In Vitro and In Vivo Studies of the Biological Activity of Novel Arylimidamides against Trypanosoma cruzi

Fifteen novel arylimidamides (AIAs) (6 bis-amidino and 9 mono-amidino analogues) were assayed against Trypanosoma cruzi in vitro and in vivo. All the bis-AIAs were more effective than the mono-AIAs, and two analogues, DB1967 and DB1989, were further evaluated in vivo. Although both of them reduced parasitemia, protection against mortality was not achieved. Our results show that the number of amidino-terminal units affects the efficacy of arylimidamides against T. cruzi.     

Total Neoadjuvant Therapy (TNT) in Rectal Cancer

Purpose of Review

This review summarizes the relevant literature on the use of total neoadjuvant therapy (TNT) for patients with locally advanced rectal cancer. It highlights the most notable literature published and briefly discusses future directions.

Recent Findings

Recent randomized trials evaluating TNT show improved rates of pathologic complete response and patient treatment tolerance with this approach.

Summary

The rationale for TNT includes the poor patient tolerance of adjuvant chemotherapy and the persistent risk of distant disease in patients with locally advanced rectal cancer, despite improvements in local control. Randomized trials have focused on short-term pathologic endpoints. Ongoing phase 3 trials are evaluating long-term disease-related outcomes, allowing for a more thorough evaluation of this treatment paradigm. TNT may also facilitate organ preservation in appropriately selected patients.

     

Improving Access to Standardized Fertility Preservation Information for Older Adolescents and Young Adults with Cancer: Using a User-Centered Approach with Young Adult Patients,Survivors, and Partners to Refine Fertility Knowledge Transfer

Adolescent and young adult (AYA) cancer patients under 40 should be made aware of their fertility risks and preservation options throughout their care. However, discussions on fertility preservation (FP) do not routinely occur. With a dearth of FP resources, oncology providers may lack knowledge around FP. Thus, informational needs can be unmet, leading to anxiety and distress in patients. Provision of pertinent and timely information can help patients cope better with their diagnosis. FP pamphlets were developed for men and women with cancer. A cross-sectional in-house survey, using convenience sampling, evaluated the pamphlets’ effectiveness and measured ease of understanding, acceptability, and perceived utility. Patients and partners were also asked to provide recommendations and complete the Short Test of Functional Health Literacy in Adults (S-TOFHLA) measuring health literacy level. This helps determine if health literacy influences perception of pamphlet effectiveness. All participants (n = 56) reviewed both pamphlets. Fifty-four participants (96 %) found the pamphlet for men useful, while 29 participants (52 %) improved their male fertility knowledge. The pamphlet for women was useful for 52 participants (93 %) and improved knowledge in 35 (63 %) of them. Although the majority of participants had adequate health literacy (98 %), there was insufficient sample diversity to determine if health literacy influenced the pamphlet’s effectiveness. Participants indicated preference in receiving verbal (73 %) and written (66 %) information over watching videos or in-class education. They recommended including fertility clinics, financial resources, and statistics in the brochures. These FP pamphlets were concluded as effective in supporting patients in making FP decisions.     

An evaluation of the Weber classification of ankle fractures

This retrospective study over a 3 year follow-up was designed to establish the significance of the Weber classification of ankle fractures with regards to functional and radiographic outcome. One hundred and seven patients were available for follow-up, of which 88 ankles could be classified with the Weber system. Medial malleolar fractures alone and pilon fractures could not be classified with this system. A correlation was found between the type of Weber fracture and the overall ankle score. This held true for unimalleolar fractures alone. More complex bimalleolar and trimalleolar fractures did not follow this convention. Logistical regression analysis was used to evaluate other predictors of outcome. Bimalleolar and trimalleolar fractures were statistically significant predictors of a poorer outcome (P = 0.033, P = 0.021). The initial degree of displacement was also determined to be a predictor of outcome (P = 0.0133) as was the operative reduction (P = 0.0113). Using linear regression, older age (> 62 years) was also established as a predictor of a poorer outcome (P < 0.05). The Weber classification was found to be a predictor of outcome in unimalleloar ankle fractures and not for multimalleolar fractures. We have identified further predictors of a poorer outcome in ankle fractures as the degree of initial injury, the number of malleoli fractured and older age. These factors were found to have greater significance in predicting outcome than the level of fibular fracture alone. We have identified a deficiency of the Weber system in excluding these criteria and have addressed this by modifying the existing system to include the number of malleoli involved, thus providing a more useful prognostic tool.     

X-ray-induced DNA double-strand breaks in human sperm

A methodology for quantifying DNA double-strand breaks in humansperm is described. Sperm from three healthy human donors onthree separate days each were irradiated with 12.5,25,50 and100 cGy X-rays. Linear dose-response effects were observed inmigrated DNA from sperm nuclei when electrophoresed under neutralconditions. RNase and proteinase K treatments for longer durationwere necessary, to decondense the chromatin and presumably torelease the broken DNA for migration in the electrophoreticfield in a dose-dependent manner. An increase in DNA migrationwas observed with as low as 12.5 cGy, but damage was observedin all samples at 25 cGy. No evidence of repair of these X-ray-inducedDNA double-strand breaks was observed during a 2 h period. ³To whom correspondence should be addressed. Tel: +1 206 685 2060; Fax: +1 206 685 2060; Email: narendra{at}u.washington.edu     

Prisoners' knowledge and attitude toward prophylactic treatment and therapy

Identifying factors that hinder an inmate's compliance with Pneumocystis carinii pneumonia (PCP) prophylaxis therapy can be critical in preventing or decreasing the occurrence of PCP in this population. Anticipated factors include lack of knowledge about PCP and its proposed treatment, fear of the adverse effects of prophylaxis therapy, and lack of trust in the correctional facility medical team. Structured interviews were administered to HIV-positive male inmates chosen randomly (n = 104) at a medium- to maximum-security medical correctional facility located in the western portion of the United States. A basic "HIV 101 and Early Intervention" program encompassed the presentation of HIV facts and knowledge as well as safer sex practices. The results revealed that 95% of the respondents were knowledgeable about PCP and the side effects of their medications, and 56% of the respondents were afraid of the medications' side effects. Significant differences based on age were recorded for several specific knowledge questions, including the preventable nature of PCP.