Clinical Characteristics and Mortality of Intensive Care Patients With Intracerebral Hemorrhage and COVID-19: A Retrospective Cohort Analysis.

BACKGROUND: Since the COVID-19 pandemic, many studies have reported severe neurologic effects of the infection on the brain. Intracerebral hemorrhage (ICH) is a particular pathology that can result in these devastating neurologic effects. OBJECTIVES: The primary aim of our study is to investigate the possible difference in the clinical and laboratory characteristics of ICH between patients with positive COVID-19 tests and those with negative tests. The potential effect of this difference on the prognosis of the patients during their stay in the intensive care unit (ICU) is a secondary aim of the study. METHODS: In this retrospective cohort review, our data were collected from the electronic medical database of the Benghazi Medical Center (BMC) for the period from January 2021 to June 2022. We depended mainly on the admission paper information documented by emergency doctors, and mortality was measured depending on the clinical status after discharge from the ICU. RESULTS: This study included a sample of 72 patients, 34 patients (47.2%) were considered COVID-19 positive, and 38 patients (52.8%) were COVID-19 negative. The difference between groups was significant in ICH score ≥3 (higher in positive patients), INR (lower in positive patients), the incidence of new-onset hypertension (higher in positive patients), location of hematoma (infratentorial in positive patients), and intraventricular hemorrhage (IVH) extension (more in positive patients). Also, COVID-19 was significantly associated with ICH score ≥3 (OR 4.6, 95% CI 1.2 - 18.6, p = 0.03, R2 = 0.16), INR (𝛃 = 0.35, 95% CI 0.09 - 0.62, p < 0.003, R2 = 0.136), risk of ventilation (OR 14.1, 95% CI 3.5 - 56.9, p < 0.001, R2 = 0.26), hydrocephalus (OR 9.41, 95% CI 2.72 - 32.5, p = 0.001, R2 = 0.19), infratentorial location (OR 3.7, 95% CI 1.1 - 12.5, p = 0.04, R2 = 0.14), IVH extension (OR 3.5, 95% CI 1.2 - 10.4, p = 0.03, R2 = 0.09), new-onset hypertension (OR 4.2, 95% CI 1.5 - 11.9, p = 0.007, R2 = 0.10), and mortality (OR 4.9, 95% CI 1.6 - 15.3, p = 0.04, R2 = 0.15). The difference in survivability between groups was statistically insignificant (X2 = 0.41, log-rank, P = 0.53). CONCLUSION: The current study demonstrates, with sufficient evidence, that COVID-19 infection causes a significant change in some critical baseline characteristics like INR values, location, and IVH extension that influence the prognosis of ICH in ICU patients.

Enriching Anticancer Drug Pipeline with Potential Inhibitors of Cyclin-Dependent Kinase-8 Identified from Natural Products.

Cyclin-dependent kinase 8 (CDK8) is highly expressed in various cancers and common complex human diseases, and an important therapeutic target for drug discovery and development. The CDK8 inhibitors are actively sought after, especially among natural products. We performed a virtual screening using the ZINC library comprising approximately 90,000 natural compounds. We applied Lipinski's rule of five, absorption, distribution, metabolism, excretion, and toxicity properties, and pan-assay interference compounds filter to eliminate promiscuous binders. Subsequently, the filtered compounds underwent molecular docking to predict their binding affinity and interactions with the CDK8 protein. Interaction analysis were carried out to elucidate the interaction mechanism of the screened hits with binding pockets of the CDK8. The ZINC02152165, ZINC04236005, and ZINC02134595 were selected with appreciable specificity and affinity with CDK8. An all-atom molecular dynamic (MD) simulation followed by essential dynamics was performed for 200 ns. Taken together, the results suggest that ZINC02152165, ZINC04236005, and ZINC02134595 can be harnessed as potential leads in therapeutic development. Moreover, the binding of the molecules brings change in protein conformation in a way that blocks the ATP-binding site of the protein, obstructing its kinase activity. These new findings from natural products offer insights into the molecular mechanisms underlying CDK8 inhibition. CDK8 was previously associated with behavioral and neurological diseases such as autism spectrum disorder, and cancers, for example, colorectal, prostate, breast, and acute myeloid leukemia. Hence, we call for further research and experimental validation, and with an eye to inform future clinical drug discovery and development in these therapeutic fields.

