-
Biomolecules May 2024Encapsulins are self-assembling nano-compartments that naturally occur in bacteria and archaea. These nano-compartments encapsulate cargo proteins that bind to the... (Review)
Review
Encapsulins are self-assembling nano-compartments that naturally occur in bacteria and archaea. These nano-compartments encapsulate cargo proteins that bind to the shell's interior through specific recognition sequences and perform various metabolic processes. Encapsulation enables organisms to perform chemical reactions without exposing the rest of the cell to potentially harmful substances while shielding cargo molecules from degradation and other adverse effects of the surrounding environment. One particular type of cargo protein, the ferritin-like protein (FLP), is the focus of this review. Encapsulated FLPs are members of the ferritin-like protein superfamily, and they play a crucial role in converting ferrous iron (Fe) to ferric iron (Fe), which is then stored inside the encapsulin in mineralized form. As such, FLPs regulate iron homeostasis and protect organisms against oxidative stress. Recent studies have demonstrated that FLPs have tremendous potential as biosensors and bioreactors because of their ability to catalyze the oxidation of ferrous iron with high specificity and efficiency. Moreover, they have been investigated as potential targets for therapeutic intervention in cancer drug development and bacterial pathogenesis. Further research will likely lead to new insights and applications for these remarkable proteins in biomedicine and biotechnology.
Topics: Ferritins; Humans; Iron; Bacterial Proteins; Bacteria
PubMed: 38927029
DOI: 10.3390/biom14060624 -
BMC Cancer Jun 2024Breast cancer (BrCa) is a predominant malignancy, with metastasis occurring in one in eight patients, nearly half of which target the bone, leading to serious...
BACKGROUND
Breast cancer (BrCa) is a predominant malignancy, with metastasis occurring in one in eight patients, nearly half of which target the bone, leading to serious complications such as pain, fractures, and compromised mobility. Structural rigidity, crucial for bone strength, becomes compromised with osteolytic lesions, highlighting the vulnerability and increased fracture risk in affected areas. Historically, two-dimensional radiographs have been employed to predict these fracture risks; however, their limitations in capturing the three-dimensional structural and material changes in bone have raised concerns. Recent advances in CT-based Structural Rigidity Analysis (CTRA), offer a promising, more accurate non-invasive 3D approach. This study aims to assess the efficacy of CTRA in monitoring osteolytic lesions' progression and response to therapy, suggesting its potential superiority over existing methodologies in guiding treatment strategies.
METHODS
Twenty-seven female nude rats underwent femoral intra-medullary inoculation with MDA-MB-231 human breast cancer cells or saline control. They were divided into Control, Cancer Control, Ibandronate, and Paclitaxel groups. Osteolytic progression was monitored weekly using biplanar radiography, quantitative computed tomography (QCT), and dual-energy X-ray absorptiometry (DEXA). CTRA was employed to predict fracture risk, normalized using the contralateral femur. Statistical analyses, including Kruskal-Wallis and ANOVA, assessed differences in outcomes among groups and over time.
RESULTS
Biplanar radiographs showed treatment benefits over time; however, only certain time-specific differences between the Control and other treatment groups were discernible. Notably, observer subjectivity in X-ray scoring became evident, with significant inter-operator variations. DEXA measurements for metaphyseal Bone Mineral Content (BMC) did not exhibit notable differences between groups. Although diaphyseal BMC highlighted some variance, it did not reveal significant differences between treatments at specific time points, suggesting a limited ability for DEXA to differentiate between treatment effects. In contrast, the CTRA consistently demonstrated variations across different treatments, effectively capturing bone rigidity changes over time, and the axial- (EA), bending- (EI), and torsional rigidity (GJ) outcomes from the CTRA method successfully distinguished differences among treatments at specific time points.
CONCLUSION
Traditional approaches, such as biplanar radiographs and DEXA, have exhibited inherent limitations, notably observer bias and time-specific inefficacies. Our study accentuates the capability of CTRA in capturing real-time, progressive changes in bone structure, with the potential to predict fractures more accurately and provide a more objective analysis. Ultimately, this innovative approach may bridge the existing gap in clinical guidelines, ushering in enhanced Clinical Decision Support Tool (CDST) for both surgical and non-surgical treatments.
