Understanding facilitators of research participation among adults with self-reported chronic pain - a survey examining hypothetical research participation.

BACKGROUND: An inability to successfully recruit participants into clinical research has consequences that negatively affect the conduct and reliability of research studies. Understanding facilitators of research participation, namely motives for participation and preferred research outcomes, may improve recruitment and retention of clinical trials related to chronic pain. The present study explored research participation facilitators among individuals with chronic pain and their association with demographic characteristics, pain-related characteristics, and factors related to future research engagement. METHODS: Individuals from Michigan who were 18 years or older and self-reported having chronic pain completed an online survey assessing motives for research participation and desired research outcomes. Analyses were conducted in three stages. First, we evaluated underlying factors of motives for participation and research outcome preferences using principal components analysis. Second, we classified individuals according to their patterns of facilitators using latent profile analysis. Finally, we evaluated differences between facilitator profiles in demographic characteristics, pain-related characteristics, and factors related to future research engagement using χ2 analyses and Kruskal-Wallis rank sum tests. RESULTS: Three components of motives for research participation were identified: social engagement/enjoyment; pain improvement/advancing science; and compensation. Three components of research outcome preferences were identified: co-occurring symptom reduction; behavior reduction modification; and pain and function improvement. Four potential patient-centered profiles utilizing these dimensions of facilitators were identified that had unique demographic characteristics, research participation willingness, and treatment interest. CONCLUSIONS: Our data provide a framework of motives and research outcome preferences that may inform recruitment and retention in chronic pain research. It also gives an indication of who may respond best to active or passive recruitment strategies that appeal to a given motive or preferred outcome. This information may be useful for improving recruitment and to monitor any potential biases in participant samples.

Secretory phospholipase (sPLA2-IIA) regulates breast cancer stem cells differentiation and metastatic potential.

Breast cancer is the second most cancer worldwide in females. The primary factor responsible for tumor recurrence is the presence of breast cancer stem cells (BCSCs), which escape the chemo-radiotherapy. In this study, we have investigated the role of Secretory phospholipase-A2 Group 2A (sPLA2-IIA) that is overexpressed in BCSCs of MCF7 and MDA-MB-231 breast cancer cell lines. Further, overexpression of sPLA2-IIA revealed an increased EGFR/JNK/c-JUN/c-FOS signaling in BCSCs, while sPLA2-IIA knockdown significantly reduced the percentage of BCSCs and decreased signaling in both the cell lines. Importantly, sPLA2-IIA knockdown showed differentiation of BCSCs. Strikingly, PET imaging showed a decreased metastatic potential of BCSCs. Our study revealed a novel role of sPLA2-IIA in regulating BCSCs, which play a crucial role in regulating the differentiation and metastatic potential of BCSCs.

An Interventional Response Phenotyping Study in Chronic Low Back Pain: Protocol for a Mechanistic Randomized Controlled Trial.

Evidence-based treatments for chronic low back pain (cLBP) typically work well in only a fraction of patients, and at present there is little guidance regarding what treatment should be used in which patients. Our central hypothesis is that an interventional response phenotyping study can identify individuals with different underlying mechanisms for their pain who thus respond differentially to evidence-based treatments for cLBP. Thus, we will conduct a randomized controlled Sequential, Multiple Assessment, Randomized Trial (SMART) design study in cLBP with the following three aims. Aim 1: Perform an interventional response phenotyping study in a cohort of cLBP patients (n = 400), who will receive a sequence of interventions known to be effective in cLBP. For 4 weeks, all cLBP participants will receive a web-based pain self-management program as part of a run-in period, then individuals who report no or minimal improvement will be randomized to: a) mindfulness-based stress reduction, b) physical therapy and exercise, c) acupressure self-management, and d) duloxetine. After 8 weeks, individuals who remain symptomatic will be re-randomized to a different treatment for an additional 8 weeks. Using those data, we will identify the subsets of participants that respond to each treatment. In Aim 2, we will show that currently available, clinically derived measures, can predict differential responsiveness to the treatments. In Aim 3, a subset of participants will receive deeper phenotyping (n = 160), to identify new experimental measures that predict differential responsiveness to the treatments, as well as to infer mechanisms of action. Deep phenotyping will include functional neuroimaging, quantitative sensory testing, measures of inflammation, and measures of autonomic tone.

