The Sun Also Rises: Tracing the evolution of humanistic values in anatomy pedagogy and research, including cadaveric acquisition practices.

Anatomy has always been at the intersection of the socio-cultural and political landscape, where new ideas constantly replace older wisdom. From ancient Egyptians through the Greeks, and then the Romans, finally culminating into the European Renaissance-all the significant eras of human civilisation have left their insignia and distinct marks on the evolution of anatomical practices. Despite its utility as a tool for anatomy pedagogy and research that has proven its worth over millennia, cadaveric dissection has particularly been subject to political and social vicissitudes. A major debate about anatomical dissection lay with the ethical considerations, or its lack thereof, while acquiring corpses for demonstration in the dissection halls. From antiquity, anatomical dissection-often synonymous with medical studies-had typically been carried out on the dead bodies of executed criminals with certain laws, such as the Murder Act of 1752, facilitating such uses. Gradually, the uses of unclaimed bodies, resourced primarily from the impoverished sections of society, were also introduced. However, these body acquisition protocols often missed the crucial element of humanism and ethical considerations, while knowledge augmentation was taken as sufficient reasoning. Unfortunately, a gross disregard towards humanistic values promulgated heinous and illegal practices in acquiring corpses, including grave robbery and even murders like in the case of Burke and Hare murders of 1828. Follow-up legislation, such as the Anatomy Act of 1832, and comparable laws in other European nations were passed to curb the vile. What distils from such a historical discourse on humane values in anatomy dissection, or medical science in general, is that the growth and integration of humanism in anatomy have never been linear, but there were intermittent and, yet, significant disruptions in its timeline. For example, there were serious human rights violations in anatomical practices during the Third Reich in Germany that perpetrated the holocaust. The medical community has kept evolving and introducing new moral values and principles while using such egregious events as lessons, ultimately resulting in the Declaration of Helsinki in 1964. This article revisits the heterogeneous journey of integrating humanistic values in anatomy practice. Such humanistic traits that, like medical science, have also developed over centuries through the inputs of physicians, researchers, and philosophers-from Greece to modernity with an important stopgap at the Renaissance-are a fascinating lore that deserves to be re-envisioned through the lens of contemporary values and ethos. In parallel to human medicine, humanistic values continue to influence veterinary medicine, a welcome development, as our society condemns animal cruelty in any form. There are lessons to be learned from this historical journey of how humanism shaped many of the concepts that anatomists use now. Finally, and most importantly, it might prevent the medical community from repeating the same mistakes by cautioning against the traps that are there, and in a convoluted world where morality as such is eroding from our social fabric, will always be there. Such historical account acts as a righteous, ethical, and contextual compass to guide the existing and upcoming anatomists in discerning between light and dark, right and wrong, and roads-to be or not to be-taken.

On the importance of integrating comparative anatomy and One Health perspectives in anatomy education.

As a result of many factors, including climate change, unrestricted population growth, widespread deforestation and intensive agriculture, a new pattern of diseases in humans is emerging. With increasing encroachment by human societies into wild domains, the interfaces between human and animal ecosystems are gradually eroding. Such changes have led to zoonoses, vector-borne diseases, infectious diseases and, most importantly, the emergence of antimicrobial-resistant microbial strains as challenges for human health. Now would seem to be an opportune time to revisit old concepts of health and redefine some of these in the light of emerging challenges. The One Health concept addresses some of the demands of modern medical education by providing a holistic approach to explaining diseases that result from a complex set of interactions between humans, environment and animals, rather than just an amalgamation of isolated signs and symptoms. An added advantage is that the scope of One Health concepts has now expanded to include genetic diseases due to advancements in omics technology. Inspired by such ideas, a symposium was organised as part of the 19th International Federation of Associations of Anatomists (IFAA) Congress (August 2019) to investigate the scope of One Health concepts and comparative anatomy in contemporary medical education. Speakers with expertise in both human and veterinary anatomy participated in the symposium and provided examples where these two disciplines, which have so far evolved largely independent of each other, can collaborate for mutual benefit. Finally, the speakers identified some key concepts of One Health that should be prioritised and discussed the diverse opportunities available to integrate these priorities into a broader perspective that would attempt to explain and manage diseases within the scopes of human and veterinary medicine.

Molecular Descriptors as a Facile Tool toward Designing Surface-Functionalized Nanoparticles for Drug Delivery.

