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Suk-Bae Moon Department of Surgery, Kangwon National University School of Medicine, Chuncheon, Republic of Korea Abstract: Annular pancreas (AP) is a rare cause of congenital duodenal obstruction that is usually discovered at the neonatal period, but clinical severities can vary over a wide range and definite diagnosis could be delayed until late childhood or adulthood. We report here a case of AP detected in an 11-year-old girl who had a long history of symptoms of partial duodenal obstruction. Upper gastrointestinal (UGI) study revealed narrowed second portion of duodenum by extrinsic compression, and computed tomography demonstrated complete ring of pancreatic tissue surrounding the second portion of the duodenum. Diamond-shaped duodenoduodenostomy successfully cured the patient, and the postoperative UGI study showed smooth passage through the bypass segment. Although rare, AP should be differentiated in children with unresolved symptoms of partial duodenal obstruction. Keywords: annular pancreas, children, duodenoduodenostomy

Suk-Bae MoonDepartment of Surgery, Kangwon National University Hospital, Kangwon National School of Medicine, Kangwon National University, Chuncheon, South KoreaPurpose: As an alternative to the existing fee-for-service (FFS) system, a diagnosis-related group (DRG)-based payment system has been suggested. The aim of this study was to investigate the early results of pediatric appendicitis treatment under the DRG system, focusing on health care expenditure and quality of health care services.Patients and methods: The medical records of 60 patients, 30 patients before (FFS group), and 30 patients after adoption of the DRG system (DRG), were reviewed retrospectively.Results: Mean hospital stay was shortened, but the complication and readmission rates did not worsen in the DRG. Overall health care expenditure and self-payment decreased from Korean Won (KRW) 2,499,935 and KRW 985,540, respectively, in the FFS group to KRW 2,386,552 and KRW 492,920, respectively, in the DRG. The insurer’s payment increased from KRW 1,514,395 in the FFS group to KRW 1,893,632 in the DRG. For patients in the DRG, calculation by the DRG system yielded greater overall expenditure (KRW 2,020,209 vs KRW 2,386,552) but lower self-payment (KRW 577,803 vs KRW 492,920) than calculation by the FFS system.Conclusion: The DRG system worked well in pediatric patients with acute appendicitis in terms of cost-effectiveness over the short term. The gradual burden on the national health insurance fund should be taken into consideration.Keywords: appendicitis, child, fee-for-service plans, diagnosis-related groups, quality of health care, health care expenditures

Suk-Bae MoonDepartment of Surgery, Kangwon National University Hospital, Kangwon National School of Medicine, Kangwon National University, Chuncheon, South KoreaAbstract: Neuroblastoma is the most common extracranial solid tumor in children. Mild hypertension is a frequent symptom, presumably an effect of catecholamines that tumors release. Reported herein is the rare occurrence of severe hypertension and subsequent heart failure attributable to adrenal gland neuroblastoma. A 3-year-old boy presented with anterior chest wall protrusion. Physical examination revealed severe hypertension, and left-sided cardiac failure was evident by echocardiography. Catecholamine metabolite (norepinephrine) levels were increased in serum (>2,000 pg/mL) and in urine (1,350.5 µg/day). Abdominal computed tomography scan showed a 7 cm solid mass arising from right adrenal gland. Oral phenoxybenzamine was given for hemodynamic stabilization, and right adrenalectomy was performed to remove an apparent pheochromocytoma. Ultimately, the pathologic diagnosis was ganglioneuroblastoma. Both hypertension and cardiac failure resolved postoperatively.Keywords: hypertension, heart failure, adrenal gland, pheochromocytoma

Younglim Kim, Suk-Bae MoonDepartment of Surgery, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, South KoreaAbstract: Solid pseudopapillary neoplasm (SPN) is a rare tumor of the pancreas that tends to grow silently in patients at a young age, to a large size and mass. We report here a case of a small-sized SPN detected incidentally in a 12-year-old girl following a traffic accident. The tumor was 3.5 cm in maximal diameter and was found to have hemorrhagic necrosis without a solid component. Laparoscopic spleen-preserving distal pancreatectomy was performed which cured the patient. SPN is generally accepted to be a low grade malignant tumor, but its clinical behavior is sometimes unpredictable. Tumor size and the proportion of solid portion of the tumor have both recently been identified as predictors of malignancy. Although the initial presentation in this case was that of the traffic accident, the subsequent detection of a small, totally cystic SPN, and then the complete eradication of the lesion, led to a favorable outcome for the patient. Long-term monitoring should prevent any chance of recurrence.Keywords: pancreatic neoplasm, children, distal pancreatectomy

Suk Bae Moon,1 Sang Beom Han21Department of Surgery, Kangwon National University Hospital, Kangwon National University Graduate School of Medicine, Chuncheon, Korea, 2Department of Ophthalmology, Kangwon National University Hospital, Kangwon National University Graduate School of Medicine, Chuncheon, KoreaWe read, with interest, the article by Sun et al1 entitled “Patient satisfaction with fixed-combination bimatoprost/timolol ophthalmic solution: a survey study in patients with glaucoma in China”. This observational multicenter study with excellent design was undoubtedly well conducted, and the authors successfully demonstrated that fixed-combination bimatoprost/timolol ophthalmic solution can provide the glaucoma patients with improved satisfaction.1View the original paper by Sun and colleagues.

