Molecular mechanism of actin filament elongation by formins.

Formins control the assembly of actin filaments (F-actin) that drive cell morphogenesis and motility in eukaryotes. However, their molecular interaction with F-actin and their mechanism of action remain unclear. In this work, we present high-resolution cryo-electron microscopy structures of F-actin barbed ends bound by three distinct formins, revealing a common asymmetric formin conformation imposed by the filament. Formation of new intersubunit contacts during actin polymerization sterically displaces formin and triggers its translocation. This "undock-and-lock" mechanism explains how actin-filament growth is coordinated with formin movement. Filament elongation speeds are controlled by the positioning and stability of actin-formin interfaces, which distinguish fast and slow formins. Furthermore, we provide a structure of the actin-formin-profilin ring complex, which resolves how profilin is rapidly released from the barbed end during filament elongation.

Therapist-guided remote versus in-person cognitive behavioural therapy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Cognitive behavioural therapy (CBT) has been shown to be effective for several psychiatric and somatic conditions; however, most randomized controlled trials (RCTs) have administered treatment in person and whether remote delivery is similarly effective remains uncertain. We sought to compare the effectiveness of therapist-guided remote CBT and in-person CBT. METHODS: We systematically searched MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to July 4, 2023, for RCTs that enrolled adults (aged ≥ 18 yr) presenting with any clinical condition and that randomized participants to either therapist-guided remote CBT (e.g., teleconference, videoconference) or in-person CBT. Paired reviewers assessed risk of bias and extracted data independently and in duplicate. We performed random-effects model meta-analyses to pool patient-important primary outcomes across eligible RCTs as standardized mean differences (SMDs). We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance to assess the certainty of evidence and used the Instrument to Assess the Credibility of Effect Modification Analyses (ICEMAN) to rate the credibility of subgroup effects. RESULTS: We included 54 RCTs that enrolled a total of 5463 patients. Seventeen studies focused on treatment of anxiety and related disorders, 14 on depressive symptoms, 7 on insomnia, 6 on chronic pain or fatigue syndromes, 5 on body image or eating disorders, 3 on tinnitus, 1 on alcohol use disorder, and 1 on mood and anxiety disorders. Moderate-certainty evidence showed little to no difference in the effectiveness of therapist-guided remote and in-person CBT on primary outcomes (SMD -0.02, 95% confidence interval -0.12 to 0.07). INTERPRETATION: Moderate-certainty evidence showed little to no difference in the effectiveness of in-person and therapist-guided remote CBT across a range of mental health and somatic disorders, suggesting potential for the use of therapist-guided remote CBT to facilitate greater access to evidence-based care. Systematic review registration: Open Science Framework (https://osf.io/7asrc).

One-Day Peer-Delivered Cognitive Behavioral Therapy-Based Workshops for Postpartum Depression: A Randomized Controlled Trial.

INTRODUCTION: Myriad treatment barriers prevent birthing parents with postpartum depression (PPD) from receiving timely treatment. We aimed to determine whether a peer-delivered online 1-day cognitive behavioral therapy (CBT)-based workshop added to treatment as usual (TAU) improves PPD and its comorbidities and is more cost-effective than TAU alone. METHODS: This parallel-group, randomized controlled trial took place in Ontario, Canada (June 7, 2021, to February 18, 2022). Participants were ≥18 years old, had an infant ≤12 months old, and an Edinburgh Postnatal Depression Scale (EPDS) score ≥10. Participants were allocated to receive the workshop plus TAU (n = 202) or TAU and waitlisted to complete the workshop 12 weeks later (n = 203). The primary outcome was change in PPD (EPDS score) from enrollment to 12 weeks later. The secondary outcome was cost-effectiveness and tertiary outcomes included anxiety, social support, partner relationship quality, the mother-infant relationship, parenting stress, and infant temperament. RESULTS: Participants had a mean age of 32.3 years (SD = 4.30) and 65% were White. The workshop led to a significant reduction in EPDS scores (15.95-11.37; d = 0.92, p < 0. 01) and was associated with higher odds of exhibiting a clinically significant decrease in EPDS scores (OR = 2.03; 95% CI: 1.26-3.29). The workshop plus TAU was more cost-effective than TAU alone. It also led to improvements in postpartum anxiety, infant-focused anxiety, parenting stress, and infant temperament. CONCLUSIONS: Peer-delivered 1-day CBT-based workshops can improve PPD and are a potentially scalable low-intensity treatment that could help increase treatment access.