Validation of an on-screen application-based measurement of shoulder range of motion over telehealth medium.

BACKGROUND: Shoulder range-of-motion (ROM) assessment is vital for the follow-up evaluation of operated patients and for the outcome-based research studies. The aim of this study was to investigate the accuracy and reliability of a remote on-screen application (app)-based method of shoulder ROM measurement through a telehealth medium. MATERIALS AND METHODS: A consultant shoulder surgeon, a board-certified orthopedic resident, and a graduate medical doctor served as the examiners. The cohort consisted of 24 healthy volunteers and 16 symptomatic patients with expected shoulder ROM deficits. Shoulder ROM was first examined physically using a goniometer in the clinic and then over Zoom remote conferencing using the protractor extension app of the Chrome browser. RESULTS: Instrument validity was examined by comparing the goniometer method with the protractor app-based method of the expert shoulder consultant using Bland-Altman analysis. It showed only minor mean differences between the healthy volunteers and the patients in elevation (2.0° and 5.0°, respectively), abduction (2.0° and 3.0°, respectively), external rotation with the elbow adducted (1.9° and 0.2°, respectively), external rotation with the elbow abducted at 90° (0.4° and 4°, respectively), and internal rotation with elbow abducted at 90° (2.3° and 1.2°, respectively), with limits of agreement that were below the well-established minimal clinically important difference values. The intraclass correlation coefficient (ICC) values varied between 0.83 and 0.96 for the volunteers and between 0.90 and 0.98 for the patients, indicating excellent correlation between the 2 methods. The interobserver reliability between 2 examiners for the protractor app-based method as evaluated by ICC scores was excellent; it ranged between 0.86 and 0.98 for the volunteers and between 0.88 and 0.99 for the patients. Comparison of the protractor app-based method with the gold-standard goniometer method for the resident and the graduate doctor showed excellent ICC values. CONCLUSION: A protractor app-based method of measuring shoulder ROM over a telehealth medium is accurate and reliable compared with a clinical goniometer method. This validated method can be used during remote telehealth consultation with significant benefits of saving patients travel and time during the COVID-19 (coronavirus disease 2019) pandemic and even later.

Specific Oxide Nanoclusters Enhance Intracellular Reactive Oxygen Species for Cancer-Targeted Therapy.

Bio-nanotechnology based cancer therapeutics exponentially increase every year. A therapeutic strategy to induce intracellular reactive oxygen species (ROS) has received promising success in oncotherapy. In this study, the new strategy has been exploited by the treatment of iridium (Ir) and Fe2+ ions with cancer cells to biosynthesize the biocompatible fluorescent iridium oxide (IrO2) and iron oxide nanoclusters (NCs) under the specific redox heterogeneous microenvironment of these diseased cells and tumors. The hydroxyl radical produced by the presence of Fe2+ and H2O2 in cancer cells apparently increased the ROS level in cancer cells during the process of biosynthesized NCs and, hence, simultaneously instigated apoptosis of relevant cells. Therefore, intracellular ROS-mediated in situ biosynthesis of IrO2 and iron oxide NCs may also act as anticancer agents and provide a promising pathway for targeted cancer therapy.

The structure-energy landscape of NMDA receptor gating.

N-Methyl-D-aspartate (NMDA) receptors are the main calcium-permeable excitatory receptors in the mammalian central nervous system. The NMDA receptor gating is complex, exhibiting multiple closed, open, and desensitized states; however, central questions regarding the conformations and energetics of the transmembrane domains as they relate to the gating states are still unanswered. Here, using single-molecule Förster resonance energy transfer (smFRET), we map the energy landscape of the first transmembrane segment of the Rattus norvegicus NMDA receptor under resting and various liganded conditions. These results show kinetically and structurally distinct changes associated with apo, agonist-bound, and inhibited receptors linked by a linear mechanism of gating at this site. Furthermore, the smFRET data suggest that allosteric inhibition by zinc occurs by an uncoupling of the agonist-induced changes at the extracellular domains from the gating motions leading to an apo-like state, while dizocilpine, a pore blocker, stabilizes multiple closely packed transmembrane states.

