Sinefungin analogs targeting VP39 methyltransferase as potential anti-monkeypox therapeutics: a multi-step computational approach.

The increasing spread of the Monkeypox virus (MPXV) presents a significant public health challenge, emphasising the urgent requirement for effective treatments. Our study focuses on the VP39 Methyltransferase enzyme of MPXV as a critical target for therapy. By utilising virtual screening, we investigated natural compounds with structural similarities to sinefungin, a broad-acting MTase inhibitor. From an initial set of 177 compounds, we identified three promising compounds-CNP0346326, CNP0343532, and CNP008361, whose binding scores were notably close to that of sinefungin. These candidates bonded strongly to the VP39 enzyme, hinting at a notable potential to impede the virus. Our rigorous computational assays, including re-docking, extended molecular dynamics simulations, and energetics analyses, validate the robustness of these interactions. The data paint a promising picture of these natural compounds as front-runners in the ongoing race to develop MPXV therapeutics and set the stage for subsequent empirical trials to refine these discoveries into actionable medical interventions.

Comparison of color changes, fracture strengths, and failure modes of conventional endocrowns and endocrowns with different design modifications.

BACKGROUND: Endocrowns (ECs) are alternatives for rebuilding severely damaged teeth and show superior efficacy in molars over premolars. OBJECTIVE: The objective of this in vitro study is to evaluate the effects of different preparation designs with short pulp chambers on the mean color change (Δ⁢E), fracture resistance, and failure types of mandibular molar ECs. METHOD: A total of 40 extracted mandibular molars were treated endodontically and divided into four groups. Samples in groups 1, 2, 3, and 4 had occlusal preparation depths of 5 mm, 3 mm, 3 mm with ferrule, and 3 mm with boxes, respectively. The samples were immersed in coffee and their Δ⁢E values were measured by using the Commission Internationale de l'Eclairage color system. They were also subjected to a fracture test. Next, all specimens were examined visually under a stereomicroscope to evaluate their failure modes and identify their fracture origins. Data were entered and analyzed by using Statistical Package for Social Sciences. RESULTS: Among all groups, group 4 (3 mm + boxes) presented the highest Δ⁢E (4.15) after immersion in coffee. Moreover, ANOVA revealed that the Δ⁢E of group 4 (occlusal preparation depth of 3 mm with boxes) was significantly different (p< 0.05) from that of group 2 (3 mm + ferrule, 3.07). The EC with a 3 mm chamfer and ferrule showed the highest maximum load of 2847.68 ± 693.27 N, whereas that with a 5 mm chamfer finish line had a marginally reduced load at fracture of 2831.52 ± 881.83 N. The EC with a 3 mm chamber and boxes had a slightly increased maximum load of 2700.75 ± 436.40 N, whereas that with the 3 mm chamber had the lowest maximum load at fracture of 2385.97 ± 465.61 N. One-way ANOVA showed that different EC preparation designs had no effect on maximum fracture load (F [3,16] = 0.550, p= 0.6). CONCLUSION: The recorded Δ⁢E values of ECs in all groups were equal or marginally higher than the acceptable values. The EC with a 3 mm chamfer and ferrule displayed the highest mean maximum load. The EC with a 5 mm chamfer finish line had a marginally lower maximum load at fracture than other ECs. Failures, such as ceramic fracture, split fracture, and ceramic and tooth splitting above the cemento-enamel junction (CEJ) or vertically were predominant in samples with occlusal preparation depths of 3 mm with ferrule and 5 mm.

Radiographic Assessment of 121 Glass Fiber Post Procedures in 32 Patients Aged 21-60 Years Performed by 6th-Year Dental Students During the 2022-2023 Academic Year at the College of Dentistry, Jazan University, Saudi Arabia.

BACKGROUND The restoration of endodontically treated teeth (ETT) and severely damaged teeth has been a concern of clinicians. Glass Fiber Post (GFPs) combine the strength of carbon fiber posts with the esthetic appearance of glass to resemble natural dentin during dental restoration procedures. This radiographical study assessed the GFP carried out by students enrolled in the Clinical Comprehensive Course at the College of Dentistry, Jazan University. MATERIAL AND METHODS A total of 32 patients treated by 18 6th-year dental students with 121 GFPs were assessed in this cross-sectional radiographic study. The assessment covered tooth type, arch, post-to-root width, length of post in relation to the crown and root lengths, amount of remaining gutta percha (GP), and gap between GP and post. Data were analyzed using SPSS, and associations between variables were determined using the chi-square test. RESULTS Maxillary teeth were the most frequently restored with posts (88.4%) with most being (58.7%) anterior teeth, and 50.4% of posts had widths that were one-third that of the root. The percentage of posts was twice (71.1%) or equal to (26.4%) the crown length, whereas two-thirds of the tested GFPs were >5 mm of the remaining GP. Significant differences were observed in location and position of teeth with post width, post length in relation to crown or root length, and amount of remaining GP, with P values of 0.018, 0.000, and 0.001, respectively. CONCLUSIONS The assessed radiographs revealed that the performance of sixth year students in accomplishment GFP radiographically was satisfactory and within the values recommended in the literature.