Background: The global pandemic caused by SARS-CoV-2 has underlined the significance of strict genomic surveillance to track virus evolution and the possible emergence of new variants, particularly in densely populated countries like Bangladesh. This study outlines a strategic framework of genomic surveillance to track the evolution of the virus in Bangladesh between June 2021 and December 2022 through the National SARS-CoV-2 Variant Surveillance (NSVS) program involving collaboration across 4 major institutes and 13 hospitals nationwide., Methods: We aimed to capture the variants of SARS-CoV-2 throughout the country utilizing standardized procedures, modern sequencing technology, and stringent quality control, promoting data accuracy and the timely detection of new variants of concern. We sequenced over 2200 genomes, documenting the prevalence of the Delta variant initially, followed by the emergence of Omicron variants BA.1, BA.2, BA.5, and XBB, each affecting transmission rates and vaccine efficacy differently., Results: The clinical manifestations of the variants differed, with some symptoms occurring more frequently in Delta cases and vice versa. Vaccinated individuals were more affected by Omicron cases compared to Delta cases. These variants were responsible for two major COVID-19 waves in the country, each with significant clinical effects. Phylogenetic analyses placed the local SARS-CoV-2 variants within a global context, indicating the Delta variant likely entered from India and Omicron from Europe., Conclusion: This research highlights the significance of collaborative surveillance strategies for guiding public health choices and the critical role of genomic analysis in monitoring virus evolution, shaping targeted pandemic responses. Bangladesh's contributions significantly enhance global insight into COVID-19's genomic evolution., (© 2024 The Author(s). Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Candida auris , initially identified in 2009, has rapidly become a critical concern due to its antifungal resistance and significant mortality rates in healthcare-associated outbreaks. To date, whole-genome sequencing (WGS) has identified five unique clades of C. auris , with some strains displaying resistance to all primary antifungal drug classes. In this study, we presented the first WGS analysis of C. auris from Bangladesh, describing its origins, transmission dynamics, and antifungal susceptibility testing (AFST) profile. Ten C. auris isolates collected from hospital settings in Bangladesh were initially identified by CHROMagar Candida Plus, followed by VITEK2 system, and later sequenced using Illumina NextSeq 550 system. Reference-based phylogenetic analysis and variant calling pipelines were used to classify the isolates in different clades. All isolates aligned ~90% with the Clade I C. auris B11205 reference genome. Of the 10 isolates, 8 were clustered with Clade I isolates, highlighting a South Asian lineage prevalent in Bangladesh. Remarkably, the remaining two isolates formed a distinct cluster, exhibiting >42,447 single-nucleotide polymorphism differences compared to their closest Clade IV counterparts. This significant variation corroborates the emergence of a sixth clade (Clade VI) of C. auris in Bangladesh, with potential for international transmission. AFST results showed that 80% of the C. auris isolates were resistant to fluconazole and voriconazole, whereas Clade VI isolates were susceptible to azoles, echinocandins, and pyrimidine analogue. Genomic sequencing revealed ERG11 _Y132F mutation conferring azole resistance while FCY1 _S70R mutation found inconsequential in describing 5-flucytosine resistance. Our study underscores the pressing need for comprehensive genomic surveillance in Bangladesh to better understand the emergence, transmission dynamics, and resistance profiles of C. auris infections. Unveiling the discovery of a sixth clade (Clade VI) accentuates the indispensable role of advanced sequencing methodologies.IMPORTANCE Candida auris is a nosocomial fungal pathogen that is commonly misidentified as other Candida species. Since its emergence in 2009, this multidrug-resistant fungus has become one of the five urgent antimicrobial threats by 2019. Whole-genome sequencing (WGS) has proven to be the most accurate identification technique of C. auris which also played a crucial role in the initial discovery of this pathogen. WGS analysis of C. auris has revealed five distinct clades where isolates of each clade differ among themselves based on pathogenicity, colonization, infection mechanism, as well as other phenotypic characteristics. In Bangladesh, C. auris was first reported in 2019 from clinical samples of a large hospital in Dhaka city. To understand the origin, transmission dynamics, and antifungal-resistance profile of C. auris isolates circulating in Bangladesh, we conducted a WGS-based surveillance study on two of the largest hospital settings in Dhaka, Bangladesh., Competing Interests: The authors declare no conflict of interest.

Antimicrobial resistance (AMR) in bacteria poses a global health emergency due to limited treatment options. Here, we report a lytic bacteriophage belonging to Stephanstirmvirinae family against an AMR Escherichia coli (ST2089). Escherichia phage iGC_PHA_EC001 is of genus Phapecoctavirus and 148,445 bp in length, encoding 269 predicted protein-coding sequences and 10 tRNAs. The phage encodes two lytic proteins containing phage_lysozyme (PF00959.22) and cell wall hydrolase_2 (PF07486.15) as catalytic domains, respectively., Competing Interests: The authors declare no conflict of interest.

Caffeine is one of the most widely consumed psychoactive drugs in the general population. It has a neuroprotective effect in degenerative neurological disorders; however, the association between caffeine and traumatic brain injury (TBI) outcomes is contradictory. The objective of this study was to evaluate the association between serum caffeine concentration at the time of injury and long-term functional outcomes of patients with TBI visiting the emergency department (ED). This was a prospective multi-center cohort study including adult patients with intracranial injury confirmed by radiological examination, who visited five participating EDs within 72 h after TBI. The main exposure was the serum caffeine level within 4 h after injury, and the study outcome was a favorable functional recovery at 6 months after injury. Multi-variable logistic regression analysis adjusted for potential confounders was performed to calculate adjusted odds ratios (AORs) with 95% confidence intervals (CIs). Among the 334 study participants, caffeine was not detected in 102 patients (30.5 %). In patients with identifiable caffeine level, serum caffeine level was categorized into tercile groups; low (0.01-0.58 μg/mL), intermediate (0.59-1.66 μg/mL), and high (1.67-10.00 μg/mL). The proportions of patients with a 6-month favorable functional recovery were 56.9% in the no-caffeine group, 79.2% in the low-caffeine group, 75.3% in the intermediate-caffeine group, and 66.7% in the high-caffeine group ( p  = 0.006). In multi-variable logistic regression analysis, the low- and intermediate-caffeine groups were significantly associated with a higher probability of 6-month favorable functional recovery compared with the no-caffeine group [AORs (95% CI): 2.82 (1.32-6.02) and 2.18 (1.06-4.47], respectively. This study showed a significant association between a serum caffeine concentration of 0.01 to 1.66 μg/mL and good functional recovery at 6 months after injury compared with the no-caffeine group of patients with TBI with intracranial injury. These results suggest the possibility of using serum caffeine level as a potential biomarker for TBI outcome prediction and of using caffeine as a therapeutic agent in the clinical care of patients with TBI.

