Parenteral nutrition (PN) has revolutionized the care of patients with intestinal failure by providing nutrition intravenously. Worldwide, PN remains a standard tool of nutrition delivery in neonatal, pediatric, and adult patients. Though the benefits are evident, patients receiving PN can suffer serious cholestasis due to lack of enteral feeding and sometimes have fatal complications from liver injury and gut atrophy, including PN-associated liver disease or intestinal failure-associated liver disease. Recent studies into gut-systemic cross talk via the bile acid-regulated farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) axis, gut microbial control of the TGR5-glucagon-like peptide (GLP) axis, sepsis, and role of prematurity of hepatobiliary receptors are greatly broadening our understanding of PN-associated injury. It has also been shown that the composition of ω-6/ω-3 polyunsaturated fatty acids given parenterally as lipid emulsions can variably drive damage to hepatocytes and cell integrity. This manuscript reviews the mechanisms for the multifactorial pathogenesis of liver disease and gut injury with PN and discusses novel ameliorative strategies. (Nutr Clin Pract. 2020;35:63-71)

Background: Total parenteral nutrition (TPN) provides all nutritional needs intravenously. Although lifesaving, enthusiasm is significantly tempered due to side effects of liver and gut injury, as well as lack of mechanistic understanding into drivers of TPN injury. We hypothesized that the state of luminal nutritional deprivation with TPN drives alterations in gut–systemic signaling, contributing to injury, and tested this hypothesis using our ambulatory TPN model. Methods: A total of 16 one-week-old piglets were allocated randomly to TPN (n = 8) or enteral nutrition (EN, n = 8) for 3 weeks. Liver, gut, and serum were analyzed. All tests were two-sided, with a significance level of 0.05. Results: TPN resulted in significant hyperbilirubinemia and cholestatic liver injury, p = 0.034. Hepatic inflammation (cluster of differentiation 3 (CD3) immunohistochemistry) was higher with TPN (p = 0.021). No significant differences in alanine aminotransferase (ALT) or bile ductular proliferation were noted. TPN resulted in reduction of muscularis mucosa thickness and marked gut atrophy. Median and interquartile range for gut mass was 0.46 (0.30–0.58) g/cm in EN, and 0.19 (0.11–0.29) g/cm in TPN (p = 0.024). Key gut–systemic signaling regulators, liver farnesoid X receptor (FXR; p = 0.021), liver constitutive androstane receptor (CAR; p = 0.014), gut FXR (p = 0.028), G-coupled bile acid receptor (TGR5) (p = 0.003), epidermal growth factor (EGF; p = 0.016), organic anion transporter (OAT; p = 0.028), Mitogen-activated protein kinases-1 (MAPK1) (p = 0.037), and sodium uptake transporter sodium glucose-linked transporter (SGLT-1; p = 0.010) were significantly downregulated in TPN animals, whereas liver cholesterol 7 alpha-hydroxylase (CyP7A1) was substantially higher with TPN (p = 0.011). Conclusion: We report significant alterations in key hepatobiliary receptors driving gut–systemic signaling in a TPN piglet model. This presents a major advancement to our understanding of TPN-associated injury and suggests opportunities for strategic targeting of the gut–systemic axis, specifically, FXR, TGR5, and EGF in developing ameliorative strategies.

This article focuses on the 'return' of second-generation Indian-American professionals from the US to their parental homeland, India. Based on qualitative interviews with forty-eight second-generation Indian-Americans working in the cities of New Delhi, Mumbai and Hyderabad, it examines the question of why they 'return' to India. Data suggest that better job opportunities in India motivated and enabled respondents to 'return'. Importantly, they also 'returned' to develop an independent and personal relationship with the country. Their migration decisions were shaped by their transnational praxis and cultural affiliations to India and the stage in the life-course. My findings also suggest that for some second-generation immigrants, 'return' does not necessarily imply permanent settlement in the parental homeland or mark the end of the migration cycle.

Background To study the outcome of fluticasone nasal sprays in smell disorders and triamcinolone paste in taste dysfunction in a population of laboratory-confirmed SARS-CoV-2 patients as the test group. The control group will not be given any intervention and only monitoring of these symptoms will be done to compare the recovery time. Methods This prospective interventional study was conducted from June to Nov 2020 at, Datta Meghe University during the COVID-19 outbreak. The 120 enrolled patients were tested at days 1 and 5 after proven infection by RT-PCR test. Result The mean age for all cases is 50.88 ± 15.93 years, whereas for the controls mean age is 51.2 ± 14.89. 2. Among cases 45 (75%) were males and 15 (25%) were females, among controls 43 (71.66%) were males and 17 (28.33%) were females. Among the case group, after the use of fluticasone spray in the nose and triamcinolone paste in the mouth there was a statistically significant improvement in recognizing all the odours and taste on day 5 compared to day 1. On comparing the smell and taste of cases and control group, either there is no improvement or worsening in smell or taste on day 5 in the control group. Conclusion The use of fluticasone nasal spray and triamcinolone paste had immensely influenced the basic senses such as smell and taste. Our study showed that olfactory and taste function significantly improved in patients with COVID-19. For all anosmia and dysgeusia cases who received fluticasone nasal spray and triamcinolone medications the recovery of smell senses and the taste was within a week.

