The Clinical Differentiation of Cerebellar Infarction from Common Vertigo Syndromes

This article summarizes the emergency department approach to diagnosing cerebellar infarction in the patient presenting with vertigo. Vertigo is defined and identification of a vertigo syndrome is discussed. The differentiation of common vertigo syndromes such as benign paroxysmal positional vertigo, Meniere’s disease, migrainous vertigo, and vestibular neuritis is summarized. Confirmation of a peripheral vertigo syndrome substantially lowers the likelihood of cerebellar infarction, as do indicators of a peripheral disorder such as an abnormal head impulse test. Approximately 10% of patients with cerebellar infarction present with vertigo and no localizing neurologic deficits. The majority of these may have other signs of central vertigo, specifically direction-changing nystagmus and severe ataxia

STAT signaling in the pathogenesis and treatment of myeloid malignancies

STAT transcription factors play a critical role in mediating the effects of cytokines on myeloid cells. As STAT target genes control key processes such as survival, proliferation and self-renewal, it is not surprising that constitutive activation of STATs, particularly STAT3 and STAT5, are common events in many myeloid tumors. STATs are activated both by mutant tyrosine kinases as well as other pathogenic events, and continued activation of STATs is common in the setting of resistance to kinase inhibitors. Thus, the targeting of STATs, alone or in combination with other drugs, will likely have increasing importance for cancer therapy

A Chemical Biology Approach to Developing STAT Inhibitors: Molecular Strategies for Accelerating Clinical Translation

STAT transcription factors transduce signals from the cell surface to the nucleus, where they regulate the expression of genes that control proliferation, survival, self-renewal, and other critical cellular functions. Under normal physiological conditions, the activation of STATs is tightly regulated. In cancer, by contrast, STAT proteins, particularly STAT3 and STAT5, become activated constitutively, thereby driving the malignant phenotype of cancer cells. Since these proteins are largely dispensable in the function of normal adult cells, STATs represent a potentially important target for cancer therapy. Although transcription factors have traditionally been viewed as suboptimal targets for pharmacological inhibition, chemical biology approaches have been particularly fruitful in identifying compounds that can modulate this pathway through a variety of mechanisms. STAT inhibitors have notable anti-cancer effects in many tumor systems, show synergy with other therapeutic modalities, and have the potential to eradicate tumor stem cells. Furthermore, STAT inhibitors identified through the screening of chemical libraries can then be employed in large scale analyses such as gene expression profiling, RNA interference screens, or large-scale tumor cell line profiling. Data derived from these studies can then provide key insights into mechanisms of STAT signal transduction, as well as inform the rational design of targeted therapeutic strategies for cancer patients

Trends and correlates of marijuana use among late middle-aged and older adults in the United States, 2002–2014

BACKGROUND: Recent trend studies suggest that marijuana use is on the rise among the general population of adults ages 18 and older in the United States. However, little is known about the trends in marijuana use and marijuana-specific risk/protective factors among American adults during the latter part of adulthood. METHOD: Findings are based on repeated, cross-sectional data collected from late middle-aged (ages 50–64) and older adults (ages 65 and older) surveyed as part of the National Survey on Drug Use and Health between 2002 and 2014. RESULTS: The prevalence of past-year marijuana use among late middle-aged adults increased significantly from a low of 2.95% in 2003 to a high of 9.08% in 2014. Similarly, the prevalence of marijuana use increased significantly among older adults from a low of 0.15% in 2003 to a high of 2.04% in 2014. Notably, the upward trends in marijuana use remained significant even when accounting for sociodemographic, substance use, behavioral, and health-related factors. We also found that decreases in marijuana-specific protective factors were associated with the observed trend changes in marijuana use among late middle-aged and older adults, and observed a weakening of the association between late-middle aged marijuana use and risk propensity, other illicit drug use, and criminal justice system involvement over the course of the study. CONCLUSIONS: Findings from the present study provide robust evidence indicating that marijuana use among older Americans has increased markedly in recent years, with the most evident changes observed between 2008 and 2014

Using a commercially available DNA extraction kit to obtain high quality human genomic DNA suitable for PCR and genotyping from 11-year-old saliva saturated cotton spit wads