The aim of this study is to investigate the potential impact of catheterization on intimal hyperplasia and explore the efficacy of Paclitaxel loaded PLGA nanoparticles (PTX-NPs) in preventing stenosis at the site of venous injury. Under general anesthesia, Central Venous Catheters were inserted into the rat's right internal jugular veins (IJV) using the cut-down technique. Twenty bare catheters (C) and twenty PTX-NPs coated catheters (P) were assigned to one of four groups (C2, C4, P2, or P4) based on catheter type and expected survival time. 2 or 4 weeks after surgery, IJVs were completely harvested by formalin fixation and gelatin infusion and slides were stained with H&E (Haematoxylin and Eosin) and Masson's technique. The P2 (Paclitaxel coating, 2 weeks) group showed the most proliferation among the four groups and the P4 (Paclitaxel coating, 4 weeks) showed a tendency to decrease proliferation. Additionally, the lumen size in the P4 group was about 6% smaller than in the P2 group, and there was a lower prevalence of stenotic grade in the P4 group. Our study suggests that PTX-NPs coated catheters may be effective in preventing venous stenosis if the intended usage is prolonged, rather than for a short-term period., Graphical Abstract: Schematic representation of catheter functionalization and coating of PTX-NPs on Catheter., Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00282-y., Competing Interests: Conflict of interestAll of the authors has no conflict of interest., (© Korean Society of Medical and Biological Engineering 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Competing Interests: The authors declare no conflict of interest.

Serum biomarkers have potential to help predict prognosis of traumatic brain injury (TBI). The objective of this study was to evaluate the association between serum acylcarnitine levels and functional outcomes at 1 month/6 months after injury for TBI patients with intracranial hemorrhage or diffuse axonal injury. This study is a multi-center prospective cohort study in which adult TBI patients with intracranial injury visiting the emergency departments (EDs) from December 2018 to June 2020 were enrolled. Serum acylcarnitine levels at the time of ED arrival were categorized into four groups: low (1.2-5.5 μmol/L), low-normal (5.6-10.0 μmol/L), high-normal (10.1-14.5 μmol/L), and high (1.4.6-56.6 μmol/L). The study outcome was set as poor functional recovery at 1 month/6 months after injury (Glasgow Outcome Scale score, 1-3). Multi-level logistic regression analyses were conducted to estimate association between serum acylcarnitine and functional outcomes. Among total of 549 patients, poor functional recovery at 1 month and 6 months after injury were observed in 29.1% (160/549) and 29.1% (158/543, follow-up loss n  = 6). The odds for 1-month poor functional outcome increased in the high-normal and the high groups [adjusted odds ratios, AORs (95% confidence intervals, CIs): 1.56 (1.09-2.23) and 2.47 (1.63-3.75)], compared with the low-normal group) and also as a continuous variable [1.05 (1.03-1.07) for each 1 μmol/L]. Regarding 6-month mortality, the high group had significantly higher odds when compared with the low-normal group [AOR (95% CI): 2.16 (1.37-3.40)]. Higher serum acylcarnitine levels are associated with poor functional outcomes at 1 month/6 months after injury for TBI patients with intracranial injury.

Serum zinc levels in the acute stages after traumatic brain injury (TBI) may be capable of predicting cinical and functional prognoses. This study aimed to evaluate the association between serum zinc levels and long-term survival and neurological outcomes in TBI patients with intracranial injury. This multicenter prospective cohort study enrolled adult TBI patients with intracranial injury who visited emergency departments between December 2018 and June 2020. Serum zinc levels drawn within 24 h after injury were categorized into four groups: low (<80.0 mcg/dL), low−normal (80.0−100.0 mcg/dL), high−normal (100.1−120.0 mcg/dL), and high (>120.0 mcg/dL). The study outcomes were 6-month mortality and disability (Glasgow Outcome Scale, 1−3). A multilevel multivariable logistic regression analysis was conducted to estimate associations between serum zinc and study outcomes. From the eligible TBI patients (N = 487), the median (interquartile range) serum zinc level was 112.0 mcg/dL (95.0−142.0). Six-month mortality and disability were 21.1% (103/487) and 29.6% (144/487), respectively. Compared to the high−normal zinc group, there were significant associations with 6-month mortality and disability observed in the low zinc group (aORs (95% CIs): 1.91 (1.60−2.28) and 1.95 (1.62−2.36) for the low group; 1.14 (0.67−1.94) and 1.15 (0.91−1.46) for the low−normal group; and 0.72 (0.44−1.16) and 0.88 (0.61−1.27) for the high group, respectively). Among the 122 TBI patients with diabetes mellitus, the low zinc group showed a higher incidence of 6-month mortality (aOR (95% CI): 9.13 (4.01−20.81)) compared to the high−normal zinc group. Moreover, the low and low−normal groups had higher odds for 6-month disability (aORs (95% CIs): 6.63 (3.61−12.15) for the low group and 2.37 (1.38−4.07) for the low−normal group). Serum zinc deficiency is associated with a higher incidence of 6-month mortality and disability after injury for TBI patients with intracranial injury.

Background: Traumatic brain injury (TBI) is a major public health problem with high mortality and disability. Vitamin E, one of the antioxidants for treatment of TBI, has not been sufficiently evaluated for predicting prognosis of TBI. This study aimed to evaluate the prognostic value of vitamin E on functional outcomes of TBI patients with intracranial injury., Methods: A multi-center prospective cohort study was conducted in five university hospitals between 2018 and 2020. Adult TBI patients who visited the emergency department (ED) with intracranial hemorrhage or diffuse axonal injury confirmed by radiological examination were eligible. Serum vitamin E levels (mg/dL) were categorized into 4 groups: low (0.0-5.4), low-normal (5.5-10.9), high-normal (11.0-16.9), and high (17.0-). Study outcomes were set as 1- and 6-month disability (Glasgow outcome scale (GOS) 1-4). Multilevel logistic regression analysis was conducted to calculate the adjusted odds ratios (AORs) of vitamin E for related outcomes., Results: Among 550 eligible TBI patients with intracranial injury, the median (IQR) of serum vitamin E was 10.0 (8.0-12.3) mg/dL; 204/550 (37.1%) had 1-month disability and 197/544 (36.1%) had 6-month disability of GOS 1-4. Compared with the high-normal group, the odds of 1-month disability and 6-month disability increased in the low and low-normal group (AORs (95% CIs): 3.66 (1.62-8.27) and 2.60 (1.15-5.85) for the low group and 1.63 (1.08-2.48) and 1.60 (1.04-2.43) for the low-normal group, respectively)., Conclusion: Low serum vitamin E level was associated with poor prognosis at 1 and 6 months after TBI with intracranial injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Park, Ro, Yoon, Lee, Jung, Moon, Kim, Shin and Pan-Asia Trauma Outcomes Study for Traumatic Brain Injury (PATOS-TBI) research network.)

