Carob seeds as a source of bioactive flavonoid derivatives: isolation, network pharmacology-guided anti-cancer activity, and HPLC standardization.

INTRODUCTION:  Carob, Ceratonia siliqua L. (CS), is a legume well-known for its edible pod pulp. Its seeds are used almost exclusively as a source of the food additive E410. Although a variety of metabolites have been identified by HPLC and LC-MS analysis in CS, reports concerned with their isolation are scarce.   Methodology: In this study, two flavonoid derivatives were isolated from the methanolic extract of CS seeds, namely, quercetin-3-O-rhamnoside and 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside. Network pharmacology was unusually used as a guide for estimation of the biological potential of the isolated compounds. Finally, the methanolic extract of CS seeds and its ethyl acetate fraction were standardized for their 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside content by HPLC. RESULTS:  The identified isolates displayed the ability to interfere with the activity of several target proteins associated with renal and colon cancers. Their cytotoxic effect on renal and colorectal cancer cell lines was investigated in comparison to Doxorubicin. The selectivity of the isolated compounds was evaluated on normal human fetal fibroblast cell lines. The isolated 4'-p-hydroxybenzoylisorhamnetin-3,7-di-O-rhamnoside showed very potent cytotoxic activity against the tested cell lines with the highest selectivity. CONCLUSION:  CS seeds can be used as a source of bioactive flavonoid derivatives that can be incorporated in pharmaceutical industries.

Thermal, mechanical, and electrical properties of Si-stacked nanosheet transistors using machine learning interatomic potentials.

Thermal and mechanical properties play a key role in optimizing the performance of nanoelectronic devices. In this study, the lattice thermal conductivity (κL) and elastic constants of Si nanosheets at different sheet thicknesses were determined using recently developed machine learning interatomic potentials (MLIPs). A Si nanosheet with a minimum thickness of 10 atomic layers was used for model training to predict the properties of sheets with greater thicknesses. The training dataset was efficiently constructed using stochastic sampling of the potential energy surface (PES). Density functional theory (DFT) calculations were used to extract the MLIP, which served as the basis for further analysis. The Moment Tensor Potential (MTP) method was used to obtain the MLIP in this study. The results showed that, at sub-6 nm sheet thickness, the thermal conductivity dropped to ∼ 7 % of its bulk value, whereas some stiffness tensor components dropped to ∼ 3 % of the bulk values. These findings contribute to the understanding of heat transport and mechanical behavior of ultrathin Si nanosheets, which is crucial for designing and optimizing nanoelectronic devices. The technological implications of the extracted parameters on nanosheet field-effect transistor (NS-FET) performance at advanced technology nodes were evaluated using TCAD device simulations.

A Study at Wad Madani, Sudan: Are We Documenting Acute Ankle Fractures Effectively?

BACKGROUND: Medical records are essential documents that outline a patient's medical history and current health status. It involves maintaining records that include assessments of patient outcomes, care plans, and interventions necessary to meet patient needs. A patient's medical record encompasses details about their condition, as documented by healthcare professionals, including clinical assessments, evaluations, and professional opinions related to the delivery of care. METHODS:  This retrospective study aimed to evaluate the adequacy of our documentation for acute ankle fractures in accordance with the British Orthopaedic Association Standards for Trauma and Orthopaedics (BOAST) guidelines, encompassing a total of 41 cases. The research was conducted at the Gezira Center for Orthopedic Surgery and Traumatology (GCOST) in Wad Madani, Sudan, from May 12 to July 12, 2022. RESULTS: Of the 41 recorded notes for acute ankle fractures, 26 (63.4%) were documented by medical officers and 15 (36.6%) by orthopaedic trainees. Most fractures (25 cases, 61%) occurred in individuals aged 18-40 years, and the gender distribution showed that males accounted for most fractures, with 29 cases (70.7%). Additionally, all patients (100%) had a documented cause of injury. Skin integrity was noted in 38 patients (92.7%). Vascular examination was documented in 18 patients (43.9%), while neurological examination was recorded in 16 patients (39%). CONCLUSION: Although the cause of ankle fractures was reported in all patients, the neurovascular examination was insufficiently documented, compromising patient care and failing to meet national standards, as highlighted in our study. We recommend implementing the BOAST guidelines to ensure proper documentation and essential assessments.

