Stigmatization of substance use disorders among internal medicine residents.

BACKGROUND: Evidence suggests that some physicians harbor negative attitudes towards patients with substance use disorders (SUDs). The study sought to (1) measure internal medicine residents' attitudes towards patients with SUDs and other conditions; (2) determine whether demographic factors influence regard for patients with SUDs; and (3) assess the efficacy of a 10-hour addiction medicine course for improving attitudes among a subset of residents. METHODS: A prospective cohort study of 128 internal medicine residents at an academic medical center in New York City. Scores from the validated Medical Condition Regard Scale (MCRS) were used to assess attitude towards patients with alcoholism, dependence on narcotic pain medication, heartburn, and pneumonia. Demographic variables included gender, postgraduate training year, and prior addiction education. RESULTS: Mean baseline MCRS scores were lower (less regard) for patients with alcoholism (41.4) and dependence on narcotic pain medication (35.3) than for patients with pneumonia (54.5) and heartburn (48.9) (P < .0001). Scores did not differ based upon gender, prior hours of addiction education, or year of training. After the course, MCRS scores marginally increased for patients with alcoholism (mean increased by 0.16, P = .04 [95% confidence interval, CI: 0.004-0.324]) and dependence on narcotic pain medication (mean increased by 0.09, P = .10 [95% CI: 0.02-0.22]). CONCLUSIONS: Internal medicine residents demonstrate less regard for patients with SUDs. Participation in a course in addiction medicine was associated with modest attitude improvement; however, other efforts may be necessary to ensure that patients with potentially stigmatized conditions receive optimal care.

Hemophagocytic lymphohistiocytosis secondary to Ehrlichia chaffeensis infection: a case report.

SUMMARY: Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially life-threatening condition that is characterized by fever, splenomegaly, and cytopenia in 2 or more peripheral blood lineages, hypertriglyceridemia, hypofibrinogenemia, and hemophagocytosis. HLH may be primary or may be triggered by numerous etiologies, including infections. Identification of underlying etiology of HLH is important as proper treatment can completely resolve the disease process. We present a patient whose clinical presentation fulfilled the diagnostic criteria for HLH but whose illness was caused by infection with Ehrlichia chaffeensis, emphasizing the need to explore all possible etiologies during evaluation of patients presenting with illnesses consistent with HLH.

The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design.

The ribosomal P70 S6 kinases play a crucial role in PI3K/mTOR regulated signalling pathways and are therefore potential targets for the treatment of a variety of diseases including diabetes and cancer. In this study we describe the identification of three series of chemically distinct S6K1 inhibitors. In addition, we report a novel PKA-S6K1 chimeric protein with five mutations in or near its ATP-binding site, which was used to determine the binding mode of two of the three inhibitor series, and provided a robust system to aid the optimisation of the oxadiazole-substituted benzimidazole inhibitor series. We show that the resulting oxadiazole-substituted aza-benzimidazole is a potent and ligand efficient S6 kinase inhibitor, which blocks the phosphorylation of RPS6 at Ser235/236 in TSC negative HCV29 human bladder cancer cells by inhibiting S6 kinase activity and thus provides a useful tool compound to investigate the function of S6 kinases.

Brain state evolution during seizure and under anesthesia: a network-based analysis of stereotaxic eeg activity in drug-resistant epilepsy patients.

Epilepsy is a neurological condition with a prevalence of 1%, and 14-34% have medically refractory epilepsy (MRE). Seizures in focal MRE are generated by a single epileptogenic zone (or focus), thus there is potentially a curative procedure - surgical resection. This procedure depends significantly on correct identification of the focus, which is often uncertain in clinical practice. In this study, we analyzed intracranial stereotaxic EEG (sEEG) data recorded in two human patients with drug-resistant epilepsy prior to undergoing resection surgery. We view the sEEG data as samples from the brain network and hypothesize that seizure foci can be identified based on their network connectivity during seizure. Specifically, we computed a time sequence of connectivity matrices from EEG recordings that represent network structure over time. For each patient, connectivity between electrodes was measured using the coherence in a given frequency band. Matrix structure was analyzed using singular value decomposition and the leading singular vector was used to estimate each electrode's time dependent centrality (importance to the network's connectivity). Our preliminary study suggests that seizure foci may be the most weakly connected regions in the brain during the beginning of a seizure and the most strongly connected regions towards the end of a seizure. Additionally, in one of the patients analyzed, the network connectivity under anesthesia highlights seizure foci. Ultimately, network centrality computed from sEEG activity may be used to develop an automated, reliable, and computationally efficient algorithm for identifying seizure foci.