Discovery of N-(1,4-Benzoxazin-3-one) urea analogs as Mode-Selective TRPV1 antagonists.

A series of 1,4-benzoxazin-3-one analogs were investigated to discover mode-selective TRPV1 antagonists, since such antagonists are predicted to minimize target-based adverse effects. Using the high-affinity antagonist 2 as the lead structure, the structure activity relationship was studied by modifying the A-region through incorporation of a polar side chain on the benzoxazine and then by changing the C-region with a variety of substituted pyridine, pyrazole and thiazole moieties. The t-butyl pyrazole and thiazole C-region analogs provided high potency as well as mode-selectivity. Among them, antagonist 36 displayed potent and capsaicin-selective antagonism with IC50 = 2.31 nM for blocking capsaicin activation and only 47.5 % inhibition at 3 µM concentration toward proton activation, indicating that more than a 1000-fold higher concentration of 36 was required to inhibit proton activation than was required to inhibit capsaicin activation. The molecular modeling study of 36 with our homology model indicated that two π-π interactions with the Tyr511 and Phe591 residues by the A- and C-region and hydrogen bonding with the Thr550 residue by the B-region were critical for maintaining balanced and stable binding. Systemic optimization of antagonist 2, which has high-affinity but full antagonism for activators of all modes, led to the mode-selective antagonist 36 which represents a promising step in the development of clinical TRPV1 antagonists minimizing side effects such as hyperthermia and impaired heat sensation.

Discovery of N-(1-(2-hydroxyethyl)quinolin-2-one)-N'-(1-phenyl-1H-pyrazol-5-yl)methyl) urea as Mode-Selective TRPV1 antagonist.

To discover mode-selective TRPV1 antagonists as thermoneutral drug candidates, the previous potent antagonist benzopyridone 2 was optimized based on the pharmacophore A- and C-regions. The structure activity relationship was investigated systematically by modifying the A-region by incorporating a polar side chain on the pyridone and then by changing the C-region with a variety of substituted pyridine and pyrazole moieties. The 3-t-butyl and 3-(1-methylcyclopropyl) pyrazole C-region analogs provided high potency as well as mode-selectivity. Among them, 51 and 54 displayed potent and capsaicin-selective antagonism with IC50 = 2.85 and 3.27 nM to capsaicin activation and 28.5 and 31.5 % inhibition at 3 µM concentration toward proton activation, respectively. The molecular modeling study of 51 with our homology model indicated that the hydroxyethyl side chain in the A-region interacted with Arg557 and Glu570, the urea B-region engaged in hydrogen bonding with Tyr511 and Thr550, respectively, and the pyrazole C-region made two hydrophobic interactions with the receptor. Optimization of antagonist 2, which has full antagonism for activators of all modes, lead to mode-selective antagonists 51 and 54. These observations will provide insight into the future development of clinical TRPV1 antagonists without target-based side effects.

Effectiveness and Tolerability of Combination Pharmacotherapy With Stimulant and Non-Stimulant in Children With Attention Deficit Hyperactivity Disorder.

Objectives: This study aimed to investigate the effectiveness and safety of combining psychostimulants and nonstimulants for patients under treatment for attention deficit hyperactivity disorder (ADHD). Methods: The study included 96 patients aged 6-12 years who were diagnosed with ADHD, among whom 34 received combination pharmacotherapy, 32 received methylphenidate monotherapy, and 30 received atomoxetine monotherapy. Statistical analysis was conducted to compare treatment and adverse effects among groups and to analyze changes before and after combination pharmacotherapy. The difference between combination pharmacotherapy and monotherapy was investigated. Logistic regression analysis was used to identify the predictors of combination pharmacotherapy. Results: No significant differences were observed between the groups in terms of age or pretreatment scores. The most common adverse effect experienced by 32% of patients in the combination pharmacotherapy group was decreased appetite. Clinical global impression- severity score decreased significantly after combination pharmacotherapy. All three groups showed significant clinical global impression- severity score improvements over time, with no significant differences among them. The predictive factors for combination pharmacotherapy included the Child Behavior Checklist total score internalizing subscale. Conclusion: Combination pharmacotherapy with methylphenidate and atomoxetine is a relatively effective and safe option for patients with ADHD who do not respond to monotherapy.

