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Immunotoxins (ITs) are specialized therapeutic agents designed for targeted treatment, particularly in cancer therapy. They consist of a monoclonal antibody or antibody fragment linked to a potent cytotoxic agent, such as bacterial- or plant-derived toxins like diphtheria toxin, ricin, or pseudomonas exotoxin. The monoclonal antibody component specifically binds to antigens expressed on the surface of target cells, facilitating the internalization of the IT. Once inside the cell, the cytotoxic agent is released, disrupting essential cellular processes and leading to cell death. This targeted approach minimizes damage to healthy tissues while effectively eliminating diseased cells. The production of ITs involves two primary methods: recombinant fusion and chemical conjugation. In recombinant fusion, genetic engineering is used to create a fusion protein that combines the antibody and toxin, ensuring precise control over their ratio and functionality. In chemical conjugation, pre-existing antibodies are chemically linked to toxins, allowing for greater flexibility in combining different antibodies and cytotoxic agents. Each method has its advantages and challenges, influencing the specificity, production complexity, and therapeutic potential of the resulting ITs. As research advances, ITs continue to show promise not only in oncology but also in treating other diseases, including inflammatory conditions and atherosclerosis. The precise targeting and potent effects of ITs make them a valuable tool in the development of new therapeutic strategies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Glioblastoma patients may develop functional deficits post-operatively that affect activities of daily living and result in worse outcomes. The Activity Measure for Post-Acute Care (AM-PAC) instrument assigns patients basic mobility and daily activity scores, but it is unknown if these scores correlate with post-operative outcomes in glioblastoma patients., Methods: Adult (≥18 years) glioblastoma patients evaluated by physical/occupational therapy after resection at a single instution (June 2008-December 2020) were identified. Patient demographics, post-operative AM-PAC scores, and clinical outcomes were collected. Multivariate regression identified associations between AM-PAC scores and post-operative outcomes., Results: 600 patients were included (mean age 59.3 years, 59.2 % male); 151 (25.3 %) and 246 (43.8 %) patients had low mobility (<42.9) and activity (<39.4) scores, respectively. 103 (17.2 %) and 177 (29.5 %) patients experienced extended lengths of stay (LOS) in the ICU (≥2 days) and overall (≥7 days), respectively. 154 (25.7 %) patients had non-home discharges. The 30-day readmission rate was 13.7 %. In multivariate analysis, low mobility scores correlated with increased odds of extended overall (p < 0.0001) and ICU (p = 0.0004) LOS, non-home discharge (p < 0.0001), and 30-day readmission (p = 0.0405). Low activity scores correlated with extended overall LOS (<0.0001) and non-home discharge (p < 0.0001). In log-rank analysis, median survival time was shorter for patients with low mobility (9.5 vs. 14.7 months, p < 0.0001) and activity (10.6 vs. 16.3 months, p < 0.0001) scores than for high-scoring patients., Conclusion: AM-PAC basic mobility and daily activity scores are associated with outcomes after glioblastoma resection. These easily obtainable scores may be useful for prognosticating and guiding decision making in post-operative glioblastoma patients., 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 Elsevier Ltd. All rights reserved.)

Background: The Disintegrin and Metalloproteinase (ADAM) family, also known as the metalloproteinase/disintegrin/cysteine-rich (MDC) proteins, includes both secreted and transmembrane molecules involved in critical biological processes, such as cell migration, adhesion, and signaling. This study aimed to investigate the evolutionary relationships and structural characteristics of disintegrin and metalloproteinase proteins identified in the venom gland transcriptome of the scorpion Hemiscorpius lepturus., Methods: Using bioinformatics tools, we analyzed the open reading frame, conserved motifs, and primary, secondary, and tertiary structures of these proteins. Five proteins, named HLDis- Met1, HLDisMet2, HLDisMet3, HLDisMet4, and HLDisMet5, were identified. Their predicted 3- D structures were within normal ranges (Z-score between -4 to -9)., Results: Phylogenetic analysis revealed that HLDisMet1 shares similarities with proteins from various spider species (Nephila pilipes, Argiope bruennichi, Araneus ventricosus, and Trichonephila inaurata madagascariensis), HLDisMet2 with the scorpion Centruroides sculpturatus, HLDis- Met4 with the scorpion Tityus serrulatus, and HLDisMet5 with several snake species (Python bivittatus, Vipera anatolica senliki, Protobothrops mucrosquamatus, and Naja naja)., Conclusion: These findings highlight the significant similarities between HLDisMet proteins and those found in other venomous species, suggesting a complex and diverse evolutionary pathway for venom components. The cross-species conservation observed may indicate a convergent evolutionary strategy, where different species independently develop similar venom components to adapt to similar ecological niches or prey types. This study highlights the evolutionary significance of venom diversification and its potential applications in understanding venom biology across different species., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The use of mRNA and ribonucleoproteins (RNPs) as therapeutic agents is a promising strategy for treating diseases such as cancer and infectious diseases. This review provides recent advancements and challenges in mRNA- and RNP-based therapies, focusing on delivery systems such as lipid nanoparticles (LNPs), which ensure efficient delivery to target cells. Strategies such as microfluidic devices are employed to prepare LNPs loaded with mRNA and RNPs, demonstrating effective genome editing and protein expression in vitro and in vivo . These applications extend to cancer treatment and infectious disease management, with promising results in genome editing for cancer therapy using LNPs encapsulating Cas9 mRNA and single-guide RNA. In addition, tissue-specific targeting strategies offer potential for improved therapeutic outcomes and reduced off-target effects. Despite progress, challenges such as optimizing delivery efficiency and targeting remain. Future research should enhance delivery efficiency, explore tissue-specific targeting, investigate combination therapies, and advance clinical translation. In conclusion, mRNA- and RNP-based therapies offer a promising avenue for treating various diseases and have the potential to revolutionize medicine, providing new hope for patients worldwide., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Leukemia, a type of blood cancer marked by an abnormal increase in white blood cells, poses a significant challenge to healthcare. The key to successful treatment lies in early detection. However, traditional methods often fall short. This review investigates the potential of electrochemical biosensors for a more accurate and earlier diagnosis of leukemia. Electrochemical biosensors are compact devices that transform biological interactions into electrical signals. Their small size, ease of use, and minimal sample requirements make them perfectly suited for point-of-care applications. Their remarkable sensitivity and specificity enable the detection of subtle biomolecular changes associated with leukemia, which is crucial for early disease detection. This review delves into studies that have utilized these biosensors to identify various types of leukemia. It examines the roles of electrodes, biorecognition elements, and signal transduction mechanisms. The discussion includes the integration of nanomaterials such as gold nanoparticles and nitrogen-doped graphene into biosensor design. These materials boost sensitivity, enhance signal amplification, and facilitate multi-analyte detection, thereby providing a more holistic view of the disease. Beyond technical advancements, the review underscores the practical benefits of these biosensors. Their portability makes them a promising tool for resource-constrained settings, enabling swift diagnosis in remote areas or at a patient's bedside. The potential for monitoring treatment effectiveness and detecting minimal residual disease to prevent relapse is also explored. This review emphasizes the transformative potential of electrochemical biosensors in combating leukemia. By facilitating earlier and more accurate diagnosis, these biosensors stand to revolutionize patient care and enhance treatment outcomes., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Burnout is recognized as a negative contributor to well-being within healthcare. The purpose of this study was to evaluate whether participation in the Peace Education Program (PEP), a 10-week wellness course, promoted durable improvement of burnout and wellness in a large academic medical center. We deployed PEP virtually through a series of free, interactive, online wellness sessions focusing on 10 domains: peace, appreciation, inner strength, self-awareness, clarity, understanding, dignity, choice, hope, and contentment. Two weeks before and six months following the sessions, we distributed de-identified surveys based upon the validated Schwartz Outcome Scale-10 (SOS-10) with Likert scale scores 0-6 to assess participant wellness. The Mann-Whitney U test was used to analyze statistical differences between post- and pre-course data. Sixty-nine faculty, trainees, and staff registered to participate, 21 participants completed the pre-course survey and 10 completed the post-course survey. The pre-course mean + standard error (SE) SOS-10 score was 43.2 ± 0.8, which improved to 51.0 ± 0.7 post-course ( P < 0.001). Overall, all 10 domains demonstrated improved mean scores over time, with the five domains of "inner strength" ( P = 0.008), "understanding" ( P = 0.030), "peace" ( P = 0.048), "choice" ( P = 0.026), and "hope" ( P = 0.020) demonstrating statistically significant score improvements six months after course completion. Participants completing ≥7 sessions benefited more than their counterparts and achieved statistically significant improvement in SOS-10 wellness scores (8.77 points) six months after course completion. Our findings demonstrate improved wellness in participants following peace education course completion. This free, interactive, online course may be utilized at other medical centers to improve wellness., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Education and Health Promotion.)

