IL-6 as a Biomarker for Therapeutic Resistance in Metastatic HR+, HER2- Breast Cancers

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Influence of spark plasma sintering and baghdadite powder on mechanical properties of hydroxyapatite

AbstractSince hydroxyapatite-based materials have similar composition and crystallinity as natural calcified tissues, can be used for bone/tissue engineering. In the present study a novel nanocomposite based on bioceramics such as Natural Hydroxyapatite (NHA) and Baghdadite (BAG), was sintered by spark plasma sintering (SPS) technique. The prepared composite was characterized using scanning electron microscopy (SEM), X-ray diffractometer (XRD) and Brunauer–Emmett–Teller (BET) techniques. The porosity of the samples was measured by Archimedes method. The cold crushing strength (CCS) test was applied to evaluate their mechanical properties. Our results demonstrated that NHA-30wt. %BAG nanocomposite specimens have the lower CCS in comparison with other examined composites. Consequently, NHA/BAG samples exhibited acceptable mechanical properties and could be suitable candidates for bone tissue engineering applications especially orthopaedic fields

Comparing road safety conditions in Iran with ten Southeast Asian countries using road safety index

Background and aims: Crashes and the related human and financial losses have been turned to be one of the challenges of human societies in a way that road death statistics shows a high number of 219172 in Iran from 2005 to 2014. Methods: In this research, using global and valid Road Safety Development Index (RSDI) that illustrates general roads safety condition and consists of nine effective parameters, roads safety in Iran and 10 countries of southeast of Asia was analyzed from March 2010 to March 2011. Considering the charechtristics of the parameters, two scaling methods entitle "Simple Average Weighting" and "Subjective Weighting" were used. Results: Iran's scores were 48.35 and 45.29 for Simple Average Weighting and Subjective Weighting respectively and was in middle level of safety also it ranked as the fourth country among 11 studied ones in 2011. Although some parameters got better, comparing three last years, in many of them especially number of death, crashes and drivers' behavior conditions were unacceptable. The important point is that Subjective Weighting method acts more accurate than Simple Average method, respects to considering change of weights according to importance and their role comparing. Conclusion: The research findings illustrated that Iran has moved toward middle level of road safety from lower levels in last years. However, regards to ranking and scores resulted from indexes it is not in desirable conditions. © 2018 Tehran University of Medical Sciences and Health Services. All rights reserved

Patient safety climate and its affecting factors among rehabilitation health care staff of hospitals and rehabilitation centers in Iran-Tehran

Objectives: Hospitals and clinical centers are concerned about patient safety. Safety climate is a perceived value of safety in an organization that could improve the safety of workers and patients. The present research was conducted to study the safety climate of patients in the hospitals and rehabilitation centers affiliated to the University of Social Welfare and Rehabilitation Sciences. Methods: This descriptive-analytical study was conducted on 300 nurses and nurse's aides (healthcare staff) who were selected by stratified sampling method, from two hospitals and three clinics, in 2017. Data collection tools included Patient Safety Climate Scale presented by Kudo and a demographic data questionnaire. The obtained data were analyzed by SPSS using descriptive statics like frequencies and percentages. Furthermore, Mann-Whitney U test and Kruskal-Wallis test were used to analyze the obtained data and compare the mean scores, respectively. Results: The Mean±SD age and work experience of study participants were 36.7±6.79 and 9.46±5.8 years, respectively. The patient safety climate sub-factors were significantly different between males and females (P 0.05). Patient safety climate was only different in nursing condition (P=0.013) among studied healthcare centers. Also, only fatigue reduction was different among various studied wards (P=0.035), where intensive care unit had the lowest score (2.12±2.0). Discussion: Overall, the poor condition of patient safety climate was found in the studied rehabilitation centers. Therefore, it is recommended to improve nurses' attitudes with the assistance of hospital managers, to enhance patient safety. © 2019 University of Social Welfare and Rehabilitation Sciences

Ergonomic assessment of posture risk factors among Iranian workers: An alternative to conventional methods

