AREAS COVERED: This paper discusses the complex process of ECM regulation in TM and explores promising therapeutic targets. The role of Transforming Growth Factor-β as a central player in ECM deposition in TM is discussed. We elaborate the key regulatory processes involved in its activation, release, signaling, and cross talk with other signaling pathways including Rho GTPase, Wnt, integrin, cytokines, and renin-angiotensin-aldosterone. Further, we summarize the therapeutic agents that have been explored to target ECM dysregulation in TM.
EXPERT OPINION: Targeting molecular pathways to reduce ECM deposition and/or enhance its degradation are of considerable significance for IOP lowering. Challenges lie in pinpointing specific targets and designing drug delivery systems to precisely interact with pathologically active/inactive signaling. Recent advances in monoclonal antibodies, fusion molecules, and vectored nanotechnology offer potential solutions.
RESULTS: Four hundred fifty-three cloacal and farm environment samples were collected from six different commercial chicken farms in Kelantan, Malaysia. E. coli was isolated using standard bacteriological methods, and the isolates were tested for antimicrobial susceptibility using disc diffusion and colistin minimum inhibitory concentration (MIC) by broth microdilution. Multiplex PCR was used to detect mcr genes, and DNA sequencing was used to confirm the resistance genes. Virulence gene detection, phylogroup, and multilocus sequence typing (MLST) were done to further characterize the E. coli isolates. Out of the 425 (94%; 425/453) E. coli isolated from the chicken and farm environment samples, 10.8% (48/425) isolates were carrying one or more colistin-resistance encoding genes. Of the 48 colistin-resistant isolates, 54.2% (26/48) of the mcr positive isolates were genotypically and phenotypically resistant to colistin with MIC of colistin ≥ 4 μg/ml. The most prominent mcr gene detected was mcr-1 (47.9%; 23/48), followed by mcr-8 (18.8%; 9/48), mcr-7 (14.5%; 7/48), mcr-6 (12.5%; 6/48), mcr-4 (2.1%; 1/48), mcr-5 (2.1%; 1/48), and mcr-9 (2.1%; 1/48) genes. One E. coli isolate originating from the fecal sample was found to harbor both mcr-4 and mcr-6 genes and another isolate from the drinking water sample was carrying mcr-1 and mcr-8 genes. The majority of the mcr positive isolates were categorized under phylogroup A followed by phylogroup B1. The most prevalent sequence typing (ST) was ST1771 (n = 4) followed by ST206 (n = 3). 100% of the mcr positive E. coli isolates were multidrug resistant. The most frequently detected virulence genes among mcr positive E. coli isolates were ast (38%; 18/48) followed by iss (23%; 11/48). This is the first research to report the prevalence of mcr-4, mcr-5, mcr-6, mcr-7, and mcr-8 genes in E. coli from broiler chickens and farm environments in Malaysia.
CONCLUSION: Our findings suggest that broiler chickens and broiler farm environments could be reservoirs of colistin-resistant E. coli, posing a risk to public health and food safety.
MATERIALS AND METHODS: A melatonin-loaded alginate-chitosan/beta-tricalcium phosphate composite hydrogel was successfully prepared and characterized. Thirty-six critical-sized bilateral class II furcation defects were created in six Mongrel dogs, and were randomly divided and allocated to three cohorts; sham, unloaded composite, and melatonin-loaded. Periodontal regenerative capacity was evaluated via histologic and histomorphometric analysis.
RESULTS: Melatonin-treated group showed accelerated bone formation and advanced maturity, with a significant twofold increase in newly formed inter-radicular bone compared with the unloaded composite. The short-term regenerative efficacy was evident 4 weeks postoperatively as a significant increase in cementum length concurrent with reduction of entrapped epithelium. After 8 weeks, the scaffold produced a quality of newly synthesized bone similar to normal compact bone, with potent periodontal ligament attachment.
CONCLUSIONS: Melatonin-loaded hydrogel template accelerated formation and enhanced quality of newly formed bone, allowing complete periodontal regeneration. Furthermore, the scaffold prevented overgrowth and entrapment of epithelial cells in furcation defects.
METHODS: We systematically searched Pubmed for population-based studies of chronic kidney disease (CKD) and ESKD epidemiology and management. Population-level data from 23 pre-designated nations were eligible for inclusion if they pertained to people receiving dialysis or kidney transplant for ESKD. When available, government websites were utilized to identify and extract data from relevant kidney registries . Measures gathered included those related to the prevalence and mortality of ESKD; the availability of nephrologists; per capita healthcare expenditures; and use of erythropoietin stimulating agents (ESAs).