Beyond Conventional Imaging: A Systematic Review and Meta-Analysis Assessing the Impact of Computed Tomography Perfusion on Ischemic Stroke Outcomes in the Late-Window.

BACKGROUND: Non-contrast CT (NCCT) and CT angiogram (CTA) have become essential for endovascular treatment (EVT) in acute stroke. Patient selection may improve when CT perfusion imaging (CTP) is also added for patient selection. We aimed to analyze the effects of implementing CTP in acute ischemic stroke (AIS) patients' treatment to assess whether stroke outcomes differ in the late window. METHODS: We searched the PubMed, Embase, and Web of Sciences databases to obtain articles related to CTA and CTP in EVT. Collected patient data was split into two groups: the CTP and control (NCCT+CTA) cohorts. Primary outcomes evaluated were modified Rankin Scale (mRS) scores, symptomatic intracranial hemorrhages (sICH), mortality, and successful recanalization. RESULTS: There were 14 studies with 5,809 total patients in the final analysis: 2,602 received CTP and 3,202 were in the control group. CTP/CTA patients showed significantly lower rates of 90-day stroke-related mortality (OR: 0.72, 95% CI 0.60-0.87, p<0.01) and significantly higher successful recanalization (OR: 1.42, 95% CI 1.06-1.94, p<0.01) compared to CTA-only patients. Analysis of other outcomes including functional independence (mRS 0-2), critical times, and intracranial hemorrhages were non-significant (p > 0.05). CONCLUSION: The study highlights the usefulness of CTP-guided therapy as a supplementary tool in EVT selection in the late window. Although the addition of CTP resulted in lower mortality, the favorable outcomes did not improve. Further evidence is required to establish a clearer understanding of the potential advantages or limitations of incorporating CTP in stroke imaging.

Bat Ear Correction Steps and Outcomes for Better Life Support.

An unusually projecting human ear is known as a prominent ear, otapostasis, or bat ear. It might be both bilateral and unilateral. The scapha and antihelix of the big concha are not well formed. It is the outcome of cartilage deformity that occurred during early ear development in utero. After the child reaches five years old, the abnormality can be corrected at any time. In order to prevent psychological suffering, the procedure should ideally be performed as soon as possible. Otoplasty correction is reshaping the ear cartilage to bring the ear closer to the side of the head. The cartilage is reshaped, but the skin is left in place. Hearing remains unaffected by the operation. It is mainly done for aesthetic reasons. Although they are uncommon, the post-operative consequences from the operation include hematoma development, keloid formation, infection, and asymmetry in the ears. Otoplasty is a cosmetic operation that involves permanent sutures to alter the size, shape, or location of the ear. The main purpose of otoplasty is to treat promin auris, or bulging ears. Promin auris, the principal indication for otoplasty, is the subject of this review. The indications, contraindications, and method utilized in otoplasty are reviewed in this exercise, which also emphasizes the need of pre- and post-operative care for patients having this surgery. Otoplasty results are generally lifelong and will improve the self-confidence. The goals of otoplasties are to make the ears appear more natural in comparison to the head and help with the overall contour of the ears. Final ear surgery results will be visible after a two week recovery period, with small improvements appearing for up to 12 months post-procedure. A proper understanding of the diagnosis, indications, and surgical techniques will lead to positive outcomes in otoplasty.

Draft genomes of 10 Vibrio cholerae isolates collected in Sudan in 2019.

This report presents the first genomes from positive cases of cholera in Sudan. Genomic analysis of 10 Vibrio cholerae isolates, profiled as serogroup O1, reveals evidence of antimicrobial resistance genes and a 139-kb IncC plasmid with 99.74% identity to the multidrug-resistant plasmid pCNRVC190243 previously reported in Yemen and Lebanon.