Topics: Animals; Female; Rats; Humans; Tomography, X-Ray Computed; Bone Neoplasms; Breast Neoplasms; Absorptiometry, Photon; Bone Density; Rats, Nude; Paclitaxel; Cell Line, Tumor; Osteolysis; Ibandronic Acid; Bone Density Conservation Agents
PubMed: 38926864
DOI: 10.1186/s12885-024-12374-8 -
BMC Nursing Jun 2024Despite the challenge of nursing shortage in the world and its subsequent impact on care quality as well as aggravation of the situation by intention to leave service,...
Relationship between mental workload and musculoskeletal disorders with intention to leave service among nurses working at neonatal and pediatric departments: a cross-sectional study in Iran.
BACKGROUND
Despite the challenge of nursing shortage in the world and its subsequent impact on care quality as well as aggravation of the situation by intention to leave service, this issue has not been properly addressed, especially among neonatal and pediatric nurses. The present study aims to identify the relationship between mental workload and musculoskeletal disorders with intention to leave the service among nurses working at neonatal and pediatric departments.
METHODS
This descriptive-analytical study was conducted on 145 nurses working at neonatal and pediatric departments in six hospitals in Bushehr Province using full-census method. The data were collected using national aeronautics and space administration-task load index (NASA-TLX), Cornell musculoskeletal discomfort questionnaire(CMDQ) and Mobley and Horner's voluntary turnover questionnaire. The data were analyzed using descriptive statistics, independent t-test, Mann-Whitney U test, one-way analysis of variance (ANOVA), Kruskal-Wallis test, Pearson's and Spearman correlation tests and hierarchical linear regression in simultaneous model in SPSS 19.0.
RESULTS
The mean score of intention to leave the service was 9.57 ± 3.20 (higher than the moderate level) and the mean mental workload was 71.65 ± 15.14 (high level). Pain in at least one of the legs (100%), back (77.3%) and knees (76.6%) was highly prevalent. However, no statistically significant correlation was found between musculoskeletal disorder categories and intention to leave the service (p > 0.05). The regression analysis results revealed among mental workload domains, only effort-induced workload was negatively and significantly correlated with intention to leave the service (p = 0.003; β=-0.078). However, the number of night shifts per month was positively and significantly correlated with intention to leave the service (p = 0.001; β = 0.176).
CONCLUSIONS
Planning for appropriate allocation of night shifts, investigating the etiology of musculoskeletal disorders and providing solutions for reducing mental workload should be prioritized by policymakers, while maintaining pediatric nurses' motivation for making efforts.
PubMed: 38926858
DOI: 10.1186/s12912-024-02112-7 -
BMC Musculoskeletal Disorders Jun 2024While risk factors for osteoarthritis (OA) are well known, it is not well understood why certain individuals maintain high mobility and joint health throughout their...
OBJECTIVE
While risk factors for osteoarthritis (OA) are well known, it is not well understood why certain individuals maintain high mobility and joint health throughout their life while others demonstrate OA at older ages. The purpose of this study was to assess which demographic, clinical and MRI quantitative and semi-quantitative factors are associated with preserving healthy knees in older individuals.
METHODS
This study analyzed data from the OA Initiative (OAI) cohort of individuals at the age of 65 years or above. Participants without OA at baseline (BL) (Kellgren-Lawrence (KL) ≤ 1) were followed and classified as incident cases (KL ≥ 2 during follow-up; n = 115) and as non-incident (KL ≤ 1 over 96-month; n = 391). Associations between the predictor-variables sex, age, BMI, race, clinical scoring systems, T relaxation times and Whole-Organ Magnetic Resonance Imaging-Score (WORMS) readings at BL and the preservation of healthy knees (KL ≤ 1) during a 96-month follow-up period were assessed using logistic regression models.
RESULTS
Obesity and presence of pain showed a significant inverse association with maintaining radiographically normal joints in patients aged 65 and above. T relaxation times of the lateral femur and tibia as well as the medial femur were also significantly associated with maintaining radiographically normal knee joints. Additionally, absence of lesions of the lateral meniscus and absence of cartilage lesions in the medial and patellofemoral compartments were significantly associated with maintaining healthy knee joints.
CONCLUSION
Overall, this study provides protective clinical parameters as well as quantitative and semi-quantitative MR-imaging parameters associated with maintaining radiographically normal knee joints in an older population over 8 years.
