Autosomal Recessive Spastic Paraplegia and Psychomotor Retardation With or Without Seizures: A Case Report From Saudi Arabia.

Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) is a rare neurodevelopmental disorder associated with autosomal recessive mutations in the HACE1 gene. This case report presents the clinical features and genetic analysis of an 11-month-old girl and her sister with SPPRS, making it the third reported case in the Middle East and the second in Saudi Arabia. The patient exhibited hypotonia, global developmental delay, speech delay, swallowing difficulties, and recurrent respiratory infections. A homozygous pathogenic variant in the HACE1 gene (p.R664*) was identified through genetic analysis, confirming the diagnosis of SPPRS. This case report emphasizes the importance of considering variations in clinical presentation, especially in rare disorders where only a few cases are reported. Further research and case studies are needed to better understand the complete phenotypic spectrum of SPPRS and its complications.

Knowledge and Attitude Toward Otitis Externa: A Saudi Arabian Perspective.

Objectives: This study intended to assess the level of awareness and attitude toward otitis externa (OE) and specific limitations that counter the attempts to uplift the understanding and notion related to OE among the general population of Saudi Arabia. Methods: A cross-sectional quantitative study using a questionnaire was done via Google Forms between May 2023 and July 2023. The scoring method was used to determine the participant's awareness or attitude; participants who scored >50% were considered aware or to have a good attitude. Results: Approximately 52.2% had a good attitude toward the OE, and majority were willing to visit healthcare professionals (81%) to provide care and receive proper education during office visits (80.1%). Of all the participants, 69%, 33.4%, and 30.8% suggested that a lack of awareness, cost, and health insurance, respectively, might prevent patients from seeking a healthcare professional. Only 10.9% of participants demonstrated good awareness (score >13) of outer ear inflammation. Conclusion: The findings indicate a poor level of awareness regarding OE, and a positive attitude toward seeking healthcare, with the majority recommending professional visits and relying on healthcare professionals for information.

Normal sonographic measurements for kidney dimensions in Saudi adult population: A cross-sectional prospective study.

BACKGROUND: The use of ultrasound-based measurements to determine renal size has proven valuable in the diagnosis of renal function and associated disorders. The dimensions of the abdominal organs are affected by an individual's body age, height, sex, and weight. The objective of this study was to establish the standard sonographic parameters for renal dimensions and to determine the correlation between body measurements and renal dimensions in a population of healthy adults residing in Jazan City, Saudi Arabia. METHODS: The present study was a prospective study conducted at a single center located in Jazan City from February to August 2022. Ninety-five participants underwent abdominal ultrasonography. The process of measuring renal size through sonography entails the measurement of various dimensions of the kidney, such as renal length, width, and thickness. The demographic information of the participants, including their sex, age, height, and weight, was documented. All analyses were performed using Statistical Package for the Social Sciences v27 software. RESULTS: The dimensions of the right kidney, specifically the length, width, and thickness, had mean value of 9.79 centimeters (cm), 5.09 cm, and 4.10 cm, respectively. The left kidney had mean dimensions of 10.1 cm, 5.09 cm, and 4.10 cm for length, width, and thickness, respectively. The left kidney was larger than the right kidney. Furthermore, male participants exhibited larger kidney measurements than their female counterparts did. A noteworthy positive correlation was observed between the thickness of the left kidney and sex, whereas no significant correlations were found with age, weight, or height. CONCLUSION: The current study revealed that the kidney dimensions were observed to be larger in males as compared to females. The research findings indicate that there is no significant correlation between kidney dimensions and various demographic factors, such as age, height, weight, and sex. In addition, this study provides reference tables for further use.

Binding selectivity analysis of new delhi metallo-beta-lactamase-1 inhibitors using molecular dynamics simulations: Exploring possibilities for decoding antimicrobial drug resistance.

