Effect of the Height of a 3D-Printed Model on the Force Transmission and Thickness of Thermoformed Orthodontic Aligners.

This research aims to investigate the influence of model height employed in the deep drawing of orthodontic aligner sheets on force transmission and aligner thickness. Forty aligner sheets (Zendura FLX) were thermoformed over four models of varying heights (15, 20, 25, and 30 mm). Normal contact force generated on the facial surface of the upper right central incisor (Tooth 11) was measured using pressure-sensitive films. Aligner thickness around Tooth 11 was measured at five points. A digital caliper and a micro-computed tomography (µ-CT) were employed for thickness measurements. The normal contact force exhibited an uneven distribution across the facial surface of Tooth 11. Model 15 displayed the highest force (88.9 ± 23.2 N), while Model 30 exhibited the lowest (45.7 ± 15.8 N). The force distribution was more favorable for bodily movement with Model 15. Thickness measurements revealed substantial thinning of the aligner after thermoforming. This thinning was most pronounced at the incisal edge (50% of the original thickness) and least at the gingivo-facial part (85%). Additionally, there was a progressive reduction in aligner thickness with increasing model height, which was most significant on the facial tooth surfaces. We conclude that the thermoplastic aligner sheets undergo substantial thinning during the thermoforming process, which becomes more pronounced as the height of the model increases. As a result, there is a decrease in both overall and localized force transmission, which could lead to increased tipping by the aligner and a diminished ability to achieve bodily movement.

Comparable antibody levels in heterologous and homologous mRNA COVID-19 vaccination, with superior neutralizing and IgA antibody responses in mRNA homologous boosting.

BACKGROUND: Priming with two doses of AZD1222 (Oxford-AstraZeneca; ChAd) followed by a third mRNA vaccine boosting is considered in several countries, yet comparisons between heterologous and homologous booster efficacy remain unexplored. AIM: To evaluate and contrast the immunogenicity of homologous and heterologous boosting regimens. METHOD: The study examined antibody responses in 1113 subjects, comprising 895 vaccine-naïve individuals across different vaccination strategies (partial, primary series, heterologous booster, homologous booster) and 218 unvaccinated, naturally infected individuals. Assessments included neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA levels. RESULTS: The study found mRNA vaccines to exhibit superior immunogenicity in primary series vaccination compared to ChAd, with mRNA-1273 significantly enhancing NTAbs, TAbs, anti-S-RBD IgG, and anti-S1 IgA levels (p < 0.001). Both booster types improved antibody levels beyond primary outcomes, with no significant difference in TAbs and anti-S-RBD IgG levels between regimens. However, homologous mRNA boosters significantly outperformed heterologous boosters in enhancing NTAbs and anti-S1 IgA levels, with the BNT/BNT/BNT regimen yielding particularly higher enhancements (p < 0.05). CONCLUSION: The study concludes that although TAbs and anti-S-RBD IgG antibody levels are similar for both regimens, homologous mRNA boosting outperform heterologous regimen by enhancing anti-S1 IgA and neutralizing antibody levels.

Normal cardiac dimensions by magnetic resonance imaging and topographic anatomy of the adult arabian one-humped camel (Camelus dromedarius).

BACKGROUND: Dromedaries' normal heart architecture and size have not been adequately examined utilizing magnetic resonance imaging (MRI) and topographic anatomy. RESULT: we aimed to investigate the regular appearance of the heart and its dimensions, using MRI and cross-sectional anatomy, in mature Arabian one-humped camels (Camelus dromedarius). We also analyzed hematological and cardiac biochemical markers. MRI scans were conducted on twelve camel heart cadavers using a closed 1.5-Tesla magnet with fast spin echo (FSE) weighted sequences. Subsequently, the hearts were cross-sectionally sliced. Additionally, hematobiochemical studies were conducted on ten mature live camels. The study analyzed standard cardiac dimensions including HL, BW, RA, LA, RV, LV, IVS, LAD, RAD, RVD, AoD, TCVD, and MVD. The results showed a strong positive correlation between the cardiac dimensions obtained from both gross analysis and MR images, with no significant difference between them. On both gross and MRI images, the usual structures of the heart were identified and labeled. Along with the cardiac markers (creatine kinase and troponin), the average hematological values and standard biochemical parameters were also described. CONCLUSION: According to what we know, this investigation demonstrates, for the first time the typical heart structures and dimensions of the heart in dromedaries, and it could serve as a basis for diagnosing cardiac disorders in these animals.