RESULTS: We obtained data from the United States (US), 7 nations in Eastern Europe, 4 each in Western Europe, Latin America, and Africa, and 3 in Asia. Documented prevalence of ESKD per million population varied from a high of 3,600 (Malaysia) to a low of 67 (Senegal). Annual mortality associated with ESKD varied from 31% (Ethiopia and Senegal) to 10% (UK). Nephrologist availability per million population varied from 40 (Japan) to <1 (South Africa) and was associated with per capita healthcare expenditures.
CONCLUSIONS: The delivery of kidney care related to ESKD varies widely among countries. Higher per capita healthcare spending is associated with increased delivery of kidney care. However, in part because documentation of kidney disease varies widely, it is difficult to determine how outcomes related to ESKD may vary across nations.
METHODS: For this integrative analysis, we identified regions in the world where there was evidence of a connection between EIDs and anthropogenic land-use changes between Nov 9, 1999, and Oct 25, 2021, through a targeted literature review of academic literature and grey literature to identify evidence of drivers of anthropogenic land-use change and their association with commodity production in these regions. We only included publications in English that showed a connection between deforestation and the production of one or more commodities. Publications merely describing spatial or temporal land-use change dynamics (eg, a reduction of forest or an increase of palm-oil plantations) were excluded. As we were assessing financial influence on corporate activities through ownership specifically, we focused our analysis on publicly listed companies. Equity data and data about ownership structure were extracted from Orbis, a company information database. We assessed financial influence by identifying financial entities with the largest equity ownership, descriptively mapping transboundary connections between investors and publicly listed companies.
FINDINGS: 227 public and private companies operating in five economic sectors (ie, production of palm oil, pulp and wood products, cocoa, soybeans, and beef) between Dec 15, 2020, and March 8, 2021, were identified. Of these 227, 99 (44%) were publicly listed companies, with 2310 unique shareholders. These publicly listed companies operated in six geographical regions, resulting in nine case-study regions. 54 (55%) companies with complete geographical information were included in the countries network. Four financial entities (ie, Dimensional, Vanguard, BlackRock, and Norway's sovereign wealth fund) each had ownership in 39 companies or more in three of the case-study regions (ie, north America, east Asia, and Europe). Four large US-based asset managers (ie, Vanguard, BlackRock, T Rowe Price, and State Street) were the largest owners of publicly listed companies in terms of total equity size, with ownership amounts for these four entities ranging from US$8 billion to $21 billion. The specific patterns of cross-national ownership depended on the region of interest; for example, financial influence on EIDs risks that was associated with commodity production in southeast and east Asia came from not only global asset managers but also Malaysian, Chinese, Japanese, and Korean financial entities. India, Brazil, the USA, Mexico, and Argentina were the countries towards which investments were most directed.
INTERPRETATION: Although commodity supply chains and financial markets are highly globalised, a small number of investors and countries could be viewed as disproportionally influential in sectors that increase EIDs risks. Such financial influence could be used to develop and implement effective policies to reduce ecological degradation and mitigate EIDs risks and their effects on population health.
FUNDING: Formas and Networks of Financial Rupture-how cascading changes in the climate and ecosystems could impact on the financial sector.
METHODS: A two-phase mixed-methods approach was used. Phase 1 involved qualitative interviews with hypertensive patients from two health clinics in Kuala Lumpur, Malaysia. The themes extracted from these interviews were used to generate items for the MAANS. In Phase 2, data from 213 participants were analysed using exploratory factor analysis (EFA) to establish the scale's factor structure, thereby created the modified version of the MAANS. Confirmatory factor analysis (CFA) was then conducted on a separate dataset of 205 participants to confirm the factor structure, resulted in the final version of the MAANS. The reliability of the final MAANS version was assessed using Cronbach's alpha coefficient. The MAANS scores were used to predict subscales of the Malay version of the WHO Quality-of-Life (QOL) BREF, demonstrating the scale's predictive validity.
RESULTS: Ten qualitative interviews yielded 73 items. The EFA produced a modified MAANS with 21 items grouped into five factors. However, the CFA retained three factors in the final scale: Perceived Non-Susceptibility, Poor Doctor-Patient Relationship, and Unhealthy Lifestyle. The final 14-item, 3-factor MAANS demonstrated moderate reliability (Cronbach's alpha coefficient = 0.64) and exhibited partial predictive validity, with the Poor Doctor-Patient Relationship and Unhealthy Lifestyle subscales significantly predicting Social QOL and Environmental QOL.
CONCLUSION: The MAANS is a reliable, valid, and multidimensional scale specifically developed to evaluate non-adherence to anti-hypertensive medications in local clinical settings with the potential to further the advancement of research and practice in sociomedical and preventive medicine.