Drug dependency and drug use behaviour among male illicit drug users in selected rehabilitation centres in Sri Lanka

Background: Illicit drug use has become a growing public health phenomenon in Sri Lanka. Many illicit drug users end up with drug dependency, becoming a burden to the country.Objectives: To describe drug dependency and drug use behaviour among male illicit drug users in selected rehabilitation centres in Sri Lanka.Methods: A cross-sectional study was conducted among 431 male illicit drug users in five selected rehabilitation centres in Galle, Colombo, Gampaha and Kandy districts, Sri Lanka. An interviewer-administered questionnaire was used for data collection. Drug dependency was identified using ICD symptom checklist for substance use disorder.Results: Majority of the sample were Sinhala (82.4%) and Buddhists (70.5%). Mean age (SD) was 32 (10.3) years. The highest percentage of the drug users were from Western province (75.6%). Of all illicit drug users, 97% were drug dependents according to ICD 10 symptom checklist. Heroin was most commonly addicted illicit drug (86.5%). Cannabis addiction was identified among 4.3% and all of them were from rural areas. Approximately 4% were addicted to multiple drugs. Injecting drug practices were reported among 23.4%. Mobile transfer of funds (eZ cash) was a popular method used to purchase drugs by drug users (21.8%) outside the Western province. In a shortage of the regular drug, 32.9% of drug users used alternative illicit drug, 3.2% used alcohol and 16.9% had a period of abstinence. Interestingly, 46.9% never experienced a shortage of drugs. Drug overdose was experienced by 25.1% of drug users.Conclusions: Drug dependency is a significant problem among illicit drug users. A proper system for early identification of drug dependents at community level is required to deliver better preventive care

The Effect of Pressure Gradient on the Aeroacoustics and WakDynamics of a Finite Wall-Mounted Square Cylinder

This paper reports an experimental investigation of the wake flow structures and noise production of a square finite-wall-mounted cylinder (FWMC) with an aspect ratio of 2.4. The cylinder was immersed in flows with favourable-, near-zero-and adverse-pressure gradients at a Reynolds number of 48000, based on cylinder width. Acoustic and particle image velocimetry measurements were taken simultaneously using the newly developed open-jet pressure gradient test rig in the UNSW Anechoic Wind Tunnel. An adverse pressure gradient was found to enhance the cylinder junction upwash, weaken the free-end downwash and suppress the primary tonal noise at a Strouhal number of approximately 0.1. Conversely, a favourable-pressure gradient promotes downwash over the free-end and leads to a higher tonal noise level. Wake flow structures that correlated with the far-field sound pressure were identified to understand noise generation or suppression mechanisms

The Effect of Pressure Gradient on the Unsteady Surface Pressure and Wake Dynamics of a Finite Wall-Mounted Square Cylinder

An experimental investigation of the wake flow structures and surface pressure fluctuations of a square finite wall-mounted cylinder with an aspect ratio of 2.4 is presented. The cylinder was immersed in flows with favourable, near-zero and adverse pressure gradients at a Reynolds number of 48000, based on cylinder width. Unsteady surface pressure and particle image velocimetry measurements were taken simultaneously on the open-jet pressure gradient test rig in the UNSW Anechoic Wind Tunnel. A favourable pressure gradient was found to reduce the size of the recirculation region in the wake, which intensified the free-end downwash and suppressed the junction upwash. The intensities of the pressure fluctuations are slightly increased at the primary and secondary shedding Strouhal numbers of approximately 0.1 and 0.2. Conversely, the recirculation region expands under an adverse pressure gradient, with the downwash weakened and the upwash enhanced. The peaks in the surface pressure spectra are noticeably attenuated at the primary shedding Strouhal number and completely suppressed at the secondary Strouhal number. Wake flow structures that are correlated with the surface pressure fluctuations were identified to understand the enhancement or suppression mechanisms of the surface pressure fluctuations and the associated shedding regimes

Profiling DNA methylation based on next-generation sequencing approaches: New insights and clinical applications

