Biologics for treating axial spondyloarthritis

Introduction: Spondyloarthritis (SpA) encompasses a heterogeneous group of diseases sharing genetic, immunological, clinical and imaging features. Axial spondyloarthritis (axSpA) refers to a subgroup characterised predominately by inflammation of the axial skeleton with subsequent symptoms of chronic (often inflammatory) back pain and sacroiliitis. There is a strong association with the major histocompatibility complex (MHC) class I allele human leukocyte antigen (HLA) B27. In the last decade, there has been significant progress in earlier detection of the disease and the molecular mechanisms involved in its pathogenesis. The subsequent introduction of anti-tumour necrosis factor (TNF) has revolutionised the treatment of patients with axSpA.

Areas covered: In this article, we review the current biologic therapies for axSpA, the emergence of biosimilars, predictors of response, primary and secondary failure and new biologics on the horizon.

Expert opinion: There have been significant advances in the treatment of axSpA. Beyond the clear efficacy of anti-TNF inhibition, IL-17 offers an alternative therapeutic target and there is promise from inhibition of the IL-17/IL-23 pathway and small molecules, such as Janus kinase (JAK) inhibitors. Biosimilars have offered greater affordability and choice within this increasingly growing field of therapeutics.     

Household Debt and Relation to Intimate Partner Violence and Husbands' Attitudes Toward Gender Norms: A Study Among Young Married Couples in Rural Maharashtra,India

Objective

Evidence has linked economic hardship with increased intimate partner violence (IPV) perpetration among males. However, less is known about how economic debt or gender norms related to men''s roles in relationships or the household, which often underlie IPV perpetration, intersect in or may explain these associations. We assessed the intersection of economic debt, attitudes toward gender norms, and IPV perpetration among married men in India.

Methods

Data were from the evaluation of a family planning intervention among young married couples (n=1,081) in rural Maharashtra, India. Crude and adjusted logistic regression models for dichotomous outcome variables and linear regression models for continuous outcomes were used to examine debt in relation to husbands'' attitudes toward gender-based norms (i.e., beliefs supporting IPV and beliefs regarding male dominance in relationships and the household), as well as sexual and physical IPV perpetration.

Results

Twenty percent of husbands reported debt. In adjusted linear regression models, debt was associated with husbands'' attitudes supportive of IPV (b=0.015, p=0.004) and norms supporting male dominance in relationships and the household (b=0.006, p=0.003). In logistic regression models adjusted for relevant demographics, debt was associated with perpetration of physical IPV (adjusted odds ratio [AOR] = 1.4, 95% confidence interval [CI] 1.1, 1.9) and sexual IPV (AOR=1.6, 95% CI 1.1, 2.1) from husbands. These findings related to debt and relation to IPV were slightly attenuated when further adjusted for men''s attitudes toward gender norms.

