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Background: Pembrolizumab, a monoclonal antibody against PD-1, has shown limited efficacy in patients with microsatellite stable or mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (CRC). We evaluated vicriviroc (small-molecule C-C motif chemokine ligand 5 antagonist) plus pembrolizumab in patients with advanced or metastatic MSS/pMMR CRC., Patients and Methods: This open-label, phase 2 trial (NCT03631407) enrolled adults with histologically confirmed, locally advanced, unresectable or metastatic CRC that was MSS per local assessment. All patients had received previous treatment with standard therapies. Patients were randomized 1:1 to vicriviroc 150 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks or vicriviroc 250 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks for up to 35 cycles (2 years). Primary endpoints were the objective response rate (ORR) as assessed by the investigator per RECIST v1.1, dose-limiting toxicities (DLTs), adverse events (AEs), and discontinuations due to AEs., Results: Forty patients were enrolled and treated. ORR was 5% (95% CI, 0.1%-24.9%) in both treatment groups. There were no complete responses; 1 patient in each treatment group experienced a partial response. No patient in the vicriviroc 150 mg plus pembrolizumab group experienced a DLT. Two patients in the vicriviroc 250 mg plus pembrolizumab group experienced DLTs (1 grade 4 encephalopathy and 1 grade 4 pneumonitis)., Conclusion: The combination of vicriviroc at doses of 150 or 250 mg plus pembrolizumab 200 mg showed limited antitumor activity in patients with advanced or metastatic MSS/pMMR CRC. Toxicity with the combination was manageable., Competing Interests: Disclosure Xiaofu Zhu: Advisory Board—Pfizer, Novartis, Lilly, AstraZeneca, Genomic Health, Apobiologix, Merck & Co., Inc., Rahway, NJ, USA, Leo Pharma, Amgen, and Taiho Pharma. Educational Support – Taiho Pharma and Novartis. Lucas Wong: Research funding to support study conduct from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Vincent Giranda: Former employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and stockholder in Merck & Co., Inc., Rahway, NJ, USA. Leah Suttner, Fang Liu, and Manash Chatterjee: Employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and stockholders in Merck & Co., Inc., Rahway, NJ, USA. Sunil Sharma: Received fees from Barricade Therapeutics, Celularity Inc., Elevar Therapeutics, Incyte, Stemline Therapeutics, Inc., Rappta Therapeutics, Processa Pharmaceuticals, and Novelty Nobility. All other authors have nothing to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: Appendicitis is a common surgical emergency with diverse clinical presentations, making its diagnosis challenging. Laparoscopic appendectomy has become the standard treatment, with various methods for appendiceal stump closure, including polymeric clips and endoloops. This study aims to compare the efficacy and safety of polymeric clips compared with endoloops in laparoscopic appendectomy., Methods: A systematic review and meta-analysis were conducted followingPreferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Medline, Scopus, and Embase were searched for studies up to March 25, 2024., Results: In total, 13 studies, including 6 randomized controlled trials, were analyzed. Polymeric clipping demonstrated significantly shorter surgical time compared with the endoloop (standardized mean difference 0.37, 95% confidence interval 0.22-0.53, P < .00001), with no difference in hospital stay or overall complications. However, the endoloop was associated with a greater incidence of intra-abdominal abscess (risk ratio 3.53, 95% confidence interval 1.56-8.00, P = .003). Other outcomes, including time from instrument application to appendiceal cutting, ileus, and surgical-site infection, showed no significant differences between the 2 techniques., Conclusion: Polymeric clipping appears to be superior to endoloop in terms of shorter surgical time and lower risk of intra-abdominal abscess formation in laparoscopic appendectomy for uncomplicated appendicitis. However, both techniques have similar outcomes regarding hospital stay and overall complications. Further research addressing study limitations and exploring patient-centered outcomes is warranted to guide clinical practice., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the Kingdom of Saudi Arabia, there is an increasing demand for community pharmacists to provide the highest level of clinical knowledge and services. However, evidence regarding Saudi public awareness of the clinical services offered by community pharmacies (CPs) and the barriers to using them is limited. In this cross-sectional study, we used an online questionnaire developed by adapting the Consolidated Framework for Implementation Research. A total of 273 participants completed the survey. Half the participants were generally aware of the availability of some CP services but were not informed about the full range on offer, eg, medication reviews (84%) and online counseling (89%). Most of the participants (69.6%) did not identify differences in the care provided by community pharmacists versus hospital pharmacists ( P  = 0.02). A commonly reported barrier to using CP services was a general preference for other healthcare professionals to seek pharmaceutical help (85.7%). Many other barriers were also reported, impacting the participants' use of these services. The decision-making authorities should consider improvements to increase patients' awareness and utilization of clinical services and enhance community pharmacists' performance in clinical-oriented pharmaceutical care., (© The Author(s) 2024.)

