Minding the Baby: The challenges of implementing a reflective functioning programme with high-risk families

Part 1: Literature Review: This section consists of a meta-analytic review examining the efficacy of video-feedback interventions aimed at promoting parental sensitivity and infant attachment. Outcomes from 18 RCTs contributing 20 intervention effects were examined. Results indicated that video-feedback interventions are efficacious in promoting parental sensitivity, infant attachment security and preventing infant attachment disorganisation. These findings suggest that video-feedback interventions may offer exciting potential for clinical practice. Part 2: Empirical Paper: The empirical paper reports on a qualitative study examining the challenges of implementing ‘Minding the Baby’ (MTB), a preventative parenting programme developed explicitly to promote secure parent-child attachment relationships. Semi-structured interviews were conducted with 13 practitioners delivering the programme. Transcripts were analysed thematically and themes were organised into two domains relating to the challenges of implementation and the components of MTB which practitioners identified as being crucial in engaging mothers in reflective work. Results highlight the importance of designing and delivering services which support mentalisation throughout. In addition, a strong therapeutic relationship was identified to be crucial in engaging mothers in reflective work and in responding to the challenges of implementing a mentalisation-based parenting intervention. The study was conducted in collaboration with another UCL Clinical Psychology doctoral student, whose thesis examines parents’ experiences of the therapeutic process in MTB (Burns, 2014)

Early vs. Delayed Umbilical Cord Clamping

Nearly 4 million infants are born annually in the United States. Events during birth can have life-long implications. Early cord clamping is associated with a decreased risk of jaundice, whereas delayed cord clamping is associated with a decreased risk of anemia. Parents deserve knowledge and autonomy concerning care of their infants

Motivational Interviewing for CPAP Adherence

Background: Continuous Positive Air Pressure (CPAP), is the gold standard for obstructive sleep apnea (OSA) treatment. If left untreated, patients with OSA can experience serious and potentially life-threatening consequences. However, patient CPAP adherence is an ongoing problem, as compliance rates are historically low (typically 30-60%). Engaging patients in motivational interviewing (MI) by trained providers could promote increased CPAP adherence. Question/Purpose: Assess CPAP compliance in patients who receive motivational interviewing compared to a control attention intervention. Methods: A team of medical students were trained in MI interviewing techniques through a novel training protocol. The training protocol includes reading articles and watching training videos regarding MI, observing CPAP patient education visits, and a cumulative training assessment. MI delivered via 9 phone calls over 3 months will be used in a pilot study on ten patients newly prescribed CPAP for OSA. CPAP adherence rates will be measured compared to control. Results: Results are forthcoming for this study. However, the novel training protocol has been implemented successfully, with 11 medical students trained to provide MI to CPAP patients. We expect to see increased CPAP adherence rates in patients receiving MI compared to control. Discussion: Poor CPAP adherence can have severe and potentially life-threatening consequences on patient health. Adding MI to patient care could significantly improve long and short-term patient health outcomes for OSA patients. Another important benefit of the novel MI training protocol is that medical students participating in MI training can utilize the technique with future patients, potentially increasing compliance with recommended health interventions across multiple disease states

Genetic targeting of NRXN2 in mice unveils role in excitatory cortical synapse function and social behaviors

Human genetics has identified rare copy number variations and deleterious mutations for all neurexin genes (NRXN1-3) in patients with neurodevelopmental diseases, and electrophysiological recordings in animal brains have shown that Nrxns are important for synaptic transmission. While several mouse models for Nrxn1α inactivation have previously been studied for behavioral changes, very little information is available for other variants. Here, we validate that mice lacking Nrxn2α exhibit behavioral abnormalities, characterized by social interaction deficits and increased anxiety-like behavior, which partially overlap, partially differ from Nrxn1α mutant behaviors. Using patch-clamp recordings in Nrxn2α knockout brains, we observe reduced spontaneous transmitter release at excitatory synapses in the neocortex. We also analyse at this cellular level a novel NRXN2 mouse model that carries a combined deletion of Nrxn2α and Nrxn2β. Electrophysiological analysis of this Nrxn2-mutant mouse shows surprisingly similar defects of excitatory release to Nrxn2α, indicating that the β-variant of Nrxn2 has no strong function in basic transmission at these synapses. Inhibitory transmission as well as synapse densities and ultrastructure remain unchanged in the neocortex of both models. Furthermore, at Nrxn2α and Nrxn2-mutant excitatory synapses we find an altered facilitation and N-methyl-D-aspartate receptor (NMDAR) function because NMDAR-dependent decay time and NMDAR-mediated responses are reduced. As Nrxn can indirectly be linked to NMDAR via neuroligin and PSD-95, the trans-synaptic nature of this complex may help to explain occurrence of presynaptic and postsynaptic effects. Since excitatory/inhibitory imbalances and impairment of NMDAR function are alledged to have a role in autism and schizophrenia, our results support the idea of a related pathomechanism in these disorders

