Addressing Pediatric Medical Training Needs in Noncommunicable Diseases

The importance of addressing non-communicable diseases (NCDs) has been identified by health care leaders in India and around the world. Calls to action have been made to address this issue, including the creation of effective surveillance and research systems across South Asia. These efforts include collaboration within India at the local, regional, and national levels to support these initiatives. In addition to these efforts, it is critical to assess and strengthen medical training in NCDs. This can be done by providing clinicians with curriculum development tools to augment their clinical skills, as well as enabling them to advocate and role model as educators. The authors provide recommendations on how clinicians can address the threat of NCDs as educators, role models and advocates for improved pediatric NCD training.     

Alpha-ketoglutarate and N-acetyl cysteine protect PC12 cells from cyanide-induced cytotoxicity and altered energy metabolism

Cyanide is a rapidly acting neurotoxin that inhibits cellular respiration and energy metabolism leading to histotoxic hypoxia. This results in the dissipation of mitochondrial membrane potential (MMP) accompanied by decreased cellular ATP content which in turn is responsible for increased levels of intracellular calcium ions ([Ca(2+)](i)) and total lactic acid content of the cells. Rat pheochromocytoma (PC12) cells possess much of the biochemical machinery associated with synaptic neurons. In the present study, we evaluated the cytoprotective effects of alpha-ketoglutarate (A-KG) and N-acetylcysteine (NAC) against cyanide-induced cytotoxicity and altered energy metabolism in PC12 cells. Cyanide-antagonism by A-KG is attributed to cyanohydrin formation whereas NAC is known for its antioxidant properties. Data on leakage of intracellular lactate dehydrogenase and mitochondrial function (MTT assay) revealed that simultaneous treatment of A-KG (0.5 mM) and NAC (0.25 mM) significantly prevented the cytotoxicity of cyanide. Also, cellular ATP content was found to improve, followed by restoration of MMP, intracellular calcium [Ca(2+)](i) and lactic acid levels. Treatment with A-KG and NAC also attenuated the levels of peroxides generated by cyanide. The study indicates that combined administration of A-KG and NAC protected the cyanide-challenged PC12 cells by resolving the altered energy metabolism. The results have implications in the development of new treatment regimen for cyanide poisoning.     

In vivo cellular repopulation of tubular elastin scaffolds mediated by basic fibroblast growth factor

In vivo tissue engineering has been explored as a method to repopulate scaffolds with autologous cells to create a functional, living, and non-immunogenic tissue substitute. In this study, we describe an approach to in vivo cellular repopulation of a tissue-derived tubular elastin scaffold. Pure elastin scaffolds were prepared from porcine carotid arteries (elastin tubes). Elastin tubes were filled with agarose gel containing basic fibroblast growth factor (bFGF) to allow sustained release of growth factor. These tubes were implanted in subdermal pouches in adult rats. The elastin tubes with growth factor had significantly more cell infiltration at 28 days than those without growth factor. Immunohistochemical staining indicated that most of these cells were fibroblasts, of which a few were activated fibroblasts (myofibroblasts). Microvasculature was also observed within the scaffolds. Macrophage infiltration was seen at 7 days, which diminished by 28 days of implantation. None of the elastin tubes with bFGF calcified. These results demonstrated that the sustained release of bFGF brings about repopulation of elastin scaffolds in vivo while inhibiting calcification. Results showing myofibroblast infiltration and vascularization are encouraging since such an in vivo implantation technique could be used for autologous cell repopulation of elastin scaffolds for vascular graft applications.     

Normal mouse kidneys contain activated and CD3+CD4- CD8- double-negative T lymphocytes with a distinct TCR repertoire

Healthy liver, intestine, lung, and skin harbor resident lymphocytes with conventional and unconventional phenotypes. Lymphocytes also have been detected in healthy mice kidneys; however, these cells have not been well studied and have been largely overlooked. To better characterize the intra-renal lymphocytes, we extensively perfused C57BL/6J mice with PBS and then isolated mononuclear cells for flow cytometry analysis. We observed T cells, B cells, and NK cells in normal mice kidneys after extensive perfusion. Approximately 50% of kidney T lymphocytes expressed intermediate levels of CD3 (CD3int T cells). Similar to liver and lung, a high percentage of unconventional CD3+CD4(-)CD8(-) double-negative T cells was observed in normal mice kidneys, from which 11% expressed B220 antigen. Unlike the spleen and blood, the classic CD4+ and CD8+ T lymphocytes in the kidney had a high proportion of activated CD69+ and effector/memory CD44- CD62L ligand phenotypes. Also, a small percentage of CD4+CD25+forkhead box p3+ and NKT cells was observed in perfused and exanguinated kidneys. In addition, a distinct TCR repertoire was found on intra-renal conventional and unconventional T cells compared with those from the spleen. Finally, after 24 h of renal ischemia reperfusion injury (IRI), increased production of cytokines IFN-gamma and TNF-alpha by CD4+ and CD8+ T cells, isolated from perfused kidneys, was observed. These data suggest that some of these cells harbored in the kidney could be implicated in the immune response of the IRI pathogenic process.     

