Purpose Hospital volume–outcome association has been examined for many high-risk surgical procedures. Little is known about this association for thumb replantation, a complex but essential surgical ...procedure to restore hand function. We aimed to determine patient and hospital characteristics that are associated with increased probability of replanted thumb survival and to examine volume–outcome association among hospitals that performed thumb replantation. Methods We used data from 2008 to 2012 from the National Trauma Data Bank. Our sample included 773 patients who underwent thumb replantation procedures in 1 of 180 hospitals during the study period. We used patient-level logistic models to examine the association between a hospital’s annual thumb replantation volume and the probability of survival for the replanted thumb. Results Patients with drug/alcohol abuse record, and higher numbers of comorbid conditions had lower odds of replant success. Treatment in teaching hospitals and hospitals with a higher volume of thumb replantation increased the odds of replant survival. The risk-adjusted replantation success rate in high-volume hospitals was 12% higher than in low-volume hospitals. Conclusions Regionalization of digit replantation procedures to high-volume centers can achieve the highest rate of successful revascularization. Type of study/level of evidence Economic/Decision Analysis II.
Previous studies on the Chinese famine suggested long-term effects of early-life famine exposure on health conditions. This study aims to investigate the association between exposure to the Chinese ...famine of 1959-1961 at different early-life stages and the risk of cognitive decline in adulthood. A total of 6417 adults born between 1952 and 1964 in the 2015 survey data of China Health and Retirement Longitudinal Study were included in this study. Cognitive performance was estimated through a series of comprehensive neuropsychological tests, including the Telephone Interview of Cognitive Status (TICS-10), word recall, and pentagon drawing. Multiple generalized linear model (GLM) was employed to detect the association between multi-stage early-life famine exposure and late-life cognitive performance. Compared with the unexposed group, respondents exposed to famine in the fetal period performed worse in the TICS (difference -0.52, 95% confidence interval (CI): -0.93 to -0.10), word recall (difference -0.46, 95% CI: -0.74 to -0.19), and general cognition (difference -1.05, 95% CI: -1.64 to -0.47). Furthermore, we also found negative effects of famine exposure on performance of word recall and pentagon drawing in the early (word recall difference -0.56, 95% CI: -1.00 to -0.11; pentagon drawing difference -0.76, 95% CI: -1.40 to -0.12), mid (word recall difference -0.46, 95% CI: -0.81 to -0.11; pentagon drawing difference -0.66, 95% CI: -1.16 to -0.16), and late (word recall difference -0.30, 95% CI: -0.55 to -0.04; pentagon drawing difference -0.75, 95% CI: -1.13 to -0.37) childhood-exposed groups. Early-life famine exposure in different stages is positively associated with late-life cognitive decline. Fetal famine exposure might affect the overall cognitive status in adulthood, and childhood famine exposure has potential adverse effects on visuospatial episodic memory.
It is advantageous to develop an effective purification procedure to produce recombinant protein drugs (rPDs) without any tags. To remove N- or C-terminus tags from the rPDs, several cleavage ...site-based endopeptidases were used. Separating the endopeptidase enzyme from the rPDs is a time-consuming and costly process.
To design and develop a new method for the purification of human interleukin (IL)-4 with potential application for other cytokines.
Met-like amino acids were substituted at position 120 to reduce the possibility of alteration in the structure of IL-4 and its biological activity. Based on the in silico analysis, isoleucine was chosen as an alternative amino acid, and the M120I mutant IL-4 (mIL-4) model was selected for the downstream analysis. Recombinant mIL-4 was produced in the E.coli BL21 host and purified with CNBr. Then in vitro evaluations of the native and mutant IL-4 were performed.
The results showed that both the native and mutant IL-4 had the same effect on TF-1 cell proliferation. On the other hand, there was no significant difference between the effects of native IL-4 (nIL-4) and mIL-4 on the expression of IL-4 and IL-10 in activated peripheral blood mononuclear cells. Native and mutant IL-4 have similar biological activities.
Here, an efficient and straightforward system is introduced to purify IL-4 cytokine using CNBr, which could be applied to other rPDs.
