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The ability of the body to maintain homeostasis requires constant communication between the brain and peripheral tissues. Different organs produce signals, often in the form of hormones, which are detected by the hypothalamus. In response, the hypothalamus alters its regulation of bodily processes, which is achieved through its own pathways of hormonal communication. The generation and transmission of the molecules involved in these bi-directional axes can be affected by redox balance. The essential trace element selenium is known to influence numerous physiological processes, including energy homeostasis, through its various redox functions. Selenium must be obtained through the diet and is used to synthesize selenoproteins, a family of proteins with mainly antioxidant functions. Alterations in selenium status have been correlated with homeostatic disturbances in humans and studies with animal models of selenoprotein dysfunction indicate a strong influence on energy balance. The relationship between selenium and energy metabolism is complicated, however, as selenium has been shown to participate in multiple levels of homeostatic communication. This review discusses the role of selenium in the various pathways of communication between the body and the brain that are essential for maintaining homeostasis.

Intravenous push (IVP) diltiazem and metoprolol are commonly used for management of atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED). This study's objective was to determine if there was a significant difference in blood pressure reduction between agents. This was a single-center, retrospective study of adult patients initially treated with IVP diltiazem or metoprolol in the ED from 2008 to 2018. Primary endpoint was mean reduction in systolic blood pressure (SBP) from baseline to nadir during the study period. Study period was defined as time from first dose of IVP intervention to 30 min after last dose of IVP intervention or first dose of maintenance therapy, whichever came first. A total of 63 diltiazem patients and 45 metoprolol patients met eligibility criteria. Baseline characteristics were similar except for initial ventricular rate (VR) and home beta-blocker use. Median dose of initial intervention was 10 [10−20] mg and 5 [5–5] mg for diltiazem and metoprolol respectively. Mean SBP reduction was 18 ± 22 mmHg for diltiazem compared to 14 ± 15 mmHg for metoprolol (p = .33). Clinically relevant hypotension was similar between groups 14% vs. 16% (p = .86). Rate control was achieved in 35 (56%) of the diltiazem group and 16 (36%) of the metoprolol group (p = .04). IVP diltiazem and metoprolol caused similar SBP reduction and hypotension when used for initial management of AF with RVR in the ED. However, rate control was achieved more often with diltiazem. •IVP diltiazem versus metoprolol for atrial fibrillation with rapid ventricular rate.•Hypotension and blood pressure reduction were similar between agents.•Rate control was achieved more often with diltiazem.•Fixed diltiazem dosing was commonly used and likely impacted outcomes.

Abstract The Whipple operation is oftentimes considered one of the most challenging and complex abdominal operations, usually reserved for duodenal and hepatopancreatobiliary malignancies. In cases of duodenal and/or pancreatic trauma with disruption of the biliary systems, a Whipple reconstruction can be performed. Such operative traumas are rare and carry with them a high level of morbidity and mortality. This case report presents a challenging 46-day clinical course of a 22-year-old African American female, who suffered multiple gunshot wounds, resulting in severe abdominal injuries. These injuries included a grade 3 duodenal injury, grade 4 pancreatic injury, and a grade 4 renal injury. The patient underwent a staged Whipple operation. Postoperative complications included pancreaticojejunostomy leak, feeding tube leak, and mesenteric bleeding, all of which required surgical and interventional radiology management. After a 46-day hospitalization, the patient was discharged to a rehab facility, achieving an impressive recovery 2 years post-surgery.

Abstract Resuscitative thoracotomy is an invasive, morbid procedure indicated in the emergent management of blunt or penetrating trauma to the chest. It allows for rapid access to the thoracic cavity and treatment of the underlying pathology. Survival following traumatic cardiac injury relies on a near-impeccable combination of rapid assessment by properly trained emergency medical services personnel, rapid transport to a capable emergency center, accelerated access to the thoracic cavity within 10 min of cardiopulmonary resuscitation initiation, and excellent perioperative resuscitation. Overall survival rate following resuscitative thoracotomy in the United States is 9.6%. In addition, not all who survive make an acceptable neurocognitive recovery, with one large meta-analysis quoting only 92.4%. We report on two patients who survived and made a complete neurocognitive recovery following emergency department thoracotomy secondary to penetrating cardiac trauma. Both patients were discharged from the hospital within 16 days of their emergency department thoracotomy.

The practice of relational leadership is essential for dealing with the increasingly urgent and complex social, economic and environmental issues that characterize sustainability. Despite growing attention to both relational leadership and leadership for sustainability, an ethical understanding of both is limited. This is problematic as both sustainability and relational leadership are rife with moral implications. This paper conceptually explores how the moral theory of 'ethics of care' can help to illuminate the ethical dimensions of relational leadership for sustainability. In doing so, the implications of ethics of care more broadly for the practice of relational leadership development are elaborated. From a caring perspective, a 'relational stance' or logic of effectiveness can be fostered through engaging in a reflective process of moral education through conversation. In starting this dialogue, we can begin to build capacity for relational leadership for sustainability and, thus, support the development of individual well-being and organizational and societal flourishing.