Impact of Nitric Oxide-Release Kinetics on Antifungal Activity

Pathogenic fungi are an increasing health threat due to the rise in drug resistance. The limited number of antifungals currently available and growing incidence of multi-drug-resistant fungi has caused rising healthcare costs and a decreased quality of life for patients with fungal infections. Nitric oxide (NO) has previously been shown to act as an antimicrobial agent, albeit with a limited understanding of the effects of the NO-release kinetics against pathogenic fungi. Herein, the antifungal effects of four nitric oxide-releasing small molecules were studied against the pathogenic fungi Candida albicans, Candida auris, Cryptococcus neoformans, and Aspergillus fumigatus, to demonstrate the broad-spectrum antifungal activity of NO. A bolus dose of NO was found to eradicate fungi after 24 h, where nitric oxide donors with shorter half-lives achieved antifungal activity at lower concentrations and thus had wider selectivity indexes. Each NO donor was found to cause a severe surface destruction of fungi, and all NO donors exhibited compatibility with currently prescribed antifungals against several different fungi species

Bacterial quorum-sensing signal arrests phytoplankton cell division and impacts virus-induced mortality

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Pollara, S. B., Becker, J. W., Nunn, B. L., Boiteau, R., Repeta, D., Mudge, M. C., Downing, G., Chase, D., Harvey, E. L., & Whalen, K. E. Bacterial quorum-sensing signal arrests phytoplankton cell division and impacts virus-induced mortality. Msphere, 6(3), (2021): e00009-21, https://doi.org/10.1128/mSphere.00009-21.Interactions between phytoplankton and heterotrophic bacteria fundamentally shape marine ecosystems by controlling primary production, structuring marine food webs, mediating carbon export, and influencing global climate. Phytoplankton-bacterium interactions are facilitated by secreted compounds; however, linking these chemical signals, their mechanisms of action, and their resultant ecological consequences remains a fundamental challenge. The bacterial quorum-sensing signal 2-heptyl-4-quinolone (HHQ) induces immediate, yet reversible, cellular stasis (no cell division or mortality) in the coccolithophore Emiliania huxleyi; however, the mechanism responsible remains unknown. Using transcriptomic and proteomic approaches in combination with diagnostic biochemical and fluorescent cell-based assays, we show that HHQ exposure leads to prolonged S-phase arrest in phytoplankton coincident with the accumulation of DNA damage and a lack of repair despite the induction of the DNA damage response (DDR). While this effect is reversible, HHQ-exposed phytoplankton were also protected from viral mortality, ascribing a new role of quorum-sensing signals in regulating multitrophic interactions. Furthermore, our data demonstrate that in situ measurements of HHQ coincide with areas of enhanced micro- and nanoplankton biomass. Our results suggest bacterial communication signals as emerging players that may be one of the contributing factors that help structure complex microbial communities throughout the ocean.Funding for this work was supported by an NSF grant (OCE-1657808) awarded to K.E.W. and E.L.H. K.E.W. was also supported by a faculty research grant from Haverford College as well as funding from the Koshland Integrated Natural Science Center and Green Fund at Haverford College. E.L.H. was also supported by a Sloan Foundation research fellowship. B.L.N. was supported by an NSF grant (OCE-1633939). M.C.M. was supported by an NIH training grant (T32 HG000035). Mass spectrometry was partially supported by the University of Washington Proteomics Resource (UWPR95794). D.R. was supported by funding through the Gordon and Betty Moore Foundation (grant 6000), a Simons Collaboration for Ocean Processes and Ecology grant (329108), and an NSF grant (OCE-1736280). R.B. was supported by an NSF graduate research fellowship and an NSF grant (OCE-1829761)

Persistent gating deficit and increased sensitivity to NMDA receptor antagonism after puberty in a new mouse model of the human 22q11.2 micro-deletion syndrome – a study in male mice