Background and Objectives: Surgery for the very elderly is a progressively important paradigm as life expectancy continues to rise. Patients with glioblastoma multiforme often undergo surgery, radiotherapy (RT), and chemotherapy (CT) to prolong overall survival (OS). However, the efficacy of these treatment modalities in patients aged 80 years and older has yet to be fully assessed in the literature., Methods: The National Cancer Database was used to retrospectively identify patients aged 65 years and older with glioblastoma multiforme (1989-2016). All available patient demographic characteristics, disease characteristics, and clinical outcomes were collected. To study OS, bivariable survival models were created using Kaplan-Meier estimates. A Cox proportional-hazards model was used for final adjusted analyses., Results: A total of 578 very elderly patients (aged 80 years and older) and 2836 elderly patients (aged 65-79 years) were identified. Compared with elderly patients, very elderly patients were more likely to have Medicare (odds ratio [OR] 1.899 [95% CI: 1.417-2.544], P < .001) while less likely to have private insurance status (OR 0.544 [95% CI: 0.401-0.739], P < .001). In addition, very elderly patients were more likely to travel the least distance for treatment and have multiple tumors (P < .001). When controlling for demographic and disease characteristics, very elderly patients were less likely to receive gross total resection (GTR) (OR 0.822 [95% CI: 0.681-0.991], P < .041), RT (OR 0.385 [95% CI: 0.319-0.466], P < .001), or postoperative CT (OR 0.298 [95% CI: 0.219-0.359], P < .001) relative to elderly counterparts. Within very elderly patients, GTR, RT, and CT all independently and significantly predicted improved OS (P < .001 for all). These predictive models were deployed in an online calculator (https://spine.shinyapps.io/GBM&#95;elderly)., Conclusion: Very elderly patients are less likely to receive GTR, RT, or CT when compared with elderly counterparts despite use of these therapies conferring improved OS. Selected very elderly patients may benefit from more aggressive attempts at surgical and adjuvant treatment., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background and Aims: The primary objective of this systematic review and meta-analysis was to assess the impact of dextrose prolotherapy on individuals diagnosed with knee osteoarthritis (KOA)., Methods: To conduct a thorough investigation, a variety of leading international databases were checked, including PubMed (Medline), Scopus, Web of Sciences, EMBASE (Elsevier), ClinicalTrials.gov, and the Cochrane Library. The search covered a period from January 2000 to the end of June 2023, which facilitated the collection of relevant studies., Results: The findings of the study revealed that when the studies utilizing the Western Ontario McMaster Universities Index tool (WOMAC) were combined, patients with KOA who received prolotherapy experienced an improvement in function compared with those who received other treatments (SMD: 0.20; 95% Confidence Interval [1]: -0.11, 0.51; p value SMD = 0.221; I 2 : 78.49%; p heterogeneity  < 0.001). Additionally, there was a decrease in mean pain and stiffness among patients who received prolotherapy compared with those who received other treatments or a placebo [(SMD: -0.95; 95% CI: -1.14, -0.76; p value SMD < 0.001; I 2 : 59.35%; p heterogeneity  = 0.070) and (SMD: -0.21; 95% CI: -0.32, -0.10; p value SMD < 0.001; I 2 : 88.11%; p heterogeneity  < 0.001)]. Furthermore, based on the Visual Analog Scale (VAS) score, there was a reduction of 0.81 units out of 10 in mean pain for patients with KOA who received prolotherapy (SMD: -0.81; 95% CI: -5.63, 4.10; p value SMD = 0.693; I 2 : 48.54%; p heterogeneity  = 0.08)., Conclusion: Drawing from the data analysis performed in this meta-analysis, it is apparent that dextrose prolotherapy exhibits promising effectiveness in reducing joint pain and stiffness, as well as improving functional performance in individuals suffering from KOA. Furthermore, it is recommended that forthcoming studies incorporate follow-up periods to guide decisions concerning the duration of prolotherapy's effects., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Advanced molecular testing has increasingly become an integral component for accurate diagnosis of central nervous system (CNS) tumors. We sought to establish the current state of molecular testing availability and approaches for the diagnosis of CNS tumors in US hospitals that conduct high volumes of CNS tumor resections. We distributed a 16-item survey inquiring about molecular testing approaches for CNS tumors to 115 neuropathologists at US hospitals with neurosurgery residency programs. Thirty-five neuropathologists (30.4%) responded to the survey, all of whom indicated their institutions perform molecular testing on CNS tumor tissue. The most commonly offered tests were MGMT methylation profiling and next-generation sequencing. Fourteen respondents (40%) indicated that their institution is able to test for and report all of the molecular alterations included in our survey. Nine (25.7%) respondents indicated that molecular testing is performed as standard of care for all patients with resected CNS tumors. Our results suggest that even in academic hospitals with a high volume of CNS tumor resections, molecular testing for these tumors is limited. Continued initiatives are necessary to expand the availability of molecular testing for CNS tumors to ensure diagnostic accuracy and guide targeted therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc.)

Objective: Spinal chordoma treatment guidelines recommend resection. However, in patients in whom gross-total resection (GTR) is achieved, the benefits of radiation therapy (RT) are unclear. Therefore, the authors performed a systematic review to determine if RT is associated with postoperative progression-free survival (PFS) or overall survival (OS) after achieving GTR of spinal chordoma., Methods: The PubMed database was searched for studies including individualized data of patients undergoing GTR with or without RT for spinal chordoma. Patients < 18 years of age or those who underwent stereotactic body RT were excluded. Qualitative assessment was performed using Newcastle-Ottawa Scale guidelines. Log-rank tests for time-to-event data and a Cox proportional-hazards model were generated for a multivariable statistical model., Results: Complete data of 132 patients were retrieved, with 37 (28%) patients receiving adjuvant RT and 95 (72%) not receiving adjuvant RT. The mean follow-up was not statistically significantly different between those undergoing RT and not undergoing RT (54.02 months and 65.43 months, respectively). Patients were more likely not to undergo RT if their disease was located in the sacrum versus the mobile spine (p < 0.001). When controlling for age ≥ 65 years, male sex, disease location, and treatment year ≥ 2010, patients undergoing RT had similar PFS and OS when compared with those not undergoing RT on multivariable survival analysis (HR 0.935 [95% CI 0.703-2.340], p = 0.844 and HR 2.078 [95% CI 0.848-5.090], p = 0.110, respectively). However, age ≥ 65 years was associated with poorer OS in adjusted analyses (HR 2.761 [95% CI 1.185-6.432], p = 0.018) relative to patients < 65 years of age., Conclusions: After achieving GTR of spinal chordoma, the utility of RT on PFS and OS remains unclear. Age ≥ 65 years appears to be associated with OS in spinal chordoma patients. Additional multicenter prospective studies are needed to determine the utility of RT in this patient population.

Organophosphorylated coumarin derivatives were synthesized by a three-component reaction of 4-chloro-3-formylcoumarin, aromatic amines, and dialkyl phosphite in the presence of ZnCl 2 . This process includes the formation of C(sp 3 )-P and C(sp 2 )-N bonds in one pot. The modular scope of the reaction allowed rapid access to a variety of 6 H -chromeno[4,3- b ]quinolin-7-ylphosphonate derivatives in good yields. Furthermore, photophysical studies of the products revealed their stimulating fluorescence properties.