Nano in nano: Biosynthesized gold and iron nanoclusters cargo neoplastic exosomes for cancer status biomarking.

Timely detection is crucial for successful treatment of cancer. The current study describes a new approach that involves utilization of the tumor cell environment for bioimaging with in-situ biosynthesized nanoscale gold and iron probes and subsequent dissemination of Au-Fe nanoclusters from cargo exosomes within the circulatory system. We have isolated the Au-Fe cargo exosomes from the blood of the treated murine models after in situ biosyntheses from their respective pre-ionic solutions (HAuCl4, FeCl2), whereas Na2SeO3 supplementation added into Au lethal effect. The microarray data of various differentially expressed genes revealed the up-regulated tumor ablation and metal binding genes in SGC-7901 cell lines after treatment with Au-Fe-Se triplet ionic solution. The isolation of Au-Fe nanoclusters cargo exosomes (nano in nano) after secretion from deeply seated tumors may help in early diagnosis and reveal the tumor ablation status during and after the relevant treatment like radio-chemo therapies et al.

The DA Vinci Diet.

Ample evidence implicating diet as the root cause of diseases exists in the scientific arena. It is always intruiging to know the diet pattern of our ancestors. Leonardo da Vinci was a 'universal genius' with universal appeal. This article describes the basic principles of the diet that he followed. "Dining discipline" and moderation in eating should be coupled with the aim of savouring smell, taste, and texture of food. Fresh, fibre rich, vegetarian food forms the bulk of the da Vinci diet. Saturated fat, salt and sugar use is minimal, but water and water-rich food intake is encouraged.

Conformational Selection and Submillisecond Dynamics of the Ligand-binding Domain of the N-Methyl-d-aspartate Receptor.

The N-methyl-d-aspartate (NMDA) receptors are heteromeric non-selective cation channels that require the binding of glycine and glutamate for gating. Based on crystal structures, the mechanism of partial agonism at the glycine-binding site is thought to be mediated by a shift in the conformational equilibrium between an open clamshell and a closed clamshell-like structure of the bilobed ligand-binding domain (LBD). Using single-molecule Förster resonance energy transfer (smFRET) and multiparameter fluorescence detection, which allows us to study the conformational states and dynamics in the submillisecond time scale, we show that there are at least three conformational states explored by the LBD: the low FRET, medium FRET, and high FRET states. The distance of the medium and low FRET states corresponds to what has been observed in crystallography structures. We show that the high FRET state, which would represent a more closed clamshell conformation than that observed in the crystal structure, is most likely the state initiating activation, as evidenced by the fact that the fraction of the protein in this state correlates well with the extent of activation. Furthermore, full agonist bound LBDs show faster dynamic motions between the medium and high FRET states, whereas they show slower dynamics when bound to weaker agonists or to antagonists.

Radiotherapy improves serum fatty acids and lipid profile in breast cancer.

