Continuous renal replacement therapy circuit failure after antidote administration

A 73-year-old man was transferred to the emergency department (ED). He was found unconscious in his house along with an empty 200-mL bottle of Basta^?, a herbicide containing 18% glufosinate. He was comatose with a Glasgow Coma Scale score of 3. As his blood pressure dropped to 60/30 mmHg despite fluids and norepinephrine, 20% intravenous fat emulsion product was injected. He experienced repeated cardiopulmonary arrests during his first 4 h in the ED. When the arrests occurred, standard cardiopulmonary resuscitation was performed, and boluses of fat emulsion were given. He was given a total of 1500 mL of 20% fat emulsion. In an attempt to correct the acidosis, continuous renal replacement therapy (CRRT) was started. Within 5 min of starting CRRT, the transmembrane pressure increased sharply and the machine stopped.     

The Prevalence and Emergency Department Utilization of Patients Who Underwent Single and Double Inter-hospital Transfers in the Emergency Department: a Nationwide Population-based Study in Korea, 2016–2018

BackgroundInter-hospital transfer (IHT) for emergency department (ED) admission is a burden to high-level EDs. This study aimed to evaluate the prevalence and ED utilization patterns of patients who underwent single and double IHTs at high-level EDs in South Korea.MethodsThis nationwide cross-sectional study analyzed data from the National Emergency Department Information System for the period of 2016–2018. All the patients who underwent IHT at Level I and II emergency centers during this time period were included. The patients were categorized into the single-transfer and double-transfer groups. The clinical characteristics and ED utilization patterns were compared between the two groups.ResultsWe found that 2.1% of the patients in the ED (n = 265,046) underwent IHTs; 18.1% of the pediatric patients (n = 3,556), and 24.2% of the adult patients (n = 59,498) underwent double transfers. Both pediatric (median, 141.0 vs. 208.0 minutes, P < 0.001) and adult (median, 189.0 vs. 308.0 minutes, P < 0.001) patients in the double-transfer group had longer duration of stay in the EDs. Patient''s request was the reason for transfer in 41.9% of all IHTs (111,076 of 265,046). Unavailability of medical resources was the reason for transfer in 30.0% of the double transfers (18,920 of 64,054).ConclusionThe incidence of double-transfer of patients is increasing. The main reasons for double transfers were patient''s request and unavailability of medical resources at the first-transfer hospitals. Emergency physicians and policymakers should focus on lowering the number of preventable double transfers.     

Acute hyperglycemia and activation of the beta-adrenergic system do not exhibit synergistic inhibitory actions on thyrotropin-releasing hormone (TRH)-induced thyroid stimulating hormone (TSH) secretion

Thyrotropin-releasing hormone (TRH)-stimulated thyroid stimulating hormone (TSH) response in normal subjects is suppressed by oral glucose administration. Pharmacologic studies indicate that this suppressive action of glucose is mediated by an increase in hypothalamic somatostatin (SRIH) tone. Since activation of the beta-adrenergic system also suppresses basal TSH secretion by enhancing SRIH release we sought to determine whether isoproterenol alters the suppression of TRH-induced TSH response induced by the stimulation of glucose. Four tests were performed in seven healthy young men: Test 1: 200 microg TRH (iv) at 0 min; Test 2: 100 g oral glucose at -30 min and TRH at 0 min; Test 3: TRH at 0 min with isoproterenol (0.012 microg/kg, iv) infused continuously; Test 4: oral glucose at -30 min, TRH at 0 min with isoproterenol infused continuously. Pretreatment with glucose significantly suppressed TRH-induced TSH secretion. Isoproterenol infusion also suppressed the TRH-induced TSH secretion, but it did not enhance the inhibitory action of glucose on TSH secretion. The degree of suppression induced by glucose was significantly higher than that achieved by isoproterenol. These data suggest that combined administration of glucose and isoproterenol does not exhibit synergistic inhibitory actions on TRH-stimulated TSH secretion, and that the glucose-TRH test could be used for the evaluation of the hypothalamic somatostatinergic activity.     