Modulating the surface chemistry of nanoparticles, often by grafting hydrophilic polymer brushes (e.g., polyethylene glycol) to prepare nanoformulations that can resist opsonization in a hematic environment and negotiate with the mucus barrier, is a popular strategy toward developing biocompatible and effective nano-drug delivery systems. However, there is a need for tools that can screen multiple surface ligands and cluster them based on both structural similarity and physicochemical attributes. Molecular descriptors offer numerical readouts based on molecular properties and provide a fertile ground for developing quick screening platforms. Thus, a study was conducted with 14 monomers/repeating blocks of polymeric chains, namely, oxazoline, acrylamide, vinylpyrrolidone, glycerol, acryloyl morpholine, dimethyl acrylamide, hydroxypropyl methacrylamide, hydroxyethyl methacrylamide, sialic acid, carboxybetaine acrylamide, carboxybetaine methacrylate, sulfobetaine methacrylate, methacryloyloxyethyl phosphorylcholine, and vinyl-pyridinio propanesulfonate, capable of imparting hydrophilicity to a surface when assembled as polymeric brushes. Employing free, Web-based, and user-friendly platforms, such as SwissADME and ChemMine tools, a series of molecular descriptors and Tanimoto coefficient of molecular pairs were determined, followed by hierarchical clustering analyses. Molecular pairs of oxazoline/dimethyl acrylamide, hydroxypropyl methacrylamide/hydroxyethyl methacrylamide, acrylamide/glycerol, carboxybetaine acrylamide/vinyl-pyridinio propanesulfonate, and sulfobetaine methacrylate/methacryloyloxyethyl phosphorylcholine were clustered together. Similarly, the molecular pair of hydroxypropyl methacrylamide/hydroxyethyl methacrylamide demonstrated a high Tanimoto coefficient of >0.9, whereas the pairs oxazoline/vinylpyrrolidone, acrylamide/dimethyl acrylamide, acryloyl morpholine/dimethyl acrylamide, acryloyl morpholine/hydroxypropyl methacrylamide, acryloyl morpholine/hydroxyethyl methacrylamide, carboxybetaine methacrylate/sulfobetaine methacrylate, and glycerol/hydroxypropyl methacrylamide had a Tanimoto coefficient of >0.8. The analyzed data not only demonstrated the ability of such in silico tools as a facile technique in clustering molecules of interest based on their structure and physicochemical characteristics but also provided vital information on their behavior within biological systems, including the ability to engage an array of possible molecular targets when the monomers are self-assembled on nanoparticulate surfaces.

Predictors of the diets consumed by adolescent girls, pregnant women and mothers with children under age two years in rural eastern India.

Adolescents, pregnant women and mothers of children under 2 years of age are in stages of life characterized by higher nutritional demands. The study measured the dietary diversity of 17,680 adolescent girls, pregnant women and mothers of children under age 2 years in the eastern Indian states of Bihar, Chhattisgarh and Odisha using data from the Swabhimaan baseline survey conducted in 2016. The association of women's mean Dietary Diversity Scores with socioeconomic, health and nutrition service indicators was assessed. The sampled population was socioeconomically more vulnerable than the average Indian population. There was not much variation in the types of foods consumed daily across target groups, with diet being predominantly cereal (98%) and vegetable (83%) based. Nearly 30% of the mothers had low Dietary Diversity Scores, compared with 25% of pregnant women and 24% of adolescent girls. In each target group, more than half of the respondents were unable to meet the Minimum Dietary Diversity score of at least five of ten food groups consumed daily. Irrespective of their background characteristics, mean Dietary Diversity Scores were significantly lower in Bihar than in Chhattisgarh and Odisha for all target groups. Having at least 6 years of education, belonging to a relatively rich household and possessing a ration card predicted mean dietary diversity. Project interventions of participatory women's group meetings improved mean Dietary Diversity Scores for mothers and adolescent girls. Considering the association between poverty and dietary diversity, the linkage between girls and women and nutrition-focused livelihoods and supplementary nutrition programmes needs to be tested.

Shedding Light on the Trehalose-Enabled Mucopermeation of Nanoparticles with Label-Free Raman Spectroscopy.