Purpose: There is limited literature describing care coordination for patients with glioblastoma (GBM). We aimed to investigate the impact of primary care and electronic health information exchange (HIE) between neurosurgeons, oncologists, and primary care providers (PCP) on GBM treatment patterns, postoperative outcomes, and survival., Methods: We identified adult GBM patients undergoing primary resection at our institution (2007-2020). HIE was defined as shared electronic medical information between PCPs, oncologists, and neurosurgeons. Multivariate logistic regression analyses were used to determine the effect of PCPs and HIE upon initiation and completion of adjuvant therapy. Kaplan-Meier and multivariate Cox regression models were used to evaluate overall survival (OS)., Results: Among 374 patients (mean age ± SD: 57.7 ± 13.5, 39.0% female), 81.0% had a PCP and 62.4% had electronic HIE. In multivariate analyses, having a PCP was associated with initiation (OR: 7.9, P < 0.001) and completion (OR: 4.4, P < 0.001) of 6 weeks of concomitant chemoradiation, as well as initiation (OR: 4.0, P < 0.001) and completion (OR: 3.0, P = 0.007) of 6 cycles of maintenance temozolomide thereafter. Having a PCP (median OS [95%CI]: 14.6[13.1-16.1] vs. 10.8[8.2-13.3] months, P = 0.005) and HIE (15.40[12.82-17.98] vs. 13.80[12.51-15.09] months, P = 0.029) were associated with improved OS relative to counterparts in Kaplan-Meier analysis and in multivariate Cox regression analysis (hazard ratio [HR] = 0.7, [95% CI] 0.5-1.0, P = 0.048). In multivariate analyses, chemoradiation (HR = 0.34, [95% CI] 0.2-0.7, P = 0.002) and maintenance temozolomide (HR = 0.5, 95%CI 0.3-0.8, P = 0.002) were associated with improved OS relative to counterparts., Conclusion: Effective care coordination between neurosurgeons, oncologists, and PCPs may offer a modifiable avenue to improve GBM outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Socioeconomic status (SES) is a major determinant of quality of life and outcomes. However, SES remains difficult to measure comprehensively. Distress communities index (DCI), a composite of 7 socioeconomic factors, has been increasingly recognized for its correlation with poor outcomes. As a result, the objective of the present study is to determine the predictive value of the DCI on outcomes following intracranial tumor surgery., Methods: A single institution, retrospective review was conducted to identify adult intracranial tumor patients undergoing resection (2016-2021). Patient ZIP codes were matched to DCI and stratified by DCI quartiles (low:0-24.9, low-intermediate:25-49.9, intermediate-high:50-74.9, high:75-100). Univariate followed by multivariate regressions assessed the effects of DCI on postoperative outcomes. Receiver operating curves were generated for significant outcomes., Results: A total of 2389 patients were included: 1015 patients (42.5%) resided in low distress communities, 689 (28.8%) in low-intermediate distress communities, 445 (18.6%) in intermediate-high distress communities, and 240 (10.0%) in high distress communities. On multivariate analysis, risk of fracture (adjusted odds ratio = 1.60, 95% confidence interval 1.26-2.05, P < 0.001) and 90-day mortality (adjusted odds ratio = 1.58, 95% confidence interval 1.21-2.06, P < 0.001) increased with increasing DCI quartile. Good predictive accuracy was observed for both models, with receiver operating curves of 0.746 (95% CI 0.720-0.766) for fracture and 0.743 (95% CI 0.714-0.772) for 90-day mortality., Conclusions: Intracranial tumor patients from distressed communities are at increased risk for adverse events and death in the postoperative period. DCI may be a useful, holistic measure of SES that can help risk stratifying patients and should be considered when building healthcare pathways., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The Hospital Frailty Risk Score (HFRS) is a recently developed tool that uses ICD-10 codes to measure patient frailty. However, the effectiveness of HFRS has not yet been assessed in meningioma patients specifically. The present study aimed to evaluate the effectiveness of HFRS in predicting surgical outcomes for patients with meningiomas., Methods: This retrospective study utilized data from patients undergoing meningioma resection at a single institution (2017-2019). Data were obtained through a combination of automated data retrieval and manual chart review. Bivariate logistic regression was used to assess the prognostic ability of several frailty indices for predicting postoperative outcomes. Further, discrimination for each model was assessed using the area under the receiver operating characteristic curve (AUROC). Generalized linear models with gamma error distributions and a log-link function were used to model hospital length of stay (LOS), total charges, complications, and disposition., Results: A total of 464 meningioma patients (mean age 58.20 years, 72.8 % female, 66.4 % white) were included. HFRS had a significantly greater AUROC when compared to ASA (p = 0.0074) for postoperative complications, and HFRS significantly outperformed ASA (p = 0.0021) and mFI-5 (p = 0.018) when predicting nonroutine discharge. On multivariate analysis, increasing HFRS scores were significantly and independently associated with greater LOS (p < 0.0001), higher hospital charges (p < 0.0001), higher odds of postoperative complications (OR = 1.05, p = 0.019), and nonroutine discharge (OR = 1.12, p < 0.0001). The HFRS was non-inferior compared to the mFI-5, CCI, ASA and mFI-11 in terms of model discrimination., Conclusion: HFRS effectively predicts postoperative outcomes for meningiomas and outperforms other indices in predicting complications and nonroutine discharge. This novel index may be used to improve clinical decision-making and reduce adverse postoperative outcomes among meningioma patients., 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 Elsevier Ltd. All rights reserved.)

Background: Patient-reported outcome measures (PROMs) are increasingly used to assess patients' perioperative health. The PROM Information System 29 (PROMIS-29) is a well-validated global health assessment instrument for patient physical health, though its utility in cranial neurosurgery is unclear., Objective: To investigate the utility of preoperative PROMIS-29 physical health (PH) summary scores in predicting postoperative outcomes in brain tumor patients., Methods: Adult brain tumor patients undergoing resection at a single institution (January 2018-December 2021) were identified and prospectively received PROMIS-29 surveys during pre-operative visits. PH summary scores were constructed and optimum prediction thresholds for length of stay (LOS), discharge disposition (DD), and 30-day readmission were approximated by finding the Youden index of the associated receiver operating characteristic curves. Bivariate analyses were used to study the distribution of low (z-score≤-1) versus high (z-score>-1) PH scores according to baseline characteristics. Logistic regression models quantified the association between preoperative PH summary scores and post-operative outcomes., Results: A total of 157 brain tumor patients were identified (mean age 55.4±15.4 years; 58.0% female; mean PH score 45.5+10.5). Outcomes included prolonged LOS (24.8%), non-routine discharge disposition (37.6%), and 30-day readmission (19.1%). On bivariate analysis, patients with low PH scores were significantly more likely to be diagnosed with a high-grade tumor (69.6% vs 38.85%, p=0.010) and less likely to have elective surgery (34.8% vs 70.9%, p=0.002). Low PH score was associated with prolonged LOS (26.1% vs 22%, p<0.001), nonroutine discharge (73.9% vs 31.3%, p<0.001) and 30-day readmission (43.5% vs 14.9%, p=0.003). In multivariate analysis, low PH scores predicted greater LOS (odds ratio [OR]=6.09, p=0.003), nonroutine discharge (OR=4.25, p=0.020), and 30-day readmission (OR=3.93, p=0.020)., Conclusion: The PROMIS-29 PH summary score predicts short-term postoperative outcomes in brain tumor patients and may be incorporated into prospective clinical workflows., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The aim of this study was to delineate the clinical and socioeconomic variables associated with shunt revision in pediatric patients presenting to the emergency department (ED) with concerns of ventricular shunt malfunction., Methods: A retrospective analysis of pediatric ED consultations for shunt malfunction over a 1-year period was conducted, examining clinical symptoms, radiographic findings, and socioeconomic variables. Sensitivities, specificities, and positive and negative predictive values were calculated for each presenting symptom collected. Logistic regression models were used to estimate the odds ratios for shunt revision based on these variables, and multivariate analyses were used to adjust for potential confounders., Results: Of the 271 ED visits from 137 patients, 19.2% resulted in shunt revision. Increased ventricle size on imaging (OR 11.38, p < 0.001), shunt site swelling (OR 9.04, p = 0.01), bradycardia (OR 7.08, p < 0.001), and lethargy (OR 5.77, p < 0.001) were significantly associated with shunt revision. Seizure-like activity was inversely related to revision needs (OR 0.24, p < 0.001). Patients with private or self-pay insurance were more likely to undergo revision compared with those with public insurance (p = 0.028). Multivariate analysis further confirmed the significant associations of increased ventricle size, lethargy, and bradycardia with shunt revision, while also revealing that seizure-like activity inversely affected the likelihood of revision. Patients with severe cognitive and language disabilities were more likely to be admitted to the hospital from the ED but were not more likely to undergo revision., Conclusions: Clinical signs such as increased ventricle size, shunt site swelling, bradycardia, and lethargy may be strong predictors of the need for shunt revision in pediatric patients presenting to the ED with concerns of shunt malfunction. Socioeconomic factors play a less clear role in predicting shunt revision and admission from the ED; however, the nature of their influence is unclear. These findings can help inform clinical decision-making and optimize resource utilization in the ED.

