Identification and Development of Cyclic Peptide Inhibitors of Hypoxia Inducible Factors 1 and 2 That Disrupt Hypoxia-Response Signaling in Cancer Cells.

Hypoxia inducible factor (HIF) is a heterodimeric transcription factor composed of an oxygen-regulated α subunit and a constitutively expressed ß subunit that serves as the master regulator of the cellular response to low oxygen concentrations. The HIF transcription factor senses and responds to hypoxia by significantly altering transcription and reprogramming cells to enable adaptation to a hypoxic microenvironment. Given the central role played by HIF in the survival and growth of tumors in hypoxia, inhibition of this transcription factor serves as a potential therapeutic approach for treating a variety of cancers. Here, we report the identification, optimization, and characterization of a series of cyclic peptides that disrupt the function of HIF-1 and HIF-2 transcription factors by inhibiting the interaction of both HIF-1α and HIF-2α with HIF-1ß. These compounds are shown to bind to HIF-α and disrupt the protein-protein interaction between the α and ß subunits of the transcription factor, resulting in disruption of hypoxia-response signaling by our lead molecule in several cancer cell lines.

Dead in the water - Role of relic DNA and primer choice for targeted sequencing surveys of anaerobic sewage sludge intended for biological monitoring.

DNA-based monitoring of microbial communities that are responsible for the performance of anaerobic digestion of sewage wastes has the potential to improve resource recoveries for wastewater treatment facilities. By treating sludge with propidium monoazide (PMA) prior to amplicon sequencing, this study explored how the presence of DNA from dead microbial biomass carried over with feed sludge may mislead process-relevant biomarkers, and whether primer choice impacts such assessments. Four common primers were selected for amplicon preparation, also to determine if universal primers have sufficient taxonomic or functional coverage for monitoring ecological performance; or whether two domain-specific primers for Bacteria and Archaea are necessary. Anaerobic sludges of three municipal continuously stirred-tank reactors in Victoria, Australia, were sampled at one time-point. A total of 240 amplicon libraries were sequenced on a Miseq using two universal and two domain-specific primer pairs. Untargeted metabolomics was chosen to complement biological interpretation of amplicon gene-based functional predictions. Diversity, taxonomy, phylogeny and functional potentials were systematically assessed using PICRUSt2, which can predict community wide pathway abundance. The two chosen universal primers provided similar diversity profiles of abundant Bacteria and Archaea, compared to the domain-specific primers. About 16 % of all detected prokaryotic genera covering 30 % of total abundances and 6 % of PICRUSt2-estimated pathway abundances were affected by PMA. This showed that dead biomass in the anaerobic digesters impacted DNA-based assessments, with implications for predicting active processes, such as methanogenesis, denitrification or the identification of organisms associated with biological foams. Hence, instead of running two sequencing runs with two different domain-specific primers, we propose conducting PMA-seq with universal primer pairs for routine performance monitoring. However, dead sludge biomass may have some predictive value. In principal component analysis the compositional variation of 239 sludge metabolites resembled that of 'dead-plus-alive' biomass, suggesting that dead organisms contributed to the potentially process-relevant sludge metabolome.

Assessing the impact of immobilisation on the bioavailability of PFAS to plants in contaminated Australian soils.

Per- and polyfluoroalkyl substances (PFAS) have become a key concern to both environmental and human health due to their extreme persistence in the environment and their ability to bioaccumulate in plants, animals, and humans. In this mesocosm study, Australian PFAS-contaminated soil with a mean total concentration of 8.05 mg/kg and a mean combined PFHxS + PFOS concentration of 7.89 mg/kg was treated with an immobilisation sorbent (RemBind®) at different application rates (0.5, 1, 1.5, 2, 3, 4, and 5% w/w). To assess the efficacy of this immobilisation treatment, PFAS leachability, PFAS plant uptake, and ecotoxicity tests were conducted. Leachability testing was performed according to the Australian Standard Leaching Procedure (ASLP) at pH 5 and 7. A grass species (Dactylis glomerata) was used to measure plant uptake of PFAS from untreated and treated contaminated soil. In addition, the Microtox test was used to assess the associated ecotoxicity. The immobilisation treatment resulted in a significant reduction of 88.5-99.8% in the total PFAS leachability and 88.7-99.8% in the combined PFOS and PFHxS leachability at pH 5. Similarly, significant reductions (5-12-fold) were observed in the plant uptake of total PFAS and combined PFOS and PFHxS in all treated soil samples. In addition, although the Microtox test showed relatively low ecotoxicity in all the experimental samples, including the untreated soil, a significant decrease in the ecotoxicity of treated soil samples was observed. The results from this study highlight that this treatment approach has the potential to reduce both PFAS leachability and plant bioavailability with a relatively low associated ecotoxicity. This is likely to reduce the risk of the transfer of PFAS into higher trophic levels. This immobilisation treatment may, therefore, reduce the risk associated with PFAS-contaminated soils and may be an important remediation tool for managing certain PFAS-contaminated soils.