Molecular mechanisms of inorganic-phosphate release from the core and barbed end of actin filaments.

The release of inorganic phosphate (Pi) from actin filaments constitutes a key step in their regulated turnover, which is fundamental to many cellular functions. The mechanisms underlying Pi release from the core and barbed end of actin filaments remain unclear. Here, using human and bovine actin isoforms, we combine cryo-EM with molecular-dynamics simulations and in vitro reconstitution to demonstrate how actin releases Pi through a 'molecular backdoor'. While constantly open at the barbed end, the backdoor is predominantly closed in filament-core subunits and opens only transiently through concerted amino acid rearrangements. This explains why Pi escapes rapidly from the filament end but slowly from internal subunits. In a nemaline-myopathy-associated actin variant, the backdoor is predominantly open in filament-core subunits, resulting in accelerated Pi release and filaments with drastically shortened ADP-Pi caps. Our results provide the molecular basis for Pi release from actin and exemplify how a disease-linked mutation distorts the nucleotide-state distribution and atomic structure of the filament.

Fidelity Assessment of Peer-Delivered Cognitive-Behavioral Therapy for Postpartum Depression.

OBJECTIVE: Fidelity assessment of peer-administered interventions (PAIs) by expert therapists can be costly and limit scalability. This study's objective was to determine whether peer facilitators could assess the fidelity of peer-delivered group cognitive-behavioral therapy (CBT) for postpartum depression as effectively as an expert psychiatrist or a trained graduate student. METHODS: Intervention adherence and competence were assessed by three peers (N=9 sessions) and by one expert psychiatrist and one graduate student (N=18 sessions). Interrater reliability was assessed with intraclass correlation coefficients (ICCs). RESULTS: ICCs were good to excellent (0.88-0.98) for adherence and competence ratings among the three types of raters (psychiatrist vs. peers, psychiatrist vs. student, and student vs. peers). CONCLUSIONS: Trained peers may be able to reliably rate the fidelity of a PAI for postpartum depression. This preliminary study represents the first step toward peer-led feedback as an alternative to expert-led supervision of peer-delivered group CBT for postpartum depression.

Online peer-delivered group cognitive-behavioral therapy for postpartum depression: A randomized controlled trial.

BACKGROUND: Postpartum depression (PPD) affects up to one in five mothers and birthing parents, yet just 10% receive evidence-based care. This randomized controlled trial aimed to determine if a synchronous online 9-week group cognitive-behavioral therapy (CBT) intervention delivered by mothers who have recovered from postpartum depression (i.e., peers) could effectively improve PPD and its comorbidities. METHODS: Participants (n = 183) in this study lived in Ontario, Canada, were ≥18 years-old, had an infant <12 months, were fluent in English, and scored ≥10 on the Edinburgh Postnatal Depression Scale (EPDS). They were randomized to experimental (received intervention plus treatment as usual (TAU)) or waitlist control (TAU plus the intervention after a 9-week wait) groups. Depression, anxiety, social support, mother-infant bonding, and infant temperament were assessed at baseline and 9 weeks later. Outcomes were assessed in the experimental group 3 months post-intervention to assess stability. RESULTS: Statistically significant reductions were observed in EPDS (B = 5.99; p < 0.001; d = 1.32) and Generalized Anxiety Disorder Questionnaire-7 scores (B = 5.94; p < 0.001; d = 1.22), improvements that remained stable 3 months post-intervention in the experimental group. Maternal social support (p = 0.02; d = 0.40), infant-focused anxiety (p = 0.02; d = 0.54), and infant negative emotionality (p < 0.01; d = 0.23) also improved post-intervention and remained stable 3 months later. CONCLUSION: Online peer-delivered group CBT for PPD can effectively treat PPD and anxiety, and improve social support, infant-focused anxiety, and negative emotionality in infants. This intervention could provide the means to increase access to treatment for those experiencing PPD and improve outcomes for mothers, birthing parents, and families.