BACKGROUND: Breast cancer is a disease with diverse clinical symptoms, molecular profiles, and its nature to response its therapeutic treatments. Radiotherapy (RT), along with surgery and chemotherapy is a part of treatment in breast cancer. The aim of present study was to investigate pre and post treatment effects of radiotherapy in serum fatty acids and its lipids profile in patients with breast cancer. METHODS: In this comparative as well as follow up study, Serum fatty acids were performed by gas chromatography to investigate fatty acids and Microlab for analysis of lipid profile. RESULTS: Among serum free and total fatty acids the major saturated fatty acids (SFAs) in serum lipids of breast cancer patients (pre and post treated) were stearic acid (18:0) and palmitic acid (16:0). These fatty acids contributed about 35-50% of total fatty acids. The decreased concentrations of linoleic acid (C18:2) and arachidonic acid (C20:4) with a lower ratio of C18:2/C18:1 was found in pretreated breast cancer patients as compared to controls. The n-3/n-6 ratio of breast cancer patients was decreased before treatment but it was 35% increased after treatment. In addition, plasma activity of D6 desaturase was increased in the breast cancer patients, while the activity of D5 desaturase was decreased. Increased levels of SFAs, monounsaturated fatty acids (MUFAs) and decreased polyunsaturated fatty acids (PUFAs) levels in breast cancer patients (pre and post treated) as compared to controls. Serum total cholesterol (TC) (224.4 mg/dL) and low density lipoprotein cholesterol (LDL-C) (142.9 mg/dL) were significantly increased in pretreated breast cancer patients but after the radiotherapy treatment, the TC (150.2 mg/dL) and LDL-C (89.8 mg/dL) were decreased. CONCLUSION: It seems that RT would have played a potential role in the treatment of BC. After RT the serum levels of PUFAs, TC, and LDL-C are improved. Our study reinforces the important role of RT in the management of BC. The level of PUFAs, TC, and LDL-C can be used as the biomarkers for early diagnosis in individuals with risk of breast cancer.

Phospholamban and sarcolipin: Are they functionally redundant or distinct regulators of the Sarco(Endo)Plasmic Reticulum Calcium ATPase?

In muscle, the Sarco(Endo)plasmic Reticulum Calcium ATPase (SERCA) activity is regulated by two distinct proteins, PLB and SLN, which are highly conserved throughout vertebrate evolution. PLB is predominantly expressed in the cardiac muscle, while SLN is abundant in skeletal muscle. SLN is also found in the cardiac atria and to a lesser extent in the ventricle. PLB regulation of SERCA is central to cardiac function, both at rest and during extreme physiological demand. Compared to PLB, the physiological relevance of SLN remained a mystery until recently and some even thought it was redundant in function. Studies on SLN suggest that it is an uncoupler of the SERCA pump activity and can increase ATP hydrolysis resulting in heat production. Using genetically engineered mouse models for SLN and PLB, we showed that SLN, not PLB, is required for muscle-based thermogenesis. However, the mechanism of how SLN binding to SERCA results in uncoupling SERCA Ca(2+) transport from its ATPase activity remains unclear. In this review, we discuss recent advances in understanding how PLB and SLN differ in their interaction with SERCA. We will also explore whether structural differences in the cytosolic domain of PLB and SLN are the basis for their unique function and physiological roles in cardiac and skeletal muscle.

Sarcolipin Is a Key Determinant of the Basal Metabolic Rate, and Its Overexpression Enhances Energy Expenditure and Resistance against Diet-induced Obesity.

Sarcolipin (SLN) is a novel regulator of sarcoplasmic reticulum Ca(2+) ATPase (SERCA) in muscle. SLN binding to SERCA uncouples Ca(2+) transport from ATP hydrolysis. By this mechanism, SLN promotes the futile cycling of SERCA, contributing to muscle heat production. We recently showed that SLN plays an important role in cold- and diet-induced thermogenesis. However, the detailed mechanism of how SLN regulates muscle metabolism remains unclear. In this study, we used both SLN knockout (Sln(-/-)) and skeletal muscle-specific SLN overexpression (Sln(OE)) mice to explore energy metabolism by pair feeding (fixed calories) and high-fat diet feeding (ad libitum). Our results show that, upon pair feeding, Sln(OE) mice lost weight compared with the WT, but Sln(-/-) mice gained weight. Interestingly, when fed with a high-fat diet, Sln(OE) mice consumed more calories but gained less weight and maintained a normal metabolic profile in comparison with WT and Sln(-/-) mice. We found that oxygen consumption and fatty acid oxidation were increased markedly in Sln(OE) mice. There was also an increase in both mitochondrial number and size in Sln(OE) muscle, together with increased expression of peroxisome proliferator-activated receptor δ (PPARδ) and PPAR γ coactivator 1 α (PGC1α), key transcriptional activators of mitochondrial biogenesis and enzymes involved in oxidative metabolism. These results, taken together, establish an important role for SLN in muscle metabolism and energy expenditure. On the basis of these data we propose that SLN is a novel target for enhancing whole-body energy expenditure.