Wood biochar enhances methanogenesis in the anaerobic digestion of chicken manure under ammonia inhibition conditions.

The process of breaking down chicken manure through anaerobic digestion is an effective waste management technology. However, chicken manure can be a challenging feedstock, causing ammonia stress and digester instability. This study examined the impacts of adding wood biochar and acid-alkali-treated wood biochar to anaerobically digest chicken manure under conditions of ammonia inhibition. The results highlighted that only the addition of 5 % acid-alkali-treated wood biochar by volume can achieve cumulative methane production close to the typical methane potential range of chicken manure. The treated wood biochar also exhibited highest total ammonia nitrogen removal compared to the Control treatment. Scanning Electron Microscope revealed growing interactions between biochar and methanogens over time. Real-time polymerase chain reaction showed that treated wood biochar produced the highest number of bacterial biomass. In addition, 16S amplicon-based sequencing identified a more robust archaeal community from treated biochar addition. Overall, the acid-alkali treatment of biochar represents an effective method of modifying biochar to improve its performance in anaerobic digestion.

Prospective Subunit Nanovaccine against Mycobacterium tuberculosis Infection─Cubosome Lipid Nanocarriers of Cord Factor, Trehalose 6,6' Dimycolate.

An improved vaccine is urgently needed to replace the now more than 100-year-old Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) disease, which represents a significant burden on global public health. Mycolic acid, or cord factor trehalose 6,6' dimycolate (TDM), a lipid component abundant in the cell wall of the pathogen Mycobacterium tuberculosis (MTB), has been shown to have strong immunostimulatory activity but remains underexplored due to its high toxicity and poor solubility. Herein, we employed a novel strategy to encapsulate TDM within a cubosome lipid nanocarrier as a potential subunit nanovaccine candidate against TB. This strategy not only increased the solubility and reduced the toxicity of TDM but also elicited a protective immune response to control MTB growth in macrophages. Both pre-treatment and concurrent treatment of the TDM encapsulated in lipid monoolein (MO) cubosomes (MO-TDM) (1 mol %) induced a strong proinflammatory cytokine response in MTB-infected macrophages, due to epigenetic changes at the promoters of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in comparison to the untreated control. Furthermore, treatment with MO-TDM (1 mol %) cubosomes significantly improved antigen processing and presentation capabilities of MTB-infected macrophages to CD4 T cells. The ability of MO-TDM (1 mol %) cubosomes to induce a robust innate and adaptive response in vitro was further supported by a mathematical modeling study predicting the vaccine efficacy in vivo. Overall, these results indicate a strong immunostimulatory effect of TDM when delivered through the lipid nanocarrier, suggesting its potential as a novel TB vaccine.

Cubosome Lipid Nanocarriers As a Drug Delivery Vehicle for Intracellular Mycobacterium tuberculosis Infections.

