Jacob K. Greenberg

Behavioral plasticity in honey bees is associated with differences in brain microRNA transcriptome.

Small, non‐coding microRNAs (miRNAs) have been implicated in many biological processes, including the development of the nervous system. However, the roles of miRNAs in natural behavioral and neuronal plasticity are not well understood. To help address this we characterized the microRNA transcriptome in the adult worker honey bee head and investigated whether changes in microRNA expression levels in the brain are associated with division of labor among honey bees, a well‐established model for socially regulated behavior. We determined that several miRNAs were downregulated in bees that specialize on brood care (nurses) relative to foragers. Additional experiments showed that this downregulation is dependent upon social context; it only occurred when nurse bees were in colonies that also contained foragers. Analyses of conservation patterns of brain‐expressed miRNAs across Hymenoptera suggest a role for certain miRNAs in the evolution of the Aculeata, which includes all the eusocial hymenopteran species. Our results support the intriguing hypothesis that miRNAs are important regulators of social behavior at both developmental and evolutionary time scales.

Resorufin analogs preferentially bind cerebrovascular amyloid: potential use as imaging ligands for cerebral amyloid angiopathy

BackgroundCerebral amyloid angiopathy (CAA) is characterized by deposition of fibrillar amyloid β (Aβ) within cerebral vessels. It is commonly seen in the elderly and almost universally present in patients with Alzheimers Disease (AD). In both patient populations, CAA is an independent risk factor for lobar hemorrhage, ischemic stroke, and dementia. To date, definitive diagnosis of CAA requires obtaining pathological tissues via brain biopsy (which is rarely clinically indicated) or at autopsy. Though amyloid tracers labeled with positron-emitting radioligands such as [11C]PIB have shown promise for non-invasive amyloid imaging in AD patients, to date they have been unable to clarify whether the observed amyloid load represents neuritic plaques versus CAA due in large part to the low resolution of PET imaging and the almost equal affinity of these tracers for both vascular and parenchymal amyloid. Therefore, the development of a precise and specific non-invasive technique for diagnosing CAA in live patients is desired.ResultsWe found that the phenoxazine derivative resorufin preferentially bound cerebrovascular amyloid deposits over neuritic plaques in the aged Tg2576 transgenic mouse model of AD/CAA, whereas the congophilic amyloid dye methoxy-X34 bound both cerebrovascular amyloid deposits and neuritic plaques. Similarly, resorufin-positive staining was predominantly noted in fibrillar Aβ-laden vessels in postmortem AD brain tissues. Fluorescent labeling and multi-photon microscopy further revealed that both resorufin- and methoxy-X34-positive staining is colocalized to the vascular smooth muscle (VSMC) layer of vessel segments that have severe disruption of VSMC arrangement, a characteristic feature of CAA. Resorufin also selectively visualized vascular amyloid deposits in live Tg2576 mice when administered topically, though not systemically. Resorufin derivatives with chemical modification at the 7-OH position of resorufin also displayed a marked preferential binding affinity for CAA, but with enhanced lipid solubility that indicates their use as a non-invasive imaging tracer for CAA is feasible.ConclusionsTo our knowledge, resorufin analogs are the fist class of amyloid dye that can discriminate between cerebrovascular and neuritic forms of amyloid. This unique binding selectivity suggests that this class of dye has great potential as a CAA-specific amyloid tracer that will permit non-invasive detection and quantification of CAA in live patients.

Causes of 30-day readmission after aneurysmal subarachnoid hemorrhage.

OBJECTIVE Hospital readmission is a common but controversial quality measure increasingly used to influence hospital compensation in the US. The objective of this study was to evaluate the causes for 30-day hospital readmission following aneurysmal subarachnoid hemorrhage (SAH) to determine the appropriateness of this performance metric and to identify potential avenues for improved patient care. METHODS The authors retrospectively reviewed the medical records of all patients who received surgical or endovascular treatment for aneurysmal SAH at Barnes-Jewish Hospital between 2003 and 2013. Two senior faculty identified by consensus the primary medical/surgical diagnosis associated with readmission as well as the underlying causes of rehospitalization. RESULTS Among 778 patients treated for aneurysmal SAH, 89 experienced a total of 97 readmission events, yielding a readmission rate of 11.4%. The median time from discharge to readmission was 9 days (interquartile range 3-17.5 days). Actual hydrocephalus or potential concern for hydrocephalus (e.g., headache) was the most frequent diagnosis (26/97, 26.8%), followed by infections (e.g., wound infection [5/97, 5.2%], urinary tract infection [3/97, 3.1%], and pneumonia [3/97, 3.1%]) and thromboembolic events (8/97, 8.2%). In most cases (75/97, 77.3%), we did not identify any treatment lapses contributing to readmission. The most common underlying causes for readmission were unavoidable development of SAH-related pathology (e.g., hydrocephalus; 36/97, 37.1%) and complications related to neurological impairment and immobility (e.g., thromboembolic event despite high-dose chemoprophylaxis; 21/97, 21.6%). The authors determined that 22/97 (22.7%) of the readmissions were likely preventable with alternative management. In these cases, insufficient outpatient medical care (for example, for hyponatremia; 16/97, 16.5%) was the most common shortcoming. CONCLUSIONS Most readmissions after aneurysmal SAH relate to late consequences of hemorrhage, such as hydrocephalus, or medical complications secondary to severe neurological injury. Although a minority of readmissions may potentially be avoided with closer medical follow-up in the transitional care environment, readmission after SAH is an insensitive and likely inappropriate hospital performance metric.