This study investigated the influence of pH on the retention of solutes using a mixed-mode column with carboxyl (-COOH) groups acting as weak cation exchanger bonded to the terminal of C18 ligands (C18-WCX column) and a traditional reversed-phase C18 column. First, a model based on electrostatic theory was derived and successfully used to predict the retention of charged solutes (charged, and ionizable) as a function of mobile phase pH on a C18-WCX column. While the Horváth model predicts the pH-dependent retention of ionizable solutes in reversed-phase liquid chromatography (RPLC) solely based on solute ionization, the developed model incorporates the concept of surface potential generated on the surface of the stationary phase and its variation with pH. To comprehensively understand the adsorption process, adsorption isotherms for these solutes were individually acquired on the C18-WCX and reversed-phase C18 columns. The adsorption isotherms followed the Langmuir model for the uncharged solute and the electrostatically modified Langmuir model for charged solutes. The elution profiles for the single components were calculated from these isotherms using the equilibrium dispersion column model and were found to be in close agreement with the experimental elution profiles. To enable modelling of two-component cases involving charged solute(s), a competitive adsorption isotherm model based on electrostatic theory was derived. This model was later successfully used to calculate the elution profiles of two components for scenarios involving (a) a C18 Column: two charged solutes, (b) a C18 Column: one charged and one uncharged solute, and (c) a C18-WCX Column: two charged solutes. The strong alignment between the experimental and calculated elution profiles in all three scenarios validated the developed competitive adsorption model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Intracerebral hemorrhage (ICH) is a serious medical condition associated with high mortality and disability rates. Surgical interventions, including neuro-endoscopic surgery (NES) and craniotomy, are employed to manage ICH and improve patient outcomes. This meta-analysis compares the effectiveness of NES versus craniotomy in treating ICH., Methods: A systematic literature search was conducted to identify relevant studies comparing NES with craniotomy for ICH. Inclusion criteria encompassed primary or secondary results from randomized controlled trials (RCTs) or observational studies (OSs) with confirmed supratentorial ICH. Data were extracted, and methodological quality was assessed using appropriate tools. Statistical analysis was performed using Comprehensive Meta-Analysis., Results: Twenty-six studies (n=3237 patients) were included in the analysis. NES was associated with significantly lower mortality compared to craniotomy (OR: 0.45, 95% CI 0.33 to 0.60, p < 0.00001). Hematoma evacuation rates were higher with NES (SDM: 1.505, 95% CI 0.835 to 2.160, p < 0.00001). NES also showed better functional outcomes (OR: 3.31, 95% CI 1.78 to 6.17, p = 0.0002) and reduced blood loss (SDM: -3.06, 95% CI -3.979 to -2.141, p = 0.000). Additionally, NES was associated with shorter hospital and ICU stays, shorter operative times, and fewer complications such as infection and rebleeding., Conclusion: NES emerges as a promising alternative to craniotomy for treating ICH, offering advantages in terms of mortality reduction, improved functional outcomes, and fewer complications. Future studies should explore advancements in neuro-endoscopic techniques to optimize patient outcomes further., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Recent studies have suggested an association between sleep duration and cardiovascular diseases; however, the link to AF is inconclusive. This study aimed to explore the relationship between sleep duration and AF by conducting a systematic review and meta-analysis of primary studies to provide evidence of the link between insufficient sleep and AF., Methods: A review of the existing literature was conducted to identify the primary studies that examined the association between AF and sleep duration. The inquiry spanned databases, including PubMed, Embase, MEDLINE, and Google Scholar, from their inception through October 2023., Results: Meta-analysis revealed a statistically significant association (p < 0.01) between shorter sleep duration and the incidence of AF (hazard ratio (HR), 1.18; 95% CI, 1.03-1.34; I 2  = 89%). Conversely, longer sleep duration did not exhibit a statistically significant association with the incidence of AF (HR, 1.03; 95% CI, 0.92-1.14; I 2  = 66%, p = 0.02). The sensitivity analysis demonstrated reduced heterogeneity after excluding specific studies., Conclusion: Insufficient sleep duration was associated with an increased risk of AF, whereas a longer sleep duration did not show a significant correlation. Standardized methods for sleep assessment and AF diagnosis as well as adjustments for confounding factors are suggested for future studies to improve the clarity and understanding of these associations., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Since the end of the twentieth century, the world has observed a considerable upsurge in carbon emissions as several countries have surfaced as industrial centers and production monsters worldwide. The present study contributes to the existing literature examining the effects of carbon-based emissions, industrial value added, trade openness, transport services, railway lines, and globalization index on per capita GDP growth in China. The study covers a period of 40 years, from 1982 to 2021, introducing the impact of railway transport on GDP growth in contemporary environmental empirics. A vector error correction model (VECM) was applied to achieve the study's envisaged objectives. The findings of this study reveal that carbon emissions are responsible for the reduction of per capita GDP growth in China. On the contrary, industrial value added, transport services, railway lines, and globalization index positively support the per capita GDP growth-dependent variable. The study proposes that pragmatic policies are needed to control pollution resulting from carbon emissions. The eventual effect of maintaining greenhouse gases is expected to assist in achieving sustainable growth of per capita GDP leading to the accomplishment of sustainable development goals in the economy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The Directly Observed Treatment-Short Course (DOTS) Programme was implemented by WHO and includes a combination of four anti-tuberculosis (TB) drugs (isoniazid, pyrazinamide, ethambutol and rifampicin) for a period of six months to eradicate the TB infection completely. Diabetes mellitus (DM) is recognized as one of a strong contributor of TB according to World Health Organization (WHO). The presence of diabetes mellitus type 2 (DM type 2) makes TB treatment complicated. Thus, the objective of the current meta-analysis was to identify and quantify the impact of type 2 DM on treatment outcomes of TB patients treated under the DOTS Programme., Methods: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Through a systematic review of relevant literature, we focused on studies investigating treatment outcomes including extended treatment duration and recurrence for individuals with both TB and DM undergoing DOTS therapy. The extracted information included study designs, sample sizes, patient characteristics and reported treatment results., Results: In 44 studies from different parts of the world, the pooled HR for the impact of DM on extended treatment duration and reoccurrence were HR 0.72, 95% CI 0.56-0.83, p  < .01 and HR 0.93, 95% CI 0.70-1.04, p  = .08, respectively. The pooled HR for impact of DM on composite TB treatment outcomes was calculated as 0.76 (95% CI 0.60-0.87), p  < .01 with an effect size of 41.18. The heterogeneity observed among the included studies was moderate ( I 2  = 55.79%)., Conclusions: A negative impact of DM was found on recurrence and extended treatment duration in TB patients treated with DOTS therapy. DM type 2 is responsible for the TB treatment prolongation and TB recurrence rates. By implementing effective management strategies and advancing research, the challenges can be mitigated, arising due to the complex interaction between DM and TB.

Levosimendan, a novel drug, a calcium-sensitizing inotrope, has emerged as a potential therapeutic modulator for heart failure (HF). This review appraises the efficacy and safety of levosimendan in managing HF, in different clinical settings. The study aims to examine the clinical outcomes reported in the selected trials to determine the effectiveness of levosimendan in improving key parameters related to HF. Seven relevant studies encompassing 1200 participants were identified from three databases. Inclusion criteria included clinical trials that investigated the therapeutic efficacy of levosimendan in the treatment of HF, and studies involving both adult and pediatric participants. Exclusion criteria involved studies with insufficient data, studies other than clinical trials, case reports, letters to the editor, conference papers, grey literature, and studies published in a language other than English. Upon evaluating the included studies, it was found that levosimendan shows improved hemodynamics and clinical efficacy in patients with severe septic cardiomyopathy. Levosimendan enhanced right ventricular (RV) function in patients with RV dysfunction after mitral valve (MV) surgeries and decreased the amount of N-terminal pro-B-type natriuretic peptide (NT-ProBNP) in non-ST elevated myocardial infarction (NSTEMI) patients with elevated NT-proBNP, all without increasing the overall cost or duration of hospitalization. Despite variations in study designs and participant characteristics, evidence suggests levosimendan significantly improves left ventricular ejection fraction (LVEF) and exercise tolerance measured by a six-minute walk distance. Notably, its safety profile appears favorable with minimal arrhythmic events and comparable rates of adverse effects to a placebo. This systematic review highlights levosimendan's promising potential for HF management, warranting further research to solidify its clinical role., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ali et al.)