Mycobacterium tuberculosis (MTB) causes the infectious disease tuberculosis (TB), responsible for more deaths than any other single infectious disease in history. Intracellular MTB are slow growing and difficult to target with traditional antitubercular drugs, leading to the emergence of multidrug resistance in TB infection, which is a major global public health issue. Recent advances in innovative lipid nanotechnologies for drug delivery have demonstrated promising outcomes for chronic infectious diseases but have not yet been tested as potential delivery systems for intracellular infections such as TB. The current study evaluates the potential of monoolein (MO)-based cationic cubosomes for the encapsulation and delivery of the first line antitubercular drug rifampicin (RIF) against an MTB-H37Ra in vitro culture model. In particular, we show that the use of cationic cubosomes as delivery vehicles reduced the minimum inhibitory concentration (MIC) of RIF by 2-fold against actively replicating MTB-H37Ra (compared to that of the free drug) and also shortened the lifecycle duration of axenic MTB-H37Ra from 5 to 3 days. The cubosome-mediated delivery was also found to be effective against intracellular MTB-H37Ra within THP-1 human macrophages, with a 2.8 log reduction in viability of the bacilli after 6 days incubation at the MIC. The killing time was also reduced from 8 to 6 days without distressing the host macrophages. Mechanistic studies on the uptake of RIF-loaded cationic cubosomes using total internal reflection fluorescence microscopy (TIRFM) demonstrated the capacity of these lipid particles to effectively target intracellular bacteria. Overall, these results demonstrate that cationic cubosomes are a potent delivery system for the antitubercular drug RIF for therapeutic management of TB.

Novel Fault Diagnosis of a Conveyor Belt Mis-Tracking via Motor Current Signature Analysis.

For the first time ever worldwide, this paper proposes, investigates, and validates, by multiple experiments, a new online automatic diagnostic technology for the belt mis-tracking of belt conveyor systems based on motor current signature analysis (MCSA). Three diagnostic technologies were investigated, experimentally evaluated, and compared for conveyor belt mis-tracking diagnosis. The proposed technologies are based on three higher-order spectral diagnostic features: bicoherence, tricoherence, and the cross-correlation of spectral moduli of order 3 (CCSM3). The investigation of the proposed technologies via comprehensive experiments has shown that technology based on the CCSM3 is highly effective for diagnosing a conveyor belt mis-tracking via MCSA.

Novel Investigation of Higher Order Spectral Technologies for Fault Diagnosis of Motor-Based Rotating Machinery.

In the last decade, research centered around the fault diagnosis of rotating machinery using non-contact techniques has been significantly on the rise. For the first time worldwide, innovative techniques for the diagnosis of rotating machinery, based on electrical motors, including generic, nonlinear, higher-order cross-correlations of spectral moduli of the third and fourth order (CCSM3 and CCSM4, respectively), have been comprehensively validated by modeling and experiments. The existing higher-order cross-correlations of complex spectra are not sufficiently effective for the fault diagnosis of rotating machinery. The novel technology CCSM3 was comprehensively experimentally validated for induction motor bearing diagnosis via motor current signals. Experimental results, provided by the validated technology, confirmed high overall probabilities of correct diagnosis for bearings at early stages of damage development. The novel diagnosis technologies were compared with existing diagnosis technologies, based on triple and fourth cross-correlations of the complex spectra. The comprehensive validation and comparison of the novel cross-correlation technologies confirmed an important non-traditional novel outcome: the technologies based on cross-correlations of spectral moduli were more effective for damage diagnosis than the technologies based on cross-correlations of the complex spectra. Experimental and simulation validations confirmed a high probability of correct diagnosis via the CCSM at the early stage of fault development. The average total probability of incorrect diagnosis for the CCSM3 for all experimental results of 8 tested bearings, estimated via 6528 diagnostic features, was 1.475%. The effectiveness gains in the total probability of incorrect diagnosis for the CCSM3 in comparison with the CCCS3 were 26.8 for the experimental validation and 18.9 for the simulation validation. The effectiveness gains in the Fisher criterion for the CCSM3 in comparison with the CCCS3 were 50.7 for the simulation validation and 104.7 for the experimental validation.

Development of A Rapid, Low-Cost Portable Detection Assay for Enterococci in Wastewater and Environmental Waters.

