Molecular basis of anaphylatoxin binding, activation, and signaling bias at complement receptors.

The complement system is a critical part of our innate immune response, and the terminal products of this cascade, anaphylatoxins C3a and C5a, exert their physiological and pathophysiological responses primarily via two GPCRs, C3aR and C5aR1. However, the molecular mechanism of ligand recognition, activation, and signaling bias of these receptors remains mostly elusive. Here, we present nine cryo-EM structures of C3aR and C5aR1 activated by their natural and synthetic agonists, which reveal distinct binding pocket topologies of complement anaphylatoxins and provide key insights into receptor activation and transducer coupling. We also uncover the structural basis of a naturally occurring mechanism to dampen the inflammatory response of C5a via proteolytic cleavage of the terminal arginine and the G-protein signaling bias elicited by a peptide agonist of C3aR identified here. In summary, our study elucidates the innerworkings of the complement anaphylatoxin receptors and should facilitate structure-guided drug discovery to target these receptors in a spectrum of disorders.

Structural snapshots uncover a key phosphorylation motif in GPCRs driving ß-arrestin activation.

Agonist-induced GPCR phosphorylation is a key determinant for the binding and activation of ß-arrestins (ßarrs). However, it is not entirely clear how different GPCRs harboring divergent phosphorylation patterns impart converging active conformation on ßarrs leading to broadly conserved functional responses such as desensitization, endocytosis, and signaling. Here, we present multiple cryo-EM structures of activated ßarrs in complex with distinct phosphorylation patterns derived from the carboxyl terminus of different GPCRs. These structures help identify a P-X-P-P type phosphorylation motif in GPCRs that interacts with a spatially organized K-K-R-R-K-K sequence in the N-domain of ßarrs. Sequence analysis of the human GPCRome reveals the presence of this phosphorylation pattern in a large number of receptors, and its contribution in ßarr activation is demonstrated by targeted mutagenesis experiments combined with an intrabody-based conformational sensor. Taken together, our findings provide important structural insights into the ability of distinct GPCRs to activate ßarrs through a significantly conserved mechanism.

Targeting DNA polymerase to DNA double-strand breaks reduces DNA deletion size and increases templated insertions generated by CRISPR/Cas9.

Most insertions or deletions generated by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) endonucleases are short (<25 bp), but unpredictable on-target long DNA deletions (>500 bp) can be observed. The possibility of generating long on-target DNA deletions poses safety risks to somatic genome editing and makes the outcomes of genome editing less predictable. Methods for generating refined mutations are desirable but currently unavailable. Here, we show that fusing Escherichia coli DNA polymerase I or the Klenow fragment to Cas9 greatly increases the frequencies of 1-bp deletions and decreases >1-bp deletions or insertions. Importantly, doing so also greatly decreases the generation of long deletions, including those >2 kb. In addition, templated insertions (the insertion of the nucleotide 4 nt upstream of the protospacer adjacent motif) were increased relative to other insertions. Counteracting DNA resection was one of the mechanisms perturbing deletion sizes. Targeting DNA polymerase to double-strand breaks did not increase off-targets or base substitution rates around the cleavage sites, yet increased editing efficiency in primary cells. Our strategy makes it possible to generate refined DNA mutations for improved safety without sacrificing efficiency of genome editing.

Ensuring carbon neutrality via algae-based wastewater treatment systems: Progress and future perspectives.

The emergence of algal biorefineries has garnered considerable attention to researchers owing to their potential to ensure carbon neutrality via mitigation of atmospheric greenhouse gases. Algae-derived biofuels, characterized by their carbon-neutral nature, stand poised to play a pivotal role in advancing sustainable development initiatives aimed at enhancing environmental and societal well-being. In this context, algae-based wastewater treatment systems are greatly appreciated for their efficacy in nutrient removal and simultaneous bioenergy generation. These systems leverage the growth of algae species on wastewater nutrients-including carbon, nitrogen, and phosphorus-alongside carbon dioxide, thus facilitating a multifaceted approach to pollution remediation. This review seeks to delve into the realization of carbon neutrality through algae-mediated wastewater treatment approaches. Through a comprehensive analysis, this review scrutinizes the trajectory of algae-based wastewater treatment via bibliometric analysis. It subsequently examines the case studies and empirical insights pertaining to algae cultivation, treatment performance analysis, cost and life cycle analyses, and the implementation of optimization methodologies rooted in artificial intelligence and machine learning algorithms for algae-based wastewater treatment systems. By synthesizing these diverse perspectives, this study aims to offer valuable insights for the development of future engineering applications predicated on an in-depth understanding of carbon neutrality within the framework of circular economy paradigms.