Green Innovation and Synthesis of Honeybee Products-Mediated Nanoparticles: Potential Approaches and Wide Applications.

Bee products, abundant in bioactive ingredients, have been utilized in both traditional and contemporary medicine. Their antioxidant, antimicrobial, and anti-inflammatory properties make them valuable for food, preservation, and cosmetics applications. Honeybees are a vast reservoir of potentially beneficial products such as honey, bee pollen, bee bread, beeswax, bee venom, and royal jelly. These products are rich in metabolites vital to human health, including proteins, amino acids, peptides, enzymes, sugars, vitamins, polyphenols, flavonoids, and minerals. The advancement of nanotechnology has led to a continuous search for new natural sources that can facilitate the easy, low-cost, and eco-friendly synthesis of nanomaterials. Nanoparticles (NPs) are actively synthesized using honeybee products, which serve dual purposes in preventive and interceptive treatment strategies due to their richness in essential metabolites. This review aims to highlight the potential role of bee products in this line and their applications as catalysts and food preservatives and to point out their anticancer, antibacterial, antifungal, and antioxidant underlying impacts. The research used several online databases, namely Google Scholar, Science Direct, and Sci Finder. The overall findings suggest that these bee-derived substances exhibit remarkable properties, making them promising candidates for the economical and eco-friendly production of NPs.

The characteristics of frozen-thawed rooster sperm using various intracellular cryoprotectants.

Cryopreservation of rooster semen is essential for conserving genetic resources, genetic improvement, and increasing productivity. However, the nature of avian sperm presents a global issue in ensuring superior frozen semen for artificial insemination. Thus, the present study aimed to evaluate the impact of using dimethylacetamide (DMA), dimethyl sulfoxide (DMSO), and ethylene glycol (EG) as cryoprotectants on post-thawed sperm motility, quality, antioxidant indicators, and fertilizing capacity. Twice a week, fresh semen ejaculates were collected from 15 adult roosters and immediately evaluated to constitute a pool from clean and qualified samples. The pooled semen was further diluted at a ratio of 1:2 (v/v) with an extender and then subjected to a freezing protocol in a liquid nitrogen vapor after adding a cryoprotectant solution containing 6% of either DMA, DMSO, or EG, respectively. After thawing, characteristics of sperm motion, quality, antioxidants, and fertilizing ability were evaluated and compared to fresh and cooled semen as controls. The results demonstrated that semen cooling negatively affected some parameters of sperm motility, quality, antioxidant biomarkers, and fertility. In comparison to the DMSO and EG groups, employing DMA considerably (P < 0.05) raised the percentages of sperm progressive motility, viability, plasma membrane intactness, and DNA integrity. The DMA group showed a significant increase in the catalase and glutathione reduced antioxidant enzyme activity and a reduction in nitric oxide and lipid peroxidation. After artificial insemination, the DMA and DMSO groups exhibited considerably (P < 0.05) better rates of hatchability and fertility than the EG group. It is concluded that freezing extenders containing 6% DMA is better than DMSO or EG to improve the post thaw semen quality and fertility in chickens.

Two-dimensional antimonene as a potential candidate for dioxin capture.

Among the serious environmental problems that attracted much attention from the broader public is the high toxicity of dioxins. Considerable efforts have been made to develop techniques and materials that could help in their efficient removal from the environment. Due to its high specific surface area, numerous active sites, and outstanding structural and electronic properties, antimonene is considered for a variety of potential applications in different fields such as energy storage, electrocatalysis, and biomedicine. The present study adds to this portfolio by suggesting antimonene as a promising candidate for dioxin capture. Using density functional theory calculations, we studied the adsorption of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on pristine as well as Ca-, Ti-, and Ni-doped antimonene. Three spatial configurations of the adsorption of TCDD on antimonene were analyzed. The results obtained from the calculation of adsorption energies, charge transfer, and densities of states provide evidence that antimonene outperforms other nanomaterials that have been previously suggested for dioxin capture applications. Therefore, we propose these substrates (i.e., pristine and doped antimonene) as potential capture agents for removing such toxic organic pollutants.

