Modulation of Acetylation: Creating a Pro-survival and Anti-Inflammatory Phenotype in Lethal Hemorrhagic and Septic Shock

Histone deacetylases (HDACs) play a key role in homeostasis of protein acetylation in histone and nonhistone proteins and in regulating fundamental cellular activities. In this paper we review and discuss intriguing recent developments in the use of histone deacetylase inhibitors (HDACIs) to combat some critical conditions in an animal model of hemorrhagic and septic shock. HDACIs have neuroprotective, cardioprotective, renal-protective, and anti-inflammatory properties; survival improvements have been significantly shown in these models. We discuss the targets and mechanisms underlying these effects of HDACIs and comment on the potential new clinical applications for these agents in the future. This paper highlights the emerging roles of HDACIs as acetylation modulators in models of hemorrhagic and septic shock and explains some contradictions encountered in previous studies

Hypothermia in bleeding trauma: a friend or a foe?

The induction of hypothermia for cellular protection is well established in several clinical settings. Its role in trauma patients, however, is controversial. This review discusses the benefits and complications of induced hypothermia--emphasizing the current state of knowledge and potential applications in bleeding patients. Extensive pre-clinical data suggest that in advanced stages of shock, rapid cooling can protect cells during ischemia and reperfusion, decrease organ damage, and improve survival. Yet hypothermia is a double edged sword; unless carefully managed, its induction can be associated with a number of complications. Appropriate patient selection requires a thorough understanding of the pre-clinical literature. Clinicians must also appreciate the enormous influence that temperature modulation exerts on various cellular mechanisms. This manuscript aims to provide a balanced view of the published literature on this topic. While many of the advantageous molecular and physiological effects of induced hypothermia have been outlined in animal models, rigorous clinical investigations are needed to translate these promising findings into clinical practice

Resuscitation speed affects brain injury in a large animal model of traumatic brain injury and shock

Background: Optimal fluid resuscitation strategy following combined traumatic brain injury (TBI) and hemorrhagic shock (HS) remain controversial and the effect of resuscitation infusion speed on outcome is not well known. We have previously reported that bolus infusion of fresh frozen plasma (FFP) protects the brain compared with bolus infusion of 0.9% normal saline (NS). We now hypothesize reducing resuscitation infusion speed through a stepwise infusion speed increment protocol using either FFP or NS would provide neuroprotection compared with a high speed resuscitation protocol. Methods: 23 Yorkshire swine underwent a protocol of computer controlled TBI and 40% hemorrhage. Animals were left in shock (mean arterial pressure of 35 mmHg) for two hours prior to resuscitation with bolus FFP (n = 5, 50 ml/min) or stepwise infusion speed increment FFP (n = 6), bolus NS (n = 5, 165 ml/min) or stepwise infusion speed increment NS (n = 7). Hemodynamic variables over a 6-hour observation phase were recorded. Following euthanasia, brains were harvested and lesion size as well as brain swelling was measured. Results: Bolus FFP resuscitation resulted in greater brain swelling (22.36 ± 1.03% vs. 15.58 ± 2.52%, p = 0.04), but similar lesion size compared with stepwise resuscitation. This was associated with a lower cardiac output (CO: 4.81 ± 1.50 l/min vs. 5.45 ± 1.14 l/min, p = 0.03). In the NS groups, bolus infusion resulted in both increased brain swelling (37.24 ± 1.63% vs. 26.74 ± 1.33%, p = 0.05) as well as lesion size (3285.44 ± 130.81 mm3 vs. 2509.41 ± 297.44 mm3, p = 0.04). This was also associated with decreased cardiac output (NS: 4.37 ± 0.12 l/min vs. 6.35 ± 0.10 l/min, p < 0.01). Conclusions: In this clinically relevant model of combined TBI and HS, stepwise resuscitation protected the brain compared with bolus resuscitation

Varietal Performance and Effect of Planting Method on Yield and Yield Contributing Characteristics of Rice

The experiment was carried out to study the performance of two aman rice varieties (BRRI dhan31 and BRRI dhan41) under different planting methods (line sowing with sprouted seeds by drum seeder, haphazard transplanting and transplanting in line). Both the variety and planting method had significant effect on crop characters plant height, number of total tillers m-2, effective tillers m-2, grains panicle-1, sterile spikelet's panicle-1, total spikelet's panicle-1, grain yield except panicle length and 1000-grain weight. BRRI dhan41 produced the highest grain yield (4.06 t ha-1). Line sowing method with sprouted seeds by drum seeder showed better performance in respect of no. total tillers m-2 (415.81), effective tillers m-2 (401.85) and grain yield (4.80 t ha-1). The highest no. of total tillers m-2 (421.12), effective tillers m-2 (410.65) and grain yield (5.08 t ha-1) were recorded due to effect of the interaction of line sowing method with sprouted seeds by drum seeder and the variety BRRI dhan41

eClinic: increasing use of telehealth as a risk reduction strategy during the covid-19 pandemic

Prior to the covid-19 pandemic, telehealth was already being rapidly adopted nationally by healthcare systems. During the covid-19 pandemic, increased use of telehealth may be considered as a risk reduction strategy. Benefits of this strategy may be conferred to both patients and health providers.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155565/1/Kemp_Williams_Alam_eClinic.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155565/4/DeepBluepermissions_agreement-CCBYandCCBY-NC_ORCID.pdfDescription of Kemp_Williams_Alam_eClinic.pdf : ArticleDescription of DeepBluepermissions_agreement-CCBYandCCBY-NC_ORCID.pdf : Deep Blue sharing agreemen