Inhalable Nitric Oxide Delivery Systems for Pulmonary Arterial Hypertension Treatment.

Pulmonary arterial hypertension (PAH) is a severe medical condition characterized by elevated blood pressure in the pulmonary arteries. Nitric oxide (NO) is a gaseous signaling molecule with potent vasodilator effects; however, inhaled NO is limited in clinical practice because of the need for tracheal intubation and the toxicity of high NO concentrations. In this study, inhalable NO-releasing microspheres (NO inhalers) are fabricated to deliver nanomolar NO through a nebulizer. Two NO inhalers with distinct porous structures are prepared depending on the molecular weights of NO donors. It is confirmed that pore formation can be controlled by regulating the migration of water molecules from the external aqueous phase to the internal aqueous phase. Notably, open porous NO inhalers (OPNIs) can deliver NO deep into the lungs through a nebulizer. Furthermore, OPNIs exhibit vasodilatory and anti-inflammatory effects via sustained NO release. In conclusion, the findings suggest that OPNIs with highly porous structures have the potential to serve as tools for PAH treatment.

Occlusive membranes for guided regeneration of inflamed tissue defects.

Guided bone regeneration aided by the application of occlusive membranes is a promising therapy for diverse inflammatory periodontal diseases. Symbiosis, homeostasis between the host microbiome and cells, occurs in the oral environment under normal, but not pathologic, conditions. Here, we develop a symbiotically integrating occlusive membrane by mimicking the tooth enamel growth or multiple nucleation biomineralization processes. We perform human saliva and in vivo canine experiments to confirm that the symbiotically integrating occlusive membrane induces a symbiotic healing environment. Moreover, we show that the membrane exhibits tractability and enzymatic stability, maintaining the healing space during the entire guided bone regeneration therapy period. We apply the symbiotically integrating occlusive membrane to treat inflammatory-challenged cases in vivo, namely, the open and closed healing of canine premolars with severe periodontitis. We find that the membrane promotes symbiosis, prevents negative inflammatory responses, and improves cellular integration. Finally, we show that guided bone regeneration therapy with the symbiotically integrating occlusive membrane achieves fast healing of gingival soft tissue and alveolar bone.

Rottlerin-Liposome Inhibits the Endocytosis of Feline Coronavirus Infection.

Rottlerin (R) is a natural extract from Mallotus philippensis with antiviral properties. Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV) that is characterized by systemic granulomatous inflammation and high mortality. We investigated the antiviral effect of liposome-loaded R, i.e., rottlerin-liposome (RL), against FCoV. We demonstrated that RL inhibited FCoV replication in a dose-dependent manner, not only in the early endocytosis stage but also in the late stage of replication. RL resolved the low solubility issue of rottlerin and improved its inhibition efficacy at the cellular level. Based on these findings, we suggest that RL is worth further investigation as a potential treatment for FCoV.

Zwitterionic Inhaler with Synergistic Therapeutics for Reprogramming of M2 Macrophage to Pro-Inflammatory Phenotype.

Myriad lung diseases are life threatening and macrophages play a key role in both physiological and pathological processes. Macrophages have each pro-/anti-inflammatory phenotype, and each lung disease can be aggravated by over-polarized macrophage. Therefore, development of a method capable of mediating the macrophage phenotype is one of the solutions for lung disease treatment. For mediating the phenotype of macrophages, the pulmonary delivery system (PDS) is widely used due to its advantages, such as high efficiency and accessibility of the lungs. However, it has a low drug delivery efficiency ironically because of the perfect lung defense system consisting of the mucus layer and airway macrophages. In this study, zwitterion-functionalized poly(lactide-co-glycolide) (PLGA) inhalable microparticles (ZwPG) are synthesized to increase the efficiency of the PDS. The thin layer of zwitterions formed on PLGA surface has high nebulizing stability and show high anti-mucus adhesion and evasion of macrophages. As a reprogramming agent for macrophages, ZwPG containing dexamethasone (Dex) and pirfenidone (Pir) are treated to over-polarized M2 macrophages. As a result, a synergistic effect of Dex/Pir induces reprogramming of M2 macrophage to pro-inflammatory phenotypes.

High protein-containing new food by cell powder meat.