Background: The hemizygous 22q11.2 micro-deletion is a common copy number variant in humans. The deletion confers high risk of neurodevelopmental disorders including autism and schizophrenia. Up to 41% of deletion carriers experience psychotic symptoms. Methods: We present a new mouse model (Df(h22q11)/+) of the deletion syndrome (22q11.2DS) and report on the most comprehensive study undertaken in 22q11.2DS models. The study was conducted in male mice. Results: We found elevated post-pubertal NMDA receptor antagonist induced hyper-locomotion, age-independent prepulse inhibition (PPI) deficits and increased acoustic startle response (ASR). The PPI deficit and increased ASR was resistant to antipsychotic treatment. The PPI deficit was not a consequence of impaired hearing measured by auditory brain stem responses. The Df(h22q11)/+ mice also displayed increased amplitude of loudness-dependent auditory evoked potentials. Prefrontal cortex and dorsal striatal (DStr) elevations of the dopamine metabolite DOPAC and increased DStr expression of the AMPA receptor subunit GluR1 was found. The Df(h22q11)/+ mice did not deviate from wild-type mice in a wide range of other behavioural and biochemical assays. Limitations: The 22q11.2 micro-deletion has incomplete penetrance in humans and the severity of disease depends on the complete genetic makeup in concert with environmental factors. In order to obtain more marked phenotypes reflecting the severe conditions related to 22q11.2DS it is suggested to expose the Df(h22q11)/+ mice to environmental stressors which may unmask latent psychopathology. Conclusion: The Df(h22q11)/+ model will be a valuable tool for increasing our understanding of the aetiology of schizophrenia and other psychiatric disorders associated with the 22q11DS.The research leading to these results was conducted as part of NEWMEDS and received support from the Innovative Medicine Initiative Joint Undertaking under grant agreement n° 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). This work was further supported by grants from the Danish Advanced Technology Foundation (File no. 001-2009-2) and by the Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)

Genomics in neurodevelopmental disorders: an avenue to personalized medicine

Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders (e.g., autism spectrum disorder, intellectual disability) remains a great challenge. Recent advancements in genomics, such as whole-exome or whole-genome sequencing, have enabled scientists to identify numerous mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that have been discovered, the etiological variability and the heterogeneous clinical presentation, the need for genotype — along with phenotype- based diagnosis of individual patients has become a requisite. In this review we look at recent advancements in genomic analysis and their translation into clinical practice

Kisspeptin neurones in the posterodorsal medial amygdala modulate sexual partner preference and anxiety in male mice.

The posterodorsal medial amygdala (MePD) is a neural site in the limbic brain involved in regulating emotional and sexual behaviours. There is however limited information on the specific neuronal cell type in the MePD functionally mediating these behaviours in rodents. The recent discovery of a significant kisspeptin neurone population in the MePD has raised interest in the possible role of kisspeptin and its cognate receptor in sexual behaviour. This study therefore tested the hypothesis that the MePD kisspeptin neurone population is involved in regulating attraction towards opposite sex conspecifics, sexual behaviour, social interaction and anxiety response by selectively stimulating these neurones using the novel pharmacosynthetic DREADDs (designer receptors exclusively activated by designer drugs) technique. Adult male Kiss-Cre mice received bilateral stereotaxic injections of a stimulatory DREADD viral construct (AAV-hSyn-DIO-hM3D(Gq)-mCherry) targeted to the MePD which were activated by intraperitoneal (i.p.) injection of clozapine-N-oxide (CNO). Socio-sexual behaviours were assessed in a counter-balanced fashion after i.p. injection of either saline or CNO (5mg/kg). Selective activation of MePD kisspeptin neurones by CNO significantly increased the time spent by male mice in investigating an oestrous female as well as duration of social interaction. Additionally, after CNO injection the mice appeared less anxious; evidenced by longer exploratory time in the open arms of the elevated plus maze. However, levels of copulatory behaviour were comparable between CNO and saline treated controls. These data indicate that DREADD-induced activation of MePD kisspeptin neurones enhances sexual partner preference in males and social interaction and decreases anxiety, suggesting a key role played by MePD kisspeptin in sexual motivation and social behaviour. This article is protected by copyright. All rights reserved.This work was supported by the Medical Research Council, UK. DAA is a Commonwealth Scholar funded by the UK Government