Online Public Health Nurse-Delivered Group Cognitive Behavioral Therapy for Postpartum Depression: A Randomized Controlled Trial During the COVID-19 Pandemic.

Objective: Rates of postpartum depression (PPD) increased during the COVID-19 pandemic, further highlighting the need for effective, accessible treatments for PPD. While public health nurses (PHNs) can be trained to help treat PPD, it is not known if they can effectively deliver evidence-based psychotherapies online to those with PPD.Methods: Mothers (n = 159) living in Ontario, Canada, with an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 10 and an infant < 12 months of age were randomized to receive a 9-week group cognitive behavioral therapy (CBT) intervention delivered by PHNs over Zoom, between October 2020 and November 2021. Experimental group participants received CBT plus treatment as usual (TAU), and control participants received TAU alone. Participants were assessed at baseline (T1), 9 weeks later (T2), and 6 months after T2 (T3). Primary outcomes were changes in EPDS score and current major depressive disorder (MDD) as measured by the Mini International Neuropsychiatric Interview. Secondary outcomes included worry, social support, the mother-infant relationship, and infant temperament.Results: At T2, experimental group participants showed clinically and statistically significant reductions on the EPDS (d = 0.65) and decreases in postpartum worry (d = 0.38) and rejection and pathological anger toward their infant (d = 0.44). They were also less likely to meet diagnostic criteria for current MDD compared to control participants (OR = 5.09; 95% CI, 1.18-21.98; number needed to treat [NNT: 3.7]). These improvements remained stable 6 months later (T3).Conclusions: PHNs can be trained to deliver effective online group CBT for PPD to reduce depression and worry and improve aspects of the mother-infant relationship, and they represent an important way to increase access to effective treatment for PPD.Trial Registration: ClinicalTrials.gov identifier: NCT04928742.

In-person 1-day cognitive behavioral therapy-based workshops for postpartum depression: a randomized controlled trial.

BACKGROUND: Postpartum depression (PPD) affects up to one in five mothers and birthing parents, yet as few as 10% access evidence-based treatment. One-day cognitive behavioral therapy (CBT)-based workshops for PPD have the potential to reach large numbers of sufferers and be integrated into stepped models of care. METHODS: This randomized controlled trial of 461 mothers and birthing parents in Ontario, Canada with Edinburgh Postnatal Depression Scale (EPDS) scores ⩾10, age ⩾18 years, and an infant <12 months of age compared the effects of a 1-day CBT-based workshop plus treatment as usual (TAU; i.e. care from any provider(s) they wished) to TAU alone at 12-weeks post-intervention on PPD, anxiety, the mother-infant relationship, offspring behavior, health-related quality of life, and cost-effectiveness. Data were collected via REDCap. RESULTS: Workshops led to meaningful reductions in EPDS scores (m = 15.77 to 11.22; b = -4.6, p < 0.01) and were associated with three times higher odds of a clinically significant decrease in PPD [odds ratio (OR) 3.00, 95% confidence interval (CI) 1.93-4.67]. Anxiety also decreased and participants had three times the odds of clinically significant improvement (OR 3.20, 95% CI 2.03-5.04). Participants reported improvements in mother-infant bonding, infant-focused rejection and anger, and effortful control in their toddlers. The workshop plus TAU achieved similar quality-adjusted life-years at lower costs than TAU alone. CONCLUSIONS: One-day CBT-based workshops for PPD can lead to improvements in depression, anxiety, and the mother-infant relationship and are cost-saving. This intervention could represent a perinatal-specific option that can treat larger numbers of individuals and be integrated into stepped care approaches at reasonable cost.

From WRC to Arp2/3: Collective molecular mechanisms of branched actin network assembly.

