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Background: Improper use of standards for measurement instruments can impact the accuracy of study results. Objectives: This study systematically reviews the Instruments for measuring pain intensity during venous catheter insertion in preschool children. Methods: In this systematic review, conducted from October 2023 to January 2023, an open search was carried out for articles in domestic databases, such as scientific information database (SID), MagIran, and Iran Medex, and international databases, including PubMed, CINAHL, Web of Science, and Scopus using the following keywords: Preschool period, pain intensity, cannulation, vein removal, pain scale, pain relief, pain perception, and pain sensation. The objective of this search was to examine the measurement tools utilized to assess pain intensity during venipuncture in preschool-aged children without a time restriction. Duplicate articles were excluded, and other studies meeting the inclusion criteria were reviewed. Articles were assessed by two researchers, and any discrepancies were resolved by a third author. Results: Among all the reviewed studies, 21 articles that were conducted between 2001 and 2023 met the inclusion criteria. The tools utilized in these studies to assess pain intensity during venous catheter insertion in preschool children included face, legs, activity, cry, and consolability (FLACC), Wong-Baker, Oucher scale, visual analog scale, and Poker Chip scale. The Wong-Baker instrument was a self-assessment, FLACC were assessed by both the researcher and a reviewer, Oucher was a self-assessment, the visual analog scale was assessed by parents and reviewers, and the Poker Chip scale was a self-assessment. Conclusions: Researchers who do not adhere to tool standards often opt to utilize tools based on the methods of other studies or their requirements, which could potentially impact the outcomes of their studies

Abstract The hypothalamus contains a remarkable diversity of neurons that orchestrate behavioural and metabolic outputs in a highly plastic manner. Neuronal diversity is key to enabling hypothalamic functions and, according to the neuroscience dogma, it is predetermined during embryonic life. Here, by combining lineage tracing of hypothalamic pro-opiomelanocortin (Pomc) neurons with single-cell profiling approaches in adult male mice, we uncovered subpopulations of ‘Ghost’ neurons endowed with atypical molecular and functional identity. Compared to ‘classical’ Pomc neurons, Ghost neurons exhibit negligible Pomc expression and are ‘invisible’ to available neuroanatomical approaches and promoter-based reporter mice for studying Pomc biology. Ghost neuron numbers augment in diet-induced obese mice, independent of neurogenesis or cell death, but weight loss can reverse this shift. Our work challenges the notion of fixed, developmentally programmed neuronal identities in the mature hypothalamus and highlight the ability of specialised neurons to reversibly adapt their functional identity to adult-onset obesogenic stimuli.

Background: This study aimed to evaluate the impact of photodynamic therapy (PDT) using two photosensitizers, methylene blue and indocyanine green, on the microtensile bond strength of a universal adhesive to caries-affected dentin. Methods: The occlusal enamel of 60 third molars was cut to expose the inner one-third of the dentin. Artificial caries were induced through a pH cycling process. The samples were divided into three groups: M (Methylene blue+ diode laser), I (Indocyanine green agents+ diode laser irradiation), and control. Each group was further divided into two subgroups according to the adhesive protocol (self-etch, total-etch). After restoring with Gradia composite resin, teeth were sectioned and exposed to 5000 thermal cycles. Microtensile bond strength was measured using a universal testing machine. The data were subjected to two- and one-way ANOVA and paired comparisons were performed by the Tamhane and Tukey tests. Results: The study found significant effects of the photosensitizer, etching pattern, and their interactions on the microtensile bond strength of composite resin to caries-affected dentin (P < 0.001). In the self-etching mode, PDT with indocyanine green exhibited significantly higher bond strength values compared to PDT with methylene blue (P = 0.001) and the control groups (P < 0.001). However, no significant differences were observed in the total-etch mode. (P = 0.54). Conclusions: The etching mode played a more significant role in the bond strength when using the universal adhesive alongside PDT with methylene blue and indocyanine green. Employing two photosensitizers in PDT during the self-etch mode significantly increased the bond strength values.

