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Abstract Background and Aim This study aimed to clarify whether several single‐nucleotide polymorphisms (SNPs)‐related chronic pancreatitis such as carboxypeptidase A1 (CPA1), carboxypeptidase B1 (CPB1), Gamma‐glutamyltransferase 1 (GGT1), G‐protein‐coupled receptor Class C Group 6 Member A (GPRC6A), and serine protease inhibitor, Kazal type 1 (SPINK‐1) genotypes were associated with clinical characteristics of patients with intraductal papillary mucinous neoplasm (IPMN) and worrisome features of IPMN. Methods We enrolled 100 patients with IPMN and 116 patients as a control. Serum p‐amylase, lipase, trypsin, phospholipase A2 (PLA2), and elastase‐1 levels were measured. An Olympus EUS (GF‐UCT 260) was used to perform endosonography in 100 patients with IPMN. Total EUS score was evaluated using endosonography. DNA was isolated from the duodenal tissue using a commercial system and polymerase chain reaction (PCR) was performed on 7500 Fast PCR System. Results There were no associations between glucose tolerances, lipid levels and genotypes of CPA1, GGT1, GPRC6A, and SPINK‐1 in patients with IPMN. CPA1 genotype was significantly associated with the pathophysiology of IPMN. Then, GGT1 genotype was also significantly associated with EUS total score and the size of cyst more than 20 mm and more than 30 mm as one of worrisome features of IPMN. Conclusion Genotypes of carboxypeptidase A1 and gamma‐glutamyltransferase 1 may be useful tools for the diagnosis and the predictor of worrisome features of IPMN.

ObjectivePreemptive thoracic endovascular aortic repair (TEVAR) has the potential to improve the prognosis of Stanford type B aortic dissection (TBAD), however it is important to determine whether it could be safely performed as a prophylactic treatment. This study aimed to determine the short- and long-term outcomes of preemptive TEVAR for uncomplicated TBAD with a small aortic aneurysm.DesignRetrospective multicenter analysis.MethodsWe analyzed 212 patients with medically treated uncomplicated subacute TBAD between July 2004 and October 2019 in two Japanese academic centers. The short- and long-term prognosis of patients who underwent preemptive TEVAR and the changes in aortic diameter over time after TEVAR were analyzed. Aorta-related complications, aortic-related death and postoperative complications were recorded and analyzed. Analysis was performed on an intension-to-treat basis.ResultsDuring follow-up, patients were divided into two groups: optimal medical treatment [OMT; n = 185 (87%)] and preemptive TEVAR [n = 27 (13%)]. In all cases, aortic enlargement was the reason for therapeutic intervention in the preemptive TEVAR group. Propensity score matching yielded a cohort of 27 control patients with OMT (group A) and 27 patients who underwent preemptive TEVAR (group B). Preoperative characteristics were similar between groups. In group B, only one patient developed type A dissection at a late stage and died from aortic rupture. Freedom from aortic-related death at 1/5/10 years was 100%/92%/92% in group B. Overall growth (mm/year) of max aorta was significantly smaller in the TEVAR group than in the control group (−3.7 ± 2.9 vs. 0.4 ± 5.6, p

Abstract Objective In patients with stable hemodynamic status after an acute coronary syndrome (ACS), coronary artery bypass grafting (CABG) after preoperative investigations can provide outcomes comparable to those of emergency surgery. However, no established guidelines exist regarding the preparation period before surgery. We report the results of the use of an inpatient cardiac rehabilitation program followed by CABG after an ACS to improve post-operative outcomes and prognosis after discharge. Methods From 2005 to 2017, 471 patients underwent either isolated or combined CABG at our institution, and of those, the 393 who received isolated CABG were included in the analysis. Twenty-seven patients (6.9%) were admitted with ACS and underwent preoperative rehabilitation before undergoing CABG, with a subsequent review of surgical morbidity and mortality rates. Propensity score matching yielded a cohort of 26 patients who underwent preoperative rehabilitation (group A) and 26 controls (group B). Preoperative characteristics were similar between groups. Results The completion rate of the rehabilitation program was 96.3%. All programs were conducted with inpatients, with an average length of stay of 23 ± 12 days. All patients completed in-bed exercises, and 85% completed out-of-bed exercises. The 30-day postoperative mortality was 0% in both groups A and B, and the rate of postoperative major adverse cardiac or cerebrovascular events at 12 months did not differ significantly between groups (7.7% vs 3.9%, respectively; p = 1.0). The duration of mechanical ventilation (1.3 ± 0.3 vs 1.5 ± 0.3 days, respectively; p = 0.633), length of intensive care unit stay (4.4 ± 2.1 vs 4.8 ± 2.3 days, respectively; p = 0.584) and length of hospital stay (25 ± 13 vs 22 ± 9 days, respectively; p = 0.378) did not differ significantly between groups. Conclusions No complications of preoperative rehabilitation were observed, suggesting that it is an acceptable option for patients who experience ACS and undergo CABG. These results are promising in offering more robust designs of future trials.

Abstract NEMO is a ubiquitin-binding protein which regulates canonical NF-κB pathway activation in innate immune signaling, cell death regulation and host-pathogen interactions. Here we identify an NF-κB-independent function of NEMO in proteostasis regulation by promoting autophagosomal clearance of protein aggregates. NEMO-deficient cells accumulate misfolded proteins upon proteotoxic stress and are vulnerable to proteostasis challenges. Moreover, a patient with a mutation in the NEMO-encoding IKBKG gene resulting in defective binding of NEMO to linear ubiquitin chains, developed a widespread mixed brain proteinopathy, including α-synuclein, tau and TDP-43 pathology. NEMO amplifies linear ubiquitylation at α-synuclein aggregates and promotes the local concentration of p62 into foci. In vitro, NEMO lowers the threshold concentrations required for ubiquitin-dependent phase transition of p62. In summary, NEMO reshapes the aggregate surface for efficient autophagosomal clearance by providing a mobile phase at the aggregate interphase favoring co-condensation with p62.