Pt-N catalytic centres concisely enhance interfacial charge transfer in amines functionalized Pt@MOFs for selective conversion of CO2 to CH4.

Improving ligand-to-active metal charge transfer (LAMCT) by finely tuning the organic ligand is a decisive strategy to enhance charge transfer in metal organic frameworks (MOFs)-based catalysts. However, in most MOFs loaded with active metal catalysts, electron transmission encounters massive obstacle at the interface between the two constituents owing to poor LAMCT. Herein, amines (-NH2) functionalized MOFs (NH2-MIL-101(Cr)) encapsulated active metal Pt nanoclusters (NCs) catalysts are synthesized by the polyol reduction method and utilized for the photoreduction of CO2. Surprisingly, the introduction of -NH2 (electron donating) groups within the matrix of MIL-101(Cr) improved the electron migration through the LAMCT process, fostering a synergistic interaction with Pt. The combined experimental analysis exposed the high number of metallic Pt (Pt0) in Pt@NH2-MIL-101(Cr) catalyst through seamless electron shuttling from N of -NH2 group to excited Pt generating versatile hybrid Pt-N catalytic centres. Consequently, these versatile hybrid catalytic centres act as electro-nucleophilic centres, which enable the efficient and selective conversion of CO bond in CO2 to harvest CH4 (131.0 µmol.g-1) and maintain excellent stability and selectivity for consecutive five rounds, superior to Pt@MIL-101(Cr) and most reported catalysts. Our study verified that the precise tuning of organic ligands in MOFs immensely improves the surface-active centres, electron migration, and catalytic selectivity of the excited Pt NCs catalysts encaged inside MOFs through an improved LAMCT pathway.

Impact of Blood Sampling Methods on Blood Loss and Transfusion After Pediatric Cardiac Surgery: An Observational Study.

OBJECTIVES: The aims of this study were to assess the impact of the closed-loop sampling method on blood loss and the need for blood transfusion in pediatric patients following cardiac surgery. DESIGN: Retrospective observational study. SETTING: A single tertiary center. PARTICIPANTS: All pediatric patients younger than 4 years old who were admitted to the pediatric intensive care unit (PICU) after cardiac surgery were enrolled. The study included 100 pediatric patients in the conservative (postimplementation) group and 43 pediatric patients in the nonconservative group (preimplementation). INTERVENTIONS: Observational. MEASUREMENTS: The primary outcome was the volume of blood loss during the PICU follow-up period. The secondary outcomes were the requirement for blood transfusion in each group, duration of mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, and mortality. MAIN RESULTS: In the conservative (postimplementation) group, blood loss during the follow-up period was 0.67 (0.33-1.16) mL/kg/d, while it was 0.95 (0.50-2.30) mL/kg/d in the nonconservative (preimplementation) group, demonstrating a significant reduction in blood loss in the conservative group (p = 0.012). The groups showed no significant differences in terms of the required blood transfusion volume postoperatively during the first 24 hours, first 48 hours, or after 48 hours (p = 0.061, 0.536, 0.442, respectively). The frequency of blood transfusion was comparable between the groups during the first 24 hours, first 48 hours, or after 48 hours postoperatively (p = 0.277, 0.639, 0.075, respectively). In addition, the groups did not show significant differences in the duration of mechanical ventilation, length of ICU stay, length of hospital stay, or mortality. CONCLUSIONS: The closed-loop sampling method can be efficient in decreasing blood loss during postoperative PICU follow-up for pediatric patients after cardiac surgeries. However, its application did not reduce the frequency or the volume of blood transfusion in these patients.