Waterborne diseases are known as a leading cause of illness and death in both developing and developed countries. Several pathogens can be present in contaminated water, particularly waters containing faecal material; however, routine monitoring of all pathogens is not currently possible. Enterococcus faecalis, which is present in the microflora of human and animals has been used as a faecal indicator in water due to its abundance in surface water and soil. Accurate and fast detection methods are critical for the effective monitoring of E. faecalis in the environment. Although conventional and current molecular detection techniques provide sufficient sensitivity, specificity and throughput, their use is hampered by the long waiting period (1-6 days) to obtain results, the need for expensive laboratory equipment, skilled personnel, and cold-chain storage. Therefore, this study aimed to develop a detection system for E. faecalis that would be simple, rapid, and low-cost, using an isothermal DNA amplification assay called recombinase polymerase amplification (RPA), integrated with a lateral flow assay (LFA). The assay was found to be 100% selective for E. faecalis and capable of detecting rates as low as 2.8 × 103 cells per 100 mL from water and wastewater, and 2.8 × 104 cells per 100 mL from saline water. The assay was completed in approximately 30 min using one constant temperature (38 °C). In addition, this study demonstrated the quantitation of E. faecalis using a lateral flow strip reader for the first time, enhancing the potential use of RPA assay for the enumeration of E. faecalis in wastewater and heavily contaminated environmental waters, surface water, and wastewater. However, the sensitivity of the RPA-LFA assay for the detection of E. faecalis in tap water, saline water and in wastewater was 10-1000 times lower than that of the Enterolert-E test, depending on the water quality. Nevertheless, with further improvements, this low-cost RPA-LFA may be suitable to be used at the point-of-need (PON) if conjugated with a rapid field-deployable DNA extraction method.

Investigations into valorisation of trade wastewater for biomethane production.

Biogas production from wastewater is one way that industrial sites can work towards the UN Sustainable Development Goals, while recovering a valuable resource. The objective of this study was to investigate the suitability of data collected by municipal wastewater service providers as a method of classifying and screening waste producers as potential sites for biogas resource recovery by anaerobic digestion. Industrial wastewater samples, including raw effluent and treated waste ready for discharge, were examined, and biomethane potential assays performed. Results of chemical analysis and lab-scale digestion were compared to historical service provider data, and patterns were observed. Biomethane yields of up to 357 mL/gVS and 287mL/gVS were achieved from raw and treated effluent respectively. Digestion at the top four prospects could produce over 4690 GJ of methane and save $47,000 in natural gas costs, offsetting 490 tonnes of CO2 equivalent annually. These streams, from logistics, waste management, food and animal product businesses, combined high levels of degradable substrates and low levels of inhibitory components. While it is unlikely that this type of screening program can be completely accurate, certain parameters, including high sodium concentration, are applicable for discounting the potential for biogas production. This knowledge can be a valuable tool in the process of selecting sites for future resource recovery, therefore increasing the uptake of these processes, resulting in economic, environmental, and climate change mitigation benefits.

Intelligent fault diagnosis of helical gearboxes with compressive sensing based non-contact measurements.

Helical gearboxes play a critical role in power transmission of industrial applications. They are vulnerable to various faults due to long-term and heavy-duty operating conditions. To improve the safety and reliability of helical gearboxes, it is necessary to monitor their health conditions and diagnose various types of faults. The conventional measurements for gearbox fault diagnosis mainly include lubricant analysis, vibration, airborne acoustics, thermal images, electrical signals, etc. However, a single domain measurement may lead to unreliable fault diagnosis and the contact installation of transducers is not always accessible, especially in harsh and dangerous environments. In this article, a Compressive Sensing (CS)-based Dual-Channel Convolutional Neural Network (CNN) method was proposed to accurately and intelligently diagnose common gearbox faults based on two complementary non-contact measurements (thermal images and acoustic signals) from a mobile phone. The raw acoustic signals were analysed by the Modulation Signal Bispectrum (MSB) to highlight the coupled modulation components relating to gear faults and suppress the irrelevant components and random noise, which generates a series of two-dimensional matrices as sparse MSB magnitude images. Then, CS was used to reduce the image redundancy but retain key information owing to the high sparsity of thermal images and acoustic MSB images, which significantly accelerates the CNN training speed. The experimental results convincingly demonstrate that the proposed CS-based Dual-Channel CNN method significantly improves the diagnostic accuracy (99.39% on average) of industrial helical gearbox faults compared to the single-channel ones.