Topics: Humans; Male; Aged; Female; Magnetic Resonance Imaging; Knee Joint; Osteoarthritis, Knee; Follow-Up Studies; Risk Factors; Aged, 80 and over; Obesity
PubMed: 38926717
DOI: 10.1186/s12891-024-07590-z -
BMC Medical Ethics Jun 2024Childhood cancers affect about 350 children every year in Sweden and are life-threatening diseases. During the treatment period, situations arise that can become morally...
BACKGROUND
Childhood cancers affect about 350 children every year in Sweden and are life-threatening diseases. During the treatment period, situations arise that can become morally challenging for the child. When knowing children's values and morally challenging situations in childhood cancer care, targeted ethics support could be developed and used in care.
AIM
To explore children's values and moral dilemmas when undergoing cancer treatment.
METHODS
This is a qualitative study based on empirical data. The data collection was conducted through three focus group interviews and six individual interviews with children between 10 and 18 years (n = 16). A content analysis methodology was used to generate themes. Children who were/have been treated for cancer at three childhood cancer centres in Sweden were invited to participate. The study was approved by the Swedish Ethical Review Authority. The children's participation was based on voluntariness and consent/assent.
FINDINGS
During the analysis, five themes of values emerged: Personal relationships, Bodily ease and identity, Feeling in control and being involved, Positive distractions and Right care that is needed. Their moral dilemmas were thematized into: Should I consider others or not? Should I rest or not? and Should I refuse treatment or not?
CONCLUSION
Children undergoing cancer treatment want to have personal relationships with healthcare professionals. Their moral dilemmas were about questioning their own physical and psychological well-being against their expectations, the values of others and the treatment required. Further research is needed to understand how to deal with moral dilemmas in children undergoing cancer treatment.
Topics: Humans; Neoplasms; Child; Qualitative Research; Female; Sweden; Male; Adolescent; Morals; Focus Groups; Social Values
PubMed: 38926715
DOI: 10.1186/s12910-024-01075-3 -
Nature Communications Jun 2024Idiopathic inflammatory myopathies (IIMs) are severe autoimmune diseases with poorly understood pathogenesis and unmet medical needs. Here, we examine the role of...
Idiopathic inflammatory myopathies (IIMs) are severe autoimmune diseases with poorly understood pathogenesis and unmet medical needs. Here, we examine the role of interferon γ (IFNγ) using NOD female mice deficient in the inducible T cell co-stimulator (Icos), which have previously been shown to develop spontaneous IFNγ-driven myositis mimicking human disease. Using muscle proteomic and spatial transcriptomic analyses we reveal profound myofiber metabolic dysregulation in these mice. In addition, we report muscle mitochondrial abnormalities and oxidative stress in diseased mice. Supporting a pathogenic role for oxidative stress, treatment with a reactive oxygen species (ROS) buffer compound alleviated myositis, preserved muscle mitochondrial ultrastructure and respiration, and reduced inflammation. Mitochondrial anomalies and oxidative stress were diminished following anti-IFNγ treatment. Further transcriptomic analysis in IIMs patients and human myoblast in vitro studies supported the link between IFNγ and mitochondrial dysfunction observed in mice. These results suggest that mitochondrial dysfunction, ROS and inflammation are interconnected in a self-maintenance loop, opening perspectives for mitochondria therapy and/or ROS targeting drugs in myositis.
Topics: Animals; Oxidative Stress; Interferon-gamma; Myositis; Humans; Female; Reactive Oxygen Species; Mice; Mice, Inbred NOD; Mitochondria; Muscle, Skeletal; Disease Models, Animal; Mitochondria, Muscle; Mice, Knockout; Myoblasts
PubMed: 38926363
DOI: 10.1038/s41467-024-49460-1 -
Journal of Yeungnam Medical Science Jun 2024Myofascial pain syndrome (MPS) is a common musculoskeletal disorder characterized by muscle pain, tenderness, and trigger points. Ultrasonography has emerged as a key...