Effect of thermomechanical ageing on force transmission by orthodontic aligners made of different thermoformed materials: An experimental study.

OBJECTIVES: Investigating the impact of thermal and mechanical loading on the force generation of orthodontic aligners made from various thermoplastic materials and different compositions. MATERIALS AND METHODS: Five distinct materials were utilized including, three multi-layer (Zendura FLX, Zendura VIVA, CA Pro) and two single-layer (Zendura A and Duran). A total of 50 thermoformed aligners (n = 10) underwent a 48-hour ageing protocol, which involved mechanical loading resulting from a 0.2 mm facial malalignment of the upper right central incisor (Tooth 11) and thermal ageing through storage in warm distilled water at 37°C. The force exerted on Tooth 11 of a resin model was measured both before and after ageing using pressure-sensitive films and a biomechanical setup. RESULTS: Before ageing, pressure-sensitive films recorded normal contact forces ranging from 83.1 to 149.7 N, while the biomechanical setup measured resultant forces ranging from 0.1 to 0.5 N, with lingual forces exceeding facial forces. Multi-layer materials exhibited lower force magnitudes compared to single-layer materials. After ageing, a significant reduction in force was observed, with some materials experiencing up to a 50% decrease. Notably, multi-layer materials, especially Zendura VIVA, exhibited lower force decay. CONCLUSIONS: The force generated by aligners is influenced by both the aligner material and the direction of movement. Multi-layer materials exhibit superior performance compared to single-layer materials, primarily because of their lower initial force, which enhances patient comfort, and their capability to maintain consistent force application even after undergoing ageing.

Molecular Markers and Antimicrobial Resistance Patterns of Extraintestinal Pathogenic Escherichia coli from Camel Calves Including Colistin-Resistant and Hypermucoviscuous Strains.

Extraintestinal pathogenic Escherichia coli (ExPEC) strains are capable of causing various systemic infections in both humans and animals. In this study, we isolated and characterized 30 E. coli strains from the parenchymatic organs and brains of young (<3 months of age) camel calves which died in septicemia. Six of the strains showed hypermucoviscous phenotype. Based on minimum inhibitory concentration (MIC) values, seven of the strains were potentially multidrug resistant, with two additional showing colistin resistance. Four strains showed mixed pathotypes, as they carried characteristic virulence genes for intestinal pathotypes of E. coli: three strains carried cnf1, encoding cytotoxic necrotizing factor type 1, the key virulence gene of necrotoxigenic E. coli (NTEC), and one carried eae encoding intimin, the key virulence gene of enteropathogenic E. coli (EPEC). An investigation of the integration sites of pathogenicity islands (PAIs) and the presence of prophage-related sequences showed that the strains carry diverse arrays of mobile genetic elements, which may contribute to their antimicrobial resistance and virulence patterns. Our work is the first to describe ExPEC strains from camels, and points to their veterinary pathogenic as well as zoonotic potential in this important domestic animal.

Withaferin A as a Potential Therapeutic Target for the Treatment of Angiotensin II-Induced Cardiac Cachexia.

In our previous studies, we showed that the generation of ovarian tumors in NSG mice (immune-compromised) resulted in the induction of muscle and cardiac cachexia, and treatment with withaferin A (WFA; a steroidal lactone) attenuated both muscle and cardiac cachexia. However, our studies could not address if these restorations by WFA were mediated by its anti-tumorigenic properties that might, in turn, reduce the tumor burden or WFA's direct, inherent anti-cachectic properties. To address this important issue, in our present study, we used a cachectic model induced by the continuous infusion of Ang II by implanting osmotic pumps in immunocompetent C57BL/6 mice. The continuous infusion of Ang II resulted in the loss of the normal functions of the left ventricle (LV) (both systolic and diastolic), including a significant reduction in fractional shortening, an increase in heart weight and LV wall thickness, and the development of cardiac hypertrophy. The infusion of Ang II also resulted in the development of cardiac fibrosis, and significant increases in the expression levels of genes (ANP, BNP, and MHCß) associated with cardiac hypertrophy and the chemical staining of the collagen abundance as an indication of fibrosis. In addition, Ang II caused a significant increase in expression levels of inflammatory cytokines (IL-6, IL-17, MIP-2, and IFNγ), NLRP3 inflammasomes, AT1 receptor, and a decrease in AT2 receptor. Treatment with WFA rescued the LV functions and heart hypertrophy and fibrosis. Our results demonstrated, for the first time, that, while WFA has anti-tumorigenic properties, it also ameliorates the cardiac dysfunction induced by Ang II, suggesting that it could be an anticachectic agent that induces direct effects on cardiac muscles.