Nanoparticle-based drug delivery systems have attracted significant interest owing to their promise as tunable platforms that offer improved intracellular release of cargo therapeutics. However, significant challenges remain in maintaining the physiological stability of the mucosal matrix due to the nanoparticle-induced reduction in the matrix diffusivity and promotion of mucin aggregation. Such aggregation also adversely impacts the permeability of the nanoparticles, and thus, diminishes the efficacy of nanoparticle-based formulations. Here, an entirely complementary approach is proposed to the existing nanoparticle functionalization methods to address these challenges by using trehalose, a naturally occurring disaccharide that offers exceptional protein stabilization. Plasmon-enhanced Raman spectroscopy and far-red fluorescence emission of the plasmonic silver nanoparticulate clusters are harnessed to create a unique dual-functional, aggregating, and imaging agent that obviates the need of an additional reporter to investigate mucus-nanoparticle interactions. These spectroscopy-based density mapping tools uncover the mechanism of mucus-nanoparticle interactions and establish the protective role of trehalose microenvironment in minimizing the nanoparticle aggregation. Thus, in contrast to the prevailing belief, these results demonstrate that nonfunctionalized nanoparticles may rapidly penetrate through mucus barriers, and by leveraging the bioprotectant attributes of trehalose, an in vivo milieu for efficient mucosal drug delivery can be generated.

WASH practices and its association with nutritional status of adolescent girls in poverty pockets of eastern India.

BACKGROUND: Water, Sanitation, and Hygiene (WASH) practices may affect the growth and nutritional status among adolescents. Therefore, this paper assesses WASH practices and its association with nutritional status among adolescent girls. METHODS: As a part of an intervention programme, this study is based on baseline cross-sectional data. It was conducted between May 2016-April 2017 in three Indian states (Bihar, Odisha, and Chhattisgarh). From a sample of 6352 adolescent girls, information on WASH practices, accessibility to health services and anthropometric measurements (height, weight and mid upper arm circumference (MUAC)) was collected. Descriptive statistics were used to examine WASH practices, and nutritional status among adolescent girls. Determinants of open defecation and menstrual hygiene were assessed using logistic regression. Association between WASH and nutritional status of adolescent girls was determined using linear regression. RESULTS: Findings showed 82% of the adolescent girls were practicing open defecation and 76% were not using sanitary napkins. Significant predictors of open defecation and non use of sanitary napkin during menstruation were non Hindu households, households with poorer wealth, non availability of water within household premise, non visit to Anganwadi Centre, and non attendance in Kishori group meetings. One-third of adolescent girls were stunted, 17% were thin and 20% had MUAC < 19 cm. Poor WASH practices like water facility outside the household premise, unimproved sanitation facility, non use of soap after defecation had significant association with poor nutritional status of adolescent girls. CONCLUSIONS: Concerted convergent actions focusing on the provision of clean water within the household premise, measures to stop open defecation, promotion of hand washing, accessibility of sanitary napkins, poverty alleviation and behavior change are needed. Health, nutrition and livelihood programmes must be interspersed, and adolescents must be encouraged to take part in these programmes.

Nanoparticle passage through porcine jejunal mucus: Microfluidics and rheology.

A micro-slide chamber was used to screen and rank sixteen functionalized fluorescent silica nanoparticles (SiNP) of different sizes (10, 50, 100 and 200 nm) and surface coatings (aminated, carboxylated, methyl-PEG1000ylated, and methyl-PEG2000ylated) according to their capacity to permeate porcine jejunal mucus. Variables investigated were influence of particle size, surface charge and methyl-PEGylation. The anionic SiNP showed higher transport through mucus whereas the cationic SiNP exhibited higher binding with lower transport. A size-dependence in transport was identified - 10 and 50 nm anionic (uncoated or methyl-PEGylated) SiNP showed higher transport compared to the larger 100 and 200 nm SiNP. The cationic SiNP of all sizes interacted with the mucus, making it more viscous and less capable of swelling. In contrast, the anionic SiNP (uncoated or methyl-PEGylated) caused minimal changes in the viscoelasticity of mucus. The data provide insights into mucus-NP interactions and suggest a rationale for designing oral nanomedicines with improved mucopermeability.

India's vitamin A supplementation programme is reaching the most vulnerable districts but not all vulnerable children. New evidence from the seven states with the highest burden of mortality among under-5s.

