In living cells, a fluctuating torque is exerted on the nuclear surface but the origin of the torque is unclear. In this study, we found that the nuclear rotation angle is directionally persistent on a time scale of tens of minutes, but rotationally diffusive on longer time scales. Rotation required the activity of the microtubule motor dynein. We formulated a model based on microtubules undergoing dynamic instability, with tensional forces between a stationary centrosome and the nuclear surface mediated by dynein. Model simulations suggest that the persistence in rotation angle is due to the transient asymmetric configuration of microtubules exerting a net torque in one direction until the configuration is again randomized by dynamic instability. The model predicts that the rotational magnitude must depend on the distance between the nucleus and the centrosome. To test this prediction, rotation was quantified in patterned cells in which the cell's centrosome was close to the projected nuclear centroid. Consistent with the prediction, the angular displacement was found to decrease in these cells relative to unpatterned cells. This work provides the first mechanistic explanation for how nuclear dynein interactions with discrete microtubules emanating from a stationary centrosome cause rotational torque on the nucleus.

Benzodiazepines are the drug of choice for alcohol withdrawal syndrome (AWS); however, phenobarbital is an alternative agent used with or without concomitant benzodiazepine therapy. In this systematic review, we evaluate patient outcomes with phenobarbital for AWS. Medline, Cochrane Library, and Scopus were searched from 1950 through February 2017 for controlled trials and observational studies using ["phenobarbital" or "barbiturate"] and ["alcohol withdrawal" or "delirium tremens."] Risk of bias was assessed using tools recommended by National Heart, Lung, and Blood Institute. From 294 nonduplicative articles, 4 controlled trials and 5 observational studies (n = 720) for AWS of any severity were included. Studies were of good quality (n = 2), fair (n = 4), and poor (n = 3). In 6 studies describing phenobarbital without concomitant benzodiazepine therapy, phenobarbital decreased AWS symptoms ( < .00001) and displayed similar rates of treatment failure versus comparator therapies (38% vs 29%). A study with 2 cohorts showed similar rates of intensive care unit (ICU) admission (phenobarbital: 16% and 9% vs benzodiazepine: 14%) and hospital length of stay (phenobarbital: 5.85 and 5.30 days vs benzodiazepine: 6.64 days). In 4 studies describing phenobarbital with concomitant benzodiazepine therapy, phenobarbital groups had similar ICU admission rates (8% vs 25%), decreased mechanical ventilation (21.9% vs 47.3%), decreased benzodiazepine requirements by 50% to 90%, and similar ICU and hospital lengths of stay and AWS symptom resolution versus comparator groups. Adverse effects with phenobarbital, including dizziness and drowsiness, rarely occurred. Phenobarbital, with or without concomitant benzodiazepines, may provide similar or improved outcomes when compared with alternative therapies, including benzodiazepines alone.

Heart failure (HF) is a societal burden due to its high prevalence, frequent admissions for acute decompensated heart failure (ADHF), and the economic impact of direct and indirect costs associated with HF and ADHF. Common etiologies of ADHF include medication and diet noncompliance, arrhythmias, deterioration in renal function, poorly controlled hypertension, myocardial infarction, and infections. Appropriate medical management of ADHF in patients is guided by the identification of signs and symptoms of fluid overload or low cardiac output and utilization of evidence-based practices. In patients with fluid overload, various strategies for diuresis or ultrafiltration may be considered. Depending on hemodynamics and patient characteristics, vasodilator, inotropic, or vasopressor therapies may be of benefit. Upon ADHF resolution, patients should be medically optimized, have lifestyle modifications discussed and implemented, and medication concierge service considered. After discharge, a multidisciplinary HF team should follow up with the patient to ensure a safe transition of care. This review article evaluates the management options and considerations when treating a patient with ADHF.

An 11-day-old Caucasian male developed acquired methemoglobinemia as a result of repeated exposure to topical lidocaine/prilocaine cream following a circumcision. Our patient responded well with treatment of a single dose of intravenous (IV) methylene blue. Methemoglobinemia is a rare but well-explained complication of local anesthetics. It is important for providers to prescribe local anesthetics safely to avoid serious complications, especially with neonates who are at higher risk of developing methemoglobinemia.