Conclusion

Findings suggest the need for combined gender equity and economic promotion interventions to address high levels of debt and related IPV reported among married couples in rural India.Intimate partner violence (IPV) perpetrated by male partners or husbands occurs in high proportions globally as well as in low- to middle-income countries such as India.^1,2 One recent multi-country household study found that 37% of men in India reported having ever perpetrated physical violence against a female intimate partner in their lifetime. The health burden of IPV has been well demonstrated, with significant effects on women''s sexual and reproductive health (e.g., increased sexually transmitted infections, unintended pregnancy, and poor pregnancy outcomes),^3–5 mental health (e.g., anxiety, depression, and substance use),^6,7 as well as a multitude of other poor health outcomes among women and their children (e.g., maternal and child malnutrition and infant death).^8,9Recent research among women has identified economic hardship (e.g., financial dependence on male partners and economic instability) as increasing women''s vulnerability to IPV.^10,11 Although studies have found an association between economic stressors and reports of male IPV perpetration,^12–16 no research has examined debt in relation to these outcomes.Debt and other economic decisions in the context of marriage, particularly in rural India, are largely under the control of husbands. Taking on debt may be associated with economic hardship, heightening stress levels among men, and, in turn, IPV. Also, previous work documenting the association between economic hardship and increased IPV perpetration by males^12–15 has largely been explained by perceptions related to men''s roles financially within the family (e.g., men who do not feel that they are providing financially for their families may perceive that they are not fulfilling their roles as husbands/males, and this perception related to lack of role fulfillment may escalate into violence). Given that a decision to take on debt appears to be largely controlled by men in this context and likely tied to their perceived role of providing financially for the family, a man''s decision to take out loans may be determined, in part, by their support of masculine gender norms (e.g., a man''s role in the family and male dominance and control in the household). In addition, given previous work highlighting the association between masculine gender norms and a number of risk behaviors among boys and men (e.g., substance and tobacco use and behaviors resulting in unintentional injury),^17–21 such gender norms may also be linked to taking on risks associated with debt, as well as debt-acquiring behaviors (e.g., spending money on nonessential goods such as alcohol).Gender norms pertaining to IPV, relationships, and the household are also important driving factors in terms of understanding men''s behaviors related to IPV. Cross-cultural research has shown that societies with greater gender inequities in social norms and policies have a higher prevalence of IPV.²¹ In the context of India and elsewhere, women''s low status in families and high levels of societal tolerance and acceptance of IPV promote IPV.²²More research is needed to understand economic hardship, and debt specifically, in relation to attitudes toward gender norms and IPV perpetration. Many studies have hypothesized that stress related to economic hardship and debts increases IPV perpetration;^12–15 however, less research has sought to understand the role of attitudes supportive of men''s more traditional gender norms in relationships or households in contributing to decisions to take on debt as well as in terms of explaining its association with increased IPV perpetration. Increased understanding of the mechanisms that explain associations between economic hardship/debt and IPV is needed to inform prevention approaches, particularly given the increasing number of economic promotion interventions being implemented globally and throughout India.Thus, the primary objective of the current study was to assess household debt in relation to husbands'' support of gender-inequitable norms and norms promoting IPV as well as husbands'' use of IPV against wives. The secondary objective of this study was to assess whether or not gender-based attitudes are important factors in debt and IPV, as well as in explaining an association between debt and increased risk for IPV perpetration among husbands.     

Quantification of Antioxidant Contents in Sweet Pepper as Influenced by Planting Time and Fruit Picking Stage

The present study reports the quantification of changes in the contents of plant pigments and ascorbic acid as influenced by the planting time and fruit picking stages in sweet pepper. The crop was planted on five different dates at 10 days interval in randomized block design under open field conditions in temperate area to quantify the changes which took place in the contents of plant pigments and ascorbic acid in green and red fruits. The results showed that the planting time and fruit picking stage had significant (p ≤ 0.05) influence on plant pigments and ascorbic acid contents in sweet pepper. The last week of May was observed as the optimal planting time when fruits exhibited higher contents of lycopene, β-carotene and ascorbic acid. The red fruit picking stage had significantly higher concentration of these phytonutrients than the green picking stage. In order to pick-up fruits at right stage and time with high plant pigments and ascorbic acid contents, these results would help meet out the increasing demand of sweet pepper quality fruits.     

Biodistribution and targeting potential assessment of mucoadhesive chitosan nanoparticles designed for ulcerative colitis via scintigraphy

In the present investigation we have prepared and characterized curcumin (CN)-containing chitosan nanoparticles (CS-NPs) coated with Eudragit FS 30D for colon-specific drug delivery for treatment of ulcerative colitis. Methods: CS-NPs were prepared by ionic gelation using tripolyphosphate. To specify pH sensitive delivery, CS–CN-NPs were coated with Eudragit FS 30D by using a solvent evaporation method. Different process parameters were evaluated, and the optimized formulation was characterized by particle size, size distribution, zeta potential and encapsulation efficiency before lyophilization. The lyophilized product was further subjected to Fourier-transform infrared spectroscopy, and particle morphology and in vitro drug release in different media were studied. Results: the kinetics of in vitro drug release from the CS–CN-NPs revealed sustained release behaviour of the developed carriers. In vivo biodistribution study by gamma-scintigraphy showed good accumulation of the developed nanocarriers in the colonic region. Conclusion: sustained and pH stimulated delivery of CN to the colon was successfully attained via coating of CS-NPs with Eudragit FS 30D to circumvent poor absorption and availability of CN.

In the present investigation we have prepared and characterized curcumin (CN)-containing chitosan nanoparticles (CS-NPs) coated with Eudragit FS 30D for colon-specific drug delivery for treatment of ulcerative colitis.     