Impact of different gastric acid suppressants on chronic unpredictable mild stress-induced cognitive impairment in rats: A possible involvement of gut dysbiosis.

Recently, clinical evidence indicates that gastric acid suppressants are associated with an increased risk of the development of cognitive impairment and dementia, especially in elderly patients and those with mild cognitive impairment. Therefore, the aim of this research was to explore the impact of different gastric acid suppressants use, famotidine (Famo), esomeprazole (Esome) and vonoprazan (Vono) in the absence or the presence of chronic unpredictable mild stress (CUMS) on several memory tasks with examination of the role of gut dysbiosis. In the present study, rats received famotidine (3.7 mg/kg/day, p.o.) or esomeprazole (3.7 mg/kg/day, p.o.) or vonoprazan (1.85 mg/kg/day, p.o.) for 7 weeks with or without exposure to CUMS. Remarkably, CUMS with different acid suppressants caused a significant decrease in all memory tasks in late CUMS in the current investigation. CUMS with acid suppressants also revealed a marked alteration in the fecal Firmicutes/Bacteroidetes ratio compared to CUMS alone. This gut microbiome alteration was associated with an alteration in gut membrane integrity, as revealed by colonic histopathology and an elevation of systemic inflammatory markers. Besides, upregulation of hippocampal amyloid ß and p-tau proteins and modification of brain histopathology were noticed. Our findings support the detrimental effect of gastric acid suppressants, especially proton pump inhibitors, on cognitive impairment in the presence of stress, with the possible involvement of gut dysbiosis.

Improving Blood Transfusion Request Form Documentation: A Quality Improvement Project.

BACKGROUND: The transfusion quality improvement project (QIP) serves as a valuable tool for assessing and educating individuals who request blood components. The World Health Organization (WHO) recommends that each institution utilize a blood transfusion request form to ensure the effective conveyance of patient information to the hospital's blood bank. This QIP aimed to implement a transfusion request form and measure compliance with its use. METHODS: A prospective study was conducted at Al Managil Teaching Hospital, Sudan, from May 1 to August 3, 2024, to address the lack of standardized transfusion request forms. The study included three cycles involving pre-intervention analysis, two phases of intervention with training sessions, and post-intervention evaluations. The interventions focused on developing and implementing a new transfusion request form, training clinical physicians, and reinforcing the form's use. Data from 100 randomly selected transfusion request forms were analyzed for completeness and adherence. RESULTS: The study showed significant improvements in the completeness of transfusion request forms across three cycles. In the first cycle, no data were collected, highlighting the absence of standardized forms. During the second cycle, with the introduction of the new form, the completion rates varied: some fields, such as patient information and clinical details, were fully completed in 50 cases (100%), while critical clinical parameters, such as current hemoglobin (Hb) and platelet (PLT) levels, were completed in only four requests (8%). By the third cycle, there was a substantial increase in completion rates across all domains. For example, patient information fields achieved 100% completion in 50 cases, and clinical parameters saw significant improvement, with current Hb and PLT levels documented in 48 cases (96%). The mean percentage completion increased from 68.1% in the second cycle to 97.9% in the third cycle, demonstrating the effectiveness of the interventions and training sessions. Minor decreases were observed in health insurance documentation and certain clinical details, indicating areas for further improvement. CONCLUSION: The systematic implementation and iterative evaluation of transfusion request forms significantly enhanced documentation completeness.

Functional Outcomes of a Dynamic Condylar Screw for Unstable Femoral Intertrochanteric Fractures in Patients Above 50.