The N Terminus of Sarcolipin Plays an Important Role in Uncoupling Sarco-endoplasmic Reticulum Ca2+-ATPase (SERCA) ATP Hydrolysis from Ca2+ Transport.

The sarcoendoplasmic reticulum Ca(2+)-ATPase (SERCA) is responsible for intracellular Ca(2+) homeostasis. SERCA activity in muscle can be regulated by phospholamban (PLB), an affinity modulator, and sarcolipin (SLN), an uncoupler. Although PLB gets dislodged from Ca(2+)-bound SERCA, SLN continues to bind SERCA throughout its kinetic cycle and promotes uncoupling of Ca(2+) transport from ATP hydrolysis. To determine the structural regions of SLN that mediate uncoupling of SERCA, we employed mutagenesis and generated chimeras of PLB and SLN. In this study we demonstrate that deletion of SLN N-terminal residues (2)ERSTQ leads to loss of the uncoupling function even though the truncated peptide can target and constitutively bind SERCA. Furthermore, molecular dynamics simulations of SLN and SERCA interaction showed a rearrangement of SERCA residues that is altered when the SLN N terminus is deleted. Interestingly, transfer of the PLB cytosolic domain to the SLN transmembrane (TM) and luminal tail causes the chimeric protein to lose SLN-like function. Further introduction of the PLB TM region into this chimera resulted in conversion to full PLB-like function. We also found that swapping PLB N and C termini with those from SLN caused the resulting chimera to acquire SLN-like function. Swapping the C terminus alone was not sufficient for this conversion. These results suggest that domains can be switched between SLN and PLB without losing the ability to regulate SERCA activity; however, the resulting chimeras acquire functions different from the parent molecules. Importantly, our studies highlight that the N termini of SLN and PLB influence their respective unique functions.

Sarcolipin protein interaction with sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) is distinct from phospholamban protein, and only sarcolipin can promote uncoupling of the SERCA pump.

Sarco(endo)plasmic reticulum Ca(2+)ATPase (SERCA) pump activity is modulated by phospholamban (PLB) and sarcolipin (SLN) in cardiac and skeletal muscle. Recent data suggest that SLN could play a role in muscle thermogenesis by promoting uncoupling of the SERCA pump (Lee, A.G. (2002) Curr. Opin. Struct. Biol. 12, 547-554 and Bal, N. C., Maurya, S. K., Sopariwala, D. H., Sahoo, S. K., Gupta, S. C., Shaikh, S. A., Pant, M., Rowland, L. A., Bombardier, E., Goonasekera, S. A., Tupling, A. R., Molkentin, J. D., and Periasamy, M. (2012) Nat. Med. 18, 1575-1579), but the mechanistic details are unknown. To better define how binding of SLN to SERCA promotes uncoupling of SERCA, we compared SLN and SERCA1 interaction with that of PLB in detail. The homo-bifunctional cross-linker (1,6-bismaleimidohexane) was employed to detect dynamic protein interaction during the SERCA cycle. Our studies reveal that SLN differs significantly from PLB: 1) SLN primarily affects the Vmax of SERCA-mediated Ca(2+) uptake but not the pump affinity for Ca(2+); 2) SLN can bind to SERCA in the presence of high Ca(2+), but PLB can only interact to the ATP-bound Ca(2+)-free E2 state; and 3) unlike PLB, SLN interacts with SERCA throughout the kinetic cycle and promotes uncoupling of the SERCA pump. Using SERCA transmembrane mutants, we additionally show that PLB and SLN can bind to the same groove but interact with a different set of residues on SERCA. These data collectively suggest that SLN is functionally distinct from PLB; its ability to interact with SERCA in the presence of Ca(2+) causes uncoupling of the SERCA pump and increased heat production.

