A prospective study of cultural consonance and depressive symptoms in urban Brazil

Cultural consonance refers to the degree to which individuals, in their own beliefs and behaviors, approximate the prototypes for belief and behavior encoded in shared cultural models. In previous cross-sectional studies, lower cultural consonance in several cultural domains was associated with worse health outcomes, including greater psychological distress. The current paper extends these findings in three ways. First, the effect of cultural consonance on depressive symptoms is tested in a prospective study. Second, it is hypothesized that the effect of cultural consonance in a specific cultural domain will depend on the degree of cultural consensus within that domain: the higher the cultural consensus, the greater the effect of change in cultural consonance in that domain on depressive symptoms. Third, it is hypothesized that cultural consonance will have an inverse effect on depressive symptoms independent of the occurrence of stressful life events (a well-known risk factor for depression). We tested these hypotheses in a study conducted in urban Brazil, and found that change in cultural consonance (assessed as a general construct) was associated with depressive symptoms at a 2-year follow-up. Furthermore, cultural consonance in the domains in which there was highest cultural consensus—the domains of family life and lifestyle—was more strongly associated with depressive symptoms at follow-up than cultural consonance in domains with lower cultural consensus. Finally, all of these effects were independent of stressful life events. These results lend further support to the importance of cultural consonance in relation to human health.     

The prince and the pauper. A tale of anticancer targeted agents

Cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000 to 15 million in 2020. Regarding the pharmacological treatment of cancer, we currently are in the interphase of two treatment eras. The so-called pregenomic therapy which names the traditional cancer drugs, mainly cytotoxic drug types, and post-genomic era-type drugs referring to rationally-based designed. Although there are successful examples of this newer drug discovery approach, most target-specific agents only provide small gains in symptom control and/or survival, whereas others have consistently failed in the clinical testing. There is however, a characteristic shared by these agents: -their high cost-. This is expected as drug discovery and development is generally carried out within the commercial rather than the academic realm. Given the extraordinarily high therapeutic drug discovery-associated costs and risks, it is highly unlikely that any single public-sector research group will see a novel chemical "probe" become a "drug". An alternative drug development strategy is the exploitation of established drugs that have already been approved for treatment of non-cancerous diseases and whose cancer target has already been discovered. This strategy is also denominated drug repositioning, drug repurposing, or indication switch. Although traditionally development of these drugs was unlikely to be pursued by Big Pharma due to their limited commercial value, biopharmaceutical companies attempting to increase productivity at present are pursuing drug repositioning. More and more companies are scanning the existing pharmacopoeia for repositioning candidates, and the number of repositioning success stories is increasing. Here we provide noteworthy examples of known drugs whose potential anticancer activities have been highlighted, to encourage further research on these known drugs as a means to foster their translation into clinical trials utilizing the more limited public-sector resources. If these drug types eventually result in being effective, it follows that they could be much more affordable for patients with cancer; therefore, their contribution in terms of reducing cancer mortality at the global level would be greater.     

Test-retest reliability in tympanometry.

Test-retest reliability for tympanometric measures was evaluated across five sessions in 20 subjects with normal hearing and normal middle-ear function. Tympanograms were obtained on each ear for probe frequencies of 226, 678, and 1000 Hz using both ascending and descending directions of pressure change. Across all conditions, the tympanometric measure that consistently demonstrated the highest test-retest reliability was compensated static acoustic admittance. Test-retest correlations for peak compensated static acoustic admittance measures were higher than those for ambient measures across all probe frequencies and both directions of pressure change; the differences in correlations for peak and ambient measures, however, reached significance only for 226-Hz conditions. Across-session correlations for tympanogram width did not differ significantly for measures referenced to the lowest tympanogram tail and those referenced to +200 daPa.     

Gamete intrafallopian transfer vs superovulation with intrauterine insemination for the treatment of infertility

Superovulation with intrauterine insemination (SO-IUI) has been suggested as an alternative to gamete intrafallopian transfer (GIFT), despite the absence of controlled or comparative trials. We retrospectively analyzed all GIFT and SO-IUI cycles performed concurrently from January 1985 to August of 1987 at a single university center. Pregnancy rates were significantly better for GIFT than SO-IUI (P<0.001), with an odds ratio of 3.25 (P=0.001). Stepwise multiple logistic regression identifield factors that correlate with pregnancy: absence of endometriosis (P=0.05), infertility<3 years' duration (P=0.002), TMS 30×10⁶ (P=0.005), and treatment with GIFT rather than SO-IUI (P=0.001). These data give a first approximation of the increased efficacy of GIFT versus SO-IUI and provide valuable insight into significant confounding variables to be considered when planning a randomized, prospective trial to evaluate these techniques.     

