CT109-SN-38, a Novel Antibody-drug Conjugate with Dual Specificity for CEACAM5 and 6, Elicits Potent Killing of Pancreatic Cancer Cells.

BACKGROUND: CEACAM5 and CEACAM6 are glycosylphosphatidylinositol (GPI)- linked members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family, which are frequently upregulated in epithelial cancers where they contribute to invasion, metastasis, immune evasion, and resistance to anoikis. CT109 is a novel antibody with dual specificity to both CEACAM5 and 6. OBJECTIVE: In this study, we aimed to perform the preclinical characterization of CT109 and antibody- drug conjugate (ADCs) derivatives of CT109, focusing on CT109-SN-38. METHODS: CT109's cognate epitope was characterized by scanning mutagenesis. CT109 specificity and internalization kinetics were assessed by immunoblot and flow cytometry, respectively. Cognate antigen expression prevalence in colorectal cancer and normal tissue arrays was determined by immunohistochemistry. CT109 conjugations were generated by the reaction of reduced CT109 cysteines with maleimide-functionalized payload linkers. In vitro cytotoxic activity of CT109 ADCs was characterized on antigen-positive and negative pancreatic ductal adenocarcinoma cell (PDAC) lines using a luminometric viability assay. In vivo efficacy of CT109-SN-38 was assessed on a PDAC tumor xenograft model at 10 and 25 mg/kg concentrations. RESULTS: CT109 showed to bind a glycoepitope centered on N309. CT109 is internalized in the CEACAM5+/CEACAM6+ double-positive PDAC line, BxPC-3, with a t1/2 of 2.3 hours. CT109 ADCs elicit a dose and antigen-dependent cytotoxic effect, with CT109-SN-38 exhibiting an IC50 value of 21 nM in BxPC-3 cells. In a BxPC-3 tumor xenograft model, CT109-SN-38 reduced tumor growth and induced regression in 3/10 mice at 25 mg/kg concentration. CONCLUSIONS: These data suggest that further preclinical and clinical development of CT109-SN-38 is warranted.

Development and Validation of Nutrition and Food Safety Educational Material for Fish Processors in Nigeria.

INTRODUCTION: fish can be an affordable and accessible animal-source food in many Low- and Middle-Income Countries (LMIC). BACKGROUND: Traditional fish processing methods pose a risk of exposing fish to various contaminants that may reduce their nutritional benefit. In addition, a lack of literacy may increase women fish processors' vulnerability to malnutrition and foodborne diseases. OBJECTIVE: The overall aim of the project was to educate women and youth fish processors in Delta State, Nigeria about the benefit of fish in the human diet and to develop low literacy tools to help them better market their products. The objective of this study was to describe the development and validation of a low-literacy flipbook designed to teach women fish processors about nutrition and food safety. METHOD: developing and validating instructional material requires understanding the population, high-quality and relevant graphics, and the involvement of relevant experts to conduct the content validation using the Content Validity Index (CVI) and the index value translated with the Modified Kappa Index (k). RESULT: The Item-level Content Validity Index (I-CVI) value of all domains evaluated at the initial stage was 0.83 and the Scale-level Content Validity Index (S-CVI) was 0.90. At the final stage, the material was validated with CVI 0.983 by four experts and satisfied the expected minimum CVI value for this study (CVI ≥ 0.83, p-value = 0.05). The overall evaluation of the newly developed and validated flipbook was "excellent". CONCLUSIONS: the developed material was found to be appropriate for training fish processors in Nigeria in nutrition and food safety and could be modified for a population of fish processors in other LMICs.

Perceived impacts of a pilot agricultural livelihood and microfinance intervention on agricultural practices, food security and nutrition for Kenyans living with HIV.