The Pain Research Enrichment Program (PREP): Developing an immersive program for research assistants at an academic medical center.

Research experience is often important for academic and career development. This paper describes the implementation and impact of a training program for temporary research assistants (RAs) at an academic medical center. The program includes a 9-month didactic lecture series covering research and professional development skills, a Quality Improvement project focused on improving research processes, and manuscript writing. Overall, the program goals of increasing confidence, self-efficacy, job satisfaction, and well-being, as well as providing an opportunity for career exploration, were met. Thus, this program has the potential to support temporary RAs and enhance their early research experiences.

Amrubicin encapsulated PLGA NPs inhibits the PI3K/AKT signaling pathway by activating PTEN and inducing apoptosis in TMZ-resistant Glioma.

Glioblastoma (GBM) remains a challenging malignancy due to its aggressive nature and the lack of efficacious therapeutic interventions. Nanotechnology-based approaches exhibit promise in GBM treatment; however, the successful translation of these strategies from preclinical models to clinical settings is hindered by inefficient nanoparticle clearance from vital organs. Addressing this concern, we investigated the therapeutic potential of amrubicin (AMR) encapsulated within poly (lactic-co-glycolic acid) nanoparticles (AMR-PLGA-NPs) in combating temozolomide (TMZ) resistant GBM. The study demonstrated that AMR-PLGA-NPs exerted a pronounced inhibitory effect on the cellular viability and migratory capacity of TMZ-resistant GBM cells. Furthermore, these nanoparticles exhibited considerable efficacy in downregulating the PI3K/AKT signaling pathway, thereby inducing apoptosis specifically in TMZ-resistant glioma cells and glioma stem-like cells through the activation of PTEN. Notably,in vivoexperimentation revealed the ability of AMR-PLGA-NPs to traverse biological barriers within murine models. Collectively, these findings underscore the potential therapeutic utility of AMR-PLGA-NPs as a versatile nanoplatform for addressing the formidable challenges posed by GBM, particularly in mitigating drug resistance mechanisms. The study substantiates the stability and safety profile of AMR-PLGA-NPs, positioning them as a promising avenue for combating drug resistance in GBM therapeutics.

Effect of ankle versus thigh tourniquets on post-operative pain in foot and ankle surgery.

BACKGROUND: Tourniquets are commonly used in elective extremity orthopaedic surgery to reduce blood loss, improve visualization in the surgical field, and to potentially reduce surgical time. There is a lack of consensus in existing guidelines regarding the optimal tourniquet pressure, placement site, and duration of use. There is a paucity of data on the relationship between the site of a tourniquet and postoperative pain in foot and ankle surgery. AIM: To explore the relationship between tourniquet site and intensity of post-operative pain scores in patients undergoing elective foot and ankle surgery. METHODS: Retrospective analysis of prospectively collected data on 201 patients who underwent foot and ankle surgery in a single institution was undertaken. Intraoperative tourniquet duration, tourniquet pressure and site, and postoperative pain scores using Visual Analogue Score were collected in immediate recovery, at six hours and at 24 h post-op. Scatter plots were used to analyse the data and to assess for the statistical correlation between tourniquet pressure, duration, site, and pain scores using Pearson correlation coefficient. RESULTS: All patients who underwent foot and ankle surgery had tourniquet pressure of 250 mmHg for ankle tourniquet and 300 mmHg for thigh. There was no correlation between the site of the tourniquet and pain scores in recovery, at six hours and after 24 h. There was a weak correlation between tourniquet time and Visual Analogue Score immediately post-op (r = 0.14, P = 0.04) but not at six or 24 h post-operatively. CONCLUSION: This study shows that there was no statistically significant correlation between tourniquet pressure, site and post-op pain in patients undergoing foot and ankle surgery. The choice of using a tourniquet is based on the surgeon's preference, with the goal of minimizing the duration of its application at the operative site.

