Endogenous cannabinoids are not involved in cocaine reinforcement and development of cocaine-induced behavioural sensitization.

The endogenous cannabinoid system is a relatively novel discovered system consisting of cannabinoid CB1 receptors, which are expressed both in the periphery and in the central nervous system, peripheral cannabinoid CB2 receptors and endogenous cannabinoids, which are anandamide and 2-arachidonyl glycerol. The cannabinoid CB1 receptors have recently been implicated in rewarding aspects of not only the cannabinoid drug Delta9-tetrahydrocannabinol (Delta9-THC), but also of other drugs of abuse, including cocaine. The present study was designed to further investigate the role of CB1 receptors in reward-related effects of cocaine. Using the CB1 receptor selective antagonist SR141716A, the involvement of CB1 receptors in cocaine reinforcement was determined by intravenous cocaine self-administration. In addition, the effects of the CB1 receptor selective antagonist SR141716A upon the development of cocaine-induced behavioural sensitization were investigated. SR141716A did not affect cocaine reinforcement nor did it affect the development of behavioural sensitization to the locomotor stimulant effects of cocaine. These findings suggest that CB1 receptors are not involved in acute cocaine reinforcement nor in cocaine-induced behavioural sensitization.     

Crack and cocaine use among female prostitutes in Glasgow: Risky business

The experience of cocaine and 'crack' use among participants involved in (n = 19) or exiting (n = 10) prostitution in Glasgow, Scotland, is described. In-depth semi-structured qualitative interviews enquired about their use and experience of using cocaine and their perception of its effect on working practice. Twenty-three of 29 participants had used cocaine and 15 out of 29 had used crack cocaine. In reality, freebase not 'crack' was being self-manufactured from cocaine powder. Participants considered that cocaine use in the city was not restricted to prostitution but was reflected throughout the drug scene generally. One possible reason suggested for this was a perceived reduction in heroin availability at a time when cocaine was increasingly readily available. There was no evidence from participants to suggest that they were first introduced to cocaine through prostitution. Most participants believed that using cocaine did not affect how they worked, however they perceived that other prostitutes were prepared to take more risks to support their cocaine use and had to work longer hours to finance a cocaine habit compared to financing a heroin habit. Only participants recruited from the east end of the city spoke about their desperation for money and the sexual risks that they were prepared to take to buy cocaine. Harm-reduction messages should address the sexual and personal risks that some female prostitutes may be taking to support their cocaine use. Treatment and support services in the city, traditionally established to work with problematic heroin users, need to adapt to the changing drug trends among female drug users, including those involved in prostitution, and offer appropriate treatment options and harm-reduction advice to cocaine users.     

Cortical Atrophy Predicts Visual Performance in Long-Term Central Retinal Disease; GCL,pRNFL and Cortical Thickness Are Key Biomarkers

PurposeThe aim of this study was to assess both retinal and cortical structure in a cohort of patients with long-term acquired central retinal disease in order to identify potential disease biomarkers and to explore the relationship between the anterior and posterior visual pathways.MethodsFourteen participants diagnosed with long-term central retinal disease underwent structural assessments of the retina using spectral-domain optical coherence tomography, including macular ganglion cell layer (GCL) and peripapillary retinal nerve fiber layer (pRNFL) thickness. Structural magnetic resonance imaging was used to measure visual cortex, including cortical volume of the entire occipital lobe and cortical thickness of the occipital pole and calcarine sulcus, representing the central and peripheral retina, respectively.ResultsMean thickness was significantly reduced in both the macular GCL and the inferior temporal pRNFL across patients. Cortical thickness was significantly reduced in both the occipital pole and calcarine sulcus, representing the central and peripheral retina, respectively. Disease duration significantly correlated with GCL thickness with a large effect size, whereas a medium effect size suggests the possibility that cortical thickness in the occipital pole may correlate with visual acuity.ConclusionsLong-term central retinal disease is associated with significant structural changes to both the retina and the brain. Exploratory analysis suggests that monitoring GCL thickness may be a sensitive biomarker of disease progression and reductions in visual cortical thickness may be associated with reduced visual acuity. Although this study is limited by its heterogeneous population, larger cohort studies would be needed to better establish some of the relationships detected between disease dependent structural properties of the anterior and posterior visual pathway given the effect sizes reported in our exploratory analysis.     

The Second Wave of COVID-19: Clinical Pharmacy Services During a Field Hospital Operation

The second wave of COVID-19 emerged in the late fall months in the state of Massachusetts and inadvertently caused a rise in the number of cases requiring hospitalization. With a field hospital previously opened in central Massachusetts during the Spring of 2020, the governor decided to reimplement the field hospital. Although operations were effectively accomplished during the first wave, the reimplementation of the field hospital came with its new set of challenges for operating a satellite pharmacy. Experiences gathered include new pharmacy operation workflows, the clinical role of pharmacy services, introduction of remdesivir treatment, and pharmacy involvement in newly diagnosed diabetes patients requiring insulin teaching. Pharmacy services were successful in adapting to the rapidly growing number in patients with a total of over 600 patients served in a course of 2 months.     