Sleep duration and health-related quality of life in Korean adults: 2007-2015 Korea National Health and Nutrition Examination Survey

Sleep and Breathing - To evaluate the association of sleep duration with health-related quality of life (HRQOL) and examine the influence of age, sex, and common comorbidities on this association....     

Effectiveness and safety of neuroablation for severe and treatment-resistant obsessive–compulsive disorder: a systematic review and meta-analysis

BackgroundSeveral neuroablative procedures are available for severe and treatment-resistant obsessive–compulsive disorder (OCD), but limited knowledge about their relative clinical advantages and disadvantages poses obstacles for treatment decision-making.MethodsWe searched PubMed, Embase, Scopus, Web of Knowledge and the Cochrane Library for reports up to February 2019. We reviewed the literature on the effectiveness (assessed using the Yale–Brown Obsessive Compulsive Scale [Y-BOCS]) and safety of various neuroablative interventions for severe and treatment-resistant OCD.ResultsWe included 23 studies involving 487 patients in the systematic review; 21 studies with 459 patients were included in the meta-analysis. Overall, neuroablation achieved a response rate (proportion of patients with ≥ 35% reduction in Y-BOCS) of 55%. Most of the adverse events (88.4%) were mild and transient. The top 3 adverse events were headache (14.9%), cognitive deficits (9.1%) and behaviour problems (8.1%). Severe or permanent adverse events included personality changes (2.3%) and brain edema or brain cyst (1.5%). The response rates associated with capsulotomy, limbic leucotomy and cingulotomy were 59% (95% confidence interval [CI] 54–65), 47% (95% CI 23–72) and 36% (95% CI 23–50), respectively. Interventions with different coverages of the dorsal part of the internal capsule were associated with different adverse-event profiles but were unlikely to modify clinical effectiveness.LimitationsThe level of evidence of most included studies was relatively low.ConclusionAblative surgeries are safe and effective for a large proportion of patients with severe and treatment-resistant OCD. Among the available procedures, capsulotomy seemed to be the most effective. Further research is needed to improve clinical effectiveness and minimize risks.     

Does Religiosity Affect Health Risk Behaviors in Pregnant and Postpartum Women?

Objectives We examined the association between religious involvement and health risk behaviors such as smoking, drinking, marijuana use, and having multiple sex partners among a multiethnic sample of pregnant and postpartum women. Methods Using data from the National Survey of Family Growth, we estimated multivariate logistic regression models to determine the association between various aspects of religious involvement (e.g., attendance, salience, and denomination) and certain behaviors known to be risky for pregnant women and their offspring. Results Frequent (more than once a week) and regular (once a week) attenders at religious services had 80% and 60% (respectively) lower odds of drinking alcohol compared to women who attended less than once a week. Similar patterns surfaced with regard to smoking tobacco with the odds of smoking roughly 85% lower (OR = 0.146, P < 0.001) among frequent attenders, and nearly 65% lower among regular attenders (OR = 0.369, P < 0.001). For smoking marijuana, religious attendance again emerges as a strong predictor. The odds of marijuana smoking are nearly 75% lower for women who attend services frequently (OR = 0.260, P < 0.05) and more than 65% lower for those who attend regularly (OR = 0.343, P < 0.01), as compared with their counterparts who attend services less often. Conclusions Religious attendance emerged as an important correlate of less-risky health behaviors among this nationwide sample of pregnant and postpartum women. Future research should include an examination of the links between religious involvement and other important lifestyle factors that may influence maternal and child health.     

The efficacy and safety of prone positioning in adults patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

Background

Prone positioning for acute respiratory distress syndrome (ARDS) has no impact on mortality despite significant improvements in oxygenation. However, a recent trial demonstrated reduced mortality rates in the prone position for severe ARDS. We evaluated effects of prone position duration and protective lung strategies on mortality rates in ARDS.

