Filamentous Fungi Are Potential Bioremediation Agents of Semi-Synthetic Textile Waste.

Textile waste contributes to the pollution of both terrestrial and aquatic ecosystems. While natural textile fibres are known to be biodegraded by microbes, the vast majority of textiles now contain a mixture of processed plant-derived polymers and synthetic materials generated from petroleum and are commonly dyed with azo dyes. This presents a complex recycling problem as the separation of threads and removal of dye are challenging and costly. As a result, the majority of textile waste is sent to landfill or incinerated. This project sought to assess the potential of fungal bioremediation of textile-based dye as a step towards sustainable and environmentally-friendly means of disposal of textile waste. Successful development of an agar-independent microcosm enabled the assessment of the ability of two fungal species to grow on a range of textiles containing an increasing percentage of elastane. The white rot fungus Hypholoma fasciculare was shown to grow well on semi-synthetic textiles, and for the first time, bioremediation of dye from textiles was demonstrated. Volatile analysis enabled preliminary assessment of the safety profile of this process and showed that industrial scale-up may require consideration of volatile capture in the design process. This study is the first to address the potential of fungi as bioremediation agents for solid textile waste, and the results suggest this is an avenue worthy of further exploration.

Multi-methodological approach for the Quality assessment of Senecionis scandentis Herba (Qianliguang) in the herbal market.

We set forth to assess the quality of an herbal medicine sold in Hong Kong called Qianliguang by employing a multi-methodological approach. The quality is set by its identity, chemical composition, and bioactivities, among others. Qianliguang (Senecionis scandentis Herba, Senecio scandens Buch.-Ham. ex D.Don) has known antibacterial properties. However, it is poisonous and overconsumption can result in liver damage. Eighteen Qianliguang samples were purchased from herbal shops at various districts in Hong Kong. Samples were first authenticated organoleptically. DNA barcoding at the psbA-trnH, ITS2, and rbcL loci was then conducted to confirm the species. HPLC-UV was performed to screen for the presence of the chemical compounds and to quantify the flavonoid hyperoside. UPLC-MS was used to quantify the amount of the toxic pyrrolizidine alkaloid (PA) adonifoline. Microdilution assay was performed to show the antibacterial effect on Streptococcus aureus and S. pneumoniae. Results showed that five samples were found to be substituted by species belonging to the genus Lespedeza; four samples were mixtures containing not only Qianliguang but also Achyranthes aspera L., Lonicera confusa DC., or Solanum nigrum L. HPLC-UV showed that only ten contained enough hyperoside to meet the standard requirement. In addition, nine samples had adonifoline that exceeded the toxicity standard requirement. In the microdilution assay, samples containing Qianliguang showed inhibition on S. aureus and S. pneumoniae, while among the five Lespedeza sp. samples the antibacterial effects on S. aureus were not detectable; only one sample showed inhibition to S. pneumoniae. Our study illustrated the necessity of using a multi-methodological approach for herbal medicine quality assessment. We also showed that Qianliguang samples in the Hong Kong market were either toxic or adulterated. It is therefore essential to improve the quality control of Qianliguang and probably other herbs in the herbal market.

Benzyl and benzoyl benzoic acid inhibitors of bacterial RNA polymerase-sigma factor interaction.

Transcription is an essential biological process in bacteria requiring a core enzyme, RNA polymerase (RNAP). Bacterial RNAP is catalytically active but requires sigma (σ) factors for transcription of natural DNA templates. σ factor binds to RNAP to form a holoenzyme which specifically recognizes a promoter, melts the DNA duplex, and commences RNA synthesis. Inhibiting the binding of σ to RNAP is expected to inhibit bacterial transcription and growth. We previously identified a triaryl hit compound that mimics σ at its major binding site of RNAP, thereby inhibiting the RNAP holoenzyme formation. In this study, we modified this scaffold to provide a series of benzyl and benzoyl benzoic acid derivatives possessing improved antimicrobial activity. A representative compound demonstrated excellent activity against Staphylococcus epidermidis with minimum inhibitory concentrations reduced to 0.5 µg/mL, matching that of vancomycin. The molecular mechanism of inhibition was confirmed using biochemical and cellular assays. Low cytotoxicity and metabolic stability of compounds demonstrated the potential for further studies.

