Precise regulation of cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase family, is critical for proper neuronal development and functions. Cdk5 is activated through its association with the neuron-specific activator p35 or p39. Nonetheless, how its kinase activity is regulated in neurons is not well understood. In this study, we found that Cdk5 activity is regulated by S-nitrosylation, a post-translational modification of protein that affects a plethora of neuronal functions. S-nitrosylation of Cdk5 occurs at Cys83, which is one of the critical amino acids within the ATP-binding pocket of the kinase. Upon S-nitrosylation, Cdk5 exhibits reduced kinase activity, whereas mutation of Cys83 to Ala on Cdk5 renders the kinase refractory to such inhibition. Importantly, S-nitrosylated Cdk5 can be detected in the mouse brain, and blocking the S-nitrosylation of Cdk5 in cultured hippocampal neurons enhances dendritic growth and branching. Together, our findings reveal an important role of S-nitrosylation in regulating Cdk5 kinase activity and dendrite growth in neurons during development.

Key Points Question What is the etiology of pneumonia among patients with alcohol use disorder, and is alcohol use disorder associated with poorer outcomes? Findings In this cohort study of 137 496 patients with pneumonia, the most common cause of pneumonia among patients with alcohol use disorder was Streptococcus pneumoniae ; resistant gram-negative infections were rare. In comorbidity-adjusted models, alcohol use disorder was not significantly associated with inpatient mortality, but patients with alcohol use disorder undergoing alcohol withdrawal more frequently required late mechanical ventilation, vasopressors, and intensive care unit admissions and had increased lengths of stay and hospital costs. Meaning This study suggests that alcohol use disorder alone is not an independent risk factor for resistant infection or mortality, but alcohol withdrawal is associated with clinical deterioration and higher use of health care resources.

IMPORTANCE Administrative databases may offer efficient clinical data collection for studying epidemiology, outcomes, and temporal trends in health care delivery. However, such data have seldom been validated against microbiological laboratory results. OBJECTIVE To assess the validity of International Classification of Diseases, Ninth Revision (ICD-9) organism-specific administrative codes for pneumonia using microbiological data (test results for blood or respiratory culture, urinary antigen, or polymerase chain reaction) as the criterion standard.

Objective To describe the epidemiology, risk factors and outcomes of community-acquired Escherichia coli pneumonia in comparison to other gram-negative and pneumococcal pneumonias. Methods E.coli is an under recognized cause of bacterial community-acquired pneumonia (CAP). We conducted a large retrospective cohort study of adult patients admitted with pneumonia to 173 US hospitals included in Premier Research database from July 2010–June 2015. Patients were included if they had principal diagnosis code for pneumonia, or a principal diagnosis of respiratory failure or sepsis with secondary diagnosis of pneumonia and had a positive blood or respiratory culture obtained on hospital day 1. The primary outcome was in-hospital case fatality. Secondary outcomes included intensive care unit (ICU) admission, invasive mechanical ventilation (IMV) and use of vasopressors. Results Of 8,680 patients with pneumonia and positive blood or respiratory cultures, 1,029 (7.7%) had E.coli CAP. Patients with E.coli pneumonia were older and more likely to have a principal diagnosis of sepsis. Patients with E.coli pneumonia had significantly higher case fatality than patients with pneumococcal pneumonia (adjusted odds ratio, 1.55 [95% CI, 1.23–1.97]) but not significantly different than other gram-negative pneumonias (adjusted odds ratio, 1.06 [95% CI, 0.85–1.32]). Approximately 36% of the isolates were resistant to fluoroquinolones; 9.3% were resistant to ceftriaxone. Conclusions E.coli is an important cause of severe CAP; with higher mortality than pneumococcal pneumonia but similar to other gram-negative pneumonias. The rate of fluoroquinolone resistance was high and empiric fluoroquinolones should be used with caution in these patients.

Background Patient satisfaction with in-person medical visits includes patient-clinician engagement. However, communication, empathy, and other relationship-centered care measures in virtual visits have not been adequately investigated. Objective This study aims to comprehensively consider patient experience, including relationship-centered care measures, to assess patient satisfaction during virtual visits. Methods We conducted a large survey study with open-ended questions to comprehensively assess patients’ experiences with virtual visits in a diverse patient population. Adults with a virtual visit between June 21, 2017, and July 12, 2017, were invited to complete a survey of 21 Likert-scale items and textboxes for comments following their visit. Factor analysis of the survey items revealed three factors: experience with technology, patient-clinician engagement, and overall satisfaction. Multivariable logistic regression was used to test the associations among the three factors and patient demographics, clinician type, and prior relationship with the clinician. Using qualitative framework analysis, we identified recurrent themes in survey comments, quantitatively coded comments, and computed descriptive statistics of the coded comments. Results A total of 65.7% (426/648) of the patients completed the survey; 64.1% (273/426) of the respondents were women, and the average age was 46 (range 18-86) years. The sample was geographically diverse: 70.2% (299/426) from Ohio, 6.8% (29/426) from Florida, 4.2% (18/426) from Pennsylvania, and 18.7% (80/426) from other states. With regard to insurance coverage, 57.5% (245/426) were undetermined, 23.7% (101/426) had the hospital’s employee health insurance, and 18.7% (80/426) had other private insurance. Types of virtual visits and clinicians varied. Overall, 58.4% (249/426) of patients had an on-demand visit, whereas 41.5% (177/426) had a scheduled visit. A total of 41.8% (178/426) of patients had a virtual visit with a family physician, 20.9% (89/426) with an advanced practice provider, and the rest had a visit with a specialist. Most patients (393/423, 92.9%) agreed that their virtual visit clinician was interested in them as a person, and their virtual visit made it easy to get the care they needed (383/421, 90.9%). A total of 81.9% (344/420) of respondents agreed or strongly agreed that their virtual visit was as good as an in-person visit by a clinician. Having a prior relationship with their virtual visit clinician was associated with less comfort and ease with virtual technology among patients (odds ratio 0.58, 95% CI 0.35-0.98). In terms of technology, patients found the interface easy to use (392/423, 92.7%) and felt comfortable using it (401/423, 94.8%). Technical difficulties were associated with lower odds of overall satisfaction (odds ratio 0.46, 95% CI 0.28-0.76). Conclusions Patient-clinician engagement in virtual visits was comparable with in-person visits. This study supports the value and acceptance of virtual visits. Evaluations of virtual visits should include assessments of technology and patient-clinician engagement, as both are likely to influence patient satisfaction.