Abstract Background Iatrogenic aortic dissection during cardiac surgery is a rare but critical complication. At present, no strategies have been developed to prevent it. We herein report a case of intraoperative aortic dissection during aortic root replacement in an older patient with Loeys–Dietz syndrome type III who had no family history of aortic disease. Case presentation A 60-year-old man was admitted to the hospital for Stanford type B acute aortic dissection and given conservative treatment. He was found to have aortic root dilatation and severe aortic regurgitation. Thus, elective Bentall procedure was performed. Postoperative computed tomography showed new Stanford type A aortic dissection that may have developed due to aortic cannulation during surgery. The patient was given conservative treatment and successfully discharged to home at postoperative day 34. Although he had no family history of aortic disease, a genetic test revealed an unreported SMAD3 frameshift mutation (c.742_749dup, p. Gln252ThrfsTer7), and the patient was diagnosed with Loeys–Dietz syndrome type III. Conclusion In patients with connective tissue disorder, aortic manipulations may become the cause of critical complications. Avoiding the use of invasive techniques, such as cannulation and cross-clamping, and implementing treatment strategies, such as perfusion from other sites than the aorta and open distal anastomosis, can prevent these complications, and may be useful treatment modalities. The possibility of connective tissue disease should be considered even if the patient is older and has no family history of aortic disease.

Summary: Spatial transcriptomics couples visual spatial markers with gene expression levels, but slide space and cost limit the number of samples that can be processed. Here, we present a protocol for mounting brains from multiple mice onto a single capture area of a spatial transcriptomics slide. We describe steps for conjoining frozen hippocampal sections from different brains into a single cryostat block, reducing the quantity of reagents required. This protocol is applicable to a range of existing spatial genomics platforms.For complete details on the use and execution of this protocol, please refer to Li et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Background: Contemporary series of aortic arch replacement at the time of aortic root surgery are limited in number of patients and mostly address hemiarch replacement. We describe outcomes after aortic root and concomitant arch replacement, including total arch replacement. Methods: This single-institution retrospective review studied 1196 consecutive patients from May 2004 to September 2020 who underwent first-time aortic root replacement. Patients undergoing surgery for endocarditis were excluded (n = 68, 5.7%). Patients undergoing concomitant root and arch replacement were propensity matched with patients undergoing isolated root surgery based on indication, clinical and operative characteristics, demographics, medical history including connective tissue disorders, and urgency. Multivariable Cox proportional hazards and logistic regression modeling were used to assess the primary outcome of all-cause mortality and the secondary outcomes of prolonged ventilator use, postoperative blood transfusion, and debilitating stroke, adjusted for patient and operative characteristics. Results: Among the 1128 patients who underwent aortic root intervention during the study period, 471 (41.8%) underwent concomitant aortic arch replacement. Most underwent hemiarch replacement (n = 411, 87.4%); 59 patients (12.6%) underwent total arch replacement (with elephant trunk: n = 23, 4.9%; without elephant trunk: n = 36, 7.7%). The mean follow-up time was 4.6 years postprocedure. Operative mortality was 2.2%, and total mortality over the entire study period was 9.2%. Propensity matching generated 348 matches (295 concomitant hemiarch, 53 concomitant total arch). Concomitant hemiarch (hazard ratio, 1.00; 95% confidence interval, 0.54-1.86, P = .99) and total arch replacement (hazard ratio, 1.60, 95% confidence interval, 0.72-3.57, P = .24) were not significantly associated with increased mortality. Rates of stroke were not significantly different among each group: isolated root (n = 11/348, 3.7%), root + hemiarch (n = 17/295, 5.8%), and root + total arch (n = 3/53, 5.7%) replacement (P = .50), nor was the adjusted risk of stroke. Both concomitant arch interventions were associated with prolonged ventilator use and use of postoperative blood transfusions. Conclusions: Hemiarch and total arch replacement are safe to perform at the time of aortic root intervention, with no significant differences in survival or stroke rates, but increased ventilator and blood product use.

Objective: To evaluate the effect of perioperative allogeneic packed red blood cell (RBC) transfusion during aortic root replacement. Method: We reviewed patients undergoing aortic root replacement at our institution between March 2014 and April 2020. In total, 760 patients underwent aortic root replacement, of whom 442 (58%) received a perioperative RBC transfusion. Propensity score matching was used to account for baseline and operative differences resulting in 159 matched pairs. All-cause mortality was assessed with Kaplan–Meier curves. Data were obtained from our institutional Society of Thoracic Surgeons database and chart review. Results: After propensity score matching, the RBC-transfused and -nontransfused groups were similar for all preoperative characteristics. Cardiopulmonary bypass time, crossclamp time, and lowest operative temperature were similar between the transfused and nontransfused groups (standardized mean difference

Summary: Neurons require large amounts of energy, but whether they can perform glycolysis or require glycolysis to maintain energy remains unclear. Using metabolomics, we show that human neurons do metabolize glucose through glycolysis and can rely on glycolysis to supply tricarboxylic acid (TCA) cycle metabolites. To investigate the requirement for glycolysis, we generated mice with postnatal deletion of either the dominant neuronal glucose transporter (GLUT3cKO) or the neuronal-enriched pyruvate kinase isoform (PKM1cKO) in CA1 and other hippocampal neurons. GLUT3cKO and PKM1cKO mice show age-dependent learning and memory deficits. Hyperpolarized magnetic resonance spectroscopic (MRS) imaging shows that female PKM1cKO mice have increased pyruvate-to-lactate conversion, whereas female GLUT3cKO mice have decreased conversion, body weight, and brain volume. GLUT3KO neurons also have decreased cytosolic glucose and ATP at nerve terminals, with spatial genomics and metabolomics revealing compensatory changes in mitochondrial bioenergetics and galactose metabolism. Therefore, neurons metabolize glucose through glycolysis in vivo and require glycolysis for normal function.