Nusbiarylins Inhibit Transcription and Target Virulence Factors in Bacterial Pathogen Staphylococcus aureus.

The emergence of multidrug resistance in the clinically significant pathogen Staphylococcus aureus is a global health burden, compounded by a diminishing drug development pipeline, and a lack of approved novel antimicrobials. Our previously reported first-in-class bacterial transcription inhibitors "nusbiarylins" presented a promising prospect towards the discovery of novel antimicrobial agents with a novel mechanism. Here we investigated and characterised the lead nusbiarylin compound, MC4, and several of its chemical derivatives in both methicillin-resistant S. aureus (MRSA) and the S. aureus type strains, demonstrating their capacity for the arrest of growth and cellular respiration, impairment of RNA and intracellular protein levels at subinhibitory concentrations. In some instances, derivatives of MC4 were also shown to attenuate the production of staphylococcal virulence factors in vitro, such as the exoproteins α-toxin and Panton-Valentine Leukocidin (PVL). Trends observed from quantitative PCR assays suggested that nusbiarylins elicited these effects possibly by acting via but not limited to the modulation of global regulatory pathways, such as the agr regulon, which coordinates the expression of S. aureus genes associated with virulence. Our findings encourage the continued development of more potent compounds within this novel family of bacterial transcription inhibitors.

Discovery of Antibacterials That Inhibit Bacterial RNA Polymerase Interactions with Sigma Factors.

Formation of a bacterial RNA polymerase (RNAP) holoenzyme by a catalytic core RNAP and a sigma (σ) initiation factor is essential for bacterial viability. As the primary binding site for the housekeeping σ factors, the RNAP clamp helix domain represents an attractive target for novel antimicrobial agent discovery. Previously, we designed a pharmacophore model based on the essential amino acids of the clamp helix, such as R278, R281, and I291 (Escherichia coli numbering), and identified hit compounds with antimicrobial activity that interfered with the core-σ interactions. In this work, we rationally designed and synthesized a class of triaryl derivatives of one hit compound and succeeded in drastically improving the antimicrobial activity against Streptococcus pneumoniae, with the minimum inhibitory concentration reduced from 256 to 1 µg/mL. Additional characterization of antimicrobial activity, inhibition of transcription, in vitro pharmacological properties, and cytotoxicity of the optimized compounds demonstrated their potential for further development.

Clinical Implications of Climate Change on US Emergency Medicine: Challenges and Opportunities.

The adverse influences of climate change are manifesting as health burdens relevant to clinical practice, affecting the very underpinnings of health and stressing the health care system. Emergency medicine is likely to bear a large burden, with its focus on urgent and emergency care, through its role as a safety-net provider for vulnerable populations and as a leader in disaster medicine. Clinically, climate change is affecting emergency medicine practice through the amplification of climate-related disease patterns and epidemiologic shifts for conditions diagnosed and treated in emergency departments (EDs), especially for vulnerable populations. In addition, climate-driven intensification of extreme weather is disrupting health care delivery in EDs and health care systems. Thus, there are significant opportunities for emergency medicine to lead the medical response to climate change through 7 key areas: clinical practice improvements, building resilient EDs and health care systems, adaptation and public health engagement, disaster preparedness, mitigation, research, and education. In the face of this growing health threat, systemwide preparation rooted in local leadership and responsiveness is necessary to efficiently and effectively care for our vulnerable communities.

Ascending Thoracic Aortic Dissection: A Case Report of Rapid Detection Via Emergency Echocardiography with Suprasternal Notch Views.

Aortic dissection is a life-threatening, time-sensitive emergency. Conventional diagnostic imaging modalities such as computed tomography (CT) can be time-consuming to obtain, and require that the patient leave the emergency department (ED); as such, they are unsuitable for unstable patients. Emergency focused transthoracic echocardiography (ETTE) is commonly performed in the ED as part of the evaluation of a patient presenting with chest pain, but the suprasternal notch view (SSNV) is much less well-known and infrequently included in this assessment. We present a case of a 51-year-old previously healthy man who presented to the ED complaining of chest pain that had resolved prior to arrival, and a mild headache. His vital signs were notable for hypotension, but physical exam was unremarkable. Chest x-ray revealed a borderline widened mediastinum. A standard ETTE was within normal limits, but additional SSNV demonstrated a dissection flap in the aortic arch. The patient was taken to the operating room for surgical repair 75 minutes after the ED ultrasound was performed; the operation was successful, and the patient was discharged to home post-operatively with good outcome. Standard ETTE has limited ability to visualize the ascending aorta and aortic arch. Addition of SSNV allows visualization of these structures and may improve diagnostic accuracy and time to diagnosis of proximal aortic dissection. Topics: Aortic dissection, emergency echocardiography, point-of-care ultrasound, POCUS, emergency ultrasound, suprasternal notch view.

