Endocardium gives rise to blood cells in zebrafish embryos.

Previous studies have suggested that the endocardium contributes to hematopoiesis in murine embryos, although definitive evidence to demonstrate the hematopoietic potential of the endocardium is still missing. Here, we use a zebrafish embryonic model to test the emergence of hematopoietic progenitors from the endocardium. By using a combination of expression analysis, time-lapse imaging, and lineage-tracing approaches, we demonstrate that myeloid cells emerge from the endocardium in zebrafish embryos. Inhibition of Etv2/Etsrp or Scl/Tal1, two known master regulators of hematopoiesis and vasculogenesis, does not affect the emergence of endocardial-derived myeloid cells, while inhibition of Hedgehog signaling results in their reduction. Single-cell RNA sequencing analysis followed by experimental validation suggests that the endocardium is the major source of neutrophilic granulocytes. These findings will promote our understanding of alternative mechanisms involved in hematopoiesis, which are likely to be conserved between zebrafish and mammalian embryos.

Thyroid Malignancy among Fine Needle Aspiration Cytology of Thyroid Lesions in a Tertiary Care Centre.

Introduction: The most prevalent endocrine cancer in the world is thyroid cancer, and its incidence is on the rise. The distinction between benign and malignant thyroid nodules must be made, which is why fine needle aspiration cytology of thyroid lesion is necessary and required. This study aimed to find out the prevalence of thyroid malignancy among fine needle aspiration cytology of thyroid lesions in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among fine needle aspiration cytology of thyroid lesions in a tertiary care centre after obtaining ethical approval from the Institutional Review Committee. Data from 13 April 2020 to 13 April 2023 was collected between 19 May 2023 to 19 June 2023. All the patients with complete hospital record data were included in this study. However, repetitive fine needle aspiration cytology of thyroid lesion were excluded from the study. Fine needle aspiration cytology diagnoses were categorized in this study as per the Bethesda system for reporting thyroid cytopathology. The point estimate was calculated at a 95% Confidence Interval. Results: Among 398 fine needle aspiration cytology of thyroid lesions, thyroid malignancy was seen in 12 (3.02%) (1.34-4.70, 95% Confidence Interval) patients. Conclusions: The prevalence of thyroid malignancy was found to be lower than other studies done in similar settings. Keywords: cytology; malignancy; prevalence; thyroid.

Quantifying the potential epidemiological impact of a 2-year active case finding for tuberculosis in rural Nepal: a model-based analysis.

OBJECTIVES: Active case finding (ACF) is an important tuberculosis (TB) intervention in high-burden settings. However, empirical evidence garnered from field data has been equivocal about the long-term community-level impact, and more data at a finer geographic scale and data-informed methods to quantify their impact are necessary. METHODS: Using village development committee (VDC)-level data on TB notification and demography between 2016 and 2017 in four southern districts of Nepal, where ACF activities were implemented as a part of the IMPACT-TB study between 2017 and 2019, we developed VDC-level transmission models of TB and ACF. Using these models and ACF yield data collected in the study, we estimated the potential epidemiological impact of IMPACT-TB ACF and compared its efficiency across VDCs in each district. RESULTS: Cases were found in the majority of VDCs during IMPACT-TB ACF, but the number of cases detected within VDCs correlated weakly with historic case notification rates. We projected that this ACF intervention would reduce the TB incidence rate by 14% (12-16) in Chitwan, 8.6% (7.3-9.7) in Dhanusha, 8.3% (7.3-9.2) in Mahottari and 3% (2.5-3.2) in Makwanpur. Over the next 10 years, we projected that this intervention would avert 987 (746-1282), 422 (304-571), 598 (450-782) and 197 (172-240) cases in Chitwan, Dhanusha, Mahottari and Makwanpur, respectively. There was substantial variation in the efficiency of ACF across VDCs: there was up to twofold difference in the number of cases averted in the 10 years per case detected. CONCLUSION: ACF data confirm that TB is widely prevalent, including in VDCs with relatively low reporting rates. Although ACF is a highly efficient component of TB control, its impact can vary substantially at local levels and must be combined with other interventions to alter TB epidemiology significantly.

Colorectal carcinoma presenting as spontaneous colocutaneous fistula - A rare case report and review of literature.

INTRODUCTION AND IMPORTANCE: Colon cancer presenting as spontaneous enterocutaneous fistula are rare with only few cases reported in the literature. Such presentation signifies locally advanced disease with poorer outcomes. Enterocutaneous fistula increases morbidity and mortality in cancer and may potentially delay the definitive care. It poses a difficulty in management in terms of patient optimization, determining the type of resection (palliative or curative) and the operative timeline. CASE PRESENTATION: A 47 years old female presented with complaints of foul smelling discharge from a fistulous opening in right iliac fossa with occasional per rectal bleeding for the past six months. Imaging showed ascending colon mass breaching the peritoneum with fistulous tract opening into subcutaneous plane. Exploratory laparotomy with right hemicolectomy and en bloc resection was performed. CLINICAL DISCUSSION: Cutaneous fistula can be caused by traumatic, postoperative etiologies and about 20 % are of spontaneous etiologies. Colon cancer has the ability to mimic any abdominal disease with a wide spectrum of presentations. The locoregional extension from the bowel creates a passage of colonic contents to evacuate from the external opening. The fistulous tract of colon cancer is less likely to close spontaneously and may require surgical intervention following appropriate resuscitation. Due to features suggestive of bowel obstruction an early single stage surgery was performed in our case. CONCLUSION: There are no existing guidelines for colon cancer with colocutaneous fistula because they are the same for benign fistulas (resuscitation, control of output, eradication of the infection, nutritional optimization, surgery) along with a multidisciplinary oncology team approach.

