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Abstract Background Benign choledochojejunal anastomotic stricture (CJS) is a common complication of pancreaticoduodenectomy and choledochojejunostomy. CJS is generally treated with balloon dilation, using balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP); however, its long- and short-term outcomes have not been fully evaluated. Therefore, we evaluated the treatment outcomes of balloon dilation with BE-ERCP for CJS. Methods We retrospectively analyzed 40 patients who had undergone balloon dilation with BE-ERCP for CJS between January 2009 and December 2022. The primary outcomes were technical and clinical success, and adverse event rates of balloon dilation using BE-ERCP for CJS. The secondary outcomes were long-term treatment outcomes for CJS recurrence, and evaluation of risk factors for recurrence. Result Technical and clinical success rates were 93% (37/40) and 100% (37/37), respectively. CJS recurrence occurred in 32% (20/37). No procedure-related adverse events were observed. The significant risk factors of CJS after balloon dilation were its early occurrence after surgery (unit hazard ratio [HR] for month, 0.87; 95% confidence interval [CI], 0.76–0.99; p-value = 0.04) and residual waist during balloon dilation (HR, 5.46; 95% CI, 1.18–25.1; p-value = 0.03). Receiver operating characteristic curve analysis of time from surgery to balloon dilation revealed an area under the curve of 0.80 (95% CI, 0.65–0.94) and the cut-off value was 13.2 months. Conclusion Treatment of CJS with balloon dilation was effective, although CJS recurrence occurred in one-third of the patients. The risk factors for recurrence were early occurrence of CJS after surgery and remaining waist circumference during balloon dilation.

Global healthcare systems have faced unprecedented strain due to the COVID-19 pandemic, with a profound impact on individuals with non-communicable diseases (NCDs), a scenario particularly pronounced in low-income countries like Nepal. This study aimed to understand the experiences of and challenges faced by patients with NCDs in Nepal during the pandemic, focusing on healthcare service availability and identifying factors affecting healthcare use, with the goal of being prepared for future emergencies. This study utilized a telephonic survey of 102 patients with NCDs and 10 qualitative interviews with healthcare providers in the Kavrepalanchok and Nuwakot districts of Nepal. We used mixed methods, with both qualitative and quantitative approaches. Specifically, multiple correspondence analysis, hierarchical cluster analysis, and classification tree analysis were used as exploratory methods. The study revealed that while 69.6% of the participants reported no difficulty in obtaining medication, other questions revealed that 58.8% experienced challenges in accessing routine medical care. Major barriers, such as fear of infection, unavailability of medicine in rural areas, and lack of transportation, were found through the qualitative interviews. Meanwhile, participants identified innovative strategies, such as telemedicine and community-based awareness programs, as potential facilitators for addressing barriers that arise during pandemic situations such as COVID-19. The COVID-19 pandemic exacerbated challenges in accessing healthcare services for patients with NCDs in Nepal. Our findings suggest the need to design and implement telemedicine services for patients with NCDs, as well as community-based programs that aim to improve health literacy, encourage healthy behavior, prevent development of NCDs, and ensure continuity of care during such crises, especially in countries with limited resources.

PurposeTo compared the vessel density (VD) around the optic nerve head (ONH) in eyes with cone-rod dystrophy (CORD) and healthy control eyes in a sector-wise manner and to investigate the relationship between VD around the ONH and visual function in CORD eyes.MethodsTwenty-six eyes in 14 CORD patients and 25 eyes in 25 healthy control subjects were examined. Using OCT angiography images, the VDs in the superficial and deep capillary plexus at the macula (sVDm and dVDm) and those around the ONH in the superior, temporal, inferior and nasal region (VDnh_s, VDnh_t, VDnh_i, and VDnh_n, respectively) were measured for each eye. Patient age, visual acuity (VA) and VDs were then compared between two groups. Moreover, the relationships between VA and the VDs were analyzed using a linear mixed model and AICc model selection.ResultsNo significant difference in age was seen between the CORD and control groups (p = 0.87, Wilcoxon rank sum test), but the VA was significantly lower in the CORD group (pConclusionsIn addition to the VD in the deep capillary plexus at the macula, the measurement of temporal VD around the ONH might be useful for predicting visual function in eyes with CORD.