Middle Meningeal Artery Embolization for "Trial-Ineligible" Chronic Subdural Hematomas.

BACKGROUND AND OBJECTIVES: The benefit of middle meningeal artery embolization (MMAE) in the treatment of chronic subdural hematoma (CSDH) has been recently demonstrated in a series of clinical trials. Whether MMAE benefits "trial-ineligible" patients remains elusive. We thus sought to explore the potential benefit of MMAE in neurologically stable (modified Rankin Scale ≤3) patients with "trial-ineligible" CSDHs because of large size: Thickness >15 mm and/or midline shift ≥5 mm. METHODS: A prospectively maintained database was reviewed to identify trial-ineligible CSDHs undergoing standalone MMAE. Surgical rescue rate, hematoma resolution, and neurological deterioration after hematoma progression were evaluated and compared with trial-eligible counterparts. Effect sizes were adjusted for demographic, clinical, and radiological features using multivariable regression. RESULTS: Of 150 standalone MMAE procedures, 92 (61%) were performed in "trial-ineligible" cases: 41% with CSDH thickness >15 mm, 21% with midline shift ≥5 mm, and 38% with both. The surgical rescue rate was 7.6% in the trial-ineligible cohort. Over a median follow-up of 62.5 days, 88.9% cases achieved satisfactory hematoma resolution (≥50% in thickness); 76% had satisfactory resolution at 90-day follow-up. Antithrombotic resumption was a risk factor for surgical rescue (adjusted odds ratio 9.64 [95% CI, 1.33-69.74]; P = .02). Surgical rescue and hematoma resolution did not significantly differ between trial-ineligible and trial-eligible cohorts (P = .87 for surgical rescue rate and P = .85 for hematoma resolution rate). CONCLUSION: This study emphasizes the considerable prevalence of potentially "trial-ineligible" patients with CSDHs because of large size that may still benefit from standalone MMAE.

Sitagliptin synergizes 5-fluorouracil efficacy in colon cancer cells through MDR1-mediated flux impairment and down regulation of NFκB2 and p-AKT survival proteins.

5-fluorouracil (5-FU) is an inexpensive treatment for colon cancer; however, its efficacy is limited by chemoresistance. This study investigates the combination therapy approach of 5-FU with Sitagliptin (Sita), a diabetic drug with potential cancer-modulating effects. The combination was evaluated in vitro and in silico, focusing on the effects of Sita and 5-FU on colon cancer cells. The results showed that the addition of Sita significantly decreased the IC50 of 5-FU compared to 5-Fu monotherapy. The study also found that Sita and 5-FU interact synergistically, with a combination index below 1. Sita successfully lowered the 5-FU dosage reduction index, decreasing the expression of MDR1 mRNA and p-AKT and NFκB2 subunits p100/p52 protein. Molecular docking analyses confirmed Sita's antagonistic action on MDR1 and thymidylate synthase proteins. The study concludes that sitagliptin can target MDR1, increase apoptosis, and significantly reduce the expression of p-AKT and NFκB2 cell-survival proteins. These effects sensitize colon cancer cells to 5-FU. Repurposing sitagliptin may enhance the anticancer effects of 5-FU at lower dosages.

Potential (co-)contamination of dairy milk with AFM1 and MC-LR and their synergistic interaction in inducing mitochondrial dysfunction in HepG2 cells.