Use of Emergency Medical Services by Police.

OBJECTIVES: Many police officers receive medical training for limited assessments and interventions. In most situations where medical issues arise, however, emergency medical services (EMS) are called for evaluation, treatment, and transport. Given the limited amount of information about such encounters we examined officer calls for EMS help in a single system to better describe these encounters. METHODS: Requests for medical help from a fire-based EMS system by police in a moderate-sized city in 2014 and 2015 were identified. In this system, fire department resources are requested for initial evaluations of any medical complaint. Data were extracted from fire records including disposition, transportation from scene, type of injury or illness, and vital signs. Data analysis used descriptive statistics. RESULTS: 4,792 calls were made, representing 2.2% of all police-citizen interactions and 4.2% of all EMS calls. A total of 61.2% of calls resulted in transport to hospital. Of those, 5.6% required fire-based advanced life support; the remainder were transported by private basic life support ambulance or non-medical means. Most requests were for trauma (51.4%), followed by medical (24.7%), drug/alcohol use (17.1%), and psychiatric (6.7%). Vital signs tended to be within normal limits including 72.7% of pulses, 65.1% of systolic blood pressures, and 90.5% of respiratory rates. CONCLUSION: Requests for EMS assistance from police were common. Most calls involved patients with normal vital signs who did not require advanced life support transport. Further research is needed to identify situations where increased officer training and change in protocols could potentially change EMS response models and improve efficiency of the system.

Myocardial Irritation from a Left Ventricular Assist Device Resulting in Refractory Ventricular Tachycardia.

BACKGROUND: Due to an increasing prevalence of heart failure but a steady rate of heart transplantation, the number of left ventricular assist devices (LVADs) implanted is growing. These patients present to emergency departments (EDs) with a variety of complications from their implanted device as well as their baseline cardiomyopathy. One-third of patients will present with a dysrhythmia, the most common of which is ventricular tachycardia. CASE REPORT: A 77-year-old man with nonischemic cardiomyopathy and HeartMate II LVAD presented with sustained ventricular tachycardia and 43 automatic implantable cardioverter-defibrillator (AICD) discharges. Due to left ventricular remodeling, ongoing diuresis, and positioning of his LVAD inflow cannula against his interventricular septum, a likely dysrhythmogenic foci, he quickly decompensated with sedation while in the ED. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Refractory ventricular tachycardia is a common dysrhythmia for LVAD patients and may lead to full cardiopulmonary arrest. Common strategies such as chest compressions are used only in limited scenarios, but medical management is possible. This should focus on resolution of the dysrhythmia and identification of the etiology, including possible mechanical compromise.

Missed appendicitis: did unexpected intraluminal densities play a role?

A healthy 19-year-old boy presented to our emergency department with abdominal pain. His history, examination and laboratory evaluation raised concern for appendicitis. A CT study of the abdomen and pelvis was carried out by the radiologist and emergency physician and was notable only for a large amount of unexpected high-attenuation intraluminal material. With further history, this was thought to be most likely retained bismuth from over-the-counter medicine ingestion. The patient was discharged home without a diagnosis. Further review of the CT scan by a second radiologist revealed a concern for appendiceal enlargement and associated free fluid. The patient was called back for further evaluation and treatment and ultimately an appendectomy was performed. Physicians should be aware of the causes and impact of unexpected radiopaque intraluminal contents on radiological studies. Most commonly from ingested medicine, such findings can obscure mucosal details, mimic active bleeding or create a distraction from other abnormalities.

Early access to vocational rehabilitation for spinal cord injury inpatients.