Abstract Background Open surgery for thoracoabdominal aortic aneurysm is highly invasive. Staged repair for extensive TAAA is effective because it has low morbidity and mortality, and preserves spinal cord perfusion. An initial total arch replacement can create a proximal landing zone for thoracic endovascular aneurysm repair. Case presentation We performed a staged hybrid thoracoabdominal aortic aneurysm repair after total arch replacement, which consisted of a primary open repair procedure as Crawford Extent III and IV thoracoabdominal aortic aneurysms, and a secondary thoracic endovascular aneurysm repair for the residual lesions for four patients. No spinal cord injury was observed. In one patient, the residual descending aortic aneurysm ruptured six months after the primary open surgery. Conclusions Overall, staged hybrid repair is effective and shows low morbidity and mortality. Secondary thoracic endovascular aneurysm repair should be performed as soon as possible to reduce the risk of residual aneurysm rupture.

Cell death is a critical process in health and disease, yet available markers record later stages of cell death once a cell has already begun to decompose. Here the authors show the use of a genetically encoded calcium indicator that demarcates an irreversible stage of cell death earlier than previously possible.

The Warburg effect, aerobic glycolysis, is a hallmark feature of cancer cells grown in culture. However, the relative roles of glycolysis and respiratory metabolism in supporting in vivo tumor growth and processes such as tumor dissemination and metastatic growth remain poorly understood, particularly on a systems level. Using a CRISPRi mini-library enriched for mitochondrial ribosomal protein and respiratory chain genes in multiple human lung cancer cell lines, we analyzed in vivo metabolic requirements in xenograft tumors grown in distinct anatomic contexts. While knockdown of mitochondrial ribosomal protein and respiratory chain genes (mito-respiratory genes) has little impact on growth in vitro, tumor cells depend heavily on these genes when grown in vivo as either flank or primary orthotopic lung tumor xenografts. In contrast, respiratory function is comparatively dispensable for metastatic tumor growth. RNA-Seq and metabolomics analysis of tumor cells expressing individual sgRNAs against mito-respiratory genes indicate overexpression of glycolytic genes and increased sensitivity of glycolytic inhibition compared to control when grown in vitro, but when grown in vivo as primary tumors these cells down-regulate glycolytic mechanisms. These studies demonstrate that discrete perturbations of mitochondrial respiratory chain function impact in vivo tumor growth in a context-specific manner with differential impacts on primary and metastatic tumors.

Basal cell adenoma (BCA) is a relatively rare benign tumor of the salivary glands. However, BCA rarely occurs in the minor salivary glands. Herein, we report a rare case of BCA that originated in the left buccal mucosa of a 47-year-old female. Magnetic resonance imaging revealed a mass with a diameter of 1.5 cm and a well-defined periphery in a high-signal area on a T2-weighted image. The mass was located between the buccal and masseter muscles on the left side of the face. A biopsy was performed, and the results indicated a pathological diagnosis of BCA. Thereafter, excision of the mass was performed under local anesthesia. Histopathological examination showed that the tumor was covered with a fibrous capsule and filled with basal cell-like cells that proliferated in a solid, tubular, and trabecular pattern, with no cellular atypia or infiltrative growth. Immunohistochemistry analysis revealed that the tumor cells inside the luminal-tubular structure showed positive immunoreactivity for CK1/3, whereas those outside expressed αSMA and vimentin. However, most of the tumor cells were p63-positive. The Ki-67 labeling index of the tumor was 3%.In addition to this report, we present a review of cases of salivary gland tumors reported from 1991 to date. The review of the 20 cases (including the present case) indicated that the most common sites of occurrence were the upper lip and palate (7 [35%] cases), buccal mucosa (4 [20%] cases), and alveolar region (2 [10%] cases). The most common histopathological type was the solid type (12 cases).

Inferior mesenteric artery obstruction rarely causes critical mesenteric ischemia, because of the good collateral blood supply. We report a rare case of critical mesenteric ischemia due to sole inferior mesenteric artery obstruction accompanied by acute aortic dissection. Early diagnosis and treatment of mesenteric ischemia are important. (Level of Difficulty: Advanced.)

Energy metabolism and ATP levels are controlled by an interlocking network of pathways. Here, the authors apply a genome-wide CRISPR screen to define genes that increase or decrease ATP levels to define the “ATPome”, a map of pathways that contribute to cellular ATP regulation.

Abstract Introduction: The number of cases for which the Batista procedure is indicated is small, but some patients with appropriate indication can achieve good therapeutic results. Objective: To avoid incorrect left ventricular incision and obtain good surgical results in patients with dilated cardiomyopathy suitable for partial left ventriculectomy, we employed intraoperative direct echocardiography to determine the exact extent and position of the myocardial incision, even for surgeons who are not very experienced with the Batista procedure. Methods: A 72-year-old man with dilated cardiomyopathy underwent the Batista procedure with the aid of epicardial echocardiography to confirm the location of both the papillary muscles and the diseased myocardium. Results: We were able to accurately perform left ventricular incision and remove the diseased lateral ventricular wall. Two years later, the patient had no symptoms of heart failure, and his brain natriuretic peptide (BNP) level decreased from 1155 to 49.3 pg/mL. Conclusions: We believe that the use of intraoperative echocardiography may have the potential to make the Batista procedure less technically demanding and more reproducible for surgeons with little experience in the procedure.