The stimulator of the interferon genes (STING) signaling pathway plays a crucial role in innate immunity by detecting cytoplasmic DNA and initiating antiviral host defense mechanisms. The STING cascade is triggered when the enzyme cyclic GMP-AMP synthase (cGAS) binds cytosolic DNA and synthesizes the secondary messenger cGAMP. cGAMP activates the endoplasmic reticulum adaptor STING, leading to the activation of kinases TBK1 and IRF3 that induce interferon production. Secreted interferons establish an antiviral state in infected and adjacent cells. Beyond infections, aberrant DNA in cancer cells can also activate the STING pathway. Preclinical studies have shown that pharmacological STING agonists like cyclic dinucleotides elicit antitumor immunity when administered intratumorally by provoking innate and adaptive immunity. Combining STING agonists with immune checkpoint inhibitors may improve outcomes by overcoming tumor immunosuppression. First-generation STING agonists encountered challenges like poor pharmacokinetics, limited tumor specificity, and systemic toxicity. The development of the next-generation STING-targeted drugs to realize the full potential of engaging this pathway for cancer treatment can be a solution to overcome the current challenges, but further studies are required to determine optimal applications and combination regimens for the clinic. Notably, the controlled activation of STING is needed to preclude adverse effects. This review explores the mechanisms and effects of STING activation, its role in cancer immunotherapy, and current challenges., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Optical biosensors based on plasmonic nanostructures have attracted great interest due to their ability to detect small refractive index changes with high sensitivity. In this work, a novel plasmonic coupled cavity waveguide is proposed for refractive index sensing applications. The structure consists of a metal-insulator-metal waveguide side coupled to an array of asymmetric H-shape element, designed to provide dual-band resonances. The sharp transmission dips and large field enhancements associated with dual-band resonances can enable sensitive detection of material under test. The resonator array creates a slow light effect to improve light-matter interactions. The structure was simulated using the finite integration technique as the full-wave technique, and the sensitivity and figure of merit were extracted for different ambient refractive indices. The maximum sensitivity of 1774 nm/RIU and high figure of merit of 2 × 10 4 RIU -1 for the basic model and 1.15 × 10 5 RIU -1 for the modified model were achieved, demonstrating the potential for high-performance sensing. The unique transmission characteristics also allow for combined spectral shaping and detection over a broad bandwidth. The simple, compact geometry makes the design suitable for on-chip integration. This work demonstrates a promising refractive index sensor based on coupled dual-band resonators in a plasmonic waveguide., (© 2024. The Author(s).)

Objective: The Hospital Frailty Risk Score (HFRS) is a tool for quantifying patient frailty using International Classification of Diseases, Tenth Revision codes. This study aimed to determine the utility of the HFRS in predicting surgical outcomes after resection of glioblastoma (GBM) and compare its prognostic ability with other validated indices such as American Society of Anesthesiologists score and Charlson Comorbidity Index., Methods: A retrospective analysis was conducted using a GBM patient database (2017-2019) at a single institution. HFRS was calculated using International Classification of Diseases, Tenth Revision codes. Bivariate logistic regression was used to model prognostic ability of each frailty index, and model discrimination was assessed using area under the receiver operating characteristic curve. Multivariate linear and logistic regression models were used to assess for significant associations between HFRS and continuous and binary postoperative outcomes, respectively., Results: The study included 263 patients with GBM. The HFRS had a significantly greater area under the receiver operating characteristic curve compared with American Society of Anesthesiologists score (P = 0.016) and Charlson Comorbidity Index (P = 0.037) for predicting 30-day readmission. On multivariate analysis, the HFRS was significantly and independently associated with hospital length of stay (P = 0.0038), nonroutine discharge (P = 0.018), and 30-day readmission (P = 0.0051)., Conclusions: The HFRS has utility in predicting postoperative outcomes for patients with GBM and more effectively predicts 30-day readmission than other frailty indices. The HFRS may be used as a tool for optimizing clinical decision making to reduce adverse postoperative outcomes in patients with GBM., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Having a preterm infant is a stressful experience for parents, especially for mothers. This study was conducted to identify the effect of kangaroo mother care on the resilience of mothers with preterm infant hospitalized in Neonatal Intensive Care Unit., Materials and Methods: In this randomized controlled trial study, 60 mothers with preterm infant hospitalized in Neonatal Intensive Care Unit were randomly selected and allocated to intervention and control groups (30 per group), in Fatemiyeh Hospital, Hamadan, Iran. Data collection tool included demographic information and Conner & Davidson Resilience Questionnaire (CD-RISC), which were completed by mothers before and after the intervention. Kangaroo Mother Care (KMC) as an intervention was run in at least one hour daily for a week in the intervention group. The mother-infant pairs in the control group only received conventional method of care (CMC)., Results: There was a significant increase in the total resilience score of the mothers in the KMC group (from 58.87±14.71 to 69.67±14.50) after intervention (P<0.001); however, resilience score decreased significantly in the mothers of CMC group (from 57.77±13.33 to 51.63±12.20)., Conclusion: Kangaroo mother care could increase the resilience of mothers of preterm infants. Therefore using this approach as a complementary, effective, Low-cost, non-invasive care is recommended to maintain and promote the health of mothers with preterm infant., Competing Interests: Conflict of Interests Authors declare no conflict of interests., (Copyright © 2024 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

Background: Infertility is one of the most common problems in the world; there is a growing demand for herbal medicines to treat infertility-related problems., Materials and Methods: A randomized controlled trial with three groups was conducted, each with 30 participants. The first group was administered 1.5 grams of Carob daily, the second group was administered 1.5 grams of Ginseng daily, and the third group received a placebo. The treatment was administered for 12 weeks, and before and after the intervention, semen parameters, testosterone, prolactin, luteinizing hormone, follicle-stimulating hormone, thyroid hormones, and sexual function were evaluated. Sexual function was assessed using the International Index of Erectile Function Questionnaire., Results: The mean (SD) age of participants was 34.83 (6.22), 34.60 (5.78), and 33.67 (5.82) years in Carob, Ginseng, and Placebo groups, respectively. The results showed that in the Carob group, the normal volume of semen (Z 133 = 3.05, p = 0.02) and the normal shape of sperm (Z 134 = 2.97, p = 0.01) increased significantly compared to the control group. In the Ginseng group, the normal volume (Z 133 = 3.90, p = 0.001) and the normal viscosity of semen (Z 133 = 2.36, p = 0.01) increased significantly compared to the control group.The Carob group showed a significant increase in normal sperm counts and testosterone hormone levels (Z 131 = 2.81, p = 0.05). The Ginseng group demonstrated a significant improvement in orgasm function (H 2 = 6.14, p = 0.04) and the total score of the International Index of Erectile Function (IIEF) (H 2 = 5.8, p = 0.05)., Conclusions: Carob supplements are suggested to enhance some semen parameters and male sex hormones. For infertile men, Ginseng can be beneficial in improving sexual function., Competing Interests: Nothing to declare., (Copyright: © 2024 Iranian Journal of Nursing and Midwifery Research.)

The way multipacting develops, depends strongly on the secondary emission property of the surface material. The knowledge of secondary electron yield is crucial for accurate prediction of the multipacting threshold. Variations in secondary electron yield parameters from experimental measurements create uncertainty, stemming from handling and surface preparation, and these uncertainties significantly affect multipacting threshold predictions. Despite their significance, the previous studies on the multipacting phenomenon did not adequately address the effect of an assumed random distribution of the secondary emission parameters on the multipacting threshold. Therefore, this paper aims to provide a comprehensive statistical study on how the different random distributions of the secondary emission parameters and, as a result, the uncertainty in the secondary electron yield affect multipacting thresholds. We focus on three commonly used distributions, namely uniform, normal, and truncated normal distributions, to define the uncertainty of random inputs. We use the chaos polynomial expansion method to determine how much each of the random parameters contributes to the multipacting threshold uncertainty. Additionally, we calculate Sobol sensitivity indices to evaluate the impact of the individual parameters or groups of parameters on the model outputs and study how different random distributions of these parameters affected the Sobol index results., (© 2024. The Author(s).)

