Thomsongupta8270
Neuroprotection targeting mitochondrial dysfunction has been proposed as a potential therapeutic strategy for Parkinson's disease (PD). Ursodeoxycholic acid (UDCA) has been shown to prevent neuronal damage; however, the role of UDCA in PD is poorly understood. This study aimed to investigate the neuroprotective effects of UDCA on PD and its underlying mechanisms. We used MPTP/MPP+-induced PD models, including MPTP-induced mice, primary cultures of mice mesencephalic neurons and MPP+-treated neuro-2a cells to examine the effects of UDCA on PD pathogenesis. The results showed that UDCA improved behavioral performance and protected dopaminergic neurons in MPTP mice. UDCA improved cell viability and decreased cell death in MPP+-treated cells. UDCA inhibited reactive oxygen species accumulation, mitochondrial membrane potential collapse, and ATP depletion in neuro-2a cells. UDCA improved movement dysfunction, ameliorated autophagic flux and alleviated apoptosis. Furthermore, UDCA could activate the AMPK/mTOR and PINK1/Parkin pathways. In conclusion, UDCA may improve PD by regulating mitochondrial function, autophagy, and apoptosis, involving AMPK/mTOR and PINK1/Parkin pathways. These results open new perspectives for pharmacological use of UDCA in PD.
Paramedics may perform endotracheal intubation (ETI) while treating patients with out-of-hospital cardiac arrest (OHCA). The gum elastic Bougie (Bougie) is an intubation adjunct that may optimize intubation success. There are few reports of Bougie-assisted intubation in OHCA nor its association with outcomes. We compared intubation success rates and OHCA outcomes between Bougie-assisted and non-Bougie ETI in the out-of-hospital Pragmatic Airway Resuscitation Trial (PART).
This was a secondary analysis of patients receiving ETI enrolled in the Pragmatic Airway Resuscitation Trial (PART), a multicenter clinical trial comparing intubation-first vs. laryngeal tube-first strategies of airway management in adult OHCA. The primary exposure was use of Bougie for ETI-assistance. The primary endpoint was first-pass ETI success. Secondary endpoints included overall ETI success, time to successful ETI, return of spontaneous circulation, 72-h survival, hospital survival and hospital survival with favorable neurologic es, Bougie-assisted ETI entailed longer airway placement times and potentially lower survival. UNC 3230 in vitro The role of the Bougie assistance in ETI of OHCA remains unclear.
While exhibiting slightly higher ETI overall success rates, Bougie-assisted ETI entailed longer airway placement times and potentially lower survival. The role of the Bougie assistance in ETI of OHCA remains unclear.
International early warning scores (EWS) including the additive National Early Warning Score (NEWS) and logistic EWS currently utilise physiological snapshots to predict clinical deterioration. We hypothesised that a dynamic score including vital sign trajectory would improve discriminatory power.
Multicentre retrospective analysis of electronic health record data from postoperative patients admitted to cardiac surgical wards in four UK hospitals. Least absolute shrinkage and selection operator-type regression (LASSO) was used to develop a dynamic model (DyniEWS) to predict a composite adverse event of cardiac arrest, unplanned intensive care re-admission or in-hospital death within 24 h.
A total of 13,319 postoperative adult cardiac patients contributed 442,461 observations of which 4234 (0.96%) adverse events in 24 h were recorded. The new dynamic model (AUC = 0.80 [95% CI 0.78-0.83], AUPRC = 0.12 [0.10-0.14]) outperforms both an updated snapshot logistic model (AUC = 0.76 [0.73-0.79], AUPRC = 0.08 [0.60-0.10]) and the additive National Early Warning Score (AUC = 0.73 [0.70-0.76], AUPRC = 0.05 [0.02-0.08]). Controlling for the false alarm rates to be at current levels using NEWS cut-offs of 5 and 7, DyniEWS delivers a 7% improvement in balanced accuracy and increased sensitivities from 41% to 54% at NEWS 5 and 18% to -30% at NEWS 7.
Using an advanced statistical approach, we created a model that can detect dynamic changes in risk of unplanned readmission to intensive care, cardiac arrest or in-hospital mortality and can be used in real time to risk-prioritise clinical workload.
Using an advanced statistical approach, we created a model that can detect dynamic changes in risk of unplanned readmission to intensive care, cardiac arrest or in-hospital mortality and can be used in real time to risk-prioritise clinical workload.
Ventricular fibrillation amplitude spectral area (AMSA) and end-tidal carbon dioxide (ETCO
) are predictors of shock success, understood as restoration of an organized rhythm, and return of spontaneous circulation (ROSC). However, little is known about their combined use. We aimed to assess the prediction accuracy when combined, and to clarify if they are correlated in out of hospital cardiac arrest' victims.
Records acquired by external defibrillators in out-of-hospital cardiac arrest patients of the Lombardia Cardiac Arrest registry were processed. The 1-min pre-shock ETCO
median value (METCO
) was computed from the capnogram and AMSA (2-48 mV.Hz range) computed applying the Fast Fourier Transform to a 2-second pre-shock filtered ECG interval (0.5-30 Hz). Support Vector Machine (SVM) predictive models based on METCO
, AMSA and their combination were fit; results were given as the area under the curve (AUC) of the receiver operating characteristic (ROC) curves.
We considered 112 patients with 391 shocks delivered. METCO
and AMSA were predictors of shock success [AUC (IQR) of the ROC curve 0.59 (0.56-0.62); 0.68 (0.65-0.72), respectively] and of ROSC [0.56 (0.53-0.59); 0.74 (0.71-0.78),]. Their combination in a SVM model increased the accuracy for predicting shock success [AUC (IQR) of the ROC curve 0.71 (0.68-0.75)] and ROSC [0.77 (0.73-0.8)]. AMSA and METCO
were significantly correlated only in patients who achieved ROSC (rho = 0.33 p = 0.03).
AMSA and ETCO
predict shock success and ROSC after every shock, and their predictive power increases if combined. Notably, they were correlated only in patients who achieved ROSC.
AMSA and ETCO2 predict shock success and ROSC after every shock, and their predictive power increases if combined. Notably, they were correlated only in patients who achieved ROSC.