Human chorionic gonadotropin isoforms in the diagnosis of ectopic pregnancy

This paper has set the scene for re-defining clinical chemistry data for the diagnosis of ectopic pregnancy. Indeed it has proved some assumptions on hCG levels to be false. Professor Iles was/is the principal investigator on these studies

Development of a Clinical MALDI-ToF Mass Spectrometry Assay for SARS-CoV-2: Rational Design and Multi-Disciplinary Team Work.

The COVID-19 pandemic caused by the SARS-CoV-2 coronavirus has stretched national testing capacities to breaking points in almost all countries of the world. The need to rapidly screen vast numbers of a country's population in order to control the spread of the infection is paramount. However, the logistical requirement for reagent supply (and associated cost) of RT-PCR based testing (the current front-line test) have been hugely problematic. Mass spectrometry-based methods using swab and gargle samples have been reported with promise, but have not approached the task from a systematic analysis of the entire diagnostic process. Here, the pipeline from sample processing, the biological characteristics of the pathogen in human biofluid, the downstream bio- and physical-chemistry and the all-important data processing with clinical interpretation and reporting, are carefully compiled into a single high-throughput and reproducible rapid process. Utilizing MALDI-ToF mass spectrometric detection to viral envelope glycoproteins in a systems biology-multidisciplinary team approach, we have achieved a multifaceted clinical MALDI ToF MS screening test, primarily (but not limited to) SARS-CoV-2, with direct application to other future epidemics/pandemics that may arise. The clinical information generated not only includes SARS-CoV-2 coronavirus detection-(Spike protein fragments S1, S2b, S2a peaks), but other respiratory viral infections detected as well as an assessment of generalised oral upper respiratory immune response (elevated total Ig light chain peak) and a measure of the viral immune response (elevated intensity of IgA heavy chain peak). The advantages of the method include; (1) ease of sampling, (2) speed of analysis, and much reduced cost of testing. These features reveal the diagnostic utility of MALDI-ToF mass spectrometry as a powerful and economically attractive global solution

The 2021 NICE guidelines for assessment and management of chronic pain: A cross-sectional study mapping against a sample of 1,000* in the community

Objectives: To characterise the prevailing pharmacological and non-pharmacological pain management strategies among adults with chronic pain, comparing these against the newly published NICE guidelines NG-193, and examine these pre-NG-193 pain management strategies in relation to pain severity, pain interference, sleep quality and mental health outcomes. Design: This study was conducted using a cross-sectional online survey study design. Setting: This study was conducted on a community-dwelling cohort. Participants: Adults aged 18+, living in the UK, with diagnosis of chronic pain by a health care professional. Main outcome measures: Primary outcomes were characterisation of the pain management strategies utilised. Secondary outcomes were related to pain severity, pain interference, sleep quality, depression and anxiety via validated self-report measures. Results Several strategies were employed by respondents to manage their chronic pain condition including physical therapy, exercise, psychological therapy and pharmacological therapy. The data also indicated a high level of joint-care planning among patients and their clinicians. Some group differences were found in relation to pain, sleep and mental health outcomes. Conclusion: This study set a comparative starting baseline to which the efficacy of the NG-193 may be compared in future years. There is evidence that NICE recommendations are being followed for the management of chronic primary pain conditions; however, pharmacological use of opioid drugs is still reported by 47%. Despite the confirmed evidence in this study of small efficacy of chronic pain by pharmacological agent, the reduction in the use of pain relief medications be it over the counter medications or prescription opioids, as recommended by NG-193, may be slow to be adopted. The data suggest that more care provision is needed to meet the recommendations around pharmacological management and review

Estradiol, progesterone, testosterone profiles in human follicular fluid and cultured granulosa cells from luteinized pre-ovulatory follicles

BACKGROUND: The production of sex steroids by follicular cells is proposed to be influenced by the maturity of the incumbent oocyte. Thus steroid levels may reflect suitability of an oocyte for IVF. We examined follicular fluids and granulosa cell production of steroid from IVF patients in order to test the relationship between steroid levels and fertilization. METHODS: Follicular fluid and granulosa cells were extracted from 206 follicles of 35 women undergoing controlled ovarian stimulation. Follicular fluid was assayed for estradiol, progesterone and testosterone. Granulosa cells were cultured from individual follicles and their culture media assayed for production of these hormones after 24 hrs in vitro. Levels of steroids were correlated with follicular diameter, oocyte recovery and subsequent fertilization. RESULTS: Follicular fluid levels of progesterone were 6100 times higher than that of estradiol, and 16,900 times higher that of testosterone. Despite the size of follicle triggered after controlled luteinization, the levels of progesterone and testosterone were maintained at relatively constant levels (median 98.1 micromoles/L for progesterone, and 5.8 nanomoles/L for testosterone). However, estradiol levels were slightly lower in the larger follicles (follicular diameter 10-15 mm, median 25.3 nanomoles/L; follicles > = 15 mm, median 15.1 nanomoles/L; linear correlation r = -0.47, p < 0.0001). With respect to oocyte recovery, no steroid showed a significant association in follicular fluid levels. Similarly no difference in follicular fluid steroid levels was found for those oocytes that did or did not fertilize. Significant quantities of progesterone were produced by the granulosa cells but production was constant regardless of the size of follicle from which the cells originated. Estradiol levels were only detectable in 10 of 121 cultures examined, and testosterone in none. Interestingly, when an oocyte was present follicular estradiol levels correlated with progesterone levels. However, when absent, follicular estradiol levels correlated with testosterone levels but not with progesterone. CONCLUSIONS: The principle steroid product of luteinized pre-ovulatory granulosa is progesterone, a differentiation triggered by the gonadotropin surge. However, absolute steroid levels are associated with follicular size, not oocyte maturation/ability to fertilize