Natural bioactive compounds: antibiotics

Antibiotics are powerful therapeutic agents that are produced by diverse living organisms. Over the last several decades, natural bioactive products particularly antibiotics have continued to play a significant role in drug discovery and has expanded the process for developing drugs with high degree of therapeutic index and specific action. Today, there is an alarming deficiency of new antibiotics in the pharmaceutical industry that could be due to the emergence of antibiotic resistance properties of some pathogens, toxicity and undesirable side effects of some used antibiotics. Although much progress has been performed in the field of chemical synthesis and engineered biosynthesis of antimicrobial compounds. Hence, there is a need in approach for novel antibiotics and research to improve the safety as well as therapeutic efficiency of the discovered bioactive compounds as part of the strategy to control the emerging drug-resistant pathogens in research programme around the world. This article reviews the history of antibiotics, different types of antibiotics, mechanisms of antibiotic action and new challenges in antibiotics.KEYWORDS: Secondary metabolites; microorganisms; Actinomycetes; Antimicrobialactivity; Pharmaceuticals

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

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

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

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

Low-molecular-weight cyclin E: the missing link between biology and clinical outcome

Cyclin E, a key mediator of transition during the G(1)/S cellular division phase, is deregulated in a wide variety of human cancers. Our group recently reported that overexpression and generation of low-molecular-weight (LMW) isoforms of cyclin E were associated with poor clinical outcome among breast cancer patients. However, the link between LMW cyclin E biology in mediating a tumorigenic phenotype and clinical outcome is unknown. To address this gap in knowledge, we assessed the role of LMW isoforms in breast cancer cells; we found that these forms of cyclin E induced genomic instability and resistance to p21, p27, and antiestrogens in breast cancer. These findings suggest that high levels of LMW isoforms of cyclin E not only can predict failure to endocrine therapy but also are true prognostic indicators because of their influence on cell proliferation and genetic instability

DEAR1 Is a Dominant Regulator of Acinar Morphogenesis and an Independent Predictor of Local Recurrence-Free Survival in Early-Onset Breast Cancer

Ann Killary and colleagues describe a new gene that is genetically altered in breast tumors, and that may provide a new breast cancer prognostic marker

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).

BACKGROUND: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. PATIENTS AND METHODS: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8\u2009mg/kg loading dose, then 6\u2009mg/kg every 3\u2009weeks (q3w)] and pertuzumab (840\u2009mg loading dose, then 420\u2009mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54\u2009years; 29% had received prior trastuzumab. Median treatment duration was 16\u2009months for pertuzumab and trastuzumab and 4\u2009months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1\u2009months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). CONCLUSIONS: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. CLINICALTRIALS.GOV: NCT01572038

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design