Knee osteoarthritis (OA) is one of the leading causes of disability within the adult population. Current treatment options for OA of the knee include intra-articular (IA) hyaluronic acid (HA), a ...molecule found intrinsically within the knee joint that provides viscoelastic properties to the synovial fluid. A variety of mechanisms in which HA is thought to combat knee OA are reported in the current basic literature.
We conducted a comprehensive literature search to identify currently available primary non-clinical basic science articles focussing on the mechanism of action of IA-HA treatment. Included articles were assessed and categorized based on the mechanism of action described within them. The key findings and conclusions from each included article were obtained and analyzed in aggregate with studies of the same categorical assignment.
Chondroprotection was the most frequent mechanism reported within the included articles, followed by proteoglycan and glycosaminoglycan synthesis, anti-inflammatory, mechanical, subchondral, and analgesic actions. HA-cluster of differentiation 44 (CD44) receptor binding was the most frequently reported biological cause of the mechanisms presented. High molecular weight HA was seen to be superior to lower molecular weight HA products. HA derived through a biological fermentation process is also described as having favorable safety outcomes over avian-derived HA products.
The non-clinical basic science literature provides evidence for numerous mechanisms in which HA acts on joint structures and function. These actions provide support for the purported clinical benefit of IA-HA in OA of the knee. Future research should not only focus on the pain relief provided by IA-HA treatment, but the disease modification properties that this treatment modality possesses as well.
Objective
Osteoarthritis (OA) is one of the leading causes of disability in the adult population. Common nonoperative treatment options include nonsteroidal anti-inflammatory drugs (NSAIDs), ...intra-articular corticosteroids, and intra-articular injections of hyaluronic acid (HA). HA is found intrinsically within the knee joint providing viscoelastic properties to the synovial fluid. HA therapy provides anti-inflammatory relief through a number of different pathways, including the suppression of pro-inflammatory cytokines and chemokines.
Methods
We conducted a systematic review to summarize the published literature on the anti-inflammatory properties of hyaluronic acid in osteoarthritis. Included articles were categorized based on the primary anti-inflammatory responses described within them, by the immediate cell surface receptor protein assessed within the article, or based on the primary theme of the article. Key findings aimed to describe the macromolecules and inflammatory-mediated responses associated with the cell transmembrane receptors.
Results
Forty-eight articles were included in this systematic review that focused on the general anti-inflammatory effects of HA in knee OA, mediated through receptor-binding relationships with cluster determinant 44 (CD44), toll-like receptor 2 (TLR-2) and 4 (TLR-4), intercellular adhesion molecule-1 (ICAM-1), and layilin (LAYN) cell surface receptors. Higher molecular weight HA (HMWHA) promotes anti-inflammatory responses, whereas short HA oligosaccharides produce inflammatory reactions.
Conclusions
Intra-articular HA is a viable therapeutic option in treating knee OA and suppressing inflammatory responses. HMWHA is effective in suppressing the key macromolecules that elicit the inflammatory response by short HA oligosaccharides.
Abstract
This concluding chapter provides an overview of the chapters, as well as briefly highlighting the relevant normative frameworks applicable to the issues addressed in this special edition ...journal. The authors have addressed structural, institutional, and individual gaps and challenges in the refugee protection sphere and have raised concerns about the lack of adequate acknowledgement of gendered aspects of the asylum frameworks and processes, and crucially the differential impact thereof. The gaps in the legally binding instruments governing this area of human rights protection, and the minimal attention to the connection between theory and practice and its resulting consequences, are highlighted by some authors.
Aims: To review the antidiabetic properties, pharmacological characteristics, and phytochemical research on Momordica Ccharantia (bitter gourd) and assess its potential as a therapeutic agent for ...diabetes and cancer prevention. Study Design: Review of existing literature and research studies, including pre-clinical trials and animal and in vitro studies. Methodology: Analysis of traditional uses, pharmacological data, and phytochemical research on M. Charantia. Evaluation of anti-diabetic and anti-HIV properties based on available studies. Results: Charantia has shown anti-diabetic and hypoglycemic effects in pre-clinical studies. Limited and unreliable clinical data due to poor research design and inadequate statistical power. Recent studies indicate potential anti-tumor, anti-diabetic, and anti-HIV properties. Plant extract components have demonstrated effectiveness in cancer prevention through immune function enhancement, induction of cell death, and inhibition of cancer-related processes. Conclusion: M. Charantia holds promise as a therapeutic agent for diabetes management and cancer prevention. However, there is a need for better-designed clinical trials to confirm its efficacy and establish reliable clinical evidence.
