Recent evidence indicates that the United States is facing a public health crisis of alcohol misuse and alcohol use disorder (AUD), which has been fueled in part by dramatic rises in binge and heavy drinking and prevalence of AUD in women. Historically, alcohol misuse and AUD have been more prevalent in men than in women. However, recent evidence on data from the past decade shows increases in AUD prevalence rates that are associated with substantially higher binge and heavy drinking and AUD prevalence in women compared to men. This paper first addresses the key roles of stress, trauma, childhood maltreatment, negative affect, and mood and anxiety disorders; sex differences in the presentation of these psychosocial and psychological factors; and their contributions to alcohol misuse, escalation to binge and heavy drinking, and transition to AUD in women. Also examined are potential central and peripheral biological mechanisms by which stressors and traumatic experiences, as well as chronic stress states-including depression and anxiety-may facilitate differential pathways to alcohol misuse, escalation, and transition to AUD in women. Finally, this paper discusses major gaps in the literature on sex differences in these areas as well as the need for greater research on sex-specific pathways to alcohol misuse and transition to AUD, so as to support a more comprehensive understanding of AUD etiology and for the development of new strategies for prevention and treatment of alcohol misuse and AUD in women.

Key Points Question What are common health care utilization patterns for management of newly diagnosed acute neck pain and how are they associated with care delivery? Findings In this cross-sectional study of 679 030 adults conducted between 2008 and 2015, early imaging was common and often occurred before conservative treatment. However, early conservative therapy before imaging was associated with lower health care costs and reduced opioid use. Meaning These findings suggest a need for improved care standardization with prompt conservative therapy initiation to reduce treatment cost and increase effectiveness.

BRAF and MEK inhibitor combinations have shown promising results against several types of BRAF V600E mutated cancers. Patients with high-grade BRAF V600E mutated gliomas frequently experience therapy failure with concurrent BRAF V600E and MEK inhibition (BRAFi+MEKi). A step toward overcoming therapy resistance includes improving the understanding how these inhibitors affect tumor cells and (immune) microenvironment. In novel syngeneic murine models and patient-derived cell lines of BRAF V600E-mutated high-grade astrocytomas we analyzed effects of BRAF V600E expression and BRAF V600E inhibitor Dabrafenib and MEK inhibitor Trametinib. BRAFi+MEKi promoted glial differentiation as determined by immunostaining and RNA expression profiling. In addition, increased interferon alpha and gamma signatures and pro-inflammatory cytokines were detected in response to BRAFi+MEKi. Quantitative rtPCR validated upregulation of known downstream targets of interferon gamma, the major histocompatibility genes, and programmed death (PD-1) receptor signaling. Cytometry analyses showed heightened frequency of tumor-infiltrating T cells positive for PD-1 and tumor cells co-expressing programmed death ligand-1 (PD-L1). Combining BRAFi+MEKi with dual immune checkpoint inhibition by anti-PD-L1 and anti-CTLA-4 treatment decreased T cell deactivation and resulted in a T cell-dependent survival benefit of mice with orthotopic BRAF V600E-mutated high-grade glioma. These data showed that clinically relevant BRAFi+MEKi sensitizes BRAF V600E-mutated gliomas to the anti-tumor activity of concurrent dual immune checkpoint blockade. Immunofluorescence staining identified an active T cell infiltrate in human MAPK pathway altered gliomas. Collectively, our data suggest that an improved therapeutic benefit could be derived from combining BRAFi+MEKi with immune checkpoint inhibitors in patients with BRAF V600E high-grade gliomas.

Polyvinylpyrrolidone catheters showed the lowest median cell attachment after cell marker staining (<1 cells per 0.07 mm 2 ) compared to antibiotic coated (4.0 cells per 0.07 mm 2 ), barium stripe (3.5 per 0.07 mm 2 ) or barium impregnated (2.0 per 0.07 mm 2 ).CONCLUSIONS: Polyvinylpyrrolidone catheters were least likely to be occluded by astrocytes or choroid cells during testing in a novel ventricular replicating system due to lower cellular adhesion. Our findings may have clinical significance when choosing proximal ventricular catheters that are least likely to occlude and prevent proximal shunt failure.

The most frequent hashtags were #neurosurgery, #medicine, and #surgery. When comparing the 30 profiles with the most followers to the rest of the field, average interaction (437.13 vs. 136.44; p < 0.001), uploads (569.43 vs 199.65; p = 0.003), likes given in the top posts (791.16 vs 217.78; p < 0.001), and comments given in the top posts (32.67 vs 17.19; p = 0.03) were significantly higher in the top 30. Although the top 30 profiles had an average increased posts per week (2.15 vs. 1.34; p = 0.18) posts per month (8.06 vs. 4.87; p = 0.16), and lifestyle posts (3.9 vs. 2.83), those were not significant.CONCLUSIONS: Neurosurgeons may be able to increase their footprint and reach a wider audience by increasing their upload rate. Our analyses found that most neurosurgeons' posts are centered around clinical and professional interests.