This project aimed to produce a biosimilar version of aflibercept (AFL) and evaluate the effect of the co-treatment of AFL with other vascular endothelial growth factor (VEGF) blocker drugs. For this ...purpose, the optimized gene was inserted into the pCHO1.0 plasmid and transfected into the CHO-S cell line. The final concentration of biosimilar-AFL for the selected clone was 782 mg/L. Results revealed that the inhibition potential of the biosimilar-AFL on HUVEC cells was significant at 10 and 100 nM concentrations and in a dose-dependent manner. Furthermore, co-treatment of biosimilar-AFL with Everolimus (EVR), Lenvatinib (LEN), and Sorafenib (SOR) could reduce HUVEC cell viability/proliferation, more than when used alone. When LEN and SOR were co-treated with biosimilar-AFL, their cytotoxicity increased 10-fold. The most and least efficient combination was seen when biosimilar-AFL combined with LEN and EVR, respectively. Finally, biosimilar-AFL may improve the efficiency of LEN, EVR, and SOR in reducing the VEGF effect on endothelial cells.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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There are a number of distinct challenges and complexities associated with administering IL-15 for cancer immunotherapy that must be taken into consideration.
The purpose of this ...study was to design a fusion protein for targeting cytotoxic immune cells and enhance IL-15 efficiency.
A fusokine that contains IL-15(N72D), a Sushi domain, and anti-NKG2D scFv was designed. The fusion protein was in-silico modeled using the Swiss model server, followed by docking and molecular dynamics simulations. The in-vitro purified fusokine was evaluated using dot blot and Western blot. Then, flow cytometry was employed to evaluate biological properties such as proliferation, cytotoxicity, and degranulation.
Fusokine and IL-15(N72D)/Sushi, which had molecular weights of about 52 kDa and 26 kDa, respectively, were expressed in CHO-K1 cells. The fusokine binds 69.6 % of the CHO-NKG2D+ cells that express 83.1 % NKG2D. Both the fusokine and the IL-15(N72D)/Sushi significantly stimulate the proliferation of lymphocytes. After 14 days of growth, the vitality of untreated cells decreased to about 17.5 %, but 82.2 % and 56.6 % of cells were still alive when fusokine and IL-15(N72D)/Sushi were present. Furthermore, administration of fusokine was associated with the highest rates of target tumor cell cytotoxicity. Additionally, although it was not statistically significant, fusokine increased the expression of CD107a and granzyme B by 1.25 times and 2.4 times, respectively.
The fusokine possesses the capability to stimulate the survival and multiplication of lymphocytes, as well as their ability to eliminate tumors. These characteristics have led to its consideration as a potential treatment for immunotherapy.
Extracellular vesicles (EVs) harbor several signaling molecules to maintain intercellular communication. Based on the exosomal cargo type, metabolic, genomic, and proteomic status of parent cells can ...be investigated. Due to the existence of trivial levels of target molecules inside EVs, the application of accurate and sensitive detection methods is mandatory. Here, we used an electrochemical immunosensor using a biotinylated monoclonal CD63 antibody as the capturing element for the detection of EVs isolated from MDA-MB-231 cells and cancer patients. Simultaneously, breast cancer biomarker CA-15-3 was detected in isolated EVs using a sandwich method to increase specificity. Data indicated a linear dynamic range of 2000–10000 EVs/µL and a lower limit of quantification of 2000 EVs/µL. Based on data from real sample analysis, the levels of exosomal CA-15-3 can differ according to the severity and systemic content of this factor. Pd-perovskite-based immunosensor provides a platform for quick and in-depth analysis of EVs isolated for cancer cells.
