Cellular kinetics of prednimustine versus chlorambucil plus prednisolone in vitro

Summary Intracellular concentrations of prednimustine (PM), chlorambucil (CLB), phenylacetic acid mustard (PAAM) and prednisolone (P) were measured in different experimental tumor cell lines that had been incubated with either PM or CLB+P. For intracellular analytical determination, we modified a high-pressure liquid chromatographic method for the detection of these substances in plasma. Intact PM could be detected in the intracellular compartment of the incubated tumor cells. PM-incubated cells from PM-injected rats exhibited a higher intracellular concentration-time integral (PAAM) and longer concentration-time profiles for drugs with alkylating capacity than did cells exposed to the CLB+P mixture or to CLB. PAAM was not detectable after incubation of cells with PM, whereas in CLB-incubated cells the AUC of PAAM exceeded that of the parent drug CLB. Our in vitro results therefore favour the concept of a facilitated intracellular uptake and an increased antiproliferative effect for PM versus CLB and CLB+P.Dedicated to Prof. Dr. H. J. Dengler on the occasion of his 65th birthday. This study was supported by the Ministry of Science and Research of Nordrhein-Westfalen     

Synthesis and characterization of acrylate-terminated unsaturated copolyesters

The reaction of the potassium salt of acrylic acid with the potassium salt of a dicarboxylic acid and 1,4-dibromobutane was applied to the synthesis of three series of acrylate-terminated copolyesters: poly(tetramethylene maleate-co-tetramethylene phthalate) (BMPA), poly(tetramethylene fumarate-co-tetramethylenephthalate) (BFPA) and poly(tetramethylene phthalate-co-tetramethylene succinate) (BPSA). The monofunctional monomer, the potassium salt of acrylic acid, was used for the introduction of double bonds at the end of the chains and for the regulation of the molecular weight of the polyesters. The telechelic copolyesters were characterized by ¹H and ¹³C NMR spectroscopy, in almost all cases providing an acrylate functionality of two.     

Emerging Biomarker-Guided Therapies in Prostate Cancer

Prostate cancer remains one of the leading causes of cancer death in men worldwide. In the past decade, several new treatments for advanced prostate cancer have been approved. With a wide variety of available drugs, including cytotoxic agents, androgen receptor axis-targeted therapies, and alpha-emitting radiation therapy, identifying their optimal sequencing remains a challenge. Progress in the understanding of the biology of prostate cancer has provided an opportunity for a more refined and personalized treatment selection process. With the advancement of molecular sequencing techniques, genomic precision through the identification of potential treatment targets and predictive biomarkers has been rapidly evolving. In this review, we discussed biomarker-driven treatments for advanced prostate cancer. First, we presented predictive biomarkers for established, global standard treatments for advanced diseases, such as chemotherapy and androgen receptor axis-targeted agents. We also discussed targeted agents with recent approval for special populations, such as poly ADP ribose polymerase (PARP) inhibitors in patients with metastatic castrate-resistant prostate cancer with homologous recombination repair-deficient tumors, pembrolizumab in patients with high levels of microsatellite instability or high tumor mutational burden, and prostate-specific membrane antigen (PSMA) directed radioligand theragnostic treatment for PSMA expressing tumors. Additionally, we discussed evolving treatments, such as cancer vaccines, chimeric antigen receptor T-cells (CAR-T), Bispecific T-cell engagers (BiTEs), other targeted agents such as AKT inhibitors, and various combination treatments. In summary, advances in molecular genetics have begun to propel personalized medicine forward in the management of advanced prostate cancer, allowing for a more precise, biomarker-driven treatment selection with the goal of improving overall efficacy.     

Swab2know: An HIV-Testing Strategy Using Oral Fluid Samples and Online Communication of Test Results for Men Who Have Sex With Men in Belgium

Background

As HIV remains a public health concern, increased testing among those at risk for HIV acquisition is important. Men who have sex with men (MSM) are the most important group for targeted HIV testing in Europe. Several new strategies have been developed and implemented to increase HIV-testing uptake in this group, among them the Swab2know project.

Objective

In this project, we aim to assess the acceptability and feasibility of outreach and online HIV testing using oral fluid samples as well as Web-based delivery of test results.

Methods

Sample collection happened between December 2012 and April 2014 via outreach and online sampling among MSM. Test results were communicated through a secured website. HIV tests were executed in the laboratory. Each reactive sample needed to be confirmed using state-of-the-art confirmation procedures on a blood sample. Close follow-up of participants who did not pick up their results, and those with reactive results, was included in the protocol. Participants were asked to provide feedback on the methodology using a short survey.

Results

During 17 months, 1071 tests were conducted on samples collected from 898 men. Over half of the samples (553/1071, 51.63%) were collected during 23 outreach sessions. During an 8-month period, 430 samples out of 1071 (40.15%) were collected from online sampling. Additionally, 88 samples out of 1071 (8.22%) were collected by two partner organizations during face-to-face consultations with MSM and male sex workers. Results of 983 out of 1071 tests (91.78%) had been collected from the website. The pickup rate was higher among participants who ordered their kit online (421/430, 97.9%) compared to those participating during outreach activities (559/641, 87.2%; P<.001). MSM participating during outreach activities versus online participants were more likely to have never been tested before (17.3% vs 10.0%; P=.001) and reported more sexual partners in the 6 months prior to participation in the project (mean 7.18 vs 3.23; P<.001). A total of 20 participants out of 898 (2.2%) were confirmed HIV positive and were linked to care. Out of 1071 tests, 28 (2.61%) with a weak reactive result could not be confirmed, and were thereby classified as false reactive results. Most of the 388 participants who completed posttest surveys (388/983, 39.5%) were very positive about their experience. The vast majority (371/388, 95.6%) were very satisfied, while 17 out of 388 (4.4%) reported mixed feelings.