The progression and pathogenesis of membranous glomerulonephritis (MGN) are inextricably linked to chronic inflammation. Despite improving clinical remission rates due to the application of cyclophosphamide (CYC), treatment of MGN still requires further exploration. Ruxolitinib (Ruxo) negatively affects the signaling pathways participating in the production of pro-inflammatory cytokines. Hence, we investigated whether the combination of CYC and Ruxo can modulate inflammation through influencing T helper 17 (Th17) lineages and regulatory T cells (Tregs). Passive Heymann nephritis (PHN), an experimental model of MGN, was induced in a population of rats. Then, the animals were divided into five groups: PHN, CYC-receiving, Ruxo-receiving, CYC-Ruxo-receiving PHN rats, and healthy controls. After 28 days of treatment, biochemistry analysis was performed and splenocytes were isolated for flowcytometry investigation of Th17 cells and Tregs. The correlative transcription factors of the cells, alongside their downstream cytokine gene expressions, were also assessed using real-time PCR. Furthermore, serum cytokine signatures for the lymphocytes were determined through ELISA. The combination of CYC and Ruxo significantly reduced the serum values of urea in rats versus the PHN group (24.62 ± 7.970 vs. 40.60 ± 10.81 mg/dL). In contrast to Treg's activities, the functionality of Th17 cells noticeably increased not only in PHN rats but also in CYC or Ruxo-receiving PHN animals when compared with the control (10.60 ± 2.236, 8.800 ± 1.465, 8.680 ± 1.314 vs. 4.420 ± 1.551 %). However, in comparison to the PHN group, the incidence of Th17 cells notably fell in rats receiving CYC and Ruxo (10.60 ± 2.236 vs. 6.000 ± 1.373 %) in favor of the Treg's percentage (5.020 ± 1.761 vs. 8.980 ± 1.178 %), which was verified by the gene expressions and cytokine productions correlative to these lymphocytes. The combination of CYC and Ruxo was able to decline Th17 cells in favor of Tregs improvement in PHN rats, suggesting an innovative combination therapy in MGN treatment approaches.

Abstract Background Limb girdle muscular dystrophies (LGMDs) constitute a heterogeneous group of neuromuscular disorders with a very variable clinical presentation and overlapping traits. The clinical symptoms of LGMD typically appear in adolescence or early adulthood. Genetic variation in the dysferlin gene (DYSF) has been associated with LGMD. Methods We characterized a recessive LGMD in a young adult from consanguineous Irani families using whole-exome sequencing (WES) technology. Sanger sequencing was performed to verify the identified variant. Computational modeling and protein-protein docking were used to investigate the impact of the variant on the structure and function of the DYSF protein. Results By WES, we identified a novel homozygous missense variant in DYSF (NM_003494.4: c.5876T > C: p. Leu1959Pro) previously been associated with LGMD phenotypes. Conclusions The identification and validation of new pathogenic DYSF variant in the present study further highlight the importance of this gene in LGMD.

Abstract The immunotherapeutic application of interleukin-2 (IL-2) in cancer treatment is limited by its off-target effects on different cell populations and insufficient activation of anti-tumor effector cells at the site of the tumor upon tolerated doses. Targeting IL-2 to the tumor microenvironment by generating antibody-cytokine fusion proteins (immunocytokine) would be a promising approach to increase efficacy without associated toxicity. In this study, a novel nanobody-based immunocytokine is developed by the fusion of a mutant (m) IL-2 with a decreased affinity toward CD25 to an anti-vascular endothelial growth factor receptor-2 (VEGFR2) specific nanobody, denoted as VGRmIL2-IC. The antigen binding, cell proliferation, IFN-γ-secretion, and cytotoxicity of this new immunocytokine are evaluated and compared to mIL-2 alone. Furthermore, the pharmacokinetic properties are analyzed. Flow cytometry analysis shows that the VGRmIL2-IC molecule can selectively target VEGFR2-positive cells. The results reveal that the immunocytokine is comparable to mIL-2 alone in the stimulation of Primary Peripheral Blood Mononuclear Cells (PBMCs) and cytotoxicity in in vitro conditions. In vivo studies demonstrate improved pharmacokinetic properties of VGRmIL2-IC in comparison to the wild or mutant IL-2 proteins. The results presented here suggest VGRmIL2-IC could be considered a candidate for the treatment of VEGFR2-positive tumors.