Little attention has been paid to neglected tropical diseases (NTDs) in high-income countries and no literature provides an overview of NTDs in Japan. This scoping review aims to synthesize the latest evidence and information to understand epidemiology of and public health response to NTDs in Japan. Using three academic databases, we retrieved articles that mentioned NTDs in Japan, written in English or Japanese, and published between 2010 and 2020. Websites of key public health institutions and medical societies were also explored. From these sources of information, we extracted data that were relevant to answering our research questions. Our findings revealed the transmission of alveolar echinococcosis, Buruli ulcer, Chagas disease, dengue, foodborne trematodiases, mycetoma, scabies, and soil-transmitted helminthiasis as well as occurrence of snakebites within Japan. Other NTDs, such as chikungunya, cystic echinococcosis, cysticercosis, leishmaniasis, leprosy, lymphatic filariasis, rabies, and schistosomiasis, have been imported into the country. Government agencies tend to organize surveillance and control programs only for the NTDs targeted by the Infectious Disease Control Law, namely, echinococcosis, rabies, dengue, and chikungunya. At least one laboratory offers diagnostic testing for each NTD except for dracunculiasis, human African trypanosomiasis, onchocerciasis, and yaws. No medicine is approved for treatment of Chagas disease and fascioliasis and only off-label use drugs are available for cysticercosis, opisthorchiasis, human African trypanosomiasis, onchocerciasis, schistosomiasis, and yaws. Based on these findings, we developed disease-specific recommendations. In addition, three policy issues are discussed, such as lack of legal frameworks to organize responses to some NTDs, overreliance on researchers to procure some NTD products, and unaffordability of unapproved NTD medicines. Japan should recognize the presence of NTDs within the country and need to address them as a national effort. The implications of our findings extend beyond Japan, emphasizing the need to study, recognize, and address NTDs even in high-income countries.

Background: Japanese Spotted Fever (JSF) is a Spotted Fever Group (SFG) rickettsiosis caused by Rickettsia japonica. More than 300 cases are diagnosed annually in Japan, and the number of reported cases has been increasing. Correct diagnoses depend on the triad of symptoms and signs, including fever, rash, and eschar, which can be seen at the site of vector bites. JSF is not life-threatening if treated appropriately without diagnostic delay but there are some fatal cases every year. This negligence leads to disseminated intravascular coagulation (DIC) and multiple organ failure (MOF), and poor prognoses, consequently. Prompt diagnosis of JSF is difficult when the aforementioned triad of signs and symptoms is not initially present. Case report: This report describes three JSF cases: an 87-year-old woman with fever, shock, pancytopenia, DIC, and MOF; a 79-year-old man with fever and difficulty in movement; and a 78-year-old man with fever, general fatigue, and appetite loss. All patients had a rash and eschar, which led to prompt diagnosis and appropriate treatment immediately. All patients were treated without any complications. Why should an emergency physician be aware of this?: As mentioned above, JFS can be fatal with delayed diagnoses and treatment initiations. The key for a prompt diagnosis is to recognize the triad of symptoms and signs, which are not often present initially, and it makes JSF diagnosis challenging. Repeated comprehensive physical examinations are essential for prompt diagnosis and improve prognosis of JSF.

X-ray Microcomputed Tomography (µCT) is rapidly becoming an important analytical technique for examining the precise morphometry of small objects. The most notable feature of this technique is that it enables nondestructive, highly accurate morphometric measurements at micrometer-order resolution. In the Earth sciences, this makes µCT extremely useful for clarifying how genetic associations and the surrounding environment affect the morphology of micro-sized organisms. However, the actual analytical methods and the points that must be considered to produce reliable data have rarely been discussed in detail. Here, to address this lack of discussion, we describe in detail our methodology for precise µCT-based morphometry by using a test of the planktonic foraminifer and marine calcifier Globorotalia inflata. In addition to demonstrating the long-term stability of our µCT setup and analytical approach, we also propose a new methodology for test bulk density calibration using artificial carbonate phantoms. We expect that µCT together with our artificial phantom-based methodology will be useful for calculating accurate test bulk densities of micro-sized marine calcifiers.