An Integrated Plasmo‐Photoelectronic Nanostructure Biosensor Detects an Infection Biomarker Accompanying Cell Death in Neutrophils

Bacterial infections leading to sepsis are a major cause of deaths in the intensive care unit. Unfortunately, no effective methods are available to capture the early onset of infectious sepsis near the patient with both speed and sensitivity required for timely clinical treatment. To fill the gap, the authors develop a highly miniaturized (2.5 × 2.5 µm2) plasmo‐photoelectronic nanostructure device that detected citrullinated histone H3 (CitH3), a biomarker released to the blood circulatory system by neutrophils. Rapidly detecting CitH3 with high sensitivity has the great potential to prevent infections from developing life‐threatening septic shock. To this end, the author’s device incorporates structurally engineered arrayed hemispherical gold nanoparticles that are functionalized with high‐affinity antibodies. A nanoplasmonic resonance shift induces a photoconduction increase in a few‐layer molybdenum disulfide (MoS2) channel, and it provides the sensor signal. The device achieves label‐free detection of serum CitH3 with a 5‐log dynamic range from 10−4 to 101 ng mL and a sample‐to‐answer time <20 min. Using this biosensor, the authors longitudinally measure the dynamic CitH3 profiles of individual living mice in a sepsis model at high resolution over 12 hours. The developed biosensor may be poised for future translation to personalized management of systemic bacterial infections.The lack of an appropriate biosensing technology to detect the early onset of bacterial infections has prohibited timely clinical treatment of sepitc shock. This article presents a highly miniaturized plasmo‐photoelectronic device incorporating high‐affinity antibody‐conjugated hemispherical gold nanoparticles and a few‐layer molybdenum disulfide (MoS2) photoconductive channel to detect a blood biomarker released by neutrophils with high speed and sensitivity.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152883/1/smll201905611-sup-0001-SuppMat.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152883/2/smll201905611_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152883/3/smll201905611.pd

Fresh Frozen Plasma Resuscitation Provides Neuroprotection Compared to Normal Saline in a Large Animal Model of Traumatic Brain Injury and Polytrauma

We have previously shown that early treatment with fresh frozen plasma (FFP) is neuroprotective in a swine model of hemorrhagic shock (HS) and traumatic brain injury (TBI). However, it remains unknown whether this strategy would be beneficial in a more clinical polytrauma model. Yorkshire swine (42?50?kg) were instrumented to measure hemodynamic parameters, brain oxygenation, and intracranial pressure (ICP) and subjected to computer-controlled TBI and multi-system trauma (rib fracture, soft-tissue damage, and liver injury) as well as combined free and controlled hemorrhage (40% blood volume). After 2?h of shock (mean arterial pressure, 30?35?mm Hg), animals were resuscitated with normal saline (NS; 3?volume) or FFP (1?volume; n=6/group). Six hours postresuscitation, brains were harvested and lesion size and swelling were evaluated. Levels of endothelial-derived vasodilator endothelial nitric oxide synthase (eNOS) and vasoconstrictor endothelin-1 (ET-1) were also measured. FFP resuscitation was associated with reduced brain lesion size (1005.8 vs. 2081.9?mm3; p=0.01) as well as swelling (11.5% vs. 19.4%; p=0.02). Further, FFP-resuscitated animals had higher brain oxygenation as well as cerebral perfusion pressures. Levels of cerebral eNOS were higher in the FFP-treated group (852.9 vs. 816.4?ng/mL; p=0.03), but no differences in brain levels of ET-1 were observed. Early administration of FFP is neuroprotective in a complex, large animal model of polytrauma, hemorrhage, and TBI. This is associated with a favorable brain oxygenation and cerebral perfusion pressure profile as well as higher levels of endothelial-derived vasodilator eNOS, compared to normal saline resuscitation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140168/1/neu.2014.3535.pd

Resuscitation with Valproic Acid Alters Inflammatory Genes in a Porcine Model of Combined Traumatic Brain Injury and Hemorrhagic Shock

Traumatic brain injury and hemorrhagic shock (TBI+HS) elicit a complex inflammatory response that contributes to secondary brain injury. There is currently no proven pharmacologic treatment for TBI+HS, but modulation of the epigenome has been shown to be a promising strategy. The aim of this study was to investigate whether valproic acid (VPA), a histone deacetylase inhibitor, modulates the expression of cerebral inflammatory gene profiles in a large animal model of TBI+HS. Ten Yorkshire swine were subjected to computer-controlled TBI+HS (40% blood volume). After 2?h of shock, animals were resuscitated with Hextend (HEX) or HEX+VPA (300?mg/kg, n?=?5/group). Six hours after resuscitation, brains were harvested, RNA was isolated, and gene expression profiles were measured using a porcine microarray. Ingenuity Pathway Analysis? (IPA), gene ontology (GO), Parametric Gene Set Enrichment Analysis (PGSEA), and DAVID (Database for Annotation, Visualization, and Integrated Discovery) were used for pathway analysis. Key microarray findings were verified using real-time polymerase chain reaction (PCR). IPA analysis revealed that VPA significantly down-regulated the complement system (p?Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140171/1/neu.2015.4163.pd