Objectives: Work-related musculoskeletal disorders are a global problem which evolves at different workplaces such as industries, administrative, and agriculture sectors. In various studies, such disorders were assessed through multiple methods. It is necessary to evaluate different tools to use them in diverse communities. The aim of this study was to assess the validity of the new ergonomic evaluating method of Novel Ergonomic Postural Assessment (NERPA) method in Iran. Methods: The employees (n=455) of operational units of four companies (drug producers, printing and publishing houses, dairy, and drinks producers) were assessed in 2014. It was a cross-sectional and descriptive-analytical study. One of the researchers developed a questionnaire that was applied to collect demographic data. The NERPA, Rapid Upper Limb Assessment (RULA), and Rapid Entire Body Assessment (REBA) methods were utilized to analyze posture risk factors. Spearman correlation and Kappa agreement were used to analyze the collected data through SPSS V22. Results: Findings indicated that printing company had the best and pharmaceutical industries had the worst state regarding RULA's results. The risk levels between NERPA and REBA were not statistically significant (P > 0.05), however, that was significant with RULA's outcome. Also, the results of NERPA and other two methods were correlated significantly (P < 0.05). Pain in the lumbar area was implied to be the most prevalent problem (35.1). Discussion: Data of the present study suggest that NERPA method was a valid tool compared to RULA. The NERPA method could be used to evaluate standing tasks among industrial workers. However, the concurrent validity of NERPA method compared with results of REBA, as a widely used method, were not verified

Ergonomic assessment of posture risk factors among Iranian workers: An alternative to conventional methods

Objectives: Work-related musculoskeletal disorders are a global problem which evolves at different workplaces such as industries, administrative, and agriculture sectors. In various studies, such disorders were assessed through multiple methods. It is necessary to evaluate different tools to use them in diverse communities. The aim of this study was to assess the validity of the new ergonomic evaluating method of Novel Ergonomic Postural Assessment (NERPA) method in Iran. Methods: The employees (n=455) of operational units of four companies (drug producers, printing and publishing houses, dairy, and drinks producers) were assessed in 2014. It was a cross-sectional and descriptive-analytical study. One of the researchers developed a questionnaire that was applied to collect demographic data. The NERPA, Rapid Upper Limb Assessment (RULA), and Rapid Entire Body Assessment (REBA) methods were utilized to analyze posture risk factors. Spearman correlation and Kappa agreement were used to analyze the collected data through SPSS V22. Results: Findings indicated that printing company had the best and pharmaceutical industries had the worst state regarding RULA's results. The risk levels between NERPA and REBA were not statistically significant (P > 0.05), however, that was significant with RULA's outcome. Also, the results of NERPA and other two methods were correlated significantly (P < 0.05). Pain in the lumbar area was implied to be the most prevalent problem (35.1). Discussion: Data of the present study suggest that NERPA method was a valid tool compared to RULA. The NERPA method could be used to evaluate standing tasks among industrial workers. However, the concurrent validity of NERPA method compared with results of REBA, as a widely used method, were not verified

Cytoplasmic cyclin E is an independent marker of aggressive tumor biology and breast cancer-specific mortality in women over 70 years of age

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Multi-cohort analysis demonstrated that cytoplasmic cyclin E expression in primary breast tumors predicts aggressive disease. However, compared to their younger counterparts, older patients have favorable tumor biology and are less likely to die of breast cancer. Biomarkers therefore require interpretation in this specific context. Here, we assess data on cytoplasmic cyclin E from a UK cohort of older women alongside a panel of >20 biomarkers. Between 1973 and 2010, 813 women ≥70 years of age underwent initial surgery for early breast cancer, from which a tissue microarray was constructed (n = 517). Biomarker expression was assessed by immunohistochemistry. Multivariate analysis of breast cancer-specific survival was performed using Cox’s proportional hazards. We found that cytoplasmic cyclin E was the only biological factor independently predictive of breast cancer-specific survival in this cohort of older women (hazard ratio (HR) = 6.23, 95% confidence interval (CI) = 1.93–20.14; p = 0.002). At ten years, 42% of older patients with cytoplasmic cyclin E-positive tumors had died of breast cancer versus 8% of negative cases (p < 0.0005). We conclude that cytoplasmic cyclin E is an exquisite marker of aggressive tumor biology in older women. Patients with cytoplasmic cyclin E-negative tumors are unlikely to die of breast cancer. These data have the potential to influence treatment strategy in older patients

The Impact of Different Self-Selected Walking Speeds on Muscle Synergies in Transfemoral Amputees during Transient-State Gait