Abstract Background Preemptive thoracic endovascular aortic repair (TEVAR) is an advanced treatment that has possibility to improve late outcomes in patients with subacute type B aortic dissection. However, it may not be the treatment of choice for elderly patients with uncomplicated subacute type B aortic dissection because of their inherent frailty and increased risk of periprocedural complications. Methods Data were collected between July 2004 and October 2017 in Yamagata university hospital and between February 2016 and May 2018 in Nihonkai General hospital. A total of 152 medically treated subacute type B aortic dissection patients were enrolled in this study. Patients were divided into two groups: age 80 year and older group (Group O, n = 33, 22%) and a group

Background Male patients with Marfan syndrome have a higher risk of aortic events and root dilatation compared with females. The role androgens play during Marfan syndrome aneurysm development in males remains unknown. We hypothesized that androgens potentiate transforming growth factor beta induced Erk (extracellular‐signal‐regulated kinase)/Smad activation, contributing to aneurysm progression in males. Methods and Results Aortic diameters in Fbn1C1039G/+ and littermate wild‐type controls were measured at ages 6, 8, 12, and 16 weeks. Fbn1C1039G/+ males were treated with (1) flutamide (androgen receptor blocker) or (2) vehicle control from age 6 to 16 weeks and then euthanized. p‐Erk1/2, p‐Smad2, and matrix metalloproteinase (MMP) activity were measured in ascending/aortic root and descending aorta specimens. Fbn1C1039G/+ male and female ascending/aortic root‐derived smooth muscle cells were utilized in vitro to measure Erk/Smad activation and MMP‐2 activity following dihydrotestosterone, flutamide or transforming growth factor beta 1 treatment. Fbn1C1039G/+ males have increased aneurysm growth. p‐Erk1/2 and p‐Smad2 were elevated in ascending/aortic root specimens at age 16 weeks. Corresponding with enhanced Erk/Smad signaling, MMP‐2 activity was higher in Fbn1C1039G/+ males. In vitro smooth muscle cell studies revealed that dihydrotestosterone potentiates transforming growth factor beta‐induced Erk/Smad activation and MMP‐2 activity, which is reversed by flutamide treatment. Finally, in vivo flutamide treatment reduced aneurysm growth via p‐Erk1/2 and p‐Smad2 reduction in Fbn1C1039G/+ males. Conclusions Fbn1C1039G/+ males have enhanced aneurysm growth compared with females associated with enhanced p‐Erk1/2 and p‐Smad2 activation. Mechanistically, in vitro smooth muscle cell studies suggested that dihydrotestosterone potentiates transforming growth factor beta induced Erk/Smad activation. As biological proof of concept, flutamide treatment attenuated aneurysm growth and p‐Erk1/2 and p‐Smad2 signaling in Fbn1C1039G/+ males.

Motor fluctuations can be seen even during treatment with continuous levodopa-carbidopa intestinal gel infusion (LCIG). We report on a middle-aged man with advanced Parkinson's disease (PD) on LCIG in which motor fluctuations have been improved with an anticholinergic. To the best of our knowledge, there have been no previous LCIG cases reported with motor fluctuations responding to non-dopaminergic agent, which might reveal some clues to its pathophysiology. Long-term oral levodopa treatment is associated with development of potentially disabling motor complications including motor fluctuations and dyskinesias in the majority of patients with PD. It has been suggested that motor complications are related to the nonphysiological restoration of brain dopamine with intermittent administration of standard oral levodopa. LCIG significantly reduces “off” time and increases “on” time without dyskinesia in comparison to standard oral levodopa through consistent plasma concentration of levodopa to restore brain dopamine in a more physiological manner. However, it has been reported that PD patients on LCIG often worsen during the afternoon hours, even with stable plasma concentration of levodopa. This raises the possibility that additional factors to dopamine deficiency could play a role in occurrence of motor fluctuations. Here we offer a hypothesis that altered cholinergic signaling could also be involved in the pathophysiology of motor fluctuations, based on our clinical evidence that anticholinergic drug has eliminated motor fluctuations during LCIG in a patient with PD. Further studies for non-dopaminergic along with dopaminergic signaling may be needed to better understand the pathophysiological basis of motor complications in PD.

OBJECTIVE:Intra-aortic balloon pump (IABP) is one of the most commonly used mechanical circulatory assist devices for high-risk patients undergoing cardiac surgery. In an effort to validate previously reported clinical outcomes, we describe the preoperative characteristics and outcomes of patients who underwent prophylactic IABP in high-risk patients undergoing coronary artery bypass grafting (CABG). DESIGN:A prospective observational study. METHODS:From 2005 to 2017, 471 patients underwent either isolated or combined CABG at our institution. Of those, 393 patients underwent isolated CABG and were included for the analysis. Eighty-five patients (22%) were considered high-risk and underwent prophylactic IABP, with subsequent review of surgical morbidity and mortality rates. RESULTS:The 30-day postoperative mortality (prophylactic IABP group vs non prophylactic IABP group: 0% vs 1.6%, p = 0.589) and major adverse cardiac or cerebrovascular events (5.9% vs 3.3%, p = 0.333) were not significantly different between the two groups. Prolonged mechanical ventilation (>72 hours) (12.5% vs 4.2%, p = 0.014) occurred more frequently in the prophylactic IABP group. CONCLUSIONS:No IABP-related complications were noted, emphasizing that the use of prophylactic IABP in high-risk patients undergoing CABG is an acceptable option.