Demand for a new protein source to replace meat is increasing to solve various issues such as limited resources and food shortages. Diverse protein sources are being developed, but alternative proteins such as plants or insects need to improve people's perceptions and organoleptic properties. Therefore, cell-based meat research is intensively conducted, and most studies are aimed at scale-up and cost-down via the research of scaffolds and culture media. Here, we proposed a new food by cell powder meat (CPM), which has a high protein content and a meaty flavor. The powder was manufactured 76% more cost-effectively with less serum than the conventional culture medium and without 3D scaffold. Due to its comprehensive characteristics, the potential applicability of CPM in the cell-based meat industry could be expected.

Porcine Reproductive and Respiratory Syndrome Virus Engineered by Serine Substitution on the 44th Amino Acid of GP5 Resulted in a Potential Vaccine Candidate with the Ability to Produce High Levels of Neutralizing Antibody.

N-linked glycans covering GP5 neutralizing epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) have been proposed to act as a sheath blocking the production of neutralizing antibodies. Herein, we genetically engineered PRRSV with serine (S) substitution on the 44th asparagine (N) on the GP5 ectodomain of PRRSV-2 lineage-1. To evaluate the recombinant PRRSV, in vivo experiments were performed in piglets. The recombinant virus group showed no viremia until 42 days post-inoculation (dpi), and the rectal temperature and average daily weight gain were in the normal range at the same time point as the negative control group. On the 42 dpi, both groups were challenged with the wild-type virus. The recombinant PRRSV group showed lower rectal temperature, viremia, and the lung lesions than that of the negative control group for 19 days post-challenge (dpc). Additionally, the recombinant virus induced 4.50 ± 3.00 (log2) and 8.25 ± 0.96 (log2) of neutralizing antibody before and after challenge, respectively. Taken together, this study confirmed that N44S substitution can create an infectious PRRSV that strongly induces neutralizing antibodies. In addition, the vCSL1-GP5-N44S mutant that we produced was confirmed to have potential as a vaccine candidate, showing good safety and protective effects in pigs.

Association between Prehospital Visits and Poor Health Outcomes in Korean Acute Stroke Patients: A National Health Insurance Claims Data Study.

This study aimed to determine whether prehospital visits to other medical institutions before admission are associated with prolonged hospital stay, readmission, or mortality rates in acute stroke patients. Using the claims data from the Korean Health Insurance Service, a cross-sectional study was conducted on 58,418 newly diagnosed stroke patients aged ≥ 20 years from 1 January 2019 to 31 December 2019. Extended hospital stay (≥7 days; median value) following initial admission, readmission within 180 days after discharge, and all-cause mortality within 30 days were measured as health outcomes using multiple logistic regression analysis after adjusting for age, sex, income, residential area, and medical history. Stroke patients with a prehospital visit (10,992 patients, 18.8%) had a higher risk of long hospitalization (odds ratio = 1.06; 95% confidence interval = 1.02-1.10), readmission (1.19; 1.14-1.25), and mortality (1.23; 1.13-1.33) compared with patients without a prehospital visit. Female patients and those under 65 years of age had increased unfavorable outcomes (p < 0.05). Prehospital visits were associated with unfavorable health outcomes.

Oncogenic signaling pathways and hallmarks of cancer in Korean patients with acral melanoma.

Acral melanoma (AM), a rare subtype of cutaneous melanoma, shows higher incidence in Asians, including Koreans, than in Caucasians. However, the genetic modification associated with AM in Koreans is not well known and has not been comprehensively investigated in terms of oncogenic signaling, and hallmarks of cancer. We performed whole-exome and RNA sequencing for Korean patients with AM and acquired the genetic alterations and gene expression profiles. KIT alterations (previously known to be recurrent alterations in AM) and CDK4/CCND1 copy number amplifications were identified in the patients. Genetic and transcriptomic alterations in patients with AM were functionally converge to the hallmarks of cancer and oncogenic pathways, including 'proliferative signal persistence', 'apoptotic resistance', and 'activation of invasion and metastasis', despite the heterogeneous somatic mutation profiles of Korean patients with AM. This study may provide a molecular understanding for therapeutic strategy for AM.

Shared Interoperable Clinical Decision Support Service for Drug-Allergy Interaction Checks: Implementation Study.