BACKGROUND: New Delhi metallo-beta-lactamase-1 (NDM1) confers resistance to several bacterial species against a broad range of beta-lactam antibiotics and turning them into superbugs that pose a significant threat to healthcare systems worldwide. As such, it is a potentially relevant biological target for counteracting bacterial infections. Given the lack of effective treatment options against NDM1 producing bacteria, finding a reliable inhibitor for the NDM1 enzyme is crucial. METHODS: Using molecular dynamics simulations, the binding selectivities and affinities of three ligands, viz. PNK, 3S0, and N1G were investigated against NDM1. RESULTS: The results indicate that N1G binds with more affinity to NDM1 than PNK and 3S0. The binding energy decomposition analysis revealed that residues I35, W93, H189, K211, and N220 showed significant binding energies with PNK, 3S0, and N1G, and hence are crucially involved in the binding of the ligands to NDM1. Molecular dynamics trajectory analysis further elicited that the ligands influence dynamic flexibility of NDM1 morphology, which contributes to the partial selectivities of PNK, 3S0, and N1G. CONCLUSIONS: This in silico study offers a vital information for developing potential NDM1 inhibitors with high selectivity. Nevertheless, in vitro and in vivo experimental validation is mandated to extend the possible applications of these ligands as NDM1 inhibitors that succor in combating antimicrobial resistance.

Retrocaval Ureter With Ureteric Stones: A Case Report.

The retrocaval ureter is an uncommon anomaly where the ureter passes behind the inferior vena cava. Open surgery had been the gold standard for treatment. We are presenting a case of the retrocaval ureter with ureteral calculi, which was effectively managed by open surgery. A 27-year-old male presented with a nine-month history of flank pain. He had no history of chronic illnesses. Physical examinations and laboratory findings were within normal. A computed tomography (CT) scan was done to confirm the diagnosis of retrocaval ureter with ureteral stones. The subcostal incision was made. Then, the proximal and lower ureter was transected at the point where it went retrocaval. The stones were extracted; then, watertight anastomosis was done. Ultrasound used for the follow-up of the patient for six months showed no hydronephrosis. Retrocaval ureteral may have no symptoms or be linked to nonspecific symptoms. The diagnosis of the retrocaval ureter is frequently delayed. Surgical management is utilized in the majority of cases.

Knowledge, Attitude, Motivators, and Barriers to Blood Donation Among Adults in Al-Qunfudah Governorate, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Blood transfusion is one of the most important aspects of managing patients with a variety of medical disorders like thalassemia and sickle cell anemia. Despite this fact, many Saudis hesitate to donate blood and do not know whether blood banks need blood. OBJECTIVES: To evaluate the knowledge, attitude, motivators, and barriers to blood donation among adults in Al-Qunfudah governorate, Saudi Arabia. METHODS: A descriptive cross-sectional study was performed on a convenience sample of 416 adults living in Al-Qunfudah governorate and its dependence, using an online self-administered questionnaire. The obtained data were analyzed statistically using SPSS version 21 (IBM Corp., Armonk, New York, USA). RESULTS: Among 416 respondents, exactly 232 (55.8%) had overall good knowledge regarding blood donation, and 334 (80.3%) positively perceived it. The best knowledge about blood donation was detected among those aged 21-24 years (p = 0.012), males (p = 0.008), university-educated (p = 0.048), having a government job (p = 0.001), and having a history of donating blood (p = 0.001). The motivators included religious motives (88.2%, n = 367), feelings of self-satisfaction (63.2%, n = 263), and restoring blood circulation (56.7%, n = 236). Barriers to blood donation were fear of being infected (27.6%, n = 115), needle phobia (23.6%, n = 98), fear of general weakness (22.8%, n = 95), didn't know how to donate (16.8%, n = 70), and fear of seeing blood (13.2%, n = 55). CONCLUSION: Although adults in the Al-Qunfudah governorate of Saudi Arabia had positive attitudes toward blood donation, they possessed inadequate knowledge about it. Being younger, male, university-educated, having government jobs, and having a past history of donating blood were factors associated with good knowledge of blood donation. The most common motivators were religious, financial, and maintaining health. However, fear of infection, needle sticks, fear of pain, and hemophobia were the recorded barriers. Public health education is recommended to tackle public concerns regarding blood donation and present its benefits.

Utilizing Artificial Intelligence Among Patients With Diabetes: A Systematic Review and Meta-Analysis.