Synthesis of non-toxic,biocompatible, and colloidal stable silver nanoparticle using egg-white protein as capping and reducing agents for sustainable antibacterial application

For nearly a decade, silver nanoparticles (AgNPs) have been the most prevalent commercial nanomaterials products widely used in different biomedical applications due to their broad-spectrum antimicrobial activity. However, their poor long-term stability in different environments, namely, pH, ionic strength, and temperature, and cytotoxicity toward mammalian cells has restricted their more extensive applications. Hence, there is urgent need to develop highly biocompatible, non-toxic, and stable silver nanoparticles for wide-ranging environments and applications. In the present study, a simple, sustainable, cost-effective and green method has been developed to prepare highly stable aqueous colloidal silver nanoparticles (AgNPs-EW) using the ovalbumin, ovotransferrin, and ovomucoid of egg-white as reducing and capping agents accomplished under the irradiation of direct sunlight. Then, we evaluated the effects of freezing–drying (lyophilization) and freeze–thaw cycles on the stability of AgNPs-EW in aqueous solution under visual inspection, transmission electron microscopy, and absorbance spectroscopy. In addition, we studied the antibacterial activity against Salmonella typhimurium and Escherichia coli, carried out biocompatibility studies on chicken blood, and tested acute, chronic toxicity in Drosophila melanogaster. The results suggest that AgNPs-EW did not aggregate upon freeze-thawing and lyophilization, thus exhibiting remarkable stability. The antibacterial activity results showed that the AgNPs-EW had the highest antibacterial activity, and the minimum inhibitory concentration (MIC) of AgNPs-EW for E. Coli and S. typhimurium were 4 and 6 μg ml⁻¹, respectively. The biocompatibility study revealed that the AgNPs-EW did not induce any hemolytic effect or structural damage to the cell membranes of chicken erythrocytes up to a concentration of 12 μg ml⁻¹. Similarly, no acute and chronic toxicity was observed on melanization, fecundity, hatchability, viability, and the duration of development in the 1^st generation of Drosophila melanogaster at the concentration range of 10 mg L⁻¹ to 100 mg L⁻¹ of AgNPs-EW, and all the flies completed their full developmental cycle. Therefore, the present study successfully demonstrated the green and sustainable preparation of non-toxic AgNPs-EW having good biocompatibility, enhanced colloidal stability, and antibacterial activity. Hence, the synthesized AgNPs-EW could be used for the development of an antimicrobial formulation for controlling microbial infection.

For nearly a decade, silver nanoparticles (AgNPs) have been the most prevalent commercial nanomaterials products widely used in different biomedical applications due to their broad-spectrum antimicrobial activity.     

WHO HEARTS: A Global Program to Reduce Cardiovascular Disease Burden: Experience Implementing in the Americas and Opportunities in Canada

Globally, cardiovascular diseases (CVDs) are the leading cause of death. Viewed as a threat to the global economy, the United Nations included reducing noncommunicable diseases, including CVDs, in the 2030 sustainable development goals, and the World Health Assembly agreed to a target to reduce noncommunicable diseases 25% by the year 2025. In response, the World Health Organisation led the development of HEARTS, a technical package to guide governments in strengthening primary care to reduce CVDs. HEARTS recommends a public health and health system approach to introduce highly simplified interventions done systematically at a primary health care level and has a focus on hypertension as a clinical entry point. The HEARTS modules include healthy lifestyle counselling, evidence-based treatment protocols, access to essential medicines and technology, CVD risk-based management, team-based care, systems for monitoring, and an implementation guide. There are early positive global experiences in implementing HEARTS. Led by the Pan American Health Organisation, many national governments in the Americas are adopting HEARTS and have shown early success. Unfortunately, in Canada hypertension control is declining in women since 2010-2011 and the dramatic reductions in rates of CVD seen before 2010 have flattened when age adjusted and increased for rates that are not age adjusted, and there are marked increases in absolute numbers of Canadians with adverse CVD outcomes. Several steps that Canada could take to enhance hypertension control are outlined, the core of which is to implement a strong governmental nongovernmental collaborative strategy to prevent and control CVDs, focusing on HEARTS.