BACKGROUND: Clinical decision support (CDS) can improve health care with respect to the quality of care, patient safety, efficiency, and effectiveness. Establishing a CDS system in a health care setting remains a challenge. A few hospitals have used self-developed in-house CDS systems or commercial CDS solutions. Since these in-house CDS systems tend to be tightly coupled with a specific electronic health record system, the functionality and knowledge base are not easily shareable. A shared interoperable CDS system facilitates the sharing of the knowledge base and extension of CDS services. OBJECTIVE: The study focuses on developing and deploying the national CDS service for the drug-allergy interaction (DAI) check for health care providers in Korea that need to introduce the service but lack the budget and expertise. METHODS: To provide the shared interoperable CDS service, we designed and implemented the system based on the CDS Hooks specification and Health Level Seven (HL7) Fast Healthcare Interoperability Resources (FHIR) standard. The study describes the CDS development process. The system development went through requirement analysis, design, implementation, and deployment. In particular, the concept architecture was designed based on the CDS Hooks structure. The MedicationRequest and AllergyIntolerance resources were profiled to exchange data using the FHIR standard. The discovery and DAI check application programming interfaces and rule engine were developed. RESULTS: The CDS service was deployed on G-Cloud, a government cloud service. In March 2021, the CDS service was launched, and 67 health care providers participated in the CDS service. The health care providers participated in the service with 1,008,357 DAI checks for 114,694 patients, of which 33,054 (3.32%) cases resulted in a "warning." CONCLUSIONS: Korea's Ministry of Health and Welfare has been trying to build an HL7 FHIR-based ecosystem in Korea. As one of these efforts, the CDS service initiative has been conducted. To promote the rapid adoption of the HL7 FHIR standard, it is necessary to accelerate practical service development and to appeal to policy makers regarding the benefits of FHIR standardization. With the development of various case-specific implementation guides using the Korea Core implementation guide, the FHIR standards will be distributed nationwide, and more shared interoperable health care services will be introduced in Korea.

Regulation of the Inevitable Water-Responsivity of Silk Fibroin Biopolymer by Polar Amino Acid Activation.

In nature, water is vital for maintaining homeostasis. Particularly, organisms (e.g., plant leaf, bird feather) exploit water fluidics for motions. Hydration-adaptive crystallization is the representative water-responsive actuation of biopolymers. This crystallization has inspired the development of intelligent human-robot interfaces. At the same time, it hinders the consistent adhesion of tissue adhesive. As hydration-adaptive crystallization is inevitable, the on-demand control of crystallization is desirable in the innovative biopolymeric biomedical systems. To this end, this study developed an amino acid-based technology to artificially up- or down-regulate the inevitable crystallization of silk fibroin. A case II diffusion model was constructed, and it revealed that the activity of polar amino acid is related to crystallization kinetics. Furthermore, the water dynamics study suggested that active amino acid stabilizes crystallization-triggering water molecules. As a proof-of-concept, we verified that a 30% increase in the activity of serine resulted in a 50% decrease in the crystallization rate. Furthermore, the active amino acid-based suppression of hydration-adaptive crystallization enabled the silk fibroin to keep its robust adhesion (approximately 160 kJ m-3) by reducing the water-induced loss of adhesive force. The proposed silk fibroin was demonstrated as a stable tissue adhesive applied on ex vivo porcine mandible tissue. This amino acid-based regulation of hydration-adaptive crystallization will pioneer next-generation biopolymer-based healthcare.

Standard Document Development for Health Information Exchange in Korea.

BACKGROUND: Health information exchange (HIE) allows healthcare providers to access a patient's medical information to improve patient care continuity. The standardized data realize the HIE values. Since the Health Level 7 Clinical Document Architecture (CDA) is flexible, implementation guides (IG) are needed for use cases. Although many CDA IGs have been developed, they did not describe how these CDA IGs were developed. A national CDA IG that meets the local requirements is demanded since the data differs according to the digital divide and social-cultural background of the country that wants to establish HIE. Due to their localized contents, other countries cannot directly adopt the published CDA IGs. OBJECTIVES: We developed the national CDA IG, namely, Korean (K)-CDA IG that meets the local requirement, including reusable structured templates, value sets, and object identifiers (OIDs). We present a detailed description of the development process and the technical methods of the national CDA IG in the Korean context. METHODS: The K-CDA IG was developed in the following stages: analysis, development, and evaluation. First, we investigated the health information environment and electronic health record (EHR) systems and conducted a gap analysis with published CDA IGs. Second, a templated CDA approach was taken for designing modular. Lastly, we consulted a technical advisory group for comments on the validity of the K-CDA IG. RESULTS: A total of 35 CDA templates were developed. We improved 28 value sets of which 13 were Korea specific and 15 were based on the ones used in other IGs, and made a set of rules to establish the OID structure. CONCLUSION: We presented the development process and the technical specifications of K-CDA IG. We explored how the results can be used as interoperability criteria in the national EHR systems certification program. Finally, we provided recommendations that could guide other entities planning their HIE programs.