Changes in pediatric trauma during COVID-19 stay-at-home epoch at a tertiary pediatric hospital

BackgroundTrauma is the leading cause of morbidity and mortality in the pediatric population. However, during the societal disruptions secondary to the coronavirus (COVID-19) stay-at-home regulations, there have been reported changes to the pattern and severity of pediatric trauma. We review our two-institution experience.MethodsPediatric trauma emergency department (ED) encounters from the National Trauma Registry for a large, tertiary, metropolitan level 1 pediatric trauma center and pediatric burn admission at the regional burn center were extracted for children less than 19 years from March 15th thru May 15th during the years 2015–2020. The primary outcome was the difference in encounters during the COVID-19 (2020) epoch versus the pre-COVID-19 epoch (2015–2019).ResultsThere were 392 pediatric trauma encounters during the COVID-19 epoch as compared to 451, 475, 520, 460, 432 (mean 467.6) during the pre-COVID-19 epoch. Overall trauma admissions and ED trauma encounters were significantly lower (p < 0.001) during COVID-19. Burn injury admissions (p < 0.001) and penetrating trauma encounters (p = 0.002) increased during the COVID-19 epoch while blunt trauma encounters decreased (p < 0.001). Trauma occurred among more white (p = 0.01) and privately insured (p < 0.001) children, but no difference in suspected abuse, injury severity, mortality, age, or gender were detected. Sub-analysis showed significant decreases in motor vehicle crashes (p < 0.001), pedestrians struck by automobile (p < 0.001), all-terrain vehicle (ATV)/motorcross/bicycle/skateboard involved injuries (p = 0.02), falls (p < 0.001), and sports related injuries (p < 0.001). Fewer injuries occurring in the playground or home play equipment such as trampolines neared significance (p = 0.05). Interpersonal violence (assault, NAT, self-harm) was lower during the COVID-19 era (p = 0.04). For burn admissions, there was a significant increase in flame burns (p < 0.001).ConclusionsStay-at-home regulations alter societal patterns, leading to decreased overall and blunt traumas. However, the proportion of penetrating and burn injuries increased. Owing to increased stressors and time spent at home, healthcare professionals should keep a high suspicion for abuse and neglect.     

An fMRI study of causal judgments

The capacity to evaluate causal relations is fundamental to human cognition, and yet little is known of its neurocognitive underpinnings. A functional magnetic resonance imaging study was performed to investigate an hypothesized dissociation between the use of semantic knowledge to evaluate specifically causal relations in contrast to general associative relations. Identical pairs of words were judged for causal or associative relations in different blocks of trials. Causal judgments, beyond associative judgments, generated distinct activation in left dorsolateral prefrontal cortex and right pre-cuneus. These findings indicate that the evaluation of causal relations in semantic memory involves additional neural mechanisms relative to those required to evaluate associative relations.     

Acute toxicity of some synthetic cyanogens in rats and their response to oral treatment with alpha-ketoglutarate

Oral toxicity of several cyanogens and their reversal by alpha-ketoglutarate (A-KG; oral) were studied in rats. LD₅₀ of acetonitrile (ATCN), acrylonitrile (ACN), malononitrile (MCN), propionitrile (PCN), sodium nitroprusside (SNP), and succinonitrile (SCN) was 4891, 143.3, 69.8, 122.9, 69.8 and 488.7 mg/kg, respectively while the protection index of A-KG (ratio of LD₅₀ of cyanogens in the presence or absence of A-KG) was >2.0 against MCN (7.6), PCN (2.7) and SNP (3.6) only. We further studied the efficacy of A-KG against acute toxicity of these three cyanogens (0.75 LD₅₀) on various hematological and biochemical variables in blood and soft tissues 24 h post-exposure. We observed increase in white blood cells (SNP), plasma alanine (PCN, SNP) and aspartate (PCN) aminotransferase, lactate dehydrogenase (MCN, PCN, SNP), Na⁺ (MCN, PCN) and cyanide (PCN), and decrease in K⁺ (MCN, SNP) accompanied by an increase in brain, kidney and liver malondialdehyde (PCN), decrease in brain glutathione peroxidase, glutathione reductase (PCN, SNP), reduced glutathione (MCN, PCN, SNP) and cytochrome oxidase (PCN), liver rhodanese (PCN, SNP), and kidney cytochrome oxidase (PCN). The study indicates that (i) PCN was most toxic among all the cyanogens and (ii) beside cyanide, A-KG could be considered as an effective antidote for cyanogens.