Universal biological scaling and mortality.

Universal scaling relations for basal metabolism, heart rate, and life-span are presented in a physically transparent form with no adjustable parameters. Their accuracy is a few percent for animals ranging from invertebrates to mammals. They suggest that natural death is related to irreparable molecular damage to specific cells or molecules.     

Modulation of the immune response using Rapana thomasiana hemocyanin

We have investigated the non-specific immunostimulatory and specific immunomodulatory effects of hemocyanin from marine gastropod Rapana thomasiana (RtH). The purified RtH, its structural subunits RtH1 and RtH2 and a construct with influenza virus hemagglutinin intersubunit peptide (IP) were used in immunization protocols of Balb/c mice. Antibody formation against RtH, RtH1, RtH2, RtH-IP as well as anti-RtH IgG antibody isotypes were determined by ELISA. The immune homology between both subunits and the whole RtH molecule was investigated by cross-blotting technique. The retaining of the B-cell epitope of IP, coupled to the RtH was recognised by Western blot. The results obtained demonstrate that the immunization with RtH or its subunits in experimental models resulted in strong immune response in vivo. Common epitope of influenza A virus hemagglutinin jointed to RtH results in generation of molecule with increased immunogenicity. Our results are the first demonstration that RtH and/or its subunits could be used in different immunization protocols as an adjuvant or as a protein-carrier.     

Longitudinal investigation of the impact of anxiety and mood disorders in adolescence on subsequent substance use disorder onset and vice versa

Objective

A large body of epidemiological research indicates that anxiety and mood disorders are highly comorbid with substance use disorders (SUDs). However, longitudinal research regarding their temporal relations is limited. The goal of this study was to assess whether emotional disorders (i.e., anxiety and mood disorders) predict the onset of SUDs, whether SUDs predict the onset of emotional disorders, or both.

Method

The current study used data from baseline assessment (N = 627) and four years of follow-up assessments from the NU/UCLA Youth Emotion Project to examine this question.

Results

In line with the self-medication hypothesis of emotional disorder/SUDs comorbidity, anxiety and unipolar mood disorders at baseline assessment were associated with later onsets of SUDs. In particular, social anxiety disorder (SAD) at baseline predicted onset of alcohol use disorders and PTSD predicted the onset of all SUDs. SUDs did not predict any anxiety or unipolar mood disorders with the exception that alcohol use disorders predicted the onset of obsessive compulsive disorder (OCD).

Conclusions

These findings, as well as the clinical implications and future directions for research, are discussed.     

Introduction to the older patient: a "first exposure" to geriatrics for medical students

In 2003, Weill Cornell Medical College developed a 4-hour module to introduce the geriatric patient within the required first-year doctoring course. The educational intervention highlights the importance of communication between older patients and physicians, the utility of an enhanced social history and functional assessment, and the pitfalls of ageism in the medical setting. The module incorporates film, the performing arts, and small-group exposure to a community-residing older person. To evaluate the module's effect, four successive classes of first-year medical students (2003-2006) responded to a 14-item questionnaire and three opened-ended questions at the end of the 4-hour curriculum. Quantitative and qualitative analysis reveal consistently strong positive student feedback to this module. Almost all students agreed that the learning objectives were clear (99%) and had been met (99%). Several curricular interventions received high endorsement from the respondents in their questionnaire and narrative comments. Most (94%) were in strong agreement that meeting the older patient in the small group was a worthwhile experience. Also, students appreciated observing an example of a substandard interview (76% in strong agreement) and then a demonstration of effective communication (83% in strong agreement) through dramatic enactments. The majority of students (97%) commented that exposure to these presentations enabled them to see ageist behavior firsthand and to observe how ageist attitudes interfere with appropriate diagnosis and medical care. This approach to introducing the older patient may be of use at other medical schools. Future studies will need to evaluate the long-term effect of this educational intervention.     

HSP90 inhibitor, DMAG, synergizes with radiation of lung cancer cells by interfering with base excision and ATM-mediated DNA repair

Inhibition of heat shock protein 90 (HSP90) leads to inappropriate processing of proteins involved in cell survival pathways. We found that HSP90 inhibitor, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (DMAG), is synergistic with radiation for non-small cell lung cancer cell lines, NCI-H460 and A549. To establish the optimal schedule for this combination, cells were radiated before, after, or simultaneously with DMAG, and survival was scored by clonogenic assay. The sequence of DMAG administration was critical for synergy with radiation, and pretreatment for 16 h led to maximal synergy. Similar radiosensitization was observed in isogenic cells in which expression of wild-type p53 was silenced by RNA interference, although p53 loss rendered cells overall less radiosensitive. The mechanistic basis for synergy was studied by Western blotting, cell cycle analysis, alkaline comet assay, and direct measurement of the activities of key base excision repair enzymes. Regardless of schedule of administration, DMAG led to degradation of proteins involved in activation of cell survival pathways after radiation, which did not explain the differences in the schedule of administration observed in clonogenic assays. In addition to previously reported decrease in activation of ATM, pretreatment with DMAG blocked activation of base excision repair machinery and activity of key enzymes, apurinic/apyrimidinic endonuclease, and DNA polymerase-beta. Similarly, pretreatment with specific apurinic/apyrimidinic endonuclease inhibitor, CRT0044876, reproduced the effects of DMAG. Thus, administration of HSP90 inhibitors before radiation is critical for optimizing their use as radiosensitizers.