Acute pancreatitis caused by duodenal bezoar and treated with endoscopic procedures.

Background: Acute pancreatitis triggered by causative agents, including alcohol consumption, gallstones, dyslipidemia, drugs, and infection, is frequently addressed. However, reports of acute pancreatitis caused by duodenal bezoars are limited. Case Presentation: A 75-year-old man experiencing abdominal pain and frequent vomiting was transferred to our hospital. His medical records presented history of diabetes, hypertension, dyslipidemia, and gastric cancer surgery. Computed tomography of the abdomen indicated duodenal dilatation, enlarged pancreas, and fluid retention, with no bile duct stones present. Minor bleeding and duodenal bezoar were endoscopically detected with esophagogastroduodenoscopy (EGD). He was diagnosed with severe acute pancreatitis caused by a bezoar and admitted to the intensive care unit. The duodenal bezoar was dissected and removed with three repetitions of EGD, and the patient was discharged without any complications. Conclusion: Herein, we report a case showing that endoscopic procedures could be effective treatment options in severe pancreatitis caused by duodenal bezoars.

A Collaborative Study on the Classification of Silicone Oil Droplets and Protein Particles Using Flow Imaging Method.

In this study, we conducted a collaborative study on the classification between silicone oil droplets and protein particles detected using the flow imaging (FI) method toward proposing a standardized classifier/model. We compared four approaches, including a classification filter composed of particle characteristic parameters, principal component analysis, decision tree, and convolutional neural network in the performance of the developed classifier/model. Finally, the points to be considered were summarized for measurement using the FI method, and for establishing the classifier/model using machine learning to differentiate silicone oil droplets and protein particles.

Total activation mapping in a patient with an epicardial accessory pathway.

A 42-year-old man was admitted for recurrent atrioventricular reciprocating tachycardia. We performed a total activation mapping, which included a range from the ventricular to atrial waves during right ventricular pacing. The mapping revealed a delayed ventriculoatrial conduction on the left lateral wall. We performed ablation within the coronary sinus, and the ventriculoatrial conduction was lost. By widening the range, we could easily visualize the ventriculoatrial conduction through the accessory pathway. This mapping showed that the conduction in the area of the accessory pathway was delayed, and it was easy to estimate that the conduction pathway included the coronary sinus.

Comprehensive analysis for detecting radiation-specific molecules expressed during radiation-induced rat thyroid carcinogenesis.

Although the association between radiation exposure and thyroid carcinogenesis is epidemiologically evident, 'true' radiation-induced cancers cannot be identified from biological evidence of radiation-associated cases. To assess the individual risk for thyroid cancer due to radiation exposure, we aimed to identify biomarkers that are specifically altered during thyroid carcinogenesis after irradiation in a time-dependent manner in an animal model. Thyroid glands were obtained from rats (n = 175) at 6-16 months after local X-ray (0.1-4 Gy) irradiation of the neck at 7 weeks of age. The gene expression profile in thyroid glands was comprehensively analyzed using RNA microarray. Subsequently, the expression levels of the genes of interest were verified using droplet digital PCR (ddPCR). The expression level of candidate genes as biomarkers for irradiated thyroid was examined in a randomized, controlled, double-blind validation study (n = 19) using ddPCR. The incidence of thyroid cancer increased in a dose- and time-dependent manner and was 33% at 16 months after irradiation with 4 Gy. The Ki-67 labeling index in non-tumorous thyroid was significantly higher in the exposed group than in the control. Comprehensive analysis identified radiation-dependent alteration in 3329 genes. Among them, ddPCR revealed a stepwise increase in CDKN1A expression from early pre-cancerous phase in irradiated thyroid compared to that in the control. The irradiated thyroids were accurately distinguished (positive predictive value 100%, negative predictive value 69%) using 11.69 as the cut-off value for CDKN1A/ß-actin. Thus, CDKN1A expression can be used as a biomarker for irradiated thyroid glands at the pre-cancerous phase.

[A case of elderly-onset myasthenia gravis mimicking stroke with dysarthria and left upper extremity paresis].