Retraction: Isolated Superior Mesenteric Artery Dissection After Methamphetamine Use: A Rare Adverse Effect.

[This retracts the article DOI: 10.7759/cureus.19551.].

CASE FATALITY RATE OF CHILDHOOD TUBERCULOSIS: EXPERIENCE FROM FEDERAL TEACHING HOSPITAL GOMBE: A TWO DECADE REVIEW.

Introduction: Tuberculosis (TB) was the leading cause of death from an infectious agent worldwide, until the Coronavirus (COVID-19) pandemic, ranking above HIV/AIDS. Nigeria ranks 6th among the 30 TB high-burden countries (TB, TB/HIV, DRTB) and 1st in Africa. The estimated case fatality rate (CFR) of TB in Sub-Sahara Africa (SSA) is 15%. Objective: To review the Tuberculosis case fatality rate (TCFR) in children diagnosed with TB from 2000-2019 in Federal Teaching Hospital Gombe. Methodology: All cases of Tuberculosis (TB) diagnosed in children using ICD 10 classification were retrieved and analyzed. These included deaths from TB. The mainstay of TB diagnosis was clinical using TB Score (81%), Gene Xpert was 7%, and AFB was 10%. Results: 26,716 children were admitted; 383 had TB out of which 208(54.3%) were males and 175 (45.7%) females. TB constituted 1.4% of Paediatric admissions. Children 0 -5 years constituted 46.7% (179/383) of cases and 11 - 18 years were 31.3% (120/383). Fulani, Hausa, and Tangale constituted 43.6% (167), 21.1% (81), and 6.8% (26) of TB cases respectively. TB admissions were highest between 2015 and 2019 (31.8%). TB adenitis was the most common extrapulmonary TB. Tuberculosis/HIV co-infection accounted for 103(27%), out of which 74% (44) died. Overall TCFR was 15.6%; TCFR was 16.3% in males and 14.8% in females. The TCFR was 46.7% in 0-5yrs; 15% in 6-9yrs and 38.3% in 10-18yrs.Fulani had the highest CFR (11.9%). Tuberculosis CFR was highest between 2010-2014 (30.0%) and lowest in 2005-2009 (21.6%). Conclusion: The Tuberculosis CFR is comparable to SSA CFR.

REVEALING THE VARIED REALITY OF MALARIA-RELATED DEATHS IN CHILDREN ACROSS GENDER, AGE, AND ETHNICITY IN FEDERAL TEACHING HOSPITAL GOMBE OVER 20 YEARS: AN ESSENTIAL EPIDEMIOLOGIC IMPERATIVE.

Introduction: Nigeria recorded 31% of 619,000 malaria deaths globally and accounts for 25-30% of all childhood mortality in the country. Few studies in Nigeria, have reported malaria's case fatality rate over a long period. Objective: To determine Malaria Case Fatality Rate among Children admitted from 2000-2019. Methodology: All severe malaria cases and deaths amongst children aged 0-18 over the last two decades were analysed using ICD-10. The diagnosis was based on clinical and microscopic findings. Results: 26,716 children were admitted, 2494 (9.3%) were diagnosed with malaria and 209 died. Malaria constituted 5.3% (209/3956) of all childhood mortality. Males constituted 58.9 % (1468/2494) while 65% (1642/2494) were aged 0-5 years. Of the malaria admissions, Fulani and Hausa constituted 948(38%) and 438(17.6%) respectively. Admissions were highest in October (15%) and in 2012 (9.6%). The overall malaria CFR was 8.3%; 8.8% in Females (91/1026) and 8.03% in Males P-value <0.05 (X2=54.735); 8.6% in children aged 0-5years, 8.2% in 6-10 years and 7.4% in 11-18 years, P-value <0.05 (X2=893.164). CFR was highest in April (11.4%)and lowest in November (5.2%). Kanuri and Igbo had CFR of 70% and 38.4% respectively while it was lowest in Tera tribe (4.3%), P-value<0.05. The CFR was highest in the year 2004 (22%), 3.5% in 2000 and 2006. Over the years, case fatality rate was 15.9% between 2000-2004, 6.1% from 2005-2009. Between 2010-2015, it was 7.3% and 8.5% from 2016-2019. Conclusion: This study revealed the deadly reality of severe malaria with increased CFR among females, aged 0-5 and the Kanuri tribe.

EPIDEMIOLOGIC TREND AND CASE FATALITY OF CHILDHOOD TETANUS IN FEDERAL TEACHING HOSPITAL GOMBE; A 20YEARS REVIEW.