Coexistence of tetragonal and cubic phase induced complex magnetic behaviour in CoMn2O4nanoparticles.

CoMn2O4, known for its extensive range of applications, has been subject to limited investigations regarding its structure dependent magnetic properties. Here, we have examined the structure dependent magnetic properties of CoMn2O4nanoparticles synthesized through a facile coprecipitation technique and are characterized using x-ray diffractometer, x-ray photoelectron spectroscopy (XPS), RAMAN spectroscopy, transmission electron microscopy and magnetic measurements. Rietveld refinement of the x-ray diffraction pattern reveals the coexistence of 91.84% of tetragonal and 8.16% of cubic phase. The cation distribution for tetragonal and cubic phases are (Co0.94Mn0.06)[Co0.06Mn1.94]O4and (Co0.04Mn0.96)[Co0.96Mn1.04]O4, respectively. While Raman spectra and selected area electron diffraction pattern confirm the spinel structure, both +2 and +3 oxidation states for Co and Mn confirmed by XPS further corroborate the cation distribution. Magnetic measurement shows two magnetic transitions, Tc1at 165 K and Tc2at 93 K corresponding to paramagnetic to a lower magnetically ordered ferrimagnetic state followed by a higher magnetically ordered ferrimagnetic state, respectively. While Tc1is attributed to the cubic phase having inverse spinel structure, Tc2corresponds to the tetragonal phase with normal spinel. In contrast to general temperature dependentHCobserved in ferrimagnetic material, an unusual temperature dependentHCwith high spontaneous exchange bias of 2.971 kOe and conventional exchange bias of 3.316 kOe at 50 K are observed. Interestingly, a high vertical magnetization shift (VMS) of 2.5 emu g-1is observed at 5 K, attributed to the Yafet-Kittel spin structure of Mn3+in the octahedral site. Such unusual results are discussed on the basis of competition between the non-collinear triangular spin canting configuration of Mn3+cations of octahedral sites and collinear spins of tetrahedral site. The observed VMS has the potential to revolutionize the future of ultrahigh density magnetic recording technology.

Fate of pesticides in agricultural runoff treatment systems: Occurrence, impacts and technological progress.

The levels of pesticides in air, water, and soil are gradually increasing due to its inappropriate management. In particular, agricultural runoff inflicts the damages on the ecosystem and human health at massive scale. Present study summarizes 70 studies in which investigations on removal or treatment of pesticides/insecticides/herbicides are reported. A bibliometric analysis was also done to understand the recent research trends through the analysis of 2218 publications. The specific objectives of this study are as follows: i) to inventorize the characteristics details of agriculture runoff and analyzing the occurrence and impacts of pesticides, ii) analyzing the role and interaction of pesticides in different environmental segments, iii) investigating the fate of pesticides in agriculture runoff treatment systems, iv) summarizing the experiences and findings of most commonly technology deployed for pesticides remediation in agriculture runoff including target pesticide(s), specifications, configuration of technological intervention. Among the reported technologies for pesticide treatment in agriculture runoff, constructed wetland was at the top followed by algal or photobioreactor. Among various advanced oxidation processes, photo Fenton method is mainly used for pesticides remediation such as triazine, methyl parathion, fenuron and diuron. Algal bioreactors are extensively used for a wide range of pesticides treatment including 2,4-Dichlorophenoxyacetic acid, 2-methyl-4-chlorophenoxyacetic acid, alachlor, diuron, chlorpyrifos, endosulfan, and imidacloprid; especially at lower hydraulic retention time of 2-6 h. This study highlights that hybrid approaches can offers potential opportunities for effective removal of pesticides in a more viable manner.

The CBP KIX domain regulates long-term memory and circadian activity.