Novel Diagnosis Technologies for a Lack of Oil Lubrication in Gearmotor Systems, Based on Motor Current Signature Analysis.

Due to the wide use of gearmotor systems in industry, many diagnostic techniques have been developed/employed to prevent their failures. An insufficient lubrication of gearboxes of these machines could shorten their life and lead to catastrophic failures and losses, making it important to ensure a required lubrication level. For the first time in worldwide terms, this paper proposed to diagnose a lack of gearbox oil lubrication using motor current signature analysis (MCSA). This study proposed, investigated, and experimentally validated two new technologies to diagnose a lack of lubrication of gear motor systems based on MCSA. Two new diagnostic features were extracted from the current signals of a three-phase induction motor. The effectiveness of the proposed technologies was evaluated for different gear lubrication levels and was compared for three phases of motor current signals and for a case of averaging the proposed diagnostic features over three phases. The results confirmed a high effectiveness of the proposed technologies for diagnosing a lack of oil lubrication in gearmotor systems. Other contributions were as follows: (i) it was shown for the first time in worldwide terms, that the motor current nonlinearity level increases with the reduction of the sgearbox oil level; (ii) novel experimental validations of the proposed two diagnostic technologies via comprehensive experimental trials (iii) novel experimental comparisons of the diagnosis effectiveness of the proposed two diagnostic technologies.

Trigger Points and Contracture/Contraction Knots: What's in a Name? Reply to Dommerholt, J.; Gerwin, R.D. Contracture Knots vs. Trigger Points. Comment on "Ball et al. Ultrasound Confirmation of the Multiple Loci Hypothesis of the Myofascial Trigger Point and the Diagnostic Importance of Specificity in the Elicitation of the Local Twitch Response. Diagnostics 2022, 12, 321".

We are responding to the comment by Dommerholt and Gerwin that we have reverse-defined "myofascial trigger point" (MTrP) and "contracture/contraction knot." In attempting to maintain philosophical agreement with specific and implied aspects of their integrated hypothesis of trigger-point formation (namely a MTrP being ischemic and hypoxic), we referred to the MTrP as the small hyperechoic signal rather than the larger hypoechoic (and therefore hyperperfused) structure surrounding it. It was never our intent to re-define nor contribute to confusion. In making this concession with respect to Dommerholt and Gerwin's preferred nomenclature, however, we must instead now reconcile what we image as a hypoechoic (and therefore hyperperfused) MTrP with it being concurrently hypoxic.

Assessment of a three-axis on-rotor sensing performance for machining process monitoring: a case study.

Online monitoring of cutting conditions is essential in intelligent manufacturing, and vibrations are one of the most effective signals in monitoring machining conditions. Generally, traditional wired accelerometers should be installed on a motionless or stable platform, such as a tool holder or lathe bed, to sense vibrations. Such installation methods would cause the signals to suffer more serious noise interferences and a low signal-to-noise ratio, resulting in less sensitivity to valuable information. Therefore, this study developed a novel three-axis wireless on-rotor sensing (ORS) system for monitoring the turning process. The Micro Electromechanical System (MEMS) accelerometer sensor node can be mounted on a rotating workpiece or spindle rotor and is more sensitive in detecting the vibrations of the entire rotor system without any modification of the lathe system and interference in the cutting procedure. The processor, data acquisition, and Bluetooth Low Energy (BLE) 5.0+ modules were developed and debugged to cooperate with a piezoelectric triaxial accelerometer, with a vibration amplitude not larger than ± 16 g. A series of turning tests were conducted and the results were compared with those from the commercial wired accelerometers, which proved that the ORS system can measure the vibration signal of the rotor system more effectively and sensitively than wired accelerometers, thus demonstrating the accurate monitoring of machining parameters.

Comparative Analysis of Antibody Titers against the Spike Protein of SARS-CoV-2 Variants in Infected Patient Cohorts and Diverse Vaccination Regimes.