OBJECTIVE: To characterize the coverage of India's national vitamin A supplementation (VAS) programme and document its performance in reaching children in the districts with higher concentration of poor households (2006-2011). DESIGN: Analysis of VAS programme coverage data collated and collected using standardized bottom-up procedures, data from India's Office of the Registrar General and Census Commissioner, and data from India's District Level Household Survey to compute exposure (poverty) and outcome (full VAS coverage) variables. SETTING: Seven Indian states with the highest burden of mortality in children (74 % of all deaths among under-5s in the country in 2006). SUBJECTS: Children 6-59 months old. RESULTS: Between 2006 and 2011, the mean full VAS coverage (two VAS doses per child per year) in these seven states increased from 44·7 % to 67·3 % while the number of districts with high (≥80 %) full VAS coverage increased from twenty-four (9·4 %) to 131 (51·4 %). The highest increases in full VAS coverage figures were recorded in the districts with the highest concentration of poor households. The estimated number of poor children (i.e. children living in households classified as poor) who did not receive two VAS doses annually decreased from 8·5 million in 2006 to 5·1 million in 2011 (40·3 % decrease); 2·5 million (49·1 %) of these children lived in the districts with the lowest proportion of poor households. CONCLUSIONS: Despite significant improvements in VAS, a large number of Indian children are not benefitting yet from this life-protecting intervention, particularly among those who are potentially the most vulnerable. Future programme action needs to give priority to sub-district level units - blocks and villages - with higher concentrations of poor households.

A review of the vitamin A supplementation program in India: reasons for success in the states of Bihar and Odisha.

BACKGROUND: Preventive vitamin A supplementation (VAS) is an essential child survival intervention. In India, VAS program coverage has remained relatively low, with wide interstate variation. OBJECTIVE: To review the VAS program in India, particularly in Bihar and Odisha, the two states that have had the most successful VAS programs, to define best practices and identify critical success factors. METHODS: A thorough review of existing relevant literature was carried out, supplemented by field visits and interviews with selected partners. RESULTS: Both states have adopted a biannual approach to reach out to children 1 to 5 years of age with VAS every 6 months, while infants below 1 year of age receive their first VAS dose with the measles immunization at 9 months. The critical success factors for the VAS program in the two states include strong leadership and ownership by the state government; close coordination between the two departments that are involved in the VAS program; effective microplanning prior to each biannual round; flexible dosing mechanisms that enhance coverage in hard-to-reach areas; a stable procurement and distribution mechanism to ensure an adequate, timely, and sustainable supply of VAS; intensive social mobilization and communication; and appropriate training and supervision of staff. CONCLUSIONS: The governments of Bihar and Odisha have demonstrated that it is feasible to implement a successful and inclusive VAS program in India. The challenge now is to reach out to the remaining 30% to 40% of children who are undoubtedly the hardest to reach and potentially the most vulnerable.

Public human dissection and societal connect of anatomical sciences: A glorious association in the past but ethically forbidden practice at present.

Under the futuristic vision of anatomical sciences, a strong societal connection is mandatory. The anatomical practice experienced robust societal participation through public human dissection from the 16th century onward. With a perspective to explore the intersection of spirituality with anatomy, the present study analyzed this momentous period. From a spiritual perspective, the study also reflects on two relevant but presently uncoupled entities of public human dissection and societal connection through the prism of current regulations. Strong representation from the general public during public human dissection was primarily driven by spiritual proclivity and an endorsement from religious authorities. To regulate large gatherings and maintain academic sanctity, anatomical theaters emerged as dedicated spaces for such a merger. With time and growing financial support, the theaters transformed from temporary structures to elaborate architectural marvels, further propelling already robust societal connections associated with the practice. Nevertheless, a confluence of multiple factors led to the violation of spiritual principles and a consequent decrease in societal participation from the early 18th century, eventually culminating in the demise of such spectacle. Presently, public human dissection-when done-is mostly conducted for commercial gains and in contravention of ethical norms. It is against the essence of spirituality and harbors a bleak prospect for societal connection. Contrastingly, measures adopted to promote societal participation (mostly related to body donation) were quite effective and followed the principles of spirituality. Societal connections served anatomy in the past and can lead to its advancement if approached through a righteous path.

An arch worth revisiting: a study on the feline humeral supracondylar foramen and its evolutionary significance.