The use of glucocorticoid medications is known to cause metabolic side effects such as overeating, excess weight gain, and insulin resistance. The hypothalamus, a central regulator of feeding behavior and energy expenditure, is highly responsive to glucocorticoids, and it has been proposed that it plays a role in glucocorticoid-induced metabolic defects. Glucocorticoids can alter the expression and activity of antioxidant enzymes and promote the accumulation of reactive oxygen species. Recent evidence indicates that selenium can counter the effects of glucocorticoids, and selenium is critical for proper hypothalamic function. This study sought to determine whether selenium is capable of protecting hypothalamic cells from dysfunction caused by glucocorticoid exposure. We treated mHypoE-44 mouse hypothalamic cells with corticosterone to study the effects on cellular physiology and the involvement of selenium. We found that corticosterone administration rendered cells more vulnerable to endoplasmic reticulum stress and the subsequent impairment of insulin signaling. Supplementing the cell culture media with additional selenium alleviated endoplasmic reticulum stress and promoted insulin signaling. These findings implicate a protective role of selenium against chronic glucocorticoid-induced hypothalamic dysfunction.

The efficient retrieval of synaptic vesicle membrane and cargo in central nerve terminals is dependent on the efficient recruitment of a series of endocytosis modes by different patterns of neuronal activity. During intense neuronal activity the dominant endocytosis mode is activity-dependent endocytosis (ADBE). Triggering of ADBE is linked to calcineurin-mediated dynamin I dephosphorylation since the same stimulation intensities trigger both. Dynamin I dephosphorylation is maximised by a simultaneous inhibition of its kinase glycogen synthase kinase 3 (GSK3) by the protein kinase Akt, however it is unknown how increased neuronal activity is transduced into Akt activation. To address this question we determined how the activity-dependent increases in intracellular free calcium ([Ca 2+ ] i ) control activation of Akt. This was achieved using either trains of high frequency action potentials to evoke localised [Ca 2+ ] i increases at active zones, or a calcium ionophore to raise [Ca 2+ ] i uniformly across the nerve terminal. Through the use of either non-specific calcium channel antagonists or intracellular calcium chelators we found that Akt phosphorylation (and subsequent GSK3 phosphorylation) was dependent on localised [Ca 2+ ] i increases at the active zone. In an attempt to determine mechanism, we antagonised either phosphatidylinositol 3-kinase (PI3K) or calmodulin. Activity-dependent phosphorylation of both Akt and GSK3 was arrested on inhibition of PI3K, but not calmodulin. Thus localised calcium influx in central nerve terminals activates PI3K via an unknown calcium sensor to trigger the activity-dependent phosphorylation of Akt and GSK3.

Chronic stress, a frequently reported issue among adults, is known to have detrimental effects on health, particularly in the brain. Chronic stress is linked to mood and memory disturbances thought to be caused, in part, by alterations in hippocampal functions. Chronic stress hormone exposure causes neuronal cell death, dendritic spine shrinkage, and loss of neuronal stem cells, among other impairments, which are thought to precede mood and memory disturbances. Long-term stress hormone exposure is also known to dysregulate antioxidant functions in the brain, making the brain susceptible to oxidative stress. Selenoproteins, on the other hand, help combat oxidative stress in the brain. These proteins are distinguishable by the inclusion of a selenocysteine amino acid containing the dietary element selenium (Se), making them well-suited for detoxifying reactive oxygen species (ROS). The brain is highly reliant on selenium supply to maintain selenoprotein synthesis, and the brain preferentially retains selenium compared to other tissues when dietary selenium levels are low. One reason is that the brain is highly metabolically active, which generates ROS that can damage cells. Regulation of brain selenium levels is mostly controlled by interactions between the selenium transport protein, selenoprotein P (SELENOP) and its receptor, low-density lipoprotein receptor 8 (LRP8), the latter being expressed on both neuronal and blood-brain-barrier-associated cells for entry. To date, studies have not adequately addressed the role of dietary selenium and selenoproteins in the context of long-term exposure to elevated stress hormones in the brain. We hypothesized that prolonged exposure to stress hormones causes a dysregulation in selenoprotein levels in the hippocampus leading to behavioral changes in mood and memory, and that this dysregulation is cell-type specific. To test this hypothesis, we employed both in vitro and in vivo experimentation. We treated both immortalized hippocampal, HT22, cells and primary neurons isolated from the hippocampus of postnatal mice with corticosterone (CORT), the principal stress hormone in rodents. We investigated the impacts of glucocorticoid and mineralocorticoid signaling, selenium levels, and cell-type specific selenoprotein changes in hippocampal cells. To assess behavior, we performed behavioral experiments to test alterations in positive and negative valence traits and spatial memory. We also utilized primary neurons to assess cell death vulnerability in cultures treated with and without CORT and erastin, a ferroptotic death inducer, and changes in electrophysiological properties of our cultures. We discovered that changes in selenoproteins, which require both glucocorticoid and mineralocorticoid receptor signaling, happen in a cell-type specific manner. Transcriptional alterations in genes encoding glutathione peroxidase 3 (Gpx3), selenoprotein T (Selenot), Selenop, and Lrp8 were the most frequently influenced by CORT in different cell populations. Finally, differences in selenium distribution were observed in tissues of CORT-treated mice. Brain selenium levels decreased, while selenium and serum selenoprotein levels increased in circulation. However, we were unable to demonstrate that behavioral alterations occurred in mice treated with CORT via injection or increased susceptibility to death in CORT-treated neuronal cultures, possibly due to treatment methodology. Together, these findings establish that long-term CORT treatment significantly alters selenoprotein expression in a cell-type dependent manner in the hippocampus and influences distribution of selenium throughout the body, reducing selenium supply to the brain and possibly making the brain more susceptible to oxidative damage.