The presence of neutralizing antibodies against SARS-CoV-2 correlates with protection against infection and severe COVID-19 disease courses. Understanding the dynamics of antibody development against the SARS-CoV-2 virus is important for recommendations on vaccination strategies and on control of the COVID-19 pandemic. This study investigates the dynamics and extent of α-Spike-Ab development by different vaccines manufactured by Johnson & Johnson, AstraZeneca, Pfizer-BioNTech and Moderna. On day 1 after vaccination, we observed a temporal low-grade inflammatory response. α-Spike-Ab titers were reduced after six months of vaccination with mRNA vaccines and increased 14 days after booster vaccinations to a maximum that exceeded titers from mild and critical COVID-19 and Long-COVID patients. Within the group of critical COVID-19 patients, we observed a trend for lower α-Spike-Ab titers in the group of patients who survived COVID-19. This trend accompanied higher numbers of pro-B cells, fewer mature B cells and a higher frequency of T follicular helper cells. Finally, we present data demonstrating that past infection with mild COVID-19 does not lead to long-term increased Ab titers and that even the group of previously infected SARS-CoV-2 patients benefit from a vaccination six months after the infection.

Intramuscular Electrical Stimulation to Trigger Points: Insights into Mechanisms and Clinical Applications-A Scoping Review.

Intramuscular electrical stimulation (IMES) is a modality used by clinicians to treat myofascial pain. Recent studies have shown positive results for the use of IMES on pain outcomes, yet studies investigating the potential mechanisms of IMES directly to trigger points (TrPs) are lacking. We performed a scoping review of the literature to summarize the current evidence from human and animal studies on the mechanisms of IMES to the TrP location, and to identify gaps in the existing literature. Electronic literature searches were conducted across five databases from inception to 15 August 2022, including PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), Scopus and Cochrane Register of Controlled Trials. Four studies met our full criteria for inclusion in this review. Three studies assessed the effects of IMES to TrPs on human subjects with MPS, and only one study used an animal model with experimentally generated TrPs. Based on the results of the included studies, IMES within a TrP region was reported to normalize muscle blood flow, decrease endplate noise of the TrP and elicit antinociceptive effects, at least partially, through engaging supraspinal descending pain inhibitory systems. At present, no clinical implications can be determined on the use of IMES to TrPs due to the limited amount and quality of the available evidence. Further studies investigating the clinical effectiveness and also underlying mechanisms of IMES to TrPs are clearly needed.

The co-application of biochar with bioremediation for the removal of petroleum hydrocarbons from contaminated soil.

Soil pollution from petroleum hydrocarbon is a global environmental problem that could contribute to the non-actualisation of the United Nations Sustainable Development Goals. Several techniques have been used to remediate petroleum hydrocarbon-contaminated soils; however, there are technical and economical limitations to existing methods. As such, the development of new approaches and the improvement of existing techniques are imperative. Biochar, a low-cost carbonaceous product of the thermal decomposition of waste biomass has gained relevance in soil remediation. Biochar has been applied to remediate hydrocarbon-contaminated soils, with positive and negative results reported. Consequently, attempts have been made to improve the performance of biochar in the hydrocarbon-based remediation process through the co-application of biochar with other bioremediation techniques as well as modifying biochar properties before use. Despite the progress made in this domain, there is a lack of a detailed single review consolidating the critical findings, new developments, and challenges in biochar-based remediation of petroleum hydrocarbon-contaminated soil. This review assessed the potential of biochar co-application with other well-known bioremediation techniques such as bioaugmentation, phytoremediation, and biostimulation. Additionally, the benefits of modification in enhancing biochar suitability for bioremediation were examined. It was concluded that biochar co-application generally resulted in higher hydrocarbon removal than sole biochar treatment, with up to a 4-fold higher removal observed in some cases. However, most of the biochar co-applied treatments did not result in hydrocarbon removal that was greater than the additive effects of individual treatment. Overall, compared to their complementary treatments, biochar co-application with bioaugmentation was more beneficial in hydrocarbon removal than biochar co-application with either phytoremediation or biostimulation. Future studies should integrate the ecotoxicological and cost implications of biochar co-application for a viable remediation process. Lastly, improving the synergistic interactions of co-treatment on hydrocarbon removal is critical to capturing the full potential of biochar-based remediation.

Remediation of groundwater contaminated with dye using carbon dots technology: Ecotoxicological and microbial community responses.