Systematic Evidence Map for Over One Hundred and Fifty Per- and Polyfluoroalkyl Substances (PFAS)

Background: Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic (man-made) chemicals widely used in consumer products and industrial processes. Thousands of distinct PFAS exist in commerce. The 2019 U.S. Environmental Protection Agency (U.S. EPA) Per- and Polyfluoroalkyl Substances (PFAS) Action Plan outlines a multiprogram national research plan to address the challenge of PFAS. One component of this strategy involves the use of systematic evidence map (SEM) approaches to characterize the evidence base for hundreds of PFAS.Objective: SEM methods were used to summarize available epidemiological and animal bioassay evidence for a set of ∼150 PFAS that were prioritized in 2019 by the U.S. EPA’s Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing.Methods: Systematic review methods were used to identify and screen literature using manual review and machine-learning software. The Populations, Exposures, Comparators, and Outcomes (PECO) criteria were kept broad to identify mammalian animal bioassay and epidemiological studies that could inform human hazard identification. A variety of supplemental content was also tracked, including information on in vitro model systems; exposure measurement–only studies in humans; and absorption, distribution, metabolism, and excretion (ADME). Animal bioassay and epidemiology studies meeting PECO criteria were summarized with respect to study design, and health system(s) were assessed. Because animal bioassay studies with ≥21-d exposure duration (or reproductive/developmental study design) were most useful to CCTE analyses, these studies underwent study evaluation and detailed data extraction. All data extraction is publicly available online as interactive visuals with downloadable metadata.Results: More than 40,000 studies were identified from scientific databases. Screening processes identified 44 animal and 148 epidemiology studies from the peer-reviewed literature and 95 animal and 50 epidemiology studies from gray literature that met PECO criteria. Epidemiological evidence (available for 15 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Animal evidence (available for 40 PFAS) commonly assessed effects in the reproductive, developmental, urinary, immunological, and hepatic systems. Overall, 45 PFAS had evidence across animal and epidemiology data streams.Discussion: Many of the ∼150 PFAS were data poor. Epidemiological and animal evidence were lacking for most of the PFAS included in our search. By disseminating this information, we hope to facilitate additional assessment work by providing the initial scoping literature survey and identifying key research needs. Future research on data-poor PFAS will help support a more complete understanding of the potential health effects from PFAS exposures. https://doi.org/10.1289/EHP10343     

LOH at 6q and 10q in fractionated circulating DNA of ovarian cancer patients is predictive for tumor cell spread and overall survival

ABSTRACT: BACKGROUND: We recently showed that LOH proximal to M6P/IGF2R locus (D6S1581) in primary ovarian tumors is predictive for the presence of disseminated tumor cells (DTC) in the bone marrow (BM). For therapy-monitoring, it would be highly desirable to establish a blood-based biomarker. Therefore, we quantified circulating DNA (cirDNA) in sera of 63 ovarian cancer patients before surgery and after chemotherapy, measured incidence of LOH at four cancer-relevant chromosomal loci, correlated LOH with tumor cell spread to the BM and evaluated prognostic significance of LOH. Patients and Methods: cirDNA was fractionated into high- and low molecular-weight fraction (HMWF, LMWF) for LOH-profiling, utilizing PCR-based fluorescence microsatellite analysis. BM aspirates were analyzed for DTC by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. RESULTS: cirDNA levels in the HMWF before surgery were predictive for residual tumor load (p=0.017). After chemotherapy, we observed a significant decline of cirDNA in the LMWF (p=0.0001) but not in the HMWF. LOH was prevalently detected in the LMWF with an overall frequency of 67 %, only moderately ablating after chemotherapy (45 %). Before surgery, LOH in the LMWF at marker D10S1765 and D13S218 significantly correlated with tumor grading and FIGO stage (p=0.033, p=0.004, respectively). In both combined fractions, LOH at D6S1581 additionally associated with overall survival (OS) (p=0.030). Moreover, solely LOH at D10S1765 in LMWF after therapy correlated with DTC in BM after therapy (p=0.017). CONCLUSION: We demonstrate the applicability and necessity of DNA-fractionation prior to analyzing circulating LOH and identify LOH at D10S1765 and D6S1581 as novel blood-based biomarkers for ovarian cancer, being relevant for therapy-monitoring.     

Increased gonadotrophin stimulation does not improve IVF outcomes in patients with predicted poor ovarian reserve

Purpose

This retrospective study was carried out to evaluate whether increasing the starting dose of FSH stimulation above the standard dose of 150 IU/day in patients with low predicted ovarian reserve can improve IVF outcomes.

Method

A total of 122 women aged less than 36 years in their first cycle of IVF were identified as having likely low ovarian reserve based on a serum AMH measurement below 14 pmol/l. Thirty five women were administered the standard dose of 150 IU/day FSH, while the remaining 87 received a higher starting dose (200–300 IU/day FSH). There were no significant differences in age, BMI, antral follicle count, serum AMH, FSH or aetiology of infertility between the two dose groups.

Results

No significant improvement in oocyte and embryo yield or pregnancy rates was observed following an upward adjustment of FSH starting dose. While increasing the dose of FSH above 150 IU/day did not produce any adverse events such as OHSS, it did consume an extra 1,100 IU of FSH per IVF cycle.

Conclusion

The upward FSH dose adjustment in anticipation of low ovarian reserve can not be advocated as it is both expensive and of no proven clinical value.