Diabetes mellitus, a condition characterized by dysregulation of blood glucose levels, poses significant health challenges globally. This meta-analysis and systematic review aimed to evaluate the effectiveness of artificial intelligence (AI) in managing diabetes, underpinned by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review scrutinized articles published between January 2019 and February 2024, sourced from six electronic databases: Web of Science, Google Scholar, PubMed, Cochrane Library, EMBASE, and MEDLINE, using keywords such as "Artificial intelligence use in medicine, Diabetes management, Health technology, Machine learning, Diabetic patients, AI applications, and Health informatics." The analysis revealed a notable variance in the prevalence of diabetes symptoms between patients managed with AI models and those receiving standard treatments or other machine learning models, with a risk ratio (RR) of 0.98 (95% CI: 0.88-1.08, I2 = 0%). Sub-group analyses, focusing on symptom detection and management, consistently showed outcomes favoring AI interventions, with RRs of 0.97 (95% CI: 0.87-1.08, I2 = 0%) for symptom detection and 0.97 (95% CI: 0.56-1.57, I2 = 0%) for management, respectively. The findings underscore the potential of AI in enhancing diabetes care, particularly in early disease detection and personalized lifestyle recommendations, addressing the significant health risks associated with diabetes, including increased morbidity and mortality. This study highlights the promising role of AI in revolutionizing diabetes management, advocating for its expanded use in healthcare settings to improve patient outcomes and optimize treatment efficacy.

Malaria during COVID-19 Travel Restrictions in Makkah, Saudi Arabia.

Malaria is a parasitic infection that may result in an acute, life-threatening illness. It is a major public health problem in the tropical world. The disease is caused by the parasites of the genus Plasmodium and is transmitted by female Anopheles mosquitoes. Saudi Arabia is in the elimination phase of malaria control. Several parts of Saudi Arabia report cases of imported malaria among travelers and visitors. The city of Makkah in Saudi Arabia has a population of about 2.3 million. Moreover, over 6 million religious visitors from different parts of the world visit Makkah annually. During the COVID-19 outbreak, travel restrictions were enforced in Makkah to contain the spread of COVID-19. We compare the total reported cases of malaria in Makkah before, during, and after COVID-19 travel restrictions in this retrospective cross-sectional study. Data on demographics, clinical data, and laboratory parameters were collected from the medical records of the Ministry of Health, Saudi Arabia. The annual malaria incidence rates in Makkah were 29.13/million people (2018), 37.82/million people (2019), 15.65/million people (2020), 12.61/million people (2021), and 48.69/million people (2022). Most of the malaria cases in Makkah were caused by Plasmodium falciparum, followed by P. vivax. Sudan, Nigeria, Yamen, Pakistan, and India are the top five countries contributing to malaria cases in Makkah. Weekly malaria case analyses revealed that COVID-19-related travel restrictions resulted in zero malaria cases in Makkah, indicating the magnitude of the travel-related malaria burden in the city.

UHRF1 poly-auto-ubiquitination induced by the anti-cancer drug, thymoquinone, is involved in the DNA repair machinery recruitment.

DNA methylation is one of the most important epigenetic mark involved in many physiologic cellular processes and pathologies. During mitosis, the transmission of DNA methylation patterns from a mother to the daughter cells is ensured through the action of the Ubiquitin-like, containing PHD and RING domains, 1/DNA methyltransferase 1 (UHRF1/DNMT1) tandem. UHRF1 is involved in the silencing of many tumor suppressor genes (TSGs) via mechanisms that remain largely to be deciphered. The present study investigated the role and the regulation of UHRF1 poly-ubiquitination induced by thymoquinone, a natural anti-cancer drug, known to enhance or re-activate the expression of TSGs. We found that the auto-ubiquitination of UHRF1, induced by TQ, is mediated by reactive oxygen species, and occurs following DNA damage. We demonstrated that the poly-ubiquitinated form of UHRF1 is K63-linked and can still silence the tumor suppressor gene p16INK4A/CDKN2A. We further showed that TQ-induced auto-ubiquitination is mediated via the activity of Tip60. Since this latter is known as a nuclear receptor co-factor, we investigated if the glucocorticoid receptor (GR) might be involved in the regulation of UHRF1 ubiquitination. Activation of the GR, with dexamethasone, did not influence auto-ubiquitination of UHRF1. However, we could observe that TQ induced a K48-linked poly-ubiquitination of GR, probably involved in the proteosomal degradation pathway. Mass-spectrometry analysis of FLAG-HA-tagged UHRF1 identified UHRF1 partners involved in DNA repair and showed that TQ increased their association with UHRF1, suggesting that poly-ubiquitination of UHRF1 is involved in the DNA repair process. We propose that poly-ubiquitination of UHRF1 serves as a scaffold to recruit the DNA repair machinery at DNA damage sites.