<p>Abstract</p> <p>Background</p> <p>We sought to describe the integrity of human genomic DNA extracted from saliva saturated cotton spit wads stored at -20°C for approximately 11 years. 783 spit wad samples were collected from an ADHD sample population (Vermont Family Study) during 1996–2000. Human genomic DNA was extracted from the spit wads using a commercially available kit; QIAamp DNA Blood Midi Kit (Qiagen, Inc., Valencia, CA.) with a few modifications.</p> <p>Results</p> <p>The resulting DNA yield was more than adequate for genetic analysis and ranged from approximately 1 μg to a total of 80 μg (mean 17.3 μgs ± 11.9 μgs). A₂₆₀/A₂₈₀ratios for the human genomic DNA extracted from the spit wads was consistently within the generally acceptable values of 1.7–2.0, with the lowest purity being 1.70, and a mean value of 1.937 ± 0.226 for the 783 samples. The DNA also was suitable for PCR reactions as evidenced by the amplification of the serotonin-transporter-linked polymorphic region, 5HTTLPR. 5HTTLPR is a functional polymorphism in the promoter region of the serotonin transporter gene (<it>HTT, SLC6A4</it>, or <it>SERT</it>), consisting of two intensively studied alleles. 770 of the 783 samples (98.3%) produced fragments after PCR of the expected size with primers specific for 5HTTLPR.</p> <p>Conclusion</p> <p>High quality and abundant genomic DNA can be successfully retrieved from saliva saturated cotton spit wads using the commercially available kit, QIAamp DNA Blood Midi Kit from Qiagen, Inc. Furthermore, the DNA can be extracted in less than 3 hours and multiple samples can be processed simultaneously thus reducing processing time.</p

Obesity Management: Clinical Review and Update of the Pharmacologic Treatment Options

The toolbox of medications available for medical weight management is more robust than ever and includes a wide variety of mechanisms of actions and options for patients

Visual and Motor Connectivity and the Distribution of Calcium-Binding Proteins in Macaque Frontal Eye Field: Implications for Saccade Target Selection

The frontal eye field (FEF) contributes to directing visual attention and saccadic eye movement through intrinsic processing, interactions with extrastriate visual cortical areas (e.g., V4), and projections to subcortical structures (e.g., superior colliculus, SC). Several models have been proposed to describe the relationship between the allocation of visual attention and the production of saccades. We obtained anatomical information that might provide useful constraints on these models by evaluating two characteristics of FEF. First, we investigated the laminar distribution of efferent connections from FEF to visual areas V4 + TEO and to SC. Second, we examined the laminar distribution of different populations of GABAergic neurons in FEF. We found that the neurons in FEF that project to V4 + TEO are located predominantly in the supragranular layers, colocalized with the highest density of calbindin- and calretinin-immunoreactive inhibitory interneurons. In contrast, the cell bodies of neurons that project to SC are found only in layer 5 of FEF, colocalized primarily with parvalbumin inhibitory interneurons. None of the neurons in layer 5 that project to V4 + TEO also project to SC. These results provide useful constraints for cognitive models of visual attention and saccade production by indicating that different populations of neurons project to extrastriate visual cortical areas and to SC. This finding also suggests that FEF neurons projecting to visual cortex and SC are embedded in different patterns of intracortical circuitry

Taking Stock of Circumboreal Forest Carbon With Ground Measurements, Airborne and Spaceborne LiDAR

The boreal forest accounts for one-third of global forests, but remains largely inaccessible to ground-based measurements and monitoring. It contains large quantities of carbon in its vegetation and soils, and research suggests that it will be subject to increasingly severe climate-driven disturbance. We employ a suite of ground-, airborne- and space-based measurement techniques to derive the first satellite LiDAR-based estimates of aboveground carbon for the entire circumboreal forest biome. Incorporating these inventory techniques with uncertainty analysis, we estimate total aboveground carbon of 38 +/- 3.1 Pg. This boreal forest carbon is mostly concentrated from 50 to 55degN in eastern Canada and from 55 to 60degN in eastern Eurasia. Both of these regions are expected to warm >3 C by 2100, and monitoring the effects of warming on these stocks is important to understanding its future carbon balance. Our maps establish a baseline for future quantification of circumboreal carbon and the described technique should provide a robust method for future monitoring of the spatial and temporal changes of the aboveground carbon content