BACKGROUND: CREB-dependent transcription necessary for long-term memory is driven by interactions with CREB-binding protein (CBP), a multi-domain protein that binds numerous transcription factors potentially affecting expression of thousands of genes. Identifying specific domain functions for multi-domain proteins is essential to understand processes such as cognitive function and circadian clocks. We investigated the function of the CBP KIX domain in hippocampal memory and gene expression using CBPKIX/KIX mice with mutations that prevent phospho-CREB (Ser133) binding. RESULTS: We found that CBPKIX/KIX mice were impaired in long-term memory, but not learning acquisition or short-term memory for the Morris water maze. Using an unbiased analysis of gene expression in the dorsal hippocampus after training in the Morris water maze or contextual fear conditioning, we discovered dysregulation of CREB, CLOCK, and BMAL1 target genes and downregulation of circadian genes in CBPKIX/KIX mice. Given our finding that the CBP KIX domain was important for transcription of circadian genes, we profiled circadian activity and phase resetting in CBPKIX/KIX mice. CBPKIX/KIX mice exhibited delayed activity peaks after light offset and longer free-running periods in constant dark. Interestingly, CBPKIX/KIX mice displayed phase delays and advances in response to photic stimulation comparable to wildtype littermates. Thus, this work delineates site-specific regulation of the circadian clock by a multi-domain protein. CONCLUSIONS: These studies provide insight into the significance of the CBP KIX domain by defining targets of CBP transcriptional co-activation in memory and the role of the CBP KIX domain in vivo on circadian rhythms.

A high-throughput LC-MS/MS method for determination of flunarizine in human plasma: Pharmacokinetic study with different doses.

A high-throughput and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the determination of flunarizine in human plasma. Liquid-liquid extraction under acidic conditions was used to extract flunarizine and flunarizine-d8 from 100 µL human plasma. The mean extraction recovery obtained for flunarizine was 98.85% without compromising the sensitivity of the method. The chromatographic separation was performed on Hypersil Gold C18 (50 × 2.1 mm, 3 µm) column using methanol-10 mm ammonium formate, pH 3.0 (90:10, v/v) as the mobile phase. A tandem mass spectrometer (API-5500) equipped with an electrospray ionization source in the positive ion mode was used for detection of flunarizine. Multiple reaction monitoring was selected for quantitation using the transitions, m/z 405.2 → 203.2 for flunarizine and m/z 413.1 → 203.2 for flunarizine-d8. The validated concentration range was established from 0.10 to 100 ng/mL. The accuracy (96.1-103.1%), intra-batch and inter-batch precision (CV ≤ 5.2%) were satisfactory and the drug was stable in human plasma under all tested conditions. The method was used to evaluate the pharmacokinetics of 5 and 10 mg flunarizine tablet formulation in 24 healthy subjects. The pharmacokinetic parameters Cmax and AUC were dose-proportional.

Production of trans-free interesterified fat using indigenously immobilized lipase.

Enzymatic interesterification was carried out between high-oleic canola oil and fully hydrogenated soybean oil using indigenously immobilized Thermomyces lanuginosus lipas substrate concentration, moisture content of enzyme, and enzyme load. Interesterification resulted in a decrease in the concentration of tri-unsaturated and trisaturated TAG and an increase of mono- and di-saturated TAG as observed by reversed-phase HPLC. The alteration in TAG composition and the presence of new TAG species after interesterification was correlated with extended plasticity characterized by lower slip melting point with a significant change in functionality and consistency of the interesterified product. Thermal and structural properties of the blends before and after interesterification were assessed by differential scanning calorimetry (DSC), X-ray diffraction and polarized light microscopy. Trans-fat analysis indicated the absence of any trans fatty acid in the final interesterified product. The resultant interesterified products with varying slip melting points can be used in the formulation of healthier fat and oil products and address a critical industrial demand for trans free formulations for base-stocks of spreads, margarines, and confectionary fats.

Overcoming interference of plasma phospholipids using HybridSPE for the determination of trimetazidine by UPLC-MS/MS.

An improved, precise and reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the quantification of trimetazidine, using trimetazidine-d8 as the internal standard (IS). Interference owing to plasma phospholipids during sample preparation was overcome using a hybrid solid-phase extraction-phospholipid ultra cartridge. The mean extraction recovery of trimetazidine (98.66%) and trimetazidine-d8 (97.63%) from spiked plasma was consistent and reproducible. Chromatographic analysis was performed on a UPLC Ethylene Bridged Hybrid (BEH) C18 (50 × 2.1 mm, 1.7 µm) column with isocratic elution using acetonitrile-5 mm ammonium formate, pH 3.5 (40:60, v/v) as the mobile phase. The parent → product ion transitions for trimetazidine (m/z 267.1 → 181.1) and trimetazidine-d8 (m/z 275.2 → 181.1) were monitored on a triple quadrupole mass spectrometer with electrospray ionization functioning in the positive multiple reaction monitoring mode. The linearity of the method was established in the concentration range of 0.05-100 ng/mL for trimetazidine. The intra-batch and inter-batch accuracy and precision (CV) were 97.3-103.1 and 1.7-5.3%, respectively. Qualitative and quantitative assessment of matrix effect showed no interference of endogenous/exogenous components. The developed method was used to measure plasma trimetazidine concentration for a bioequivalence study with 12 healthy subjects.