BACKGROUND: Hip fractures are among the most common fractures encountered in the emergency departments by orthopedic trauma teams. The optimal treatment method and implant choice for unstable intertrochanteric fractures are subject to debate, with various options available, including intramedullary and extramedullary implants. METHODS: In this descriptive cross-sectional study, the researchers examined patients with unstable intertrochanteric fractures (classified as 31A2 according to the AO Foundation/Orthopaedic Trauma Association (AO/OTA) classification) who had undergone open reduction and internal fixation with a 95° dynamic condylar screw (DCS). The study was conducted at the Gezira Centre for Orthopedic Surgery and Traumatology (GCOST) during the latter half of 2022. Functional outcomes were assessed using the modified Harris Hip Score (mHHS). RESULTS: A total of 30 patients were enrolled in this study, with a mean age of 73 ± 12.27 years. Of these, 11 (36.7%) were male, and 19 (63.3%) were female. The mHHS was 73.6 ± 14.654. Among the surveyed patients, seven (23.3%) reported poor outcomes, 13 (43.3%) reported fair outcomes, six (20%) reported good outcomes, and four (13.3%) reported excellent outcomes. The Kruskal-Wallis test revealed statistically differences in mean mHHS scores between gender groups (p = 0.024) and between age groups (p = 0.04). However, no significant differences were found across different modes of trauma groups (p = 0.73), affected hip groups (p = 0.35), comorbidity groups (p = 0.84), or postoperative complication groups (p = 0.06). CONCLUSION: Our study found that DCS treatment for unstable intertrochanteric fractures yielded acceptable functional outcomes, making it a viable and effective treatment option.

How Can We Show That Artificial Intelligence May Improve Our Assessment and Management of Lower Urinary Tract Dysfunctions?-ICI-RS 2024.

AIMS: The integration of artificial intelligence (AI) into functional urology management must be assessed for its clinical utility, but hopefully will change, perhaps to revolutionize the way LUTD and other conditions are assessed, the aim being to offer patients more rapid and effective management which enhances patient outcomes. The aim of this proposal, discussed at the ICI-RS annual meeting, is to evaluate the available evidence on AI and the way it might change the approach to urodynamic (UDS) diagnoses, including overactive bladder syndrome (OAB), and perhaps other LUTDs such as bladder outflow obstruction. METHODS: A compendium of discussion based on the current evidence related to AI and its potential applications in UDS and OAB. RESULTS: AI-powered diagnostic tools are being developed to analyze complex datasets from urodynamic studies, imaging, and other diagnostic tests. AI systems can leverage large volumes of clinical data to recommend personalized treatment plans based on individual patient profiles to optimize surgical procedures, enhance diagnostic precision, tailor the therapy, reduce the risk of complications, and improve outcomes. In the future, AI will be able to provide tailored counseling regarding the outcomes and potential side effects of drugs and procedures to a given patient. CONCLUSION: AI's role in functional urology has been poorly investigated, and its implementation across several areas may improve clinical care and the pathophysiological understanding of functional urologic conditions.

Melatonin mitigates vincristine-induced peripheral neuropathy by inhibiting TNF-α/astrocytes/microglial cells activation in the spinal cord of rats, while preserving vincristine's chemotherapeutic efficacy in lymphoma cells.

Vincristine (VCR), an anti-tubulin chemotherapy agent, is known to cause peripheral and central nerve damage, inducing severe chemotherapy-induced peripheral neuropathy (CIPN). Although melatonin has been recently recognized for its potential anti-neuropathic effects, its efficacy in countering VCR-induced neuropathy remains unclear. This study examines the neuroprotective potential of melatonin against VCR-induced neuropathy using a rat model. Neuropathic pain was induced through 10 VCR injections (0.1 mg/kg/day i.p.), administered in two five-day cycles with a two-day break. Melatonin treatment started two days before VCR administration and continued daily throughout the experiment. Rats were assigned to five groups: control, VCR, and three melatonin-treated groups receiving VCR with melatonin (5, 10, or 20 mg/kg/day i.p.). We assessed mechanical (von-Frey and Randall-Selitto tests) and thermal (hot-plate and tail-flick tests) hyperalgesia, motor coordination (rotarod test), and sciatic nerve conduction velocity (NCV). Changes in body weight, spinal cord histopathology (H&E), and proinflammatory markers (TNF-α, IL-1ß, and IL-6), reactive astrocytes (GFAP) and microglial cells (IBA-1) were also assessed, as well as spinal cord degeneration (Nissl stain) and demyelination (LFB stain and MBP). Finally, the effect of melatonin on the cytotoxic activity of VCR against EL4 lymphoma cells was assessed using an MTT assay. Our results indicated that melatonin coadministration with VCR preserved spinal cord architecture, elevated nociceptive thresholds, improved motor coordination, enhanced NCV, and maintained normal body weight gain. Melatonin also reduced inflammation, decreased reactive astrocytes and microglia, and prevented neurodegeneration and demyelination in the spinal cord. Importantly, melatonin did not affect VCR's cytotoxic activity in cancer cells.