An 80-year-old woman presented with sudden-onset dysarthria and left-side dominant quadriparesis and transferred to our hospital. A neurologic examination revealed slurred speech, prominent left upper extremity weakness and mild weakness of the other extremities. Brain MRI revealed a history of right-side cerebral artery bypass surgery, but no new lesions indicative of stroke. Left upper extremity weakness had improved soon after admission, so a transient ischemic attack was suspected. After admission, the dysarthria fluctuated. The patient's respiratory condition deteriorated several days later and she required ventilation support. Assessment of the cause of the respiratory failure revealed positive muscle-specific kinase (MuSK) antibodies, which suggested myasthenia gravis (MG). The symptoms gradually improved with immunotherapy and we were able to completely withdraw her from the ventilator after a few months. There were some reports that dysphagia and dysarthria present suddenly like stroke without fluctuation of symptoms in elderly-onset MG. It is necessary to note that MG diagnosis may be difficult if elderly patients have multiple comorbidities and unclear diurnal fluctuations.

Hypothetical novel simulations to explain the evolutionary survival of the hypo-reproductive extreme tail in the complex human diversity.

Hierarchical structures which lie hidden between human complex conditions and reproductivity cannot be simple, and trends of each population component does not necessarily pertain to evolutionary theories. As an illustration, the fitness of individuals with heritable extreme conditions can be low across continuing generations in observational data. Autism and schizophrenia are characterized by such evolutionary paradox of survival and hypo-reproductivity in the complex human diversity. Theoretical mechanisms for the observational fact were evaluated using a simple formula which was established to simulate stochastic epistasis-mediated phenotypic diversity. The survival of the hypo-reproductive extreme tail could be imitated just by the predominant presence of stochastic epistasis mechanism, suggesting that stochastic epistasis might be a genetic prerequisite for the evolutionary paradox. As supplemental cofactors of stochastic epistasis, a random link of the extreme tail to both un- and hyper-reproductivity and group assortative mating were shown to be effective for the paradox. Especially, the mixed localization of un- and hyper-reproductivity in the tail of a generational population evidently induced the continuous survival of outliers and extremes. These hypothetical considerations and mathematical simulations may suggest the significance of stochastic epistasis as the essential genetic background of complex human diversity.

Minimizing the expected value of the asymmetric loss function and an inequality for the variance of the loss.

The coefficients of regression are usually estimated for minimization problems with asymmetric loss functions. In this paper, we rather correct predictions so that the prediction error follows a generalized Gaussian distribution. In our method, we not only minimize the expected value of the asymmetric loss, but also lower the variance of the loss. Predictions usually have errors. Therefore, it is necessary to use predictions in consideration of these errors. Our approach takes into account prediction errors. Furthermore, even if we do not understand the prediction method, which is a possible circumstance in, e.g. deep learning, we can use our method if we know the prediction error distribution and asymmetric loss function. Our method can be applied to procurement of electricity from electricity markets.

Immunofluorescence analysis of DNA damage response protein p53-binding protein 1 in a case of uterine dedifferentiated leiomyosarcoma arising from leiomyoma.

AIMS: Genomic instability has been indicated during the dedifferentiation process from leiomyoma (LM) to leiomyosarcoma (LMS). Previously, we have described that nuclear expression pattern of DNA damage response protein p53-binding protein 1 (53BP1), detected by immunofluorescence, reflects the magnitude of genomic instability during malignancy. Here, we present a case of LMS arising from LM with molecular analysis of 53BP1, which showed transitional magnitude of DNA damage response within a tumor. METHODS AND RESULTS: A fifty-year-old female with abdominal mass underwent hysterectomy. Histologically, the tumor consisted of LMS with highly atypical multinucleated giant cells as well as an LM component with transitional atypical spindle cells in the border area. LMS showed diffuse nuclear staining of 53BP1 expression, which has been previously described as high DNA damage response pattern. In contrast, the LM component lacked 53BP1 immunoreactivity and focal expression was observed in transitional lesion. Furthermore, double-labelled immunofluorescence revealed co-localization of 53BP1 with p53 and Ki-67 in the LMS component, which indicated abnormal DNA damage response in proliferative state. CONCLUSIONS: This study revealed that diffuse-type 53BP1 expression may be beneficial to estimate genomic instability during dedifferentiation from LM to DLMS.

