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Aims and Method: Functional neurological disorder (FND) most often presents in women of childbearing age, but little is known about its course and outcomes during pregnancy, labour and postpartum (the perinatal period). We searched MEDLINE, PsycInfo and Embase combining search terms for FND and the perinatal period. We extracted data on patient demographics, subtype of FND, timing of symptom onset, comorbidities, medications, type of delivery, investigations, treatment, pregnancy outcomes and FND symptoms at follow-up., Results: We included 36 studies (34 case reports and 2 case series) describing 43 patients. Six subtypes of FND were identified: functional (dissociative) seizures, motor weakness, movement disorder, dissociative amnesia, speech disorders and visual symptoms. New onset of perinatal FND was more common in the third trimester and onwards. Some women with functional seizures were exposed to unnecessary anti-seizure prescriptions and intensive care admissions., Clinical Implications: Prospective studies are urgently needed to explore how FND interacts with women's health in the perinatal period.

Background: Perinatal anxiety (PNA) occurs during pregnancy and up to 12 months post-partum. PNA affects more than 21% of women and can impact adversely on mothers, children and their families. National Institute for Health and Care Excellence (NICE) guidance identified evidence gaps around non-pharmacological interventions for PNA., Aim: This qualitative study aimed to understand the perspectives of a variety of Perinatal Mental Health (PMH) stakeholders about non-pharmacological interventions for PNA., Method: Ethics approval. Semi-structured interviews with women with lived experience of PNA, healthcare professionals (HCPs), voluntary community and social enterprise (VCSE) stakeholders and commissioners. Topic guide modified in response to emerging themes. Interviews digitally recorded with consent, transcribed, and analysed thematically. A patient advisory group was involved throughout the study., Results: There were 25 interviews conducted. Women with PNA expressed a wish to choose from a range of non-pharmacological interventions, which are often delivered by VSCE organisations or not commissioned within the NHS. HCPs described a hierarchy of interventions that can be offered to women, often related to severity of a woman's PNA. PMH VCSE stakeholders emphasised that their services are flexible and accessible for women with PNA., Conclusion: Tension exists between what is currently recommended by NICE and thus commissioned, and the types of intervention that women want to access, including support from VCSE services. Clinicians should be aware of local VCSE organisations which provide care for women with PNA. There is an evidence gap around the effectiveness of various interventions delivered by VCSE organisations, which requires further exploration., (© British Journal of General Practice 2024.)

Background: Perinatal anxiety (PNA) occurs throughout the antenatal period or up to 1 year after childbirth, with a prevalence of 21%., Aim: To investigate if primary care records could be used to identify women at 'higher risk' of PNA., Method: Mixed-methods approach using quantitative and qualitative methods. Quantitative data analysis used Clinical Practice Research Datalink and IQVIA Medical Research Data to identify risk factors for PNA. Interviews explored the lived experiences of women with PNA about predisposing factors for PNA and acceptability of being informed of risk; and perspectives of primary healthcare professionals and Voluntary, Community, and Social Enterprise practitioners about risk communication. Interviews were conducted online, digitally recorded with consent, transcribed, and anonymised prior to analysis. Data were thematically analysed. Patient and clinical advisory groups informed each stage of the research., Results: Women reflected on both positive and negative impacts of being identified at higher risk of PNA, a lack of understanding of how primary care records are used, and who has access to them. All interview participants suggested predisposing factors that would not be coded in primary care records. Quantitative analysis demonstrated that some predisposing factors for PNA can be identified in a woman's primary care records. Initial analysis suggests associations between PNA and infant health and healthcare use., Conclusion: While identification of higher risk of PNA may be acceptable, some factors that may contribute to PNA are not coded in primary care records. Identifying and managing PNA is needed to improve infant health., (© British Journal of General Practice 2024.)