Protease-activated receptor-1 (PAR1) is highly expressed in murine colonic smooth muscles. Responses to PAR1 activation are complex and result from responses in multiple cell types. We investigated whether PAR1 responses are altered in inflamed colon induced by dextran sodium sulfate (DSS)-treatment. Colitis was induced in C57BL/6 mice by administration of 3% DSS in drinking water for 7 days. Measurements of isometric force, transmembrane potentials from impaled smooth muscle cells, quantitative PCR and Western blots were performed. Thrombin, an activator of PAR1, caused transient hyperpolarization and relaxation of untreated colons, but these responses decreased in DSS-treated colons. Apamin caused depolarization and increased contractions of muscles from untreated mice. This response was decreased in DSS-treated colons. Expression of Kcnn3 and Pdgfra also decreased in DSS-treated muscles. A second phase of thrombin responses is depolarization and increased contractions in untreated muscles. However, thrombin did cause depolarization in DSS-treated colon, yet it increased colonic contractions. The latter effect was associated with enhanced expression of MYPT1 and CPI-17. The propagation velocity and frequency of colonic migrating motor complexes in DSS-treated colon was significantly higher compared to control colons. In summary, DSS treatment causes loss of transient relaxations due to downregulation of SK3 channels in PDGFRα + cells and may increase contractile responses due to increased Ca 2+  sensitization of smooth muscle cells via PAR1 activation., (© 2022. The Author(s).)

Vitamin D may be important for neuroprotection after traumatic brain injury (TBI) by modifying the inflammatory response. The objective of this study was to evaluate the association between vitamin D deficiency and functional and survival outcomes in patients with TBI and intracranial injury. This study was a prospective multi-center cohort study conducted on adult TBI patients, with intracranial hemorrhage or diffuse axonal injury confirmed by radiological examination, admitted to five participating emergency departments (EDs) from December 2018 to June 2020. The study outcomes were good functional recovery at hospital discharge and survival at 6-months after injury. The primary exposure was serum vitamin D deficiency (0-10 ng/mL). Multi-level logistic regression analysis was performed to estimate the association between vitamin D deficiency and the study outcomes. Among 606 patients, 101 (16.7%) patients had vitamin D deficiency at the time of ED arrival. Good functional recovery was observed in 65.2% (395/606) of total population, and this proportion was significantly lower in the vitamin D deficiency group than the non-deficiency group (56.4 vs. 66.9%, p  = 0.04, adjusted odds ratio (OR; 95% confidence interval [CI]): 0.56 (0.36-0.88)). Overall survival rate at 6 months after injury was 79.5% (434/546), and patients with vitamin D deficiency had significantly lower likelihood of survival at 6 months than patients without deficiency [75.0 vs. 80.3%, adjusted OR (95% CI): 0.59 (0.39-0.89)]. Vitamin D deficiency is associated with poor functional outcomes at hospital discharge and mortality at 6-months after injury in TBI patients with intracranial hemorrhage or diffuse axonal injury.

Obesity is a critical risk factor of several life-threatening diseases and the prevalence in adults has dramatically increased over the past ten years. In the USA the age-adjusted prevalence of obesity in adults was 42.4%, i.e., with a body mass index (BMI, weight (kg)/height (m)2) that exceeds 30 kg/m2. Obese individuals are at the higher risk of obesity-related diseases, co-morbid conditions, lower quality of life, and increased mortality more than those in the normal BMI range i.e., 18.5-24.9 kg/m2. Surgical treatment continues to be the most efficient and scientifically successful treatment for obese patients. Sleeve gastrectomy or vertical sleeve gastrectomy (VSG) is a relatively new gastric procedure to reduce body weight but is now the most popular bariatric operation. To date there have been few studies examining the changes in the cellular components and pacemaker activity that occur in the gastric wall following VSG and whether normal gastric activity recovers following VSG. In the present study we used a murine model to investigate the chronological changes of gastric excitability including electrophysiological, molecular and morphological changes in the gastric musculature following VSG. There is a significant disruption in specialized interstitial cells of Cajal in the gastric antrum following sleeve gastrectomy. This is associated with a loss of gastric pacemaker activity and post-junctional neuroeffector responses. Over a 4-month recovery period there was a gradual return in interstitial cells of Cajal networks, pacemaker activity and neural responses. These data describe for the first time the changes in gastric interstitial cells of Cajal networks, pacemaker activity and neuroeffector responses and the time-dependent recovery of ICC networks and normalization of motor activity and neural responses following VSG., Competing Interests: The authors have declared that no competing interests exist.