Facing above-knee amputation poses a significant hurdle due to its profound impact on walking ability. To overcome this challenge, a complex adaptation strategy is necessary at the neuromuscular level to facilitate safe movement with a prosthesis. Prior research conducted on lower-limb amputees has shown a comparable amount of intricacy exhibited by the neurological system, regardless of the level of amputation and state of walking. This research investigated the differences in muscle synergies among individuals with unilateral transfemoral amputations during walking at three different speeds of transient-state gait. Surface electromyography was recorded from eleven male transfemoral amputees’ intact limbs (TFA), and the concatenated non-negative matrix factorization technique was used to identify muscle synergy components, synergy vectors (S), and activation coefficient profiles (C). Results showed varying levels of correlation across paired-speed comparisons in TFA, categorized as poor (S1), moderate (S3 and S4), and strong (S2). Statistically significant differences were observed in all activation coefficients except C3, particularly during the stance phase. This study can assist therapists in understanding muscle coordination in TFA during unsteady gait, contributing to rehabilitation programs for balance and mobility improvement, and designing myoelectric prosthetic systems to enhance their responsiveness to trips or falls

Abemaciclib Is Effective in Palbociclib-Resistant Hormone Receptor-Positive Metastatic Breast Cancers

Cyclin-dependent kinases 4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) is standard of care for patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). However, resistance to CDK4/6is plus ET remains a clinical problem with limited therapeutic options following disease progression. Different CDK4/6is might have distinct mechanisms of resistance, and therefore using them sequentially or targeting their differentially altered pathways could delay disease progression. To understand pathways leading to resistance to the CDK4/6is palbociclib and abemaciclib, we generated multiple in vitro models of palbociclib-resistant (PR) and abemaciclib-resistant (AR) cell lines as well as in vivo patient-derived xenografts (PDX) and ex vivo PDX-derived organoids (PDxO) from patients who progressed on CDK4/6i. PR and AR breast cancer cells exhibited distinct transcriptomic and proteomic profiles that sensitized them to different classes of inhibitors; PR cells upregulated G2-M pathways and responded to abemaciclib, while AR cells upregulated mediators of the oxidative phosphorylation pathway (OXPHOS) and responded to OXPHOS inhibitors. PDX and organoid models derived from patients with PR breast cancer remained responsive to abemaciclib. Resistance to palbociclib while maintaining sensitivity to abemaciclib was associated with pathway-specific transcriptional activity but was not associated with any individual genetic alterations. Finally, data from a cohort of 52 patients indicated that patients with HR-positive/HER2-negative MBC who progressed on palbociclib-containing regimens can exhibit a meaningful overall clinical benefit from abemaciclib-based therapy when administered after palbociclib. These findings provide the rationale for clinical trials evaluating the benefit of abemaciclib treatment following progression on a prior CDK4/6i

STAT3 Protects Hematopoietic Stem Cells by Preventing Activation of a Deleterious Autocrine Type-I Interferon Response

Hematopoietic stem and progenitor cells (HSPCs) maintain blood-forming and immune activity, yet intrinsic regulators of HSPCs remain elusive. STAT3 function in HSPCs has been difficult to dissect as Stat3-deficiency in the hematopoietic compartment induces systemic inflammation, which can impact HSPC activity. Here, we developed mixed bone marrow (BM) chimeric mice with inducible Stat3 deletion in 20% of the hematopoietic compartment to avoid systemic inflammation. Stat3-deficient HSPCs were significantly impaired in reconstitution ability following primary or secondary bone marrow transplantation, indicating hematopoietic stem cell (HSC) defects. Single-cell RNA sequencing of Lin-ckit+Sca1+ BM cells (LSKs) revealed aberrant activation of cell cycle, p53, and interferon (IFN) pathways in Stat3-deficient HSPCs. Stat3-deficient LSKs accumulated γH2AX and showed increased expression of DNA sensors and type-I IFN (IFN-I), while treatment with A151-ODN inhibited expression of IFN-I and IFN-responsive genes. Further, the blockade of IFN-I receptor signaling suppressed aberrant cell cycling, STAT1 activation, and nuclear p53 accumulation. Collectively, our results show that STAT3 inhibits a deleterious autocrine IFN response in HSCs to maintain long-term HSC function. These data signify the importance of ensuring therapeutic STAT3 inhibitors are targeted specifically to diseased cells to avoid off-target loss of healthy HSPCs