Cell-Autonomous versus Systemic Akt Isoform Deletions Uncovered New Roles for Akt1 and Akt2 in Breast Cancer.

Studies in three mouse models of breast cancer identified profound discrepancies between cell-autonomous and systemic Akt1- or Akt2-inducible deletion on breast cancer tumorigenesis and metastasis. Although systemic Akt1 deletion inhibits metastasis, cell-autonomous Akt1 deletion does not. Single-cell mRNA sequencing revealed that systemic Akt1 deletion maintains the pro-metastatic cluster within primary tumors but ablates pro-metastatic neutrophils. Systemic Akt1 deletion inhibits metastasis by impairing survival and mobilization of tumor-associated neutrophils. Importantly, either systemic or neutrophil-specific Akt1 deletion is sufficient to inhibit metastasis of Akt-proficient tumors. Thus, Akt1-specific inhibition could be therapeutic for breast cancer metastasis regardless of primary tumor origin. Systemic Akt2 deletion does not inhibit and exacerbates mammary tumorigenesis and metastasis, but cell-autonomous Akt2 deletion prevents breast cancer tumorigenesis by ErbB2. Elevated circulating insulin level induced by Akt2 systemic deletion hyperactivates tumor Akt, exacerbating ErbB2-mediated tumorigenesis, curbed by pharmacological reduction of the elevated insulin.

Efficacy and Safety of Endoscopic Stricturotomy in Inflammatory Bowel Disease-Related Strictures: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIM: Luminal strictures, common in inflammatory bowel disease (IBD), especially Crohn's disease (CD), are typically treated with endoscopic balloon dilatation (EBD). The newer endoscopic stricturotomy (ESt) approach shows promise, but data is limited. This systematic review and meta-analysis assess the effectiveness and safety of ESt in IBD-related strictures. METHODS: A comprehensive literature search was conducted until November 2023 for studies assessing ESt efficacy and safety in IBD. Primary outcomes were clinical and technical success, with secondary endpoints covering adverse events, subsequent stricture surgery, additional endoscopic treatments (ESt or EBD), medication escalation, disease-related emergency department visits, and hospitalization post-ESt. Technical success was defined as passing the scope through the stricture, and clinical success was defined as symptom improvement. Single-arm meta-analysis (CMA version 3) calculated the event rate per patient with a 95% confidence interval (CI). Heterogeneity was evaluated using I2. RESULTS: Nine studies were included, involving 640 ESt procedures on 287 IBD patients (169 CD, 118 ulcerative colitis). Of these, 53.3% were men, with a mean age of 43.3 ± 14.3 years and a mean stricture length of 1.68 ± 0.84 cm. The technical success rate was 96.4% (95% CI 92.5-98.3, p-value < 0.0001), and the clinical success rate was 62% (95% CI 52.2-70.9, p-value = 0.017, I2 = 34.670). The bleeding rate was 10.5% per patient, and the perforation rate was 3.5%. After an average follow-up of 0.95 ± 1.1 years, 16.4% required surgery for strictures post-ESt, while 44.2% needed additional endoscopic treatment. The medication escalation rate after ESt was 14.7%. The disease-related emergency department visit rate was 14.7%, and the disease-related hospitalization rate post-procedure was 21.3%. CONCLUSION: Our analysis shows that ESt is safe and effective for managing IBD-related strictures, making it a valuable addition to the armamentarium of endoscopists. Formal training efforts should focus on ensuring its widespread adoption.

Predictors of early and late postoperative seizures in meningioma patients: a systematic review and meta-analysis.

