Broussardacosta6331
Nurses play an important role in educating patients on breast cancer and have a positive influence in encouraging women to participate in breast screening. This current study aimed to use a train-the-trainer model to improve the level of knowledge of nurses on breast cancer and screening in Ras Al Khaimah, United Arab Emirates. The study also focused on the nurses' ability to train other nurses in assisting women to engage in breast screening. This interventional study used a mixed-method design. Seventeen female nurses (aged 28-60 years) were recruited from public and private health centers and participated in a breast cancer train-the-trainer workshop. They completed a survey before and after the workshop. The surveys included a series of open and closed questions to assess their knowledge of breast cancer symptoms, risk factors, diagnosis, and patient communication. The study found that nurse participants had good baseline knowledge of breast cancer topics, including breast self-examinations, clinical breast examinations, and mammography. Responses were deemed accurate if they answered open-ended questions without incorrect information and correct options were selected in the quantitative sections. However, training improved the detail and accuracy of the participant responses. Training also improved the confidence of nurse participants to teach other women and nurses how to perform breast self-examinations and provide breast cancer information. There were significant increases in nurse participants' knowledge of risk factors (p less then 0.001, r = 0.6) and symptoms (p = 0.003, r = 0.5). The nurse participants perceived that health education was the best means of encouraging women to participate in breast screening.In an effort to minimize protocol noncompliance in neurological research studies that can potentially compromise patient safety, delay completion of the study, and result in premature termination and added costs, we determined the effect of investigator trainings and site initiation visits (SIVs) on the occurrence of noncompliance events. Results of protocol audits conducted at the National Institute of Neurological Disorders and Stroke from 2003 to 2019 on 97 research protocols were retrospectively analyzed. Based on the depth of auditing and provision of investigator research training, audit data were separated into four arms 1) Early Period, 2003 to 2012; 2) Middle Period, 2013 to 2016; and Late Period, 2017 to 2019, further divided into 3) Late Period without SIVs; and 4) Late Period with SIVs. Events of noncompliance were classified by the type of protocol deviation, the category, and the cause. In total, 952 events occurred across 1080 participants. Protocols audited during the Middle Period, compared to the Early Period, showed a decrease in the percentage of protocols with at least 1 noncompliance event. Protocols with SIVs had a further decrease in major, minor, procedural, eligibility, and policy events. Additionally, protocols audited during the Early Period had on average 0.46 major deviations per participant, compared to 0.26 events in protocols audited during the Middle Period, and 0.08 events in protocols audited during the Late Period with SIVs. Protocol deviations and noncompliance events in neurological clinical trials can be reduced by targeted investigator trainings and SIVs. These measures have major impacts on the integrity, safety, and effectiveness of human subjects research in neurology.Activated microglia can suppress neurite outgrowth and synapse recovery in the acute stage following traumatic brain injury (TBI). However, the underlying mechanism has not been clearly elucidated. Exosomes derived from microglia have been reported to play a critical role in microglia-neuron interaction in healthy and pathological brains. Here, we aimed to investigate the role of microglia-derived exosomes in regulating neurite outgrowth and synapse recovery following TBI. In our study, exosomes derived from microglia were co-cultured with stretch-injured neurons in vitro and intravenously injected into mice that underwent fluid percussion injury (FPI) by tail vein injection in vivo. The results showed that microglia-derived exosomes could be absorbed by neurons in vitro and in vivo. Moreover, exosomes derived from stretch-injured microglia decreased the protein levels of GAP43, PSD-95, GluR1, and Synaptophysin and dendritic complexity in stretch-injured neurons in vitro, and reduced GAP43+ NEUN cell percentage and apical dendritic spine density in the pericontusion region in vivo. Motor coordination was also impaired in mice treated with stretch-injured microglia-derived exosomes after FPI. A microRNA microarray showed that the level of miR-5121 was decreased most greatly in exosomes derived from stretch-injured microglia. Overexpression of miR-5121 in stretch-injured microglia-derived exosomes partly reversed the suppression of neurite outgrowth and synapse recovery of neurons both in vitro and in vivo. Moreover, motor coordination in miR-5121 overexpressed exosomes treated mice was significantly improved after FPI. Following mechanistic study demonstrated that miR-5121 might promote neurite outgrowth and synapse recovery by directly targeting RGMa. In conclusion, our finding revealed a novel exosome-mediated mechanism of microglia-neuron interaction that suppressed neurite outgrowth and synapse recovery of neurons following TBI.
One of the most common malignancies in women worldwide is breast cancer. Erector spinae plane block (ESPB) can reduce pain after modified radical mastectomy for breast cancer. The duration of nerve block analgesia is limited if local anesthetic agents are used alone. The purpose of this study was to evaluate the effect of dexmedetomidine on postoperative analgesia during a single injection of local anesthetics.