A Selective Gas Chromatography-Tandem Mass Spectrometry Method for Quantitation of Ethylene and Diethylene Glycol in Paediatric Syrups.

Ethylene Glycol (EG) and diethylene Glycol (DEG) are two contaminants known to cause various human health problems. These glycols might be present in drug syrups that are based on glycerol, sorbitol, or polyethylene glycol. In late 2022, several batches of cough, antipyretics, and antihistamine syrups were reported to contain toxic levels of EG and DEG in multiple countries; this incident concerned the World Health Organization (WHO). From an analytical perspective, several methods of glycols analysis in pharmaceuticals have been reported in the literature, with the majority being dedicated to raw material analysis. This study aims to develop a selective method capable of evaluating a wide range of paediatric syrups in order to assess the safety of commercially available paediatric syrups currently distributed in the local market. This research introduces a method for determining glycols utilizing gas chromatography-tandem mass spectrometry (GC-MS/MS), which offers significantly higher selectivity than conventional single quadrupole gas chromatography-mass spectrometry (GC-MS). The developed method meets the current International Council for Harmonisation (ICH) guidelines for validation. The absence of any interfering peaks in both the unspiked sample of promethazine syrup and the reference standard solutions proved the method's selectivity. Furthermore, 2,2,2-trichloroethanol was used as an internal standard, and a new GC-MS/MS method was developed to analyze it. The calibration curves for EG and DEG were linear within the selected concentration range of 1-10 µg/mL. The detection limit for both EG and DEG was 400 ng/mL, while the quantification limit was 1 µg/mL. Recovery values for both EG and DEG met the accuracy acceptance criterion. Thus, the developed method proved to be efficient and accurate for determining EG and DEG levels in suspected contaminated syrups.

The role of molecular imaging in detecting fibrosis in Crohn's disease.

Fibrosis is a pathological process that occurs due to chronic inflammation, leading to the proliferation of fibroblasts and the excessive deposition of extracellular matrix (ECM). The process of long-term fibrosis initiates with tissue hypofunction and progressively culminates in the ultimate manifestation of organ failure. Intestinal fibrosis is a significant complication of Crohn's disease (CD) that can result in persistent luminal narrowing and strictures, which are difficult to reverse. In recent years, there have been significant advances in our understanding of the cellular and molecular mechanisms underlying intestinal fibrosis in inflammatory bowel disease (IBD). Significant progress has been achieved in the fields of pathogenesis, diagnosis, and management of intestinal fibrosis in the last few years. A significant amount of research has also been conducted in the field of biomarkers for the prediction or detection of intestinal fibrosis, including novel cross-sectional imaging modalities such as positron emission tomography (PET) and single photon emission computed tomography (SPECT). Molecular imaging represents a promising biomedical approach that enables the non-invasive visualization of cellular and subcellular processes. Molecular imaging has the potential to be employed for early detection, disease staging, and prognostication in addition to assessing disease activity and treatment response in IBD. Molecular imaging methods also have a potential role to enabling minimally invasive assessment of intestinal fibrosis. This review discusses the role of molecular imaging in combination of AI in detecting CD fibrosis.

Bidirectional glenn surgery without palliative pulmonary artery banding in univentricular heart with unrestricted pulmonary flow. Retrospective multicenter experience.