The ketogenic diet (KD), characterized by high-fat and low-carbohydrate intake, is currently gaining widespread popularity as a treatment for drug-resistant epilepsy (DRE). In addition to the traditional ketogenic diet, several variants have been introduced to enhance compliance and flexibility, such as the modified Atkins diet (MAD) and the low glycemic index diet (LGID). These adaptations aim to provide patients with more manageable and sustainable options while harnessing the potential therapeutic benefits of DRE. The objective of this study is to evaluate the efficacy and safety of the KD in pediatric patients who exhibit DRE. In this study, we conducted a thorough review of existing literature by searching Cochrane, Embase, Medline, and PubMed. Our approach involved predefined criteria for data extraction and the assessment of study quality. Eleven RCTs with 788 participants were included in this study. The pooled effect estimates revealed a significant association between dietary interventions and seizure frequency reduction of > 50% (OR 6.68, 96% CI 3.52, 12.67) and > 90% (OR 4.37, 95% CI 2.04, 9.37). Dietary interventions also increased the odds of achieving seizure freedom (OR 4.13, 95% CI 1.61, 10.60). The common adverse effects included constipation (39.07%) and vomiting (10%). In conclusion, dietary interventions, notably the KD, hold promise for pediatric DRE, reducing seizures and achieving freedom. These non-pharmacological options improve the quality of life of non-responsive and non-surgical patients. The KD has emerged as a potential therapeutic approach. Further research is needed to address the limitations and investigate their long-term effects., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Our previous studies have revealed that L. acidophilus possesses inhibitory effects on PCV2 proliferation in vivo , although the underlying mechanisms remain elusive. Probiotics like L. acidophilus are known to exert antiviral through their metabolites. Therefore, in this study, non-targeted metabolomics was used to detect the changes in metabolites of L. acidophilus after 24 h of proliferation. Subsequently, high-throughput molecular docking was utilized to analyze the docking scores of these metabolites with PCV2 Cap and Rep, aiming to identify compounds with potential anti-PCV2 effects. The results demonstrated that 128 compounds such as Dl-lactate were significantly increased. The results of high-throughput molecular docking indicated that compounds such as ergocristine, and telmisartan formed complexes with Cap and Rep, suggesting their potential anti-PCV2 properties. Furthermore, compounds like vitamin C, exhibit pharmacological effects consistent with L. acidophilus adding credence to the idea that L. acidophilus may exert pharmacological effects through its metabolites. These results will provide a foundation for the study of L. acidophilus ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cao, Ling, Haseeb, Sun, Zhang, Yin, Fan, Yang, Zhang, Zhong, Sun, Sun and Li.)

Canine mammary tumors (CMTs) are the most common type of tumor in female dogs. In this study, we obtained a metastatic key protein, Fascin-1, by comparing the proteomics data of in situ tumor and metastatic cell lines from the same individual. However, the role of Fascin-1 in the CMT cell line is still unclear. Firstly, proteomics was used to analyze the differential expression of Fascin-1 between the CMT cell lines CHMm and CHMp. Then, the overexpression (CHMm-OE and CHMp-OE) and knockdown (CHMm-KD and CHMp-KD) cell lines were established by lentivirus transduction. Finally, the differentially expressed proteins (DEPs) in CHMm and CHMm-OE cells were identified through proteomics. The results showed that the CHMm cells isolated from CMT abdominal metastases exhibited minimal expression of Fascin-1. The migration, adhesion, and invasion ability of CHMm-OE and CHMp-OE cells increased, while the migration, adhesion, and invasion ability of CHMm-KD and CHMp-KD cells decreased. The overexpression of Fascin-1 can upregulate the Tetraspanin 4 (TSPAN4) protein in CHMm cells and increase the number of migrations. In conclusion, re-expressed Fascin-1 could promote cell EMT and increase lamellipodia formation, resulting in the enhancement of CHMm cell migration, adhesion, and invasion in vitro. This may be beneficial to improve female dogs' prognosis of CMT.