Preliminary Study on Multi-Scale Modeling of Asphalt Materials: Evaluation of Material Behavior through an RVE-Based Approach.

This study employs a microstructure-based finite element modeling approach to understand the mechanical behavior of asphalt mixtures across different length scales. Specifically, this work aims to develop a multi-scale modeling approach employing representative volume elements (RVEs) of optimal size; this is a key issue in asphalt modeling for high-fidelity fracture modeling of heterogeneous asphalt mixtures. To determine the optimal RVE size, a convergence analysis of homogenized elastic properties is conducted using two types of RVEs, one made with polydisperse spherical inclusions, and another made with polydisperse truncated cylindrical inclusions, each aligned with the American Association of State Highway and Transportation Official's maximum density gradation curve for a 12.5 mm Nominal Maximum Aggregate Size (NMAS). The minimum RVE lengths for this NMAS were found to be in the range of 32-34 mm. After the optimal RVE size for each inclusion shape is obtained, computational models of heterogeneous Indirect Tensile Asphalt Cracking Test samples are then generated. These models include the components of viscoelastic mastic, linear elastic aggregates, and cohesive zone modeling to simulate the rate-dependent failure evolution from micro- to macro-cracking. Examination of load-displacement responses at multiple loading rates shows that both heterogeneous models replicate experimentally measured data satisfactorily. Through micro- and macro-level analyses, this study enhances our understanding of the composition-performance relationships in asphalt pavement materials. The procedure proposed in this study allows us to identify the optimal RVE sizes that preserve computational efficiency without significantly compromising their ability to capture the asphalt material behavior under specific operational conditions.

Gross morphological and ultrasonographic dimensions of normal feline kidney with reference to resistive index.

Ultrasonography with color Doppler is the most quantitative analysis method for intra-renal parameters. There is a wide variation between authors in the measurement site and referencing the inter-lobar resistivity index (RI) in felines. Our objective is to morphometrically and ultrasonographically investigate the normal renal dimensions and vasculatures and draw up a normal reference value for the renal inter-lobar artery resistivity index (RI) using a Pulsed wave-Doppler ultrasonography. A total of twelve adult domestic cats were sedated and treated according to IACUC regulation guidelines to be examined using Doppler ultrasound. The same cats were used for morphometric investigation and divided into three groups regarding the used technique. The size difference between the right and left kidneys is slight, measuring 17 g (weight), 3.65 ± 0.06 cm (length), 2.54 ± 0.08 cm (width), and 2.21 ± 0.03 cm (thickness) for the right kidney, and about 15 g, 3.42 ± 0.06 cm, 2.32 ± 0.05 cm, and 2.13 ± 0.03 cm for the left one, respectively. There are three patterns of renal arteries' point of origin. The mean RI values of both kidneys were 0.57 ± 0.08 (0.50-0.67) in the right kidney and 0.60 ± 0.08 (0.51-0.69) in the left kidney. The gross examination and ultrasonography measurements did not have a statistically different effect on the actual renal dimensions. Moreover, 0.69 is considered the standard resistivity index (RI) threshold of the feline inter-lobar artery with no correlation to the animal's body weight.