The supracondylar foramen with a (seemingly) osseous peripheral arch noticed on the medio-distal feline humeri had remained disputed among anatomists. Some scholars have argued in favor of homology between this foramen and the supracondyloid foramen formed in presence of the ligament of Struthers in humans. Other theories include its presence as a retinaculum holding the median nerve and brachial artery to their anatomical position in a flexed elbow. Unfortunately, these theories lack investigative rigor. The emergence of non-invasive imaging modalities, such as micro-computed tomography, has enabled researchers to inspect the internal anatomy of bones without dismantling them. Thus, a micro-computed tomographic investigation was conducted on three feline (Felis catus) humeri specimens while the internal anatomy of the supracondylar foramina was examined. Unlike the humerus, the thin peripheral arch of the feline supracondylar foramen failed to elicit any osseous trabeculae or foci of calcification. While adhering to the humeral periosteum at its origin, the non-osseous arch, typical of a muscular tendon, attaches into the bony saddle related to the medial humeral epicondyle suggestive of a tendon or aponeurotic extension of a (vestigial) brachial muscle, with the coracobrachialis longus emerging to be the most likely candidate.

Radiomics-based machine learning approach for the prediction of grade and stage in upper urinary tract urothelial carcinoma: a step towards virtual biopsy.

OBJECTIVES: Upper tract urothelial carcinoma (UTUC) is a rare, aggressive lesion, with early detection a key to its management. This study aimed to utilise computed tomographic urogram data to develop machine learning models for predicting tumour grading and staging in upper urothelial tract carcinoma patients and to compare these predictions with histopathological diagnosis used as reference standards. METHODS: Protocol-based computed tomographic urogram data from 106 patients were obtained and visualised in 3D. Digital segmentation of the tumours was conducted by extracting textural radiomics features. They were further classified using 11 predictive models. The predicted grades and stages were compared to the histopathology of radical nephroureterectomy specimens. RESULTS: Classifier models worked well in mining the radiomics data and delivered satisfactory predictive machine learning models. The multilayer panel showed 84% sensitivity and 93% specificity while predicting UTUC grades. The Logistic Regression model showed a sensitivity of 83% and a specificity of 76% while staging. Similarly, other classifier algorithms [e.g. Support Vector classifier (SVC)] provided a highly accurate prediction while grading UTUC compared to clinical features alone or ureteroscopic biopsy histopathology. CONCLUSION: Data mining tools could handle medical imaging datasets from small (<2 cm) tumours for UTUC. The radiomics-based machine learning algorithms provide a potential tool to model tumour grading and staging with implications for clinical practice and the upgradation of current paradigms in cancer diagnostics. CLINICAL RELEVANCE: Machine learning based on radiomics features can predict upper tract urothelial cancer grading and staging with significant improvement over ureteroscopic histopathology. The study showcased the prowess of such emerging tools in the set objectives with implications towards virtual biopsy.

Signatures of quantum phases in a dissipative system.

Lindbladian formalism, as tuned to dissipative and open systems, has been all-pervasive to interpret non-equilibrium steady states of quantum many-body systems. We study the fate of free fermionic and superconducting phases in a dissipative one-dimensional Kitaev model-where the bath acts both as a source and a sink of fermionic particles with different coupling rates. As a function of these two couplings, we investigate the steady state, its entanglement content, and its approach from varying initial states. Interestingly, we find that the steady state phase diagram retains decipherable signatures of ground state critical physics. We also show that early-time fidelity is a useful marker to find a subclass of phase transitions in such situations. Moreover, we show that the survival of critical signatures at late-times, strongly depend on the thermal nature of the steady state. This connection hints at a correspondence between quantum observables and classical magnetism in the steady state of such systems. Our work uncovers interesting connections between dissipative quantum many-body systems, thermalization of a classical spin and many-body quantum critical phenomena.

The osseous fusion patterns in an equine limb: A theoretical deconstruction of the evolutionary mechanisms.

Adaptations in equine limbs, including fusion of its bones, such as the metapodials II and IV (splint bones) with metapodial III (cannon bone), have been debated. It is argued that cursorial adaptations in equine limbs with a progressive reduction in the number of digits lighten up the limbs and facilitate fast running. Similar fusions in other bones, such as the radius and ulna, tend to exhibit similar traits. For example, the fusion often occurs in a disto-proximal direction while leaving sharp ridges. This article proposes a model to understand the biomechanical advantages that a fused symmetric system of cannon and splint bones offers and tries to investigate osseous fusion from an evolutionary perspective. It demonstrated the uniqueness of this system from the context of symmetry and the presence of an array of parallel axes of rotation in equine limbs that amplifies the kinetic energy by maximizing the moment of inertia. The model highlighted the robustness of such an evolutionary mechanism in place and elucidated why it is a preferable construct. Furthermore, the discourse proposes a zipping action to describe the osseous fusion before making predictions on where the equine limb adaptations are perhaps heading.