The clinical significance of long non-coding RNAs MALAT1 and CASC2 in the diagnosis of HCV-related hepatocellular carcinoma.

BACKGROUND: Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. OBJECTIVE: This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. MATERIALS AND METHODS: The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. RESULTS: The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). CONCLUSION: Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.

Prevalence of hepatitis B and C viruses among migrant workers in Qatar.

Limited data exist on viral hepatitis among migrant populations. This study investigated the prevalence of current hepatitis B virus (HBV) infection and lifetime hepatitis C virus (HCV) infection among Qatar's migrant craft and manual workers (CMWs), constituting 60% of the country's population. Sera collected during a nationwide COVID-19 population-based cross-sectional survey on CMWs between July 26 and September 9, 2020, underwent testing for HBsAg and HCV antibodies. Reactive samples underwent confirmatory testing, and logistic regression analyses were employed to explore associations with HBV and HCV infections. Among 2528 specimens tested for HBV infection, 15 were reactive, with 8 subsequently confirmed positive. Three samples lacked sufficient sera for confirmatory testing but were included in the analysis through multiple imputations. Prevalence of current HBV infection was 0.4% (95% CI 0.2-0.7%). Educational attainment and occupation were significantly associated with current HBV infection. For HCV infection, out of 2607 specimens tested, 46 were reactive, and 23 were subsequently confirmed positive. Prevalence of lifetime HCV infection was 0.8% (95% CI 0.5-1.2%). Egyptians exhibited the highest prevalence at 6.5% (95% CI 3.1-13.1%), followed by Pakistanis at 3.1% (95% CI 1.1-8.0%). Nationality, geographic location, and occupation were significantly associated with lifetime HCV infection. HBV infection is relatively low among CMWs, while HCV infection falls within the intermediate range, both compared to global and regional levels.

The role of Interleukin-21 (IL-21) in allergic disorders: Biological insights and regulatory mechanisms.

In recent decades, allergic diseases subsequent from an IgE-mediated response to specific allergens have become a progressively public chronic disease worldwide. They have shaped an important medical and socio-economic burden. A significant proportion of allergic disorders are branded via a form 2 immune response relating Th2 cells, type 2 natural lymphoid cells, mast cells and eosinophils. Interleukin-21 (IL-21) is a participant of the type-I cytokine family manufactured through numerous subsets of stimulated CD4+ T cells and uses controlling properties on a diversity of immune cells. Increasingly, experimental sign suggests a character for IL-21 in the pathogenesis of numerous allergic disorders. The purpose of this review is to discuss the biological properties of IL-21 and to summaries current developments in its role in the regulation of allergic disorders.

Follow-Up and Comparative Assessment of SARS-CoV-2 IgA, IgG, Neutralizing, and Total Antibody Responses After BNT162b2 or mRNA-1273 Heterologous Booster Vaccination.