Evaluation of inflammatory markers interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) in asthma.

INTRODUCTION: Even though IL-6 and MMP-9 are associated with airway inflammation in asthma, there is paucity of data in Indian population. OBJECTIVE: To determine the levels of IL-6 and MMP-9 in the serum of patients suffering from asthma, and correlate with (a) disease severity, as per GINA guidelines; (b) clinical phenotypes; and (c) response to treatment. METHODOLOGY: The levels of IL-6 and MMP-9 were compared between moderate persistent asthma (n = 25), severe persistent asthma (n = 25) and normal controls (n = 30). IL-6 and MMP-9 were measured by ELISA (R&D Systems Inc., USA and Canada) and compared between controls and asthmatics and between groups of different asthma severity, clinical variables, spirometry, and allergen sensitization. Spirometry was repeated after 2 months of ICS+LABA to assess response to treatment in relation to baseline IL-6 and MMP-9 levels. RESULTS: We observed a significant difference in both IL-6 and MMP-9 levels among asthmatics versus controls (p < 0.001), moderate versus severe persistent asthma (p < 0.001). A significant negative correlation was observed between MMP-9 and pre-bronchodilator FEV1 and FVC, but not with IL-6. There was no association between IL-6 and MMP-9 with asthma duration, total IgE, AEC, number of allergens sensitized and degree of sensitization. No significant correlation (p > 0.5) was observed with IL-6 and MMP-9 levels and FEV1 improvement after 2 months of ICS+LABA. CONCLUSION: Higher levels of IL-6 and MMP-9 were observed in asthmatics as compared to controls and in severe persistent asthma as compared to moderate persistent asthma, higher levels of MMP-9 was associated with lower lung functions.

Green enzymatic production of glyceryl monoundecylenate using immobilized Candida antarctica lipase B.

Enzymatic synthesis of glyceryl monoundecylenate (GMU) was performed using indigenously immobilized Candida anatarctica lipase B preparation (named as PyCal) using glycerol and undecylenic acid as substrates. The effect of molar ratio, enzyme load, reaction time, and organic solvent on the reaction conversion was determined. Both batch and continuous processes for GMU synthesis with shortened reaction time were developed. Under optimized batch reaction conditions such as 1:5 molar ratio of undecylenic acid and glycerol, 2 h of reaction time at 30% substrate concentration in tert-butyl alcohol, conversion of 82% in the absence of molecular sieve, and conversion of 93% in the presence of molecular sieve were achieved. Packed bed reactor studies resulted in high conversion of 86% in 10-min residence time. Characterization of formed GMU was performed by FTIR, MS/MS. Enzymatic process resulted in GMU as a predominant product in high yield and shorter reaction time periods with GMU content of 92% and DAG content of 8%. Optimized GMU synthesis in the present study can be used as a useful reference for industrial synthesis of fatty acid esters of glycerol by the enzymatic route.

First Indian single center experience with pipeline embolization device for complex intracranial aneurysms.

BACKGROUND: Flow diversion is a novel method of therapy wherein an endoluminal sleeve, the flow diverter stent is placed across the neck of complex aneurysms to curatively reconstruct abnormal vasculature. We present the first Indian single center experience with the pipeline embolization device (PED) and 6 months follow-up results of 5 patients. SUBJECTS AND METHODS: Five complex or recurrent intracranial aneurysms in five patients were treated with PED. The patients were followed-up with magnetic resonance angiography (MRA) after 4 weeks and conventional angiography after 6 months. Feasibility, complications, clinical outcome, early 1-month MRA and 6 months conventional angiographic follow-up results were analyzed. RESULTS: Of the five aneurysms treated, four were in the anterior circulation and one in the posterior circulation. All five patients were treated with a single PED in each, and additionally coils were used in one patient. At 1-month MRA follow-up, complete occlusion was seen in 2 (40%) of the five cases. Post 6 months conventional angiography showed complete occlusion of the aneurysm sac in all five cases (100%). Side branch ostia were covered in three patients, all of which were patent (100%). There was no incidence of major neurological morbidity or mortality. One patient (20%) who had basilar top aneurysm experienced minor neurological disability after 5 days which partially improved. CONCLUSIONS: Pipeline embolization device for complex and recurrent aneurysms is technically feasible, safe, offers low complication rate, and definitive vascular reconstruction. PED can be used without fear of occlusion of covered eloquent side branches and perforators.