Meningioma is the most common type of primary brain tumor which presents with a variety of neurological manifestations. Surgical resection tends to be the preferred treatment. The occurrence of seizures after resection is common, which occur either early, within seven days of operation, or late. Our meta-analysis investigated the possible predictors of early and late postoperative seizures. We assessed the relevant observational studies on predictors of postoperative seizures published in PubMed, Scopus, and Web of Science from January 2000 to September 2022, and those that met inclusion criteria were included. We calculated the association between potential predicting factors and postoperative seizures, odds ratios (ORs) with 95% confidence intervals (CIs) applying either random or fixed-effect models. The early and late postoperative seizures were evaluated individually. Thirteen observational studies involving 4176 patients were included. Seizures occurred in 250 (6%) and 584 (14%) patients, respectively, in the early and late postoperative phases. Shared predictors for early and late seizures included tumors involving the motor cortex (OR = 2.7; 95% CI: 1.67-4.38, OR = 2.46; 95% CI: 1.68-3.61), postoperative neurological deficit (OR = 4.68; 95% CI: 2.67-8.22, OR = 2.01; 95% CI: 1.39-2.92), and preoperative seizures (OR = 2.52; 95% CI: 1.82-3.49, OR = 4.35; 95% CI: 3.29-5.75). Peritumoral edema (OR = 1.99; 95% CI: 1.49-2.64) was a significant factor only among late postoperative seizure patients while surgical complications (OR = 3.77; 95% CI: 2.39-5.93) was a significant factor solely for early postoperative seizures. Meningioma patients commonly experience early and late postoperative seizures. Identifying predictors of postoperative seizures is essential to diagnose and manage them effectively.

Stochastic and deterministic dynamics in networks with excitable nodes.

Networks of excitable systems provide a flexible and tractable model for various phenomena in biology, social sciences, and physics. A large class of such models undergo a continuous phase transition as the excitability of the nodes is increased. However, models of excitability that result in this continuous phase transition are based implicitly on the assumption that the probability that a node gets excited, its transfer function, is linear for small inputs. In this paper, we consider the effect of cooperative excitations, and more generally the case of a nonlinear transfer function, on the collective dynamics of networks of excitable systems. We find that the introduction of any amount of nonlinearity changes qualitatively the dynamical properties of the system, inducing a discontinuous phase transition and hysteresis. We develop a mean-field theory that allows us to understand the features of the dynamics with a one-dimensional map. We also study theoretically and numerically finite-size effects by examining the fate of initial conditions where only one node is excited in large but finite networks. Our results show that nonlinear transfer functions result in a rich effective phase diagram for finite networks, and that one should be careful when interpreting predictions of models that assume noncooperative excitations.

The role of MicroRNA as a potential diagnostic and prognostic biomarker for cerebral aneurysms.

OBJECTIVES: To identify the dysregulated functional miRNAs, miRNA-16, miRNA-143, and miRNA-200 as potential biomarkers of cerebral aneurysms(CAs) to aid in diagnosis and prognosis. METHODS: This is a prospective case-control study conducted among patients with CA. All patients' computed tomography angiography (CTA) and interventional angiogram were assessed and studied. The miRNAs were isolated and quantified from peripheral blood samples and the expression profiling was done using TaqMan chemistry on Real-Time PCR. RESULTS: A total of 37 samples were included. Three cases had double aneurysms and 10 cases presented with aneurysmal rupture. miRNA-16, miRNA-143, and miRNA-200 were upregulated with an absolute fold-change of >8 in the CA group in comparison to controls (p<0.05). miRNA-200 showed double expression in patients with single aneurysm. A statically significant increase was observed in the expression of miRNA-143 in patients who had an aneurysmal rupture with p<0.05. Diabetic patients showed an obvious increase in miRNA-200 (13.03 folds) and miRNA-16 (26.82 folds) expression. Also, there was a notable elevation in miRNA-16, miRNA-143, and miRNA-200 in patients who had hypertension in comparison to those who did not. CONCLUSION: miRNA-16, miRNA-143, and miRNA-200 showed statically significant higher expression among cases with cerebral aneurysms in comparison to controls. Thus, these preliminary results of miRNAs biomarkers are promising future tool to be used for aneurysmal screening.

Amalgam regulates the receptor tyrosine kinase pathway through Sprouty in glial cell development in the Drosophila larval brain.

The receptor tyrosine kinase (RTK) pathway plays an essential role in development and disease by controlling cell proliferation and differentiation. Here, we profile the Drosophila larval brain by single-cell RNA-sequencing and identify Amalgam (Ama), which encodes a cell adhesion protein of the immunoglobulin IgLON family, as regulating the RTK pathway activity during glial cell development. Depletion of Ama reduces cell proliferation, affects glial cell type composition and disrupts the blood-brain barrier (BBB), which leads to hemocyte infiltration and neuronal death. We show that Ama depletion lowers RTK activity by upregulating Sprouty (Sty), a negative regulator of the RTK pathway. Knockdown of Ama blocks oncogenic RTK signaling activation in the Drosophila glioma model and halts malignant transformation. Finally, knockdown of a human ortholog of Ama, LSAMP, results in upregulation of SPROUTY2 in glioblastoma cell lines, suggesting that the relationship between Ama and Sty is conserved.