Myofascial pain syndrome (MPS) is a common musculoskeletal disorder characterized by muscle pain, tenderness, and trigger points. Ultrasonography has emerged as a key tool for diagnosing and treating MPS owing to its ability to provide precise, minimally invasive guidance. This review discusses the use of ultrasonography in various approaches to evaluate and manage MPS. Studies have shown that shear-wave sonoelastography can effectively assess muscle elasticity and offer insights into trapezius stiffness in patients with MPS. Ultrasound-guided interfascial hydrodissection, especially with visual feedback, has demonstrated effectiveness in treating trapezius MPS. Similarly, ultrasound-guided rhomboid interfascial plane blocks and perimysium dissection for posterior shoulder MPS have significantly reduced pain and improved quality of life. The combination of extracorporeal shockwave therapy with ultrasound-guided lidocaine injections has been particularly successful in reducing pain and stiffness in trapezius MPS. Research regarding various guided injections, including dry needling, interfascial plane blocks, and fascial hydrodissection, emphasizes the importance of ultrasonography for accuracy and safety. Additionally, ultrasound-guided delivery of local anesthetics and steroids to the quadratus lumborum muscle has shown lasting pain relief over a 6-month period. Overall, these findings highlight the pivotal role of ultrasonography in the assessment and treatment of MPS.
PubMed: 38925874
DOI: 10.12701/jyms.2024.00416 -
BMJ Open Jun 2024To explore if there are differences in the design and/or conduct of studies that have tested the STarTBack treatment approach for the management of low back pain (LBP),... (Review)
Review
Evaluating the STarTBack stratified treatment approach for low back pain: exploring study-level factors potentially explaining differences in results of studies - a literature review.
OBJECTIVE
To explore if there are differences in the design and/or conduct of studies that have tested the STarTBack treatment approach for the management of low back pain (LBP), potentially explaining differences in study results.
DESIGN
A literature review.
DATA SOURCES
MEDLINE, CINAHL and EMBASE were searched from inception to 26 July 2023.
ELIGIBILITY CRITERIA
We included studies that included (1) participants with LBP and/or leg pain, (2) randomised controlled trials, controlled clinical trials and interrupted time series designs, (3) used the STarTBack Tool to stratify participants into subgroups and (4) studies provided matched treatments according to participants STarTBack score.
DATA EXTRACTION AND SYNTHESIS
Two review authors independently reviewed the search results and extracted data into the data extraction form. Due to the exploratory nature of this study, results are presented descriptively.
RESULTS
11 studies conducted across 5 countries were included. There were substantial differences in the proportion of participants allocated to the different risk groups; low-risk group (range: 19%-58%), medium risk group (range: 31%-52%) and high-risk group (range: 6%-38%). There were large differences between studies in the implementation of the STarTBack approach. The original STarTBack trial (Hill 2011) had a more explanatory design while in many subsequent studies, the design was more pragmatic/real world. Only the two original studies provided clear evidence that the implementation of the STarTBack tool led to a higher proportion of participants receiving matched treatment. In the other studies, there was no evidence of a difference, or it was unclear. In two studies, a researcher made the decision about which matched treatment participants received based on the STartTback Tool, while in nine studies, this was done by a clinician. Most studies recommended the same matched treatment for each risk group as per the original study except for a small number of studies. Only three studies reported whether the clinician delivering matched treatment followed the recommended treatment as per the tool. There was substantial variability in the training clinicians received.
CONCLUSIONS
Reporting of important study-level factors (eg, differences in study design, whether clinicians were trained and how the tool was used in each study) in how the STarTBack approach was implemented was unclear. There is some suggestion that key factors may include the individual who implemented the STarTBack tool, whether the recommendations of the tool were followed, the amount of training the clinician delivering the matched treatment received, and whether clinicians actually delivered the matched treatment.
Topics: Low Back Pain; Humans; Randomized Controlled Trials as Topic
PubMed: 38925707
DOI: 10.1136/bmjopen-2023-081704 -
BMJ Open Jun 2024To assess compliance with statutory requirements to register and report outcomes in interventional trials of mesenchymal stromal cells (MSCs) for musculoskeletal...
OBJECTIVE
To assess compliance with statutory requirements to register and report outcomes in interventional trials of mesenchymal stromal cells (MSCs) for musculoskeletal disorders and to describe the trials' clinical and design characteristics.
DESIGN
A systematic review of published trials and trials submitted to public registries.
DATA SOURCES
The databases Medline, Cochrane Library and McMaster; six public clinical registries. All searches were done until 31 January 2023.
ELIGIBILITY CRITERIA
Trials submitted to registries and completed before January 2021. Prospective interventional trials published in peer-reviewed journals.