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Extensive bowel resection results in short bowel syndrome. Absence of the ileocecal valve and length of remaining bowel are important prognostic factors. Such patients require total parenteral nutrition for survival, which has significant side effects, thus understanding mechanisms driving total parenteral nutrition-associated complications in short bowel syndrome is a major research focus. We hypothesized that we could develop an ambulatory total parenteral nutrition-short bowel syndrome piglet model recapitulating human short bowel syndrome for advanced research. Fourteen neonatal pigs received duodenal, jugular catheters, and a jacket with a miniaturized pump. Animals were randomly allocated to enteral nutrition ( n = 5), total parenteral nutrition only ( n = 5) or total parenteral nutrition with 75% small bowel, ileocecal valve resection, and ileo-colonic anastomosis ( n = 4). Blood, liver, and gut were analyzed. Animals underwent successful bowel resection and anastomosis. Increased bilirubin was noted in short bowel syndrome and total parenteral nutrition. Mean conjugated bilirubin (mg/dL)±SE was 0.036 ± 0.004 for enteral nutrition ( P = 0.03), 1.29 ± 0.613 for total parenteral nutrition ( P = 0.01), and 3.89 ± 0.51 for short bowel syndrome ( P = 0.000064). Linear gut density was reduced in short bowel syndrome and total parenteral nutrition vs. enteral nutrition. The mean linear gut density (g/cm)±SE for distal gut was 0.30 ± 0.02 for enteral nutrition ( P = 0.0005); 0.16 ± 0.01 for total parenteral nutrition ( P = 0.01), and 0.11 ± 0.008 for short bowel syndrome ( P = 0.0001). We noted gut adaptation in short bowel syndrome ( P = 0.015) with significant reduction in gut FXR, gut FGF19, and enhanced hepatic CyP7A1 expression in short bowel syndrome and total parenteral nutrition ( P < 0.05). We successfully created an ambulatory total parenteral nutrition-short bowel syndrome model with distal small bowel and ileocecal valve resection recapitulating human short bowel syndrome. Our model validated total parenteral nutrition-related hyperbilirubinemia and gut changes, as noted in human short bowel syndrome. This model holds great potential for future innovative research and clinical applications. Impact statement Short bowel syndrome is associated with significant comorbidities and mortality. This study is important as unlike current systems, it provides a validated piglet model which mirrors anatomical, histological, and serological characteristics observed in human SBS. This model can be used to advance knowledge into mechanistic pathways and therapeutic modalities to improve outcomes for SBS patients. This study is novel in that in addition to significant reduction in the remnant bowel and noted liver disease, we also developed a method to emulate ileocecal valve resection and described gut adaptive responses which has important clinical implications in humans.

IntroductionCoronavirus disease 2019 (COVID-19)has been a difficult enemy to beat for healthcare professionals around the world. However, even before the end of the COVID-19 pandemic, there has been an emergence of a new combatant in the form of opportunistic fungal infections with a high rate of morbidity and mortality, creating havoc throughout the globe. MethodsA case-control single-center study was conducted in Datta Meghe Institute of Medical Sciences, Wardha, Maharashtra. All the subjects who were included in the study were tested positive for COVID-19 through the reverse transcriptase-polymerase chain reaction (RT-PCR) method and the cases were defined as patients with biopsy-proven mucormycosis, whereas control were subjects who did not develop mucormycosis. The duration of the study was three months, from June 2021 to August 2021. ResultA total of 55 cases and 50 controls were enrolled in the study. The use of zinc was found to be significantly associated with COVID-19-associated mucormycosis, with 89.1% of the cases having a history of zinc intake and only 52% of controls having a history of zinc intake( p-value <0.001). Diabetes mellitus was found to be significantly associated with COVID-19-associated mucormycosis with 83.6% of the cases and 16% of the controls having diabetes mellitus (p-value <0.001). Although the use of steroids in cases was more with 98.2% of the cases and 54% of the control receiving steroids; this difference was not significant statistically (p-value of 1.00). ConclusionWe conclude that apart from diabetes mellitus and other immunosuppressive states, zinc might be the hidden culprit behind the sudden surge of COVID-19-associated mucormycosis worldwide owing to the selfadministration of zinc by the patients to acquire innate immunity and over-prescription of multivitamins by the treating clinicians. However, this association required further studies in order to be proved.

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