Conjugated polymers such as polypyrrole, polyaniline, and polythiophene have developed as capable candidates for scaffold fabrication due to their electrical conductivity, tunable surface properties, and ability to deliver bioactive molecules. When blended with other biomaterials and nanoparticles enables the formation of composites that leverage the advantages of both components. The main focus areas of the review include the use of conjugated polymer-based composites (CPCs) for tissue engineering e.g., neural, cardiac, bone, and skin. Within each section, specific examples are provided of conjugated polymer-biomolecule composite systems that have been explored along with a discussion of their composition, fabrication, and performance for supporting cell growth and tissue regeneration. Finally, current challenges and future perspectives are discussed in applying CPCs toward engineering clinically relevant tissues and organs. Overall, this comprehensive review covers fundamental design considerations in developing conjugated polymer composite scaffolds and their emerging applications in tissue engineering.

Abstract This study introduces and compares computational fluid dynamics of Newtonian and non‐Newtonian blood flows in coronary arteries, with and without considering stents. Three blood flow models, including Newtonian, Carreau, and non‐Newtonian power‐law models, were simulated to investigate their effect, and the solution algorithm includes drawing the geometry, creating the desired mesh, and then simulating Newtonian and non‐Newtonian blood flow different models and comparing them with each other, is presented in the article. A Newtonian fluid model has been commonly used in the simulation of blood flow, whereas blood has non‐Newtonian properties due to the nature of a solution containing suspended particles. The goal of this research is to investigate the differences between the models built with Newtonian and non‐Newtonian fluid assumptions. In addition, a stent was designed and the effect of the stent on blood flow parameters was investigated for all three flow models, including Newtonian, Carreau, and non‐Newtonian power‐law models. Stents are medical devices that can be placed in arteries to open up blood flow in a blocked vessel. Stents can affect the wall shear stress. Knowing the slight deformation of the shear stress makes the importance of stent implantation and also helps to optimize the design of the intravascular stent, which can affect the occlusion of the vessels. The distribution of the velocity, pressure, and wall shear stress in all blood flow models with and without considering the effect of stents have been investigated and finally compared. Therefore, in general, the innovation of this article is to find the effect of implanted stents on blood flow parameters with different blood flow models, both Newtonian and non‐Newtonian. A comparison of Newtonian and non‐Newtonian flows showed that in the case of the Carreau non‐Newtonian model, the wall shear stress was higher. In addition, in the results of the geometric model with a stent effect compared to the geometric model without a stent effect, it is evident that there was a higher velocity and wall shear stress.

Abstract Background and Aim Staging liver fibrosis is important, and liver biopsy is the gold standard diagnostic tool. We aim to design and evaluate an artificial neural network (ANN) method by taking advantage of the Teaching Learning‐Based Optimization (TLBO) algorithm for the prediction of liver fibrosis stage in blood donors and hepatitis C patients. Methods We propose a method based on a selection of machine learning classification methods including multilayer perceptron (MLP) neural network, Naive Bayesian (NB), decision tree, and deep learning. Initially, the synthetic minority oversampling technique (SMOTE) is performed to address the imbalance in the dataset. Afterward, the integration of MLP and TLBO is implemented. Results We propose a novel algorithm that reduces the number of required patient features to seven inputs. The accuracy of MLP using 12 features is 0.903, while that of the proposed MLP with TLBO is 0.891. Besides, the diagnostic accuracy of all methods, except the model designed with the Bayesian network, increases when the SMOTE balancer is applied. Conclusion The decision tree‐based deep learning methods show the highest levels of accuracy with 12 features. Interestingly, with the use of TLBO and seven features, MLP reached an accuracy rate of 0.891, which is quite satisfactory when compared with those of similar studies. The proposed model provides high diagnostic accuracy, while reducing the required number of properties from the samples. The results of our study show that the recruited algorithm of our study is more straightforward, with a smaller number of required properties and similar accuracy.