Black garlic (BG) is a newly explored food stuff obtained via fermentation of raw, healthy garlic, especially in Asian countries. Interstitial cells of Cajal (ICC) are the pacemaker cells of gastrointestinal (GI) motility. The purpose of this study was to investigate the effects of BG extract on the pacemaker potentials of the ICC in the small intestines of mice and the possibility of controlling GI motility. The antioxidant activity of BG extract was also investigated. The whole-cell electrophysiological method was used to measure pacemaker potentials of the ICC in vitro , whereas GI motility was measured using the intestinal transit rate (ITR) in vivo . BG extract depolarized the pacemaker potentials of the ICC. Y25130 and RS39604 5-HT receptor antagonists could not inhibit the effect of BG extract on the pacemaker potentials of the ICC, whereas the 5-HT receptor antagonist SB269970 could. Pre-treatment with external Na + (5 mM) or Ca 2+ -free solution inhibited the BG extract-induced depolarization of the ICC. With SB203580, PD98059, or c-jun NH 2 -terminal kinase II inhibitor pre-treatment, BG extract did not induce pacemaker potential depolarization. Moreover, the ITR values were increased by BG extract. Elevation of the ITR due to BG extract was related with increased protein expression of the 5-HT 7 receptors. In addition, BG extract showed antioxidant activity. Collectively, these results highlight the ability of BG extract to regulate GI motility and the possibility of using it to develop GI motility modulators in the future. Moreover, BG showed immense potential as an antioxidant., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Sialic acid (SA) is present in glycoconjugates and important in cell-cell recognition, cell adhesion, and cell growth and as a receptor. Among the four mammalian sialidases, cytosolic NEU2 has a pivotal role in muscle and neuronal differentiation in vitro. However, its biological functions in vivo remain unclear due to its very low expression in humans. However, the presence of cytoplasmic glycoproteins, gangliosides, and lectins involved in cellular metabolism and glycan recognition has suggested the functional importance of cytosolic Neu2 sialidases. We generated a Neu2 knockout mouse model via CRISPR/Cas9-mediated genome engineering and analyzed the offspring littermates at different ages to investigate the in vivo function of cytosolic Neu2 sialidase. Surprisingly, knocking out the Neu2 gene in vivo abrogated overall lipid metabolism, impairing motor function and leading to diabetes. Consistent with these results, Neu2 knockout led to alterations in sialylated glycoproteins involved in lipid metabolism and muscle function, as shown by glycoproteomics analysis., (© 2022. The Author(s).)

Gene therapy would benefit from a miniature CRISPR system that fits into the small adeno-associated virus (AAV) genome and has high cleavage activity and specificity in eukaryotic cells. One of the most compact CRISPR-associated nucleases yet discovered is the archaeal Un1Cas12f1. However, Un1Cas12f1 and its variants have very low activity in eukaryotic cells. In the present study, we redesigned the natural guide RNA of Un1Cas12f1 at five sites: the 5' terminus of the trans-activating CRISPR RNA (tracrRNA), the tracrRNA-crRNA complementary region, a penta(uridinylate) sequence, the 3' terminus of the crRNA and a disordered stem 2 region in the tracrRNA. These optimizations synergistically increased the average indel frequency by 867-fold. The optimized Un1Cas12f1 system enabled efficient, specific genome editing in human cells when delivered by plasmid vectors, PCR amplicons and AAV. As Un1Cas12f1 cleaves outside the protospacer, it can be used to create large deletions efficiently. The engineered Un1Cas12f1 system showed efficiency comparable to that of SpCas9 and specificity similar to that of AsCas12a., (© 2021. The Author(s).)

Volume accommodation occurs via a novel mechanism involving interstitial cells in detrusor muscles. The interstitial cells in the bladder are PDGFRα + , and they restrain the excitability of smooth muscle at low levels and prevents the development of transient contractions (TCs). A common clinical manifestation of spinal cord injury (SCI)-induced bladder dysfunction is detrusor overactivity (DO). Although a myogenic origin of DO after SCI has been suggested, a mechanism for development of SCI-induced DO has not been determined. In this study we hypothesized that SCI-induced DO is related to loss of function in the regulatory mechanism provided by PDGFRα + cells. Our results showed that transcriptional expression of Pdgfra and Kcnn3 was decreased after SCI. Proteins encoded by these genes also decreased after SCI, and a reduction in PDGFRα + cell density was also documented. Loss of PDGFRα + cells was due to apoptosis. TCs in ex vivo bladders during filling increased dramatically after SCI, and this was related to the loss of regulation provided by SK channels, as we observed decreased sensitivity to apamin. These findings show that damage to the mechanism restraining muscle contraction during bladder filling that is provided by PDGFRα + cells is causative in the development of DO after SCI., (© 2021. The Author(s).)

Prime editors (PEs) enable targeted precise editing, including the generation of substitutions, insertions and deletions, in eukaryotic genomes. However, their genome-wide specificity has not been explored. Here, we developed Nickase-based Digenome-seq (nDigenome-seq), an in vitro assay that uses whole-genome sequencing to identify single-strand breaks induced by CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) nickase. We used nDigenome-seq to screen for potential genome-wide off-target sites of Cas9 H840A nickase, a PE component, targeted to nine human genomic sites. Then, using targeted amplicon sequencing of off-target candidates identified by nDigenome-seq, we showed that only five off-target sites showed detectable PE-induced modifications in cells, at frequencies ranging from 0.1 to 1.9%, suggesting that PEs provide a highly specific method of precise genome editing. We also found that PE specificity in human cells could be further improved by incorporating mutations from engineered Cas9 variants, particularly eSpCas9 and Sniper Cas9, into PE., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Forme fruste choledochal cyst (FFCC), characterized by a minimally dilated common bile duct (CBD) and associated pancreaticobiliary maljunction (PBM), is difficult to diagnose in a timely manner in clinical practice. However, endoscopic retrograde cholangiopancreatography (ERCP) can clearly delineate CBD and PBM. Hence, we evaluated the value of ERCP in the diagnosis and management of FFCC., Methods: The medical records of patients diagnosed with FFCC were retrospectively reviewed. From January 2003 to December 2010, patients underwent surgery without ERCP (non-ERCP group); from January 2011, all patients underwent pre-operative ERCP (ERCP group). Demographics, laboratory results, perioperative data and post-operative complications were compared between the two groups., Results: There were 24 patients in the ERCP group and 11 in the non-ERCP group. Laboratory data improved to a greater extent after ERCP. ERCP was superior to both magnetic resonance cholangiopancreatography and ultrasonography in delineating CBD and PBM. In the ERCP group, 20 of the 24 patients were noted to have filling defects in the biliary tract and underwent pre-operative endoscopic sphincterotomy. Intra-operative blood loss was lower and transfusion less frequent in the ERCP group (P < 0.05). There were no ERCP-related complications., Conclusions: ERCP can accurately delineate the minimal CBD dilatation, associated pancreaticobiliary tract abnormalities and PBM of FFCC. ERCP can improve the perioperative and post-operative results of paediatric patients with FFCC., (© 2020 Royal Australasian College of Surgeons.)