INTRODUCTION: Agriculture is the primary source of income and household food for >75% of rural Kenyans, including people living with HIV (PLHIV), making agricultural yields an important factor in food security and nutrition. Previous studies have shown the interconnectedness of food insecurity, malnutrition, and poor HIV health by elucidating that having one of these conditions increases the likelihood and severity of having another. However, few studies have explored the linkages between agricultural practices, food security and nutrition for PLHIV, or how agricultural livelihood interventions may affect these domains. This study aimed to examine the mechanisms through which an agricultural livelihood intervention can positively or negatively affect agricultural practices, food security, and nutrition for PLHIV. METHODS: From July 2012-August 2013, we interviewed participants with HIV on antiretroviral therapy (ART) enrolled in a pilot randomized controlled trial (RCT) of an agricultural livelihood and finance intervention to understand the mechanisms through which the intervention may have affected HIV health outcomes. The intervention included agricultural and finance training and a microfinance loan to purchase the MoneyMaker hip pump, a human-powered water pump, seeds, and other farming implements. A purposive sample of 45 intervention and a random subset of 9 control participants were interviewed at 12-month endline visit with a subset of 31 intervention participants interviewed longitudinally at both the 3- and 12-month visits. Transcripts were double coded using an inductive-deductive approach and analyzed for impacts of the intervention on agricultural practices, food security, and nutrition using analytic reports for each key theme. RESULTS: All intervention participants described improvements in agricultural practices and yields attributed to the intervention while many also described improvements in income; these changes in turn contributed to improved HIV health, including suppressed viral loads, and a few people noted improved immunologic parameters. Key mechanisms included the knowledge gained from agricultural training which led to improved yields and access to new markets. The use of the irrigation pump was also identified as an additional, lesser important mechanism. All intervention participants reported sustained improvements in food security and nutrition through increased yields and income from the sale of excess crops used to purchase food, and diversification of fresh fruits and vegetables consumed through agricultural production. This led to self-reported weight gain which was a nutritional mechanism towards improved health. CONCLUSIONS: Agricultural and finance interventions that improve farming practices could lead to improved health outcomes through the pathways of improved food security, income, and diversified diet. The results from this study helped the team to enhance the intervention prior to implementation of the larger cluster RCT (cRCT). By understanding how agricultural livelihood interventions act upon pathways towards improved health, policy options can be developed and implemented to include components that are needed to achieve sustainable outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01548599.

Fish and Fish-Based Products for Nutrition and Health in the First 1000 Days: A Systematic Review of the Evidence from Low and Middle-Income Countries.

Fish provide essential nutrients for the critical window of growth and development in the first 1000 d of life and are thus an attractive option for inclusion in nutrition-sensitive and nutrition-specific programming. We conducted a systematic review of the evidence for fish and fish-based products for nutrition and health outcomes during the first 1000 d of life in low- and middle-income countries, searching the peer-reviewed and gray literature from 1999 to 2020. Databases included PubMed, Web of Science, Embase, ProQuest, and the Clinical Trials repository. Our search returned 1135 articles, 39 of which met the inclusion criteria. All studies were dual evaluated for risk of bias. Of the included studies, 18 measured maternal health and nutrition outcomes and 24 measured infant/child outcomes (3 measured both). Our search uncovered 10 impact evaluations, all of which measured consumption of fish or fish-based complementary food products in children aged 6-24 mo. We did not find strong evidence for fish consumption in children improving child growth from the impact evaluations; however, the studies were highly heterogeneous in their design and likely underpowered to detect an effect. Results from observational studies were mixed but provided evidence that adding fish to maternal and child diets is associated with improved nutrition outcomes, such as reducing the risk of anemia and improving vitamin D status. Given the nutrient richness of fish and the fact that production is often more environmentally friendly as compared with other animal source foods, more robust evidence is needed on the role of fish consumption in nutrition interventions to inform policy and programming recommendations in low- and middle-income countries.

A randomised controlled trial to test the effects of fish aggregating devices (FADs) and SBC activities promoting fish consumption in Timor-Leste: A study protocol.

Timor-Leste is one of the world's most malnourished nations where micronutrient-deficient diets are a contributing factor to the prevalence of child stunting, currently estimated to be 45.6% of children under five. Fish are an important source of nutrients and one that may assist the country's predominantly rural population of agriculturalists to exit poverty and malnutrition. However, a small national fishing fleet producing low catch volumes places fish out of reach of most inland and upland populations where it is needed most. Fish consumption is very low in rural, inland areas compared to coastal, regional, and global averages. This study is a one-year, partially masked, cluster-randomized controlled trial among families living in rural, inland Timor-Leste. We aim to test and compare the effects of two treatments, alone and in combination, on the frequency and volume of household fish consumption in rural, inland areas as a proxy for improved dietary diversity and micronutrient intake. Treatment 1 is the installation of nearshore, moored fish aggregating devices (FADs) to improve catch rates with existing fishing gears. Treatment 2 is a social and behaviour change (SBC) activity to promote fish consumption. Villages in inland communities will be randomized to receive treatment 1, treatment 2, both treatments, or neither treatment. Data will be collected at baseline (prior to the rollout of the treatments) and endline. Our study will determine the impact of an improved supply of fish, along with nutrition-oriented SBC activities, on the fish purchasing and consumption practices of rural, inland households. Findings from this study are urgently needed by Small Island Developing States to guide policy and investment decisions on how best to improve households' diets using locally available, nutrient-dense foods such as fish. Investments such as these are needed to break the cycle of malnutrition. This trial is registered at clinicaltrials.gov (NCT04729829). Trial registration: Trial registered at clinicaltrials.gov Identifier: NCT04729829.