Background: Vascular Endothelial Growth Factor Receptors (VEGFR1 and VEGFR2) are tyrosine kinase receptors expressed on endothelial cells and tumor vessels and play an important role in angiogenesis. In this study, three repeats of VEGFR1 and VEGFR2 binding peptide (VGB3) were genetically fused to the truncated diphtheria toxin (TDT), and its in vitro activity was evaluated., Methods: The recombinant construct (TDT-triVGB3) was expressed in bacteria cells and purified with nickel affinity chromatography. The binding capacity and affinity of TDT-triVGB3 were evaluated using the enzyme-linked immunosorbent assay. The inhibitory activity of TDT-triVGB3 on viability, migration, and tube formation of human endothelial cells was evaluated using MTT, migration, and tube formation assays., Results: TDT-triVGB3 selectively detected VEGFR1 and VEGFR2 with high affinity in an enzyme- linked immunosorbent assay and significantly inhibited viability, migration, and tube formation of human endothelial cells., Conclusion: The developed TDT-triVGB3 is potentially a novel agent for targeting VEGFR1/ VEGFR2 over-expressing cancer cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Colorectal cancer (CRC) is one of the world's most common types of malignancy. The proliferation of precancerous lesions causes this type of cancer. Two distinct pathways for CRC carcinogenesis have been identified: the conventional adenoma-carcinoma pathway and the serrated neoplasia pathway. Recently, evidence has demonstrated the regulatory roles of noncoding RNAs (ncRNAs) in the initiation and progression of precancerous lesions, especially in the adenoma-carcinoma pathway and serrated neoplasia pathway. By expanding the science of molecular genetics and bioinformatics, several studies have identified dysregulated ncRNAs that function as oncogenes or tumor suppressors in cancer initiation and formation by diverse mechanisms via intracellular signaling pathways known to act on tumor cells. However, many of their roles are still unclear. This review summarizes the functions and mechanisms of ncRNAs (such as long non-coding RNAs, microRNAs, long intergenic non-coding RNAs, small interfering RNAs, and circRNAs) in the initiation and formation of precancerous lesions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Targeted cancer therapy can be considered as a new strategy to overcome the side effects of current cancer treatments. Neuropilin-1 (NRP-1) is a transmembrane glycoprotein that is expressed in endothelial cells and tumor vessels to stimulate angiogenesis progression. Targeted diphtheria toxin (DT)- based therapeutics are promising tools for cancer treatment. This study aimed to construct a novel NRP-1 binding peptide (as three repeats) (CRGDK) as a fusion to truncated DT (DTA) (DTA-triCRGDK) for targeted delivery of DT into NRP-1 expressing cells., Methods: The concept of DTA-triCRGDK was designed, synthesized and cloned into the bacterial host. Expression of DTA-triCRGDK was induced by Isopropyl ß-D-1-thiogalactopyranoside (IPTG) and purification was performed using Ni-NTA chromatography. Biological activity of DTA-triCRGDK was evaluated using MTT, apoptosis, and wound healing assays. In addition, expression levels of apoptotic Bax, Bcl2, and Casp3 genes were determined by Real-time PCR., Results: Cytotoxicity analysis showed the IC 50 values of DTA-triCRGDK for A549 and MRC5 were 0.43 nM and 4.12 nM after 24 h, respectively. Bcl2 expression levels decreased 0.4 and 0.72 fold in A549 and MRC5, respectively. However, Bax and Casp3 expression level increased by 6.75 and 8.19 in A549 and 2.51 and 3.6 in MRC5 cells., Conclusion: Taken together, DTA-triCRGDK is a promising tool for targeted therapy of NRP-1 overexpressing cancer cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Drug delivery is an important topic that has attracted the attention of researchers in recent years. Albumin nanoparticles play a significant role in drug delivery as a carrier due to their unique characteristics. Albumin is non-toxic, biocompatible, and biodegradable. Its structure is such that it can interact with different drugs, which makes the treatment of the disease faster and also reduces the side effects of the drug. Albumin nanoparticles can be used in the diagnosis and treatment of many diseases, including cancer, diabetes, Alzheimer's, etc. These nanoparticles can connect to some compounds, such as metal nanoparticles, antibodies, folate, etc. and create a powerful nanostructure for drug delivery. In this paper, we aim to investigate albumin nanoparticles in carrier format for drug delivery application. In the beginning, different types of albumin and their preparation methods were discussed, and then albumin nanoparticles were discussed in detail in diagnosing and treating various diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Inhibition of FGFR2 signaling is promising in targeted therapy of FGFR2-related tumors. In this study, anti-FGFR2 nanobodies (Nbs) were isolated through screening of an immune camelid phage display library. Four rounds of biopanning were carried out with commercial human FGFR2 antigen and enrichment was assessed by ELISA and phage titration. The gene of Nb was sub-cloned into the expression vector, and the recombinant vector was transformed into Escherichia coli WK6 cells. The recombinant protein was purified using Ni-NTA affinity chromatography. The anti-FGFR2 Nb (C13) was characterized by SDS-PAGE, western blotting, competitive inhibition ELISA, flow cytometry, MTT, and migration assay. C13 Nb recognized FGFR2 with high specificity and no cross-reactivity was observed with other tested antigens. The affinity of C13 Nb was calculated to be 1.5 × 10 -9 M. Results of cytotoxicity showed that C13 Nb (10 µg/ml) inhibited 85% of the proliferation of T-47D cells ( p  < 0.001). In addition, C13 inhibited the migration of 68% of T-47D toward the source of the growth factor ( p  < 0.01). The flow cytometry showed that C13 Nb bound to the surface of FGFR2 + cells, T-47D cell line (96%). Results indicate the potential of anti-FGFR2 Nb for targeted therapy of FGFR2-overexpressing tumors after complementary investigations.

Introduction: Breast cancer is considered the most frequent type of cancer in women with high mortality worldwide, and most importantly, it is the second most common cancer. However, some breast cancer-related risk factors remain unknown. So, the current study was designed to evaluate the effect of Toxocara canis on the biomarkers correlated with proliferation, apoptosis, inflammation, and angiogenesis in 4T1 tumor-bearing mice infected with Toxocara canis for the first time., Methods: Mice were categorized into four groups: A) control, B) treated with 4T1+ Toxocara canis , C) treated with Toxocara canis , and D) treated with 4T1. The expression of Ki-67 and P53 was then evaluated by using the immunohistochemical technique. In addition, the levels of transforming growth factor-β, Interferon gamma-γ, Interleukin 10, tumor necrosis factor-α and vascular endothelial growth factor as well as anti- Toxocara canis IgG were determined using the enzyme-linked immunosorbent assay method., Results: The expression of Ki-67 was significantly increased in the 4T1+ Toxocara canis group than control and Toxocara canis groups ( P < 0.001 and P < 0.001, respectively). Moreover, a significant decrease in P53 was found in the 4T1+ Toxocara canis group than in the control and Toxocara canis groups ( P < 0.001 and P < 0.001, respectively). Also, the 4T1+ Toxocara canis group significantly reduced the expression of P53 more than 4T1 tumor-bearing mice ( P = 0.005). In addition, the 4T1+ Toxocara canis group had an increasing tumor necrosis factor-α and vascular endothelial growth factor than controls ( P = 0.004 and P = 0.002, respectively). Furthermore, a significant reduction in Interleukin 10 was found in the 4T1+ Toxocara canis group than in the control group ( P = 0.004)., Conclusion: Our findings showed that Toxocara canis could probably increase the potential of breast cancer by reducing P53 in 4T1 tumor-bearing mice infected with Toxocara canis more than other groups., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Objective: Snakebite envenoming is a serious public health issue causing more than 135,000 annual deaths worldwide. Naja Naja Oxiana is one of the most clinically important venomous snakes in Iran and Central Asia. Conventional animal-derived polyclonal antibodies are the major treatment of snakebite envenoming. Characterization of venom components helps to pinpoint the toxic protein responsible for clinical manifestations in victims, which aids us in developing efficient antivenoms with minimal side effects. Therefore, the present study aimed to identify the major lethal protein of Naja Naja Oxiana by top-down proteomics., Methods: Venom proteomic profiling was performed using gel filtration (GF), reversed-phase (RP) chromatography, and intact mass spectrometry. The toxicity of GF-, and RP-eluted fractions was analyzed in BALB/c mice. The rabbit polyclonal antisera were produced against crude venom, GF fraction V (FV), and RP peak 1 (CTXP) and applied in neutralization assays., Results: Toxicity studies in BALB/c identified FV as the major toxic fraction of venom. Subsequently, RP separation of FV resulted in eight peaks, of which peak 1, referred to as "CTXP" (cobra toxin peptide), was identified as the major lethal protein. In vivo neutralization assays using rabbit antisera showed that polyclonal antibodies raised against FV and CTXP are capable of neutralizing at least 2-LD50s of crude venom, FV, and CTXP in all tested mice., Conclusion: Surprisingly, the Anti-CTXP antibody could neutralize 8-LD50 of the CTXP peptide. These results identified CTXP (a 7 kDa peptide) as a potential target for the development of novel efficient antivenom agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Recently, the effect of an aqueous extract of asafetida on acute angiotensin II hypertensive rats was evaluated. The present study evaluated the antihypertensive and antioxidant effects of asafetida on a rat model of renovascular hypertension (RVH) using four groups. RVH was induced by clipping the renal artery; the sham group underwent surgery but without clipping. The RVH rats received losartan (Los, an AT1 receptor antagonist) or asafetida by gavage for 4 weeks. On the 28th day, the femoral artery was cannulated, and the systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were recorded. Finally, the levels of superoxide dismutase (SOD) activity, malondialdehyde (MDA), and total thiol content in the kidney and heart tissues were measured. In RVH rats, SBP and MAP significantly increased compared with the control. Los and the extract significantly reduced the changes in SBP, MAP, and HR that were induced in the RVH rats (P <0.05-0.001). In RVH rats, levels of MDA significantly increased and the content of total thiol and SOD decreased in both the heart and kidney tissues. Los plus the extract significantly decreased MDA and increased total thiol and SOD in the heart and kidney tissues. We concluded that an aqueous extract of asafetida gum has antihypertensive and antioxidant effects in the RVH rat model. The effect of the extract is similar to that of Los, which suggests that this effect of asafetida is mediated via an effect on the angiotensin Type I receptor., (Copyright © 2023 Copyright: © 2023 Saudi Journal of Kidney Diseases and Transplantation.)