Methods

We extensively searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) reporting on prone positioning during acute respiratory failure in adults for inclusion in our meta-analysis.

Results

Eight trials met our inclusion criteria, Totals of 1,099 and 1,042 patients were randomized to the prone and supine ventilation positions. The mortality rates associated with the prone and supine positions were 41% and 47% [risk ratio (RR), 0.90; 95% confidence interval (CI), 0.82-0.98, P=0.02], but the heterogeneity was moderate (P=0.01, I²=61%). In a subgroup analysis, the mortality rates for lung protective ventilation (RR 0.73, 95% CI, 0.62-0.86, P=0.0002) and duration of prone positioning >12 h (RR 0.75, 95% CI, 0.65-0.87, P<0.0001) were reduced in the prone position. Prone positioning was not associated with an increased incidence of cardiac events (RR 1.01, 95% CI, 0.87-1.17) or ventilator associated pneumonia (RR 0.88, 95% CI, 0.71-1.09), but it was associated with an increased incidence of pressure sores (RR 1.23, 95% CI, 1.07-1.41) and endotracheal dislocation (RR 1.33, 95% CI, 1.02-1.74).

Conclusions

Prone positioning tends to reduce the mortality rates in ARDS patients, especially when used in conjunction with a lung protective strategy and longer prone position durations. Prone positioning for ARDS patients should be prioritized over other invasive procedures because related life-threatening complications are rare. However, further additional randomized controlled design to study are required for confirm benefit of prone position in ARDS.     