Several toxic metabolites, such as aflatoxin M1 (AFM1), are known to contaminate dairy milk. However, as mentioned in an external EFSA report, there is a knowledge gap regarding the carry-over of certain emerging toxins such as microcystin-LR (MC-LR). Therefore, this work aimed to develop an LC-MS/MS method for MC-LR quantification in dairy milk. Also, the method included AFM1 as a common fungal metabolite and applied to analyze 113 dairy milk samples collected directly after the end of the summer peak. Both toxins were below their LODs, keeping the question on MC-LR carry-over still unanswered. Moreover, an in silico analysis, using a 3D molecular modeling was performed, pointing to a possible interaction between MC-LR and milk proteins, especially ß-lactoglobulin. Since AFM1 and MC-LR are hepatotoxic, their interaction in inducing mitochondrial dysfunction in HepG2 cells was investigated at low (subcytotoxic) concentrations. Live cell imaging-based assays showed an inhibition in cell viability, without involvement of caspase-3/7, and a hyperpolarization in the mitochondrial membrane potential after the exposure to a mixture of 100 ng mL-1 AFM1 and 1000 ng mL-1 MC-LR for 48h. Extracellular flux analysis revealed inhibitions of several key parameters of mitochondrial function (basal respiration, ATP-linked respiration, and spare respiratory capacity).

Impact of breast cancer on in-hospital mortality and health care utilization in female heart failure patients: a retrospective cohort study.

Background: Heart failure (HF) and breast cancer are major health concerns with overlapping risk factors. This study investigated the impact of breast cancer on in-hospital mortality, length of stay, and health care charges in patients with HF. Methods: A retrospective cohort study was conducted using data from the National Inpatient Sample, focusing on female patients diagnosed with both breast cancer and HF. A control group of patients with HF without breast cancer was also analyzed. Main outcomes included in-hospital mortality, length of stay, and health care charges. Statistical analysis involved logistic and linear regression models. Results: The study included 17,551 unweighted cases of breast cancer, corresponding to 87,755 weighted cases. Breast cancer, particularly metastatic, was associated with increased in-hospital mortality across various types of HF. Patients with breast cancer and HF had longer hospital stays, which was more pronounced in metastatic cases. However, the impact on hospital charges was not consistent across the different HF types. Racial disparities were evident, with Native Americans showing the highest mortality risk in acute HF. Conclusion: Breast cancer significantly increases the in-hospital mortality risk and length of hospital stay in patients with HF. These findings highlight the need for integrated cardiovascular and oncological care, especially in the presence of metastatic breast cancer. The study underscores the importance of tailored management strategies for patients with HF with concurrent breast cancer and points toward the necessity for addressing racial disparities in health care.

Shifting tides in cardiology fellowship: an analysis of trends and the virtual interview revolution, 2017 to 2021.

Introduction: This investigation aimed to delineate the trends in cardiology fellowship applications and match rates between 2017 and 2021, with a particular focus on the effect of the COVID-19 pandemic. Methods: Utilizing data from the National Resident Matching Program and the American Board of Internal Medicine covering 6693 applicants, we conducted chi-square tests to assess match rate variations. IBM SPSS version 23 was used for statistical analysis. Results: The study noted an increase in matched US MD applicants (from 482 in 2017 to 549 in 2021, P = 0.0001) but a decrease in their match rate (from 89.8% to 83.1%). Matched US DO applicants rose significantly from 60 in 2017 to 103 in 2021 (P = 0.0001). A decline in first-choice matches and an increase in matches beyond the third choice were observed after the shift to virtual interviews. Conclusions: The study's analysis of cardiology fellowship trends from 2017 to 2021 underscores the escalating competitiveness in this field and signals a critical need for further research.

Rosemary officinalis extract mitigates potassium dichromate-induced testicular degeneration in male rats: Insights from the Nrf2 and its target genes signaling pathway.