Osthole (Ost) and icariin (Ica) are extracted from traditional Chinese medicine Cnidium monnieri and Epimedii Folium, respectively, and both exhibit estrogen-like biological activity. This study aimed to determine the efficacy and safety of combining Ost with Ica on the production performance of laying hens and to explore their possible mechanisms. The production performance, egg quality, residues of Ost and Ica in eggs, serum reproductive hormone levels, expression of ovarian reproductive hormone receptor, proliferation of granulosa cells in small yellow follicles (SYF), and progesterone secretion in large yellow follicles (LYF) related genes and proteins expression were detected. The results showed that adding 2 mg/kg Ost + 2 mg/kg Ica to the feed increased the laying rate, average egg weight, Haugh unit, and protein height of laying hens. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and progesterone (P4) levels increased, and the expression of ovarian estrogen receptor (ER), follicle-stimulating hormone receptor (FSHR), and progesterone receptor (PGR) mRNA was up-regulated. Additionally, the mRNA and protein levels of steroidogenesis acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) increased in LYF. Furthermore, mRNA and protein levels of proliferating cell nuclear antigen (PCNA), cyclin E1, and cyclin A2 were up-regulated in SYF. The residues of Ost and Ica in egg samples were not detected by high-performance liquid chromatography (HPLC). In conclusion, dietary supplementation of Ost and Ica increased granulosa cells proliferation in SYF and increased P4 secretion in granulosa cells of LYF, ultimately improving the production performance of laying hens., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This comprehensive review delves into the current updates and challenges associated with the management of low-grade gliomas (LGG), the predominant primary tumors in the central nervous system. With a general incidence rate of 5.81 per 100000, gliomas pose a significant global concern, necessitating advancements in treatment techniques to reduce mortality and morbidity. This review places a particular focus on immunotherapies, discussing promising agents such as Zotiraciclib and Lerapolturev. Zotiraciclib, a CDK9 inhibitor, has demonstrated efficacy in glioblastoma treatment in preclinical and clinical studies, showing its potential as a therapeutic breakthrough. Lerapolturev, a viral immunotherapy, induces inflammation in glioblastoma and displays positive outcomes in both adult and pediatric patients. Exploration of immunotherapy extends to Pembrolizumab, Nivolumab, and Entrectinib, revealing the challenges and variabilities in patient responses. Despite promising preclinical data, the monoclonal antibody Depatuxizumab has proven ineffective in glioblastoma treatment, emphasizing the critical need to understand resistance mechanisms. The review also covers the success of radiation therapy in pediatric LGG, with evolving techniques, such as proton therapy, showing potential improvements in patient quality of life. Surgical treatment is discussed in the context of achieving a balance between preserving the patient's quality of life and attaining gross total resection, with the extent of surgical resection significantly influencing the survival outcomes. In addition to advancements in cancer vaccine development, this review highlights the evolving landscape of LGG treatment, emphasizing a shift toward personalized and targeted therapies. Ongoing research is essential for refining strategies and enhancing outcomes in the management of LGG., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Competing Interests: The author declares no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Objective: This study aimed to assess the impact of establishing a pre-hospital definitive airway on mortality and morbidity compared with no prehospital airway in cases of severe traumatic brain injury (TBI)., Background: Traumatic brain injury (TBI) is a global health concern that is associated with substantial morbidity and mortality. Prehospital intubation (PHI) has been proposed as a potential life-saving intervention for patients with severe TBI to mitigate secondary insults, such as hypoxemia and hypercapnia. However, their impact on patient outcomes remains controversial., Methods: A systematic review and meta-analysis were conducted to assess the effects of prehospital intubation versus no prehospital intubation on morbidity and mortality in patients with severe TBI, adhering to the PRISMA guidelines., Results: 24 studies, comprising 56,543 patients, indicated no significant difference in mortality between pre-hospital and In-hospital Intubation (OR 0.89, 95% CI 0.65-1.23, p = 0.48), although substantial heterogeneity was noted. Morbidity analysis also showed no significant difference (OR 0.83, 95% CI 0.43-1.63, p = 0.59). These findings underscore the need for cautious interpretation due to heterogeneity and the influence of specific studies on the results., Conclusion: In summary, an initial assessment did not reveal any apparent disparity in mortality rates between individuals who received prehospital intubation and those who did not. However, subsequent analyses and randomized controlled trials (RCTs) demonstrated that patients who underwent prehospital intubation had a reduced risk of death and morbidity. The dependence on biased observational studies and the need for further replicated RCTs to validate these findings are evident. Despite the intricacy of the matter, it is crucial to intervene during severe airway impairment., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests and there is no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The target and mechanism of ellagic acid (EA) against rotavirus (RV) were investigated by network pharmacology, computational biology, and surface plasmon resonance verification. The target of EA was obtained from 11 databases such as HIT and TCMSP, and RV-related targets were obtained from the Gene Cards database. The relevant targets were imported into the Venny platform to draw a Venn diagram, and their intersections were visualized. The protein-protein interaction networks (PPI) were constructed using STRING, DAVID database, and Cytoscape software, and key targets were screened. The target was enriched by Gene Ontology (GO) and KEGG pathway, and the 'EA anti-RV target-pathway network' was constructed. Schrodinger Maestro 13.5 software was used for molecular docking to determine the binding free energy and binding mode of ellagic acid and target protein. The Desmond program was used for molecular dynamics simulation. Saturation mutagenesis analysis was performed using Schrodinger's Maestro 13.5 software. Finally, the affinity between ellagic acid and TLR4 protein was investigated by surface plasmon resonance (SPR) experiments. The results of network pharmacological analysis showed that there were 35 intersection proteins, among which Interleukin-1β (IL-1β), Albumin (ALB), Nuclear factor kappa-B1 (NF-κB1), Toll-Like Receptor 4 (TLR4), Tumor necrosis factor alpha (TNF-α), Tumor protein p53 (TP53), Recombinant SMAD family member 3 (SAMD3), Epidermal growth factor (EGF) and Interleukin-4 (IL-4) were potential core targets of EA anti-RV. The GO analysis consists of biological processes (BP), cellular components (CC), and molecular functions (MF). The KEGG pathways with the highest gene count were mainly related to enteritis, cancer, IL-17 signaling pathway, and MAPK signaling pathway. Based on the crystal structure of key targets, the complex structure models of TP53-EA, TLR4-EA, TNF-EA, IL-1β-EA, ALB-EA, NF-κB1-EA, SAMD3-EA, EGF-EA, and IL-4-EA were constructed by molecular docking (XP mode of flexible docking). The MMGBS analysis and molecular dynamics simulation were also studied. The Δaffinity of TP53 was highest in 220 (CYS → TRP), 220 (CYS → TYR), and 220 (CYS → PHE), respectively. The Δaffinity of TLR4 was highest in 136 (THR → TYR), 136 (THR → PHE), and 136 (THR → TRP). The Δaffinity of TNF-α was highest in 150 (VAL → TRP), 18 (ALA → GLU), and 144 (PHE → GLY). SPR results showed that ellagic acid could bind TLR4 protein specifically. TP53, TLR4, and TNF-α are potential targets for EA to exert anti-RV effects, which may ultimately provide theoretical basis and clues for EA to be used as anti-RV drugs by regulating TLR4/NF-κB related pathways., (© 2024. The Author(s).)

Background: The Entrapped Temporal Horn (ETH) is characterized by localized enlargement of the temporal horn of the lateral ventricle of the brain. This study aimed to investigate the factors, development, prognosis, and effective treatment., Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a systematic search was conducted in major research databases. The inclusion criteria included patients of all ages with TTH diagnosis in cohort studies, case series, and case reports., Results: Our study included 160 patients and 49 studies. The major causes of TTH were neoplastic lesions (42.3%), infections (22.3%), and cystic disease (13.08%). Of these cases, 71 were unrelated to cranial surgery, while 89 were unrelated to prior surgeries. Headache was the most common symptom (41.91%), followed by seizures (13.20%), drowsiness (12.50%) and memory loss (11.00%). Surgery was not required in 17 patients. Fenestration of the trapped temporal horn was performed in 24 patients, while VP/VA shunt surgeries were performed in the majority (57 patients) owing to favorable outcomes, lower revision rates, and extensive experience. However, TTH recurred in six of the 21 patients who underwent endoscopic ventriculocisternostomy. Tumors were the main cause, and isolated headache was the most frequent symptom. Ventriculoperitoneal shunts (VPS) are preferred because of their positive outcomes, lower revision rates, and wider expertise. Tumors near the trigonal area pose a higher risk., Conclusion: Although TTH remains a rare condition, VPS continues to be the most widely preferred procedure among surgeons., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Authors.)