Drug-induced gingival overgrowth (DIGO), induced by certain immunosuppressive drugs, antihypertensive agents, and antiepileptic drugs, may contribute to the formation of deeper periodontal pockets and intractableness in periodontitis. To date, multiple factors such as enhanced matrix production, inflammation, and reduced matrix degradation might be involved in the pathogenesis of DIGO. We have previously reported that SPOCK-1, a heparan sulfate proteoglycan, could affect gingival thickening by promoting epithelial-to-mesenchymal transition (EMT) in gingival keratinocytes. However, few studies have investigated whether a combination of these factors enhances the DIGO phenotype in animal models. Therefore, we investigated whether SPOCK-1, periodontal inflammation, and cyclosporin-A (CsA) could cooperatively promote gingival overgrowth. We first confirmed that Spock-1 overexpressing (Spock1-Tg) mice showed significantly thicker gingiva and greater alveolar bone loss than WT mice in response to ligature-induced experimental periodontitis. DIGO was induced by the combination of CsA administration and experimental periodontitis was significantly enhanced in Spock1-Tg mice compared to that in WT mice. Ligature-induced alveolar bone loss in CsA-treated Spock1-Tg mice was also significantly greater than that in CsA-treated WT mice, while being accompanied by an increase in Rankl and Col1a1 levels and a reduction in matrix metalloprotease expression. Lastly, SPOCK-1 promoted RANKL-induced osteoclast differentiation in both human peripheral blood mononuclear cells and murine macrophages, while peritoneal macrophages from Spock1-Tg mice showed less TNFα and IL-1β secretion than WT mice in response to Escherichia coli lipopolysaccharide. These results suggest that EMT, periodontal inflammation, and subsequent enhanced collagen production and reduced proteinase production contribute to CsA-induced DIGO pathogenesis.

Reactive oxygen species (ROS) like hydrogen peroxide (H2O2) are transient species that have broad actions in signaling and stress, but spatioanatomical understanding of their biology remains insufficient. Here, we report a tandem activity-based sensing and labeling strategy for H2O2 imaging that enables capture and permanent recording of localized H2O2 fluxes. Peroxy Green-1 Fluoromethyl (PG1-FM) is a diffusible small-molecule probe that senses H2O2 by a boronate oxidation reaction to trigger dual release and covalent labeling of a fluorescent product, thus preserving spatial information on local H2O2 changes. This unique reagent enables visualization of transcellular redox signaling in a microglia-neuron coculture cell model, where selective activation of microglia for ROS production increases H2O2 in nearby neurons. In addition to identifying ROS-mediated cell-to-cell communication, this work provides a starting point for the design of chemical probes that can achieve high spatial fidelity by combining activity-based sensing and labeling strategies.

Abstract Background With the increasing popularity of endoscopic ultrasound (EUS)-guided transmural interventions, walled-off necrosis (WON) of the pancreas is increasingly managed via non-surgical endoscopic interventions. However, there has been an ongoing debate over the appropriate treatment strategy following the initial EUS-guided drainage. Direct endoscopic necrosectomy (DEN) removes intracavity necrotic tissue, potentially facilitating early resolution of the WON, but may associate with a high rate of adverse events. Given the increasing safety of DEN, we hypothesised that immediate DEN following EUS-guided drainage of WON might shorten the time to WON resolution compared to the drainage-oriented step-up approach. Methods The WONDER-01 trial is a multicentre, open-label, superiority, randomised controlled trial, which will enrol WON patients aged ≥ 18 years requiring EUS-guided treatment in 23 centres in Japan. This trial plans to enrol 70 patients who will be randomised at a 1:1 ratio to receive either the immediate DEN or drainage-oriented step-up approach (35 patients per arm). In the immediate DEN group, DEN will be initiated during (or within 72 h of) the EUS-guided drainage session. In the step-up approach group, drainage-based step-up treatment with on-demand DEN will be considered after 72–96 h observation. The primary endpoint is time to clinical success, which is defined as a decrease in a WON size to ≤ 3 cm and an improvement of inflammatory markers (i.e. body temperature, white blood cell count, and C-reactive protein). Secondary endpoints include technical success, adverse events including mortality, and recurrence of the WON. Discussion The WONDER-01 trial will investigate the efficacy and safety of immediate DEN compared to the step-up approach for WON patients receiving EUS-guided treatment. The findings will help us to establish new treatment standards for patients with symptomatic WON. Trial registration ClinicalTrials.gov NCT05451901, registered on 11 July 2022. UMIN000048310, registered on 7 July 2022. jRCT1032220055, registered on 1 May 2022.