This study aimed to investigate the protective effects of Rosemary ethanol extract (ROEE) on testicular damage induced by potassium Dichromate (PDC) in male rats regarding the signaling pathway of Nrf2 and its target genes and proteins. A total of 28 male rats were divided into four groups: control, PDC only (15 mg/kg b.w. orally), PDC + low dose ROEE (220 mg/kg b.w.), and PDC + high dose ROEE (440 mg/kg b.w.). After 28 days of consecutive treatment, the rats were sacrificed for histological, immunohistochemistry, and biochemical analyses. The results revealed that the ROEE treatment up-regulated the Nrf2 and its target genes (NQO1, HO-1) mRNA expressions compared to the PDC group. correspondingly, the protein levels of GCLM, GSH, SOD, and catalase were significantly increased in the ROEE-treated animals compared to the PDC-treated animals. Furthermore, ROEE administration led to increased serum levels of testosterone (T4) and decreased levels of estrogen (E2) compared to the PDC group. Semen analysis and histopathology demonstrated that ROEE administration significantly improved spermatological impairment caused by PDC. The immunoexpression of cytoplasmic HSP-90 was reduced in the ROEE-treated groups, while the expression of androgen receptor (AR) was markedly improved. ROEE exhibited protective effects against PDC-induced testicular damage, likely due to its antioxidant properties. However, further investigation is required to elucidate the underlying mechanisms of action.

Phage-resistant Streptomyces abietis and its telomycin bioactive metabolite as a possible alternative to antibiotics.

Multidrug-resistant pathogens are now thought to be the primary global causes of disease and death. Therefore, it is imperative to develop new effective bioactive compounds from microbial sources, such as Streptomyces species. Nevertheless, the pharmaceutical industry suffered financial losses and low-quality end products as a result of Streptomyces bacteriophage contamination. To reduce the likelihood of phage-induced issues in the medical industry, it is crucial to develop a method for finding phage-resistant strains. Hence, we aimed to isolate and characterize Streptomyces spp. and Streptomyces phages from various rhizospheric soil samples in Egypt and to investigate their antibacterial activities. Moreover, we targeted development of a Streptomyces phage-resistant strain to extract its active metabolites and further testing its antibacterial activity. Herein, the antibacterial activities of the isolated 58 Streptomyces isolates showed that 10 (17.2 %) Streptomyces isolates had antibacterial activities against the tested bacteria including Listeria monocytogenes, E. coli O157, Acinetobacter baumannii, methicillin resistant-vancomycin-intermediate Staphylococcus aureus (MRSA-VISA) and Micrococcus luteus. Three lytic bacteriophages (ϕPRSC1, ϕPRSC2, and ϕPRSC4) belonging to the families Siphoviridae and Podoviridae were obtained from the rhizospheric soil samples using the most potent S. abietis isolate as the host strain. The three isolated Streptomyces phages were thermostable, ultraviolet stable, infectious, and had a wide range of hosts against the 10 tested Streptomyces isolates with antibacterial activities. The DNA of the ϕPRSC1 and ϕPRSC4 phages were resistant to digestion by EcoRI and HindIII, but the DNA of ϕPRSC2 was resistant to digestion by EcoRI and sensitive to digestion by HindIII. Of note, we developed a S. abietis strain resistant to the three isolated phages and its antibacterial activities were twice that of the wild strain. Finally, telomycin was recognized as an antibacterial metabolite extracted from phage-resistant S. abietis strain, which was potent against the tested Gram-positive bacteria including L. monocytogenes, MRSA-VISA, and M. luteus. Thus, our findings open new horizons for researching substitute antimicrobial medications for both existing and reemerging illnesses.

Thymoquinone, artemisinin, and thymol attenuate proliferation of lung cancer cells as Sphingosine kinase 1 inhibitors.