Metal Contents in Fish from the Bay of Bengal and Potential Consumer Exposure-The EAF-Nansen Programme.

Fish represent an important part of the Sri Lankan and Bangladeshi diet. However, fish is also a source of contaminants that may constitute a health risk to consumers. The aim of this study was to analyse the contents of arsenic, cadmium, mercury, and lead in 24 commonly consumed marine fish species from the Bay of Bengal and to assess the potential health risk associated with their consumption. Mercury and lead contents did not exceed the maximum limits for any of the sampled species, and consumer exposure from estimated daily consumption was assessed to be minimal for adults and children. Numerous samples exceeded the maximum limit for cadmium (58%), particularly those of small size (≤25 cm). However, consumer exposure was insignificant, and health assessment showed no risk connected to consumption. These data represent an important contribution to future risk/benefit assessments related to the consumption of fish.

Dried small fish provide nutrient densities important for the first 1000 days.

Inadequate nutrient intakes are prevalent among many populations in sub-Saharan Africa and increasing fish consumption among pregnant/lactating women and children is one strategy to improve diets and address nutrient deficiencies. We report the nutrient content of two fish-based recipes-fish powder and fish chutney-that contain dried small fish available in local markets in Zambia. The contribution of a serving of each recipe to the recommended daily intakes of iron, zinc, calcium and docosahexaenoic acid (DHA) for pregnant/lactating women and children 6-24 months was calculated because these nutrients are commonly deficient in African diets. We found that one 10-g serving of fish powder provides 20% or more of the daily calcium recommendation and 37% or more of the daily DHA recommendation for both pregnant/lactating women and children. A 30-g serving of fish chutney provides over 40% of the daily calcium recommendation for pregnant women and over 50% for lactating women. Additionally, we investigated the nutrient density (nutrients per kilocalorie) of the fish powder and compared it with the nutrient density of a small-quantity lipid-based nutrient supplement plus (SQ-LNS-plus). SQ-LNS-plus is designed to enhance children's diets by providing micronutrients and DHA. Fish powder is similar to SQ-LNS-plus in iron and zinc density and even higher in calcium and DHA density. Consuming dried small fish as part of a daily meal can be a viable strategy for combatting nutrient deficiencies in the first 1000 days.

Selective adsorption of arsenic over phosphate by transition metal cross-linked chitosan.

The ability of transition metal chitosan complexes (TMCs) of varying valence and charge to selectively adsorb As(III) and As(V) over their strongest adsorptive competitor, phosphate is examined. Fe(III)-chitosan, Al(III)-chitosan, Ni(II)-chitosan, Cu(II)-chitosan, and Zn(II)-chitosan are synthesized, characterized via Attenuated Total Reflectance-Fourier Transform Infrared spectroscopy (ATR-FTIR) and X-ray Diffractometry (XRD), and their selective sorption capabilities towards As(III) and As(V) in the presence of phosphate are evaluated. It was found that the stability of the metal-chitosan complexes varied, with Al(III)- and Zn(II)-chitosan forming very unstable complexes resulting in precipitation of gibbsite, and Wulfingite and Zincite, respectively. Cu(II)-, Ni(II)-, and Fe(III)-chitosan formed a mixture of monodentate and bidentate complexes. The TMCs which formed the bidentate complex (Cu(II)-, Ni(II)-, and Fe(III)-) showed greater adsorption capability for As(V) in the presence of phosphate. Using the binary separation factor ∝t/c, it can be shown that only Fe(III)-chitosan is selective for As(V) and As(III) over phosphate. Density Functional Theory (DFT) modeling and extended X-ray adsorption fine structure (EXAFS) determined that Fe(III)-chitosan and Ni(II)-chitosan adsorbed As(V) and As(III) via inner-sphere complexation, while Cu(II)-chitosan formed mainly outer-sphere complexes with As(V) and As(III). These differences in complexation likely result in the observed differences in selective adsorption capability towards As(V) and As(III) over phosphate. It is hypothesized that the greater affinity of Fe(III)- and Ni(II)-chitosan towards As(V) and As(III) compared to Cu(II)-chitosan is due to their forming less-stable, more reactive chitosan complexes as predicted by the Irving Williams Series.

