Difficult questions are confronting clinicians attempting to improve hepatocellular carcinoma (HCC) outcomes. A large animal model with genetic, anatomical, and physiological similarities to humans is required to transition from mouse models to human clinical trials to address unmet clinical needs. To validate our previously reported inducible porcine cancer model (Oncopig) as a transitional HCC model, Oncopig hepatocyte cultures were transformed using Cre recombinase. The resulting porcine HCC cells (pHCC) expressed oncogenic TP53R167H and KRASG12D, and displayed nuclear pleomorphisms with pale to granular cytoplasm arranged in expanded plates similar to human HCC histopathology. Human HCC transcriptional hallmarks were detected in pHCC cells using RNA-seq, including TERT reactivation, apoptosis evasion, angiogenesis activation, and Wnt signaling activation. Master regulators of gene expression were conserved across Oncopig and 18 human HCC cell lines. pHCC injection into SCID mice resulted in tumors recapitulating human HCC characteristics, including thick trabeculae formation, pseudoacini patterning, and sheets of well-vascularized stroma. Finally, autologous injection of pHCC cells subcutaneously yielded a tumor histologically characterized as Edmondson Steiner (HCC nuclear grade assessment system) grade 2 HCC with trabecular patterning and T-lymphocyte infiltration. These data demonstrate the Oncopig HCC model's utility for improving detection, treatment, and biomarker discovery relevant to human HCC.

The pig was first used in biomedical research in ancient Greece and over the past few decades has quickly grown into an important biomedical research tool. Pigs have genetic and physiological traits similar to humans, which make them one of the most useful and versatile animal models. Owing to these similarities, data generated from porcine models are more likely to lead to viable human treatments than those from murine work. In addition, the similarity in size and physiology to humans allows pigs to be used for many experimental approaches not feasible in mice. Research areas that employ pigs range from neonatal development to translational models for cancer therapy. Increasing numbers of porcine models are being developed since the release of the swine genome sequence, and the development of additional porcine genomic and epigenetic resources will further their use in biomedical research.

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Repurposing of existing cancer drugs to overcome their physical limitations, such as insolubility, represents an attractive strategy to achieve enhanced therapeutic efficacy and broaden the range of clinical applications. Such an approach also promises to offer substantial cost savings in drug development efforts. Here we use repurposed FDA-approved topical agent bexarotene (Targretin™), currently in limited use for cutaneous manifestations of T-cell lymphomas, and re-engineer it for use in solid tumor applications by forming self-assembling nanobubbles. Physicochemical characterization studies of the novel prodrug nanobubbles demonstrated their stability, enhanced target cell-internalization capability and highly controlled release profile in response to application of focused ultrasound energy. Using an in vitro model of hepatocellular carcinoma and an in vivo large animal model of liver ablation, we demonstrate the effectiveness of bexarotene prodrug nanobubbles when used in conjunction with catheter-based ultrasound, thereby highlighting the therapeutic promise of this trimodal approach.

Background:Nephrotic syndrome, a primarily paediatric disease, is associated with a high relapse rate. Studies have reported behavioral and psychological difficulties in children with nephrotic syndrome, their caregivers and siblings, a factor that is likely to influence the overall outcome of the disease in an adverse manner. In clinical practice, however, the psychosocial aspects of care may be overlooked in the pressure to treat the disease process, unless their importance is stressed by appropriate evidence.Objectives:The study aims to assess the prevalence of behavior abnormalities in children with nephrotic syndrome attending the renal clinic of a state medical college in eastern India and to compare this with the prevalence in a control group of school children without any detectable physical illness. It also aims to explore the relationship between sociodemographic, disease, and treatment related variables and behavioral abnormalities in the nephrotic syndrome group.Materials and Methods:We assessed the prevalence of behavior abnormalities in 50 consecutive children with nephrotic syndrome attending the renal clinic of a state medical college and 51 school children as controls using the Developmental Psychopathology Checklist (DPCL). We also assessed the statistical association between sociodemographic, disease and treatment related variables and behavior profile in the nephrotic children group.Results:Prevalence of behavior disturbance in children with nephrotic syndrome was 68%, significantly higher than that in the control group (21.6%). The behavior abnormalities found in the nephrotic syndrome group were hyperkinesis, obsessive compulsive neurosis, conduct disorder, and emotional disorder, in that order. Frequency of relapse and low socioeconomic status showed significant association with presence of behavior disturbance in the nephrotic syndrome group. This association persisted even after adjusting for other sociodemographic, disease, and treatment related variables, including steroid therapy.

A B S T R A C TBackground and Objectives: Neonatal hypoglycemia, a common metabolic problem, often goes unnoticed owing to lack of specifi c symptoms. We designed this study to assess the incidence of hypoglycemia in healthy normal birth weight and low birth weight babies, including both preterm and small for gestational age (SGA) newborns, to evaluate the impact of early breastfeeding on hypoglycemia and to assess the impact of exclusive breast feeding on glucose values up to 48 h of age. Design and Settings: A hospital-based prospective longitudinal study. Materials and Methods: The study was conducted over six months involving one hundred fi fty healthy (both term and preterm) appropriate for gestational age (AGA) or SGA babies with birth weight between 1.5 kg and 3.99 kg. Blood glucose values were measured at the age of 1 h, 6 h, 12 h, 24 h and 48 h after delivery which was independent of feeding time. Blood glucose value less than 40 mg/dl (2.2 mmol/l) was defi ned as hypoglycemia. Sick newborns, those less than 34 weeks of gestation or less than 1500 g, infant of diabetic mother, those with birth asphyxia, congenital malformations and endocrine defi ciencies were excluded. Results: Overall incidence of hypoglycemia was 32%. Hypoglycemia was signifi cantly greater in SGA and preterm as compared to AGA and term newborns respectively (P<0.001). Incidence of hypoglycemia was signifi cantly more in newborns with delayed breast feeding than early breast feeding (64% vs 17%; P<0.001). Conclusion: Low birth weight babies (both preterm and small-for-date) are prone to develop hypoglycemia especially in fi rst 24 h of life with delayed introduction of breast feeding being an additional risk.

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The present study evaluates the effect of dietary zinc supplementation on reproductive and productive performance of Teressa goat, an indigenous species ofAndaman and Nicobar Islands.