Introduction: Tetanus is a vaccine-preventable disease, it remains a significant cause of morbidity and mortality in both neonatal and post-neonatal periods, especially in developing countries with limited health facilities and inadequate vaccination. The overall case fatality rate (CFR) is 13.2% globally, highest in the neonatal period and in sub-Saharan Africa. CFR is 64%, 47%, and 43% in Nigeria, Uganda, and Tanzania respectively. Objectives: To determine the Case Fatality Rate of Childhood tetanus in FTHG from 2000-2019. Methodology: All cases and deaths from tetanus amongst children aged 0-18 years in paediatric medical ward of FTHG over the last two decades diagnosed clinically and classified using ICD-10 were analysed. Results: 95 cases of tetanus out of 26,716 total admissions constituting 0.004%. There were 49 tetanus deaths out of 3956 total childhood deaths (0.012%) over the study period. Males constituted 66% (63/95). 30% (28/95) were aged 0-28 days; 23.1% (22/95) were adolescents. Fulani and Hausa constituted 37% (34/95) and 31% (29/95) respectively. Admission was highest in the dry season 52% (50/95 %). The overall tetanus CFR was 51.6%; 78% of deaths were in males (38/49), 30% in neonates, and 23% in adolescents. CFR was highest during the dry season (67.3%). Hausa and Fulani had CFR of 51% and 40% respectively. P-value <0.05 The CFR was 88% between 2000-2004, 72% from 2005-2009, 71% between 2010-2014 and 33% from 2015-2019. Conclusion: Tetanus CFR is still high among neonates and adolescents. Maternal tetanus vaccine and booster doses in children need strengthening.

IN-PATIENT PNEUMONIA BURDEN AND CASE FATALITY RATES IN CHILDREN OVER TWO DECADES IN FEDERAL TEACHING HOSPITAL, GOMBE (FTHG).

Introduction: Pneumonia is the leading cause of death among children globally accounting for an estimated 1.2 million (18%) total deaths annually. The number of childhood-related deaths from pneumonia is approximately 2000-fold higher in developing than in developed countries. Nigeria contributes the highest of pneumonia-related deaths globally. Objectives: To determine the case fatality rates (CFR) of pneumonia from 2000-2019 in paediatric ward, FTHG. Methodology: All cases of pneumonia admissions and deaths in patients aged 0-18 years, using ICD-10 classification, were retrieved and analysed. The mainstay of diagnosis is clinical and/or radiographic features. Results: A total of 26,716 children were admitted during this period, 1151 had pneumonia (4.3%) and 118 died. Males constituted 647 (56.2%) and females 43.8% of the total pneumonia admissions. Children aged 0-5 years had the highest pneumonia admissions, followed by 6-9 years. Admissions were highest in the wet than the dry season. Pneumonia CFR was 10.2%; 10.9% in females and 9.7% in males. Under-5 constituted 84% (969/1151) of pneumonia admission with a CFR of 9.3%. CFR were 10.3% and 21% in 6-10 years, and 11-18 years respectively. The CFR between2000-2004 was 14.1%, 2005-2009:21.1%, 2010-2014:10.2% and 2015-2019:7.2%. Kanuri had the highest CFR of 56.2%.(P <0.05) Other ethnic groups were 29.4% in Waja, 25% in Tula, 21.4% in Igbo, 16.6% in Yoruba, 12.1% in Tangale, 10.2% in Hausa, 8.8%in Bolewa and 8.3% in Fulani. The CFR was highest in February20.2%. Conclusion: Pneumonia Case fatality is high.

Knowledge and Attitudes Regarding Clinical Trial Participation: A Cross-Sectional Study in the Eastern Province, Saudi Arabia.

Objective This study aims to assess the knowledge and attitudes toward clinical trial (CT) participation among the adult population in the Eastern Province of Saudi Arabia. Material and methods This cross-sectional study was conducted among the population of the Eastern Province of Saudi Arabia. A self-administered questionnaire was distributed among the general population using an online survey. Results A total of 334 participants completed the questionnaire. Participants' ages ranged from 18 to 65 years, with a mean age of 31.2 ± 13.9 years, 56.6% of whom were males, 42.2% were employed, 29.6% were students, and 23.1% were unemployed. Surprisingly, only a small percentage of respondents (7.5%) were requested to participate in a randomized controlled trial (RCT), of which the majority did partake. Additionally, 25.4% of participants believe CTs are used to evaluate new drugs; others believe that CTs are used to understand diseases and human behavior. The data show that most participants believe that CTs improve patient care, welfare, and society. Also, participants were more likely to take part if they were aware of the study's purpose and findings and were given more time to consider their options. Conclusion Participants believed that the biggest obstacle was a lack of knowledge of CTs. It is crucial to educate patients more about CTs. Multimodal strategies such as improved patient-provider communication and online information for trial information sharing may be effective in boosting knowledge and CT recruitment.