Histotripsy is a noninvasive medical technique that uses high-intensity focused ultrasound (HIFU) to treat liver tumours. The two main histotripsy methods are boiling histotripsy and cavitation cloud histotripsy. Boiling histotripsy uses prolonged ultrasound pulses to create small boiling bubbles in the tissue, which leads to the breakdown of the tissue into smaller subcellular fragments. Cavitation cloud histotripsy uses the ultrasonic cavitation effect to disintegrate target tissue into precisely defined liquefied lesions. Both methods show similar treatment effectiveness; however, boiling histotripsy ensures treatment stability by producing a stable boiling bubble with each pulse. The therapeutic effect is ascribed to mechanical damage at the subcellular level rather than thermal damage. This article discusses the mechanisms, treatment parameters, and potential of histotripsy as a minimally invasive procedure that provides precise and controlled subcellular damage., Competing Interests: The authors declare no potential conflicts of interest concerning the research, authorship, and/or publication of this article.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Acute subdural hematoma (ASDH) stands as a significant contributor to morbidity after severe traumatic brain injuries (TBI). The primary treatment approach for patients experiencing progressive neurological deficits or notable mass effects is the surgical removal of the hematoma, which can be achieved through craniotomy (CO) or decompressive craniectomy (DC). Nevertheless, the choice between these two procedures remains a subject of ongoing debate and controversy., Materials and Methods: We conducted a comprehensive literature review, utilizing prominent online databases and manually searching references related to craniotomy and craniectomy for subdural hematoma evacuation up to November 2023. Our analysis focused on outcome variables such as the presence of residual subdural hematoma, the need for revision procedures, and overall clinical outcomes., Results: We included a total of 11 comparative studies in our analysis, encompassing 4269 patients, with 2979 undergoing craniotomy and 1290 undergoing craniectomy, meeting the inclusion criteria. Patients who underwent craniectomy displayed significantly lower scores on the Glasgow Coma Scale (GCS) during their initial presentation. Following surgery, the DC group exhibited a significantly reduced rate of residual subdural (P = 0.009). Additionally, the likelihood of a poor outcome during follow-up was lower in the CO group. Likewise, the mortality rate was lower in the CO group compared to the craniectomy group (OR 0.63, 95% CI 0.41-0.98, I 2  = 84%, P = 0.04)., Conclusion: Our study found that CO was associated with more favorable outcomes in terms of mortality, reoperation rate, and functional outcome while DC was associated with less likelihood of residual subdural hematoma. Upon further investigation of patient characteristics who underwent into either of these interventions, it was very clear that patients in DC cohort have more serious and low pre-op characteristics than the CO group. Nonetheless, brain herniation and advanced age act as independent factor for predicting the outcome irrespective of the intervention., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: To learn more about the effectiveness of oral propranolol as a therapeutic alternative for preterm newborns with pre-existing retinopathy of prematurity (ROP) as well as an early prevention method for ROP, one of the most common but avoidable causes of juvenile blindness., Study Design: Meta-analysis of relevant literature., Methods: A total of 3464 papers were identified, with 2873 from PubMed, 39 from Scopus, 67 from Medline, and 16 from Embase. After screening, finally, a total of 8 studies were deemed suitable for review. Following the PRISMA guidelines, published literature was systematically assessed up to May 10, 2023. Trials and observational studies were included in which beta blockage was used to prevent severe ROP (defined as stage ≥3 or requiring treatment). A total of 3646 papers were identified, with 2873 from PubMed, 39 from Scopus, 67 from Medline, and 16 from Embase. After screening, a total of 8 studies were deemed suitable for review., Results: The use of propranolol is linked to a lower risk of disease development in ROP compared to other therapies or control groups, according to the overall risk ratio of 0.59 (95% CI = 0.42, 0.82; P = .002, I 2 = 41%). Additionally, the overall risk ratio for plus disease is 0.42 (95% CI = 0.23, 0.78; P = .006, I 2 = 0%), for laser photocoagulation is 0.48 (95% CI = 0.31, 0.74; P = .001; I 2 = 2%), and for intravitreal injection of VEGF is 0.43 (95% CI = 0.24, 0.74; P = 0.003, I 2 = 0%), suggesting that use of propranolol may reduce the likelihood of developing a disease such as plus disease, requiring laser photocoagulation or necessitating intravitreal injection of vascular endothelial growth factor for ROP, respectively. No statistically significant heterogeneity was found in this study (P > .10, I 2 = 50%). It can be concluded from this that the results of the chosen studies were sufficiently comparable and consistent., Conclusion: This study showed that oral propranolol given as a preventive treatment in premature newborns successfully prevented severe ROP. Propranolol dosage and timing must now be carefully considered in the context of the study population, as these factors may have a major impact on the observed outcomes and treatment success., (Copyright © 2023 Elsevier Inc. All rights reserved.)

SOX8 was linked in a genome-wide association study to human height heritability, but roles in chondrocytes for this close relative of the master chondrogenic transcription factor SOX9 remain unknown. We undertook here to fill this knowledge gap. High-throughput assays demonstrate expression of human SOX8 and mouse Sox8 in growth plate cartilage. In situ assays show that Sox8 is expressed at a similar level as Sox9 in reserve and early columnar chondrocytes and turned off when Sox9 expression peaks in late columnar and prehypertrophic chondrocytes. Sox8 -/- mice and Sox8 fl/fl Prx1Cre and Sox9 fl/+ Prx1Cre mice (inactivation in limb skeletal cells) have a normal or near normal skeletal size. In contrast, juvenile and adult Sox8 fl/fl Sox9 fl/+ Prx1Cre compound mutants exhibit a 15 to 20% shortening of long bones. Their growth plate reserve chondrocytes progress slowly toward the columnar stage, as witnessed by a delay in down-regulating Pthlh expression, in packing in columns and in elevating their proliferation rate. SOX8 or SOX9 overexpression in chondrocytes reveals not only that SOX8 can promote growth plate cell proliferation and differentiation, even upon inactivation of endogenous Sox9 , but also that it is more efficient than SOX9, possibly due to greater protein stability. Altogether, these findings uncover a major role for SOX8 and SOX9 in promoting skeletal growth by stimulating commitment of growth plate reserve chondrocytes to actively proliferating columnar cells. Further, by showing that SOX8 is more chondrogenic than SOX9, they suggest that SOX8 could be preferred over SOX9 in therapies to promote cartilage formation or regeneration in developmental and degenerative cartilage diseases., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: This study addresses the pervasive issue of heightened preoperative anxiety in healthcare, particularly among pediatric patients. Recognizing the various sources of anxiety, we explored both pharmacological and nonpharmacological interventions. Focusing on distraction techniques, including active and passive forms, our meta-analysis aimed to provide comprehensive insights into their impact on preoperative anxiety in pediatric patients., Methods: Following the PRISMA and Cochrane guidelines, this meta-analysis and systematic review assessed the efficacy of pharmaceutical and distraction interventions in reducing pain and anxiety in pediatric surgery. This study was registered on PROSPERO (CRD42023449979)., Results: This meta-analysis, comprising 45 studies, investigated pharmaceutical interventions and distraction tactics in pediatric surgery. Risk of bias assessment revealed undisclosed risks in performance and detection bias. Distraction interventions significantly reduced preoperative anxiety compared to control groups, with notable heterogeneity. Comparison with Midazolam favored distraction techniques. Subgroup analysis highlighted varied efficacies among distraction methods, with a notable reduction in anxiety levels. Sensitivity analysis indicated stable results. However, publication bias was observed, suggesting a potential reporting bias., Conclusion: Our study confirms distraction techniques as safe and effective for reducing pediatric preoperative anxiety, offering a valuable alternative to pharmacological interventions., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=449979, PROSPERO [CRD42023449979]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Mustafa, Shafique, Zaidi, Qamber, Rangwala, Ahmed, Zaidi, Rangwala, Uddin, Ali, Siddiq and Haseeb.)