•A spatio-stochastic model is developed, this model is a discrete time and space stochastic processes based on the binomial chain models.•The model is theoretically outlined and presented in three ...variations: A lockdown model, a model with no migration but interaction and finally a model with migration and interaction accounting for the different modelling interventions.•A simulation study is done to compare existing models and the spatio-stochastic models
The spread of infectious diseases is a world-wide problem that has a greater impact on low-income countries. Mathematical modelling is a useful tool to better understand these diseases and to plan prevention and interventions. In this article, discrete-time binomial chain models, which are used for modelling the transmission of infectious diseases, have been extended by the addition of a spatial component. The spatial component is included in the function which represents the number of contacts that an individual makes. The spatio-stochastic model is derived to form three cases to match different modelling scenarios, namely: a model with only local transmission, a model with interaction between spatial units but no migration, and a model with interaction and migration between spatial units. Simulations are then used to compare the different models. The spatio-stochastic model is also demonstrated with an application to measles data. From this study, it can be seen that the type of model and inclusion of a spatial component plays an important role in the transmission of infectious diseases. The importance of choosing a model which best represents the dynamics and circumstances of an infectious disease is highlighted. The models presented in this paper allows flexibility which accommodate for a wide range of modelling cases.
The 2021 guidelines primary panel selected clinically relevant questions and produced updated recommendations, on the basis of important new findings that have emerged since the 2016 guidelines. In ...patients with clinical atherosclerosis, abdominal aortic aneurysm, most patients with diabetes or chronic kidney disease, and those with low-density lipoprotein cholesterol ≥ 5 mmol/L, statin therapy continues to be recommended. We have introduced the concept of lipid/lipoprotein treatment thresholds for intensifying lipid-lowering therapy with nonstatin agents, and have identified the secondary prevention patients who have been shown to derive the largest benefit from intensification of therapy with these agents. For all other patients, we emphasize risk assessment linked to lipid/lipoprotein evaluation to optimize clinical decision-making. Lipoprotein(a) measurement is now recommended once in a patient's lifetime, as part of initial lipid screening to assess cardiovascular risk. For any patient with triglycerides ˃ 1.5 mmol/L, either non-high-density lipoprotein cholesterol or apolipoprotein B are the preferred lipid parameter for screening, rather than low-density lipoprotein cholesterol. We provide updated recommendations regarding the role of coronary artery calcium scoring as a clinical decision tool to aid the decision to initiate statin therapy. There are new recommendations on the preventative care of women with hypertensive disorders of pregnancy. Health behaviour modification, including regular exercise and a heart-healthy diet, remain the cornerstone of cardiovascular disease prevention. These guidelines are intended to provide a platform for meaningful conversation and shared-decision making between patient and care provider, so that individual decisions can be made for risk screening, assessment, and treatment.
Le panel principal responsable des lignes directrices 2021 a sélectionné des éléments cliniquement pertinents et a soumis des recommandations actualisées, basées sur de nouvelles découvertes d'importance apparues depuis les lignes directrices de 2016. Ainsi, le traitement par statine reste recommandé pour les patients atteints d'athérosclérose clinique, d'anévrisme de l'aorte abdominale, pour la plupart des patients diabétiques ou atteints d'insuffisance rénale chronique, et chez ceux dont le cholestérol à lipoprotéines de basse densité est ≥ 5 mmol/l. Nous avons introduit la notion de seuils pour le traitement des lipides/lipoprotéines afin d'intensifier le traitement hypolipidémiant avec des agents non-statiniques, et nous avons identifié les patients en prévention secondaire distingués comme ayant tirer le plus grand bénéfice de l'intensification du traitement avec ces agents. Pour tous les autres patients, nous mettons l'accent sur l'appréciation du risque par le biais de l'évaluation des lipides/lipoprotéines afin d'optimiser la prise de décision clinique. Le dosage de la lipoprotéine (a) est maintenant recommandé une fois dans la vie d'un patient, dans le cadre du dépistage initial des lipides pour évaluer le risque cardiovasculaire. Pour tout patient présentant des taux de triglycérides ˃ 1,5 mmol/l, l'apolipoprotéine B ou le cholestérol lié aux lipoprotéines autres que celles de haute densité sont les indices lipidiques à privilégier pour le dépistage, plutôt que le cholestérol à lipoprotéines de basse densité. Nous proposons des recommandations actualisées concernant le rôle du score calcique des artères coronaires en tant qu'outil de décision clinique pour aider à la décision d'administrer un traitement par statine. Il existe de nouvelles recommandations concernant les soins préventifs des femmes souffrant de troubles hypertensifs de la grossesse. Le changement de comportement en matière de santé, incluant l'exercice physique régulier et une alimentation saine pour le coeur, reste la pierre angulaire de la prévention des maladies cardiovasculaires. Ces lignes directrices visent à fournir une plateforme pour une discussion constructive et une prise de décision partagée entre le patient et le prestataire de soins, afin que des décisions individuelles puissent être prises pour le dépistage, l'évaluation et le traitement des risques.