Exploring the Mechanisms of Selectivity for Environmentally Significant Oxo-Anion Removal during Water Treatment: A Review of Common Competing Oxo-Anions and Tools for Quantifying Selective Adsorption.

Development of novel adsorbents often neglects the competitive adsorption between co-occurring oxo-anions, overestimating realistic pollutant removal potentials, and overlooking the need to improve selectivity of materials. This critical review focuses on adsorptive competition between commonly co-occurring oxo-anions in water and mechanistic approaches for the design and development of selective adsorbents. Six "target" oxo-anion pollutants (arsenate, arsenite, selenate, selenite, chromate, and perchlorate) were selected for study. Five "competing" co-occurring oxo-anions (phosphate, sulfate, bicarbonate, silicate, and nitrate) were selected due to their potential to compete with target oxo-anions for sorption sites resulting in decreased removal of the target oxo-anions. First, a comprehensive review of competition between target and competitor oxo-anions to sorb on commonly used, nonselective, metal (hydr)oxide materials is presented, and the strength of competition between each target and competitive oxo-anion pair is classified. This is followed by a critical discussion of the different equations and models used to quantify selectivity. Next, four mechanisms that have been successfully utilized in the development of selective adsorbents are reviewed: variation in surface complexation, Lewis acid/base hardness, steric hindrance, and electrostatic interactions. For each mechanism, the oxo-anions, both target and competitors, are ranked in terms of adsorptive attraction and technologies that exploit this mechanism are reviewed. Third, given the significant effort to evaluate these systems empirically, the potential to use computational quantum techniques, such as density functional theory (DFT), for modeling and prediction is explored. Finally, areas within the field of selective adsorption requiring further research are detailed with guidance on priorities for screening and defining selective adsorbents.

Nutrient Composition of Demersal, Pelagic, and Mesopelagic Fish Species Sampled Off the Coast of Bangladesh and Their Potential Contribution to Food and Nutrition Security-The EAF-Nansen Programme.

Fish is a major part of the Bangladeshi diet, but data on the nutrient composition of marine fish species are sparse. Mesopelagic fish may be a new potential resource of food and nutrients; however, nutrient composition data are lacking. The aim of this study was to provide nutrient composition data of fish species sampled off the coast of Bangladesh and determine their potential contribution to recommended nutrient intakes (RNI). Seven species from the pelagic, mesopelagic, and demersal zones were sampled from the coast of Bangladesh with Dr. Fridtjof Nansen in 2018. Three pooled samples containing 15-840 individuals from each species were analysed at the Institute of Marine Research, Norway. The demersal species contained substantially lower concentrations of nearly all nutrients, whereas the mesopelagic species generally were more nutrient dense. All species, except for the demersal species Bombay duck (9% dry matter), were found to contribute ≥100% to the RNI of vitamin B12, eicosapentaenoic acid, docosahexaenoic acid, and selenium. All species, except for the demersal fish species, contributed ≥25% to the RNI of six or more nutrients. The data presented in this paper are an important contribution to the Bangladeshi food composition table and contribute to the understanding of fish as an important source of micronutrients.

Experimental and survey-based data on willingness to pay for seafood safety and environmental sustainability certification in Nigeria.