Low-dose clozapine monotherapy for recurrent non-suicidal self-injury: A case report.

Non-suicidal self-injury (NSSI) is a challenging issue in clinical settings. In the present case series, we report two female adolescents with recurrent depression and NSSI. Numerous approaches, such as anti-depressants, anti-psychotics, and even electroconvulsive therapy, were not effective. Clozapine has been implemented in a broad spectrum of psychiatric disorders, particularly refractory depression, impulse control problems, suicidal ideation, and NSSI. With a low dose (12.5-25 mg) of clozapine, the depressive symptoms and NSSI remarkably improved, and the improvement was sustained over four months after discharge. Low-dose clozapine monotherapy may be a treatment option with refractory depression and NSSI.

Development of a Chimeric Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)-2 Vaccine Candidate Expressing Hypo-Glycosylated Glycoprotein-5 Ectodomain of Korean Lineage-1 Strain.

Vaccination is a practical method to provide protection against porcine reproductive and respiratory syndrome virus (PRRSV), but current PRRSV vaccines show limited efficacy against divergent field strains. Lineage 1 PRRSV includes virulent strains such as NADC30 and MN184 and now has become one of the most prevalent viruses in Korea. Accordingly, there is an urgent need to develop a new vaccine for Korean lineage-1 strains. In this study, a vaccine candidate against Korean lineage-1 PRRSV, vCSL1-GP5-N33D, was developed by reverse genetics technology. vCSL1-GP5-N33D was designed as a hypo-glycosylated chimeric virus containing the glycoprotein 5 ectodomain region of the Korean lineage-1 wild-type strain. An inactivated vaccine of vCSL1-GP5-N33D was applied to a PRRS-endemic farm and elicited high serum virus neutralization (SVN) antibody titers. The vaccinated group induced SVN antibody titers of 4.40 (log2) ± 2.46, which were approximately 2-fold higher than those of the negative control at 8-weeks post-vaccination. Moreover, 60% of pigs in the vaccinated group displayed SVN antibody titers of ≥5 (log2), while none of the pigs in the negative control exhibited SVN antibody titers of ≥5 (log2). The overall results of the animal experiment suggest that the vCSL1-GP5-N33D inactivated vaccine is a promising vaccine candidate.

Transcriptome-based variant calling and aberrant mRNA discovery enhance diagnostic efficiency for neuromuscular diseases.

BACKGROUND: Whole-exome sequencing-based diagnosis of rare diseases typically yields 40%-50% of success rate. Precise diagnosis of the patients with neuromuscular disorders (NMDs) has been hampered by locus heterogeneity or phenotypic heterogeneity. We evaluated the utility of transcriptome sequencing as an independent approach in diagnosing NMDs. METHODS: The RNA sequencing (RNA-Seq) of muscle tissues from 117 Korean patients with suspected Mendelian NMD was performed to evaluate the ability to detect pathogenic variants. Aberrant splicing and CNVs were inspected to identify additional causal genetic factors for NMD. Aberrant splicing events in Dystrophin (DMD) were investigated by using antisense oligonucleotides (ASOs). A non-negative matrix factorisation analysis of the transcriptome data followed by cell type deconvolution was performed to cluster samples by expression-based signatures and identify cluster-specific gene ontologies. RESULTS: Our pipeline called 38.1% of pathogenic variants exclusively from the muscle transcriptomes, demonstrating a higher diagnostic rate than that achieved via exome analysis (34.9%). The discovery of variants causing aberrant splicing allowed the application of ASOs to the patient-derived cells, providing a therapeutic approach tailored to individual patients. RNA-Seq data further enabled sample clustering by distinct gene expression profiles that corresponded to clinical parameters, conferring additional advantages over exome sequencing. CONCLUSION: The RNA-Seq-based diagnosis of NMDs achieves an increased diagnostic rate and provided pathogenic status information, which is not easily accessible through exome analysis.