Zearalenone (ZEA) poses severe reproductive toxicity to both humans and animals. Scutellarin has been demonstrated to rescue ZEA-induced apoptosis in mouse ovarian granulosa cells (GCs), but its specific targets remain unclear. In the present study, the potential targets of scutellarin were determined to clarify the mechanisms of scutellarin against ZEA-induced ovarian damage. 287 targets of scutellarin in mouse ovarian GCs were obtained by magnetic nano-probe-based fishing assay and liquid chromatography-tandem mass spectrometry. Wnt5a had the lowest binding free energy with scutellarin at - 8.3 kcal/mol. QRT-PCR and western blot showed that scutellarin significantly increased the Wnt5a and β-catenin expression compared with the ZEA-treated group, and cleaved-caspase-3 expression was significantly increased in the scutellarin-treated group after interfering with the expression of Wnt5a. The affinity constant (K D ) of Wnt5a and scutellarin was 1.7 × 10 -5 M. The pull-down assay also demonstrated that scutellarin could specifically bind to Wnt5a protein. Molecular docking results showed that scutellarin could form hydrogen bonds with TRY52, GLN56, and SER90 on Wnt5a protein, and western blot assay confirmed SER90 was an important site for the binding. Scutellarin significantly increased Wnt5a and β-catenin expression and decreased cleaved-caspase-3 expression in ovarian tissues of mice. In conclusion, scutellarin exerted anti-apoptotic effects on ZEA-induced mouse ovarian GCs by targeting Wnt5a., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Na Sun reports financial support was provided by Central Government Guides Local Science and Technology Development Projects of Shanxi Province. Na Sun reports financial support was provided by National Natural Science Foundation of China. Hongquan Li reports financial support was provided by National Key Research and Development Program. Hongquan Li reports financial support was provided by Key Research and Development Plan of Shanxi Province. Na Sun reports financial support was provided by the special fund for Science and Technology Innovation Teams of Shanxi Province. Na Sun reports financial support was provided by earmarked fund for Modern Agro-industry Technology Research System., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The current study examined predictors of mental health treatment among Black men while incarcerated. Participants were 76 individuals who identified as Black Americans and were recruited from a correctional setting. Using secondary data analysis (Shaw, L. B., & Morgan, R. D. (2011). Inmate attitudes toward treatment: Mental health service utilization and treatment effects. Law and Human Behavior, 35(4), 249-261. https://doi.org/10.1007/s10979-010-9233-5 .), results indicated that Black men with a mental health diagnosis were more likely than those without a diagnosis to report receiving mental health treatment while incarcerated. Additionally, linear regression analyses indicated that only expectations about treatment (i.e., personal commitment; not therapy fears or history of mental health diagnosis) significantly predicted the current use of mental health treatment. Implications for research and practice are discussed., (© 2023. The Author(s).)

Background: The choice of fluid resuscitation in Traumatic Hemorrhagic shock (THS) remains a critical aspect of patient management. Bicarbonated Ringers solution (BRS) has shown promise due to its composition resembling human Extracellular Fluid and its potential benefits on hemodynamics., Objective: To evaluate the efficacy, mortality rates, hemodynamic effects, and adverse outcomes of Sodium Bicarbonate Ringer's Solution in the treatment of hemorrhagic shock, as compared to other relevant interventions., Method: A comprehensive examination of the available literature was performed by conducting systematic searches in prominent databases such as Cochrane, EMBASE, MEDLINE, and PubMed. The process employed predefined criteria to extract relevant data and evaluate the quality of the studies. The outcome measures considered encompassed survival rates, mortality, mean arterial pressure (MAP), heart rate (HR), and adverse events., Result: The meta-analysis of three studies showed that compared to the other crystalloids, the use of BRS had an odds ratio for survival of 1.86 (95% CI: 0.94, 3.71; p = 0.08; I 2  = 0%), an odds ratio for total adverse events of 0.14 (95% CI: 0.06, 0.35; p < 0.0001; I 2  = 22%), a mean difference in heart rate of -4.49 (95% CI: -7.55, -1.44; p = 0.004; I 2  = 13%), and a mean difference in mean arterial pressure of 2.31 (95% CI: -0.85, 5.47; p = 0.15; I 2  = 66%)., Conclusion: BRS demonstrated a significant reduction in complications, including adult respiratory distress syndrome (ARDS), Multiple Organ Dysfunction (MODS), and Total Adverse Effects, when compared to other solutions in the treatment of THS. Additionally, THS patients resuscitated with BRS experienced a notable decrease in heart rate. The findings suggest BRS may contribute to organ stability and potential survival improvement due to its similarity to human Extracellular Fluid and minimal impact on the liver., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background:  Laparoscopic cholecystectomy (LC) is the preferred method for gallstone removal, but bile duct injuries remain a concern. Achieving the critical view of safety (CVS) is pivotal in preventing such injuries. The aim of this study was to compare the rates of difficult LC in those with CVS achieved compared to those with CVS not achieved., Methods: We performed a single-center prospective study on all patients with ultrasound-confirmed symptomatic gallstones. Patients were excluded if they refused to consent or if they underwent LC for indications other than gallstone disease. Patients were stratified into two groups as CVS not achieved and CVS achieved groups and compared for outcomes. Our primary outcome was the rate of intraoperative difficulty on the modified Nassar scale (MNS). Statistical analysis was performed using SPSS version 25.0 (IBM Corp., Armonk, NY)., Results: We included 70 patients who underwent LC for gallstones (CVS not achieved = 24 and CVS achieved = 46). The mean (SD) age was 42.2 (12.3) years, and 73.5% were females. The mean (SD) weight in our study cohort was 74.1 (10.9) kg, and there was no difference between the two groups in terms of the baseline demographic characteristics, disease characteristics, and comorbid conditions (p > 0.05). On univariate analyses, achieving CVS was associated with lower rates of higher-grade operative difficulty on the MNS and lower rates of length of stay of more than one day., Conclusion: Achieving CVS is associated with easy LC based on significantly lower Nassar scores. These findings highlight the role of the MNS in the successful identification of the operative difficulty of LC and its correlation with achieving CVS., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Bakhtiar Khan et al.)