Cancer research in Rwanda is estimated to be less than 1% of the total African cancer research output with limited research on colorectal cancer (CRC). Rwandan patients with CRC are young, with more females being affected than males, and most patients present with advanced disease. Considering the paucity of oncological genetic studies in this population, we investigated the mutational status of CRC tissues, focusing on the Adenomatous polyposis coli (APC), Kirsten rat sarcoma (KRAS), and Homeobox B13 (HOXB13) genes. Our aim was to determine whether there were any differences between Rwandan patients and other populations. To do so, we performed Sanger sequencing of the DNA extracted from formalin-fixed paraffin-embedded adenocarcinoma samples from 54 patients (mean age: 60 years). Most tumors were located in the rectum (83.3%), and 92.6% of the tumors were low-grade. Most patients (70.4%) reported never smoking, and 61.1% of patients had consumed alcohol. We identified 27 variants of APC, including 3 novel mutations (c.4310_4319delAAACACCTCC, c.4463_4470delinsA, and c.4506_4507delT). All three novel mutations are classified as deleterious by MutationTaster2021. We found four synonymous variants (c.330C>A, c.366C>T, c.513T>C, and c.735G>A) of HOXB13. For KRAS, we found six variants (Asp173, Gly13Asp, Gly12Ala, Gly12Asp, Gly12Val, and Gln61His), the last four of which are pathogenic. In conclusion, here we contribute new genetic variation data and provide clinicopathological information pertinent to CRC in Rwanda.

Background/Aims Image-enhanced endoscopy can detect superficial oro-hypopharyngeal squamous cell carcinoma; however, reliable endoscopy of the pharyngeal region is challenging. Endoscopy under general anesthesia during transoral surgery occasionally reveals multiple synchronous lesions that remained undetected on preoperative endoscopy. Therefore, we aimed to determine the lesion detection capability of endoscopy under general anesthesia for superficial oro-hypopharyngeal squamous cell carcinoma. Methods This retrospective study included 63 patients who underwent transoral surgery for superficial oropharyngeal squamous cell carcinoma between April 2005 and December 2020. The primary endpoint was to compare the lesion detection capabilities of preoperative endoscopy and endoscopy under general anesthesia. Other endpoints included the comparison of clinicopathological findings between lesions detected using preoperative endoscopy and those newly detected using endoscopy under general anesthesia. Results Fifty-eight patients (85 lesions) were analyzed. The mean number of lesions per patient detected was 1.17 for preoperative endoscopy and 1.47 for endoscopy under general anesthesia. Endoscopy under general anesthesia helped detect more lesions than preoperative endoscopy did (p

Abstract The pink color sign in iodine unstained areas is useful to differentiate esophageal squamous cell carcinoma (ESCC) from other lesions. However, some ESCCs have obscure color findings which affect the ability of endoscopists to differentiate these lesions and determine the resection line. Using white light imaging (WLI), linked color imaging (LCI) and blue laser imaging (BLI), 40 early ESCCs were retrospectively evaluated using images before and after iodine staining. Visibility scores for ESCC by expert and non‐expert endoscopists were compared using these three modalities and color differences measured for malignant lesions and surrounding mucosa. BLI had the highest score and color difference without iodine staining. Each determination with iodine was much higher than without iodine regardless of the modality. With iodine, ESCC mainly appeared pink, purple and green using WLI, LCI and BLI, respectively and visibility scores determined by non‐experts and experts were significantly higher for LCI (both p