In this double-blind, randomized study, 60 female American Society of Anesthesiologists (ASA) I-II patients undergoing modified radical mastectomy were randomized into two groups ultrasound (US)-guided ESPB with 30mL of 0.33% ropivacaine (group R) and US-guided ESPB with 30mL of dexmedetomidine plus 0.33% ropivacaine (group DR). US-guided ESPB at the T3 vertebral level was performed preoperatively in all patients. The indicators were 1-, 6-, 12-, 24-, and 48-h visual analog scale (VAS) pain scores after surgery in the resting state and at 90-degree shoulder abduction. Other measures were a comparised for opioids during modified radical mastectomy for breast cancer.
The study was registered in the Chinese Clinical Trial Registry (ChiCTR2000031134, principal investigator Yao Lu, date of registration 2020-3-22).
The study was registered in the Chinese Clinical Trial Registry (ChiCTR2000031134, principal investigator Yao Lu, date of registration 2020-3-22).The monitoring of non-enzymatic post-translational modifications (PTMs) in therapeutic proteins is important to ensure drug safety and efficacy. Together with methionine and asparagine, aspartic acid (Asp) is very sensitive to spontaneous alterations. In particular, Asp residues can undergo isomerization and peptide-bond hydrolysis, especially when embedded in sequence motifs that are prone to succinimide formation or when followed by proline (Pro). As Asp and isoAsp have the same mass, and the Asp-Pro peptide-bond cleavage may lead to an unspecific mass difference of + 18 Da under native conditions or in the case of disulfide-bridged cleavage products, it is challenging to directly detect and characterize such modifications by mass spectrometry (MS). Here we propose a 2D NMR-based approach for the unambiguous identification of isoAsp and the products of Asp-Pro peptide-bond cleavage, namely N-terminal Pro and C-terminal Asp, and demonstrate its applicability to proteins including a therapeutic monoclonal antibody (mAb). To choose the ideal pH conditions under which the NMR signals of isoAsp and C-terminal Asp are distinct from other random coil signals, we determined the pKa values of isoAsp and C-terminal Asp in short peptides. The characteristic 1H-13C chemical shift correlations of isoAsp, N-terminal Pro and C-terminal Asp under standardized conditions were used to identify these PTMs in lysozyme and in the therapeutic mAb rituximab (MabThera) upon prolonged storage under acidic conditions (pH 4-5) and 40 °C. The results show that the application of our 2D NMR-based protocol is straightforward and allows detecting chemical changes of proteins that may be otherwise unnoticed with other analytical methods.In zebrafish, nicotine is known to regulate sensitivity to psychostimulants via epigenetic mechanisms. Little however is known about the regulation of addictive-like behavior by DNA methylation processes. To evaluate the influence of DNA methylation on nicotine-induced conditioned place preference (CPP), zebrafish were exposed to methyl supplementation through oral L-methionine (Met) administration. Met was found to reduce dramatically nicotine-induced CPP as well as behaviors associated with drug reward. The reduction was associated with the upregulation of DNA methyltransferases (DNMT1 and 3) as well as with the downregulation of methyl-cytosine dioxygenase-1 (TET1) and of nicotinic receptor subunits. Met also increased the expression of histone methyltransferases in nicotine-induced CPP groups. It reversed the nicotine-induced reduction in the methylation at α7 and NMDAR1 gene promoters. Treatment with the DNMT inhibitor 5-aza-2'-deoxycytidine (AZA) was found to reverse the effects of Met in structures of the reward pathway. Interestingly, Met did not modify the amount of the phospho-form of CREB (pCREB), a key factor establishing nicotine conditioning, whereas AZA increased pCREB levels. Our data suggest that nicotine-seeking behavior is partially dependent on DNA methylation occurring probably at specific gene loci, such as α7 and NMDAR1 receptor gene promoters. Overall, they suggest that Met should be considered as a potential therapeutic drug to treat nicotine addiction.Hypochlorite (ClO-) mediated by oxidative stress play an important role in the body's defense system due to their physiological and pathological significance. In this work, a new and simple probe was designed and synthesized to detect hypochlorite. This probe could rapidly respond to hypochlorite in a short time (20 s) in aqueous media, and showed excellent selectivity and sensitivity, and a wide pH range of 3 ̶ 12, as well as the low detection limit of 1.44 nM. In addition, it was successfully applied to the detection of ClO- in water sample, test paper experiment, and cell imaging.The aim of this study is to identify the optimal timing for cholecystectomy for acute cholecystitis. Patients undergoing cholecystectomy for acute cholecystitis from the National Surgery Quality Improvement Program database between 2014 and 2016 were included. The patients were divided into 4 groups, those who underwent surgery at days 0, 1, 2, or 3+ days. The primary outcome was short-term surgical morbidity and mortality. A total of 21,392 patients were included. After adjusting for confounders, compared to day 0 patients, those who underwent surgery at day 1 and day 2 had lower composite morbidity rate, while day 3+ patients had significantly higher bleeding and mortality rate. Subgroup analysis shows this trend to be more significant in the elderly and in diabetic patients who were delayed. Delay in cholecystectomy for over 72 h from admission is associated with statistically significant increase in bleeding and mortality.