A cell atlas of adult muscle precursors uncovers early events in fibre-type divergence in Drosophila.

In Drosophila, the wing disc-associated muscle precursor cells give rise to the fibrillar indirect flight muscles (IFM) and the tubular direct flight muscles (DFM). To understand early transcriptional events underlying this muscle diversification, we performed single-cell RNA-sequencing experiments and built a cell atlas of myoblasts associated with third instar larval wing disc. Our analysis identified distinct transcriptional signatures for IFM and DFM myoblasts that underlie the molecular basis of their divergence. The atlas further revealed various states of differentiation of myoblasts, thus illustrating previously unappreciated spatial and temporal heterogeneity among them. We identified and validated novel markers for both IFM and DFM myoblasts at various states of differentiation by immunofluorescence and genetic cell-tracing experiments. Finally, we performed a systematic genetic screen using a panel of markers from the reference cell atlas as an entry point and found a novel gene, Amalgam which is functionally important in muscle development. Our work provides a framework for leveraging scRNA-seq for gene discovery and details a strategy that can be applied to other scRNA-seq datasets.

Cost-effectiveness of Ribociclib in HER2- negative breast cancer: A synthesis of current evidence.

Background: The main aim of this study was to investigate the cost-effectiveness of Ribociclib in the treatment of patients with breast cancer by assessing the published evidence. Method: A systematic review of the published literature was conducted to identify the economic evaluations/cost-effectiveness study of Ribociclib. In this study, several databases were inspected, including PubMed, NHS Economic Evaluation, Cochran, and Scopus. Studies were eligible if they assessed the cost-effectiveness of Ribociclib and reported incremental cost-effectiveness ratio (ICER). The study was performed and conducted following the PRISMA reporting guidelines. Results: Of 70 studies identified, 8 articles meet our inclusion criteria. The cost-effectiveness threshold varied from $24,144.18 in Spain to $198,000/QALY in the USA. Moreover, the result demonstrated that the mean ICER varied across different countries $1,863.47/QALY in Spain and $813,132/QALY in the USA. Conclusion: Among all CDK4/6 inhibitors medications, current evidence indicated that the use of Ribociclib for HER2- negative breast cancer management was beneficial and considered to be cost-effective. Future research is needed to investigate the role of Ribociclib in long-term treatment.

F-EVAR does not Impair Renal Function more than Open Surgery for Juxtarenal Aortic Aneurysms: Single Centre Results.

OBJECTIVE: To compare the results of elective open surgical repair (OSR) and total endovascular repair of juxtarenal aortic aneurysms (JAA), with either the Cook Zenith or the Vascutek Anaconda fenestrated stent grafts (F-EVAR) in a university hospital setting. PATIENTS AND METHODS: Between April 1999 and July 2014, of 926 patients with an abdominal aortic aneurysm, 69 were juxtarenal, where 34 had an elective OSR and 35 had F-EVAR. A post-operative rise of baseline creatinine by >50% and/or deterioration of estimated glomerular filtration rate by 25% were defined as renal failure. RESULTS: The demographics of the patients were similar except for heart insufficiency, peripheral arterial disease, and pre-existing renal artery stenosis (p < .05). Median aneurysm diameters were 57 mm (range 50-80 mm) and 56 mm (range 36-64 mm) (p = .194), respectively, and the median pre-operative serum creatinine levels were 94 µmol/L (range 65-286 µmol/L) and 96 µmol/L (range 57-333 µmol/L) (p = .871) with median estimated glomerular filtration rate of 68 mL/min (range 21-117 mL/min) and 70 mL/min (range 18-114 mL/min) (p = .308) in the open and endovascular groups, respectively. The technical success (OSR versus F-EVAR) was 100% versus 94.3% with complete exclusion of the aneurysms in all cases. Median procedure time was 171 versus 188 min. During median in hospital stay of 11 versus 7 days (p = .05), mortality was 0 versus 2.9% and new onset of post-operative renal insufficiency was detected in 26.5% versus 8.5% patients (p = .05), although with 11.8% versus 5.7% being persistent (p = .428). During follow up, statistically similar new (late or persistent post-operative) renal insufficiency was detected in 14.7% versus 8.8% with dialysis in 3% of patients in each group with similar mortality within the 24 months. CONCLUSIONS: This retrospective analysis demonstrates that OSR might be combined with more acute post-operative renal impairment than F-EVAR for JAA, but with similar intermediate term procedure related mortality and renal outcomes.

