COVID-19, pandemic lockdowns and intimate partner violence among HIV-positive women in Ghana.

This study examines the prevalence and risk factors of physical, sexual, psychological, and economic violence during lockdowns associated with COVID-19 among HIV-positive women in Ghana. Data were collected in August 2021 from a cross-section of 538 HIV-positive women aged 18 years and older in the Lower Manya Krobo District in the Eastern region of Ghana. Logit models were used to explore relationships between women's self-reported experiences of physical, sexual, psychological /emotional, and economic violence under lockdown and key socio-economic and demographic characteristics. The findings indicate moderate to high prevalence of intimate partner violence (IPV) under lockdown in our sample: physical violence (30.1%), sexual violence (28.6%), emotional/psychological violence (53.7%), and economic violence (54.2%). IPV was higher on all four measures for educated women, poorer women, employed women, cohabiting and married women, and HIV seroconcordant couples.

OptoRheo: Simultaneous in situ micro-mechanical sensing and imaging of live 3D biological systems.

Biomechanical cues from the extracellular matrix (ECM) are essential for directing many cellular processes, from normal development and repair, to disease progression. To better understand cell-matrix interactions, we have developed a new instrument named 'OptoRheo' that combines light sheet fluorescence microscopy with particle tracking microrheology. OptoRheo lets us image cells in 3D as they proliferate over several days while simultaneously sensing the mechanical properties of the surrounding extracellular and pericellular matrix at a sub-cellular length scale. OptoRheo can be used in two operational modalities (with and without an optical trap) to extend the dynamic range of microrheology measurements. We corroborated this by characterising the ECM surrounding live breast cancer cells in two distinct culture systems, cell clusters in 3D hydrogels and spheroids in suspension culture. This cutting-edge instrument will transform the exploration of drug transport through complex cell culture matrices and optimise the design of the next-generation of disease models.

"Some are healthy and others not": Characterization of vended food products by Accra-based food retailers.

Background and objectives: Increasing the availability of healthy foods within food retail outlets can improve consumers' food environments. Such actions or inactions by food retailers may affect people's food purchasing and consumption behavior. This study explored Accra-based food retailers' perceptions and appreciation of "healthiness of food" as a concept. It also documented measures that food retailers adopt to encourage healthy food choices. Methods: In-person semi-structured interviews were conducted with owners and managers of Accra-based supermarkets (n = 7) and corner stores (n = 13) in March 2021. The interviews were recorded, transcribed, coded, and analyzed thematically. Results: The retailers' understanding of healthy food, or lack thereof, is exemplified by such expressions as "health, absence of disease, longevity, balanced diet, diversity, sanitation, and certification." A handful of retailers described what they sell as "products that meet consumer needs," "harmless," or "generally good." Very few retailers described the food they sell as "junk," high in sugar, fat, and salt, or energy-dense but nutrient poor foods, or as food that could pose some health risk to consumers. However, some retailers indicated that they advise their customers against the overconsumption of some foods. Conclusion: Overall, Accra-based retailers have a fair understanding of what constitutes healthy food - exhibiting limited knowledge of the connection between very salty, very sugary, and very fatty foods and health outcomes. Retailers in Accra require interventions that improve their food, health, and nutrition literacy. Improving retailers' food and nutrition literacy may improve the availability of healthier options in food retail outlets in Accra.

Availability of healthy and unhealthy foods in modern retail outlets located in selected districts of Greater Accra Region, Ghana.