Identification of evolutionarily conserved virulence factor by selective pressure analysis of Streptococcus pneumoniae.

Evolutionarily conserved virulence factors can be candidate therapeutic targets or vaccine antigens. Here, we investigated the evolutionary selective pressures on 16 pneumococcal choline-binding cell-surface proteins since Streptococcus pneumoniae is one of the pathogens posing the greatest threats to human health. Phylogenetic and molecular analyses revealed that cbpJ had the highest codon rates to total numbers of codons under considerable negative selection among those examined. Our in vitro and in vivo assays indicated that CbpJ functions as a virulence factor in pneumococcal pneumonia by contributing to evasion of neutrophil killing. Deficiency of cbpL under relaxed selective pressure also caused a similar tendency but showed no significant difference in mouse intranasal infection. Thus, molecular evolutionary analysis is a powerful tool that reveals the importance of virulence factors in real-world infection and transmission, since calculations are performed based on bacterial genome diversity following transmission of infection in an uncontrolled population.

Burden of Disease for Urethral Stricture Managed by Repeat Endoscopic Treatment vs Single Endoscopic Treatment or Urethroplasty in the Veterans Affairs Population.

INTRODUCTION: Male urethral stricture disease is a challenging urological condition that affects nearly a third of men 65 years old or older. Management options include dilation and urethrotomy as well as urethroplasty, an open approach with increased morbidity and durability. Presently optimal management remains debated. In this study we focus on emergent procedures required by male patients in the Veterans Health Administration after stricture treatment as an indicator of clinically significant complications, comparing treatment approaches. METHODS: We performed an institutional review board approved, retrospective, cohort study of male veterans with urethral stricture from 2005 to 2014. Our independent variable was immediate or delayed urethroplasty or continued endoscopic treatments. Our dependent variable was a stricture related procedure performed in the emergent or urgent care setting. We used a binary logistic regression model to model the likelihood of an adverse outcome as predicted by treatment type. RESULTS: In our cohort of 9,632 patients 1.8% underwent immediate urethroplasty and 3% underwent delayed urethroplasty. Of the operated men 5.3% had an adverse outcome (5% following delayed urethroplasty or continued endoscopic treatments and 1% after immediate urethroplasty, p = 0.04). On multivariate analysis repeat endoscopy and delayed urethroplasty trended toward worsening odds of adverse outcomes (p = 0.07 and p = 0.08, respectively). CONCLUSIONS: In the Veterans Health Administration system men who undergo repeated scheduled endoscopic treatments for urethral stricture may be at increased risk for emergent procedures, even if they eventually progress to urethroplasty, compared to men who undergo urethroplasty immediately after a failed endoscopic intervention.

Urologic Sequelae Following Phalloplasty in Transgendered Patients.

In recent years, the issues of the transgender population have become more visible in the media worldwide. Transgender patients at various stages of their transformation will present to urologic clinics requiring general or specialized urologic care. Knowledge of specifics of reconstructed anatomy and potential unique complications of the reconstruction will become important in providing urologic care to these patients. In this article, we have concentrated on describing diagnosis and treatment of the more common urologic complications after female-to-male reconstructions: urethrocutaneous fistulae, neourethral strictures, and symptomatic persistent vaginal cavities.

Sublamina densa-type linear IgA bullous dermatosis with IgA autoantibodies specific for type VII collagen: a case report and clinicopathological review of 32 cases.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune bullous disorder characterized by linear deposits of IgA at the basement membrane zone(BMZ) and/or by circulating IgA anti-BMZ antibodies. Comparing with other immuno-bullous diseases, LABD represents a heterogeneous disease entitywith diversity of pathogenic IgA autoantibodies to different hemidesmosomal antigens and an association with malignancies and occasional drug use. We herein present an 82-year-old Japanese man with LABD, whose indirect immunofluorescence using 1M NaCl-split skin showed positive staining for IgA at the dermal side alone. Fluorescence overlay antigen mapping using laser scanning confocal microscopy (FOAM-LSCM) was employed to examine the in vivo bound patient's IgA, which was specific for type VII collagen (COL7), a prominent antigen of the sublamina densa. One year later, he developed malignant lymphoma, suggesting the diagnosis of paraneoplastic LABD. We reviewed 32 cases of sublamina-densa type LABD with anti-COL7 IgA antibodies thus far reported in the literature to compare the clinicopathological characteristics of this rare disease variant and emphasize that COL7 is the main autoantigen in sublamina densa disease.

Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin.

Neuroendocrine neoplasms (NENs) are derived from endocrine cells in various organs and share common morphological features. This study aimed to clarify whether NENs of different organs are comparable at the molecular pathologic level. We retrospectively collected 99 cases of NENs from gastro-entero-pancreatic, lung, and other organs and reclassified these according to identical criteria. Grade, site, and molecular expression profile including NE markers, Ki-67, p53, somatostatin receptor type 2A (SSTR2A), and phosphatase and tensin homolog (PTEN) were compared. PTEN immunoreactivity was also compared with genomic copy number by fluorescence in situ hybridization (FISH) and droplet digital polymerase chain reaction (ddPCR). No significant differences were observed in the immunoreactivities of NE markers, p53, SSTR2A, or PTEN expression in NENs between the different organ sites. PTEN and p53 functional inactivation along with the loss of membranous SSTR2A expression appeared to be commonly involved in high-grade NEN. FISH results were significantly correlated with the level of PTEN immunoreactivity and with the findings of ddPCR analyses. The demonstration that these tumors are comparable at the molecular level will likely contribute to the broadening of therapeutic options such as the use of somatostatin analogues and mTOR inhibitors against NENs regardless of the affected organ, whereas molecular characterization of tumor grade will be useful for determining treatment strategy.

Evolutionary inactivation of a sialidase in group B Streptococcus.

Group B Streptococcus (GBS) is a leading cause of bacterial sepsis and meningitis in newborns. GBS possesses a protein with homology to the pneumococcal virulence factor, NanA, which has neuraminidase (sialidase) activity and promotes blood-brain barrier penetration. However, phylogenetic sequence and enzymatic analyses indicate the GBS NanA ortholog has lost sialidase function - and for this distinction we designate the gene and encoded protein nonA/NonA. Here we analyze NonA function in GBS pathogenesis, and through heterologous expression of active pneumococcal NanA in GBS, potential costs of maintaining sialidase function. GBS wild-type and ΔnonA strains lack sialidase activity, but forced expression of pneumococcal NanA in GBS induced degradation of the terminal sialic acid on its exopolysaccharide capsule. Deletion of nonA did not change GBS-whole blood survival or brain microvascular cell invasion. However, forced expression of pneumococcal NanA in GBS removed terminal sialic acid residues from the bacterial capsule, restricting bacterial proliferation in human blood and in vivo upon mouse infection. GBS expressing pneumococcal NanA had increased invasion of human brain microvascular endothelial cells. Thus, we hypothesize that nonA lost enzyme activity allowing the preservation of an effective survival factor, the sialylated exopolysaccharide capsule.

Outpatient Ultrasound Urethrogram for Assessment of Anterior Urethral Stricture: Early Experience.

OBJECTIVE: To describe the technique of ultrasound urethrogram (USUG) for the diagnosis of anterior urethral stricture performed in an ambulatory setting without any adjunctive imaging. MATERIALS AND METHODS: Between September 2013 and September 2015, 35 consecutive adult men (>18 years old) presenting for anterior urethral reconstruction underwent outpatient USUG prior to definitive management. No alternative imaging test was performed. Lengths of the strictures as determined by outpatient USUG and via direct intraoperative measurements were compared by a paired t test. RESULTS: Strictures were in the bulbar urethra in 24 men and in the penile urethra in 11 men. The differences between the outpatient USUG length measurements (mean = 1.86 cm) and the intraoperative stricture length measurements (mean = 2.02 cm) were not significantly different (P = .10). Additionally, the correlation coefficient between these length measurements was 0.84 (P < .001). CONCLUSION: Preoperative USUG performed in the ambulatory setting for the diagnosis and characterization of anterior urethral strictures is safe and feasible. This outpatient imaging modality offers an alternative to retrograde urethrogram.

Tissue transfer techniques in reconstructive urology.