Synthesis and tumor-initiating activity in mouse skin of dibenzo[a,l]pyrene syn- and anti-fjord-region diolepoxides

Dibenzo[a,l]pyrene (DB[a,l]P) is the most potent carcinogenamong polycycic aromatic hydrocarbons. Because the fjord-regiondiolepoxide (DE) pathway is one of the mech anisms of activation,(±)-trans-DB [a,l]P-11,12-dihydrodiol,(±)-anti-DB[a,l]PDEand (±)-syn-DB[a,l]PDE were synthesized. The key intermediatefor these syntheses, 12-methoxy-DB[a,l]P, was successfully obtainedby cyclizatlon of 6-(3-methoxybenzyl)benzanthrone with methanesulfonicacid, which in turn was prepared by 1,4 conjugate addition of3-methoxybenzyl magnesium bromide to benzanthrone. The presenceof the DB[a,l]P nucleus in the dihydrodiol epoxides and diolepoxideswas proven by conversion of 12-methoxyDB[a,l]P into the parentcompound in several steps. The tumor-initiating activity ofthe two diolepoxides in mouse skin was compared to that of DB[a,l]P-11,12-dihydrodioland the parent DB[a,l]P Groups of 24 8 week old female SENCARmice were topically initiated with 12, 4 or 133 nmol of compoundIn 100 µl of acetone. Starting 1 week later, promotionwith 12-O-tetradecanoylphorbol-13-acetate (1.62 nmol In 100µl acetone) was begun and continued twice weekly for 30weeks. At the 12, 4 and 1.33 nmol doses, anti-DB[a,l]PDE induced2.0, 0.7 and 0.7 tumors per mouse (t/m) respectively, whereassyn DB[a,l]PDE induced 1.8, 1.5 and 1.8 t/m. At the same threedoses, DB[a,l]P-11,12-dihydrodiol induced 4.6, 4.3 and 2.8 t/m,and DB[a,l]P resulted in 9.3,7.1 and 5.2 t/m. These resultsconfirm that DB[a,l]P is more potent than its 11,12-dihydrodloland show that the two diolepoxides are less tumorlgenic thantheir precursors. At the medium and low doses, syn-DB[a,l]PDEis more tumorigenic than its congener anti-DB[a,l]PDE.     

Reduction of Toxicity of a Vinca Alkaloid by an Anti-Vinca Alkaloid Antibody

Inadvertent oncolytic overdoses occur rarely, but can have serious consequences. We have investigated the possibility of using an antibody, 27.8.1A, reactive with vinca alkaloids, as a means of reducing the toxicity associated with overdose situations. In vitro cytotoxicity of a vinca derivative, 4-desacetyl-vinblastine-3-car-box-hydrazide (DAVLBHYD), with and without the addition of 27.8.1A, was determined. Using CCRF-CEM, a human acute lymphoblastic leukemia cell line, as a target in this assay, we observed a greater than 90% increase in cell viability using 100 μg/ml 27.8.1A with a 0.1 pglml concentration of DAVLBHYD. 27.8.1A had no effect on cell viability when doxorubicin was used as a control drug in this assay. Similarly, the addition of an irrelevant antibody, EGFrL11, had no effect on the toxicity of DAVLBHYD. In an in vivo survival experiment, nude mice were injected with a toxic dose of DAVLBHYD and subsequently given four doses of 27.8.1A. All anti vinca antibody-treated mice survived, in contrast to the untreated group or irrelevant antibody-treated group in which only 25% and 10% of the mice survived, respectively.     

Frequency selectivity and consonant intelligibility in sensorineural hearing loss

The relations between frequency selectivity and consonant intelligibility were investigated in subjects with sensorineural hearing loss in an attempt to derive predictive indices. Three matched pairs of subjects with similar audiometric configurations (high-frequency, flat or low-frequency hearing loss) but significantly different word-intelligibility scores were tested. Characteristics of psychophysical tuning curves (PTCs) for high- and low-frequency probes were compared with speech-intelligibility performance for high- and low-frequency consonant-vowel syllables. Frequency-specific relations between PTC characteristics and consonant-intelligibility performance were observed in the subject pairs with high-frequency and flat sensorineural hearing loss. Corresponding results for the subject pair with low-frequency sensorineural hearing loss were equivocal.     

The effects of tetanus toxin on the orbicularis oculi muscle

PURPOSE: Tetanus toxin can cause localized neuromuscular weakness, but it also can produce systemic tetany. The action of tetanus toxin on the orbicularis muscle has not been studied in animals immunized to prevent systemic tetany. Our objective was to determine whether tetanus toxin could be used to treat orbicularis oculi muscle spasms. METHODS: We analyzed the clinical, electrophysiologic, and histopathologic effects of tetanus toxin injected into the orbicularis oculi muscle of rabbits with passive immunity to tetanus toxin. In six rabbits, the orbicularis oculi function in both eyes was assessed clinically, and the baseline orbicularis oculi muscle action potential was measured physiologically with electromyography (EMG). The rabbits then were immunized against tetanus toxin with tetanus immunoglobulin for immediate and definitive immunity. Tetanus toxin was injected into the left orbicularis oculi muscles, leaving the right eyes as controls. Ten days later, the rabbits were again assessed by clinical examination and with EMGs on both the injected side and the noninjected side. The animals were killed at 14 days, and the orbicularis muscle was removed from both sides. The injected and control tissues were examined microscopically for signs of neuromuscular denervation. RESULTS: All six rabbits showed weakness in eye closure on the side injected with tetanus toxin. In addition, four rabbits developed complete ear ptosis on the tetanus toxin injected side because of spread of the toxin to adjacent ear muscles. EMGs showed both a denervation of the orbicularis oculi muscle and a poor blink potential on the side injected with tetanus toxin. Histopathologic studies of the orbicularis oculi muscle injected with tetanus toxin showed angulation of both slow and fast types of muscle fibers compatible with neuromuscular denervation. CONCLUSIONS: Tetanus toxin can cause localized orbicularis oculi weakness, as documented clinically, physiologically, and microscopically, without producing systemic tetany in immunized rabbits. Tetanus toxin may have a potential application in the treatment of blepharospasm and hemifacial spasm.