Background: Intake of unhealthy foods is linked to the onset of obesity and diet-related non-communicable diseases (NCDs). Availability of unhealthy (nutritionally poor) foods can influence preference, purchasing and consumption of such foods. This study determined the healthiness of foods sold at modern retail outlets- supermarkets and mini-marts in the Greater Accra Region of Ghana. Methods: All modern retail outlets located in six districts of Greater Accra were eligible. Those < 200 m2 of floor area and with permanent structures were categorized as mini-marts; and those ≥200 m2 as supermarkets. Shelf length of all available foods were measured. Healthiness of food was determined using two criteria - the NOVA classification and energy density of foods. Thus, ultra-processed foods or food items with >225 kcal/100 g were classified as unhealthy. The ratio of the area occupied by unhealthy to healthy foods was used to determine the healthiness of modern retail outlets. Results: Of 67 retail outlets assessed, 86.6% were mini-marts. 85.0% of the total SHELF area was occupied by foods categorized as unhealthy (ranging from 9,262 m2 in Ashiaman Municipality to 41,892 m2 in Accra Metropolis). Refined grains/grain products were the most available, occupying 30.0% of the total food shelf space, followed by sugar-sweetened beverages (20.1% of total shelf space). The least available food group-unprocessed staples, was found in only one high income district, and occupied 0.1% of the total food shelf space. Retail outlets in two districts did not sell fresh fruits or fresh/unsalted canned vegetables. About two-thirds of food products available (n = 3,952) were ultra-processed. Overall, the ratio of ultra-processed-to-unprocessed foods ranged from 3 to 7 with an average (SD) of 5(2). Thus, for every healthy food, there were five ultra-processed ones in the studied retail outlets. Conclusion: This study reveals widespread availability of ultra-processed foods in modern retail outlets within the selected districts. Toward a healthier food retail environment, public health and food regulators, in partnership with other stakeholders need to institute measures that improve availability of healthy foods within supermarkets and mini-marts.

Advertising of unhealthy foods and beverages around primary and junior high schools in Ghana's most urbanized and populous region.

Introduction: The advertising of energy-dense, nutrient-poor foods and beverages is a common feature in obesogenic food environments. Such advertising, within and around settings where children live, learn, and play, negatively affects their food acquisition and consumption. We examined the extent and nature of food and beverage advertising around primary and junior high schools in Ghana's most populous and urbanized region, Greater Accra. Materials and methods: Outdoor advertisements for foods and beverages within a 250 m road network distance of 200 randomly sampled schools were geocoded. For each food and beverage advertisement, information was collected on the setting, type, size, and number of product types featured in the advertisement. Promotional techniques (promotional characters and premium offers) used in advertisements were documented. Advertised foods and beverages were classified using the INFORMAS and NOVA food classification systems. Results: A total of 5,887 advertisements were identified around the schools surveyed, 42% of which were for foods and beverages. Advertisements were most prevalent at food outlets (78% of all food advertisements), but also along roads and on non-food structures. Overall, 70% of food advertisements featured non-core/unhealthy products, while 12 and 14% had core/healthy and miscellaneous (including soup cubes, seasonings, and tea) products. About 4% of food advertisements had only a product/brand name or logo displayed. One out of two of the foods and beverages advertised were ultra-processed foods, 30% processed, 3% processed culinary ingredients, and 17% unprocessed or minimally processed foods. Sugar-sweetened beverages were the most advertised food product type (32%). Promotional characters were found on 14% of all food advertisements (most-69% were cartoons or manufacturer's characters), while 8% of all food advertisements had premium offers (including price discounts and gift/collectables). Conclusions: There is an abundance of unhealthy food advertisements around primary and junior high schools in the Greater Accra Region. Policy actions such as restricting the promotion of unhealthy foods in children's settings are needed to protect pupils from such advertising practices.

Synthesis, characterisation and evaluation of hyperbranched N-(2-hydroxypropyl) methacrylamides for transport and delivery in pancreatic cell lines in vitro and in vivo.