Robotics in total knee replacement: Current use and future implications.

Robotic total knee replacement (TKR) surgery has evolved over the years with the aim of improving the overall 80% satisfaction rate associated with TKR surgery. Proponents claim higher precision in executing the pre-operative plan which results in improved alignment and possibly better clinical outcomes. Opponents suggest longer operative times with potentially higher complications and no superiority in clinical outcomes alongside increased costs. This editorial will summarize where we currently stand and the future implications of using robotics in knee replacement surgery.

Rethinking BMI and Obesity Management: The Transformative Role of Artificial Intelligence.

The body mass index (BMI) is a longstanding, simple, and cost-effective tool for classifying individuals by weight, useful for rapidly screening populations for obesity-related health risks. However, its failure to account for muscle mass, bone density, and fat distribution can lead to misclassifications. This editorial explores the transformative potential of artificial intelligence (AI) in redefining or potentially replacing BMI as a tool for enhancing weight management strategies. Furthermore, it illustrates how AI can offer personalized health assessments, predictive analytics, and tailored interventions, overcoming BMI's shortcomings. By analyzing genetic, lifestyle, and medical data, AI enables a more nuanced approach to weight management, signifying a shift toward precision or personalized medicine. AI-driven virtual assistants enhance weight management by offering continuous support, motivation, and reminders, while AI algorithms analyze medical imaging for precise body composition assessment. AI also aids in early metabolic disorder detection and fosters community support among individuals with similar health goals. However, ethical concerns, data privacy, and algorithm biases require careful attention. Collaboration among healthcare professionals, researchers, and tech developers is vital for maximizing AI's positive impact on public health.

Cross-sectional insights into exercise physiology knowledge among medical students in Jordan.

Objectives: Exercise physiology is a branch of physiology that studies how physical activity and exercise alter the structure and function of living organisms. Knowledge of exercise physiology is crucial to improve athletic performance, improve people's ability to cope with extreme circumstances and approach chronic diseases. This research aimed to evaluate the knowledge of future healthcare professionals, namely, the medical students in Jordan regarding exercise physiology. Methods: Responses were collected from 524 undergraduate medical students enrolled in clinical clerkship. An online survey that evaluated participants' basic understanding of various physiological concepts related to physical exercises, such as respiratory exchange ratio, physical fitness, V̇O2 max and exercise at high altitudes was employed in the study. Results: 63.2% of participants had a poor level of exercise physiology knowledge. Misconceptions regarding V̇O2 max definition (93.3%), application (46.4%), significance (35.6%) and related physiological factors (48.7%) were observed. Students had misconceptions about physical fitness evaluation questions (52.5%, 39%, and 41.8%, respectively). Student proportions of 37%, 41%, 80.3% and 73.1% showed misconceptions about muscle groups and energy systems during training, training prescription variables, respiratory exchange ratio, and high-altitude performance, respectively. Significant differences in knowledge levels were found based on respondent characteristics (p < 0.05). Conclusions: Knowledge of exercise physiology is more than desirable for medical professionals. Therefore, efforts must be made to increase awareness and improve knowledge about basic physiological fundamentals related to exercise physiology among medical students in Jordan, as they represent the backbone of healthcare professionals of the future who will deal with medical conditions related to physical activity and exercise.

The efficacy and safety of botulinum toxin epicardial fat injection to prevent postoperative atrial fibrillation in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials.

Background: Postoperative atrial fibrillation (POAF) is prevalent in about 30% to 60% of patients undergoing cardiac surgery, leading to worse outcomes. Botulinum toxin type A (BTX) epicardial injection has been proposed to prevent POAF by impairing cholinergic signaling. Methods: A systematic review and meta-analysis synthesized randomized controlled trials, which were retrieved by searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through November 23, 2022. RevMan version 5.4 was used to pool dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean differences (MD) presented with the corresponding confidence interval (CI). Results: Three randomized controlled trials with 509 patients (308 in the BTX group and 205 in the placebo group) were included in the analysis. There was no difference between BTX and placebo regarding POAF incidence (RR 0.81 with 95% CI [0.65, 1.00], P = 0.05), postoperative hospital length of stay in days (MD -0.03 with 95% CI [-0.54, 0.49], P = 0.91), all-cause mortality (RR 1.64 with 95% CI [0.22, 12.17], P = 0.63), any adverse event (RR 1.03 with 95% CI [0.94, 1.12], P = 0.51), or any serious adverse event (RR 0.89 with 95% CI [0.68, 1.15], P = 0.36). Conclusion: There was no difference between the epicardial fat injection of BTX versus placebo for preventing POAF.

