Acceptability and feasibility of cognitive assessments with adults with primary brain cancer and brain metastasis: A systematic review.

Routine cognitive assessment for adults with brain cancers is seldom completed but vital for guiding daily living, maintaining quality of life, or supporting patients and families. This study aims to identify cognitive assessments which are pragmatic and acceptable for use in clinical settings. MEDLINE, EMBASE, PsycINFO, CINAHL, and Cochrane were searched to identify studies published in English between 1990 and 2021. Publications were independently screened by two coders and included if they: (1) were peer-reviewed; (2) reported original data relating to adult primary brain tumor or brain metastases; (3) used objective or subjective assessments; (4) reported assessment acceptability or feasibility. The Psychometric And Pragmatic Evidence Rating Scale was used. Consent, assessment commencement and completion, and study completion were extracted along with author-reported acceptability and feasibility data. PROSPERO Registration: CRD42021234794. Across 27 studies, 21 cognitive assessments had been assessed for feasibility and acceptability; 15 were objective assessments. Acceptability data were limited and heterogeneous, particularly consent (not reported in 23 studies), assessment commencement (not reported in 19 studies), and assessment completion (not reported in 21 studies). Reasons for non-completion could be grouped into patient-factors, assessment-factors, clinician-factors, and system-factors. The three cognitive assessments with the most acceptability and feasibility data reported were the MMSE, MoCA, and NIHTB-CB. Further acceptability and feasibility data are needed including consent, commencement and completion rates. Cost, length, time, and assessor burden are needed for the MMSE, MoCA, and NIHTB-CB, along with potentially new computerized assessments suited for busy clinical settings.

Molecular evidence of a (pro)renin/ (pro)renin receptor system in human intrauterine tissues in pregnancy and its association with PGHS-2.

Prorenin stimulates decidual prostaglandin (PG) production in vitro, the (pro)renin receptor ((P)RR) may mediate this action. The role of prorenin in amnion PG synthesis has not been examined, despite this being the key site of PG synthesis. To determine if (P)RR, prorenin and PGHS-2 are co-localized in gestational tissues and if expression is altered by labour, term amnion, chorion, decidua and placenta were collected during elective caesarean section or after spontaneous labour. Prorenin, (P)RR and PGHS-2 mRNA abundance was determined by real-time RT-PCR. (P)RR protein was examined by immunohistochemistry. The effect of recombinant human (rh) prorenin on PGHS-2 mRNA abundance in amnion explants was determined. Prorenin and (P)RR mRNA were highest in decidua and placenta, respectively. Decidual prorenin, (P)RR and placental (P)RR mRNA abundance decreased with labour. (P)RR protein was present in all gestational tissues. After labour, decidual prorenin was positively correlated with amnion PGHS-2 mRNA and rh-prorenin significantly increased PGHS-2 mRNA abundance in amnion explants. We conclude that the decidua is the principal source of prorenin and is downregulated with labour. All gestational tissues are targets for prorenin. Decidual prorenin may be involved in the labour-associated increase in amnion PGHS-2 abundance via the (P)RR.

Neurosteroids in the fetus and neonate: potential protective role in compromised pregnancies.

Complications during pregnancy and birth asphyxia lead to brain injury, with devastating consequences for the neonate. In this paper we present evidence that the steroid environment during pregnancy and at birth aids in protecting the fetus and neonate from asphyxia-induced injury. Earlier studies show that the placental progesterone production has a role in the synthesis and release of neuroactive steroids or their precursors into the fetal circulation. Placental precursor support leads to remarkably high concentrations of allopregnanolone in the fetal brain and to a dramatic decline with the loss of the placenta at birth. These elevated concentrations influence the distinct behavioral states displayed by the late gestation fetus and exert a suppressive effect that maintains sleep-like behavioral states that are present for much of fetal life. This suppression reduces CNS excitability and suppresses excitotoxicity. With the availability of adequate precursors, mechanisms within the fetal brain ultimately control neurosteroid levels. These mechanisms respond to episodes of acute hypoxia by increasing expression of 5alpha-reductase and P450scc enzymes and allopregnanolone synthesis in the brain. This allopregnanolone response, and potentially that of other neurosteroids including 5alpha-tetrahydrodeoxycorticosterone (TH-DOC), reduces hippocampal cell death following acute asphyxia and suggests that stimulation of neurosteroid production may protect the fetal brain. Importantly, inhibition of neurosteroid synthesis in the fetal brain increases the basal cell death suggesting a role in controlling developmental processes late in gestation. Synthesis of neurosteroid precursors in the fetal adrenal such as deoxycorticosterone (DOC), and their conversion to active neurosteroids in the fetal brain may also have a role in neuroprotection. This suggests that the adrenal glands provide precursor DOC for neurosteroid synthesis after birth and this may lead to a switch from allopregnanolone alone to neuroprotection mediated by allopregnanolone and TH-DOC.