Exploring the prevalence of chlamydial and gonorrheal infections in pregnant women: a multicenter study in Egypt.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are widespread, treatable sexually transmitted infections (STIs) of global significance, affecting millions annually. Left untreated, they pose significant risks, including pelvic inflammatory disease (PID), infertility, and complications during pregnancy. The U.S. Centers for Disease Control recommends annual chlamydial screening for sexually active women to address these risks. Responding to this global challenge, the World Health Organization (WHO) has formulated a global health sector strategy on sexually transmitted infections, outlining priority actions to strengthen STI responses in countries. However, STI epidemiological studies encounter challenges in developing nations like Egypt due to socio-cultural factors, poverty, and limited diagnostic facilities. In Egypt, STI diagnosis primarily relies on clinical presentations, lacking structured screening programs for CT and NG. This study's main objective is to estimate the prevalence of Chlamydial and gonorrheal infections, advocating for supportive STI strategies in Egypt. Additionally, the study aims to provide a foundation for national prevalence estimates of CT and NG infections. METHODS: A cross-sectional study encompassed five antenatal clinics in different regions of Egypt. A total of 1040 pregnant women attending these clinics were consecutively sampled. Data collection involved structured questionnaires, and urine samples were subjected to the GeneXpert CT/NG qualitative real-time PCR test. RESULTS: The prevalence of CT infections was 0.29% (95% CI, 0.10-0.86%), with no detected NG infections. The three CT-positive cases were distributed across different recruitment centers, with no statistically significant differences observed between infected and non-infected participants. Notably, 40.3% of recruited women reported gynecological symptoms, primarily discharge. Additionally, 9.6% had undergone previous testing for sexually transmitted infections, with 8.2% receiving positive results. CONCLUSIONS: This study provides valuable data on the prevalence of CT and NG infections among pregnant women attending ANC clinics in Egypt. The findings underscore the importance of ongoing surveillance, routine screening, and targeted interventions to ensure the reproductive health and well-being of pregnant women and their infants. Further research is warranted to explore the broader implications of STIs in different populations and to inform evidence-based guidelines for screening and management in diverse settings. TRIAL REGISTRATION: IRB no.: 17,400,017; WHO ERC Protocol Id. A66005.

Cost-effectiveness of ace inhibitors versus ARBs in heart failure management.

BACKGROUND: Heart failure is a chronic condition that imposes a significant burden on healthcare systems worldwide. Effective management is crucial for improving patient outcomes and reducing costs. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are widely used to manage heart failure by reducing cardiac strain and preventing disease progression. Despite their common use, ACE inhibitors and ARBs differ in mechanisms, cost, and potential side effects. ACE inhibitors have long been the standard treatment, while ARBs are often prescribed to patients intolerant to ACE inhibitors, particularly due to side effects like cough. Given these differences, evaluating the cost-effectiveness of these treatments is essential. This study compares the cost-effectiveness of ACE inhibitors and ARBs from a healthcare system perspective, considering both direct medical costs and health outcomes. METHODS: A cost-effectiveness analysis was conducted using a decision-analytic Markov model to simulate heart failure progression in a hypothetical cohort. Data inputs included clinical trial outcomes, real-world effectiveness data, direct medical costs (medications, hospitalizations, monitoring), and utility values for quality of life. The primary outcome measures were the cost per quality-adjusted life year gained and the incremental cost-effectiveness ratio. Sensitivity analyses tested the robustness of results, and subgroup analyses were conducted based on age and disease severity. RESULTS: The base-case analysis showed that ACE inhibitors were associated with lower overall costs and slightly higher quality-adjusted life years than ARBs. Sensitivity analyses revealed that variations in key parameters, such as transition probabilities, mortality rates, and healthcare expenses, had limited impact on the overall cost-effectiveness conclusions. Subgroup analyses indicated that ACE inhibitors and ARBs exhibited similar cost-effectiveness profiles for patients aged <65 and ≥65 years. However, among patients with severe heart failure, ARBs demonstrated a higher incremental cost-effectiveness ratio compared with ACE inhibitors, suggesting reduced cost-effectiveness in this subgroup. CONCLUSION: ACE inhibitors are likely a more cost-effective option for managing heart failure than ARBs, particularly from a healthcare system perspective. The findings underscore the importance of tailoring treatment decisions to individual patient factors, preferences, and clinical conditions, providing valuable insights for healthcare policy and practice, particularly regarding cost-effectiveness across patient subgroups.