Insufficient or dysregulated energy metabolism may underlie diverse inherited and degenerative diseases, cancer, and even aging itself. ATP is the central energy carrier in cells, but critical pathways for regulating ATP levels are not systematically understood. We combined a pooled clustered regularly interspaced short palindromic repeats interference (CRISPRi) library enriched for mitochondrial genes, a fluorescent biosensor, and fluorescence-activated cell sorting (FACS) in a high-throughput genetic screen to assay ATP concentrations in live human cells. We identified genes not known to be involved in energy metabolism. Most mitochondrial ribosomal proteins are essential in maintaining ATP levels under respiratory conditions, and impaired respiration predicts poor growth. We also identified genes for which coenzyme Q10 (CoQ10) supplementation rescued ATP deficits caused by knockdown. These included CoQ10 biosynthetic genes associated with human disease and a subset of genes not linked to CoQ10 biosynthesis, indicating that increasing CoQ10 can preserve ATP in specific genetic contexts. This screening paradigm reveals mechanisms of metabolic control and genetic defects responsive to energy-based therapies.

Salvage radical prostatectomy is one of treatments after radiation therapy to patients with prostate cancer. To date, no case of the salvage robotic assisted radical prostatectomy (RARP) following heavy ion radiotherapy (HIRT) has been published. We report on a 70-year-old man with a history of HIRT for prostate cancer in 2011. For 3 years after. HIRT, his serum PSA levels were permissible range. However, his PSA levels were increased. We had diagnosis localized prostate cancer after HIRT. We had carried out salvage RARP. Until 10 months after salvage RARP, his PSA level was not detectable.

Transarterial chemoembolization (TACE) is usually followed by hepatic dysfunction. We evaluated the effects of L-carnitine on post-TACE impaired liver functions. Methods. 53 cirrhotic hepatocellular carcinoma patients at Osaka Medical College were enrolled in this study and assigned into either L-carnitine group receiving 600 mg oral L-carnitine daily or control group. Liver functions were evaluated at pre-TACE and 1, 4, and 12 weeks after TACE. Results. The L-carnitine group maintained Child-Pugh (CP) score at 1 week after TACE and exhibited significant improvement at 4 weeks after TACE (P

L-3,4-Dihydroxyphenylalanine (L-dopa) is the mainstay of therapy for patients with Parkinson's disease (PD), and mediates its primary effects through conversion into dopamine by aromatic L-amino acid decarboxylase (AADC). Given the loss of AADC-containing nigrostriatal dopaminergic neurons in PD, however, the location of residual AADC that converts L-dopa into dopamine remains controversial. The first objective of this study was to establish the presence of AADC expression in striatal neurons and glia using reverse transcriptase and PCR. Transcripts for the neuronal but not nonneuronal forms of AADC were detected in striatal tissue, cultured striatal neurons, and glia. We then examined whether this striatal AADC expression represents a physiologically significant source of dopamine production. No dopamine release was detected following incubation of striatal cultures with L-dopa or transduction with adenovirus expressing tyrosine hydroxylase. Our data establish the presence of AADC expression in the striatum both in vivo and in vitro, but suggest that striatal components do not represent a primary source of L-dopa decarboxylation following nigrostriatal denervation in rats. Understanding the source and localization of AADC is important in understanding the complications of L-dopa therapy and in designing rational therapeutic strategies for PD, including cellular transplantation and gene therapy.

Respiratory chain dysfunction can decrease ATP and increase reactive oxygen species (ROS) levels. Despite the importance of these metabolic parameters to a wide range of cellular functions and disease, we lack an integrated understanding of how they are differentially regulated. To address this question, we adapted a CRISPRi-and FACS-based platform to compare the effects of respiratory gene knockdown on ROS to their effects on ATP. Focusing on genes whose knockdown is known to decrease mitochondria-derived ATP, we showed that knockdown of genes in specific respiratory chain complexes (I, III, and CoQ10 biosynthesis) increased ROS, whereas knockdown of other low ATP hits either had no impact (mitochondrial ribosomal proteins) or actually decreased ROS (complex IV). Moreover, although shifting metabolic conditions profoundly altered mitochondria-derived ATP levels, it had little impact on mitochondrial or cytosolic ROS. In addition, knockdown of a subset of complex I subunits--including NDUFA8, NDUFB4, and NDUFS8--decreased complex I activity, mitochondria-derived ATP, and supercomplex level, but knockdown of these genes had differential effects on ROS. Conversely, we found an essential role for ether lipids in the dynamic regulation of mitochondrial ROS levels independent of ATP. Thus, our results identify specific metabolic regulators of cellular ATP and ROS balance that may help dissect the roles of these processes in disease and identify therapeutic strategies to independently target energy failure and oxidative stress. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Osteomas are benign tumors characterized by proliferation of dense or trabecular bone. Most osteomas of the head and neck occur in the mandible, they rarely occur in the maxillary sinus, and free osteomas are extremely rare. While usually detected incidentally on plain radiographs, symptoms appear when the osteoma obstructs the sinus orifice or invades the adjacent orbit or intracranial structures. Herein, we report a case of a patient with an isolated laminar osteoma arising in the maxillary sinus. Case Report: A 52-year-old man presented to our hospital with a radiopaque mass in the right maxillary sinus. An oval mass of size 2.7×2.3 cm was observed in the right maxillary sinus on computed tomography, and no sinusitis was present. Under general anesthesia, the mass was removed orally via the modified Caldwell-Luc method. Histopathologic examination revealed layered compact bony tissue covered by the sinus membrane. The mass was free from the inferior wall of the right maxillary sinus, and a part of the mass was covered by the sinus membrane. The postoperative course was uneventful, and no recurrence was noted after 5 years. Conclusions: We experienced a case of an extremely rare osteoma in the maxillary sinus. The osteoma was solitary and free within the maxillary sinus. The treatment performed was surgical excision using the modified Caldwell-Luc method. The cause of the free osteoma was thought to be odontogenic maxillary sinusitis caused by apical periodontitis of the nearby tooth. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Neurofibromas are benign tumors of neurological origin caused by the proliferation of Schwann cells and fibroblasts; they often occur in the skin and nerves as a symptom of von Recklinghausen disease. Solitary neurofibromas are also known to occur on their own, but solitary development in the hard palate is extremely rare and difficult to distinguish from schwannomas. The neural origin of solitary neurofibromas is also difficult to determine intraoperatively, and there have been no reports that clearly identify the neural origin of neurofibromas in the hard palate. Case Report: We report a case of a solitary neurofibroma originating in the hard palate in a 24-year-old woman. She presented to our department with a 1.2x0.8-cm dome-shaped left palate mass. After identification of the nerve at the source, the tumor was resected under general anesthesia. Histopathology was positive for S-100 and CD34 immunostaining, as well as for Alcian blue. Eventually, the mass was diagnosed as a neurofibroma. Conclusions: Solitary neurofibromas originating in the hard palate are difficult to differentiate from other neoplastic lesions, especially schwannomas, based on clinical findings alone. Therefore, it is important to perform a biopsy and immunostaining of the biopsied specimens for S-100 and CD34. In neurofibromas, tumor cells are loose and delicate, often with wavy or serpentine nuclei, and S-100 protein-positive cells are sparser than in schwannomas. An overall pathological diagnosis should be made with regard to CD34, taking into account that schwannomas are CD34-negative and neurofibromas are CD34-positive. [ABSTRACT FROM AUTHOR]