Abstract Recurrent respiratory papillomatosis (RRP) has a wide range of severity. We investigate the relationship between human papillomavirus (HPV) particle production and severity of RRP. From September 2005 to June 2021, 68 RRP samples (from 29 patients) were included. HPV type was determined. HPV viral load, physical status, and demographic and clinical characteristics were assessed. Immunohistochemistry (IHC) was performed for p16, Ki-67, L1, and E4. We used NanoSuit-CLEM (correlative light and electron microscopy) and transmission electron microscopy (TEM) to examine the samples. The total number of surgeries in HPV-positive and HPV-negative cases were 3.78 (n = 55/68, range: 1–16) and 1.30 (n = 13/68, range: 1–3), respectively (p = 0.02). IHC showed that L1 and E4 were correlated and expressed on the tumour surface. NanoSuit-CLEM and TEM revealed HPV particles in L1-positive nuclei. L1 IHC-positive cases had a shorter surgical interval (p

Abstract Background Subarachnoid hemorrhage and thyroid storm are similar in their clinical symptomatology, and diagnosis of these conditions, when they occur simultaneously, is difficult. Here, we report a rare case of concurrent subarachnoid hemorrhage and thyroid storm we encountered at our hospital. Case presentation The patient was a 52-year-old woman. While bathing at home, the patient experienced a sudden disturbance of consciousness and was brought to our hospital. The main physical findings upon admittance were Glasgow Coma Scale score of E1V2M4, elevated blood pressure (208/145 mmHg), and tachycardia with atrial fibrillation (180 bpm) along with body temperature of 36.1 °C. Brain computed tomography revealed subarachnoid hemorrhage associated with a ruptured aneurysm of the posterior communicating artery branching from the left internal carotid artery, and aneurysm clipping was performed. Blood tests upon admission revealed high levels of free T3 and free T4 and low levels of thyroid-stimulating hormone. Upon determining that the patient had hyperthyroidism, thiamazole was administered. However, due to continuous impaired consciousness, fever, and persistence of tachycardia, the patient was diagnosed with thyroid storm. Oral potassium iodide and hydrocortisone were added to the treatment. The treatment was successful as the patient’s symptoms improved, and she became lucid. In this case, we believe that in the presence of untreated hyperthyroidism, the onset of subarachnoid hemorrhage induced thyroid storm. Tachycardia of 130 bpm or higher, which is the diagnostic criterion for thyroid storm, rarely occurs with subarachnoid hemorrhage. Therefore, we believe it is an important factor for recognizing the presence of the thyroid storm. In this case, clipping surgery was prioritized which resulted in a favorable outcome. However, it is possible that invasive surgery may have exacerbated thyroid storm, suggesting that treatment should be tailored as per patient’s condition. Conclusion If a pulse rate of 130 bpm or higher is observed alongside subarachnoid hemorrhage, we recommend considering the possibility of concomitant thyroid storm and testing for thyroid hormone. If concomitant thyroid storm is present, we believe that a treatment plan tailored to the patient’s condition is critical, and early diagnosis will lead to a favorable outcome for the patient.

Flipped learning requires learners to enhance their self-regulated learning (SRL) practices which offer a lens for conceptualising how learners regulate themselves (Zimmerman & Moylan, 2009). To date, studies on flipped learning are yet to explore whether SRL is developed to the same extent in learners at undergraduate and postgraduate levels. To address this gap, this study explored differences in SRL practice by learners in an applied linguistics course offered at undergraduate and postgraduate levels at an Australian university. The data collected from two focus group interviews (six undergraduate; six postgraduate) were analysed to investigate the experiences developing/ SLR in these two cohorts. The findings show that while flipped learning provided learners with flexible learning opportunities to enhance their SLR, lack of teacher instruction associated with the flipped learning led the learners to believe that it was more time consuming and an increased workload; these perceptions, in turn, appeared to cancel the benefit associated with SLR practice. Nevertheless, postgraduate students tended to see the benefits of flipped learning more than their undergraduate counterparts. The limitations they perceived tended to relate more to the underdevelopment of their own self-regulated learning processes than to the flipped classroom method itself. These findings may inform practitioners' implementation of a flexible instructional approach in terms of learners' perceptions of the flipped learning model.