Synergistic Effect of Silver Nanoparticles with Antibiotics for Eradication of Pathogenic Biofilms.

BACKGROUND: The increase in nosocomial multidrug resistance and biofilm-forming bacterial infections led to the search for new alternative antimicrobial strategies other than traditional antibiotics. Silver nanoparticles [AgNP] could be a viable treatment due to their wide range of functions, rapid lethality, and minimal resistance potential. The primary aim of this study is to prepare silver nanoparticles and explore their antibacterial activity against biofilms. METHODS: AgNPs with specific physicochemical properties such as size, shape, and surface chemistry were prepared using a chemical reduction technique, and then characterized by DLS, SEM, and FTIR. The activity of AgNPs was tested alone and in combination with some antibiotics against MDR Gram-negative and Gram-positive planktonic bacterial cells and their biofilms. Finally, mammalian cell cytotoxicity and hemolytic activity were tested using VERO and human erythrocytes. RESULTS: The findings of this study illustrate the success of the chemical reduction method in preparing AgNPs. Results showed that AgNPs have MIC values against planktonic organisms ranging from 0.0625 to 0.125 mg/mL, with the greatest potency against gram-negative bacteria. It also effectively destroyed biofilm-forming cells, with minimal biofilm eradication concentrations [MBEC] ranging from 0.125 to 0.25 mg/ml. AgNPs also had lower toxicity profiles for the MTT test when compared to hemolysis to erythrocytes. Synergistic effect was found between AgNPs and certain antibiotics, where the MIC was dramatically reduced, down to less than 0.00195 mg/ml in some cases. CONCLUSION: The present findings encourage the development of alternative therapies with high efficacy and low toxicity.

Synergistic Antibacterial Effect of ZnO Nanoparticles and Antibiotics against Multidrug-Resistant Biofilm Bacteria.

BACKGROUND: The misuse of antibiotics leads to a global increase in antibiotic resistance. Therefore, it is imperative to search for alternative compounds to conventional antibiotics. ZnO nanoparticles (Zn NP) are one of these alternatives because they are an effective option to overcome biofilm bacterial cells and a novel way to overcome multidrug resistance in bacteria. The current research study aims to characterize the efficacy of ZnO nanoparticles alone and in combination with other antibacterial drugs against bacterial biofilms. METHODS: ZnO NPs were prepared by co-precipitation method, and their anti-biofilm and antibacterial activities alone or combined with four types of broad-spectrum antibacterial (Norfloxacin, Colistin, Doxycycline, and Ampicillin) were evaluated against E. coli and S. aureus bacterial strains. Finally, the cytotoxicity and the hemolytic activity were evaluated. RESULTS: ZnO NPs were prepared, and results showed that their size was around 10 nm with a spherical shape and a zeta potential of -21.9. In addition, ZnO NPs were found to have a strong antibacterial effect against Gram-positive and Gram-negative microorganisms, with a minimum inhibitory concentration (MIC) of 62.5 and 125 µg/mL, respectively. Additionally, they could eradicate biofilmforming microorganisms at a concentration of 125 µg/m. ZnO NPs were found to be non-toxic to erythrocyte cells. Still, some toxicity was observed for Vero cells at effective concentration ranges needed to inhibit bacterial growth and eradicate biofilm-forming organisms. When combined with different antibacterial, ZnO NP demonstrated synergistic and additive effects with colistin, and the MIC and MBEC of the combination decreased significantly to 0.976 µg/mL against planktonic and biofilm strains of MDR Gram-positive bacteria, resulting in significantly reduced toxicity. CONCLUSION: The findings of this study encourage the development of alternative therapies with high efficacy and low toxicity. ZnO nanoparticles have demonstrated promising results in overcoming multi-drug resistant bacteria and biofilms, and their combination with colistin has shown a significant reduction in toxicity. Further studies are needed to investigate the potential of ZnO nanoparticles as a viable alternative to conventional antibiotics.