Hyperbranched polymers have many promising features for drug delivery, owing to their ease of synthesis, multiple functional group content, and potential for high drug loading with retention of solubility. Here we prepared hyperbranched N-(2-hydroxypropyl)methacrylamide (HPMA) polymers with a range of molar masses and particle sizes, and with attached dyes, radiolabel or the anticancer drug gemcitabine. Reversible addition-fragmentation chain transfer (RAFT) polymerisation enabled the synthesis of pHPMA polymers and a gemcitabine-comonomer functionalised pHPMA polymer pro-drug, with diameters of the polymer particles ranging from 7-40 nm. The non-drug loaded polymers were well-tolerated in cancer cell lines and macrophages, and were rapidly internalised in 2D cell culture and transported efficiently to the centre of dense pancreatic cancer 3D spheroids. The gemcitabine-loaded polymer pro-drug was found to be toxic both to 2D cultures of MIA PaCa-2 cells and also in reducing the volume of MIA PaCa-2 spheroids. The non-drug loaded polymers caused no short-term adverse effects in healthy mice following systemic injection, and derivatives of these polymers labelled with 89Zr-were tracked for their distribution in the organs of healthy and MIA PaCa-2 xenograft bearing Balb/c nude mice. Tumour accumulation, although variable across the samples, was highest in individual animals for the pHPMA polymer of ∼20 nm size, and accordingly a gemcitabine pHPMA polymer pro-drug of ∼18 nm diameter was evaluated for efficacy in the tumour-bearing animals. The efficacy of the pHPMA polymer pro-drug was very similar to that of free gemcitabine in terms of tumour growth retardation, and although there was a survival benefit after 70 days for the polymer pro-drug, there was no difference at day 80. These data suggest that while polymer pro-drugs of this type can be effective, better tumour targeting and enhanced in situ release remain as key obstacles to clinical translation even for relatively simple polymers such as pHPMA.

Perspective: Food Environment Research Priorities for Africa-Lessons from the Africa Food Environment Research Network.

Over the last 2 decades, many African countries have undergone dietary and nutrition transitions fueled by globalization, rapid urbanization, and development. These changes have altered African food environments and, subsequently, dietary behaviors, including food acquisition and consumption. Dietary patterns associated with the nutrition transition have contributed to Africa's complex burden of malnutrition-obesity and other diet-related noncommunicable diseases (DR-NCDs)-along with persistent food insecurity and undernutrition. Available evidence links unhealthy or obesogenic food environments (including those that market and offer energy-dense, nutrient-poor foods and beverages) with suboptimal diets and associated adverse health outcomes. Elsewhere, governments have responded with policies to improve food environments. However, in Africa, the necessary research and policy action have received insufficient attention. Contextual evidence to motivate, enable, and create supportive food environments in Africa for better population health is urgently needed. In November 2020, the Measurement, Evaluation, Accountability, and Leadership Support for Noncommunicable Diseases Prevention Project (MEALS4NCDs) convened the first Africa Food Environment Research Network Meeting (FERN2020). This 3-d virtual meeting brought researchers from around the world to deliberate on future directions and research priorities related to improving food environments and nutrition across the African continent. The stakeholders shared experiences, best practices, challenges, and opportunities for improving the healthfulness of food environments and related policies in low- and middle-income countries. In this article, we summarize the proceedings and research priorities identified in the meeting to advance the food environment research agenda in Africa, and thus contribute to the promotion of healthier food environments to prevent DR-NCDs, and other forms of malnutrition.

Amorphous solid dispersions: Utilization and challenges in preclinical drug development within AstraZeneca.

The poor aqueous solubility of many active pharmaceutical ingredients (APIs) dominates much of the early drug development portfolio and poses a major challenge in pharmaceutical development. Polymer-based amorphous solid dispersions (ASDs) are becoming increasingly common and offer a promising formulation strategy to tackle the solubility and oral absorption issues of these APIs. This review discusses the design, manufacture, and utilisation of ASD formulations in preclinical drug development, with a key focus on the pre-formulation assessments and workflows employed at AstraZeneca.

Effects of Polymer 3D Architecture, Size, and Chemistry on Biological Transport and Drug Delivery In Vitro and in Orthotopic Triple Negative Breast Cancer Models.

The size, shape, and underlying chemistries of drug delivery particles are key parameters which govern their ultimate performance in vivo. Responsive particles are desirable for triggered drug delivery, achievable through architecture change and biodegradation to control in vivo fate. Here, polymeric materials are synthesized with linear, hyperbranched, star, and micellar-like architectures based on 2-hydroxypropyl methacrylamide (HPMA), and the effects of 3D architecture and redox-responsive biodegradation on biological transport are investigated. Variations in "stealth" behavior between the materials are quantified in vitro and in vivo, whereby reduction-responsive hyperbranched polymers most successfully avoid accumulation within the liver, and none of the materials target the spleen or lungs. Functionalization of selected architectures with doxorubicin (DOX) demonstrates enhanced efficacy over the free drug in 2D and 3D in vitro models, and enhanced efficacy in vivo in a highly aggressive orthotopic breast cancer model when dosed over schedules accounting for the biodistribution of the carriers. These data show it is possible to direct materials of the same chemistries into different cellular and physiological regions via modulation of their 3D architectures, and thus the work overall provides valuable new insight into how nanoparticle architecture and programmed degradation can be tailored to elicit specific biological responses for drug delivery.