Mitochondria are important sources of energy, but they are also the target of cellular stress, toxin exposure, and aging-related injury. Persistent accumulation of damaged mitochondria has been implicated in many neurodegenerative diseases. One highly conserved mechanism to clear damaged mitochondria involves the E3 ubiquitin ligase Parkin and PTEN-induced kinase 1 (PINK1), which cooperatively initiate the process called mitophagy that identifies and eliminates damaged mitochondria through the autophagosome and lysosome pathways. Parkin is a mostly cytosolic protein, but is rapidly recruited to damaged mitochondria and target them for mitophagy. Moreover, Parkin interactomes also involve signaling pathways and transcriptional machinery critical for survival and cell death. However, the mechanism that regulates Parkin protein level remains poorly understood. Here, we show that the loss of homeodomain interacting protein kinase 2 (HIPK2) in neurons and mouse embryonic fibroblasts (MEFs) has a broad protective effect from cell death induced by mitochondrial toxins. The mechanism by which Hipk2 -/- neurons and MEFs are more resistant to mitochondrial toxins is in part due to the role of HIPK2 and its kinase activity in promoting Parkin degradation via the proteasome-mediated mechanism. The loss of HIPK2 leads to higher cytosolic Parkin protein levels at basal conditions and upon exposure to mitochondrial toxins, which protects mitochondria from toxin-induced damage. In addition, Hipk2 -/- neurons and MEFs show increased expression of PGC-la (peroxisome proliferator-activated receptor-y coactivator 1), a Parkin downstream target that can provide additional benefits via transcriptional activation of mitochondrial genes. Together, these results reveal a previously unrecognized avenue to target HIPK2 in neuroprotection via the Parkin-mediated pathway. [ABSTRACT FROM AUTHOR]

A 60-year-old man was referred to our hospital because of chest tightness. CT scans showed no specific findings except a right ventricular (RV) mass. Echocardiogram revealed that the large cardiac mass was compressing the right ventricular outflow tract, and the patient thus underwent an emergency operation. As the tumour on the inlet side of the right ventricle was tightly adhered to the entire tricuspid chordae, a complete resection was impossible. Pathological findings revealed that the tumour was metastatic squamous cell carcinoma. Four cycles of chemotherapy were administered. Further investigations were conducted to identify the primary cancer focus, but there were no specific findings. Eight months after the operation, the patient returned to the hospital. Echocardiogram showed a severely occupying mass once again, and the patient died as a result. Autopsy revealed no findings relating to the primary origin of the cardiac metastases. [ABSTRACT FROM AUTHOR]

Purpose: To analyze outcomes following whole-gland salvage treatments applied to patients with pathology-proven, locally recurrent prostate cancer following primary definitive radiotherapy. Material and methods: Eighteen consecutive patients who received whole-gland salvage treatments at our institution were retrospectively reviewed. All patients underwent transperineal template-guided mapping biopsy (TTMB) using the standard iodine-125 (125I) brachytherapy (BT) setup. Twelve patients received 125I BT, and six patients underwent robot-assisted laparoscopic prostatectomy (RARP). Prostate-specific antigen (PSA) failure was determined using the Phoenix definition (nadir + 2 ng/ml) following BT and a PSA level of > 0.2 ng/ml following RARP. Toxicities were graded according to CTCAE version 4.0. Results: The median follow-up times were 71 and 11 months for the BT and RARP groups, respectively. In the BT group, the median dose to 90% of the prostate was 131 Gy. The median time to biochemical failure was 47 months, and the biochemical relapse-free survival (BRFS) rates were 56% (95% confidence interval [CI]: 33-94%) and 46% (95% CI: 25-88%) at 3 years and 5 years, respectively. Four patients (33%) developed grade 2 genitourinary (GU) toxicity, and two (17%) developed grade 3 GU toxicity. No patients developed grade ≥ 2 gastrointestinal (GI) toxicity. In the RARP group, three out of six patients (50%) had PSA failure, and four patients (67%) developed grade 2 GU toxicity. No patients developed grade 3 GU toxicity or grade ≥ 2 GI toxicity. On pre-salvage magnetic resonance imaging (MRI), no patients were suspected of having T3 or higher stage lesions. However, three patients (50%) had pT3a and two patients (33%) had pT3b (i.e., seminal vesicle invasion) stage lesions. Conclusions: Whole-gland salvage BT is an effective treatment with an acceptable toxicity profile. The pathology findings from RARP imply that there is a room for improvement in diagnoses made by MRI in the pre-salvage setting. [ABSTRACT FROM AUTHOR]