Extra-axial cerebellopontine angle nodular medulloblastoma mimicking meningioma: a case report with literature review.

Introduction: Medulloblastoma, a highly malignant embryonal tumor predominantly found in the pediatric population, typically arises within the cerebellum. This case report holds particular importance due to the rarity of medulloblastoma within the cerebellopontine angle (CPA). The distinct anatomical challenge posed by the CPA complex neurovascular structures, along with the absence of pathognomonic clinical or radiographic features, highlights the unique diagnostic and management challenge of this case. Case presentation: A 5-year-old boy presented with mild, progressively worsening headaches on CT/MRI imaging, which revealed a solid mass in the left CPA. Radiologically, the lesion closely resembled a CPA meningioma. The patient underwent a left retrosigmoid suboccipital craniectomy, utilizing a modified park bench position and careful burrhole creation. Intraoperatively, the tumor exhibited well-defined margins, firm adherence to cranial nerves, and complex tissue characteristics. Postoperatively, histopathological analysis identified nodular medulloblastoma, WHO grade IV, with immunohistochemical markers confirming its subtype. Discussion: This case highlights the critical role of surgical intervention in addressing rare tumors, emphasizing the need for multidisciplinary collaboration in both diagnosis and management to achieve a favorable outcome. Uncommon tumor locations, such as the CPA, require tailored approaches, and the utilization of advanced diagnostic techniques, including immunohistochemistry, aids in accurate subtype classification. Conclusion: This case highlights the critical role of surgical intervention in addressing rare tumors, emphasizing the need for multidisciplinary collaboration in both diagnosis and management to achieve a favorable outcome.

Prevalence of co-morbid insomnia and obstructive sleep apnoea.

INTRODUCTION: The coexistence of insomnia and obstructive sleep apnea (OSA) poses a complex and challenging clinical scenario, commonly referred to as comorbid insomnia and OSA (COMISA). The bidirectional relationship between these two sleep disorders is explored, illuminating how the presence of one can exacerbate the severity and manifestations of the other. We under took this study to understand the prevalence of COMISA in Indians which is never studied. AIM: To study the prevalence of COMISA in tertiary hospital in India. METHODS: All OSA patients diagnosed with polysomnography were interviewed with insomnia severity index. Patients having score of more than 15 were considered to have insomnia. Demographic factors, clinical and physical examination and polysomnography values were noted. RESULTS: 25% of 64 patients were diagnosed to have COMISA. Female gender, BMI, and STOP BANG score had positive association with COMISA, whereas age was not associated with increased risk. CONCLUSION: COMISA can be more complex to diagnose and manage than insomnia or OSA alone. The symptoms and mechanisms of each condition have synergistic effect and is a barrier to treating COMISA.

Neurological manifestations and complications of COVID-19 in patients admitted to a tertiary care center in Nepal during the second wave.

Neurological symptoms and signs of Coronavirus disease-19 (COVID-19) can accompany, follow, or precede respiratory symptoms and signs; hence, they are important in the diagnosis and management of COVID-19 patients. In this retrospective study conducted during the second wave of COVID-19, we included all patients diagnosed with COVID-19 using real-time polymerase chain reaction and admitted to the Tribhuvan University Teaching Hospital between June 2021 and October 2021. The patients were categorized into 2 groups: group A (with neurological manifestations or complications) and Group-B (without neurological manifestations or complications). The 2 groups were compared in terms of intensive care unit (ICU) admission, need for ventilatory support, length of hospital stay, and various outcomes. The study included 235 participants ranging in age from 13 to 102 years (mean age = 54 years, standard deviation = 18). Among the participants, 54.50% were male. The proportion of individuals in group A was higher (59.15%, N = 139) than that in Group-B (40.85%, N = 96). Notably, a significantly greater number of patients were admitted to the ICU in Group B than in Group A. However, there were no statistically significant differences in the need for ventilatory support or hospital stay between the 2 groups. Interestingly, group A showed a higher rate of improvement (Z = -3.1145, P = .00188, 95% CI), while Group-B had a higher rate of mortality (Z = 4.5562, P < .00001, 95% CI). Altered mental status and stroke have been specifically linked to poorer outcomes, whereas typical neurological manifestations, such as hyposmia, hypogeusia, dizziness, headache, and myalgia, are associated with better outcomes.

Acute paraquat poisoning in an adolescent with compromised outcome: A case report.