An unusual case of perforated stump appendicitis: A case report.

Introduction and importance: The stump appendicitis is a rare complication with incidence of 1 in 50,000 appendectomy cases. Case presentation: Patient with a history of emergency open appendectomy one year back presented with symptoms as that of acute appendicitis like pain abdomen localized in right iliac fossa, nausea, vomiting and anorexia. Complete blood count showed leukocytosis. Clinical discussion: Aside from classical clinical symptoms similar to acute appendicitis other causes of acute abdominal pain were ruled out with clinical laboratory and radiological investigations. This creates a dilemma and delay in diagnosis if investigations are not done promptly. Conclusion: Due to prior surgical history of appendectomy and low index of suspicion, the diagnosis of stump appendicitis is often delayed which may result in serious complications like stump gangrene, perforation and peritonitis.

Feasibility of HPV self-sampling pathway in Kathmandu Valley, Nepal using a human-centred design approach.

Cervical cancer is preventable and curable yet causes almost 2000 deaths in Nepali women each year. The present study aims to explore the feasibility and acceptability of a self-sampling-based approach for cervical cancer screening in urban and peri-urban Nepal and develop pathways for self-sampling using a co-design methodology. An iterative design approach was applied. Semi-structured in-depth interviews were conducted with 30 healthy women and four women who had had a prior cancer diagnosis on topics which included: sexual and reproductive health knowledge and human papillomavirus (HPV); use of the internet/social media platforms; their views regarding acceptability and usability of the self-sampling kit and the proposed user journey. Data collection was done between December 2020 and January 2021. Seven medical experts were also interviewed to explore the current service configuration for cervical cancer screening in Nepal. Knowledge regarding HPV and its association with cervical cancer was absent for the majority of participants. Although 70% (n = 21/30) had purchased items online previously, there was a general lack of trust in online shopping. Half of the women (n = 17/30; 56.7%) expressed a willingness to self-sample and provided recommendations to improve the clarity of the instructions. The proposed user journey was considered feasible in the urban area. There is a clear unmet need for information about HPV and alternative cervical screening options in Nepal. An online pathway for self-sampling service delivery to urban women is feasible but will need to be optimally designed to address barriers such as confidence in self-sampling and trust in online purchasing.

An incidental finding of ANET in a patient with perforated appendix: A case report.

INTRODUCTION AND IMPORTANCE: Appendiceal neuroendocrine tumors (ANETs) are incidentally found in 0.2-0.7% of appendectomies for suspected appendicitis. CASE PRESENTATION: A 29-year-old female presented with pain in the right lower quadrant of her abdomen for the past 48 h. On emergency appendectomy for suspected acute appendicitis, a perforated appendix was found. Histopathological examination showed grade 1 (low) ANET. CLINICAL DISCUSSION: Appendiceal neuroendocrine neoplasms (ANENs) are commonly found at the tip of the appendix and are treated with appendectomy alone. For few ANENs located at the base, or small tumors (≤2 cm) infiltrating the submucosa, the muscularis, the subserosa layer or the mesoappendix, right hemicolectomy is recommended. However, no guidelines have been established concerning patients with appendiceal perforation in case of ANENs. CONCLUSION: Although rare, ANETs should be considered in the differential diagnosis of acute appendicitis. Since, ANETs are rarely diagnosed preoperatively, subsequent patient evaluation after appendectomy is crucial for management of the patient.

Motor neuron cell bodies are actively positioned by Slit/Robo repulsion and Netrin/DCC attraction.

Motor neurons differentiate from a ventral column of progenitors and settle in static clusters, the motor nuclei, next to the floor plate. Within these cell clusters, motor neurons receive afferent input and project their axons out to muscle targets. The molecular mechanisms that position motor neurons in the neural tube remain poorly understood. The floor plate produces several types of guidance cues with well-known roles in attracting and repelling axons, including the Slit family of chemorepellents via their Robo receptors, and Netrin1 via its DCC attractive receptor. In the present study we found that Islet1(+) motor neuron cell bodies invaded the floor plate of Robo1/2 double mutant mouse embryos or Slit1/2/3 triple mutants. Misplaced neurons were born in their normal progenitor column, but then migrated tangentially into the ventral midline. Robo1 and 2 receptor expression in motor neurons was confirmed by reporter gene staining and anti-Robo antibody labeling. Mis-positioned motor neurons projected their axons longitudinally within the floor plate, and failed to reach their normal exit points. To test for potential counteracting ventral attractive signals, we examined Netrin-1 and DCC mutants, and found that motor neurons shifted dorsally in the hindbrain and spinal cord, suggesting that Netrin-1/DCC signaling normally attracts motor neurons closer to the floor plate. Our results show that motor neurons are actively migrating cells, and are normally trapped in a static position by Slit/Robo repulsion and Netrin-1/DCC attraction.