Rescue of Outer Hair Cells with Antisense Oligonucleotides in Usher Mice Is Dependent on Age of Treatment

The absence of functional outer hair cells is a component of several forms of hereditary hearing impairment, including Usher syndrome, the most common cause of concurrent hearing and vision loss. Antisense oligonucleotide (ASO) treatment of mice with the human Usher mutation, Ush1c c.216G>A, corrects gene expression and significantly improves hearing, as measured by auditory-evoked brainstem responses (ABRs), as well as inner and outer hair cell (IHC and OHC) bundle morphology. However, it is not clear whether the improvement in hearing achieved by ASO treatment involves the functional rescue of outer hair cells. Here, we show that Ush1c c.216AA mice lack OHC function as evidenced by the absence of distortion product otoacoustic emissions (DPOAEs) in response to low-, mid-, and high-frequency tone pairs. This OHC deficit is rescued by treatment with an ASO that corrects expression of Ush1c c.216G>A. Interestingly, although rescue of inner hairs cells, as measured by ABR, is achieved by ASO treatment as late as 7 days after birth, rescue of outer hair cells, measured by DPOAE, requires treatment before post-natal day 5. These results suggest that ASO-mediated rescue of both IHC and OHC function is age dependent and that the treatment window is different for the different cell types. The timing of treatment for congenital hearing disorders is of critical importance for the development of drugs such ASO-29 for hearing rescue.     

Association between prostate size and the incidence of prostate cancer: a meta-analysis and review for urologists and clinicians

Purpose

To review the literature regarding any clinically significant association between prostate size and the incidence of prostate cancer (PCa). No previous review or meta-analysis has reported this clinical question.

Methods

A thorough literature review was performed using PubMed and applying the ‘PRISMA’ guidelines. Inclusion and exclusion criteria were defined.

Results

A total of 30 articles met the search criteria. Of these 30 articles, 27 reported an inverse correlation between prostate volume (PV) and incidence of biopsy-proven PCa. The remaining three articles provided no clear statistically significant results, and there was no study showing a direct or positive correlation between PV and the incidence of PCa.

Conclusion

This review and meta-analysis is the first report summarizing the literature on the clinical question of whether prostate size affects the incidence of PCa. Ninety percent of studies (27/30) show significant evidence supporting the hypothesis that prostate size may be protective of PCa. This review and the outlined discussion should encourage other clinical investigators to explore the relationship between PV and the incidence and aggressiveness of PCa. If future studies should confirm the hypothesis of the dynamic interactions between the different prostatic zones in a growing prostate, it will have relevant clinical implications on the management of BPH and PCa.

     

Hydrothermal combustion based ZnO nanoparticles from Croton bonplandianum: Characterization and evaluation of antibacterial and antioxidant potential

The present study reports facile phytomediated synthesis of ZnO nanoparticles (ZnO NPs) using hydrothermal combustion from Croton bonplandianum Bail. The characterization studies revealed that an average 44 nm size spherical ZnO NPs with high zinc composition having good crystalline nature. FTIR analysis confirmed the presence of functional groups O–H, sp3 C–H bend, and alkoxy C–O functional groups which might be involved in capping and reduction for ZnO NPs synthesis. The biosynthesized ZnO NPs exhibited potent antibacterial activity against Gram-positive and Gram-negative bacteria. The MIC results revealed that ZnO NPs were most effective against Bacillus cereus whereas least sensitive towards Pseudomonas aeruginosa and Vibrio parahaemolyticus. This investigation suggests that biosynthesized ZnO NPs are promising agents for antibacterial and antioxidant applications in the biomedical field.     

Use of psychopharmacologic agents in the elderly

Most psychiatric disorders in elderly patients are amenable to treatment, provided that intervention is thorough and intensive. Appropriate and judicious use of psychopharmacologic agents has a potential for dramatically improving the quality of life and functional status of many elderly patients with psychiatric disorders. The decision to prescribe a psychopharmacologic agent in elderly patients is a serious and complex issue. Several basic principles need to be followed (Table 6). Although some strides have been made in the last decade regarding safety and efficacy of many psychopharmacologic agents in elderly [table: see text] patients, for many psychopharmacologic agents, large randomized controlled studies to evaluate efficacy and safety in elderly patients are lacking. Sparse data are available regarding the long-term effects of psychopharmacologic agents in elderly patients. Important gaps remain in our knowledge concerning the optimal duration of treatment for most psychiatric disorders in elderly patients. The treatment data deficiency is most striking among the oldest old (patients aged 85 and older), frail medically ill elderly patients (such as nursing home residents), and ethnic minority groups. Future research should focus on these and other relevant issues related to the use of psychopharmacologic agents in elderly patients.