Genome editing took a dramatic turn with the development of the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated proteins (Cas) system. The CRISPR-Cas system is functionally divided into classes 1 and 2 according to the composition of the effector genes. Class 2 consists of a single effector nuclease, and routine practice of genome editing has been achieved by the development of the Class 2 CRISPR-Cas system, which includes the type II, V, and VI CRISPR-Cas systems. Types II and V can be used for DNA editing, while type VI is employed for RNA editing. CRISPR techniques induce both qualitative and quantitative alterations in gene expression via the double-stranded breakage (DSB) repair pathway, base editing, transposase-dependent DNA integration, and gene regulation using the CRISPR-dCas or type VI CRISPR system. Despite significant technical improvements, technical challenges should be further addressed, including insufficient indel and HDR efficiency, off-target activity, the large size of Cas, PAM restrictions, and immune responses. If sophisticatedly refined, CRISPR technology will harness the process of DNA rewriting, which has potential applications in therapeutics, diagnostics, and biotechnology.

CRISPR technology is a two-component gene editing system in which the effector protein induces genetic alterations with the aid of a gene targeting guide RNA. Guide RNA can be produced through chemical synthesis, in vitro transcription, or intracellular transcription. Guide RNAs can be engineered to have chemical modifications, alterations in the spacer length, sequence modifications, fusion of RNA or DNA components, and incorporation of deoxynucleotides. Engineered guide RNA can improve genome editing efficiency and target specificity, regulation of biological toxicity, sensitive and specific molecular imaging, multiplexing, and editing flexibility. Therefore, engineered guide RNA will enable more specific, efficient, and safe gene editing, ultimately improving the clinical benefits of gene therapy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Rationale: The horseshoe anomaly of the vermiform appendix is extremely rare. Preoperative confirmation of this anomaly is difficult; therefore, routine procedures, such as appendectomy, may become unexpectedly challenging when such anomalies are encountered during the surgical process., Patient Concerns: A 33-year-old man presented with abdominal pain in the right lower abdomen owing to acute appendicitis confirmed via computed tomography. Immediate laparoscopic appendectomy was decided as the method for treatment., Diagnosis: Horseshoe anomaly was diagnosed as a gross finding during surgery., Intervention: First, the appendiceal base was resected and appendectomy was performed via the retrograde method because the appendiceal tip was curled behind the cecum. However, it was discovered that the appendiceal tip was connected to the lateral part of the ascending colon and showed a horseshoe-shaped anomaly. The second appendiceal base arising from the ascending colon was also ligated, and the appendectomy was completed without any further complications., Outcomes: After successful completion of appendectomy, the patient was discharged without any complications 2 days later., Lessons: An appendiceal anomaly is rarely seen during appendectomy or other forms of abdominal surgery; however, the ability of surgeons to both recognize and categorize an appendiceal anomaly is crucial if detected during surgery. After successfully recognizing the horseshoe anomaly of the appendix, it is important to know that 2 appendiceal base ligations will be required to complete the surgery successfully.

Rationale: The brain, liver, adrenal glands, and bone are the most common sites of metastatic disease in patients with lung cancer. Symptomatic gastrointestinal metastases are rare. In the present report, we describe a rare case of a patient with intestinal obstruction due to solitary colonic metastasis from primary lung adenocarcinoma, wherein the intestinal obstruction was the first symptom of lung cancer., Patient Concerns: A 74-year-old man was admitted to the emergency room with abdominal pain and vomiting, and abdominal computed tomography (CT) indicated obstruction of the ascending colon due to a huge mass., Diagnosis: The ascending colon cancer was found to be a metastatic adenocarcinoma based on the results of the pathology report. Chest CT and positron emission tomography-CT were performed to identify the cancer origin site. Moreover, immunohistochemical staining of the tissue specimen for thyroid transcription factor 1, cytokeratin 7 (CK7), and CK20 and CT-guided gun biopsy of the lung mass confirmed the presence of an adenocarcinoma that originated from the lung., Intervention: Right hemicolectomy was performed as the primary treatment., Outcomes: The patient recovered without any problems due to the surgery itself. However, malignant pleural effusion deteriorated, and no additional palliative chemotherapy was performed., Lessons: Patients with malignant bowel obstruction along with lung infiltration should be suspected of not only colon cancer with lung metastasis, but also lung cancer with colon metastasis.

Objective: To replace camera-based three-dimensional motion analyzers which are widely used to analyze body movements and gait but are also costly and require a large dedicated space, this study evaluates the validity and reliability of inertial measurement unit (IMU)-based systems by analyzing their spatio-temporal and kinematic measurement parameters., Methods: The investigation was conducted in three separate hospitals with three healthy participants. IMUs were attached to the abdomen as well as the thigh, shank, and foot of both legs of each participant. Each participant then completed a 10-m gait course 10 times. During each gait cycle, the hips, knees, and ankle joints were observed from the sagittal, frontal, and transverse planes. The experiments were conducted with both a camerabased system and an IMU-based system. The measured gait analysis data were evaluated for validity and reliability using root mean square error (RMSE) and intraclass correlation coefficient (ICC) analyses., Results: The differences between the RMSE values of the two systems determined through kinematic parameters ranged from a minimum of 1.83 to a maximum of 3.98 with a tolerance close to 1%. The results of this study also confirmed the reliability of the IMU-based system, and all of the variables showed a statistically high ICC., Conclusion: These results confirmed that IMU-based systems can reliably replace camera-based systems for clinical body motion and gait analyses.