OBJECTIVES: To describe a novel early vocational rehabilitation programme (In-Voc) for inpatients with spinal cord injury and to report early vocational outcomes. DESIGN: Observational longitudinal cohort study. SUBJECTS: One hundred adults with spinal cord injury admitted to spinal units in Sydney, Australia within a 24-month period. METHODS: In-Voc was offered to all inpatients within the first 6 months of acquired spinal cord injury and was provided by trained vocational consultants. Baseline demographics, opinions about work readiness, details of the vocational services provided and preliminary employment outcomes were documented. RESULTS: The In-Voc programme was relatively short in duration (median 11 weeks, range 3-39 weeks) with a median total of 9.1 h (range 1-75.2 h) of service delivered per participant. At case closure (median 3 weeks post-discharge), 29/84 (34.5%) of participants were in paid employment (7% full-time, 8% part-time, 7% on sick leave, and 12% working with hours unknown), 36% were unemployed (6% seeking work, 16% not seeking work, 14% job seeking status unknown), 13% were students or in-training, and 17% were in vocational rehabilitation. CONCLUSION: Our research suggests that implementing an early vocational rehabilitation programme with individuals in the hospital setting is feasible and has good potential for enhancing post-injury labour-force participation.

Completeness of reporting of setting and health worker cadre among trials on antenatal iron and folic acid supplementation in pregnancy: an assessment based on two Cochrane reviews.

BACKGROUND: Poor reporting of medical trials has triggered the development of trial reporting standards within the scientific community. In addition to a description of the proposed intervention, adequate information about the trial setting and the group of health workers (cadre) delivering the intervention would allow a better understanding of the generalizability of the trial findings, facilitate replication of trial interventions and assist with assessment of trials for inclusion in systematic reviews. This study aims to determine the completeness of reporting for trial setting and cadre among trials included in two Cochrane reviews on iron and folic acid supplementation for women during pregnancy. METHODS: From the 81 trials included in the two Cochrane reviews, we extracted data on the trial setting, including the facility type and geographic location, facility descriptors (i.e. level of care) and population descriptors (i.e. socioeconomic status); and the cadre, including professional qualifications, training and supervision. RESULTS: Almost all studies reported the facility type and location (96%). However, only 68% included this information in the "methods" section of the report. Facility descriptors and population descriptors were less commonly reported (26% and 54% respectively). For 34% of the trials, we found some account of the type of health worker that delivered the intervention. Only 4% of the trials reported any training procedures. CONCLUSIONS: Currently, complete reporting of setting and health worker cadre in iron and folic acid supplementation in pregnancy trials remains far from ideal, limiting assessments of the applicability of the trial findings. Trialists and journals need to ensure that this information is included in trial reports by adhering to and improving current reporting standards and by not making assumptions regarding readers' knowledge of the context and of the intervention delivery mechanism.

Maternal dioxin exposure combined with a diet high in fat increases mammary cancer incidence in mice.

BACKGROUND: RESULTS from previous studies have suggested that breast cancer risk correlates with total lifetime exposure to estrogens and that early-life 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure or diets high in fat can also increase cancer risk. OBJECTIVES: Because both TCDD and diet affect the estrogen pathway, we examined how TCDD and a high-fat diet (HFD) interact to alter breast cancer susceptibility. METHODS: We exposed pregnant female FVB/NJ mice (12.5 days postcoitus) to 1 microg/kg TCDD or vehicle; at parturition, the dams were randomly assigned to a low-fat diet (LFD) or a high-fat diet (HFD). Female offspring were maintained on the same diets after weaning and were exposed to 7,12-dimethylbenz[a]anthracene on postnatal days (PNDs) 35, 49, and 63 to initiate mammary tumors. A second cohort of females was treated identically until PND35 or PND49, when mammary gland morphology was examined, or PND50, when mammary gland mRNA was analyzed. RESULTS: We found that maternal TCDD exposure doubled mammary tumor incidence only in mice fed the HFD. Among HFD-fed mice, maternal TCDD exposure caused rapid mammary development with increased Cyp1b1 (cytochrome P450 1B1) expression and decreased Comt (catechol-O-methyltransferase) expression in mammary tissue. Maternal TCDD exposure also increased mammary tumor Cyp1b1 expression. CONCLUSIONS: Our data suggest that the HFD increases sensitivity to maternal TCDD exposure, resulting in increased breast cancer incidence, by changing metabolism capability. These results provide a mechanism to explain epidemiological data linking early-life TCDD exposure and diets high in fat to increased risk for breast cancer in humans.