BACKGROUND: Priming with ChAdOx1 followed by heterologous boosting is considered in several countries. Nevertheless, analyses comparing the immunogenicity of heterologous booster to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between homologous primary vaccination regimens and heterologous prime-boost vaccination using BNT162b2 or mRNA-1273. METHODS: We matched vaccinated naïve (VN) individuals (n = 673) with partial vaccination (n = 64), primary vaccination (n = 590), and primary series plus mRNA vaccine heterologous booster (n = 19) with unvaccinated naturally infected (NI) individuals with a documented primary SARS-CoV-2 infection (n = 206). We measured the levels of neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA titers. RESULTS: Homologous primary vaccination with ChAdOx1 not only showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune responses compared to primary BNT162b2 or mRNA-1273 vaccination regimens (p < 0.05) but also showed ~3-fold less anti-S1 IgA response compared to infection-induced immunity (p < 0.001). Nevertheless, a heterologous booster led to an increase of ~12 times in the immune response when compared to two consecutive homologous ChAdOx1 immunizations. Furthermore, correlation analyses revealed that both anti-S-RBD IgG and anti-S1 IgA significantly contributed to virus neutralization among NI individuals, particularly in symptomatic and pauci-symptomatic individuals, whereas among VN individuals, anti-S-RBD IgG was the main contributor to virus neutralization. CONCLUSION: The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity particularly in patients who received primary vaccination with ChAdOx1.

Safety and efficacy of intralesional polidocanol sclerotherapy in the treatment of plantar warts: a pilot study.

Plantar warts are common skin lesions that continue to represent a therapeutic challenge. They are still resistant to therapy and are highly recurrent, despite the diverse number of treatments available. Therapies targeting vasculature, such as pulsed dye laser, have been used successfully in the treatment of plantar warts. Polidocanol, a detergent sclerosant approved for the sclerotherapy of incompetent and dilated saphenous veins, has also been used as an off-label therapy for a wide range of skin conditions with vascular components such as hemangiomas and pyogenic granuloma. The current, open-label, prospective, pilot study aimed to evaluate the safety and efficacy of the intralesional polidocanol 3% in the treatment of plantar warts. Twenty patients (11 females and 9 males), with plantar warts, aged 12-50 years received biweekly sessions of intralesional polidocanol 3% until complete clearance or for a maximum of 6 sessions. Response to treatment was graded as complete (100% clearance), partial (50-99%), and no response (< 50%). At the end of the study, 12 (60%) patients achieved complete clearance of their warts after 1-5 sessions, 5 (25%) patients had only partial response, and 3 (15%) patients did not achieve any clearance of their warts. The procedure was largely tolerable by patients. Pain at the injection site and bruises were reported by 9 (45%) and 2 (10%) patients, respectively. Both side effects resolved spontaneously and completely within a few days. The findings of the current study suggest that intralesional injection of 3% polidocanol in biweekly sessions may be a safe, effective, and tolerable method for the treatment of plantar warts.

Aflatoxins in Wheat Grains: Detection and Detoxification through Chemical, Physical, and Biological Means.

Wheat (Triticum aestivum L.) is an essential food crop in terms of consumption as well as production. Aflatoxin exposure has a widespread public health impact in economically developing nations, so there is a need to establish preventive techniques for these high-risk populations. Pre-harvest and post-harvest practices are the two strategies used to control aflatoxin contamination, which include the use of genetically modified crops that show resistance against Aspergillus infection, the use of pesticides, changing the planting and harvesting time of crops, and physical, chemical, and biological methods. In this research, aflatoxin detection and quantification were performed in different wheat varieties to determine quantitative differences in comparison to the European Commission's limit of 4 ppb aflatoxins in wheat. TLC for qualitative and the ELISA kit method for quantitative analysis of aflatoxins were used. Out of 56 samples, 35 were found contaminated with aflatoxins, while the remaining 21 samples did not show any presence of aflatoxins. Out of the 35 contaminated samples, 20 samples showed aflatoxin contamination within the permissible limit, while the remaining 15 samples showed aflatoxin concentration beyond the permissible level, ranging from 0.49 to 20.56 ppb. After quantification, the nine highly contaminated wheat samples were detoxified using physical, chemical, and biological methods. The efficiency of these methods was assessed, and they showed a significant reduction in aflatoxins of 53-72%, 79-88%, and 80-88%, respectively. In conclusion, the difference in aflatoxin concentration in different wheat varieties could be due to genetic variations. Furthermore, biological treatment could be the method of choice for detoxification of aflatoxins in wheat as it greatly reduced the aflatoxin concentration with no harmful effect on the quality of the grains.

Effect of material composition and thickness of orthodontic aligners on the transmission and distribution of forces: an in vitro study.