Paraquat, a highly toxic herbicide, accounts for a substantial number of poisoning-related fatalities, primarily prevalent in agricultural regions. The ingestion gives rise to severe complications affecting various organs, including the lungs, gastrointestinal tract, kidneys and liver. This report details the case of an 18-year-old male who had been using cannabis for a year and inadvertently ingested paraquat. He presented at the emergency room exhibiting symptoms of vomiting characterized by hematemesis and regurgitated food particles, along with heartburn, dysphagia and reduced urine output. Given the absence of a specific antidote, the prognosis for paraquat poisoning remains generally unfavourable. Diagnosis relies on circumstantial evidence and clinical manifestations, necessitating a focus on supportive care. Presently, no specific antidote for paraquat poisoning is available. Efforts should concentrate on preventive measures, efficient decontamination strategies and vigilant stabilization protocols in instances of exposure.

Non-encapsulated, encapsulated, and lyophilized probiotic Limosilactobacillus reuteri SW23 influenced the growth and gut health in calves.

The present study was conducted to assess the impact of non-encapsulated, air-dried microencapsulated, and lyophilized microencapsulated probiotics in indigenous cattle calves (Bos indicus). Twenty-four (5-7 days old) indigenous cattle calves were selected and assigned into four groups, with six calves in each as follows: control (CON), fed milk and basal diet alone, and treatment groups supplemented with non-encapsulated (NEC), air-dried microencapsulated (AEC) and lyophilized microencapsulated (LEC) probiotic L. reuteri SW23 at 108 CFU/head/day in skim milk as a carrier provided for 60 days. The animals were divided into four groups, adopting a complete randomized design, and the effects were considered significant at p ≤ 0.05. Probiotics supplementation increased (p < 0.05) body weight gain (kg), average daily gain, and structural growth measurements in calves of all treatment groups. Dry matter intake (g/d), feed conversion efficiency, and fecal counts of Lactobacilli and Bifidobacteria were also increased in the treatment groups compared to CON. The fecal consistency index was highest in CON (0.70 ± 0.03), followed by NEC (0.68 ± 0.01), AEC (0.66 ± 0.02), and LEC (0.65 ± 0.02). Fecal pH and ammonia levels were reduced (p < 0.05) in the probiotic-fed groups compared to CON, with a concomitant increase in fecal lactate, acetate, and propionate levels. In addition, cell-mediated and humoral immunity were significantly increased in supplemented groups as compared to CON. Thus, it can be concluded that supplementation of the probiotics in microencapsulated/non-encapsulated forms to neonatal calves had a variety of positive effects on their health, including better performance, improved gut health, and a lower fecal consistency index. Moreover, among all supplemented groups, the lyophilized microencapsulated group outperformed air-dried microencapsulated and non-microencapsulated groups in terms of ADG, DMI, and gut health.

A rare case of esophageal variceal bleeding as a result of portal hypertension due to extra-hepatic portal vein obstruction and its management in a 7-year-old.

INTRODUCTION: Extrahepatic Portal Vein Obstruction is the most common cause of portal hypertension in children. However, it has a very low prevalence. Esophageal varices due to portal hypertension in children can lead to recurrent episodes of upper gastrointestinal bleeding, which can have a sinister outcome if timely diagnosis and treatment are not initiated. CASE PRESENTATION: A 7-year-old male child presents with recurrent episodes of upper gastrointestinal bleeding for 3 years. Clinical examination reveals pallor and splenomegaly. Laboratory investigations revealed signs of hypersplenism with anemia, leucopenia and thrombocytopenia, and Doppler ultrasonography and CT abdomen and pelvis revealed splenic vein thrombosis with splenomegaly and cavernous transformation of the portal vein. The patient was managed operatively with splenectomy with splenorenal shunting and devascularization of esophagogastric varices. DISCUSSION: Extrahepatic Portal Vein obstruction is the most common cause of noncirrhotic portal hypertension in children. Its occurrence in the pediatric population is very rare. Portal hypertension can lead to variceal bleeding and splenomegaly, which can have a significant impact on a child's long-term health. Because of its insidious nature, a meticulous workup is required for its diagnosis, and treatment in the pediatric population is difficult, and appropriate guidelines for its management specifically targeting the pediatric population are lacking. CONCLUSION: Extrahepatic Portal Vein obstruction is rare in children with a difficult diagnosis and management. Despite these hindrances, timely intervention can lift a significant burden of its detrimental outcome off the young children and drastically uplift the quality of life of these patients.