Background: Extracellular polymeric substances isolated from Aureobasidium pullulans (EAP), containing specifically 13% β-1,3/1,6-glucan, have shown various favorable bone-preserving effects. Textoria morbifera Nakai (TM) tree has been used as an ingredient in traditional medicine and tea for various pharmacological purposes. Thus, the present study was aimed to examine the synergistic anti-osteoporotic potential of mixtures containing different proportions of EAP and TM compared with that of the single formulations of each herbal extract using bilateral ovariectomized (OVX) mice, a renowned rodent model for studying human osteoporosis., Methods: Thirty five days after bilateral-OVX surgery, 9 combinations of EAP:TM (ratios = 1:1, 1:3, 1:5, 1:7, 1:9, 3:1, 5:1, 7:1, 9:1) and single separate formulations of EAP or TM were supplied orally, once a day for 35 days at a final concentration of 200 mg/kg. Variations in body weight gains during the experimental periods, as well as femur weights, bone mineral density (BMD), bone strength (failure load), and mineral content (calcium [Ca] and inorganic phosphorus [IP]) following sacrifice were measured. Furthermore, histomorphometric and histological profile analyses of serum biochemical parameters (osteocalcin content and bone specific alkaline phosphatase [bALP] activity) were conducted following sacrifice. Femurs histomorphometric analyses were also conducted for bone resorption, structure and mass. The results for the mixed formulations of EAP:TM and separate formulations were compared with those of risedronate sodium (RES)., Results: The EAP:TM (3:1) formulation synergistically enhanced the anti-osteoporotic potential of individual EAP or TM formulations, possibly due to enhanced variety of the active ingredients. Furthermore, the effects of EAP:TM were comparable to those of RES (2.5 mg/kg) treatment., Conclusion: The results of this study suggest that, the EAP:TM (3:1) combination might act as a new pharmaceutical agent and/or health functional food substance for curing osteoporosis in menopausal women.

Objective: The use of abdominal computed tomography (ACT) for nontraumatic abdominal pain in the pediatric emergency department is increasing to a remarkable extent, and every effort should be made to select patients who would benefit from ACT. The aim of this study was to investigate the clinical and laboratory predictors of positive CT yield in pediatric patients with nontraumatic abdominal pain., Methods: The medical records of 739 pediatric patients who, between January 2009 and February 2014, underwent ACT for nontraumatic abdominal pain at the emergency department were reviewed retrospectively. These patients were divided into 2 groups: a right lower quadrant (RLQ) pain group and a non-RLQ pain group. The radiology reports were reviewed to determine ACT diagnoses. Univariate and multivariate analysis was performed to elicit independent predictors of positive ACT yield. Equations predicting the probability of positive ACT diagnosis were deduced from the regression equation in both groups., Results: In the RLQ pain group, the most frequent ACT diagnosis was acute appendicitis, and in the non-RLQ pain group, enteritis was the most frequent diagnosis. In the RLQ pain group, sex, leukocytosis, neutrophil-to-lymphocyte ratio, and elevated C-reactive protein were significant independent predictors for positive ACT diagnosis. The number of synchronous predictor was significantly related to the proportion of positive ACT diagnosis. In the non-RLQ pain group, leukocytosis was the only significant predictor in multivariate analysis., Conclusions: Factors predicting positive CT yield were sex, leukocytosis, neutrophil-to-lymphocyte ratio, and elevated C-reactive protein in the RLQ pain group and leukocytosis in the non-RLQ pain group.

Anoikis is a form of anchorage-dependent apoptosis, and cancer cells adopt anokis-resistance molecular machinery to conduct metastasis. Here, we report that N-acetylglucosaminyltransferase V gene expression confers anoikis resistance during cancer progression. Overexpression of N-acetylglucosaminyltransferase V protected detached cancer cells from apoptotic death, and suppression or knockout of the gene sensitized cancer cells to the apoptotic death. The gene expression also stimulated anchorage-dependent as well as anchorage-independent colony formation of cancer cells following anoikis stress treatments. Importantly, treatment with the lectin from Sambucus sieboldiana significantly sensitized anoikis-induced cancer cell deaths in vitro as well as in vivo. We propose that the lectin alone or an engineered form could offer a new therapeutic treatment option for cancer patients with advanced tumors.

Purpose: Inhibitory effect of paclitaxel on neointimal hyperplasia after open cutdown has not been elucidated., Methods: For the control group (n = 16), silicone 2.7-Fr catheters were placed via the right external jugular vein with the cutdown method. For the treatment group (n = 16), a mixture of 0.65 mg of paclitaxel and 1 mL of fibrin glue was infiltrated around the exposed vein after cutdown. After scheduled intervals (1, 2, 4, and 8 weeks), the vein segment was harvested and morphometric analysis was performed on cross-sections., Results: Proliferation of smooth muscle cell (SMC) was strongly suppressed in the treatment group, and the ratio of neointima to vein wall was significantly reduced in the treatment group (8 weeks; 0.63 ± 0.08 vs. 0.2 ± 0.08, P < 0.05). Luminal patency was significantly more preserved in the treatment group, and the luminal area was significantly wider in the paclitaxel-treated group compared to the control group (8 weeks; 1.91 ± 0.43 mm 2 vs. 5.1 ± 0.43 mm 2 , P < 0.05). Mean SMC counts measured at 1 and 2 weeks after cutdown were significantly lower in the treatment group (2 weeks; 115 ± 22 vs. 62 ± 22). Paclitaxel was undetectable in systemic circulation (<10 ng/mL)., Conclusion: Sustained perivascular delivery of paclitaxel with fibrin glue was effective in inhibiting neointimal hyperplasia in rat jugular vein after open cutdown., Competing Interests: CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.