Background: Laparoscopic cholecystectomy (LC) is the preferred treatment option in non-complicated symptomatic cholelithiasis. In some cases, the surgery might be complicated by different factors resulting in difficult LC. Ultrasound remains the first-line modality for diagnosing symptomatic cholelithiasis; however, its role in predicting difficult LC remains unclear. The aim of this study was to validate an ultrasonographic scoring system in predicting difficult LC., Methods: We prospectively enrolled patients undergoing LC in a tertiary care unit over six months. All adult (≥18 years) patients undergoing LC for symptomatic cholelithiasis were included. Patients were excluded if they refused to consent, and those who underwent cholecystectomy for indications other than cholelithiasis. Patients were stratified into two groups based on intra-operative difficulty (easy LC and difficult LC) and were compared. Our primary outcome was radiologic difficulty among these groups. Univariate analysis and kappa statistics were performed., Results: We identified 68 patients with an overall mean (SD) age of 42.2 (12.3) years, a mean (SD) weight of 74.1 (10.9) kg, and 73.5% were female. Of the study cohort, 52 patients had easy LC and 16 patients experienced difficult LC. Amongst the total, 14.7% suffered from diabetes mellitus, 29.4% had hypertension, 7.4% had a known ischemic heart disease, and 63% had a body mass index (BMI) ≥30 kg/m 2 with no statistically significant difference between the two groups. On the Chi-square test, there was no statistical difference between the two groups in terms of ultrasonographic difficulty (p>0.05). However, we found a Kappa value of -0.127 (p=0.275) corresponding to a strong disagreement between the intraoperative and ultrasonographic difficulty., Conclusion: Despite its role in diagnosing cholelithiasis, an ultrasonographic assessment did not have a role in predicting difficult LC according to the present study. Further studies are required to develop a scoring system for predicting difficult LC based on clinical, laboratory, and ultrasonographic assessment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Bakhtiar Khan et al.)

Background: Chronic subdural hematoma (CSDH) is a condition characterized by the accumulation of fluid, blood, and blood breakdown products between the brain's arachnoid and dura mater coverings. While steroids have been explored as a potential treatment option, their efficacy and safety remain uncertain. This meta-analysis and systematic review aimed to assess the impact of steroids on CSDH management, including mortality, recurrence, complications, and functional outcomes., Methods: We conducted a comprehensive literature search in major electronic databases up to June 2023, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Cochrane Handbook for Systematic Reviews and Interventions. Inclusion criteria encompassed adult patients with CSDH, the use of steroids as monotherapy or adjuvant therapy, and clearly defined outcomes. Randomized controlled trials and cohort studies meeting these criteria were included in the study., Results: The initial search yielded 4315 articles, with 12 studies meeting the inclusion criteria. Our findings indicate a non-significant trend toward reduced mortality with steroids in combination with standard care (Odds ratios [OR] = 0.66, 95% confidence interval [CI] 0.20-2.18). However, substantial heterogeneity was observed (I 2 = 70%). Sensitivity analysis, excluding influential studies, suggested a potential increased mortality risk associated with steroids (OR = 1.47, 95% CI 0.87-2.48). Steroids showed a possible benefit in reducing the recurrence of CSDH (OR = 0.58, 95% CI 0.20-1.67), but with significant heterogeneity (I 2 = 89%). No clear advantage of steroids was observed in terms of functional outcomes at three months (modified Rankin scale scores). Furthermore, steroids were associated with a significantly higher incidence of adverse effects and complications (OR = 2.17, 95% CI 1.48-3.17)., Conclusion: Steroids may have a potential role in reducing CSDH recurrence but do not appear to confer significant advantages in terms of mortality or functional outcomes. However, their use is associated with a higher risk of adverse effects and complications. Given the limitations of existing studies, further research is needed to refine the role of steroids in CSDH management, considering patient-specific factors and treatment protocols., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Surgical Neurology International.)

Tricuspid regurgitation (TR) is a heart condition where blood flows backward through the tricuspid valve. Tricuspid valve disease constitutes a major valvular heart condition that is receiving heightened attention due to tailored treatment options and sex-specific differences in treatment outcomes. The study aims to investigate whether biological sex has a significant influence on the development, progression, and treatment outcomes of tricuspid valve disease in adults. We conducted a comprehensive search to identify studies examining the impact of sex on the pathophysiology of TR as well as treatment outcomes in patients with TR. We searched PUBMED/MEDLINE, SCOPUS, and Excerpta Medica dataBASE (EMBASE) from inception to September 2023 to identify relevant studies. Twelve studies totaling 22,574 patients met our eligibility criteria. These studies were categorized into three subgroups: patients with TR without intervention (3,848 patients, with 48.1% males and 51.9% females), those who underwent open heart surgery (17,498 patients: 46.2% males and 53.8% females), and those who underwent transcatheter tricuspid valve repair/replacement (TTVR; 1,687 patients: 41.6% males and 58.4% females). Analysis revealed no major differences in terms of TR etiology. Males tended to have a slightly lower mean age difference (mean difference (MD): -0.60 years; 95% confidence interval (CI) (-1.49, -0.04); p = 0.10) but had more frequent chronic lung disease (risk ratio (RR): 1.12, 95% CI (1.01, 1.25), p = 0.03). Males showed higher baseline TR volume (MD: 4.11, 95% CI (0.53, 7.68), p = 0.02) and lower left ventricular ejection fraction (MD: -5.85, 95% CI (-6.97, -4.73), p < 0.00001). Following open heart surgery for TR treatment, males required more frequent permanent pacemaker implantation (PPM; RR: 1.57, 95% CI (1.21, 2.03), p = 0.0006). Similarly, TTVR showed a higher need for PPM in males (RR: 1.45, 95% CI (1.10, 1.93), p = 0.010). In-hospital mortality exhibited no sex differences, but males had a slightly elevated late mortality risk. Sex differences in TR patients were notable in baseline characteristics, with males having a higher risk of certain conditions. The more frequent requirement for PPM was a major sex-based difference in terms of prognosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Khan et al.)

