CD34 Stem Cell Boost in Pediatric Allogeneic Stem Cell Transplant Recipients: A Case Series and Review of Literature.

Patients with poor graft function (PGF) or declining donor chimerism (DC) post allogeneic hematopoietic cell transplantation (HCT) may benefit from a CD34-selected stem cell boost (SCB). We retrospectively studied outcomes of fourteen pediatric patients (PGF: 12 and declining DC: 2), with a median age of 12.8 (range 0.08-20.6) years at HCT, who received a SCB. Primary and secondary endpoints included resolution of PGF or improvement in DC (≥ 15% increase), overall survival (OS) and transplant-related mortality (TRM), respectively. The median CD34 dose infused was 7.47 × 106/kg (range 3.51 × 106-3.39 × 107/kg). Among patients with PGF who survived ≥ 3 months post-SCB (n = 8), we observed a non-significant decrease in the cumulative median number of red cell transfusions, platelet transfusions, and GCSF but not intravenous immunoglobulin doses in the 3 months before and after SCB. Overall response rate (ORR) was 50%, with 29% complete and 21% partial responses. ORR was better in recipients who received lymphodepletion (LD) pre-SCB versus none (75% versus 40%; p = 0.56). The incidence of acute and chronic graft-versus-host-disease was 7% and 14%, respectively. The 1-year OS was 50% (95% CI 23-72%) and TRM was 29% (95% CI 8-58%). SCB was effective in half of our cohort with possible benefit of LD pre-SCB.

Impact of fluoxetine preexposure on MDMA-induced taste avoidance in male and female rats.

The use of both prescription and illicit drugs creates the potential for drug interactions as a function of both pharmacokinetic and pharmacodynamic processes. One such interaction is that of fluoxetine and methylenedioxymethamphetamine (MDMA) in which fluoxetine attenuates the positive-like effects of MDMA. The present work extends the analysis of their interaction by examining the impact of fluoxetine on the aversive effects of MDMA which in balance with its rewarding effects may mediate its abuse potential. Male and female Sprague-Dawley rats were given fluoxetine (10 mg/kg every 4th day for five injections) prior to taste avoidance training with MDMA (3.2 mg/kg). MDMA induced taste avoidance in males and females (faster acquisition in females). Fluoxetine preexposure attenuated this avoidance in males, but not females. For males, the attenuation was partial as MDMA-conditioned animals with fluoxetine preexposure still displayed a significant reduction in fluid intake compared to controls. Consistent with prior work assessing the interaction of fluoxetine and MDMA, fluoxetine preexposure impacted the ability of MDMA to support taste avoidance learning, specifically attenuating the aversive effect of the drug. Prior work has shown that fluoxetine attenuates MDMA's positive effects which might lead to reduced intake of the drug; however, the concurrent reduction in the drug's aversive effects may still shift the overall affective balance of these two affective properties toward continued use and abuse. The fact that the attenuation was only evident in males needs further study to investigate the sex-dependent effects of drug history. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Methylone pre-exposure differentially impacts the aversive effects of MDPV and MDMA in male and female Sprague-Dawley rats: Implications for abuse vulnerability.

BACKGROUND: Polydrug use is well documented in synthetic cathinone users, although the consequences of such use are not well characterized. In pre-clinical research, a pre-exposure to a drug has been reported to attenuate the aversive effects of other drugs which has implications for their abuse potential. The goal of the present study was to investigate the impact of pre-exposure to the synthetic cathinone methylone on the aversive effects of MDPV and MDMA. METHOD: Male and female Sprague-Dawley rats were exposed to 10 mg/kg of methylone every 4th day (for a total of five injections) prior to taste avoidance training with 1.8 mg/kg of MDPV or 1 mg/kg of MDMA. RESULTS: MDPV and MDMA induced taste avoidance in males and females (all p's < 0.05). In males, methylone pre-exposure attenuated the avoidance induced by MDPV and MDMA (all p's < 0.05) with the attenuation greater with MDPV. In females, methylone pre-exposure attenuated avoidance induced by MDPV (all p's < 0.05), but it had no effect on those induced by MDMA (all p's > 0.05). CONCLUSIONS: The effects of exposure to methylone on taste avoidance induced by MDPV and MDMA were drug- (MDPV > MDMA) and sex- (MDMA only in males) dependent. The attenuating effects of methylone pre-exposure on MDPV and MDMA were discussed in terms of their shared neurochemical action. These findings suggest that a history of methylone use may reduce the aversive effects of MDPV and MDMA which may have implications for polydrug use involving the synthetic cathinones.

International Travel as a Context for Sexual and Contraceptive Behaviors: A Qualitative Study of Young Women Traveling Outside the U.S.

International travel is popular worldwide, yet its implications for sexual and reproductive health are not fully understood. Few studies have examined the contextual factors that shape women's sexual and contraceptive behaviors-and thus, their risk of unintended pregnancy and sexually transmitted infections (STIs)-while traveling outside their home country. In this qualitative study, female university students with recent (n = 25) or upcoming (n = 19) travel outside the U.S. completed semi-structured interviews from October 2015 to March 2017. Transcripts were analyzed for themes related to contraceptive and sexual behaviors: (1) participants' pre-travel expectations of sex; (2) the circumstances surrounding sexual encounters with men while traveling; (3) negotiation about condom and contraception use with partners; and (4) factors affecting contraceptive adherence. Participants generally expected to be abstinent during travel, citing myriad rationales that included personal values, no perceived opportunities for sex, and the nature of the trip. Some travelers had unexpected sexual encounters, involving health-protecting behaviors and risk-taking (e.g., unprotected sex, substance use). New sexual partnerships were fueled by increased attention from men, situational disinhibition, and perceived heightened intimacy. International travel brought many contraceptive considerations (adequacy of supplies, access to refrigeration, time zone differences, etc.) as well as obstacles that triggered contraceptive lapses and discontinuation. Pill users described the most challenges, while travelers using intrauterine devices expressed appreciation for their maintenance-free contraception. This study suggests complex associations between international travel and young women's sexual and reproductive health. Some travelers were more vulnerable to situational risk factors, while others may have been more insulated. We identify potential intervention opportunities via clinical services, education, and policy to reduce young women's risk of adverse sexual and reproductive health outcomes while traveling abroad. We urge greater recognition of and conversations about contraceptive lapse and unintended pregnancy as potential health risks for female travelers of reproductive age, just as clinical guidelines acknowledge travel-associated STI.