Introduction: Neonatal intestinal perforation usually occurs at distal small bowel secondary to distal bowel obstruction. The aim of this report is to describe an unusual case of total colonic aganglionosis with an initial presentation of proximal jejunal perforation., Presentation of Case: A male newborn presented with jejunal perforation on the fifth day of life and was treated by laparoscopic primary repair. Abdominal distention persisted postoperatively, and radiological examination revealed an obstruction near the terminal ileum. Laparotomy showed a transition zone 30-cm proximal to the ileocecal valve, and diverting ileostomy and appendiceal biopsy was performed. Permanent section demonstrated the complete absence of ganglion cells in the appendix and total colonic aganglionosis was strongly suspected., Discussion: Contrary to the classic teaching, proximal bowel perforation can occur in case of far distal obstruction, and careful distal evaluation would direct more appropriate surgical treatment option., Conclusions: Total colonic aganglionosis can present as a proximal bowel perforation. Careful distal evaluation can provide diagnostic clues in cases of proximal intestinal perforation. Appendiceal biopsy is a reliable tool for evaluating suspected total colonic aganglionosis, but multiple colonic and rectal biopsies should be obtained to confirm the diagnosis., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The aim of this study was to review our experience of pediatric appendectomy performed by either a general surgeon (GS) or a pediatric surgeon (PS) to determine any differences in outcomes., Methods: We reviewed the medical records of pediatric appendicitis patients, 4 years before (GS group, 2007-2010) and after (PS group, 2011-2014) the introduction of a pediatric surgical practice. The records were reviewed for the following variables: operation time, length of hospital stay, complications, readmission in ≤30 days, type of operation, negative for appendicitis, drainage, open conversion, and reoperation in ≤30 days., Results: Over 8 years, 400 patients were operated on for acute appendicitis, with the PS group comprising 61 % (N = 244) of patients. The operation time (55.1 vs 43.2 min, p = 0.0001) and postoperative length of hospital stay (3.5 vs 2.7 days, p = 0.001) were shorter, more patients were treated by laparoscopy (61.3 vs 91.2 %, p = 0.0001), and a fewer patients required peritoneal drainage (29.5 vs 63.2 %, p = 0.023) in the PS group than in the GS group. The negative appendectomy rate was slightly lower in the PS group, but not to a statistically significant degree., Conclusion: The patients in the PS group enjoyed a reduced operation time and length of hospital stay, greater likelihood of laparoscopic operation, and less peritoneal drainage than the patients in the GS group.

A sinus between the colon and a retroperitoneal abscess is a rare entity that usually occurs as a complication of a primary condition such as Crohn's disease, radiation enteritis, or diverticular disease. Herein, we report a 72-year-old woman with a retroperitoneal abscess and a sinus formation between the abscess and the colon after an iatrogenic injury to her left colon. The retroperitoneal abscess was detected 1 week after the patient had undergone a left nephroureterectomy for recurrent ureteral cancer. The patient's general performance status allowed conservative management with antibiotics and percutaneous drainage. The abscess resolved, and the sinus closed after 3 weeks of treatment. In the absence of surgical pathology in the colon, and if the patient's general condition is good enough to tolerate conservative management, treatment using antibiotics plus percutaneous drainage is effective for cases of retroperitoneal abscess with a sinus between the colon and abscess.

The gastrointestinal tract is frequently in involved light-chain (AL) amyloidosis, but significant hemorrhagic complications are rare. A 71-year-old man presented to our hospital with dyspepsia and heartburn for 1 month. Gastroscopy revealed a large submucosal hematoma at the gastric fundus. Two days later, a follow-up gastroscopy indicated extensive expansion of the hematoma throughout the upper half of the stomach. The hematoma displayed ongoing expansion during the endoscopic examination, suggesting that rupture was imminent. Emergency total gastrectomy was performed, and amyloidosis was confirmed after examining the surgical specimen. Bone marrow examination revealed multiple myeloma, and serum immunoglobulin assay confirmed the diagnosis of myeloma-associated AL amyloidosis. At manuscript submission, the patient was doing well and was undergoing chemotherapy., (Copyright © 2013. Published by Elsevier Taiwan.)

Purpose: The modified Yale Preoperative Anxiety Scale (mYPAS) was developed for evaluating the level of preoperative anxiety in children. The purpose of this study was to develop a Korean version of the mYPAS (K-mYPAS) and to establish its validity and reliability based on the Korean preoperative pediatric patients., Methods: K-mYPAS was made through stringent back-translation procedure. Total enrolled 102 patients answered questionnaires of Korean version of State-Trait Anxiety Inventory for Children (K-STAIC), and were videotaped for 2 to 5 minutes before induction of anesthesia. Three observers of experienced psychiatrist, surgeon, and nurse analyzed videotape with K-mYPAS comparing to K-STAIC. The inter- and intraobservers reliability, concurrent and construct validity, sensitivity, specificity, and predictive value were analyzed., Results: The value of Cronbach α for interobservers reliability was 0.939 and intraobserver reliability was statistically significant (P < 0.001). Concurrent and construct validity were also statistically significant (P < 0.001 and P < 0.001, respectively). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 81.3%, 91.4%, 81.3%, 91.4%, and 88.2%, respectively., Conclusion: The K-mYPAS had good psychometric properties and can be used as a reliable and valid instrument for the assessment of preoperative anxiety in children.

A Gram-negative, aerobic, non-motile, catalase and oxidase positive rod-shaped bacterium, designated strain 4CoA2(T), was isolated from Cochlidinium polykrikoides culture fluid in the laboratory. The strain formed circular, glistening, grayish yellow colonies and grew at pH 7-8 and 28 °C optimally. On the basis of 16S rRNA gene sequence similarity, the strain was shown to be phylogenetically related to Roseovarius indicus B108(T) (97.6 %), Roseovarius halotolerans HJ50(T) (97.3 %), Roseovarius pacificus 2-81(T) (96.6 %), Roseovarius litoreus GSW-M15(T) (96.3 %) and Roseovarius tolerans EL-172(T) (94.27 %). Chemotaxonomic data revealed that the strain 4CoA2(T) possesses ubiquinone Q-10, and the predominant fatty acid is C18:1 ω6c or C18:1 ω7c. The polar lipids profile of the strain 4CoA2(T) included major amounts of phosphatidylglycerol, phosphatidylcholine, and diphosphatidyl glycerol. The DNA G + C content of the strain 4CoA2(T) is 62.0 %. Strain 4CoA2(T) exhibited relatively low level of DNA hybridization values (<35 %) with other Roseovarius species. On the basis of its phenotypic, genotypic properties and its phylogenetic data, strain 4CoA2(T) can be concluded to represent a novel species in the genus Roseovarius, for which the name Roseovarius algicolus sp. nov. is proposed. The type strain is 4CoA2(T) (=JCM 30823(T), =KEMB 3501-06(T)).