Inpatient outcomes of transcatheter aortic valve replacement based on class of obesity.

Transcatheter aortic valve replacement (TAVR) is a transformative option for severe aortic stenosis, especially in elderly patients. obesity's impact on TAVR outcomes is limited. Using the National Inpatient Sample from 2016 to 2020, We analyzed 217,300 TAVR hospitalizations across BMI groups. No difference in in-hospital mortality was observed, class III obesity experienced longer hospital stays (adjusted ß: 0.43 days, P < 0.05), higher costs (adjusted ß: $3,126, P < 0.05), increased heart failure exacerbation (adjusted odds ratio [aOR]: 2.68, 95% confidence interval [CI]: [1.03-7.01], p < 0.05), vascular access complications (aOR: 1.29, 95% CI: [1.07-1.52], P < 0.05), and post-operative pulmonary complications (Pneumonia (aOR: 1.42, 95% CI: [1.16-1.74], p < 0.05), acute hypoxic respiratory failure (aOR: 1.99, 95% CI: [1.67-2.36], p < 0.05), and non-invasive ventilation (aOR: 1.62, 95% CI: [1.07-2.44], p < 0.05). Complete heart block and permanent pacemaker requirement were higher in both class II and class III ((aOR: 1.30, 95% CI: [1.11-1.51], P < 0.05), (aOR:1.25, 95% CI: [1.06-1.46], P < 0.05) and ((aOR: 1.18, 95% CI: [1.00-1.40], P < 0.05), (aOR:1.22, 95% CI: [1.02-1.45], P < 0.05)) respectively. Understanding these links is crucial for optimizing TAVR care in obesity, ensuring enhanced outcomes, and procedural safety.

Evaluation of Novel HLM Peptide Activity and Toxicity against Planktonic and Biofilm Bacteria: Comparison to Standard Antibiotics.

BACKGROUND: Antibiotic resistance is one of the main concerns of public health, and the whole world is trying to overcome such a challenge by finding novel therapeutic modalities and approaches. This study has applied the sequence hybridization approach to the original sequence of two cathelicidin natural parent peptides (BMAP-28 and LL-37) to design a novel HLM peptide with broad antimicrobial activity. METHODS: The physicochemical characteristics of the newly designed peptide were determined. As well, the new peptide's antimicrobial activity [Minimum Inhibitory Concentration (MIC), Minimum Bacterial Eradication Concentration (MBEC), and antibiofilm activity] was tested on two control (Staphylococcus aureus ATCC 29213, Escherichia Coli ATCC 25922) and two resistant [Methicillin-resistant Staphylococcus aureus (MRSA) ATCC BAA41, New Delhi metallo-beta- lactamase-1 Escherichia coli ATCC BAA-2452) bacterial strains. Furthermore, synergistic studies have been applied to HLM-hybridized peptides with five conventional antibiotics by checkerboard assays. Also, the toxicity of HLM-hybridized peptide was studied on Vero cell lines to obtain the IC50 value. Besides the percentage of hemolysis action, the peptide was tested in freshly heparinized blood. RESULTS: The MIC values for the HLM peptide were obtained as 20, 10, 20, and 20 µM, respectively. Also, the results showed no hemolysis action, with low to slightly moderate toxicity action against mammalian cells, with an IC50 value of 10.06. The Biomatik corporate labs, where HLM was manufactured, determined the stability results of the product by Mass Spectrophotometry (MS) and High-performance Liquid Chromatography (HPLC) methods. The HLM-hybridized peptide exhibited a range of synergistic to additive antimicrobial activities upon combination with five commercially available different antibiotics. It has demonstrated the biofilm-killing effects in the same concentration required to eradicate the control strains. CONCLUSION: The results indicated that HLM-hybridized peptide displayed a broad-spectrum activity toward different bacterial strains in planktonic and biofilm forms. It showed synergistic or additive antimicrobial activity upon combining with commercially available different antibiotics.

The Effect of Intratumor Heterogeneity in Pancreatic Ductal Adenocarcinoma Progression and Treatment.