Conclusions

Despite a high yield and a considerable number of false reactive results, satisfaction was high among participants. The project helped us to reach the target population, both in numbers of tests executed and in newly diagnosed HIV infections. Further optimization should be considered in the accuracy of the test, the functionalities of the website (including an online counseling tool), and in studying the cost effectiveness of the methodology.     

Psychological consequences of war trauma and postwar social stressors in women in Bosnia and Herzegovina

Aim

To assess the consequences of psychotrauma in civilian women in Herzegovina who were exposed to prolonged and repetitive traumatic war events and postwar social stressors.

Methods

The study included a cluster sample of 367 adult women, divided into two groups. One group (n = 187) comprised women from West Mostar who were exposed to serious war and posttraumatic war events. The other group (n = 180) comprised women from urban areas in Western Herzegovina who were not directly exposed to war destruction and material losses, but experienced war indirectly, through military drafting of their family members and friends. Demographic data on the women were collected by a questionnaire created for the purpose of this study. Data on trauma exposure and posttraumatic stress disorder (PTSD) symptoms were collected by Harvard Trauma Questionnaire (HTQ) – Bosnia-Herzegovina version. General psychological symptoms were determined with Symptom Check List-90-revised (SCL-90-R). Data on postwar stressors were collected by a separate questionnaire.

Results

In comparison with the control group, women from Western Mostar experienced significantly more traumatic events (mean ± standard deviation [SD], 3.3 ± 3.2 vs 10.1 ± 4.9, respectively, t = 15.91; P<0.001) and had more posttraumatic symptoms (12.3 ± 10.3 vs 21.2 ± 10.9, respectively, t = 8.42; P<0.001). They also had significantly higher prevalence of PTSD (4.4% vs 28.3%, respectively; χ² = 52.56; P<0.001). The number of traumatic events experienced during the war was positively associated with postwar stressful events both in the West Mostar group (r = 0.223; P = 0.002) and control group (r = 0.276; P<0.001). Postwar stressful events contributed both to the number and intensity of PTSD symptoms and all general psychological symptoms measured with SCL-90 questionnaire, independently from the number of experienced traumatic war events.

Conclusion

Long-term exposure to war and postwar stressors caused serious psychological consequences in civilian women, with PTSD being only one of the disorders in the wide spectrum of posttraumatic reactions. Postwar stressors did not influence the prevalence of PTSD but they did contribute to the intensity and number of posttraumatic symptoms.There are few studies investigating how political violence in a community influences women, and those that do exist mostly deal with refugees (1,2). Epidemiologic research into consequences of war trauma established that posttraumatic stress disorder (PTSD), although the most frequent, was rarely the only psychological disorder among the general population of war-stricken countries (3-6) and that women had noticeably poorer mental health than the rest of the population (2,7). Studies investigating psychological consequences of military and civil trauma confirmed the correlation between the nature and intensity of trauma, previous traumatic experience, and psychological consequences (8-11).Because of its brutality, the war in Bosnia and Herzegovina has become the paradigm for traumatic experience, with the constant need for psychological and psychiatric help for victims long after its end. Previous research and local health care have mostly been focused on men, and preventive and therapeutic activities have targeted primarily the population of war veterans. However, there is no doubt that chronic war stress caused serious psychological problems in women in war-affected areas, although clinical experience about this problem is scarce. The reason why little is known about mental health of women in Bosnia and Herzegovina is that a relatively small number of psychotraumatized women seek psychiatric or psychological help (12). Previous research and local health care system dealt mostly with male population, which is the reason why most preventive and curative actions have been directed at veteran population. However, chronic war stress has doubtlessly had deep consequences on psychological health of women as well (13). Literature data and personal clinical experience indicate that clinical identification of PTSD is frequently hampered by gender prejudices, including the tendency to overlook traumatic nature of violence against women along with associated posttraumatic symptoms (14).The war did not affect all areas of Bosnia and Herzegovina equally. In some parts of the country, it was more intense and lasted longer than in others. The whole city of Mostar was a battlefield and suffered heavy destruction and human losses on everyday basis. Today, it is divided into Western Mostar and Eastern Mostar, and still struggles with devastated infrastructure and economic resources. On the other hand, urban areas in Western Herzegovina, although not too far from Mostar, were spared from everyday destruction and the civilian population was not directly exposed to life threatening situations. Also, postwar social and economic deprivation in that area has not been so pronounced as in Mostar.We expected that women exposed to war atrocities in Bosnia and Herzegovina would suffer posttraumatic psychological consequences and that a significant percentage of women in Mostar would develop posttraumatic disorders (PTSD, posttraumatic symptoms, and general psychological symptoms) as a reaction to traumatic experiences. We also expected that the percentage of women with posttraumatic disorders would be smaller in areas only indirectly affected by the war. Since postwar social stressors make the recovery more difficult, we also expected that women who were exposed to additional postwar social stressors would have more difficult recovery and more pronounced posttraumatic disorders.The aim of this study was to determine the degree of posttraumatic symptoms and symptoms of other mental disorders in women who were living in war-stricken areas for several years, determine the correlation between the number and intensity of posttraumatic symptoms and the intensity of psychotrauma, and establish the influence of postwar stressors on the manifestation and duration of posttraumatic and general psychological symptoms.