Coronary aneurysm located just above the left main coronary artery (LMT) is rare and difficult to treat. How the aneurysm is accessed is very important as it determines the result of the surgery. A 70-year-old man with a large coronary aneurysm (40 mm in diameter) in the LMT underwent surgery to prevent its rupture; however, there was severe adhesion. Initially, dissection of the ascending aorta or the pulmonary artery seemed necessary to access the aneurysm; however, the process was possible with limited dissection between the ascending aorta and the pulmonary artery, and we succeeded in firmly closing the LMT site of entry. [ABSTRACT FROM AUTHOR]

Simultaneous suppression of rice (Oryza sativa L.) uptake of As and Cd is challenging because these toxic elements are immobilized under contrasting redox conditions. Given the notion that oxygen diffusion governs redox conditions in temporarily drained paddy soil, we assume that the key to simultaneous suppression of dissolved As and Cd concentrations is air-filled porosity (AFP) of soil. The objectives of this study were to reveal relationships between AFP and dissolved As and Cd concentrations in paddy soils and to identify the optimum water management, in terms of AFP, for simultaneous reduction of As and Cd. Dissolved As and Cd concentrations were determined in soil cores collected at different depths and times during rice growing seasons. Dissolved As concentrations were appreciable (>3 mg L-1) only when AFP was below a threshold value of 0.04 to 0.10 m3 m-3, suggesting that dissolved As was rapidly immobilized once AFP exceeded the threshold value on drainage. Dissolved Cd concentrations were roughly proportional to AFP, with higher concentrations associated with lower soil pH. Although dissolved As concentrations tended to be low in soil samples with high dissolved Cd concentrations and vice versa, both concentrations were low when AFP was slightly above the threshold value for As immobilization. The results suggest that dissolved As and Cd can be simultaneously kept at low levels by appropriate water management practices that produce AFP slightly above the threshold value for As immobilization. [ABSTRACT FROM AUTHOR]

Among tumors of the major salivary glands, tumors in the sublingual gland are rare. Although mucoepidermoid carcinoma (MEC) represents a histological type of salivary gland tumor, it is occasionally difficult to diagnose due to its histological variation. The present study reports a case of MEC harboring a mastermind-like transcriptional coactivator 2 (MAML2) gene translocation in the sublingual gland. A 76-year-old Japanese woman with a mass in the left submandibular region was referred to Kurume University Hospital (Kurume, Japan). Computed tomography scans revealed that the tumor was predominantly located in the sublingual gland, and tumor resection was performed. Histologically, the tumor was composed of cells that exhibited low-grade nuclear atypia and clear and/or granular eosinophilic cytoplasm, and that were proliferating in solid patterns. Periodic acid-Schiff and alcian blue staining revealed a small number of mucinous cells in the tumor. Immunohistochemically, the tumor cells were positive for p40 and p63. Fluorescence in situ hybridization (FISH) analysis revealed a MAML2 gene split. The definitive pathological diagnosis was low-grade MEC, as the case lacked any factors indicative of high-grade malignancy. To the best of our knowledge, this is the first report of MEC in the sublingual gland with MAML2 gene translocation confirmed by FISH. [ABSTRACT FROM AUTHOR]

Background In patients with small aortic annulus, sufficient size of stented aortic bioprosthesis cannot be implanted without additional procedures. In such cases, we use stentless aortic bioprosthesis to obtain sufficient effective orifice area. In this study, we investigated long-term impact of stentless aortic bioprosthesis on clinical outcomes, compared with stented aortic bioprosthesis. Materials and Methods We retrospectively investigated 140 patients who underwent aortic valve replacement (AVR) with porcine bioprosthesis for severe aortic stenosis between 1999 and 2010. Patients who had moderate or more aortic regurgitation and who underwent concomitant mitral procedures were excluded. A total of 69 patients (49%) were implanted stentless bioprosthesis (Freestyle group; Medtronic Inc,Minneapolis, Minnesota, United States) and 71 patients (51%) were implanted stented bioprosthesis (Mosaic group; Medtronic Inc). Follow-up was complete in 97.9% patients. Median follow-up period was 4.2 years. Results Patients in Freestyle group had smaller body surface area, smaller aortic annulus diameter, smaller aortic valve area, larger mean pressure gradient, higher peak velocity across aortic valve, larger left ventricular mass index (LVMI), and lower left ventricular ejection fraction (LVEF). Mean size of implanted prosthesis was larger in Freestyle group. In-hospital mortality was 1.4% in Freestyle group and 2.8% in Mosaic group (p = 0.980). Five-year survival rate was not different between two groups (5-year survival rate was 87.5 ± 4.7% in Freestyle group and 84.1 ± 7.5% in Mosaic group; log rank, p = 0.619). Late New York Heart Association functional class was lower in Freestyle group. Late LVMI and LVEF became similar between two groups. Conclusion Stentless aortic bioprosthesis is superior in left ventricular remodeling after AVR for aortic stenosis and is especially effective for small aortic annulus. [ABSTRACT FROM AUTHOR]