Photocatalysis using natural photosynthesis is a green technology that is gaining popularity in a number of industries due to its potential for environmental applications and the use of solar energy. Focus is being placed on using inexpensive materials and light-emitting diodes (LEDs) of various wavelengths in photocatalytic reactions in order to improve the performance of solar-driven photocatalysts at a lower cost. In this study, a scalable, highly efficient photocatalytic and sonophotocatalytic method was investigated for the reduction of nitro-compounds by a water/titania/β-cyclodextrin system under sunlight and blue LED irradiation, using sodium sulfide as a sacrificial electron donor. β-Cyclodextrin, chemically bound to TiO 2 nanoparticles as an encapsulating agent, hosted nitro compounds in aqueous media and formed an inclusion complex. In addition, this method was used to successfully carry out one-pot reduction-amidation of nitroarene compounds in the presence of acetic anhydride. Interestingly, it was found that ultrasound has a synergistic effect on photocatalytic reduction and considerably reduces the duration time. In this regard, a fast, practical sonophotocatalytic reduction of nitroarenes was carried out in an ultrasound bath., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Plant-based combination strategies have been widely considered in cancer therapy to attenuate chemotherapeutics side effects. The anti-leukemic effect of the whole ginger extract was previously portrayed by our team, and the current study is centered around the cytotoxicity and mechanism of action of a phenolic subsidiary of ginger, GingerenoneA, on pediatric acute lymphoblastic leukemia. GingernoneA imposed, dose-dependently, inhibitory effects on the viability of T and B leukemia cell lines confirmed by MTT assays. Resistance to Dexamethasone, a mostly used chemotherapeutic in acute lymphoblastic leukemia treatments, was overcome by GingernoneA. A synergistic effect of Dexamethasone and GingrenoneA on T leukemia cell lines and patient primary cells was confirmed. Annexin-V/PI and acridine orange/ethidium bromide staining illustrated dose-dependent apoptosis in CCRF-CEM cells developed by GingerenoneA. The intrinsic and extrinsic apoptosis induction and antiproliferative attribution of GingerenoneA were validated by western blot and qPCR. Despite the supposed loss of function in CCRF-CEM cells, TP53 showed increased expression levels and functional activity upon treatment with GingernoneA. Bioinformatic studies revealed the conceivable impact of GingerenoneA on the reactivity of mutant P53 through its binding to Cys124. Our findings may provide novel strategies for therapeutic intervention to ameliorate pALL outcomes., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Breastfeeding behaviors are strongly influenced by self-efficacy. This research aimed to determine the effect of breastfeeding counseling based on the Ready Set Baby (RSB) education program on self-efficacy and breastfeeding performance in adolescent mothers., Methods: In 2022, a parallel randomized clinical trial was carried out in Hamadan city's comprehensive health centers, involving 64 pregnant teenagers. The block randomization method was employed to divide the participants into two groups. The data collection instruments were a demographic characteristics questionnaire, a breastfeeding self-efficacy questionnaire, and the Bristol breastfeeding checklist. Three individual counseling sessions during pregnancy were conducted based on the "RSB" program. The ANCOVA was used for comparing groups. The statistical analyst was blinded to the group assignment., Results: The study included 64 participants with a mean age of 16.97(1.30) years, data from 60 participants were analyzed. The demographic and clinical characteristics of the two groups were relatively similar (P > 0.05). Following the intervention, self-efficacy and breastfeeding performance scores were measured and adjusted for confounding factors. The mean scores for self-efficacy were 116.03(20.64) and 100.02(20.64) (P < 0.005), with effect size 0.77 [MD = 16.01 (95% CI: 5.34,26.67)], and the mean scores for breastfeeding performance were 6.30(2.07) and 4.12(2.07) (P < 0.002), with effect size 1.05 [MD = 2.18 (95% CI: 1.11,3.24)] in the intervention and control groups, respectively., Conclusions: The Ready Set Baby education program's breastfeeding counseling for primiparous adolescent pregnant women significantly boosted their self-efficacy and performance in breastfeeding. Given the crucial role of breastfeeding in ensuring the well-being of both mother and child, further research is imperative to identify suitable and impactful interventions that can encourage breastfeeding practices among adolescents., Trial Registration: The trial protocol of this study has been registered in Iranian Registry of Clinical Trials at 08/09/2021. The registration reference is IRCT20200530047596N3., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: The purpose of this study is comparison of carob with placebo in the treatment of male infertility., Materials and Methods: This study was performed as a clinical trial with two-group pretest-posttest design. Each group consisted of 30 members. The first group received 1.5 grams of carob per day, and the second group received placebo treatments. Treatment lasted for 12 weeks. Semen analysis as well as testosterone, prolactin, (LH), (FSH) and (TSH) were performed before and after drug treatment in two groups. Sexual function was assessed in the groups in two stages before and after the intervention using the standard International Index of Erectile Function. P-value less than 0.05 was considered statistically significant. Statistical analysis of data was performed using SPSS 16., Results: The participants' mean age was 34.83 ±6.22 in the placebo and 33.67 ±5.82 years in the Carob group. The results showed in the carob group compared to the placebo group, the rate of normal sperm counts increased by 17% and also the normal level of testosterone was 40% higher than the abnormal levels of the placebo group and these differences were statistically significant (P <0.05). And in most areas of sexual function, the mean scores after the intervention were higher than before (P> 0.05)., Conclusion: It is recommended to use carob supplements to improve spermogram parameters and male sex hormones., Competing Interests: Conflict of Interests Authors declare no conflict of interests., (Copyright © 2023 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

Background: Leishmaniasis is a rare infectious disease observed in subtropical and tropical areas. This disease that demonstrates different clinical characteristics is caused by intracellular Leishmania protozoan. One of the important countries facing the incidence of this infectious disease is Iran. Recently, human immunodeficiency virus-Leishmania coinfection has been indicated in Iran., Case Presentation: In the present case report, we show an atypical case of severe visceral leishmaniasis in a 52-year-old Iranian-Arab male with positive human immunodeficiency virus status. Leishmaniasis was detected by node biopsy and subsequently histopathology evaluations and confirmed by molecular methods., Conclusions: The current study was the first report of an atypical case of a patient with Leishmania-human immunodeficiency virus coinfection in southwestern Iran, which was not responsive to the treatment. Therefore, the health authorities should be aware of these reports, which require permanent clinical follow-up of the patients as well as effective treatments., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Topical skin care products often do not reach the deeper layers of the skin, and oral hydrolyzed collagen is one of the newest and most popular systemic supplementations for skin rejuvenation. However, there are limited information in case of Middle Eastern consumers OBJECTIVE: The purpose of this study was to evaluate the tolerability and efficacy of an oral collagen supplement for improvement of skin elasticity, hydration, and roughness in Middle Eastern consumers., Methods and Materials: It was a 12-week, before-after clinical study, conducted on 20 participants (18 women and 2 men) aged 44.15 ± 5.36 years with skin type III-IV. Skin elasticity parameters (R0, R2, R5, and R7), skin hydration and friction, as well as the thickness and echo density of the dermis, were measured after six and 12 weeks daily intake of the study product, as well as 4 weeks after stopping its use (week 16). Participants' satisfaction was assessed on the basis of their answers to the standard questionnaire, and tolerability of the product was assessed by monitoring the adverse effects., Results: A significant improvement was detected in R2, R5, and skin friction at week 12 (p-values 0.041, 0.012 and <0.01, respectively). At week 16, the values remained at an increased level, which indicates the persistence of the results. The increase of dermis density in week 16 was also significant (p-value = 0.03). Moderate overall satisfaction was reported with the treatment, and a few gastrointestinal complications were reported., Conclusion: The study demonstrated that oral collagen peptides could significantly improve the skin elasticity, roughness, and dermis echo density, and they also proved to be safe and well-tolerated., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

The human amniotic membrane dressing has been shown to accelerate the wound healing process in the clinic. In this study, heparin was conjugated to a human Acellular Amniotic Membrane (hAAM) to provide affinity binding sites for immobilizing growth factors. To study the acceleration of the wound healing process, we bound epidermal growth factor and fibroblast growth factor 1 to heparinized hAAMs (GF-Hep-hAAMs). The heparinized hAAMs (Hep-hAAMs) were characterized by toluidine blue staining and infrared spectroscopy. The quality control of hAAM was performed by hematoxylin staining, swelling capacity test and biomechanical evaluation. The cytotoxicity, adhesion, and migration in vitro assays of GF-Hep-hAAMs on L-929 fibroblast cells were also studied by MTT assay, scanning electron microscopy, and scratch assay, respectively. Finally, in vivo skin wound healing study was performed to investigate the wound closure rate, re-epithelization, collagen deposition, and formation of new blood vessels. The results showed that GF-Hep-hAAMs enhance the rate of wound closure and epidermal regeneration in BALB/c mice. In conclusion, GF-Hep-hAAMs could accelerate the wound healing process, significantly in the first week., (© 2023 Wiley Periodicals LLC.)

