Necrotizing enterocolitis (NEC) remains a devastating disease that affects preterm infants. Hydrogen sulfide (H
S) donors have been shown to reduce the severity of NEC, but the optimal compound has ...yet to be identified. We hypothesized that oral H
S-Mesalamine (ATB-429) would improve outcomes in experimental NEC, and its benefits would be dependent on endothelial nitric oxide synthase (eNOS) pathways. NEC was induced in 5-day-old wild-type (WT) and eNOS knockout (eNOSKO) pups by formula feeding and stress. Four groups were studied in both WT and eNOSKO mice:
) breastfed controls,
) NEC,
) NEC + 50 mg/kg mesalamine, and
) NEC + 130 mg/kg ATB-429. Mesalamine and ATB-429 doses were equimolar. Pups were monitored for sickness scores and perfusion to the gut was measured by Laser Doppler Imaging (LDI). After euthanasia of the pups, intestine and lung were hematoxylin and eosin-stained and scored for injury in a blind fashion. TLR4 expression was quantified by Western blot and IL-6 expression by ELISA.
< 0.05 was significant. Both WT and eNOSKO breastfed controls underwent normal development and demonstrated milder intestinal and pulmonary injury compared with NEC groups. For the WT groups, ATB-429 significantly improved weight gain, reduced clinical sickness score, and improved perfusion compared with the NEC group. In addition, WT ATB-429 pups had a significantly milder intestinal and pulmonary histologic injury when compared with NEC. ATB-429 attenuated the increase in TLR4 and IL-6 expression in the intestine. When the experiment was repeated in eNOSKO pups, ATB-429 offered no benefit in weight gain, sickness scores, perfusion, intestinal injury, pulmonary injury, or decreasing intestinal inflammatory markers. An H
S derivative of mesalamine improves outcomes in experimental NEC. Protective effects appear to be mediated through eNOS. Further research is warranted to explore whether ATB-429 may be an effective oral therapy to combat NEC.
•Certain regulatory agencies have suggested that covering the operating room instrument table during periods of nonuse may decrease the bioburden on the table.•Instrument table covers decrease ...bioburden on the instrument table during static and dynamic conditions.•Instrument table covers should be considered for use during periods of nonuse and during active surgery to decrease bioburden near the instruments.
Covering the instrument table during surgery may decrease contamination. We hypothesized that (1) covering the instrument table in an operating room (OR) during static periods of nonuse and dynamic periods of active use would dramatically decrease the bacterial bioburden on the table, and (2) the use of sterile plastic table covers would be equivalent to sterile impervious paper covers in reducing the bioburden in a dynamic environment.
Bacterial contamination of the instrument table was evaluated by settle plates in static and dynamic ORs. Airborne particulate and bacterial contaminants were sampled throughout the room. Tested groups included instrument tables covered with sterile impervious paper covers, sterile plastic covers, or no covers.
Covering the instrument table during static and dynamic operating room conditions resulted in a significantly decreased bacterial load on the instrument table. No differences were seen between paper and plastic covers.
A significant decrease in bacterial bioburden on the instrument table when the table was covered during static and dynamic periods was observed, suggesting the utility for covering the instrument table during periods of nonuse and during active surgeries.
Necrotizing enterocolitis (NEC) in premature infants is often a devastating surgical condition with poor outcomes. GYY4137 is a long-acting donor of hydrogen sulfide, a gasotransmitter that is ...protective against intestinal injury in experimental NEC, likely through protection against injury secondary to ischemia. We hypothesized that administration of GYY4137 would improve mesenteric perfusion, reduce intestinal injury, and reduce inflammatory responses in experimental NEC and ischemia-reperfusion injury, and that these benefits would be mediated through endothelial nitric oxide synthase–dependent pathways.
NEC was induced in C57BL/6 wild-type (WT) and endothelial nitric oxide synthase (eNOS) knockout (eNOSKO) pups via maternal separation, formula feeding, enteral lipopolysaccharide, and intermittent hypoxic and hypothermic stress. Pups received daily intraperitoneal injections of 50 mg/kg GYY4137 or phosphate buffered saline vehicle. In separate groups, adult male WT and eNOSKO mice underwent superior mesenteric artery occlusion for 60 min. Before abdominal closure, 50 mg/kg GYY4137 or phosphate buffered saline vehicle was administered into the peritoneal cavity. Laser doppler imaging was used to assess mesenteric perfusion of pups at baseline and on postnatal day 9, and the adult mice at baseline and 24 h after ischemic insult. After euthanasia, the terminal ileum of each animal was fixed, paraffin embedded, sectioned, and stained with hematoxylin and eosin. Sections were blindly graded using published injury scores. Intestinal tissue was homogenized and cytokines measured by ELISA. Data were compared using Mann–Whitney U test, and P-values <0.05 were significant.