Background Atrial fibrillation (AF) adversely affects surgical outcomes of mitral valve surgery. However, the long-term impact of Maze procedure has not been clear yet. Patients and Methods We retrospectively investigated 159 patients who underwent mitral valve repair for degenerative mitral regurgitation with persistent AF between 1991 and 2010. The mean age of patients was 63.1 ± 10.5 years. After we started performing Maze procedure in 2002, 65 patients underwent concomitant Maze procedure. The median follow-up time was 7.5 years. Results There was one operative death (0.63%). The overall survival rate was 91.0 ± 2.6% at 5 years and 79.1 ± 4.7% at 10 years. Survival was significantly better in patients who underwent Maze procedure than those who did not. The rate of freedom from AF in patients who underwent Maze procedure was 86.4 ± 4.5% at 1 year and 81.1 ± 5.6% at 5 years. The freedom rate from stroke was higher in patients who underwent Maze procedure than those who did not. Patients with postoperative AF had larger left ventricular systolic and diastolic diameters at follow-up and higher New York Heart Association functional class than patients without postoperative AF (1.4 ± 0.5 vs. 1.1 ± 0.3, p < 0.001). Conclusion Maze procedure can have a positive effect on long-term survival, freedom from stroke, and cardiac function. [ABSTRACT FROM AUTHOR]

Disruptions in mitochondrial dynamics may contribute to the selective degeneration of dopamine (DA) neurons in Parkinson's disease (PD). However, little is known about the normal functions of mitochondrial dynamics in these neurons, especially in axons where degeneration begins, and this makes it difficult to understand the disease process. To study one aspect of mitochondrial dynamics-- mitochondrial fission--in mouse DA neurons, we deleted the central fission protein dynamin-related protein 1 (Drp 1 ). Drp 1 loss rapidly eliminates the DA terminals in the caudate-putamen and causes cell bodies in the midbrain to degenerate and lose a-synuclein. Without Drpl, mitochondrial mass dramatically decreases, especially in axons, where the mitochondrial movement becomes uncoordinated. However, in the ventral tegmental area (VTA), a subset of midbrain DA neurons characterized by small hyperpolarization-activated cation currents (Ih) is spared, despite near complete loss of their axonal mitochondria. Drpl is thus critical for targeting mitochondria to the nerve terminal, and a disruption in mitochondrial fission can contribute to the preferential death of nigrostriatal DA neurons. [ABSTRACT FROM AUTHOR]

By combining experimental neuron models and mathematical tools, we developed a "systems" approach to deconvolve cellular mechanisms of neurodegeneration underlying the most common known cause of Parkinson's disease (PD), mutations in leucine-rich repeat kinase 2 (LRRK2). Neurons ectopically expressing mutant LRRK2 formed inclusion bodies (IBs), retracted neurites, accumulated synuclein, and died prematurely, recapitulating key features of PD. Degeneration was predicted from the levels of diffuse mutant LRRK2 that each neuron contained, but IB formation was neither necessary nor sufficient for death. Genetic or pharmacological blockade of its kinase activity destabilized LRRK2 and lowered its levels enough to account for the moderate reduction in LRRK2 toxicity that ensued. By contrast, targeting synuclein, including neurons made from PD patient-derived induced pluripotent cells, dramatically reduced LRRK2- dependent neurodegeneration and LRRK2 levels. These findings suggest that LRRK2 levels are more important than kinase activity per se in predicting toxicity and implicate synuclein as a major mediator of LRRK2-induced neurodegeneration. [ABSTRACT FROM AUTHOR]

Object detection in high-definition video is required in video artificial intelligence (AI) applications for edge/terminals to detect a wide range of objects with one camera at one time. Although various AI inference schemes for object detection (e.g., You Only Look Once (YOLO)) have been proposed, they have a limitation regarding the input image size, thus need to shrink the input high-definition image into that limited size. This collapses small objects, making them undetectable. This article introduces highdefinition AI inference technology we previously proposed for solving this problem, with which multiple object detectors cooperate to detect small and large objects in high-definition video. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 67-year-old man with Alzheimer's disease presented with a history of abdominal fullness and profound chronic constipation. He was admitted to the surgical hospital immediately for emergency surgical procedure to decompress the abdomen and his dilated sigmoid colon was surgically removed and an artificial anus was made. He needed treatment with antibiotics as he developed bacterial translocation due to increased permeability of the intestinal mucosal barrier.

The article reports on a case study of an 82-year old woman diagnosed with anticonvulsant valproate-associated-hypoglycemic attack. Topics discussed include the medical background of the patient, the clinical tests she underwent, her medical conditions, the treatment options given to her, and an overview of her illness.

The article discusses the case of a 78-old woman with a 50-year history of bipolar disorder who was diagnosed to have suffered the Adam-Stokes syndrome three months after the initiation of lithium therapy. Topics covered are the gastrointestinal, neurologic and cardiologic manifestations of lithium toxicity, the cardiac complications of conduction block or bradyarrythmias, the increase in deaths among psychiatric patients due to psychotropic medications.

An Nd3+:YAG pulsed laser was employed as a light source for two-photon photoemission from organic semiconducting thin films in low vacuum and air. Photoionization by the two-photon process was confirmed in both the environments by measuring photoemission current. By constructing a pump–probe system, photoemissions from transient species formed by the pump light irradiation were detected by probe light irradiation as a result of a linear increase in the photocurrent with the pump power via a one-photon process. Thus, we propose a novel method called two-photon photoelectron yield spectroscopy to determine the excited-state energy levels in ambient environments. [ABSTRACT FROM AUTHOR]