Incidence and predictors of ventilator-associated pneumonia using a competing risk analysis: a single-center prospective cohort study in Egypt.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a challenging nosocomial problem in low- and middle-income countries (LMICs) that face barriers to healthcare delivery and resource availability. This study aimed to examine the incidence and predictors of VAP in Egypt as an example of an LMIC while considering death as a competing event. METHODS: The study included patients aged ≥ 18 years who underwent mechanical ventilation (MV) in an intensive care unit (ICU) at a tertiary care, university hospital in Egypt between May 2020 and January 2023. We excluded patients who died or were transferred from the ICU within 48 h of admission. We determined the VAP incidence based on clinical suspicion, radiological findings, and positive lower respiratory tract microbiological cultures. The multivariate Fine-Gray subdistribution hazard model was used to examine the predictors of VAP while considering death as a competing event. RESULTS: Overall, 315 patients were included in this analysis. Sixty-two patients (19.7%) developed VAP (17.1 per 1000 ventilator days). The Fine-Gray subdistribution hazard model, after adjustment for potential confounders, revealed that emergency surgery (subdistribution hazard ratio [SHR]: 2.11, 95% confidence interval [CI]: 1.25-3.56), reintubation (SHR: 3.74, 95% CI: 2.23-6.28), blood transfusion (SHR: 2.23, 95% CI: 1.32-3.75), and increased duration of MV (SHR: 1.04, 95% CI: 1.03-1.06) were independent risk factors for VAP development. However, the new use of corticosteroids was not associated with VAP development (SHR: 0.94, 95% CI: 0.56-1.57). Klebsiella pneumoniae was the most common causative microorganism, followed by Pseudomonas aeruginosa. CONCLUSION: The incidence of VAP in Egypt was high, even in the ICU at a university hospital. Emergency surgery, reintubation, blood transfusion, and increased duration of MV were independently associated with VAP. Robust antimicrobial stewardship and infection control strategies are urgently needed in Egypt.

Thiophene-Linked 1,2,4-Triazoles: Synthesis, Structural Insights and Antimicrobial and Chemotherapeutic Profiles.

The reaction of thiophene-2-carbohydrazide 1 or 5-bromothiophene-2-carbohydrazide 2 with various haloaryl isothiocyanates and subsequent cyclization by heating in aqueous sodium hydroxide yielded the corresponding 4-haloaryl-5-(thiophen-2-yl or 5-bromothiophen-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 5a-e. The triazole derivatives 5a and 5b were reacted with different secondary amines and formaldehyde solution to yield the corresponding 2-aminomethyl-4-haloaryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones 6a-e, 7a-e, 8, 9, 10a and 10b in good yields. The in vitro antimicrobial activity of compounds 5a-e, 6a-e, 7a-d, 8, 9, 10a and 10b was evaluated against a panel of standard pathogenic bacterial and fungal strains. Compounds 5a, 5b, 5e, 5f, 6a-e, 7a-d, 8, 9, 10a and 10b showed marked activity, particularly against the tested Gram-positive bacteria and the Gram-negative bacteria Escherichia coli, and all the tested compounds were almost inactive against all the tested fungal strains. In addition, compounds 5e, 6a-e, 7a-d and 10a exhibited potent anti-proliferative activity, particularly against HepG-2 and MCF-7 cancer cell lines (IC50 < 25 µM). A detailed structural insight study based on the single crystals of compounds 5a, 5b, 6a, 6d and 10a is also reported. Molecular docking studies of the highly active antibacterial compounds 5e, 6b, 6d, 7a and 7d showed a high affinity for DNA gyrase. Meanwhile, the potent anti-proliferative activity of compounds 6d, 6e and 7d may be attributed to their high affinity for cyclin-dependent kinase 2 (CDK2).