OBJECTIVES: To investigate the effects of material type and thickness on force generation and distribution by aligners. MATERIALS AND METHODS: Sixty aligners were divided into six groups (n = 10): one group with a thickness of 0.89 mm using Zendura Viva (Multi-layer), four groups with a thickness of 0.75 mm using Zendura FLX (Multi-layer), CA Pro (Multi-layer), Zendura (Single-layer), and Duran (Single-layer) sheets, and one group with a thickness of 0.50 mm using Duran sheets. Force measurements were conducted using Fuji® pressure-sensitive films. RESULTS: The lowest force values, both active and passive, were recorded for the multi-layered sheets: CA Pro (83.1 N, 50.5 N), Zendura FLX (88.9 N, 60.7 N), and Zendura Viva (92.5 N, 68.5 N). Conversely, the highest values were recorded for the single-layered sheets: Duran (131.9 N, 71.8 N) and Zendura (149.7 N, 89.8 N). The highest force was recorded at the middle third of the aligner, followed by the incisal third, and then the cervical third. The net force between the incisal and cervical thirds (FI-FC) showed insignificant difference across different materials. However, when comparing the incisal and middle thirds, the net force (FI-FM) was higher with single-layered materials. Both overall force and net force (FI-FM) were significantly higher with 0.75 mm compared to those with a thickness of 0.50 mm. CONCLUSIONS: Multi-layered aligner materials exert lower forces compared to their single-layered counterparts. Additionally, increased thickness in aligners results in enhanced retention and greater force generation. For effective bodily tooth movement, thicker and single-layered rigid materials are preferred. CLINICAL RELEVANCE: This research provides valuable insights into the biomechanics of orthodontic aligners, which could have significant clinical implications for orthodontists. Orthodontists might use this information to more effectively tailor aligner treatments, considering the specific tooth movement required for each individual patient. In light of these findings, an exchangeable protocol for aligner treatment is suggested, which however needs to be proven clinically. This protocol proposes alternating between multi-layered and single-layered materials within the same treatment phase. This strategy is suggested to optimize treatment outcomes, particularly when planning for a bodily tooth movement.

New Theobromine Apoptotic Analogue with Anticancer Potential Targeting the EGFR Protein: Computational and In Vitro Studies.

AIM: The aim of this study was to design and examine a novel epidermal growth factor receptor (EGFR) inhibitor with apoptotic properties by utilizing the essential structural characteristics of existing EGFR inhibitors as a foundation. METHOD: The study began with the natural alkaloid theobromine and developed a new semisynthetic derivative (T-1-PMPA). Computational ADMET assessments were conducted first to evaluate its anticipated safety and general drug-likeness. Deep density functional theory (DFT) computations were initially performed to validate the three-dimensional (3D) structure and reactivity of T-1-PMPA. Molecular docking against the EGFR proteins was conducted to investigate T-1-PMPA's binding affinity and inhibitory potential. Additional molecular dynamics (MD) simulations over 200 ns along with MM-GPSA, PLIP, and principal component analysis of trajectories (PCAT) experiments were employed to verify the binding and inhibitory properties of T-1-PMPA. Afterward, T-1-PMPA was semisynthesized to validate the proposed design and in silico findings through several in vitro examinations. RESULTS: DFT studies indicated T-1-PMPA's reactivity using electrostatic potential, global reactive indices, and total density of states. Molecular docking, MD simulations, MM-GPSA, PLIP, and ED suggested the binding and inhibitory properties of T-1-PMPA against the EGFR protein. The in silico ADMET predicted T-1-PMPA's safety and general drug-likeness. In vitro experiments demonstrated that T-1-PMPA effectively inhibited EGFRWT and EGFR790m, with IC50 values of 86 and 561 nM, respectively, compared to Erlotinib (31 and 456 nM). T-1-PMPA also showed significant suppression of the proliferation of HepG2 and MCF7 malignant cell lines, with IC50 values of 3.51 and 4.13 µM, respectively. The selectivity indices against the two cancer cell lines indicated the overall safety of T-1-PMPA. Flow cytometry confirmed the apoptotic effects of T-1-PMPA by increasing the total percentage of apoptosis to 42% compared to 31, and 3% in Erlotinib-treated and control cells, respectively. The qRT-PCR analysis further supported the apoptotic effects by revealing significant increases in the levels of Casp3 and Casp9. Additionally, T-1-PMPA controlled the levels of TNFα and IL2 by 74 and 50%, comparing Erlotinib's values (84 and 74%), respectively. CONCLUSION: In conclusion, our study's findings suggest the potential of T-1-PMPA as a promising apoptotic anticancer lead compound targeting the EGFR.