Sphingosine-1-phosphate (S1P) formed via catalytic actions of sphingosine kinase 1 (SphK1) behaves as a pro-survival substance and activates downstream target molecules associated with various pathologies, including initiation, inflammation, and progression of cancer. Here, we aimed to investigate the SphK1 inhibitory potentials of thymoquinone (TQ), Artemisinin (AR), and Thymol (TM) for the therapeutic management of lung cancer. We implemented docking, molecular dynamics (MD) simulations, enzyme inhibition assay, and fluorescence measurement studies to estimate binding affinity and SphK1 inhibitory potential of TQ, AR, and TM. We further investigated the anti-cancer potential of these compounds on non-small cell lung cancer (NSCLC) cell lines (H1299 and A549), followed by estimation of mitochondrial ROS, mitochondrial membrane potential depolarization, and cleavage of DNA by comet assay. Enzyme activity and fluorescence binding studies suggest that TQ, AR, and TM significantly inhibit the activity of SphK1 with IC50 values of 35.52 µM, 42.81 µM, and 53.68 µM, respectively, and have an excellent binding affinity. TQ shows cytotoxic effect and anti-proliferative potentials on H1299 and A549 with an IC50 value of 27.96 µM and 54.43 µM, respectively. Detection of mitochondrial ROS and mitochondrial membrane potential depolarization shows promising TQ-induced oxidative stress on H1299 and A549 cell lines. Comet assay shows promising TQ-induced oxidative DNA damage. In conclusion, TQ, AR, and TM act as potential inhibitors for SphK1, with a strong binding affinity. In addition, the cytotoxicity of TQ is linked to oxidative stress due to mitochondrial ROS generation. Overall, our study suggests that TQ is a promising inhibitor of SphK1 targeting lung cancer therapy.

Verbena officinalis (VO) leaf extract as an anti-corrosion inhibitor for carbon steel in acidic environment.

In the present work, Verbena Officinalis (VO) leaf extract was used as potential corrosion inhibitor for the corrosion of carbon steel (CS) in 0.5 M H2SO4 medium. Further, the corrosion inhibiting nature of VO leaf extract towards the CS was evaluated using mass loss (ML), potentiodynamic polarization (PDP), electrical impedance spectroscopy (EIS) and surface morphological analyses using atomic force microscope (AFM) and X-ray photoelectron spectroscopy (XPS) techniques. Calculation of activation energy E a ∗ using Arrhenius equation shows the increase in activation energy when adding the VO leaf extract in 0.5 M H2SO4 medium and the maximum activation energy ( E a ∗ = 49.9 kJ mol-1) was observed for 1000 mg L-1 VO leaf extract in acid medium. The negative free energy values suggested the spontaneous and the stability of the adsorbed layer of VO leaf extract on the CS surface. Using EIS measurements, high percent inhibitory effectiveness of 91.1% for 1000 ppm solutions was achieved. With an increase in VO leaf extract dose, the double layer capacitance (Cdl) values fall while the values of charge transfer (Rct) increase. This showed that a protective layer of VO leaf extract on CS surface was formed. The polarization curves showed that the VO leaf extract acts as a mixed-type inhibitor. It is discovered that the adsorption of VO leaf extract molecules adhering to the CS surface followed the Langmuir isotherm. The anti-corrosion action of VO leaf extract is fully demonstrated by some surface techniques.

Investigating Pyruvate Dehydrogenase Kinase 3 Inhibitory Potential of Myricetin Using Integrated Computational and Spectroscopic Approaches.

Protein kinases are involved in various diseases and currently represent potential targets for drug discovery. These kinases play major roles in regulating the cellular machinery and control growth, homeostasis, and cell signaling. Dysregulation of kinase expression is associated with various disorders such as cancer and neurodegeneration. Pyruvate dehydrogenase kinase 3 (PDK3) is implicated in cancer therapeutics as a potential drug target. In this current study, a molecular docking exhibited a strong binding affinity of myricetin to PDK3. Further, a 100 ns all-atom molecular dynamics (MD) simulation study provided insights into the structural dynamics and stability of the PDK3-myricetin complex, revealing the formation of a stable complex with minimal structural alterations upon ligand binding. Additionally, the actual affinity was ascertained by fluorescence binding studies, and myricetin showed appreciable binding affinity to PDK3. Further, the kinase inhibition assay suggested significant inhibition of PDK3 by myricetin, revealing an excellent inhibitory potential with an IC50 value of 3.3 µM. In conclusion, this study establishes myricetin as a potent PDK3 inhibitor that can be implicated in therapeutic targeting cancer and PDK3-associated diseases. In addition, this study underscores the efficacy of myricetin as a potential lead to drug discovery and provides valuable insights into the inhibition mechanism, enabling advancements in cancer therapeutics.

Serum calgranulin C as a non-invasive predictor of activity among inflammatory bowel disease.