Comparative Analysis of Properties in Chairside Silicone Denture Liners versus Heat-Cured Molloplast-B: An In-Depth In Vitro Evaluation.

BACKGROUND We investigated the bond strength, tensile strength, and water absorption properties of 4 widely used chairside silicone long-term denture soft lining materials and compared properties with those of heat-cured silicone material. MATERIAL AND METHODS Four chairside materials (GC Reline Soft, Mucopren Soft, Sofreliner Soft, and Elite Soft Relining) and a heat-cured silicone material (Molloplast B) were investigated. For tensile and shear bond strength and tensile strength, samples were prepared according to the manufacturers' instructions and the testing machine used. For water absorption, IOS 1567 was followed to prepare specimens. Bond strengths were measured using a Lloyd Instruments materials testing machine. Ten specimens for each test were prepared for each soft liner, except for water absorption and solubility tests, for which only 5 specimens were prepared. ANOVA, Bonferroni, and Kruskal-Wallis tests were used to compare values of materials and assess changes over time. RESULTS There was strong evidence of differences in the properties between materials. GC Reline Soft showed comparable tensile bond (1.4±0.6 MPa), shear bond (1.1±0.4 MPa), tensile strength (5.44±0.98), water absorption (0.92±0.2 µg/mm³), and solubility values (0.3±0.2 µg/mm3) to that of Molloplast B (1.4±0.4; 1.6±0.5; 4.53±0.9 MPa, 1.7±0.3, and 1.0±0.3 µg/mm³, respectively). The water solubility of Sofreliner Soft was significantly lower (1.5±0.8 µg/mm³) than that of Molloplast B. CONCLUSIONS There were significant differences between some properties of 4 chairside denture soft lining materials and that of Molloplast B, which had higher shear and tensile bond strength than chairside denture silicone soft lining materials but had the highest water solubility.

Isolated Superior Mesenteric Artery Dissection After Methamphetamine Use: A Rare Adverse Effect.

Methamphetamine is the second most commonly abused drug worldwide. It is a sympathomimetic agent that works by inhibiting the reuptake of monoamine neurotransmitters, including dopamine, norepinephrine, and serotonin. Methamphetamine use is associated with early mortality, and cardiovascular complications are the leading cause of increased mortality. We discuss the case of a 41-year-old man who presented to the emergency department with a sudden abdominal pain of eight hours' duration. The pain was located in the epigastric area with radiation to the back. Upon examination, the patient appeared agitated and diaphoretic. His pupils were dilated bilaterally. His vital signs included tachycardia (120 bpm), tachypnea (24 bpm), hypertension (150/90 mmHg), and normal temperature (36.9 ℃). Abdominal examination revealed a soft and lax abdomen with no tenderness. His bowel sounds were normal. Given the physical signs, a toxicology screen was conducted and was positive for methamphetamine use. The patient reported that he used recreational drugs occasionally and admitted that the abdominal pain developed a few hours following methamphetamine use. The patient was treated with fluid resuscitation, analgesic, antihypertension medications, and anticoagulant therapy. The patient had significant improvement in his condition within 48 hours with complete resolution of the abdominal pain. Isolated superior mesenteric artery dissection is a very rare clinical condition. This case report highlights the importance of recognizing the cardiovascular adverse effects that may develop after methamphetamine use.

Rituximab as a single agent in the management of adult patients with haemophilia A and inhibitors: marked reduction in inhibitor level and clinical improvement in bleeding but failure to eradicate the inhibitor.

Management of patients with severe haemophilia A who develop inhibitors is difficult and expensive. Standard treatment of this complication is immune tolerance induction (ITI) therapy, but is successful in only 60-80% of the patients. Failure of ITI results in a higher risk of morbidity and mortality. We used rituximab, an anti-CD20 antibody, in three patients with severe haemophilia A and inhibitors. Two patients with high-titre inhibitors had marked reduction in the inhibitor level; the third patient with low-titre inhibitor had a disappearance of the inhibitor. All patients improved clinically, with fewer bleeding episodes and a better quality of life. Inhibitor level increased with time in these patients, but the clinical benefit continued in two patients with high-titre inhibitors initially, after a follow-up of 48 and 22 months. One of the patients with concomitant human immunodeficiency virus (HIV) infection and a very low CD4 lymphocyte count developed severe truncal herpes zoster after the third weekly dose of rituximab. Caution is required in such patients, and we recommend avoiding rituximab use in HIV-infected patients with very low CD4 lymphocyte count. In conclusion, rituximab is useful in reducing the inhibitor level with clinical benefit in patients with severe haemophilia A and inhibitors, but it cannot eradicate the inhibitors for long periods with the currently used protocol of up to five doses.