After NEC and ischemia reperfusion (I/R) injury, GYY4137 improved perfusion in WT mice compared to vehicle, but this effect was lost in the eNOSKO animals. Histologic injury followed a similar pattern with reduced intestinal injury in WT mice treated with GYY4137, and no significant improvement in the eNOSKO group. Cytokine expression after GYY4137 administration was altered by the ablation of eNOS in both NEC and I/R injury groups, with significant differences noted in Interleukin 6 and vascular endothelial growth factor.
GYY4137, a long-acting donor of hydrogen sulfide, has potential as a therapeutic compound for NEC. It improves mesenteric perfusion and intestinal injury in experimental NEC and intestinal I/R injury, and these benefits appear to be mediated through eNOS-dependent pathways.
Necrotizing enterocolitis (NEC) is a destructive gastrointestinal disease primarily affecting preterm babies. Despite advancements in neonatal care, NEC remains a significant cause of morbidity and ...mortality in neonatal intensive care units worldwide and the etiology of NEC is still unclear. Risk factors for NEC include prematurity, very low birth weight, feeding with formula, intestinal dysbiosis and bacterial infection. A review of the literature would suggest that supplementation of prebiotics and probiotics prevents NEC by altering the immune responses. Innate T cells, a highly conserved subpopulation of T cells that responds quickly to stimulation, develops differently from conventional T cells in neonates. This review aims to provide a succinct overview of innate T cells in neonates, encompassing their phenotypic characteristics, functional roles, likely involvement in the pathogenesis of NEC, and potential therapeutic implications.
ABSTRACTThe development of new vasculature plays a significant role in a number of chronic disease states, including neoplasm growth, peripheral arterial disease, and coronary artery disease, among ...many others. Traumatic injury and hemorrhage, however, is an immediate, often dramatic pathophysiologic insult which can also necessitate neovascularization to promote healing. Traditional understanding of angiogenesis involved resident endothelial cells branching outward from localized niches in the periphery. Additionally, there are a small number of circulating endothelial progenitor cells which participate directly in the process of neovessel formation. The bone marrow stores a relatively small number of so-called pro-angiogenic hematopoietic progenitor cells (PACs) – that is, progenitor cells of a hematopoietic potential that differentiate into key structural cells and stimulate or otherwise support local cell growth/differentiation at the site of angiogenesis. Following injury, a number of cytokines and intercellular processes are activated or modulated to promote development of new vasculature. These processes initiate and maintain a robust response to vascular insult, allowing new vessels to canalize and anastomose and provide timely oxygen delivering to healing tissue. Ultimately as we better understand the key players in the process of angiogenesis we can look to develop novel techniques to promote healing following injury.
Highlights • This study tests air quality indicators in a dynamic operating room environment. • A mock surgical procedure led by a board-certified surgeon was used to simulate actual conditions in an ...operating room to provide realistic data. • Levels of airborne contaminants in a health care setting can be accurately quantified using this testing protocol. • Environmental quality indicators, such as number of particles, microbial contaminant load, air velocity, and temperature, provide insight to the effectiveness of heating, ventilation, and air conditioning systems.
Congenital diaphragmatic hernia (CDH) carries high morbidity and mortality, and survivors commonly have neurodevelopmental, gastrointestinal, and pulmonary sequela requiring multidisciplinary care ...well beyond repair. We predict that following hospitalization for repair, CDH survivors face many barriers to receiving future medical care.
A retrospective review was conducted of all living CDH patients between ages 0 to 12 years who underwent repair at Riley Hospital for Children (RHC) from 2010 through 2019. Follow-up status with specialty providers was reviewed, and all eligible families were contacted to complete a survey regarding various aspects of their child's care, including functional status, quality of life, and barriers to care. Bivariate analysis was applied to patient data (P < 0.05 was significant) and survey responses were analyzed qualitatively.
After exclusions, 70 survivors were contacted. Thirty-three (47%) were deemed lost to follow up to specialist providers, and were similar to those who maintained follow-up with respect to defect severity type (A-D, P = 0.57), ECMO use (P = 0.35), number of affected organ systems (P = 0.36), and number of providers following after discharge (P = 0.33). Seventeen (24%) families completed the survey, of whom eight (47%) were deemed lost to follow up to specialist providers. Families reported distance and time constraints, access to CDH-specific information and care, access to CDH-specific resources, and access to healthcare as significant barriers to care. All respondents were interested in a multidisciplinary CDH clinic.
CDH survivors require multidisciplinary care beyond initial repair, but attrition to follow-up after discharge is high. A multidisciplinary CDH clinic may address caregivers’ perceived barriers.