Incidence and Severity of Adverse Drug Reactions in Medical Intensive Care Unit.

BACKGROUND: Adverse drug reactions (ADRs) curtail patients' quality of life by virtue of increasing therapeutic complexity and rising multimorbidity. In India, the frequency of ADRs for individual drugs and their economic burdens are rarely evaluated. This study aimed at identifying the incidence and severity of ADRs leading to hospitalization (ADRA) and occurring during a hospital stay (ADRH). OBJECTIVE: The objective of this study is to study the incidence and severity of ADRs in the ICU and their impact on the duration of hospitalization, along with the cost incurred to treat ADRs in the ICU. METHOD: Demographic, clinical, and pharmacological data on patients admitted to the ICU were collected, analyzed and evaluated for ADRs. According to the setting analyzed, a descriptive analysis of the reactions, suspected medicines, and associated factors was undertaken. RESULT: A total of 208 patients were admitted to the ICU during the study period, of which ADRA contributed 9.1% of the incidence rate and 8.1% of ADRH in 36 patients. Males had a higher incidence of ADRs than females. Patients who had ADRs had a substantially longer length of stay than those who did not. Electrolyte disturbance was the most commonly found ADR. According to the Hartwig scale and WHO-causality scale, 88.9% were moderate, and 97.2% were possible ADRs, respectively. CONCLUSION: In this study, a similar incidence rate of ADRA and ADRH was observed. The average cost for treating ADRA was higher than that for treating ADRH. As a result, identifying and preventing these reactions is critical, as they cause the patient greater suffering.

Bleomycin loaded exosomes enhanced antitumor therapeutic efficacy and reduced toxicity.

BACKGROUND: Bleomycin (BLM) is a chemotherapeutic agent with potent antitumor activity against the tumor. However, lung fibrosis is the main drawback that limits BLM use. Tumor targeted, safe, efficient and natural delivery of BLM is important to increase the effectiveness and reduce the toxic side effects. Although tumor derived Exosomes (Exo), provide a potential vehicle for in vivo drug delivery due to their cell tropism. This study primarily focuses on generating a natural delivery platform for Exo loaded with BLM and testing its therapeutic efficacy against cancer. METHODS: Exosomes were isolated from cancer cells and incubated with BLM. Exo were characterized by transmission electron microscopy, western blot analysis and nanoparticle tracking analysis. We performed in vitro and in vivo analyses to evaluate the effect of Exo-BLM. RESULTS: Exosomes loaded with BLM are highly cancer targeting and cause the cytotoxicity of tumor cells by ROS. The fluorescence images showed that Exo-BLM accumulated in cancer cells. The results revealed that Exo-BLM induces tumor cell apoptosis by the caspase pathway. In vivo, the treatment of Exo-BLM showed targeted ability and enhanced the antitumor activity. CONCLUSION: This study provides an avenue for specific BLM therapeutics with minimal side effects.

Implementing a mentoring program for clinical research professionals: A novel professional development initiative for university health research staff.

Clinical and translational research relies on a well-trained workforce, but mentorship programs designed expressly for this workforce are lacking. This paper presents the development of a mentoring program for research staff and identifies key programmatic outcomes. Research staff participating in this program were matched with a senior mentor. Focus groups were conducted to identify key program outcomes. Surveys were administered throughout the program period to assess participants' experience, gains in skill, and subsequent careers. Analysis of the resultant qualitative and quantitative data are used to characterize the implementation and impact of the program. A total of 47 mentees and 30 mentors participated in program between 2018 and 2023. A comprehensive logic model of short-, intermediate- and long-term outcomes was developed. Participants reported positive valuations of every programmatic outcome assessed including their program experience, learning and research careers. The pool of available mentors also grew as new mentors were successfully recruited for each cohort. This mentorship program developed and implemented by senior research staff successfully provided junior research staff with professional development support, mentorship, and professional development opportunities. Junior and senior health research staff built mentoring relationships that advanced their clinical and translational research careers.