Amphiphilic tri- and tetra-block co-polymers combining versatile functionality with facile assembly into cytocompatible nanoparticles.

In order for synthetic polymers to find widespread practical application as biomaterials, their syntheses must be easy to perform, utilising freely available building blocks, and should generate products which have no adverse effects on cells or tissue. In addition, it is highly desirable that the synthesis platform for the biomaterials can be adapted to generate polymers with a range of physical properties and macromolecular architectures, and with multiple functional handles to allow derivatisation with 'actives' for sensing or therapy. Here we describe the syntheses of amphiphilic tri- and tetra-block copolymers, using diazabicyclo[5.4.0]undec-5-ene (DBU) as a metal-free catalyst for ring-opening polymerisations of the widely-utilised monomer lactide combined with a functionalised protected cyclic carbonate. These syntheses employed PEGylated macroinitiators with varying chain lengths and architectures, as well as a labile-ester methacrylate initiator, and produced block copolymers with good control over monomer incorporation, molar masses, side-chain and terminal functionality and physico-chemical properties. Regardless of the nature of the initiators, the fidelity of the hydroxyl end group was maintained as confirmed by a second ROP chain extension step, and polymers with acryloyl/methacryloyl termini were able to undergo a second tandem reaction step, in particular thiol-ene click and RAFT polymerisations for the production of hyperbranched materials. Furthermore, the polymer side-chain functionalities could be easily deprotected to yield an active amine which could be subsequently coupled to a drug molecule in good yields. The resultant amphiphilic copolymers formed a range of unimolecular or kinetically-trapped micellar-like nanoparticles in aqueous environments, and the non-cationic polymers were all well-tolerated by MCF-7 breast cancer cells. The rapid and facile route to such highly adaptable polymers, as demonstrated here, offers promise for a range of bio materials applications.

Waiving in vivo studies for monoclonal antibody biosimilar development: National and global challenges.

Biosimilars are biological medicinal products that contain a version of the active substance of an already authorised original biological medicinal product (the innovator or reference product). The first approved biosimilar medicines were small proteins, and more recently biosimilar versions of innovator monoclonal antibody (mAb) drugs have entered development as patents on these more complex proteins expire. In September 2013, the first biosimilar mAb, infliximab, was authorised in Europe. In March 2015, the first biosimilar (Zarxio™, filgrastim-sndz, Sandoz) was approved by the US Food and Drug Administration; however, to date no mAb biosimilars have been approved in the US. There are currently major differences between how biosimilars are regulated in different parts of the world, leading to substantial variability in the amount of in vivo nonclinical toxicity testing required to support clinical development and marketing of biosimilars. There are approximately 30 national and international guidelines on biosimilar development and this number is growing. The European Union's guidance describes an approach that enables biosimilars to enter clinical trials based on robust in vitro data alone; in contrast, the World Health Organization's guidance is interpreted globally to mean in vivo toxicity studies are mandatory. We reviewed our own experience working in the global regulatory environment, surveyed current practice, determined drivers for nonclinical in vivo studies with biosimilar mAbs and shared data on practice and study design for 25 marketed and as yet unmarketed biosimilar mAbs that have been in development in the past 5y. These data showed a variety of nonclinical in vivo approaches, and also demonstrated the practical challenges faced in obtaining regulatory approval for clinical trials based on in vitro data alone. The majority of reasons for carrying out nonclinical in vivo studies were not based on scientific rationale, and therefore the authors have made recommendations for a data-driven approach to the toxicological assessment of mAb biosimilars that minimises unnecessary use of animals and can be used across all regions of the world.