-side anastomosis. The postoperative course was uneventful. Cervical computed tomography angiography showed perfect patency of the crossover bypass. The patient recovered almost completely and was independently performing daily activities. Conclusion: Carotid-to-carotid crossover bypass is a durable treatment for symptomatic CCA occlusion. Further studies are needed to compare its outcomes with those of other methods and to confirm our findings with larger sample size.

A Case of Proximal Posterior Inferior Cerebellar Artery (PICA) Aneurysm Treated with PICA-to-PICA Bypass and Trapping Surgery: Comparison with Occipital Artery-PICA Bypass.

Posterior inferior cerebellar artery (PICA) aneurysms often require cerebral vascular reconstruction for surgical treatment because of their characteristic morphology. Despite its potential complications, the occipital artery-to-posterior inferior cerebellar artery (OA-PICA) bypass is a typical treatment because of its versatility. Although a few cases of intracranial-to-intracranial bypass have been reported, this type of vascular reconstruction is only regarded as an alternative to the OA-PICA bypass because of the uncertainty of bypass feasibility and potential risk of ischemic complications. In this article, we report a case of proximal PICA ruptured aneurysm that was treated with a PICA-to-PICA (PICA-PICA) bypass. A 79-year-old man presented with a chief complaint of sudden, severe headache and disturbances in consciousness. Radiological examination revealed a right proximal PICA fusiform aneurysm. The patient had many systemic disorders such as microscopic polyangiitis and steroid-induced diabetes mellitus that could have caused wound dehiscence and cerebrospinal fluid (CSF) leakage. We performed the PICA-PICA bypass and trapping surgery rather than the OA-PICA bypass to avoid skin problems and CSF leakage. The postoperative course was uneventful, and the patient was discharged on day 64 without any neurological disorders. In comparison with the OA-PICA bypass, the PICA-PICA bypass is less likely to cause CSF leakage and skin complications, although it carries the risk of specific ischemic complications and requires advanced surgical techniques. For some patients with systemic disorders, the PICA-PICA bypass could be an optimal treatment option for proximal fusiform PICA aneurysms rather than as an alternative to the OA-PICA bypass.

Supramolecular Shear-Thinning Glycopeptide Hydrogels for Injectable Enzyme Prodrug Therapy Applications.

Transplantable catalytic reactors have attracted considerable attention as therapeutic biomedical materials. However, existing transplantable reactors such as biocatalytic films are limited by their invasiveness. Here, we report the fabrication of biocatalytic supramolecular hydrogels via self-assembly of amphiphilic glycopeptides. We show that the hydrogels have shear-thinning properties, demonstrating their potential to be administered using a syringe. Enzymes can be loaded into the hydrogels by simply adding enzyme solution, and the enzyme-loaded hydrogels can transform a prodrug into an anticancer drug that inhibits tumor cell growth. This study demonstrates the potential of these biocatalytic hydrogels as injectable therapeutic reactors for enzyme prodrug therapy.