Parrishrocha4584

Despite the known deleterious effects of obesity, clinical data indicate that overweight or obese patients experience higher rates of sepsis survival compared to normal and underweight patients; a phenomenon called the obesity paradox. Results from preclinical sepsis studies have not been able to replicate these findings. The objective of this study was to test the existence of the obesity paradox in a murine model of cecal slurry (CS)-induced sepsis with insulin-resistant diet-induced obese mice. Male C57BL/6 mice were provided high-fat (HFD) or low-fat (LFD) diets for 20 weeks. HFD-fed mice experienced higher rates of survival compared to LFD-fed mice after septic challenge induced by CS injection (66% vs. 25%, p = 0.01, survival assessed for 14 days). Despite the survival advantage, HFD-fed mice had higher rates of positive bacterial cultures and increased markers of kidney injury. Circulating levels of IL-6, IL-1β, TNFα, and IL-23 were equivalent 24 h after CS-injection; however, IL-17A was uniquely incd mice significantly upregulating glycolytic activity and HFD-fed mice decreasing glucose entry into the TCA cycle. This murine study corroborates clinical data that obesity confers a survival benefit in sepsis, albeit at the expense of more significant organ injury. The mechanisms promoting survival in the obese remain unknown; however, this model appears to be well-poised to begin answering this question. Differences in glucose utilization are a novel target to investigate this paradox.

We evaluated the effects of vitamin C and thiamine administration on biomarkers in patients with septic shock.

This was a post-hoc analysis of the Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS) trial, a multi-center, double-blind, randomized controlled trial. Patients were randomized to either a treatment group (intravenous vitamin C and thiamine for 48 h) or a control group. Interleukin (IL)-6, IL-10, angiopoietin-II (AP2), and S100β were assessed at baseline and at 72 h. The primary outcomes were the biomarker levels at 72 h, and the secondary outcome was reduction rate.

Forty-five patients were assigned to the treatment group and 52 were assigned to the control group. Baseline biomarker levels and at 72 h were not significantly different between the treatment and the placebo groups. The reduction rates were not significantly different between the two groups. These outcome variables showed fair diagnostic accuracy for predicting 28-day mortality according to the area under the receiver operating characteristic curve.

Vitamin C and thiamine administration during the early phase of septic shock did not significantly change prognostic biomarker levels of IL-6, IL-10, AP2, and S100β.

NCT, ClinicalTrials.gov NCT03756220, Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS). Registered 28 November 2018, https//clinicaltrials.gov/ct2/show/NCT03756220.

NCT, ClinicalTrials.gov NCT03756220, Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS). Registered 28 November 2018, https//clinicaltrials.gov/ct2/show/NCT03756220.

Traumatic injuries, such as burn, are often complicated by ethanol intoxication at the time of injury. This leads to a myriad of complications and post-burn pathologies exacerbated by aberrant immune responses. Recent findings suggest that immune cell dysfunction in the gastrointestinal system is particularly important in deleterious outcomes associated with burn injuries. In particular, intoxication at the time of burn injury leads to compromised intestinal T cell responses, which can diminish intestinal immunity and promote bacterial translocation, allowing for increased secondary infections in the injured host and associated sequelae, such as multiple organ failure (MOF) and sepsis. Regulatory T cells (Treg) have been identified as important mediators of suppressing effector T cell function. Therefore, the goal of this study was to assess the effects of ethanol intoxication and burn injury on Treg populations in small intestinal immune organs. Deoxycytidine We also evaluated the suppressive capability of Tregs isolateanimals. Male C57BL/6 mice were gavaged with 2.9 g/kg ethanol before receiving a ∼12.5% total body surface area scald burn. One day after injury, we identified a significant increase in Tregs number in small intestine Peyer's patches (∼1.5x) and lamina propria (∼2x). Tregs producing cytokine IL-10 were also increased in both tissues. Finally, Tregs isolated from ethanol and burn injured mice were able to suppress proliferation of effector T cells to a greater degree than sham vehicle Tregs. This was accompanied by increased levels of IL-10 and decreased levels of pro-proliferative cytokine IL-2 in cultures containing ethanol + burn Tregs compared to sham Tregs. These findings suggest that Treg populations are increased in intestinal tissues one day following ethanol intoxication and burn injury. Tregs isolated from ethanol and burn injured animals also exhibit a greater suppression of effector T cell proliferation, which may contribute to altered T cell responses following injury.