Aquatic foods, including fish, are a substantial component of animal source foods globally, and make a critical nutritional contribution to diets in many contexts. In the global North, concern among consumers and regulators over the safety and environmental sustainability of seafood, particularly in developed nations, has led to the development of increasingly stringent seafood safety standards. While such standards may constitute regularity, logistical, and economic barriers to participation in export markets by small-scale producers, they have in other contexts catalysed upgrades to production and post-harvest handling practices within value chains associated with both capture fisheries and aquaculture. The health burden of foodborne illnesses is a major concern in developing countries. As incomes rise, consumers in developing countries are increasingly willing to pay a premium for safer and environmentally sustainable foods. However, there is little empirical evidence on consumers' willingness to pay for seafood safety in developing countries, particularly in sub-Saharan Africa. Data on demand for seafood safety and environmental sustainability certification in African countries are largely unavailable in the public domain. In this paper, we describe data collected in Lagos State, Nigeria in October and November 2019. Experiments in the form of Becker-DeGroote-Marschak (BDM) auction mechanism, and post experiment surveys were conducted with 200 fish consumers in fish markets. These data can be used to assess whether consumers' demand for safe and healthy seafood from local markets can be harnessed to generate positive economic returns to producers.

Toward Realizing Multifunctionality: Photoactive and Selective Adsorbents for the Removal of Inorganics in Water Treatment.

Persistent and potentially toxic inorganic oxoanions (e.g., arsenic and selenium) are one class of contaminants of concern in drinking water for which treatment technologies must be improved. Effective removal of these oxoanions is made difficult by the varying adsorption affinity of the different oxidation states, as well as the presence of background ions with similar chemical structure and behavior that strongly compete for adsorption sites, greatly reducing removal efficiencies. Recent studies pointing to the negative health effects of inorganic oxoanion contaminants have resulted or are expected to result in new regulations lowering their allowable maximum concentration level (MCL) in drinking water. While these regulations are intended to protect human and environmental health, they must also allow for balanced economic costs. As such, the MCLs are often set at levels that are not as health protective due to high treatment costs that continue to present a significant challenge for small (500-3300 people) to very small (25-500 people) communities. In this Account, we focus on the development of novel cost-effective, sustainable, and efficient multifunctional and selective adsorbents that offer solutions to the above challenges through two platforms: nanoenabled and transition-metal cross-linked chitosan (TMCC) and crystal facet engineered nanometal oxides (NMO). These complementary platforms offer treatment solutions at different scales and flow rates (e.g., in a point-of-use device versus a small-scale community system). Multifunctional adsorbents combine processes that traditionally require multiple steps offering the potential for reducing treatment time and costs. Development of selective adsorbents can greatly increase removal efficiencies of target contaminants by either promoting their adsorption or hindering adsorption of competitive ions. The following sections describe (1) synthesis of novel nanoenabled waste sourced bioadsorbents; (2) development of multifunctional adsorbents to simultaneously photo-oxidize arsenite and adsorb arsenate; (3) development of a selective adsorbent for removal of arsenate and selenite over phosphate; (4) investigations of the conventional wisdom that increased surface area yields increased oxoanion removal using selenium sorption on nanohematite as a case study; and (5) crystal engineering of nanohematite to promote selenite adsorption. The novel technologies developed through these research efforts can serve as templates for the creation of future adsorbents tailored for use targeting other oxoanion contaminants of interest.

Multifunctional photoactive and selective adsorbent for arsenite and arsenate: Evaluation of nano titanium dioxide-enabled chitosan cross-linked with copper.

A novel multifunctional sorbent material of nano-titanium dioxide-enabled chitosan beads cross-linked with copper (CuTICB) is capable of photo-oxidation of As(III) to the less-toxic and more easily adsorbed As(V) in UV light and selective adsorption of arsenite (As(III)) and arsenate (As(V)) in the presence of phosphate, a strong adsorptive competitor and inhibitor of arsenic removal performance. CuTICB is an attractive sorbent as simultaneous photo-oxidation and adsorption reduces treatment time and cost while selective adsorption improves removal efficiency of arsenic in typical environmental conditions where competitive ions are predominant. In CuTICB, nano-titanium dioxide (n-TiO2) anatase photo-oxidizes As(III) to As(V) through generation of reactive oxygen species. Additionally, Cu-chitosan bidentate crosslinkers form through Lewis acid-base coordinate bonding between Cu(II) and chitosan amine groups resulting in cationic behavior that electrostatically favors As(V) chelation even when phosphate concentrations are orders of magnitude higher. The influence of copper and n-TiO2 loading on arsenic photo-oxidation and selective removal over phosphate was explored to optimize CuTICB design using batch experiments under varying systems conditions. For a system requiring both photo-oxidation and selective adsorption, it was found that copper and n-TiO2 act non-linearly and synergistically, where maximum loadings of both does not yield the optimal selectivity or removal efficacy.