Unique Regulation of Enterocyte Brush Border Membrane Na-Glutamine and Na-Alanine Co-Transport by Peroxynitrite during Chronic Intestinal Inflammation

Na-amino acid co-transporters (NaAAcT) are uniquely affected in rabbit intestinal villus cell brush border membrane (BBM) during chronic intestinal inflammation. Specifically, Na-alanine co-transport (ASCT1) is inhibited secondary to a reduction in the affinity of the co-transporter for alanine, whereas Na-glutamine co-transport (B0AT1) is inhibited secondary to a reduction in BBM co-transporter numbers. During chronic intestinal inflammation, there is abundant production of the potent oxidant peroxynitrite (OONO). However, whether OONO mediates the unique alteration in NaAAcT in intestinal epithelial cells during chronic intestinal inflammation is unknown. In this study, ASCT1 and B0AT1 were inhibited by OONO in vitro. The mechanism of inhibition of ASCT1 by OONO was secondary to a reduction in the affinity of the co-transporter for alanine, and secondary to a reduction in the number of co-transporters for B0AT1, which were further confirmed by Western blot analyses. In conclusion, peroxynitrite inhibited both BBM ASCT1 and B0AT1 in intestinal epithelial cells but by different mechanisms. These alterations in the villus cells are similar to those seen in the rabbit model of chronic enteritis. Therefore, this study indicates that peroxynitrite may mediate the inhibition of ASCT1 and B0AT1 during inflammation, when OONO levels are known to be elevated in the mucosa

Exploring Healthcare Seeking Behavior Among Patients with Ischemic Heart Disease and Stroke; A Cross-Sectional Study in a Tertiary Care Centre in South India

Background: Ischemic heart disease (IHD) and stroke represent the leading cause of mortality globally. Delays in seeking medical attention that result in diagnostic and treatment delays are significant roadblocks in achieving the best possible treatment outcomes for IHD and stroke. Aims and Objectives: This study aims to assess the pattern of healthcare seeking behavior among patients of IHD and stroke in a tertiary care hospital at Salem District in Tamil Nadu, South India. Materials and Methods: This cross-sectional study was conducted among 250 patients of IHD and stroke. A validated and structured questionnaire was used to collect information on socio-demographic details, knowledge, and health-care seeking behavior with regard to IHD and stroke based on the Health Belief Model. Results: The mean age of study participants was 60 years with a male preponderance (56%). About 75% of IHD patients and 61.9% of stroke patients had no formal education. The prevalence of hypertension (74%) was higher than diabetes mellitus (45.6%) among the study subjects. The seriousness of the initial symptoms of IHD and stroke was perceived only by 7.75% of IHD patients and 2.23% of stroke patients. Alarmingly, 39.66% of IHD patients and 61.2% of stroke patients were not aware of any risk factors for IHD and Stroke. Only 21.56% of IHD patients and 14.17% of stroke patients sought immediate medical assistance whereas the others ignored the symptoms or did not undergo treatment even after knowing the symptoms of the disease. Conclusion: This study depicted suboptimal healthcare seeking behavior and significant lack of knowledge about risk factors, initial symptoms, preventive measures, and reasons for pre hospital delay related to IHD and stroke. The study yields valuable references to incorporate the pattern of health-care seeking response of the community along with their sociocultural and economic factors in designing and implementation of any health program

Can charcoal improve outcomes in COVID-19 infections?

COVID-19 infection causes considerable morbidity and mortality, especially to those who are aged, have impaired renal function and are obese. We propose to examine the potential utility of oral activated charcoal with the hypothesis that such treatment would lower absorption of microbiome derived toxins and ameliorate systemic oxidant stress and inflammation

Reversal of Stathmin-Mediated Microtubule Destabilization Sensitizes Retinoblastoma Cells to A Low Dose of Antimicrotubule Agents: A Novel Synergistic Therapeutic Intervention