A Conservative Management of Perforated Peptic Ulcer: A Case Report.

Peptic ulcer disease (PUD) is a surgical emergency that affects the mucosal lining of the stomach or proximal intestine. Complications of PUD include upper gastrointestinal hemorrhage, perforation, and obstruction. The primary management approach for perforated peptic ulcers is surgery, but conservative management can be conducted in selected cases. A 54-year-old female was referred to the surgical unit with a history of severe upper abdominal pain and repeated vomiting. No other symptoms were reported and there was no significant medical or family history except the history of non-steroidal anti-inflammatory drugs. Examination revealed that the patient had a medical condition. was vitally stable with tenderness in the upper abdomen, in particular the epigastric and right hypochondrial, but no signs of generalized peritonitis. Her white cell count was elevated at 24,000x10^3/UL, and a C-reactive protein of 45.5 mg/dL. An upright CXR revealed the classic gas under the diaphragm. Abdominal CT with oral gastrograffin identified the diagnosis of perforated duodenal ulcer without ulcer leak. The case was treated by conservative management started with resuscitation, nil per os, IV fluid, IV antibiotics, and close observation and the patient was stable with no complications and completed the nonoperative management successfully till discharge after 10 days of hospital stay. The case illustrates that although this condition is uncommon to be treated without surgical intervention, there are some factors and criteria for successful NOM. Peptic ulcer perforation is a life-threatening surgical emergency. Surgery is the standard treatment for PPU and NOM can be conducted safely and successfully in highly selected cases. the surgeon should keep a wide safety window while providing nonstandard management with readiness to operate at any time. We believe that the main factor in successful nonsurgical management of our case is being fasted for a long time before perforation.

Systematic Review of Heel Puncture-Related Osteomyelitis of the Calcaneus in Newborn Infants.

INTRODUCTION: Heel puncture (HP) in neonates can result in osteomyelitis if done non-aseptically or with incorrect technique. This study summarizes clinical experience with heel puncture-related osteomyelitis of the calcaneus (HP-CO) in newborns. METHODS: We systematically reviewed studies that examined HP-CO in newborn patients using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our search included the PubMed, Embase, and Cochrane Library databases until December 31, 2023. We used the National Institutes of Health (NIH) assessment scale to evaluate the quality of our analyzed studies. RESULTS: This study analyzed 15 neonatal calcaneal osteomyelitis (CO) cases due to HP conducted in six countries from 1976 to 2016. The average age of the cases was 8.87 ± 6.13 days, with an average birth weight of 2367.27 ± 947.59 g. The infants had undergone an average of 9.00 ± 8.90 HP, with 93.33% exhibiting swelling. Staphylococcus aureus was present in 80% of cases. Beta-lactam antibiotics were used, with satisfactory outcomes in 53.33% of cases. However, in seven cases, three patients had flatfoot due to calcaneal deformity, and other complications were observed in some patients after 7-8 years. CONCLUSIONS: This study offers valuable insights into a rare condition, including its epidemiology, clinical and laboratory characteristics, and treatment options for infants with HP-CO. To prevent the risk of osteomyelitis in this vulnerable group of patients, increasing awareness and maintaining strict aseptic techniques is necessary. We recommend that infants presenting with tenderness, redness, purulent discharge, erythema, or fever and with a history of repeated HP and swollen ankles should be evaluated for suspicion of osteomyelitis. A graphical abstract is avilable for this article.