Basic Research

Implantable cardioverter defibrillators (ICDs) are medical devices proven to prevent sudden cardiac death due to ventricular arrhythmias. Their decisions are based solely upon the intra--?cardiac ECG. This is incomplete information since up to 1/3 of patients experience an 'inappropriate' shock within the first 1-3 years of receiving the implant. Receiving a shock is associated with increased mortality as well as emotional trauma.

Most successful human vaccines elicit protective antibodies. CD4+ T cell help is essential for a strong antibody response, especially against poorly immunogenic polysaccharide antigens. To accomplish this, polysaccharide antigens are typically conjugated to highly immunogenic T cell epitopes. Unfortunately, this approach is expensive, only targets a subset of capsular polysaccharide antigens, and depends on allelically variable CD4+ T cell help.

Basic Research

Chemotherapy-induced peripheral neuropathy (CIPN) and the associated pain represent a clinically relevant limit to patient treatment with anti-cancerdrugs. Currently, there is no effective treatment for CIPN. Enhanced excitability of peripheral sensory neurons is thought to contribute to the generation and progression of CIPN. By directly affecting membrane excitability, CIPN-causing chemotherapy drugs may enhance neuronal activity eventuating neuroexcitotoxicity and neuropathy.

Abuse of prescription opioids had reached epidemic levels and is responsible for increasing emergency department visits and overdose deaths. Most prescription opioid deaths involve at least one other drug, often a benzodiazepine (BZD). Up to 70% of opioid abusers also use BZDs, reportedly to enhance opioid-induced feelings of euphoria. Coabuse of opioids and BZDs increases the risk of physical dependence and overdose, and studies in humans suggest that BZD enhancement of abuse-related effects of opioids occurs in dependent, and not in nondependent, individuals.

During gestation, the excitatory neurotransmitter serotonin (5-hydroxytryptamine or 5-HT) directs synapse formation and pruning in fetal brain circuits responsible for shaping social behavior. This course of development continues to unfold after birth and with social stimulation, both in juvenile mice and in infants. The 5-HT neurotransmitter system, including its transporters and receptors, are among the earliest to appear in the brain during embryonic development. Critically, this occurs even before the fetal brain has neurons capable of producing 5-HT on their own.

Basic Research

The past 5 years have seen a dramatic increase in the abuse of synthetic cathinones (e.g., MDPV and methylone), which are marketed as 'bath salts,' and are widely available for purchase on the internet and in local shops as 'safe' and 'legal highs.' In addition to a high potential for abuse, 'bath salts' also have a high potential fr toxicity, characterized by severe cardiovascular and neuropsychiatric complications.

Basic Research