Communication Impairments in Mice Lacking Shank1: Reduced Levels of Ultrasonic Vocalizations and Scent Marking Behavior

Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1−/− null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1−/− mice as compared to wildtype Shank1+/+ littermate controls. Shank1−/− pups emitted fewer vocalizations than Shank1+/+ pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1−/− males deposited fewer scent marks in proximity to female urine than Shank1+/+ males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1+/+ mice changed their calling pattern dependent on previous female interactions, while Shank1−/− mice were unaffected, indicating a failure of Shank1−/− males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1−/− mice are consistent with a phenotype relevant to social communication deficits in autism.National Institute of Mental Health (U.S.) (Intramural Research Program)Simons Foundatio

Targeting Huntington’s disease through histone deacetylases

Huntington’s disease (HD) is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with this condition remain limited. Aberrant post-translational modification (PTM) of proteins is emerging as an important element in the pathogenesis of HD. These PTMs include acetylation, phosphorylation, methylation, sumoylation and ubiquitination. Several families of proteins are involved with the regulation of these PTMs. In this review, I discuss the current evidence linking aberrant PTMs and/or aberrant regulation of the cellular machinery regulating these PTMs to HD pathogenesis. Finally, I discuss the evidence suggesting that pharmacologically targeting one of these protein families the histone deacetylases may be of potential therapeutic benefit in the treatment of HD

Physician Documentation of Sepsis Syndrome Is Associated with More Aggressive Treatment

Introduction: Timely recognition and treatment of sepsis improves survival. The objective is to examine the association between recognition of sepsis and timeliness of treatments.Methods: We identified a retrospective cohort of emergency department (ED) patients with positive blood cultures from May 2007 to January 2009, and reviewed vital signs, imaging, laboratory data, and physician/nursing charts. Patients who met systemic inflammatory response syndrome (SIRS) criteria and had evidence of infection available to the treating clinician at the time of the encounter were classified as having sepsis. Patients were dichotomized as RECOGNIZED if sepsis was explicitly articulated in the patient record or if a sepsis order set was launched, or as UNRECOGNIZED if neither of these two criteria were met. We used median regression to compare time to antibiotic administration and total volume of fluid resuscitation between groups, controlling for age, sex, and sepsis severity.Results: SIRS criteria were present in 228/315 (72.4%) cases. Our record review identified sepsis syndromes in 214 (67.9%) cases of which 118 (55.1%) had sepsis, 64 (29.9%) had severe sepsis, and 32 (15.0%) had septic shock. The treating team contemplated sepsis (RECOGNIZED) in 123 (57.6%) patients. Compared to the UNRECOGNIZED group, the RECOGNIZED group had a higher use of antibiotics in the ED (91.9 vs.75.8%, p=0.002), more patients aged 60 years or older (56.9 vs. 33.0%, p=0.001), and more severe cases (septic shock: 18.7 vs. 9.9%, severe sepsis: 39.0 vs.17.6%, sepsis: 42.3 vs.72.5%; p<0.001). The median time to antibiotic (minutes) was lower in the RECOGNIZED (142) versus UNRECOGNIZED (229) group, with an adjusted median difference of -74 minutes (95% CI [-128 to -19]). The median total volume of fluid resuscitation (mL) was higher in the RECOGNIZED (1,600 mL) compared to the UNRECOGNIZED (1,000 mL) group. However, the adjusted median difference was not statistically significant: 262 mL (95% CI [ -171 to 694 mL]).Conclusion: Patients whose emergency physicians articulated sepsis syndrome in their documentation or who launched the sepsis order set received antibiotics sooner and received more total volume of fluid. Age <60 and absence of fever are factors associated with lack of recognition of sepsis cases. [West J Emerg Med. 2015;16(3):401–407.