Vagus nerve stimulation has been shown to exert anti-inflammation activities in sepsis. However, surgical implantation of stimulation devices is performed under general anaesthesia, which limits its clinical application. Auricular vagus nerve stimulation (AVNS) is a minimal invasive technique which delivers electrical currents to the auricular branch of the vagus nerve. The purpose of this study was to determine the effects of AVNS on systemic inflammation, lung injury, neutrophil infiltration and neutrophil extracellular traps (NETs) formation in the lung. In a lipopolysaccharide (LPS) challenge lung-injury mice model, AVNS was applied to bilateral ears. Twelve hours after LPS administration, samples of blood, bronchoalveolar lavage fluid (BALF) and lung tissues were processed for investigations. We found that the treatment with AVNS significantly attenuated histopathological changes and neutrophil infiltration in the lung tissue, inhibited inflammatory cytokine elevations in serum and BALF and decreased pe model, AVNS was applied to bilateral ears. Twelve hours after LPS administration, samples of blood, bronchoalveolar lavage fluid (BALF) and lung tissues were processed for investigations. We found that the treatment with AVNS significantly attenuated histopathological changes and neutrophil infiltration in the lung tissue, inhibited inflammatory cytokine elevations in serum and BALF and decreased protein concentrations in BALF. Besides, AVNS decreased leukocyte and neutrophil accounts in BALF. Furthermore, co-localization of citrullination of histone H3 and myeloperoxidase expressions (highly specific marker of NETs) was reduced in AVNS mice. In conclusion, AVNS reduced systemic inflammation, attenuated lung edema and inhibited neutrophil infiltration and NETs formation in the lung in LPS mice.

Collectively, an individual's ability and willingness to adjust to uncertain and complex changes in the workplace and an environment that supports employee problem-solving may facilitate individual-level adaptation to changes in the workplace and help mitigate the negative impact of work-related stressors on health care professionals' work-related behavior and mental health outcomes.

This study uses an interactionist perspective to assess how resources such as perceived adaptivity and organizational support for innovation serve as contextual boundary conditions of role overload in mitigating emotional exhaustion among health care workers.

A cross-sectional survey design was used to collect data from rural health care workers (n = 310). A moderated moderation analysis was performed to address the aims of the study.

The results indicate that role overload has a significant positive effect on emotional exhaustion. Furthermore, a statistically significant three-way interaction effect of perceived adaptivity, organizational support for innovation, and role overload on emotional exhaustion was observed. Organizational support for innovation was found to mitigate the negative impact of role overload on emotional exhaustion for employees with high perceived adaptivity, but not for those with low perceived adaptivity levels.

The findings from this study suggest that in high-stress work environments, integrating and appropriately matching personal and organizational resources could serve as a buffer against the effects of work stressors on emotional exhaustion.

Effective strategies to enhance employee emotional well-being may require the joint consideration of individual and organizational factors.

Effective strategies to enhance employee emotional well-being may require the joint consideration of individual and organizational factors.

Electrical stimulation through depth electrodes is used to map function and seizure onset during stereoelectroencephalography in patients undergoing evaluation for epilepsy surgery. Factors such as electrode design, location, and orientation are expected to impact effects of electrical stimulation.

We developed a steady-state finite element model of brain tissue including five layers (skull through white matter) and an implanted electrode to explore the impact of electrode design and placement on the activation of brain tissue by electrical stimulation. We calculated electric potentials, current densities, and volume of tissue activated (Volact) in response to constant current bipolar stimulation. We modeled two depth electrode designs (3.5- and 4.43-mm intercontact spacing) and varied electrode location and orientation.

The electrode with greater intercontact spacing produced 8% to 23% larger Volact (1% to 16% considering only gray matter). Vertical displacement of the electrodes by half intercontact smmonly used designs. Individualization of stimulation intensity at each location remains critical, especially for avoiding false-negative results.

Previously, we showed that a three-pulse train of weak transcranial magnetic stimulation (TMS) pulses-a superconditioning (SC) train-when followed by a stronger TMS pulse could enhance the inhibition or facilitation of the resultant motor evoked potential (MEP) compared with that seen with traditional dual-pulse inputs. The purpose of the present study was to establish the relative minimum intensity of SC pulses needed to influence MEP output and whether this differed for upper- versus lower-limb muscles.

We examined 33 older adult subjects, targeting abductor pollicis brevis and tibialis anterior muscles. Older subjects were included in the anticipation of using findings from this study to guide further studies in persons with amyotrophic lateral sclerosis. Three-pulse trains of SC inputs of different intensities were delivered either 1 millisecond before (for inhibition) or 10 millisecond before (for facilitation) a stronger TMS test pulse. Motor evoked potential magnitudes for SC +test sets were normalresting three-pulse MEP threshold for most abductor pollicis brevis and tibialis anterior muscles (2-millisecond interpulse intervals). For facilitation, somewhat higher intensities (70%) were typically needed to cause facilitation. Both values of SC pulses for inhibition/facilitation are considerably lower than the intensity of the conditioning pulse-often reported as 80% of the single-pulse threshold-typically used in dual-pulse TMS paradigms. This approach may allow testing of upper motor neuron function using weaker stimulus pulse intensities than are typically employed, improving testing compliance in persons whose thresholds are elevated because of injury or disease.