DNA methylation is an epigenetic modification that plays a pivotal role in regulating gene expression and, consequently, influences a wide variety of biological processes and diseases. The advances in next-generation sequencing technologies allow for genome-wide profiling of methyl marks both at a single-nucleotide and at a single-cell resolution. These profiling approaches vary in many aspects, such as DNA input, resolution, coverage, and bioinformatics analysis. Thus, the selection of the most feasible method according with the project’s purpose requires in-depth knowledge of those techniques. Currently, high-throughput sequencing techniques are intensively used in epigenomics profiling, which ultimately aims to find novel biomarkers for detection, diagnosis prognosis, and prediction of response to therapy, as well as to discover new targets for personalized treatments. Here, we present, in brief, a portrayal of next-generation sequencing methodologies’ evolution for profiling DNA methylation, highlighting its potential for translational medicine and presenting significant findings in several diseases.This research was funded by Research Center—Portuguese Oncology Institute of Porto (CI-IPOFB-GEBC-2018 and FCT (POCI-01-0145-FEDER-29043). D.B.-S. is a research fellow from CI-IPOP (BI-GEBC2018/UID/DTP/00776/POCI-01-0145-FEDER-006868), and C.J.M. is a FCT Investigador (FCT contract IF/00047/2012)

A double-edged sword: Residents' views on the health consequences of gentrification in Porto, Portugal

Gentrification is currently shaping the urban environment in important ways. It also contributes to shaping the health of the inhabitants of gentrifying cities, although it is still unclear how. Gentrification processes are often linked to different drivers and have specific local translations, further complicating the study of the relationship between gentrification and health. We investigated this relationship in Porto, Portugal, a southern European city undergoing rampant transnational gentrification. In order to study how gentrification impacts health from the point of view of that city's residents, we conducted a study using photovoice with a sample of participants recruited from a population-based cohort, which was divided into three different groups: one from gentrifying areas of Porto, another from deprived non-gentrifying areas, and the other from affluent areas. The thematic analysis of data generated six themes, each referring to a change, or a set of connected changes, related to gentrification: increasing floating population, lack of housing access and displacement, construction and rehabilitation, changing local commerce, loss of place, and broader socioeconomic change. According to the accounts from participants, these changes affect health in different ways, both beneficial and harmful. Participants also reflected on how to act on this issue. This research adds to the knowledge about the relationship between gentrification and health by providing detailed and nuanced views about this relationship considering its city-wide impacts.This work was supported by FEDER through the Operational Programme Competitiveness and Internationalisation and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) under the Unidade de Investigação em Epidemiologia - Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (UIDB/04750/2020) and Laboratório para an Investigação Integrativa e Translacional em Saúde Populacional (ITR) (LA/P/0064/2020); and the project “HUG: The health impacts of inner-city gentrification, displacement and housing insecurity: a quasi-experimental multi-cohort study” (PTDC/GES-OUT/1662/2020); Ana Isabel Ribeiro was supported by National Funds through FCT, under the ‘Stimulus of Scientific Employment – Individual Support’ programme within the contract CEECIND/02386/2018. The funding sources had no role in the research conducted neither in the preparation of this article

Expansion of human mesenchymal stem/stromal cells (hMSCs) in bioreactors using microcarriers: lessons learnt and what the future holds

Human mesenchymal stem/stromal cells (hMSCs) present a key therapeutic cellular intervention for use in cell and gene therapy (CGT) applications due to their immunomodulatory properties and multi-differentiation capability. Some of the indications where hMSCs have demonstrated pre-clinical or clinical efficacy to improve outcomes are cartilage repair, acute myocardial infarction, graft versus host disease, Crohn’s disease and arthritis. The current engineering challenge is to produce hMSCs at an affordable price and at a commercially-relevant scale whilst minimising process variability and manual, human operations. By employing bioreactors and microcarriers (due to the adherent nature of hMSCs), it is expected that production costs would decrease due to improved process monitoring and control leading to better consistency and process efficiency, and enabling economies of scale. This approach will result in off the shelf (allogeneic) hMSC-based products becoming more accessible and affordable. Importantly, cell quality, including potency, must be maintained during the bioreactor manufacturing process. This review aims to examine the various factors to be considered when developing a hMSC manufacturing process using microcarriers and bioreactors and their potential impact on the final product. As concluding remarks, gaps in the current literature and potential future areas of research are also discussed

Single-Component Electroactive Polymer Architectures for Non-Enzymatic Glucose Sensing.