PURPOSE. To explore the possibility of stathmin as an effective therapeutic target and to evaluate the synergistic combination of stathmin RNAi and the antimicrotubule agents paclitaxel and vincristine to retinoblastoma Y79 cells. METHODS. RNAi-mediated specific inhibition of stathmin expression in Y79 cells was shown by real-time quantitative RT-PCR (RT-Q-PCR), its effect on cell proliferation by MTT assay, cell invasion using matrigel, microtubule polymerization by immunohistochemistry, apoptosis, cell cycle analysis by flow cytometry analysis, and the changes in FOXM1 protein expression were studied by Western blot. The effect of combination treatment of stathmin siRNA and paclitaxel/ vincristine was studied by assessing cell viability and apoptosis. RESULTS. Short interfering RNA-mediated transient stathmin downregulation resulted in a marked inhibition of retinoblastoma cell proliferation and cell invasion in vitro. Stathmin inhibition promoted Y79 cells to G2/M phase, and ultimately there were increased apoptotic events as evidenced by higher caspase-3 activation and cleaved poly-(ADP-ribose) polymerase expression. Cells transfected with stathmin siRNA showed long and bundled microtubule polymers and sensitized the Y79 cells significantly to paclitaxel and vincristine. CONCLUSIONS. Stathmin may be a pivotal determinant for retinoblastoma tumorigenesis and chemosensitivity. Strategies to inhibit stathmin will help to enhance the cytotoxic effect of paclitaxel while reducing toxicity (or side effects) to normal cells caused by high doses. (Invest Ophthalmol Vis Sci. 2011; 52:5441-5448

Livelihood responses to Lantana camara invasion and biodiversity change in southern India: application of an asset function framework

Natural resources play key roles as assets in the livelihoods of rural communities. However, the benefits of these assets in livelihoods are frequently conceived narrowly as income generating or vulnerability reducing. We contend that they have other important roles to play in poverty reduction and livelihood change. In this paper we use a case study of two ethnic communities in a village in southern India to investigate livelihood responses to change in forest biodiversity through an examination of changes in attributes of natural assets resulting from the invasion of Lantana camara and wider socio-economic change. The invasion of forest by Lantana has contributed to changes in the attributes and functions of four key natural assets: forest grazing, bamboo for basketry, Phoenix loureie for brooms, and wild yams. We observe that differences in households’ and individuals’ ability to substitute important functions of lost or declining assets affect their ability to adapt to changes in resource availability and attributes. Analysing changes in asset attributes for different user groups allows the social effects of environmental change to be disaggregated

Advancing Global Equity in Cardiac Care as Cardiac Implantable Electronic Device Reuse Comes of Age

A nation’s health and economic development are inextricably and synergistically connected. Stark differences exist between wealthy and developing nations in the use of cardiac implantable electronic devices (CIEDs). Cardiovascular disease is now the leading cause of death in low- and middle-income countries (LMIC), with a significant burden from rhythm-related diseases. As science, technology, education, and regulatory frameworks have improved, CIED recycling for exportation and reuse in LMIC has become possible and primed for widespread adoption. In our manuscript, we outline the science and regulatory pathways regarding CIED reuse. We propose a pathway to advance this technology that includes creating a task force to establish standards for CIED reuse, leveraging professional organizations in areas of need to foster the professional skills for CIED reuse, collaborating with regulatory agencies to create more efficient regulatory expectations and bring the concept to scale, and establishing a global CIED reuse registry for quality assurance and future science

Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children

INTRODUCTION: Multisystem Inflammatory Syndrome in children (MIS-C) is a serious inflammatory sequela of SARS-CoV2 infection. The pathogenesis of MIS-C is vague and matrix metalloproteinases (MMPs) may have an important role. Matrix metalloproteinases (MMPs) are known drivers of lung pathology in many diseases. METHODS: To elucidate the role of MMPs in pathogenesis of pediatric COVID-19, we examined their plasma levels in MIS-C and acute COVID-19 children and compared them to convalescent COVID-19 and children with other common tropical diseases (with overlapping clinical manifestations). RESULTS: Children with MIS-C had elevated levels of MMPs (P < 0.005 statistically significant) in comparison to acute COVID-19, other tropical diseases (Dengue fever, typhoid fever, and scrub typhus fever) and convalescent COVID-19 children. PCA and ROC analysis (sensitivity 84–100% and specificity 80–100%) showed that MMP-8, 12, 13 could help distinguish MIS-C from acute COVID-19 and other tropical diseases with high sensitivity and specificity. Among MIS-C children, elevated levels of MMPs were seen in children requiring intensive care unit admission as compared to children not needing intensive care. Similar findings were noted when children with severe/moderate COVID-19 were compared to children with mild COVID-19. Finally, MMP levels exhibited significant correlation with laboratory parameters, including lymphocyte counts, CRP, D-dimer, Ferritin and Sodium levels. DISCUSSION: Our findings suggest that MMPs play a pivotal role in the pathogenesis of MIS-C and COVID-19 in children and may help distinguish MIS-C from other conditions with overlapping clinical presentation

Unique cellular immune signatures of multisystem inflammatory syndrome in children

The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8(+) T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4(+) and CD8(+) T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6–9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentations. Trial Registration: ClinicalTrials.gov clinicaltrial.gov. No: NCT04844242