Multiple agents exist for the reversal of oral Factor Xa inhibitor (FXa) associated bleeding, including Coagulation FXa Recombinant, Inactivated zhzo (andexanet alfa) and 4-factor prothrombin complex concentrate (4F-PCC). While classified as a 3F-PCC product, Profilnine contains up to 35 IU of Factor VII (per 100 IU of Factor IX) in addition to therapeutic levels of Factors II, IX, and X, and has demonstrated a similar impact on prothrombin time and blood product usage in non-warfarin related bleeding. This was a retrospective, multicenter study at four medical centers of adult patients who presented with major bleeding associated with oral FXa inhibitors and received either 4F-PCC (n = 64) or 3F-PCC (n = 61). The primary outcome was hemostatic effectiveness. Secondary outcomes included the incidence of thromboembolism, in-hospital mortality, and length of stay. The most common indication for reversal was intracranial bleeding. For the primary outcome, 84% of all patients were rated as effective with no difference noted between the groups (p = 0.81). No significant difference between groups was found in the multivariable analysis adjusting for baseline differences between groups including race, total body weight, type of bleeding, and the use of antiplatelet therapy. There was no difference in the length of stay, in-hospital mortality, or the incidence of thromboembolism between the groups. Overall, no significant differences were found in the effectiveness or safety of 4F-PCC and 3F-PCC use in the management of oral FXa inhibitor-associated bleeding. Further investigations are warranted to explore the use of 3F-PCC for this indication and its safety and effectiveness. Graphical Abstract 3-Factor Prothrombin Complex Concentrate versus 4-Factor Prothrombin Complex Concentrate for the Reversal of Oral Factor Xa Inhibitors.

A larger study (n = 625) found no difference in hypotension after administering diltiazem for atrial fibrillation rate control to heart failure patients with reduced ejection fraction compared to those with preserved ejection fraction [2]. Additionally, details of atrial fibrillation subtypes were often not available upon chart review.Sources of Support None.Conflicts of Interest No listed authors have any conflict of interest related to the subject matter in this manuscript. Variable Diltiazem (n = 63) Metoprolol (n = 45) p-Value Age, mean ± SD 68 ± 13 64 ± 11 0.15 Male, n(%) 32 (51) 23 (51) 0.97 Weight (kg), mean ± SD 90.6 ± 29 87.1 ± 26 0.51 Body mass index (kg/m2), mean ± SD 31 ± 9 30 ± 8 0.35 Past medical history, n(%) Atrial fibrillation 38 (60) 39 (87) 0.095 Congestive heart failure 20 (32) 16 (36) 0.68 Home medications, n(%) Amiodarone 1 (2) 1 (2) 1 Beta-blocker 38 (60) 43 (96) < 0.01 Calcium channel blocker 18 (29) 8 (18) 0.2 Digoxin 2 (3) 3 (7) 0.4 Baseline VRb (bpm), mean ± SD 146 ± 15 138 ± 13 0.003 Baseline SBPc (mmHg), median [IQR] 137 [125–148] 132 [119–140] 0.25 Baseline SBPc <120 (mmHg), n(%) 9 (14) 12 (27) 0.11 Pre-intervention fluid bolusa, n(%) 12 (19) 13 (29) 0.2 Table 1 Baseline Patient Characteristics.