All in the family: atypical Hsp70 chaperones are conserved modulators of Hsp70 activity.

Divergent relatives of the Hsp70 protein chaperone such as the Hsp110 and Grp170 families have been recognized for some time, yet their biochemical roles remained elusive. Recent work has revealed that these "atypical" Hsp70s exist in stable complexes with classic Hsp70s where they exert a powerful nucleotide-exchange activity that synergizes with Hsp40/DnaJ-type cochaperones to dramatically accelerate Hsp70 nucleotide cycling. This represents a novel evolutionary transition from an independent protein-folding chaperone to what appears to be a dedicated cochaperone. Contributions of the atypical Hsp70s to established cellular roles for Hsp70 now must be deciphered.

The effects of antipsychotic medications on eye movements in schizophrenia

Schizophrenia is the most prevalent mental disorder in the world, affecting approximately one percent of the population. Antipsychotic medications have successfully treated schizophrenic psychotic symptoms for years, however their positive effects on cognitive dysfunction, a core feature of schizophrenia, are inconclusive. Recent studies have shown that improved cognitive functioning is most often associated with the best long-term prognosis. Thus, clarifying the cognitive effects of commonly prescribed antipsychotic medications is pivotal to improving quality of life and long-term care of schizophrenic patients.^ Previous studies on cognitive dysfunction in schizophrenia utilized complex neuropsychological tasks requiring many intact areas of the brain for proper completion. These complexities make interpretation of acquired data difficult. Recently, eye movements have been identified as a more effective surrogate for investigating cognitive functioning. Eye movements are easily measured, require known discrete areas of the brain for processing, and are ubiquitous. They influence what we attend to and process in the brain; thus they are a pivotal aspect of cognitive functioning. This study sought to examine the effects of antipsychotic medications on eye movements in forty-two schizophrenic patients. These patients were divided equally into the three tested medication groups: haloperidol, olanzapine, and aripiprazole. To the extent possible, these groups were further separated into task-impaired and task-nonimpaired subgroups, and again analyzed. Clinical and neuropsychological scales were administered to assess clinical and eye movement changes.^ The results of this study found the olanzapine-treated group exhibited superior cognitive effects to the aripiprazole-treated group, who was superior to the haloperidol-treated group. Furthermore, upon subdivision into cognitively impaired and nonimpaired subgroups, both olanzapine-treated subgroups continued to show improvement, while only the aripiprazole-treated impaired subgroup showed cognitive benefit. The haloperidol-treated nonimpaired subgroup actually demonstrated worsening effects. Interestingly, despite the cognitive decline of some subgroups, the clinical assessment results indicated virtually all subgroups exhibited significant clinical improvement. Hence, careful selection of an antipsychotic medication is crucial, as this study shows some treatments may help whereas others may hinder cognitive functioning in schizophrenia. ^ The results of this study are extremely important given the relationship between cognitive improvement and long-term prognosis in schizophrenia. Finally, and perhaps most importantly, these results indicate that clinical improvement is not necessarily indicative of cognitive improvement. ^

Retrospective assesment of the levonorgestrel intrauterine device to treat complex atypical hyperplasia and early endometrioid endometrial cancer

Objective: The primary objective of this project was to describe the efficacy of the Levonorgestrel Intrauterine Device (LIUD) for treatment of Complex Endometrial Cancer (CAH) and Grade 1 Endometrial Cancer (G1EEC) in terms of rate of Complete Response (CR) and Partial Response (PR) after 6 months of therapy. Finally, we assessed if any clinical or pathologic features were associated with response to the LIUD. ^ Methods: This study was a retrospective case series designed to report the response rate of patients with CAH or G1EEC treated with LIUD therapy. In addition, this study has a laboratory component to assess molecular predictors of response to LIUD therapy. Retrospective data already collected from patients diagnosed with CAH or EEC grade 1 and treated with LIUD therapy at MD Anderson Cancer Center (MDACC) were used for this study. Patients from all ethnic and race groups were included. A Complete Response (CR) was defined in patients diagnosed with CAH if pathologic report at 6 months demonstrated either no evidence of hyperplasia or no atypia in the setting of simple or complex hyperplasia. Partial Response (PR) was recorded if disease downgraded to only CAH from G1EEC. No Response (NR) was recorded if pathologic report demonstrates no change (Stable Disease, SD) or progression to cancer (Progressive Disease, PD). We calculated the proportion of patients with complete response to LIUD therapy with 95% confidence interval. We compared the response rates (CR/PR vs NR) by obesity status (Obese if BMI > 40 kg/m2 vs non-obese if BMI <= 40 kg/m2) as well as other clinical and pathologic factors, such as age, uterine size (median size), and presence of exogenous progesterone effect. ^ Results: There were 39 patients diagnosed with either CAH or G1EEC treated with the LIUD. Of 39 patients, 12 did not have pathological results of biopsy at 6months time period. Of 27 evaluable patients, 17 were diagnosed with CAH and 10 with G1EEC. Overall response rate (RR) was 78% (95% CI = 62-94%) at 6 months, 18 patients had CR (4 in G1EEC; 14 in CAH), 3 patients had PR (3 in G1EEC), 3 had SD (1 in CAH; 2 in G1EEC), 3 had PD (2 in CAH; 1 in G1EEC). After histology stratification, RR at 6 months was 82.35% (14/17; 95%CI = 67.4-97.3%) in CAH and 70% (7/10; 95% CI = 41-98.4%) in G1EEC. ^ There was no difference in response (R) and no response (NR) based on BMI (p=0.56). He observed a trend showing association between age with response (p=0.1). There was no association between uterine size and response to therapy (p=0.17). We recorded strong association between exogenous progesterone effect and response. ^ Conclusion: LIUD therapy for the treatment of CAH and G1EEC may be effective and safe. Presence of exogenous progesterone effect may predict the response to LIUD therapy at earlier time points. There is need of further studies with larger sample size to explore the relationship of response with other clinical and pathologic factors^