BACKGROUND: Although pulmonary artery banding (PAB) has been generally acknowledged as an initial palliative treatment for patients having single ventricle (SV) physiology and unrestrictive pulmonary blood flow (UPBF), it may result in unfavorable outcomes. Performing bidirectional Glenn (BDG) surgery without initial PAB in some selected cases may avoid the complications associated with PAB and reduce the number of operative procedures for these patients. This research aimed to assess the outcome of BDG surgery performed directly without doing initial PAB in patients with SV-UPBF. METHODS: This Multicenter retrospective cohort includes all patients with SV-UPBF who had BDG surgery. Patients were separated into two groups. Patients in Group 1 included patients who survived till they received BDG (20 Patients) after initial PAB (28 patients), whereas patients in Group 2 got direct BDG surgery without first performing PAB (16 patients). Cardiac catheterization was done for all patients before BDG surgery. Patients with indexed pulmonary vascular resistance (PVRi) ≥ 5 WU.m2 at baseline or > 3 WU.m2 after vasoreactivity testing were excluded. RESULTS: Compared with patients who had direct BDG surgery, PAB patients had a higher cumulative mortality rate (32% vs. 0%, P = 0.016), with eight deaths after PAB and one mortality after BDG. There were no statistically significant differences between the patient groups who underwent BDG surgery regarding pulmonary vascular resistance, pulmonary artery pressure, postoperative usage of sildenafil or nitric oxide, intensive care unit stay, or hospital stay after BDG surgery. However, the cumulative durations in the intensive care unit (ICU) and hospital were more prolonged in patients with BDG after PAB (P = 0.003, P = 0.001respectively). CONCLUSION: Direct BDG surgery without the first PAB is related to improved survival and shorter hospital stays in some selected SV-UPBF patients.

Modulation of the crosstalk between Keap1/Nrf2/HO-1 and NF-κB signaling pathways by Tomatidine protects against inflammation/oxidative stress-driven fulminant hepatic failure in mice.

Fulminant hepatic failure (FHF) is the terminal phase of acute liver injury, which is characterized by massive hepatocyte necrosis and rapid hepatic dysfunction in patients without preexisting liver disease. There are currently no therapeutic options for such a life-threatening hepatic failure except liver transplantation; therefore, the terminal phase of the underlying acute liver injury should be avoided. Tomatidine (TOM), asteroidal alkaloid, may have different biological activities, including antioxidant and anti-inflammatory effects. Herein, the lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced FHF mouse model was established to explore the protective potential of TOM and the underlying mechanisms of action. TOM pretreatment significantly inhibited hepatocyte necrosis and decreased serum aminotransferase activities in LPS/D-GalN-stimulated mice. TOM further increased the level of different antioxidant enzymes while reducing lipid peroxidation biomarkers in the liver. These beneficial effects of TOM were shown to be associated with targeting of NF-κB signaling pathways, where TOM repressed NF-κB activation and decreased LPS/D-GalN-induced TNF-α, IL-6, IL-1ß, and iNOS production. Moreover, TOM prevented LPS/D-GalN-induced upregulation of Keap1 expression and downregulation of Nrf2 and HO-1 expression, leading to increased Nrf2-binding activity and HO-1 levels. Besides, TOM pretreatment repressed LPS/D-GalN-induced upregulation of proliferating cell nuclear antigen (PCNA) expression, which spared the hepatocytes from damage and subsequent repair following the LPS/D-GalN challenge. Collectively, our findings revealed that TOM has a protective effect on LPS/D-GalN-induced FHF in mice, showing powerful antioxidant and anti-inflammatory effects, primarily mediated via modulating Keap1/Nrf2/HO-1 and NF-κB/TNF-α/IL-6/IL-1ß/iNOS signaling pathways.

Exploration of comprehensive marine natural products database against dengue viral non-structural protein 1 using high-throughput computational studies.

Dengue virus (DENV) non-structural protein 1 (NS1) is a versatile quasi-protein essential for the multiplication of the virus. This study applied high-throughput virtual screening (HTVS) and molecular dynamics (MD) simulation to detect the potential marine natural compounds against the NS1 of DENV. The structure of the NS1 protein was retrieved from Protein Data Bank with (PDB ID: 4O6B). Missing residues were added using modeler software. Molecular operating environment (MOE) programme was used to prepare the protein before docking. Virtual screening was performed on PyRx software to identify natural compounds retrieved from Comprehensive Marine Natural Products Database (CMNPD) against the NS1 protein, and best-docked compounds were examined by molecular docking and molecular dynamic (MD) simulation. Out of 31,561 marine compounds, the top 10 compounds showed docking scores lesser than -8.0 kcal/mol. One of the best hit compounds, CMNPD6802, was further analyzed using MD simulation study at 100 nanoseconds and Molecular Mechanics with Generalized Born and Surface Area Solvation (MM/GBSA). Based on its total binding energy, determined using the MM/GBSA approach, CMNPD6802 was ranked first. Its pharmacokinetic properties concerning the target protein NS1 were also evaluated. The results of the MD simulation showed that CMNPD6802 remained in close contact with the protein throughout the activation period, mapped using principal component analysis. These findings suggest that CMNPD6802 could serve as an NS1 inhibitor and may be a potential candidate for treating DENV infections.Communicated by Ramaswamy H. Sarma.