This study investigates the impact of an inquiry-based teacher education course in nurturing second language (L2) teachers' research mindset, defined herein as their cognition and action toward research. One hundred and thirty pre- and in-service L2 teachers of various nationalities participated in a teacher education course on instructed second language acquisition (ISLA) at an Australian university. The course was designed following an inquiry-based approach, with course activities focused on promoting teacher learners' curiosity about ISLA issues and their engagement both with and in research. Data were collected before, during, and after course participation, using a precourse survey, written reflections, and focus group interviews. Findings revealed that the inquiry-based course activities enabled the teacher learners to adopt a stronger research mindset. They were able to articulate the importance of research for teaching practice and gained firsthand experience as well as increased confidence in conducting research. They also showed inclination toward research-informed teaching and were keen to maintain their newly established favorable relationship with research, despite acknowledging concerns about their future actual research engagement, mostly due to time constraint and lack of institutional support. These findings suggest implications for nurturing language teachers' research mindset within L2 teacher education courses.

Background: Extracorporeal shock wave lithotripsy (ESWL) is a common treatment for pancreatic stones in chronic pancreatitis. In contrast, peroral pancreatoscopy-guided lithotripsy (POPS-L) remains underexplored, with limited comparative studies to ESWL. This study compared the treatment outcomes of disposable POPS-L tools and ESWL for pancreatic stones. Methods: A retrospective analysis was conducted on 66 patients who had undergone pancreatic stone treatment at three institutions between 2006 and 2022. The treatment outcomes of POPS-L and ESWL were compared. Results: This study included 19 and 47 patients who had undergone POPS-L and ESWL, respectively. In a comparison between POPS-L and ESWL, the stone clearance rates were 78.9% vs. 70.2% (p = 0.55), while the procedure-related complication rates were 21% vs. 6.3% (p = 0.09). The median total session counts were 1 vs. 5 (p < 0.01). The cumulative stone recurrence rates were comparable in both groups. Multivariate analysis revealed no significant factors influencing the stone clearance rates, and the choice between POPS-L and ESWL did not affect the stone clearance rates. Conclusions: POPS-L and ESWL exhibited comparable treatment outcomes in terms of stone clearance, complications, and recurrence rates. Furthermore, POPS-L is advantageous due to the need for fewer sessions to achieve pancreatic stone clearance.

Key Clinical Message Disseminated carcinomatosis of the bone marrow is rare. We present such a case, which is useful for raising awareness about the importance of early diagnosis and treatment of carcinomas complicated by disseminated carcinomatosis of the bone marrow. Abstract This is the first autopsy report of disseminated carcinomatosis of the bone marrow (DCBM) in esophageal adenocarcinoma. Advanced poorly differentiated adenocarcinoma with signet ring cell carcinoma arising in Barrett's esophagus caused disseminated intravascular coagulation (DIC) with extensive bone marrow metastasis, resulting in death from cerebral hemorrhage. Although DCBM due to malignancy is rare with poor prognosis, it should be considered in malignancies associated with DIC, and prompt initiation of chemotherapy is the only way to improve the patient's prognosis.

ObjectiveTo evaluate the swallowing function in the advanced stages of progressive supranuclear palsy (PSP) and clarify the factors that lead to adjustment of food consistency and discontinuation of oral intake.MethodsA total of 56 patients with PSP were recruited. Based on medical records, information about the basic attributes, clinical features (including axial rigidity and dementia), food intake, the results of a videofluoroscopic swallowing study (VFSS), and the timing of nasogastric tube transition and gastrostomy were extracted. From the VFSS images, the presence or absence of aspiration and retrocollis were assessed.ResultsThe average age at the onset, diagnosis, and the final follow-up examination were 67.6 ± 6.4 years, 71.6 ± 5.8 years, and 75.4 ± 5.6 years, respectively. The average duration of illness was 64.6 ± 42.8 months. Twenty-four individuals (42.9%) were continuing oral intake, while 32 were tube-fed, among whom 16 (50.0%) underwent gastrostomy tube placement. There were significant differences in the duration from the disease onset to tube feeding between the patients with and without cognitive decline at the time of the diagnosis (p