In the era of globalization, financial development plays a key role in socioeconomic and environmental development. However, its adverse consequences on human life, environmental hazards, and high energy consumption cannot be ignored. Thus, this study investigates the non-linear relationship between globalization, financial development, and energy consumption for BRICS economies. In doing so, we have applied second-generation tests to identify cross-sectional dependence in the data. Cross-sectional augmented Dickey-Fuller (CADF) and Cross-sectional Im-Pesaran Shin (CIPS) have been performed to find the stationary level of variables. The long-term equilibrium link between the investigated variables has been established in continuance using the Westerlund Cointegration test. The Dynamic Seemingly Unrelated Regression (DSUR) indicates that U-shaped relationships exist for financial development and globalization with energy consumption. Conversely, there is an inverted U-shaped relationship exist between economic growth and energy consumption in BRICS. The Dumitrescu-Hurlin panel causality test findings show that a unidirectional link runs from energy consumption to financial development, economic growth to energy consumption, and globalization towards energy usage. Important policy implications have also been discussed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Imran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Surgical site infections are common and expensive infections that can cause fatalities or poor patient outcomes. To prevent these infections, antibiotic prophylaxis is used. However, excessive antibiotic use is related to higher costs and the emergence of antimicrobial resistance., Objectives: The present meta -analysis aimed to compare the effectiveness of a single dosage versus several doses of antibiotics in preventing the development of surgical site infections., Methods: PubMed was used to find clinical trials evaluating the effectiveness of a single dosage versus several doses of antibiotics in avoiding the development of surgical site infections. The study included trials that were published between 1984 and 2022. Seventy-four clinical trials were included in the analysis. Odds ratios were used to compare groups with 95% confidence intervals. The data were displayed using OR to generate a forest plot. Review Manager (RevMan version 5.4) was used to do the meta -analysis., Results: Regarding clean operations, there were 389 surgical site infections out of 5,634 patients in a single dose group (6.90%) and 349 surgical site infections out of 5,621 patients in multiple doses group (6.21%) (OR = 1.11, lower CI = 0.95, upper CI = 1.30). Regarding clean-contaminated operations, there were 137 surgical site infections out of 2,715 patients in a single dose group (5.05%) and 137 surgical site infections out of 2,355 patients in multiple doses group (5.82%) (OR = 0.87, lower CI = 0.68, upper CI = 1.11). Regarding contaminated operations, there were 302 surgical site infections out of 3,262 patients in a single dose group (9.26%) and 276 surgical site infections out of 3,212 patients in multiple doses group (8.59%) (OR = 1.11, lower CI = 0.84, upper CI = 1.47). In general, there were 828 surgical site infections out of 11,611 patients in a single dose group (7.13%) and 762 surgical site infections out of 11,188 patients in multiple doses group (6.81%) (OR = 1.05, lower CI = 0.93, upper CI = 1.20). The difference between groups was not significant., Conclusion: The present study showed that using a single-dose antimicrobial prophylaxis was equally effective as using multiple doses of antibiotics in decreasing surgical site infections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Antibiotics are gradually becoming less effective against bacteria worldwide, and this issue is of particular concern in economically-developing nations like Pakistan. We undertook a scoping review in order to review the literature on antimicrobial use, prescribing, dispensing and the challenges associated with antimicrobial resistance in primary care (PC) settings in Pakistan. Furthermore, this review aims to identify potential solutions to promote appropriate use of antimicrobials in Pakistan. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) checklist, a comprehensive scoping review was conducted to review the literature of antimicrobials used, prescribed and dispensed in PC settings in Pakistan. Google Scholar and Pub-Med were searched for the period 2000-2023. Papers were analyzed on the basis of eligibility i.e., included antimicrobial use, prescribing and dispensing practices by general population at homes, by prescribers in outpatient departments of hospitals and by pharmacists/dispensers in community pharmacies, respectively. Two researchers analyzed the articles thoroughly and disagreements were resolved through discussion with a third reviewer. Both quantitative and qualitative research studies were eligible for inclusion. Additionally, the selected papers were grouped into different themes. We identified 4070 papers out of which 46 studies satisfied our eligibility criteria. The findings revealed limited understanding of antimicrobial resistance (AMR) by physicians and community pharmacists along with inappropriate practices in prescribing and dispensing antibiotics. Moreover, a notable prevalence of self-medication with antibiotics was observed among the general population, underscoring a lack of awareness and knowledge concerning proper antibiotic usage. Given the clinical and public health implications of AMR, Pakistan must prioritize its policies in PC settings. Healthcare professionals (HCPs) need to reduce inappropriate antibiotic prescribing and dispensing, improve their understanding of the AWaRe (access, watch and reserve antibiotics) classification and guidance, monitor current usage and resistance trends, as well as implement antimicrobial stewardship (ASP) activities starting in targeted locations., Competing Interests: Declaration of Competing Interest The authors confirm that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The existence of Type 2 Diabetes Mellitus (DM) in tuberculosis (TB) patients is very dangerous for the health of patients. One of the major concerns is the emergence of MDR-TB in such patients. It is suspected that the development of MDR-TB further worsens the treatment outcomes of TB such as treatment failure and thus, causes disease progression., Aim: To investigate the impact of DM on the Emergence of MDR-TB and Treatment Failure in TB-DM comorbid patients., Methodology: The PubMed database was systematically searched until April 03, 2022 (date last searched). Thirty studies met the inclusion criteria and were included in this study after a proper selection process., Results: Tuberculosis-Diabetes Mellitus patients were at higher risk to develop MDR-TB as compared to TB-non-DM patients (HR 0.81, 95% CI: 0.60-0.96, p  < 0.001). Heterogeneity observed among included studies was moderate (I 2  = 38%). No significant change was observed in the results after sub-group analysis by study design (HR 0.81, 95% CI: 0.61-0.96, p  < 0.000). In the case of treatment failure, TB-DM patients were at higher risk to experience treatment failure rates as compared to TB-non-DM patients (HR 0.46, 95% CI: 0.27-0.67, p  < 0.001)., Conclusion: The results showed that DM had a significant impact on the emergence of MDR-TB in TB-diabetes comorbid patients as compared to TB-non-DM patients. DM enhanced the risk of TB treatment failure rates in TB-diabetes patients as compared to TB-non-DM patients. Our study highlights the need for earlier screening of MDR-TB, thorough MDR-TB monitoring, and designing proper and effective treatment strategies to prevent disease progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rehman, Khattak, Mushtaq, Latif, Ahmad, Rasool, Shakeel, Hayat, Hussain, Alhazmi, Alshomrani, Alalawi, Alghamdi, Imam, Almarzoky Abuhussain, Khayyat and Haseeb.)

The inappropriate prescribing of antimicrobials increases antimicrobial resistance (AMR), which poses an appreciable threat to public health, increasing morbidity and mortality. Inappropriate antimicrobial prescribing includes their prescribing in patients hospitalized with COVID-19, despite limited evidence of bacterial infections or coinfections. Knowledge of current antimicrobial utilization in Saudi Arabia is currently limited. Consequently, the objective of this study was to document current antimicrobial prescribing patterns among Saudi hospitals during the COVID-19 pandemic. This study included patients with or without COVID-19 who were admitted to five hospitals in Makkah, Saudi Arabia. Data were gathered using the Global PPS methodology and analyzed using descriptive statistics. Out of 897 hospitalized patients, 518 were treated with antibiotics (57.7%), with an average of 1.9 antibiotics per patient. There were 174 culture reports collected, representing 36.5% of all cases. The most common indication for antibiotics use was community-acquired infections, accounting for 61.4% of all cases. 'Watch' antibiotics were the most commonly prescribed antibiotics, with the cephalosporins and carbapenems representing 38.7% of all antibiotics prescribed, followed by the penicillins (23.2%). Notably, Piperacillin/Tazobactam and Azithromycin were prescribed at relatively higher rates for COVID-19 patients. These findings highlight the need for continuous efforts to optimize the rational use of antibiotics through instigating appropriate antimicrobial stewardship programs in hospitals and, as a result, reduce AMR in the country.