Tissue transfer techniques are an essential part of the reconstructive urologist's armamentarium. Flaps and graft techniques are widely used in genital and urethral reconstruction. A graft is tissue that is moved from a donor site to a recipient site without its native blood supply. The main types of grafts used in urology are full thickness grafts, split thickness skin grafts and buccal mucosa grafts. Flaps are transferred from the donor site to the recipient site on a pedicle containing its native blood supply. Flaps can be classified based on blood supply, elevation methods or the method of transfer. The most used flaps in urology include penile, preputial, and scrotal skin. We review the various techniques used in reconstructive urology and the outcomes of these techniques.

Robot-Assisted Ureteral Reconstruction Using Buccal Mucosa.

OBJECTIVE: To describe the technique of robotic buccal mucosa graft ureteroplasty as a minimally invasive alternative method of ureteral reconstruction for proximal or multifocal ureteral strictures not amenable to primary anastomosis. METHODS: Between October 2013 and May 2014, we performed robotic-assisted ureteral reconstruction using buccal mucosa grafts in four patients (mean age 41.5, range 23-67). The indication for surgery was a proximal or multifocal stricture not amenable to ureteroureterostomy or ureteropyelostomy. Buccal mucosa grafts were harvested to be the length of the strictured segment and 1 cm in width and placed in the ureter as an anterior or posterior onlay. Follow up was performed with diuretic renogram at least 3 months postoperatively and renal ultrasound as well as clinical assessment of symptoms. RESULTS: All 4 patients underwent successful robotic-assisted reconstruction of the ureter using buccal mucosa graft. There were no intraoperative complications. At a median follow up of 15.5 months (range 10.7-18.6), there has been 100% success. CONCLUSION: Robotic buccal mucosa graft ureteroplasty is a feasible option for reconstruction of proximal or multifocal ureteral strictures that are not amenable to primary anastomosis and it avoids the morbidity of alternative procedures.

Evaluation of intraspecies interactions in biofilm formation by Methylobacterium species isolated from pink-pigmented household biofilms.

Concern regarding household biofilms has grown due to their widespread existence and potential to threaten human health by serving as pathogen reservoirs. Previous studies identified Methylobacterium as one of the dominant genera found in household biofilms. In the present study, we examined the mechanisms underlying biofilm formation by using the bacterial consortium found in household pink slime. A clone library analysis revealed that Methylobacterium was the predominant genus in household pink slime. In addition, 16 out of 21 pink-pigmented bacterial isolates were assigned to the genus Methylobacterium. Although all of the Methylobacterium isolates formed low-level biofilms, the amount of the biofilms formed by Methylobacterium sp. P-1M and P-18S was significantly increased by co-culturing with other Methylobacterium strains that belonged to a specific phylogenetic group. The single-species biofilm was easily washed from the glass surface, whereas the dual-species biofilm strongly adhered after washing. A confocal laser scanning microscopy analysis showed that the dual-species biofilms were significantly thicker and tighter than the single-species biofilms.

Mutual exclusivity of hyaluronan and hyaluronidase in invasive group A Streptococcus.

A recent analysis of group A Streptococcus (GAS) invasive infections in Australia has shown a predominance of M4 GAS, a serotype recently reported to lack the antiphagocytic hyaluronic acid (HA) capsule. Here, we use molecular genetics and bioinformatics techniques to characterize 17 clinical M4 isolates associated with invasive disease in children during this recent epidemiology. All M4 isolates lacked HA capsule, and whole genome sequence analysis of two isolates revealed the complete absence of the hasABC capsule biosynthesis operon. Conversely, M4 isolates possess a functional HA-degrading hyaluronate lyase (HylA) enzyme that is rendered nonfunctional in other GAS through a point mutation. Transformation with a plasmid expressing hasABC restored partial encapsulation in wild-type (WT) M4 GAS, and full encapsulation in an isogenic M4 mutant lacking HylA. However, partial encapsulation reduced binding to human complement regulatory protein C4BP, did not enhance survival in whole human blood, and did not increase virulence of WT M4 GAS in a mouse model of systemic infection. Bioinformatics analysis found no hasABC homologs in closely related species, suggesting that this operon was a recent acquisition. These data showcase a mutually exclusive interaction of HA capsule and active HylA among strains of this leading human pathogen.