Groundwater pollution poses a serious threat to the main source of clean water globally. Nanoparticles have the potential for remediation of polluted aquifers; however, environmental safety concerns associated with in situ deployments of such technology include potential detrimental effects on microorganisms in terms of toxicity and functional disruptions. In this work, we evaluated a new and ecofriendly approach using carbon dots (CDs) as Fenton-like catalysts to catalyse the degradation of dye-containing groundwater samples. This investigation aimed at evaluating the efficacy of a novel remediation technology in terms of dye degradation and toxicity reduction while assessing its impacts on aquatic microorganisms. Uncontaminated Australian groundwater samples were spiked with methylene blue and incubated in the dark, at 18 °C, under slow agitation, using CDs at 0.5 mg mL-1 and H2O2 at 73.5 mM for 25 h. The dye degradation rate was determined as well as the toxicity of the treated solutions using the Microtox® bioassay. Further, to determine the changes in the groundwater microbial community, 16 S rRNA sequencing was used and evenness and diversity indices were analysed using Pielou's evenness and Simpson index, respectively. This study revealed that dye-containing groundwater were effectively treated by CDs showing a degradation rate of 78-82% and a significant 4-fold reduction in the toxicity. Characterisation of the groundwater microbiota revealed a predominance of at least 60% Proteobacteria phylum in all samples where diversity and evenness were maintained throughout the remediation process. The results showed that CDs could be an efficient approach to treat polluted groundwater and potentially have minimum impact on the environmental microbiome.

Differential diagnostic performance of a panel of plasma biomarkers for different types of dementia.

Introduction: We explored what combination of blood-based biomarkers (amyloid beta [Aß]1-42/1-40, phosphorylated tau [p-tau]181, neurofilament light [NfL], glial fibrillary acidic protein [GFAP]) differentiates Alzheimer's disease (AD) dementia, frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Methods: We measured the biomarkers with Simoa in two separate cohorts (n = 160 and n = 152). In one cohort, Aß1-42/1-40 was also measured with mass spectrometry (MS). We assessed the differential diagnostic value of the markers, by logistic regression with Wald's backward selection. Results: MS and Simoa Aß1-42/1-40 similarly differentiated AD from controls. The Simoa panel that optimally differentiated AD from FTD consisted of NfL and p-tau181 (area under the curve [AUC] = 0.94; cohort 1) or NfL, GFAP, and p-tau181 (AUC = 0.90; cohort 2). For AD from DLB, the panel consisted of NfL, p-tau181, and GFAP (AUC = 0.88; cohort 1), and only p-tau181 (AUC = 0.81; cohort 2). Discussion: A combination of plasma p-tau181, NfL, and GFAP, but not Aß1-42/1-40, might be useful to discriminate AD, FTD, and DLB.

Ultrasound Confirmation of the Multiple Loci Hypothesis of the Myofascial Trigger Point and the Diagnostic Importance of Specificity in the Elicitation of the Local Twitch Response.

The literature has hypothesized that a trigger point (TrP) area consists of a hyperperfused contracture knot with smaller hypoperfused TrPs within the contracture knot. By contrast, the only published ultrasound image of a TrP has it labeled hypoechoic (i.e., hyperperfused) with no commentary regarding smaller speckles of hypoperfusion within. Furthermore, the lack of clarity in objective definition of the terms associated with the TrP (namely, the palpable "contracture knot" and smaller nonpalpable "trigger point") has led to unnecessary communication difficulties between and among clinicians and researchers. In this case series of three muscles across two patients, by using high-definition musculoskeletal ultrasound imaging technology, we present what we believe to be the first reliable capture of palpable hypoechoic (e.g., hypoperfused) contracture knots (previously mislabeled as a hypoechoic TrP), and a visual support of the multiple loci hypothesis first proposed by Hong and Simons-the first reliable confirmation of the hyperechoic (i.e., hypoperfused) TrP within. Initially proposed by a histological study and supported by microdialysis study, this case series lends further support for the multiple loci hypothesis through visual confirmation of palpable hypoechoic contracture knots, with smaller hypoechoic TrPs "speckles" within.