Abstract Background Hypomyelinating leukodystrophy‐9 (HLD‐9) is caused by biallelic pathogenic variants in RARS1, which codes for the cytoplasmic tRNA synthetase for arginine (ArgRS). This study aims to evaluate the clinical, neuroradiological, and genetic characteristics of patients with RARS1‐related disease and determine probable genotype–phenotype relationships. Methods We identified three patients with RARS1 homozygous pathogenic variants. Furthermore, we performed a comprehensive review of the literature. Results Homozygous variants of RARS1 (c.2T>C (p.Met1Thr)) were identified in three patients with HLD‐9. Clinical symptoms were severe in all patients. Following the literature review, thirty HLD‐9 cases from eight studies were found. The 33 patients' main symptoms were hypomyelination, language delay, and intellectual disability or developmental delay. The mean age of onset for HLD9 in the group of 33 patients with a known age of onset was 5.8 months (SD = 8.1). The interquartile range of age of onset was 0–10 months. Of the 25 variants identified, c.5A>G (p.Asp2Gly) was identified in 11 patients. Conclusion Pathogenic variants in RARS1 decrease ArgRS activity and cause a wide range of symptoms, from severe, early onset epileptic encephalopathy with brain atrophy to a mild condition with relatively maintained myelination. These symptoms include the classic hypomyelination presentation with nystagmus and spasticity. Furthermore, the pathogenicity of the variation c.2T>C (p.Met1Thr) has been shown.

Key clinical message Subungual Onycholemmal Cyst (SOC) is a rare nail abnormality with different clinical presentations which can mimic different nail malignancies, such as melanoma, SCC, or glomus tumor. It is necessary for dermatologists and dermatopathologist to be aware of this pathology to make the proper diagnosis and treatment. SOC is a rare nail abnormality which affects the dermis of the nail bed. SOC has different clinical presentations, including onychodystrophy, ridging, clubbing, thickening, pigmentation, or even normal appearance. It can mimic different nail malignancies, such as melanoma, SCC, or glomus tumor. In this report, we describe a 54‐year‐old man with unilateral second right finger nail onychodystrophy and onycholysis for 1 year. He did not have any history of recent trauma, pain, or bleeding. It was completely resected by surgery. Nail biopsy can contribute to the early diagnosis of SOC and improvement of treatment outcomes.

Background: Falling is a significant cause of occupational injuries and fatalities among farmers, and falling from trees is one of the most common causes of injury resulting in a high number of visits to health centers. Despite this, there is limited evidence on the factors associated with falling from walnut trees. Therefore, this study aimed to identify the factors that contribute to falling from walnut trees from the perspective of farmers and farmworkers.Methods: This qualitative study was conducted using conventional content analysis. Data were collected through semi-structured interviews with 20 farmers and farmworkers who had experienced falling from walnut trees as recorded in the National Accidents Record Program from September to October 2017 in Tuyserkan county, Iran. Participants were selected through purposive sampling. Moreover, data rigor was ensured through participant and external checks. All interviews were recorded and analyzed using content analysis methods.Results: Data analysis led to the extraction of six themes, including psychological factors, physical factors, behavioral and habitual factors, economic factors, factors related to walnut trees, and atmospheric agents, along with 18 subthemes for behavioral, human, and environmental factors.Conclusion: The findings of this study suggest that with appropriate interventions and training, farmers and farmworkers can be guided and assisted so as to prevent the occurrence of falling from walnut trees. In addition to educational interventions, health promotion measures such as providing safety equipment and insurance coverage can be essential in reducing injuries.