•We found low air velocity rates at back table which could lead to contamination of instruments.•The levels of microbial contaminants measured led to the conclusion that higher ventilation rates do ...not equate to cleaner, fewer colony forming units, whereas particle data were less conclusive because of variations during Bovie use.•We developed realistic estimates of the financial cost of higher operating room ventilation rates.•We obtained actual air quality data during a dynamic mock surgical procedure to facilitate evidence-based design of operating room systems.
Hospitals face growing pressure to meet the dual but often competing goals of providing a safe environment while controlling operating costs. Evidence-based data are needed to provide insight for facility management practices to support these goals.
The quality of the air in 3 operating rooms was measured at different ventilation rates. The energy cost to provide the heating, ventilation, and air conditioning to the rooms was estimated to provide a cost-benefit comparison of the effectiveness of different ventilation rates currently used in the health care industry.
Simply increasing air change rates in the operating rooms tested did not necessarily provide an overall cleaner environment, but did substantially increase energy consumption and costs. Additionally, and unexpectedly, significant differences in microbial load and air velocity were detected between the sterile fields and back instrument tables.
Increasing the ventilation rates in operating rooms in an effort to improve clinical outcomes and potentially reduce surgical site infections does not necessarily provide cleaner air, but does typically increase operating costs. Efficient distribution or management of the air can improve quality indicators and potentially reduce the number of air changes required. Measurable environmental quality indicators could be used in lieu of or in addition to air change rate requirements to optimize cost and quality for an operating room and other critical environments.
Hydrogen sulfide (H
S) is an endogenous gasotransmitter that has vasodilatory properties. It may be a novel therapy for intestinal ischemia-reperfusion (I/R) injury. We hypothesized that
) H
S would ...improve postischemic survival, mesenteric perfusion, mucosal injury, and inflammation compared with vehicle and
) the benefits of H
S would be mediated through endothelial nitric oxide. C57BL/6J wild-type and endothelial nitric oxide synthase knockout (eNOS KO) mice were anesthetized, and a midline laparotomy was performed. Intestines were eviscerated, the small bowel mesenteric root identified, and baseline intestinal perfusion was determined using laser Doppler. Intestinal ischemia was established by temporarily occluding the superior mesenteric artery. Following ischemia, the clamp was removed, and the intestines were allowed to recover. Either sodium hydrosulfide (2 nmol/kg or 2 µmol/kg NaHS) in PBS vehicle or vehicle only was injected into the peritoneum. Animals were allowed to recover and were assessed for mesenteric perfusion, mucosal injury, and intestinal cytokines.
values < 0.05 were significant. H
S improved mesenteric perfusion and mucosal injury scores following I/R injury. However, in the setting of eNOS ablation, there was no improvement in these parameters with H
S therapy. Application of H
S also resulted in lower levels of intestinal cytokine production following I/R. Intraperitoneal H
S therapy can improve mesenteric perfusion, intestinal mucosal injury, and intestinal inflammation following I/R. The benefits of H
S appear to be mediated through endothelial nitric oxide-dependent pathways.
H
S is a gaseous mediator that acts as an anti-inflammatory agent contributing to gastrointestinal mucosal defense. It promotes vascular dilation, mucosal repair, and resolution of inflammation following intestinal ischemia and may be exploited as a novel therapeutic agent. It is unclear whether H
S works through nitric oxide-dependent pathways in the intestine. We appreciate that H
S was able to improve postischemic recovery of mesenteric perfusion, mucosal integrity, and inflammation. The beneficial effects of H
S appear to be mediated through endothelial nitric oxide-dependent pathways.
Gastrointestinal (GI) diseases have a high prevalence throughout the United States. Screening and diagnostic modalities are often expensive and invasive, and therefore, people do not utilize them ...effectively. Lack of proper screening and diagnostic assessment may lead to delays in diagnosis, more advanced disease at the time of diagnosis, and higher morbidity and mortality rates. Research on the intestinal microbiome has demonstrated that dysbiosis, or unfavorable alteration of organismal composition, precedes the onset of clinical symptoms for various GI diseases. GI disease diagnostic research has led to a shift towards non-invasive methods for GI screening, including chemical-detection tests that measure changes in volatile organic compounds (VOCs), which are the byproducts of bacterial metabolism that result in the distinct smell of stool. Many of these tools are expensive, immobile benchtop instruments that require highly trained individuals to interpret the results. These attributes make them difficult to implement in clinical settings. Alternatively, electronic noses (E-noses) are relatively cheaper, handheld devices that utilize multi-sensor arrays and pattern recognition technology to analyze VOCs. The purpose of this review is to (1) highlight how dysbiosis impacts intestinal diseases and how VOC metabolites can be utilized to detect alterations in the microbiome, (2) summarize the available VOC analytical platforms that can be used to detect aberrancies in intestinal health, (3) define the current technological advancements and limitations of E-nose technology, and finally, (4) review the literature surrounding several intestinal diseases in which headspace VOCs can be used to detect or predict disease.
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