Inflammatory bowel disease is a chronic immune-mediated disorder with a relapsing and remitting course. It leads to disabling gastrointestinal symptoms, low quality of life, and a significant burden for healthcare utilization and associated costs. Therefore, non-invasive biomarkers are needed for early diagnosis and follow up to avoid the complications of invasive diagnostic procedures. Calgranulin C is a calcium binding protein with proinflammatory properties. The aim of this study was to evaluate the role of serum calgranulin C as a non-invasive biomarker for diagnosis and prediction of activity in comparison to different biomarkers and endoscopic activity scores in inflammatory bowel disease. The study included 80 inflammatory bowel disease patients (50 Ulcerative colitis and 30 Chron's patients) and 20 normal controls. Complete blood picture, C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin and serum calgranulin C were measured. Colonoscopies with histopathological examination were done and different activity scoring systems assessed. Among ulcerative colitis group, serum calgranulin C was statistically significantly higher in comparison to control group [723.640±529.055 ng/ml versus 80.850±24.416 ng/ml]. Depending on the American college of gastroenterology ulcerative colitis activity index, fecal calprotectin and serum calgranulin C were statistically significantly higher among moderate to severe ulcerative colitis than those with mild activity and those in remission (p < 0.001, for both). Regarding Crohn's disease group, serum calgranulin C was statistically significantly higher in comparison to control group [759.233±797.963 ng/ml versus 80.850±24.416 ng/mL]. Depending on Crohn's disease activity index, both serum calgranulin C and fecal calprotectin were statistically significantly higher among active disease than those in remission (p < 0.001, for both). In conclusion, serum calgranulin C could be used as a non-invasive marker to predict activity and severity and to ensure remission among inflammatory bowel disease patients.

An overview of RAF kinases and their inhibitors (2019-2023).

Protein kinases (PKs) including RAF, perform a principal role in regulating countless cellular events such as cell growth, differentiation, and angiogenesis. Overexpression and mutation of RAF kinases are significant contributors to the development and spread of cancer. Therefore, RAF kinase inhibitors show promising outcomes as anti-cancer small molecules by suppressing the expression of RAF protein, blocking RAS/RAF interaction, or inhibiting RAF enzymes. Currently, there are insufficient reports about approving drugs with minimal degree of toxicity. Therefore, it is an urgent need to develop new RAF kinase inhibitors correlated with increased anticancer activity and lower cytotoxicity. This review outlines reported RAF kinase inhibitors for cancer treatment in patents and literature from 2019 to 2023. It highlights the available inhibitors by shedding light on their chemical structures, biochemical profiles, and current status. Additionally, we highlighted the hinge region-binding moiety of the reported compounds by showing the hydrogen bond patterns of representative inhibitors with the hinge region for each class. In recent years, RAF kinase inhibitors have gained considerable attention in cancer research and drug development due to their potential to be studied under clinical trials and their demonstration of various degrees of efficacy and safety profiles across different cancer types. However, addressing challenges related to drug resistance and safety represents a major avenue for the optimization and enhancement of RAF kinase inhibitors. Strategies to overcome such obstacles were discussed such as developing novel pan-RAF inhibitors, RAF dimer inhibitors, and combination treatments.

A Comparison of the Health Benefits of Customized Multivitamins and Standard Supplementation Post-bariatric Surgery: A Systematic Review.