Abstract Dysregulation of hypothalamic ceramides has been associated with disrupted neuronal pathways in control of energy and glucose homeostasis. However, the specific ceramide species promoting neuronal lipotoxicity in obesity have remained obscure. Here, we find increased expression of the C16:0 ceramide-producing ceramide synthase (CerS)6 in cultured hypothalamic neurons exposed to palmitate in vitro and in the hypothalamus of obese mice. Conditional deletion of CerS6 in hypothalamic neurons attenuates high-fat diet (HFD)-dependent weight gain and improves glucose metabolism. Specifically, CerS6 deficiency in neurons expressing pro-opiomelanocortin (POMC) or steroidogenic factor 1 (SF-1) alters feeding behavior and alleviates the adverse metabolic effects of HFD feeding on insulin sensitivity and glucose tolerance. POMC-expressing cell-selective deletion of CerS6 prevents the diet-induced alterations of mitochondrial morphology and improves cellular leptin sensitivity. Our experiments reveal functions of CerS6-derived ceramides in hypothalamic lipotoxicity, altered mitochondrial dynamics, and ER/mitochondrial stress in the deregulation of food intake and glucose metabolism in obesity.

Objectives: To investigate the level of troponin I and its association with mortality in patients with sepsis, severe sepsis, and septic shock. Materials and Methods: In general, 148 patients with sepsis, severe sepsis, and septic shock admitted to Kowsar hospital of Semnan in 2017-2019 were recruited in this study. Serum troponin levels were measured during the first 24 hours of admission. The second measurement was done in the next 48 hours, which aimed at increasing the likelihood of positive troponin over time. However, if the troponin was positive just once, the patient would be in the category of positive troponin. In addition, the patient’s prognosis was recorded within 30 days. Results: Based on the results, 27.7% had troponin levels higher than normal. The mortality rate in patients with normal and abnormal levels of troponin was 5.6% and 17.1%, respectively, which was a significant difference. The age of dead patients was significantly higher than the age of the living patients and the results showed that among the variables of gender, normal or abnormal level of troponin, age, and type of underlying infection, only age had a significant relationship with patients’ vital status. Conclusions: High levels of troponin were not effective in determining the prognosis of patients with sepsis, and only age had a significant relationship with patients’ vital status while the confirmation or rejection of this hypothesis will need further studies.

Introduction Pressure injuries (PIs) arise from sustained pressure on tissue, leading to reduced blood flow to the affected area. In patients with spinal cord injuries (SCIs), these PIs can significantly diminish their independence and overall quality of life. This research sought to assess the frequency of surgical complications in treatment regimens for large sacral PIs involving the anus. Specifically, the study focused on the incorporation of stoma formation in patients with SCIs. Methods A retrospective review identified 25 SCI patients who had extensive sacral PIs. These patients underwent intestinal stoma formation as a preparatory step before plastic reconstructive surgery to address the wounds between 2015 and 2020. Results Successful wound closure was achieved in all instances. Notably, each patient had experienced a minimum of three unsuccessful reconstructive surgeries elsewhere before this intervention. The observed rate of surgical complications aligned with findings from previous analogous studies. Conclusion While often viewed as a treatment of last resort, an intestinal stoma might serve as a valuable strategy, particularly for SCI patients with extensive PIs near the anal region, to promote the healing of such injuries. Tailored decision-making is essential to ensure the best possible patient outcomes.

Hepatocellular carcinoma (HCC) is one of the most prevalent forms of cancer worldwide. Therefore, it is essential to diagnose and treat HCC patients promptly. As a novel discovery, circulating tumor DNA (ctDNA) can be used to analyze the tumor type and the cancer location. Additionally, ctDNA assists the cancer stage determination, which enables medical professionals to provide patients with the most appropriate treatment. This review will discuss the HCC-related mutated genes diagnosed by ctDNA. In addition, we will introduce the different and the most appropriate ctDNA diagnosis approaches based on the facilities.