The Chiari Severity Index: a preoperative grading system for Chiari malformation type 1.

BACKGROUND To develop evidence-based treatment guidelines for Chiari malformation type 1 (CM-1), preoperative prognostic indices capable of stratifying patients for comparative trials are needed. OBJECTIVE To develop a preoperative Chiari Severity Index (CSI) integrating the clinical and neuroimaging features most predictive of long-term patient-defined improvement in quality of life (QOL) after CM-1 surgery. METHODS We recorded preoperative clinical (eg, headaches, myelopathic symptoms) and neuroimaging (eg, syrinx size, tonsillar descent) characteristics. Brief follow-up surveys were administered to assess overall patient-defined improvement in QOL. We used sequential sequestration to develop clinical and neuroimaging grading systems and conjunctive consolidation to integrate these indices to form the CSI. We evaluated statistical significance using the Cochran-Armitage test and discrimination using the C statistic. RESULTS Our sample included 158 patients. Sequential sequestration identified headache characteristics and myelopathic symptoms as the most impactful clinical parameters, producing a clinical grading system with improvement rates ranging from 81% (grade 1) to 58% (grade 3) (P = .01). Based on sequential sequestration, the neuroimaging grading system included only the presence (55% improvement) or absence (74% improvement) of a syrinx ≥6 mm (P = .049). Integrating the clinical and neuroimaging indices, improvement rates for the CSI ranged from 83% (grade 1) to 45% (grade 3) (P = .002). The combined CSI had moderately better discrimination (c = 0.66) than the clinical (c = 0.62) or neuroimaging (c = 0.58) systems alone. CONCLUSION Integrating clinical and neuroimaging characteristics, the CSI is a novel tool that predicts patient-defined improvement after CM-1 surgery. The CSI may aid preoperative counseling and stratify patients in comparative effectiveness trials.

Complications and Resource Use Associated With Surgery for Chiari Malformation Type 1 in Adults: A Population Perspective.

BACKGROUND Outcomes research on Chiari malformation type 1 (CM-1) is impeded by a reliance on small, single-center cohorts. OBJECTIVE To study the complications and resource use associated with adult CM-1 surgery using administrative data. METHODS We used a recently validated International Classification of Diseases, Ninth Revision, Clinical Modification code algorithm to retrospectively study adult CM-1 surgeries from 2004 to 2010 in California, Florida, and New York using State Inpatient Databases. Outcomes included complications and resource use within 30 and 90 days of treatment. We used multivariable logistic regression to identify risk factors for morbidity and negative binomial models to determine risk-adjusted costs. RESULTS We identified 1947 CM-1 operations. Surgical complications were more common than medical complications at both 30 days (14.3% vs 4.4%) and 90 days (18.7% vs 5.0%) postoperatively. Certain comorbidities were associated with increased morbidity; for example, hydrocephalus increased the risk for surgical (odds ratio [OR] = 4.51) and medical (OR = 3.98) complications. Medical but not surgical complications were also more common in older patients (OR = 5.57 for oldest vs youngest age category) and male patients (OR = 3.19). Risk-adjusted hospital costs were

Chiari malformation Type I surgery in pediatric patients. Part 2: complications and the influence of comorbid disease in California, Florida, and New York

22530 at 30 days and

Cerebral Amyloid Angiopathy Increases Susceptibility to Infarction After Focal Cerebral Ischemia in Tg2576 Mice

24852 at 90 days postoperatively. Risk-adjusted 90-day costs were more than twice as high for patients experiencing surgical (

Management of children with mild traumatic brain injury and intracranial hemorrhage

46264) or medical (

Validation of an International Classification of Diseases, Ninth Revision Code Algorithm for Identifying Chiari Malformation Type 1 Surgery in Adults.

65679) complications than for patients without complications (

Predictors of 30-day readmission after aneurysmal subarachnoid hemorrhage: a case-control study.

18880). CONCLUSION Complications after CM-1 surgery are common, and surgical complications are more frequent than medical complications. Certain comorbidities and demographic characteristics are associated with increased risk for complications. Beyond harming patients, complications are also associated with substantially higher hospital costs. These results may help guide patient management and inform decision making for patients considering surgery.