Rates of obesity increase worldwide year after year. This review explored if customized multivitamins (CMV) resulted in less micronutrient deficiency and higher serum levels of vitamins and minerals when compared to standard multivitamins (SMV) post-bariatric surgery in adults. Vitamins investigated were vitamins B1, B6, B12, D, parathyroid hormone (PTH), calcium, iron, hemoglobin, ferritin, folic acid, zinc, and magnesium. In Roux-en-Y gastric bypass (RYGB) patients weight loss surgeries (WLS) Forte or chewable CMV were studied, while in sleeve gastrectomy (SG) patients, WLS Optimum 1.0 (Opt. 1.0) or WLS Optimum 2.0 (Opt. 2.0) multivitamins were studied. An electronic search was performed on three databases (PubMed (n=28), Embase (n=120), and Cochrane (n=106)) to identify clinical trials and cohort studies. The inclusion criteria focused on studies since 2011 for adults ≥18 years old post-GB and SG. The keywords included bypass, sleeve, WLS, and multivitamins. Four clinical trials and three cohort studies were included. Jadad Scale was used to assess the quality and the bias risk in the clinical trials and the Newcastle-Ottawa scale (NOS) was used for the cohort studies. The PICO model and PRISMA rules were followed, where the outcomes targeted certain vitamin serum levels and the levels of deficiencies. The results of WLS Forte were better than SMV. The chewable CMV and Opt. 1.0 results were comparable to SMV. Opt. 2.0 was slightly better than Opt. 1.0. Further modifications would enhance the CMV presented in this systemic review. SMV would still be recommended until CMV are modified and tested. Multi-center trials that monitor the effect of the modified CMV on the serum levels of vitamins and minerals in the longer term in different wider populations are needed.

Comparison Between Retrograde and Antegrade Ureteroscopic Laser Lithotripsy for the Management of Medium-Sized Proximal Ureteral Stones: A Randomized Prospective Study.

OBJECTIVES: This study aimed to present the outcomes of retrograde and antegrade ureteroscopic laser lithotripsy in the treatment of proximal ureteral stones ranging in size from 10 to 20 millimeters in diameter. PATIENTS AND METHODS: From March 2023 to December 2023, 70 patients were included in this prospective randomized double-arm interventional study. Patients were divided into two groups: Group 1 (35 patients) had semi-rigid retrograde ureteroscopic laser lithotripsy, and Group 2 (35 patients) had semi-rigid antegrade ureteroscopic laser lithotripsy. RESULTS: In terms of length of hospitalization, there was a statistically significant distinction between the groups that were evaluated (p = 0.001). Group (1) showed a statistically significant distinction in Hb and HCT levels before and after the procedure (p < 0.05), whereas Group (2) showed a similar difference in Hb, creatinine, and HCT levels before and after the operation (p < 0.05). The antegrade group had much more hemorrhage than the retrograde group. Reduced hemoglobin (p = 0.008) and hemoglobin saturation (p = 0.029) were most noticeable in the antegrade group. Regarding stone-free rates (SFRs), no statistically significant difference was noted between the groups (p = 0.643). CONCLUSION: Both retrograde and antegrade ureteroscopic laser lithotripsy are dependable and successful for the treatment of proximal ureteral stones. For medium-sized proximal ureteral stones (10-20 mm), retrograde ureteroscopic laser lithotripsy may be the first option due to its shorter hospital stays, decreased bleeding rates, blood transfusion needs, and temporary rise in serum creatinine.

Management of Osteomyelitis in Autosomal Dominant Osteopetrosis: A Rare Case Report.

Albers-Schönberg disease, also known as osteopetrosis or marble bone disease, is a rare genetic disorder characterised by increased cortical bone mass due to dysfunctional osteoclast cells. This case report presents a 34-year-old male with autosomal dominant osteopetrosis (ADO), who was referred for evaluation and treatment of a chronic mandibular abscess with associated osteomyelitis and fistula. The patient's medical history included multiple fractures necessitating open reduction and internal fixation. Radiological examinations revealed the presence of chronic osteomyelitis in the mandible, marked by an increase in bone density and obliteration of medullary spaces. The treatment approach included surgical debridement, extraction of adjacent teeth, sequestrectomy, and antibiotic therapy. Notably, Enterobacter cloacae bacteria were identified through culture, leading to a tailored antibiotic regimen. Follow-up assessments, including clinical photographs and postoperative CT scans, were conducted to monitor the patient's progress. Histopathological examination confirmed osteomyelitis showing both viable and non-viable bone, surrounded by significant inflammatory infiltrate. This case underscores the complexity of managing osteomyelitis in patients with osteopetrosis and highlights the importance of early diagnosis, particularly before dental extractions, to prevent disease exacerbation. The rarity of this condition emphasises the need for further research and awareness among healthcare providers for optimal patient care.