Background: Prior research has investigated various strategies to improve health, wellbeing and the job-related outcomes of nurses. However, the scope of this evidence is not clear and the types of intervention most likely to have positive outcomes are unknown., Objective: To provide an overview and synthesis of the effectiveness of interventions conducted with the goal of improving health, wellbeing and the job-related outcomes of nurses., Methods: A systematic database search was conducted from January 2000 to December 2018, with pre-defined criteria (Cochrane Central Register of Controlled Trials; MEDLINE and PubMed; EMBASE; CINAHL; PsycINFO; and BioMed Central). In total, 136 intervention studies with a total sample of 16,129 participants (range 9-3381) were included and evaluated. Data extraction, quality assessment and risk of bias analyses were performed., Results: Studies included randomised controlled trials (RCTs; n = 52, 38%), randomised crossover design studies (n = 2, 1.5%) and non-randomised pre-post studies with a control group (n = 31, 23%) and without a control group (n = 51, 37.5%). The majority of interventions focused on education, physical activity, mindfulness, or relaxation. Thirty-seven (27%) studies had a multimodal intervention approach. On average, studies had relatively small samples (median = 61; mode = 30) and were conducted predominantly in North America (USA/Canada, n = 53). The findings were mixed overall, with some studies reporting benefits and others finding no effects. Dietary habits was the most successfully improved outcome (8/9), followed by indices of body composition (20/24), physical activity (PA) (11/14), and stress (49/66), with >70% of relevant studies in each of these categories reporting improvements. The lowest success rate was for work-related outcomes (16/32). Separate analysis of RCTs indicated that interventions that focus solely on education might be less likely to result in positive outcomes than interventions targeting behavioural change., Conclusions: Interventions targeting diet, body composition, PA, or stress are most likely to have positive outcomes for nurses' health and/or wellbeing. The methodologically strongest evidence (RCTs) is available for body composition and stress. Interventions relying solely on educational approaches are least likely to be effective. Organisational outcomes appear to be more challenging to change with lifestyle intervention, likely requiring more complex solutions including changes to the work environment. There is a need for more high-quality evidence since many studies had moderate or high risk of bias and low reporting quality., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Methylated bases in tRNA, rRNA and mRNA control a variety of cellular processes, including protein synthesis, antimicrobial resistance and gene expression. Currently, bulk methods that report the average methylation state of ~10 4 -10 7 cells are used to detect these modifications, obscuring potentially important biological information. Here, we use in situ hybridization of Molecular Beacons for single-cell detection of three methylations (m 6 2 A, m 1 G and m 3 U) that destabilize Watson-Crick base pairs. Our method-methylation-sensitive RNA fluorescence in situ hybridization-detects single methylations of rRNA, quantifies antibiotic-resistant bacteria in mixtures of cells and simultaneously detects multiple methylations using multicolor fluorescence imaging.

Local delivery of amyloid beta oligomers from the tip of a nanopipette, controlled over the cell surface, has been used to deliver physiological picomolar oligomer concentrations to primary astrocytes or neurons. Calcium influx was observed when as few as 2000 oligomers were delivered to the cell surface. When the dosing of oligomers was stopped the intracellular calcium returned to basal levels or below. Calcium influx was prevented by the presence in the pipette of the extracellular chaperone clusterin, which is known to selectively bind oligomers, and by the presence a specific nanobody to amyloid beta. These data are consistent with individual oligomers larger than trimers inducing calcium entry as they cross the cell membrane, a result supported by imaging experiments in bilayers, and suggest that the initial molecular event that leads to neuronal damage does not involve any cellular receptors, in contrast to work performed at much higher oligomer concentrations.

Protein aggregation plays a key role in neurodegenerative disease, giving rise to small oligomers that may become cytotoxic to cells. The fundamental microscopic reactions taking place during aggregation, and their rate constants, have been difficult to determine due to lack of suitable methods to identify and follow the low concentration of oligomers over time. Here we use single-molecule fluorescence to study the aggregation of the repeat domain of tau (K18), and two mutant forms linked with familial frontotemporal dementia, the deletion mutant ΔK280 and the point mutant P301L. Our kinetic analysis reveals that aggregation proceeds via monomeric assembly into small oligomers, and a subsequent slow structural conversion step before fibril formation. Using this approach, we have been able to quantitatively determine how these mutations alter the aggregation energy landscape.

Hyperpolarization-activated cyclic nucleotide gated (HCN) ion channels regulate membrane potential, neurotransmitter release, and patterning of synchronized neuronal activity. Currently, there is an intense debate as to whether or not these ion channels play a pro- or anticonvulsant role in vivo. To gain an insight into this question, we have examined how inhibitors of the response mediated by HCN channels (referred to as I(h)) affect epileptiform activity induced in adult hippocampal slices. The archetypal I(h) blocker ZD-7288 produced a concentration-dependent inhibition of both nonsynaptic- (low Ca(2+)/elevated K(+) aCSF) and synaptic- (low Mg(2+) aCSF, elevated K(+) aCSF or convulsant application (bicuculline or pentylenetetrazol)) based epileptiform activities. The IC(50) value for ZD-7288 induced inhibition of epileptiform activity was similar across all forms of epileptiform response and was below concentrations producing nonspecific inhibition of glutamatergic synaptic transmission. Furthermore, capsazepine, which exhibits similar potency to ZD-7288 at inhibiting I(h), failed to inhibit glutamatergic synaptic transmission per se but produced a significant inhibition of bicuculline-induced epileptiform activity. These data suggest that broad spectrum inhibition of I(h) reduces neuronal hyperexcitability in the hippocampus.