My commitment to securing appropriate redress for violations of women’s rights is rooted in many decades of social justice and human rights activism in my home country of South Africa. I was engaged ...in civil society activism and advocacy, both nationally and internationally, particularly around the issue of gender justice and promoted and protected gender equality during my time as head of a gender unit at a university law clinic and in my role as the former parliamentary commissioner of the Commission on Gender Equality. It was during my term as the United Nations (UN) special rapporteur on violence against women, its causes and consequences that I took up the issue of reparations and its transformative potential for women victims of violence, which was the focus of my first thematic report submitted to the UN Human Rights Council in 2010.
This article focuses on violence against women as a barrier to the realisation of women's civil, political, economic, social, cultural and developmental rights, as well as the consequences of this ...for the effective exercise of citizenship. The value of adopting a citizenship lens, identifying the nexus between violence against women and human rights, and adopting an approach that acknowledges the multiplicity, intersectionality and continuity of violence across the public and private spheres serves to assist in identifying and providing an analysis of the continuing challenges in the quest to eliminate violence against women. Owing to the scarcity of literature that explicitly highlights the link between human rights, citizenship and violence against women, the current analysis highlights some of the existing literature on a situated understanding of citizenship through a women's human rights lens, while the discussion on violence against women as a barrier to realising all human rights that enable the exercise of effective citizenship is largely underpinned by the work of the mandate of the Special Rapporteur on Violence against Women, its Causes and Consequences.
Patients in the treatment group also benefited from significant improvements in the Impact of Weight on Quality of Life-Lite Clinical Trials Version Physical Function and the Short Form-36v2 Health ...Survey acute version Physical Functioning scores. Additionally, although most participants were White (494 74%), the BMI criteria of at least 30 kg/m² or at least 27 kg/m² with one bodyweight-related comorbidity or more for inclusion in the study might not be appropriate for ethnic minorities, for whom the BMI cutoffs for adiposity-related disease are substantially lower.5 These factors limit the applicability of the study to a large number of individuals who might be considered for anti-obesity medication in the real world. The American Medical Association Council on Science and Public Health report acknowledged the limitations of BMI, describing it as an imperfect way to measure body fat.9 The landscape of obesity management would be well served by studies of longer duration, in ethnically diverse populations with specific comorbidities, across the lifespan, which report on outcomes beyond BMI and which provide head-to-head comparisons of weight loss pharmacotherapy.
Gender discrimination, both direct and indirect, is a leading cause of statelessness worldwide. Most often, direct discrimination is reflected in patriarchal nationality laws that restrict women’s ...ability to acquire, retain, and pass on their nationality to their children and/or spouses. There are also many indirect forms of discrimination owing to women’s often subordinate status that can impact women’s (and their children’s) vulnerability to statelessness. Overall, women are subject to a range of elevated and compounded risks of statelessness linked to patriarchal norms and deeply rooted gender inequalities. Despite the substantial impact of gender discrimination on statelessness, this issue is an understudied topic in the literature. This article discusses how gender discrimination impacts statelessness broadly and analyses how relevant international and selected Southern African and domestic law and policy frameworks have responded to this issue. First, the article briefly discusses some of the leading causes of statelessness arising from direct and indirect gender discrimination, and some of the key consequences of statelessness for women. Second, the article provides a critical gender analysis of the international legal framework on statelessness. It discusses how relevant international human rights legal and policy frameworks offer a robust protection of women’s nationality rights and gender equality. Third, the article analyses selected regional and national law and policy developments related to gender and statelessness in Southern Africa. Overall, while the analysis indicates progress in some areas, there remain ongoing challenges in bridging the statelessness gender discrimination gap and a need for further research in this area.
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