Background: Vitamin D is a vital neuroactive steroid for brain development and function. Vitamin D deficiency is a worldwide health problem, particularly in children and women. Gestational or developmental vitamin D deficiency is associated with an increased risk of neurodevelopmental and neuropsychiatric disorders. This study examined the effect of maternal vitamin D dietary manipulations and treadmill exercise on anxiety-and depressive-related behaviors, pro-inflammatory cytokines, and prefrontal cortex (PFC) protein levels of brain-derived neurotrophic factor (BDNF) and vitamin D receptor (VDR) in adult male offspring born to vitamin D-deficient diet (VDD)-fed dams., Methods and Results: Female rats were provided standard diet (SD) or VDD for six weeks and then were treated with SD (started a week before mating throughout gestation and lactation) and treadmill exercise (a week before mating until gestational day 20). Male offspring were separated on postnatal day (PND) 21 and fed SD chow until PND90. Our results demonstrated that maternal vitamin D deficiency increased anxiety and depression-related behaviors, increased levels of TNF-α and IL-1β in serum, and decreased prefrontal protein expressions of BDNF and VDR in adult male offspring. However, maternal vitamin D supplementation and treadmill exercise reversed these changes alone or in combination., Conclusion: It seems that developmental vitamin D deficiency disrupts brain development and has a long-lasting effect on VDR and BDNF signaling in the rat brain resulting in neuropsychiatric disorders in offspring. Therefore, vitamin D supplementation and physical exercise are reasonable strategies to prevent these neurobehavioral impairments.

According to recent researches, people with diabetes mellitus (type 1 and 2) have a higher incidence of coronavirus disease 2019 (COVID-19), which is caused by a SARS-CoV-2 infection. In this regard, COVID-19 may make diabetic patients more sensitive to hyperglycemia by modifying the immunological and inflammatory responses and increasing reactive oxygen species (ROS) predisposing the patients to severe COVID-19 and potentially lethal results. Actually, in addition to COVID-19, diabetic patients have been demonstrated to have abnormally high levels of inflammatory cytokines, increased virus entrance, and decreased immune response. On the other hand, during the severe stage of COVID-19, the SARS-CoV-2-infected patients have lymphopenia and inflammatory cytokine storms that cause damage to several body organs such as β cells of the pancreas which may make them as future diabetic candidates. In this line, the nuclear factor kappa B (NF-κB) pathway, which is activated by a number of mediators, plays a substantial part in cytokine storms through various pathways. In this pathway, some polymorphisms also make the individuals more competent to diabetes via infection with SARS-CoV-2. On the other hand, during hospitalization of SARS-CoV-2-infected patients, the use of some drugs may unintentionally lead to diabetes in the future via increasing inflammation and stress oxidative. Thus, in this review, we will first explain why diabetic patients are more susceptible to COVID-19. Second, we will warn about a future global diabetes tsunami via the SARS-CoV-2 as one of its long-term complications., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Tramadol is an analgesic drug that is mainly excreted in the urine. The entry of Tramadol into water samples causes their biological contamination. Therefore, three catalysts such as bismuth ferrite, cobalt-doped bismuth ferrite, and a magnetized Keggin type of polyoxometalate (α-Fe 2 O 3 @phosphotungstic acid), were synthesized as photocatalysts to degrade Tramadol in water samples. The morphology and properties of the prepared photocatalysts were evaluated using several techniques. Effects of several factors, including tramadol concentration, pH, hydrogen peroxide concentration, and photocatalyst amount, were studied and optimized by a design experiment procedure based on Box-Behnken design for reducing the number of experiments and cost and investigating the interactions between factors in the photocatalytic degradation process of Tramadol. These factors were optimized for each prepared photocatalyst individually. Under the optimum conditions, the percentages of tramadol degradation and kinetics of the degradation process were evaluated in the presence of each photocatalyst. The tramadol degradation percentages using bismuth ferrite, cobalt-doped bismuth ferrite, and α-Fe 2 O 3 @phosphotungstic acid were 81.10% for 120 min, 90.63% for 80 min, and 91.32% for 80 min, respectively. The rate constants of tramadol degradation were 0.0145, 0.0329, and 0.0312 min -1 for bismuth ferrite, cobalt-doped bismuth ferrite, and α-Fe 2 O 3 @phosphotungstic acid, respectively. The results indicated the highest percentage of tramadol degradation and rate of the degradation process were obtained using α-Fe 2 O 3 @phosphotungstic acid and cobalt-doped bismuth ferrite, respectively., 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 © 2022. Published by Elsevier Inc.)

Epithelial Cell Adhesion Molecule (EpCAM) is overexpressed in a variety of cancers such as colon, stomach, pancreas, and prostate adenocarcinomas. Inhibition of EpCAM is considered as a potential target for cancer therapy. In current study, anti-EpCAM immunotoxin (α-EpCAM IT) was developed using genetic fusion of α-EpCAM single domain antibody (nanobody) (α-EpCAM Nb) to truncated form of diphtheria toxin. The expression of recombinant α-EpCAM IT was induced by Isopropyl β-d-1-thiogalactopyranoside (IPTG) and confirmed by SDS-PAGE and western blot. Recombinant α-EpCAM IT was purified from the inclusion bodies and refolded using urea gradient procedure. The cytotoxicity and apoptosis activity of α-EpCAM IT on EpCAM over-expressing (MCF7), low-expressing (HEK293), and no-expressing (HUVEC) cells were evaluated by 3-4,5-Dimethylthiazol-2-yl (MTT) assay and annexin V-FITC-PI assay as well. In addition, anti-tumor activity of α-EpCAM IT was evaluated on nude mice bearing MCF7 tumor cells. Results showed success expression and purification of α-EpCAM IT. The α-EpCAM IT showed time and dose-dependent anti-proliferative activity on MCF-7 cells. However, α-EpCAM IT did not show any anti-proliferative activity on HEK293 and HUVEC cells as well. In addition, the annexin V-FITC-PI assay results showed that α-EpCAM IT significantly increased apoptotic rate in MCF-7 cells with no effect on HEK293 and HUVEC as well. Moreover, α-EpCAM IT significantly reduced tumor size in vivo study. The achieved results indicate the potential of designing α-EpCAM IT as a novel therapeutic for cancer therapy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Immunotherapy using monoclonal antibodies targeting programmed death ligand-1 (PD-L1) on cancer cells as a biomarker of escape from response to immune checkpoint has demonstrated efficacy in treating many solid tumors. In addition, some of the signals, such as vascular endothelial growth factor (VEGF), bind to receptors on the surface of normal endothelial cells and encourage angiogenesis, or the formation and survival of new blood vessels., Methods: Due to the special features of nanobodies with high specificity and affinity as a powerful new tool in cancer therapy, here, a recombinant bispecific bivalent anti-PD-L1/VEGF nanobody was constructed and its functionality in inhibition of angiogenesis in vitro was investigated., Results: Results demonstrated that bivalent anti-PD-L1/VEGF nanobody efficiently inhibited HUVEC and A431 cells proliferation and tube formation. In addition, bivalent anti-PD-L1/VEGF nanobody efficiently inhibited angiogenesis in an ex ovo Chick Chorioallantoic Membrane assay., Discussion: The results indicate for the potential of bivalent anti-PD-L1/VEGF nanobody as a novel promising tool for cancer therapy.