Development of a highly sensitive fluorescent probe using Delonix regia (Gulmohar) tree pod shell for precise sarcosine detection in human urine samples: advancing prostate cancer diagnosis.

We designed a highly sensitive fluorescent sensor for the early detection of sarcosine, a potential biomarker for prostate cancer. This sensor was based on surface-cobalt-doped fluorescent carbon quantum dots (Co-CD) using a FRET-based photoluminescent sensing platform. Blue luminescent carbon quantum dots (CQD) were synthesised through a hydrothermal approach, utilizing Delonix regia tree pod shells. Cobalt was employed to functionalize the CQD, enhancing the quantum-entrapped effects and minimizing surface flaws. To optimize Co-CD preparation, we employed a Box-Behnken design (BBD), and response surface methodology (RSM) based on single-factor experiments. The Co-CD was then used as a fluorescent probe for selective Cu2+ detection, with Cu2+ quenching Co-CD fluorescence through an energy transfer process, referred to as 'turn-off'. When sarcosine was introduced, the fluorescence intensity of Co-CD was restored, creating a 'turn-on' response. The sensor exhibited a Cu2+ detection limit (LOD) of 2.4 µM with a linear range of 0 µM to 10 µM. The sarcosine detection in phosphate buffer saline (PBS, pH 7.4) resulted in an LOD of 1.54 µM and a linear range of 0 to 10 µM. Importantly, the sensor demonstrated its suitability for clinical analysis by detecting sarcosine in human urine. In summary, our rapid and highly sensitive sensor offers a novel approach for the detection of sarcosine in real samples, facilitating early prostate cancer diagnosis.Communicated by Ramaswamy H. Sarma.

Sonographic Assessment of Renal Transplantation in Adult Saudi Patients: A Cross-Sectional Retrospective Study.

Kidney transplantation stands as a practical and cost-effective treatment option for end-stage renal disease patients, offering an improved quality of life with reduced morbidity when compared with hemodialysis. To evaluate the status of transplanted kidneys in Saudi patients, we conducted a retrospective single-center study at Jazan, Saudi Arabia, involving 46 adult renal recipients enrolled randomly from 2015 to December 2022. Using high-frequency ultrasound, we performed Duplex ultrasound examinations to assess renal allografts. The study revealed that the renal grafts exhibited normal length, with preserved cortical medullary differentiation (CMD) in 84.8% of cases and poor CMD in 15.2%. The echogenicity of the grafts remained normal in 69.6% of instances. Interestingly, we observed a significant rise in resistance index values as the graft duration increased (P = .04), whereas patients with abnormal creatinine levels displayed decreased peak systolic velocity and end-diastolic velocity. Notably, sonographic graft assessments unveiled complications, including perinephric fluid accumulation (8.7%), simple renal cysts (10.86%), hydronephrosis (8.7%), and one case of graft rejection. Receiver operating characteristics analysis for serum blood creatinine levels and abnormal parenchymal findings yielded fair to poor predictive accuracy, with varying sensitivity and specificity measures that lacked statistical significance. In conclusion, our study revealed that most Saudi renal transplant recipients exhibited grafts with normal echogenicity, preserved CMD, and limited perinephric fluid. This investigation provides valuable insights into sonographic changes and Doppler parameters of renal grafts, potentially aiding in the early detection of graft rejection and facilitating diagnostic and therapeutic planning.

Retraction: Intussusception in Adults: A Rare Etiology of Small Intestinal Obstruction.

[This retracts the article DOI: 10.7759/cureus.20502.].

Retraction: Mesenteric Panniculitis and COVID-19: A Rare Association.

[This retracts the article DOI: 10.7759/cureus.21314.].

Retraction: Urachal Abscess: A Rare Etiology of Acute Abdominal Pain in Adults.

[This retracts the article DOI: 10.7759/cureus.18193.].