An Investigation into the Acidity-Induced Insulin Agglomeration: Implications for Drug Delivery and Translation.

Insulin undergoes agglomeration with (subtle) changes in its biochemical environment, including acidity, application of heat, ionic imbalance, and exposure to hydrophobic surfaces. The therapeutic impact of such unwarranted insulin agglomeration is unclear and needs further evaluation. A systematic investigation was conducted on recombinant human insulin-with or without labeling with fluorescein isothiocyanate-while preparing insulin suspensions (0.125, 0.25, and 0.5 mg/mL) at pH 3. The suspensions were incubated (37 °C) and analyzed at different time points (t = 2, 4, 24, 48, and 72 h). Transmission electron microscopy and nanoparticle tracking analysis identified colloidally stable (zeta potential 15 ± 5 mV) spherical agglomerates of unlabeled insulin (100-500 nm). Circular dichroism established the preservation of insulin's secondary structure rich in α-helices despite exposure to an acidic environment (pH 3) for 72 h. Furthermore, fluorescence lifetime imaging microscopy illustrated an acidic core inside these spherical agglomerates, while the acidity gradually lessened toward the periphery. Some of these smaller agglomerates fused to form larger chunks with discrete zones of acidity. The data indicated a primary nucleation-driven mechanism of acid-induced insulin agglomeration under physiologically relevant conditions.

Evaluation of impact of engaging federations of women groups to improve women's nutrition interventions- before, during and after pregnancy in social and economically backward geographies: Evidence from three eastern Indian States.

BACKGROUND: Undernutrition-before, during and after pregnancy endangers the health and well-being of the mother and contributes to sub-optimal fetal development and growth. A non-randomized controlled evaluation was undertaken to assess the impact of engaging federations of women's group on coverage of nutrition interventions and on nutrition status of women in the designated poverty pockets of three Indian states-Bihar, Chhattisgarh, and Odisha. METHOD: The impact evaluation is based on two rounds of cross-sectional data from 5 resource poor blocks across 3 States, assigning 162 villages to the intervention arm and 151 villages to the control arm. The cross-sectional baseline (2016-17) and endline survey (2021-22) covered a total of 10491 adolescent girls (10-19 years), 4271 pregnant women (15-49 years) and 13521 mothers of children under age two years (15-49 years). Exposure was defined based on participation in the participatory learning and action meetings, and fixed monthly health camps (Adolescent Health Days (AHDs) and Village Health Sanitation and Nutrition Days (VHSNDs)). Logistic regression models were applied to establish the association between exposure to programme activities and improvement in coverage of nutrition interventions and outcomes. RESULTS: In the intervention area at endline, 27-38% of women participated in the participatory learning and action meetings organized by women's groups. Pregnant women participating in programme activities were two times more likely to receive an antenatal care visit in the first trimester of pregnancy (Odds ratio: 2.55 95% CI-1.68-3.88), while mothers of children under 2 were 60% more likely to receive 4 ANC visits (Odds ratio: 1.61, 95% CI- 1.30-2.02). Odds of consuming a diversified diet was higher among both pregnant women (Odds ratio: 2.05, 95% CI- 1.41-2.99) and mother of children under 2 years of age (Odds ratio: 1.38, 95% CI- 1.08-1.77) among those participating in programme activities in the intervention arm. Access to commodities for WASH including safe sanitation services (Odds ratio: 1.80, 95% CI- 1.38-2.36) and sanitary pads (Odds ratio: 1.64, 95% CI- 1.20-2.22) was higher among adolescent girls participating in programme activities. CONCLUSION: Women's groups led participatory learning and action approaches coupled with strengthening of the supply side delivery mechanisms resulted in higher coverage of health and nutrition services. However, we found that frequency of participation was low and there was limited impact on the nutritional outcomes. Therefore, higher frequency of participation in programme activities is recommended to modify behaviour and achieve quick gains in nutritional outcomes.

Cytotoxicity and cellular uptake of tri-block copolymer nanoparticles with different size and surface characteristics.