Multilayered pH-responsive hollow microcapsules with non-toxicity and biological specificity advantages were prepared from two kinds of polymers i.e., chitosan (CH) and poly (ethylene glycol dimethacrylate-co-methacrylic acid) (PE) via layer-by-layer (LbL) method, which is followed by subsequent removal of silica core. The hollow nature of obtained spherical microcapsules was found by transmission electron microscopy (TEM). The microcapsules were prepared as gemcitabine (GM) and curcumin (CR) carriers. The drugs have been loaded within the microcapsules during or after the synthetic procedure. Although acceptable loading efficiencies (LE) were obtained in both methods, the amount of drug loaded during the synthesis method is relatively higher. Values above 78% and 87%, for releasing efficiency (RE%) and encapsulation efficiency (EE%), respectively, demonstrate the high potential of the prepared microcapsules for drug delivery. In addition, the difference between the amount of drug released in acidic and neutral pH indicates the pH-responsivity of the prepared microcapsules. Moreover, the dose-dependent high cytotoxicity effect of the prepared microcapsules was observed on the HCT116 colorectal carcinoma cells., 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 © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Hydroxyurea (HU) is an anti-cancer drug that is used for the treatment of hemoglobinopathies as a γ-globin inducer. However, its dose-dependent effects have hampered its clinical reliability. Resveratrol (RSV) is an antioxidant and γ -globin inducer. The present study aimed to assess their combined effects on the γ-globin gene expression and reactive oxygen species (ROS) level of K562 cells. The results indicated that the γ-globin gene expression was approximately two folds higher in the group treated with RSV 50 µM + HU 25 µM in comparison to HU 100 μM alone (*** p  < 0.001). However, there was an inverse relationship between the expression of γ-globin gene and HU concentration in the combined groups. Furthermore, the combinations of RSV and HU significantly reduced ROS levels compared to single drugs. Overall, the combination of these compounds was an appropriate strategy for increasing γ-globin expression, reducing oxidant levels, and alleviating the adverse effects of HU.

Objective: To evaluate the effect of Neurotec® herbal capsule (100 mg twice a day for 3 months) on the tinnitus symptoms in comparison with the placebo., Design: A double-blind randomised clinical trial., Setting: Otolaryngology clinic of Baqiyatallah Hospital., Participants: Patients suffering from subjective tinnitus., Main Outcome Measures: Pure tone audiometry was measured at .5, 1, 2, 4 and 6 kHz frequencies before and after the third month of intervention. In addition, Tinnitus Handicap Inventory (THI) questionnaire as well as visual analogue scale (VAS) for tinnitus loudness, daily annoyance, daily life or sleep disturbance, daily perception and mood alteration were evaluated., Results: Finally, 103 (69 males and 34 females) patients with a mean age of 51.33 ± 13.91 years were analysed. In contrast with control group, patients in intervention group showed a remarkable decrease in THI score after 3 months of treatment (p < .05). Although both groups had improvements in VAS scores, mood disturbance, daily tinnitus perception and daily life alteration scores were only improved in the intervention group. The mean pure tone air and bone conduction were not significantly different between the control and the intervention group at baseline and 3 months after the intervention at .5, 1, 2 and 4 kHz (p > .05)., Conclusion: A 3-month treatment with Neurotec capsules in addition to patient education is of benefit for managing symptoms in patients with chronic tinnitus., (© 2022 John Wiley & Sons Ltd.)

Background: The aim of this study was to investigate the effects of the antioxidant supplement of CoQ10 and placebo in the male infertility treatment., Materials and Methods: The randomized controlled trial study was designed as a clinical trial. Samples in each group consisted of 30 members. The first group received 1 daily dose of 100 mg coenzyme Q10 capsules and the second group received a placebo treatment. Treatment in both groups lasted 12 weeks. Before and after the intervention of semen analysis, hormonal measurement of testosterone, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and thyroid stimulating hormone (TSH) were done. Sexual function was assessed before and after the intervention by using the International Index of Erectile Dysfunction questionnare., Results: The mean age of participants was 34.07 (5.26) years in the CoQ10 group and 34.83 (6.22) in the placebo one. Normal volume of semen (P=0.10), viscosity (P=0.55), sperm count (P=0.28), and sperm motility (P=0.33) in the CoQ10 group increased without statistically significant differences. But the normal sperm morphology increased with statistically significant differences in the CoQ10 group (P=0.01). There was an increase in normal FSH levels and testosterone levels in the CoQ10 group compared with the placebo patients, but these differences were not statistically significant (respectively P=0.58, P=0.61). The results also revealed that the scores of erectile function (P=0.95), orgasm (P=0.86), satisfaction with sexual intercourse (P=0.61), overall satisfaction (P=0.69) and the score of the International Index of Erectile Function (IIEF, P=0.82) were greater after the intervention in the CoQ10 group than in the placebo group although the difference was not statistically significant., Conclusion: The use of CoQ10 supplement can improve sperm morphology; however, in other sperm parameters and also in some hormones increased after the intervention, this was not statistically significant and therefore the result is not conclusive (registration number: IRCT20120215009014N322).

Background: Overexpression of programmed cell death ligand 1 (PD-L1) in tumor cells and subsequent interaction with the programmed cell death protein 1 (PD-1) in tumor-infiltrating T cells cause an immune evasion of the tumor from cytotoxic T-cells. Therefore, inhibiting such interaction by a recombinant PD-1 can hinder tumor growth and extend the survival rate., Methods: The mouse extracellular domain of PD-1 (mPD-1) was expressed in E. coli BL21 (DE3) strain and purified using nickel affinity chromatography. The binding ability of the purified protein to human PD-L1 was studied using ELISA. Finally, the tumor-bearing mice were used to evaluate the potential antitumor effect., Results: The recombinant mPD-1 showed a significant binding capacity to human PD-L1 at the molecular level. The tumor size significantly decreased in the tumor-bearing mice after the intra-tumoral injections of mPD-1. Moreover, the survival rate increased significantly after eight weeks of monitoring. The histopathology revealed the necrosis in the tumor tissue of the control group compared to the mPD-1 received mice., Conclusions: Our outcomes propose that interaction blockade between PD-1 and PD-L1 is a promising approach for targeted tumor therapy., Competing Interests: Conflict of Interests: The authors have no conflicts of interest., (Copyright © 2023, Author(s).)

The blood-brain barrier (BBB) is considered an important protective barrier in the central nervous system (CNS). The barrier is mainly formed by endothelial cells (ECs) interconnected by various junctions such as tight junctions (TJs), gap junctions, and adherent junctions. They collectively constitute an intensive barrier to the transit of different substances into the brain, selectively permitting small molecules to pass through by passive movement but holding off large ones such as peptides and proteins to cross the brain. Hence some molecules selectively transfer across the BBB by active routes via transcytosis. The BBB also forms a barrier against neurotoxins as well as pathogenic agents. Although various CNS disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) could hamper the integrity of the border. Nevertheless, the BBB acts as a barrier for CNS disorders treatment because it prevents the drugs from reaching their target in the CNS. In recent years, different strategies, including osmotic disruption of BBB or chemical modification of drugs, have been used to transfer the chemotherapeutic agents into brain substances. Nowadays, nanoparticles (NPs) have been used as an effective and non-invasive tool for drug delivery and diagnosis of CNS disorders. In this review, we discuss the structural characteristic of BBB, safe passageways to cross the BBB, and the relation of barrier lesions with different CNS disorders. In the end, we explore the progress in drug delivery, diagnosis, imaging, and treatment of CNS disorders using nanoparticles., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Programmed cell death protein 1 (PD-1) is a membrane receptor that is expressed on the surface of various immune cells, such as T cells, B cells, monocytes, natural killer T cells, and dendritic cells. In cancer, the interaction between PD-1 and its ligand PD-L1 suppresses the activation and function of T lymphocytes, leading to the impairment and apoptosis of tumor-specific T cells. This mechanism allows cancer cells to evade the immune response and promotes tumor progression., Methods: Recombinant PD-1 protein was produced and used to immunize a camel. A nanobody library was generated from the camel's peripheral blood lymphocytes and screened for PD-1 binding. A specific nanobody (3PD9) was selected and characterized by affinity measurement, western blotting, and flow cytometry analysis. The ability of the selected nanobody to block the inhibitory signal of PD-1 in peripheral blood mononuclear cells (PBMCs) was evaluated by measuring the level of interleukin-2 (IL-2)., Results: The selected nanobody showed high specificity and affinity for human PD-1. Western blot and flow cytometry analysis confirmed that 3PD9 could recognize and bind to human PD-1 on the cell surface. It was demonstrated that the level of IL-2 was significantly increased in PBMCs treated with 3PD9 compared to the control group, indicating that the nanobody could enhance the T cell response by disrupting the PD-1/PD-L1 interaction., Conclusion: The results suggested that the anti-PD-1 nanobody could be a promising candidate for cancer immunotherapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)