Stress Dissipation Encoded Silk Fibroin Electrode for the Athlete-Beneficial Silk Bioelectronics.

The kinetic body motions have guided the core-shell fabrics of wearable bioelectronics to be elastoplastic. However, the polymeric electrodes follow the trade-off relationship between toughness and stretchability. To this end, the stress dissipation encoded silk fibroin electrode is proposed as the core electrode of wearable bioelectronics. Significantly, the high degree of intrinsic stress dissipation is realized via an amino acid crosslink. The canonical phenolic amino acid (i.e., tyrosine) of silk fibroin is engineered to bridge the secondary structures. A sufficient crosslink network is constructed when tyrosine is exposed near the amorphous strand. The stress dissipative tyrosine crosslink affords 12.5-fold increments of toughness (4.72 to 58.9 MJ m-3 ) and implements the elastoplastic silk fibroin. The harmony of elastoplastic core electrodes with shell fabrics enables the wearable bioelectronics to employ mechanical performance (elastoplasticity of 750 MJ m-3 ) and stable electrical response. The proposed wearable is capable of assisting the effective workouts via triboelectricity. In principle, active mobility with suggested wearables potentially relieves muscular fatigues and severe injuries during daily fitness.

Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samples.

PURPOSE: Ulcerative colitis (UC) is known to have an association with the increased risk of colorectal cancer (CRC), and UC-associated CRC does not follow the typical progress pattern of adenoma-carcinoma. The aim of this study is to investigate molecular characteristics of UC-associated CRC and further our understanding of the association between UC and CRC. METHODS: From 5 patients with UC-associated CRC, matched normal, dysplasia, and tumor specimens were obtained from formalin-fixed paraffin-embedded (FFPE) samples for analysis. Genomic DNA was extracted and whole exome sequencing was conducted to identify somatic variations in dysplasia and tumor samples. Statistical analysis was performed to identify somatic variations with significantly higher frequencies in dysplasia-initiated tumors, and their relevant functions were investigated. RESULTS: Total of 104 tumor mutation genes were identified with higher mutation frequencies in dysplasia-initiated tumors. Four of the 5 dysplasia-initiated tumors (80.0%) have TP53 mutations with frequent stop-gain mutations that were originated from matched dysplasia. APC and KRAS are known to be frequently mutated in general CRC, while none of the 5 patients have APC or KRAS mutation in their dysplasia and tumor samples. Glycoproteins including mucins were also frequently mutated in dysplasia-initiated tumors. CONCLUSION: UC-associated CRC tumors have distinct mutational characteristics compared to typical adenoma-carcinoma tumors and may have different cancer-driving molecular mechanisms that are initiated from earlier dysplasia status.

Determining the etiology of small bowel obstruction in patients without intraabdominal operative history: a retrospective study.

PURPOSE: Most of the causes of small bowel obstruction (SBO) in patients without a history of abdominal surgery are unclear at initial assessment. This study was conducted to identify the etiology and clinical characteristics of SBO in virgin abdomens and discuss the proper management. METHODS: A retrospective review involving operative cases of SBO from a single institute, which had no history of abdominal surgery, was conducted between January 2010 and December 2020. Clinical information, including radiological, operative, and pathologic findings, was investigated to determine the etiology of SBO. RESULTS: A total of 55 patients were included in this study, with a median age of 57 years and male sex (63.6%) constituting the majority. The most frequently reported symptoms were abdominal pain and nausea or vomiting. Neoplasm as an underlying cause accounted for 34.5% of the cases, of which 25.5% were malignant cases. In patients aged ≥60 years (n=23), small bowel neoplasms were the underlying cause in 12 (52.2%), of whom 9 (39.1%) were malignant cases. Adhesions and Crohn disease were more frequent in patients aged <60 years. Coherence between preoperative computed tomography scans and intraoperative findings was found in 63.6% of the cases. CONCLUSION: There were various causes of surgical cases of SBO in virgin abdomens. In older patients, hidden malignancy should be considered as a possible cause of SBO in a virgin abdomen. Patients with symptoms of recurrent bowel obstruction who have no history of prior abdominal surgery require thorough medical history and close follow-up.