BACKGROUND: Polymer nanoparticles (PNP) are becoming increasingly important in nanomedicine and food-based applications. Size and surface characteristics are often considered to be important factors in the cellular interactions of these PNP, although systematic investigations on the role of surface properties on cellular interactions and toxicity of PNP are scarce. RESULTS: Fluorescent, monodisperse tri-block copolymer nanoparticles with different sizes (45 and 90 nm) and surface charges (positive and negative) were synthesized, characterized and studied for uptake and cytotoxicity in NR8383 and Caco-2 cells. All types of PNP were taken up by the cells. The positive smaller PNP45 (45 nm) showed a higher cytotoxicity compared to the positive bigger PNP(90) (90 nm) particles including reduction in mitochondrial membrane potential (ΔΨ(m)), induction of reactive oxygen species (ROS) production, ATP depletion and TNF-α release. The negative PNP did not show any cytotoxic effect. Reduction in mitochondrial membrane potential (ΔΨ(m)), uncoupling of the electron transfer chain in mitochondria and the resulting ATP depletion, induction of ROS and oxidative stress may all play a role in the possible mode of action for the cytotoxicity of these PNP. The role of receptor-mediated endocytosis in the intracellular uptake of different PNP was studied by confocal laser scanning microscopy (CLSM). Involvement of size and charge in the cellular uptake of PNP by clathrin (for positive PNP), caveolin (for negative PNP) and mannose receptors (for hydroxylated PNP) were found with smaller PNP45 showing stronger interactions with the receptors than bigger PNP(90). CONCLUSIONS: The size and surface characteristics of polymer nanoparticles (PNP; 45 and 90 nm with different surface charges) play a crucial role in cellular uptake. Specific interactions with cell membrane-bound receptors (clathrin, caveolin and mannose) leading to cellular internalization were observed to depend on size and surface properties of the different PNP. These properties of the nanoparticles also dominate their cytotoxicity, which was analyzed for many factors. The effective reduction in the mitochondrial membrane potential (ΔΨ(m)), uncoupling of the electron transfer chain in mitochondria and resulting ATP depletion, induction of ROS and oxidative stress likely all play a role in the mechanisms behind the cytotoxicity of these PNP.

Craft of Co-encapsulation in Nanomedicine: A Struggle To Achieve Synergy through Reciprocity.

Achieving synergism, often by combination therapy via codelivery of chemotherapeutic agents, remains the mainstay of treating multidrug-resistance cases in cancer and microbial strains. With a typical core-shell architecture and surface functionalization to ensure facilitated targeting of tissues, nanocarriers are emerging as a promising platform toward gaining such synergism. Co-encapsulation of disparate theranostic agents in nanocarriers-from chemotherapeutic molecules to imaging or photothermal modalities-can not only address the issue of protecting the labile drug payload from a hostile biochemical environment but may also ensure optimized drug release as a mainstay of synergistic effect. However, the fate of co-encapsulated molecules, influenced by temporospatial proximity, remains unpredictable and marred with events with deleterious impact on therapeutic efficacy, including molecular rearrangement, aggregation, and denaturation. Thus, more than just an art of confining multiple therapeutics into a 3D nanoscale space, a co-encapsulated nanocarrier, while aiming for synergism, should strive toward achieving a harmonious cohabitation of the encapsulated molecules that, despite proximity and opportunities for interaction, remain innocuous toward each other and ensure molecular integrity. This account will inspect the current progress in co-encapsulation in nanocarriers and distill out the key points toward accomplishing such synergism through reciprocity.

On Harvesting and Handling of Porcine Jejunal Mucus: A Few Tricks of the Trade.

As a heterogeneous hydrogel, mucus has evolved into a formidable physiological barrier protecting the human body from external pathogens and toxic molecules. With mucin as its primary solid component, the viscoelasticity of mucus remains dynamic and dependent upon a plethora of factors, including pathological state, food intake, and infection. Current nanomedicine research strives toward developing nanoformulations that can permeate through the mucus barrier and release the encapsulated cargo of drug molecules at the vicinity of epithelial lining or be directly absorbed into the bloodstream. However, it is difficult to mimic mucus in vitro while the ex vivo models remain inadequate or incompatible with many established microscopic platforms. The UCD School of Veterinary Medicine has a rich legacy of working with porcine gut mucus as an experimental model, while some interesting and innovative ideas were developed by researchers here to address these challenges. This article presents a snapshot of those ideas and life hacks that the author wishes to share with the nanomedicine research community.