BACKGROUND AND OBJECTIVES: Pancreatic cancer is one of the most lethal malignancies. Even though many substantial improvements in the survival rates for other major cancer forms were made, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Even more, no standard classification system for pancreatic cancer is based on cellular biomarkers. This review will discuss and provide updates about the role of stem cells in the progression of PC, the genetic changes associated with it, and the promising biomarkers for diagnosis. MATERIALS AND METHODS: The search process used PubMed, Cochrane Library, and Scopus databases to identify the relevant and related articles. Articles had to be published in English to be considered. RESULTS: The increasing number of studies in recent years has revealed that the diversity of cancer-associated fibroblasts is far greater than previously acknowledged, which highlights the need for further research to better understand the various cancer-associated fibroblast subpopulations. Despite the huge diversity in pancreatic cancer, some common features can be noted to be shared among patients. Mutations involving CDKN2, P53, and K-RAS can be seen in a big number of patients, for example. Similarly, some patterns of genes and biomarkers expression and the level of their expression can help in predicting cancer behavior such as metastasis and drug resistance. The current trend in cancer research, especially with the advancement in technology, is to sequence everything in hopes of finding disease-related mutations. CONCLUSION: Optimizing pancreatic cancer treatment requires clear classification, understanding CAF roles, and exploring stroma reshaping approaches.

Knowledge of cancer symptoms and risk factors: A cross-sectional study from a developing country.

The delayed presentation of cancer patients to healthcare facilities for diagnosis is a pressing issue, as late-stage cancer cases are often more challenging to treat effectively. In low-resource settings, such as those with limited access to healthcare facilities, the impact of inadequate awareness of cancer signs and symptoms can be particularly severe. Therefore, this study aimed to evaluate public knowledge of cancer signs and symptoms and risk factors in the context of Jordan. This cross-sectional study was conducted among participants from all settings. Data was obtained from an Arabic version of the cancer awareness measure (CAM), which was answered online. It described demographic data and knowledge of cancer prevalence, age-related risk, signs, symptoms, and risk factors in recall and recognition-type questions. Participants (n = 1998) completed the questionnaire with a Median age of 35 and an interquartile range of 24. About half (n = 1070) thought that cancer is unrelated to age. Most participants identified breast cancer as the most common cancer among women (81%). Awareness of cancer signs/symptoms significantly differed in the level of knowledge in favor of females. The symptom "unexplained weight loss" was most commonly recognized (66.3%) and "persistent difficulty swallowing" the least (42.6%). As for risk factors, "smoking" was the most identified (76.9%) and "eating less than 5 portions of fruits and vegetables a day" was the least (19%), and "doing <30 minutes of moderate physical activity 5 times a week" as a close second least (19.95%). Females identified "smoking," "passive smoking," "HPV infection," and "having a close relative with cancer" as risk factors significantly more than males. Those with good economic status were more aware that smoking is a cancer risk factor by 1.51 times compared to those with poor economic status. To enhance early diagnosis and presentation in Jordan, there is a need for increased public awareness of the signs, symptoms, and risk factors of cancer. One effective strategy to achieve this goal is to conduct targeted public campaigns that cater to different population groups, such as the youth, to improve their understanding and ensure that the message resonates.

The dark side of drug repurposing. From clinical trial challenges to antimicrobial resistance: analysis based on three major fields.

Drug repurposing is a strategic endeavor that entails the identification of novel therapeutic applications for pharmaceuticals that are already available in the market. Despite the advantageous nature of implementing this particular strategy owing to its cost-effectiveness and efficiency in reducing the time required for the drug discovery process, it is essential to bear in mind that there are various factors that must be meticulously considered and taken into account. Up to this point, there has been a noticeable absence of comprehensive analyses that shed light on the limitations of repurposing drugs. The primary aim of this review is to conduct a thorough illustration of the various challenges that arise when contemplating drug repurposing from a clinical perspective in three major fields-cardiovascular, cancer, and diabetes-and to further underscore the potential risks associated with the emergence of antimicrobial resistance (AMR) when employing repurposed antibiotics for the treatment of noninfectious and infectious diseases. The process of developing repurposed medications necessitates the application of creativity and innovation in designing the development program, as the body of evidence may differ for each specific case. In order to effectively repurpose drugs, it is crucial to consider the clinical implications and potential drawbacks that may arise during this process. By comprehensively analyzing these challenges, we can attain a deeper comprehension of the intricacies involved in drug repurposing, which will ultimately lead to the development of more efficacious and safe therapeutic approaches.