Organic mixed ionic-electronic conductors (OMIECs) have emerged as promising materials for biological sensing, owing to their electrochemical activity, stability in an aqueous environment, and biocompatibility. Yet, OMIEC-based sensors rely predominantly on the use of composite matrices to enable stimuli-responsive functionality, which can exhibit issues with intercomponent interfacing. In this study, an approach is presented for non-enzymatic glucose detection by harnessing a newly synthesized functionalized monomer, EDOT-PBA. This monomer integrates electrically conducting and receptor moieties within a single organic component, obviating the need for complex composite preparation. By engineering the conditions for electrodeposition, two distinct polymer film architectures are developed: pristine PEDOT-PBA and molecularly imprinted PEDOT-PBA. Both architectures demonstrated proficient glucose binding and signal transduction capabilities. Notably, the molecularly imprinted polymer (MIP) architecture demonstrated faster stabilization upon glucose uptake while it also enabled a lower limit of detection, lower standard deviation, and a broader linear range in the sensor output signal compared to its non-imprinted counterpart. This material design not only provides a robust and efficient platform for glucose detection but also offers a blueprint for developing selective sensors for a diverse array of target molecules, by tuning the receptor units correspondingly

Bacterial toxin-triggered release of antibiotics from capsosomes protects a fly model from lethal methicillin-resistant Staphylococcus aureus (MRSA) infection

Antibiotic resistance is a severe global health threat and hence demands rapid action to develop novel therapies, including microscale drug delivery systems. Herein, a hierarchical microparticle system is developed to achieve bacteria-activated single- and dual-antibiotic drug delivery for preventing methicillin-resistant Staphylococcus aureus (MRSA) bacterial infections. The designed system is based on a capsosome structure, which consists of a mesoporous silica microparticle coated in alternating layers of oppositely charged polymers and antibiotic-loaded liposomes. The capsosomes are engineered and shown to release their drug payloads in the presence of MRSA toxins controlled by the Agr quorum sensing system. MRSA-activated single drug delivery of vancomycin and synergistic dual delivery of vancomycin together with an antibacterial peptide successfully kills MRSA in vitro. The capability of capsosomes to selectively deliver their cargo in the presence of bacteria, producing a bactericidal effect to protect the host organism, is confirmed in vivo using a Drosophila melanogaster MRSA infection model. Thus, the capsosomes serve as a versatile multidrug, subcompartmentalized microparticle system for preventing antibiotic-resistant bacterial infections, with potential applications to protect wounds or medical device implants from infections

Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress

Acknowledgments We thank Alexander Johnson (yhb1D/D), Karl Kuchler (sodD/D mutants), Janet Quinn (hog1D/D, hog1/cap1D/D, trx1D/D) and Peter Staib (ssu1D/D) for providing mutant strains. We acknowledge helpful discussions with our colleagues from the Microbial Pathogenicity Mechanisms Department, Fungal Septomics and the Microbial Biochemistry and Physiology Research Group at the Hans Kno¨ll Institute (HKI), specially Ilse D. Jacobsen, Duncan Wilson, Sascha Brunke, Lydia Kasper, Franziska Gerwien, Sea´na Duggan, Katrin Haupt, Kerstin Hu¨nniger, and Matthias Brock, as well as from our partners in the FINSysB Network. Author Contributions Conceived and designed the experiments: PM HW IMB AJPB OK BH. Performed the experiments: PM CD HW. Analyzed the data: PM HW IMB AJPB OK BH. Wrote the paper: PM HW OK AJPB BH.Peer reviewedPublisher PD