DATA EXTRACTION AND SYNTHESIS
The first author searched for trials that had (1) posted trial results in a public registry, (2) presented results in a peer-reviewed publication and (3) submitted a pretrial protocol to a registry before publication. Other extracted variables included trial design, number of participants, funding source, follow-up duration and cell type.
RESULTS
In total 124 trials were found in registries and literature databases. Knee osteoarthritis was the most common indication. Of the 100 registry trials, 52 trials with in total 2 993 participants had neither posted results in the registry nor published results. Fifty-two of the registry trials submitted a protocol retrospectively. Forty-three of the 67 published trials (64%) had registered a pretrial protocol. Funding source was not associated with compliance with reporting requirements. A discrepancy between primary endpoints in the registry and publication was found in 16 of 25 trials. In 28% of trials, the treatment groups used adjuvant therapies. Only 39% of controlled trials were double-blinded.
CONCLUSIONS
A large proportion of trials failed to comply with statutory requirements for the registration and reporting of results, thereby increasing the risk of bias in outcome assessments. To improve confidence in the role of MSCs for musculoskeletal disorders, registries and medical journals should more rigorously enforce existing requirements for registration and reporting.
Topics: Humans; Registries; Musculoskeletal Diseases; Mesenchymal Stem Cell Transplantation; Clinical Trials as Topic; Guideline Adherence; Research Design; Mesenchymal Stem Cells
PubMed: 38925685
DOI: 10.1136/bmjopen-2023-081343 -
Journal of ISAKOS : Joint Disorders &... Jun 2024While previous investigations have demonstrated a positive correlation between previous concussion and risk of subsequent lower extremity musculoskeletal injury...
Playing Surface and Sport Contact Status Modulate Time to Lower Extremity Musculoskeletal Injury at a Greater Level than Concussion History Among Collegiate Student-Athletes.
OBJECTIVES
While previous investigations have demonstrated a positive correlation between previous concussion and risk of subsequent lower extremity musculoskeletal injury (LEMSKI), the effect of sport- and patient-specific factors on time to injury has not been thoroughly described. This study's main objective was to evaluate the relationship between prior concussion and time to LEMSKI among a population of collegiate student-athletes. Secondary objectives were to evaluate the relationship between playing surface, sport contact status, and biologic sex on time to LEMSKI. We hypothesized that those with previous concussion, those competing on synthetic surfaces, and those competing in collision sports would experience decreased latency to LEMSKI overall.
METHODS
A retrospective observational analysis of National Collegiate Athletic Association (NCAA) Division I student-athletes was conducted utilizing a mixed linear model analysis with contrasts. Inclusion criteria included participation in the Pac-12 Health Analytics Program with a documented LEMSKI between 2017 and 2020. Exclusion criteria included concurrent concussion and LEMSKI, injury resulting in serious morbidity or mortality, and incomplete medical record. Participants were classified by whether they sustained a concussion prior to LEMSKI in each athletic season.
RESULTS
Of 1179 athletes included, 1140 had no previous concussion and 37 had a previous concussion. There was no observed effect of previous concussion (F=0.038; p=0.846) on time to LEMSKI overall. Student-athletes competing on constructed surfaces sustained a subsequent LEMSKI 14.5 days sooner (SE=5.255; p=0.045), and those competing on organic surfaces sustained a subsequent LEMSKI 23.5 days sooner (SE=4.018; p<0.001) in the season than those competing on synthetic surfaces. Contact sport student-athletes sustained a subsequent LEMSKI 52.1 days sooner than collision sport student-athletes (SE=5.248; p<0.001), and limited contact sport student-athletes sustained a subsequent LEMSKI 42.29 days sooner than collision sport student-athletes (SE=4.463; p<0.001). There was no observed effect of biologic sex (F=0.602; p=0.438) on time to LEMSKI overall.
CONCLUSION
There was no observed impact of concussion on time to LEMSKI overall in this collegiate athletic population. Contact sports were associated with decreased time to LEMSK, while synthetic surfaces were associated with increased time to LEMSKI in this population. There was no observed impact of biologic sex on time to LEMSKI.
LEVEL OF EVIDENCE
Case-control, level of evidence III.
PubMed: 38925353
DOI: 10.1016/j.jisako.2024.06.008