In the present research work, the state-of-art label-free electrochemical genosensing platform was developed based on the hybridization process in the presence of Fe(CN)
as an efficient redox probe ...for sensitive recognition of the miRNA-21 in human gastric cell lines samples. To attain this aim, perovskite nanosheets were initially synthesized. Afterward, the obtained compound was combined with the graphene oxide resulting in an effective electrochemical modifier, which was dropped on the surface of the Au electrode. Then, AuNPs (Gold Nano Particles) have been electrochemically-immobilized on perovskite-graphene oxide/Au-modified electrode surface through the chronoamperometry (CA) technique. Finally, a self-assembling monolayer reaction of ss-capture RNA ensued by the thiol group at the end of the probe with AuNPs on the modified electrode surface. miRNA-21 has been cast on the Au electrode surface to apply the hybridization process. To find out the effectiveness of the synthesized modifier agent, the electrochemical behavior of the modified electrode has been analyzed through DPV (differential pulse voltammetry) and CV (cyclic voltammetry) techniques. The prepared biomarker-detection bioassay offers high sensitivity and specificity, good performance, and appropriate precision and accuracy for the highly-sensitive determination of miRNA-21. Different characterization methods have been used, such as XRD, Raman, EDS, and FE-SEM, for morphological characterization and investigation of particle size. Based on optimal conditions, the limit of detection and quantification have been acquired at 2.94 fM and 8.75 fM, respectively. Furthermore, it was possible to achieve a wide linear range which is between 10
and 10
for miRNA-21. Moreover, the selectivity of the proposed biosensing assay was investigated through its potential in the detection of one, two, and three-base mismatched sequences. Moreover, it was possible to investigate the repeatability and reproducibility of the related bio-assay. To evaluate the hybridization process, it is important that the planned biomarker detection bio-assay could be directly re-used and re-generated.
This study aimed to evaluate the association between cognitive and affective empathy and aggression in a sample of Iranian athletes.
We designed a cross-sectional study. The participants were ...selected by multistage random sampling among six colleges in Tehran, Iran's capital. We used the interpersonal reactivity index (IRI) to evaluate empathy, and Reactive Proactive Aggression Questionnaire, and the Buss-Perry aggression questionnaire to evaluate aggression.
In total, 492 athletes with a mean age of 27.42 years (SD = 7.72) participated in the study, of which 298 (60.6%) were male, and 194 (39.4%) were female. IRI's fantasy and personal distress subscales scores were positively associated with proactive and reactive aggression scores (p < 0.05). The score of the perspective-taking subscale of IRI was negatively associated with proactive and reactive aggression scores (p < 0.05). The score of the empathic concern subscale of IRI had a negative association with the proactive aggression score (p < 0.001). The score of the perspective-taking subscale of IRI had negative associations with all Buss-Perry aggression questionnaire subscales' scores (p < 0.05). The score of the personal distress subscale of IRI had positive associations with all Buss-Perry aggression questionnaire subscales' scores (p < 0.05), except with the verbal aggression subscale score. The score of the fantasy subscale of IRI was positively associated with the score of the hostility subscale of the Buss-Perry questionnaire (p = 0.001).
Perspective-taking is negatively associated with all kinds of aggression in athletes. Future studies can be conducted to determine the possible role of perspective-taking in preventive aggression, which can be a target for interventions. On the other hand, the score of the personal distress subscale of IRI is positively associated with all types of aggression scores, indicating that not all types of empathy inhibit aggression in athletes.
Background
Although the World Health Organization (WHO) has developed tools to standardize economic evaluations of global health interventions, little is known about the cost-effectiveness of ...surgical mission trips and their economic values. Our objective was to systematically evaluate the current literature on surgical volunteering trips to measure their adherence to WHO CHOosing Interventions that are cost-effective (WHO-CHOICE). We hypothesized that the majority of studies use some type of cost-effectiveness analysis that do not adhere to these standards.
Methods
A systematic review of Pubmed, Medline, and Embase databases was performed in accordance with PRISMA guidelines, with inclusion criteria set a priori. Of the 908 publications screened, 72 were selected for full text review; 17 met inclusion criteria.
Results
Only 17 out of 72 studies reported some type of economic analysis. We categorized the studies into service, educational, and combination (service and educational) surgical trips. Although seven of the service studies calculated the cost per disability-adjusted life year averted, the results were not based on WHO-CHOICE standards to facilitate comparisons among alternative options. Furthermore, none of the three educational trips calculated the value of the education provided, but only published cost estimates of the resources used during the trip.
Conclusions
Although a few studies performed some type of economic analysis, owing to their non-adherence to WHO-CHOICE standards, the results were not comparable to other studies. International surgical trips are expensive. To improve the efficacy and optimal use of limited resources, studies on surgical trips should follow the guidelines set by the WHO-CHOICE.
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