Dynamic allostery governs cyclophilin A–HIV capsid interplay

Host factor protein Cyclophilin A (CypA) regulates HIV-1 viral infectivity through direct interactions with the viral capsid, by an unknown mechanism. CypA can either promote or inhibit viral infection, depending on host cell type and HIV-1 capsid (CA) protein sequence. We have examined the role of conformational dynamics on the nanosecond to millisecond timescale in HIV-1 CA assemblies in the escape from CypA dependence, by magic-angle spinning (MAS) NMR and molecular dynamics (MD). Through the analysis of backbone ¹H-¹⁵N and ¹H-¹³C dipolar tensors and peak intensities from 3D MAS NMR spectra of wild-type and the A92E and G94D CypA escape mutants, we demonstrate that assembled CA is dynamic, particularly in loop regions. The CypA loop in assembled wild-type CA from two strains exhibits unprecedented mobility on the nanosecond to microsecond timescales, and the experimental NMR dipolar order parameters are in quantitative agreement with those calculated from MD trajectories. Remarkably, the CypA loop dynamics of wild-type CA HXB2 assembly is significantly attenuated upon CypA binding, and the dynamics profiles of the A92E and G94D CypA escape mutants closely resemble that of wild-type CA assembly in complex with CypA. These results suggest that CypA loop dynamics is a determining factor in HIV-1''s escape from CypA dependence.Cyclophilin A (CypA), a peptidyl-prolyl isomerase, is a host factor critical in the regulation of the HIV-1 infection, involving a direct interaction with the capsid (CA) protein (1–3). The mechanism by which CypA modulates the viral infectivity is complex and poorly understood, being dependent on the CA protein primary sequence and the host cell type (4–6). For example, it is known that mutations in the CypA-binding loop of the CA protein dramatically reduce virus infectivity (7, 8). The A92E and G94D escape mutants bind CypA with similar affinity to wild-type CA, but exhibit only 10% of the activity of wild-type CA in the presence of CypA, and full infectivity can be restored if CypA is inhibited with cyclosporin A in the host cells (8), as shown schematically in SI Appendix, Fig. S1. Alas, the molecular mechanisms underlying CypA escape remain elusive, despite numerous virological, biochemical, and structural–biological studies.The present study investigates the internal conformational dynamics of a CA protein assembly. Although static structures of HIV-1 proteins and complexes with host factors provide important clues into their assembly architecture and conformational details of the interactions, structures alone are insufficient for understanding molecular mechanisms. It is well known that biological functions can be dynamically regulated, at multiple levels of organization, from internal dynamics of individual protein molecules (9) to entire cells. This dynamic regulation certainly also applies to HIV-1 because numerous dynamic processes are associated with HIV-1 assembly, disassembly, release, and maturation (10, 11). For example, we previously demonstrated that internal conformational dynamics of the CA protein and its structural plasticity determine its ability to assemble into pleiomorphic conical capsids (12, 13) (Fig. 1). We also uncovered that, in the HIV-1 CA-SP1 maturation intermediate, dynamic disorder in the SP1 peptide plays an important role in the final step of virus maturation, permitting condensation of CA into the cores of infectious virions (14).Open in a separate windowFig. 1.(A, Left) All-atom MD-derived model of mature HIV-1 capsid constructed on the basis of cryo-electron tomography (cryo-ET) and solution NMR studies (13). The capsid comprises 216 hexamers (orange) and 12 pentamers (blue) [Protein Data Bank (PDB) ID 3J3Y]. Structural organization of a hexamer of hexamers (HOH) building block is illustrated in the expansion. Color coded are individual hexameric units comprising the HOH building block. (A, Right) The 3D structure of CA monomer [HXB2 sequence polymorph [PDB file 3NTE (42)]. (B) Cosedimentation assay of CA with CypA illustrating the efficiency of cosedimentation for different CA/CypA molar ratios. S, supernatant; P, pellet. (C) Transmission electron microscopy (TEM) images of tubular assemblies of CA and CA/CypA. (C, Upper) CA NL4-3 (Left), CA NL4-3 A92E (Center), and CA NL4-3 G94D (Right). (C, Lower) HXB2 (Left) and CA HXB2/CypA (Right). (D) Expansions around the aliphatic region for 2D NCA and combined R2-driven (CORD) MAS NMR spectra for CA HXB2 (black) and CA HXB2/CypA (orange), illustrating the multiple chemical shift perturbations observed upon formation of the complex. These perturbations are mapped onto the structure of CA monomer (A) and are confined to flexible loops and residue variation sites. The spectra are recorded at 20.0 T and the MAS frequency of 14 kHz. (E) Expansions of glycine regions for 2D NCA MAS NMR spectra for (from left to right): HXB2, HXB2/CypA, NL4-3, NL4-3 A92E, and NL4-3 G94D. Dashed lines indicate the G89 cross-peaks associated with cis- and trans-P90.In this study, we examined the residue-specific mobility of CA protein from HXB2 and NL4-3 sequence polymorphs (SI Appendix, Fig. S2) in tubular assemblies on the nanoseconds to milliseconds timescales. In particular, we compared wild-type and A92E and G94D escape mutants of the NL4-3 strain as well as wild-type HXB2 CA alone and in complex with CypA. As discussed previously (14, 15), tubular assemblies recapitulate the hexameric lattice, the predominant symmetry arrangement of the conical HIV-1 capsid core, illustrated in Fig. 1A. Dipolar tensors and resonance intensities extracted from a series of 2D and 3D homonuclear and heteronuclear magic-angle spinning (MAS) NMR experiments revealed that certain regions in both HXB2 and NL4-3 wild-type CA are unusually dynamic on all timescales. These motions are significantly attenuated upon CypA binding. Most remarkably, the dynamic profiles of the A92E and G94D escape mutants closely resemble that of CA when bound by CypA. To gain further understanding of the sequence-dependent dynamics profiles of CA assemblies, we performed extensive molecular dynamics (MD) simulations. The motionally averaged dipolar tensors extracted from the MD trajectories are in remarkable quantitative agreement with the NMR results. Together, our results suggest that changes in the sequence-dependent conformational dynamics may be a key determinant in the escape mechanism of HIV-1 CA capsid mutants from CypA dependence.