Delay between pregnancy confirmation and sickle cell and [corrected] thalassaemia screening: a population-based cohort study.

BACKGROUND: Antenatal sickle cell and thalassaemia screening sometimes occurs too late to allow couples a choice regarding termination of affected fetuses. The target gestational age for offering the test in the UK is 10 weeks. AIM: To describe the proportion of women screened before 70 days' (10 weeks') gestation and the delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening. DESIGN OF STUDY: Cohort study of reported pregnancies. SETTING: Twenty-five general practices in two UK inner-city primary care trusts offering universal screening. METHOD: Anonymised data on all pregnancies reported to participating general practices was collected for a minimum of 6 months. RESULTS: There were 1441 eligible women intending to proceed with their pregnancies, whose carrier status was not known. The median (interquartile range [IQR]) gestational age at pregnancy confirmation was 7.6 weeks (6.0-10.7 weeks) and 74% presented before 10 weeks. The median gestational age at screening was 15.3 weeks (IQR = 12.6-18.0 weeks), with only 4.4% being screened before 10 weeks. The median delay between pregnancy confirmation and screening was 6.9 weeks (4.7-9.3 weeks) After allowing for practice level variation, there was no association between delay times and maternal age, parity, and ethnic group. CONCLUSION: About 74% of women consulted for pregnancy before 10 weeks' gestation but fewer than 5% of women were screened before the target time of 10 weeks. Reducing the considerable delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening requires methods of organising and delivering antenatal care that facilitate earlier screening to be developed and evaluated.     

Gene discovery in the Entamoeba invadens genome

Entamoeba invadens, a parasite of reptiles, is a model for the study of encystation by the human enteric pathogen Entamoeba histolytica, because E. invadens form cysts in axenic culture. With approximately 0.5-fold sequence coverage of the genome, we were able to get insights into E. invadens gene and genome features. Overall, the E. invadens genome displays many of the features that are emerging from ongoing genome sequencing efforts in E. histolytica. At the nucleotide level the E. invadens genome has on average 60% sequence identity with that of E. histolytica. The presence of introns in E. invadens was predicted with similar consensus (GTTTGT em leader A/TAG) sequences to those identified in E. histolytica and Entamoeba dispar. Sequences highly repeated in the genome of E. histolytica (rRNAs, tRNAs, CXXC-rich proteins, and Leu-rich repeat proteins) were found to be highly repeated in the E. invadens genome. Numerous proteins homologous to those implicated in amoebic virulence, (Gal/GalNAc lectins, amoebapores, and cysteine proteinases) and drug resistance (p-glycoproteins) were identified. Homologs of proteins involved in cell cycle, vesicular trafficking and signal transduction were identified, which may be involved in en/excystation and cell growth of E. invadens. Finally, multiple copies of a number of E. invadens genes coding for predicted enzymes involved in core metabolism and the targets of anti-amoebic drugs were identified.     

Shared decision making in consultations for hypertension: Qualitative study in general practice

BackgroundHypertension is mainly managed in primary care. Shared decision making is widely recommended as an approach to treatment decision making. However, no studies have investigated; in detail, what happens during primary care consultations for hypertension.AimTo understand patients’ and clinicians’ experience of shared decision making for hypertension in primary care, in order to propose how it might be better supported.DesignLongitudinal qualitative study.SettingFive general practices in south‐west England.MethodInterviews with a purposive sample of patients with hypertension, and with the health‐care practitioners they consulted, along with observations of clinical consultations, for up to 6 appointments. Interviews and consultations were audio‐recorded and observational field notes taken. Data were analysed thematically.ResultsForty‐six interviews and 18 consultations were observed, with 11 patients and nine health‐care practitioners (five GPs, one pharmacist and three nurses). Little shared decision making was described by participants or observed. Often patients’ understanding of their hypertension was limited, and they were not aware there were treatment choices. Consultations provided few opportunities for patients and clinicians to reach a shared understanding of their treatment choices. Opportunities for patients to engage in choices were limited by structured consultations and the distribution of decisions across consultations.ConclusionFor shared decision making to be better supported, consultations need to provide opportunities for patients to learn about their condition, to understand that there are treatment choices, and to discuss these choices with clinicians.Patient or Public ContributionA patient group contributed to the design of this study.     

Osteoblasts Generate Testosterone From DHEA and Activate Androgen Signaling in Prostate Cancer Cells

Bone metastasis is a complication of prostate cancer in up to 90% of men afflicted with advanced disease. Therapies that reduce androgen exposure remain at the forefront of treatment. However, most prostate cancers transition to a state whereby reducing testicular androgen action becomes ineffective. A common mechanism of this transition is intratumoral production of testosterone (T) using the adrenal androgen precursor dehydroepiandrosterone (DHEA) through enzymatic conversion by 3β- and 17β-hydroxysteroid dehydrogenases (3βHSD and 17βHSD). Given the ability of prostate cancer to form blastic metastases in bone, we hypothesized that osteoblasts might be a source of androgen synthesis. RNA expression analyses of murine osteoblasts and human bone confirmed that at least one 3βHSD and 17βHSD enzyme isoform was expressed, suggesting that osteoblasts are capable of generating androgens from adrenal DHEA. Murine osteoblasts were treated with 100 nM and 1 μM DHEA or vehicle control. Conditioned media from these osteoblasts were assayed for intermediate and active androgens by liquid chromatography–tandem mass spectrometry. As DHEA was consumed, the androgen intermediates androstenediol and androstenedione were generated and subsequently converted to T. Conditioned media of DHEA-treated osteoblasts increased androgen receptor (AR) signaling, prostate-specific antigen (PSA) production, and cell numbers of the androgen-sensitive prostate cancer cell lines C4-2B and LNCaP. DHEA did not induce AR signaling in osteoblasts despite AR expression in this cell type. We describe an unreported function of osteoblasts as a source of T that is especially relevant during androgen-responsive metastatic prostate cancer invasion into bone. © 2021 American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.     

Gender Variance in Children and Adolescents with Neurodevelopmental and Psychiatric Conditions from Australia

Archives of Sexual Behavior - Gender variance is a broad term used to describe gender non-conforming behaviors. Past studies have used the parental response to Child Behavior Checklist (CBCL) Item...     

Liquid Guayule Natural Rubber,a Sustainable Processing Aid,Enhances the Processability,Durability and Dynamic Mechanical Properties of Rubber Composites

Petroleum-based oils are widely used as processing aids in rubber composites to improve processability but can adversely affect rubber composite performance and increase carbon footprint. In this research, liquid guayule natural rubber (LGNR), produced from guayule natural rubber, was used as a renewable processing aid to replace naphthenic oil (NO) in Hevea natural rubber, styrene-butadiene rubber (SBR) and guayule natural rubber (GNR) composites. The rheological properties, thermal stability, glass transition temperature, dynamic mechanical properties, aging, and ozone resistance of rubber composites with and without NO or LGNR were compared. Natural and synthetic rubber composites made with LGNR had similar processability to those made with NO, but had improved thermal stability, mechanical properties after aging, and ozone resistance. This was due to the strong LGNR–filler interaction and additional crosslinks formed between LGNR and the rubber matrices. The glass transition temperature of SBR composites was reduced by LGNR because of its increased molecular mobility. Thus, unlike NO, LGNR processing aid can simultaneously improve rubber composite durability, dynamic performance and renewability. The commercialization of LGNR has the potential to open a new sustainable processing-aid market.