Branched actin networks have emerged as major force-generating structures driving the protrusions in various distinct cell types and processes, ranging from lamellipodia operating in mesenchymal and epithelial cell migration or tails pushing intracellular pathogens and vesicles to developing spine heads on neurons. Many key molecular features are conserved among all those Arp2/3 complex-containing, branched actin networks. Here, we will review recent progress in our molecular understanding of the core biochemical machinery driving branched actin nucleation, from the generation of filament primers to Arp2/3 activator recruitment, regulation and turnover. Due to the wealth of information on distinct, Arp2/3 network-containing structures, we are largely focusing-in an exemplary fashion-on canonical lamellipodia of mesenchymal cells, which are regulated by Rac GTPases, their downstream effector WAVE Regulatory Complex and its target Arp2/3 complex. Novel insight additionally confirms that WAVE and Arp2/3 complexes regulate or are themselves tuned by additional prominent actin regulatory factors, including Ena/VASP family members and heterodimeric capping protein. Finally, we are considering recent insights into effects exerted by mechanical force, both at the branched network and individual actin regulator level.

Mechanism of threonine ADP-ribosylation of F-actin by a Tc toxin.

Tc toxins deliver toxic enzymes into host cells by a unique injection mechanism. One of these enzymes is the actin ADP-ribosyltransferase TccC3, whose activity leads to the clustering of the cellular cytoskeleton and ultimately cell death. Here, we show in atomic detail how TccC3 modifies actin. We find that the ADP-ribosyltransferase does not bind to G-actin but interacts with two consecutive actin subunits of F-actin. The binding of TccC3 to F-actin occurs via an induced-fit mechanism that facilitates access of NAD+ to the nucleotide binding pocket. The following nucleophilic substitution reaction results in the transfer of ADP-ribose to threonine-148 of F-actin. We demonstrate that this site-specific modification of F-actin prevents its interaction with depolymerization factors, such as cofilin, which impairs actin network turnover and leads to steady actin polymerization. Our findings reveal in atomic detail a mechanism of action of a bacterial toxin through specific targeting and modification of F-actin.

The molecular mechanism of load adaptation by branched actin networks.

Branched actin networks are self-assembling molecular motors that move biological membranes and drive many important cellular processes, including phagocytosis, endocytosis, and pseudopod protrusion. When confronted with opposing forces, the growth rate of these networks slows and their density increases, but the stoichiometry of key components does not change. The molecular mechanisms governing this force response are not well understood, so we used single-molecule imaging and AFM cantilever deflection to measure how applied forces affect each step in branched actin network assembly. Although load forces are observed to increase the density of growing filaments, we find that they actually decrease the rate of filament nucleation due to inhibitory interactions between actin filament ends and nucleation promoting factors. The force-induced increase in network density turns out to result from an exponential drop in the rate constant that governs filament capping. The force dependence of filament capping matches that of filament elongation and can be explained by expanding Brownian Ratchet theory to cover both processes. We tested a key prediction of this expanded theory by measuring the force-dependent activity of engineered capping protein variants and found that increasing the size of the capping protein increases its sensitivity to applied forces. In summary, we find that Brownian Ratchets underlie not only the ability of growing actin filaments to generate force but also the ability of branched actin networks to adapt their architecture to changing loads.

Public Health Nurse-delivered Group Cognitive Behavioural Therapy for Postpartum Depression: A Randomized Controlled Trial.

OBJECTIVES: To examine the effectiveness of group cognitive behavioural therapy (CBT) for postpartum depression (PPD) delivered by public health nurses with little to no previous psychiatric training at improving depression, worry, social support and the mother-infant relationship. METHODS: Mothers (n = 141) living in Ontario, Canada with Edinburgh Postnatal Depression Scale Scores ≥10 and an infant <12 months of age were randomized to receive nine weekly 2-h sessions of in-person group CBT for PPD delivered by two public health nurses plus treatment as usual (TAU; experimental group) or TAU alone (control group). Primary outcomes were change in EPDS score and current major depressive disorder (Mini International Neuropsychiatric Interview) assessed immediately post-treatment (T2). Secondary outcomes included maternal worry, social support, and quality of the mother-infant relationship. All outcomes were assessed again six months post-treatment (T3). RESULTS: Participants in the experimental group had statistically significantly greater reductions in PPD symptoms immediately post-treatment (T2) (B = -5.35, p < 0.01), were more likely to manifest a clinically significant improvement in EPDS scores (≥4 points; OR = 3.44, 95%CI: 1.49-7.94), and no longer have symptoms consistent with current MDD (OR = 5.31, 95% CI: 1.78-15.83). Six months post-treatment (T3), experimental group participants had higher odds of clinically significant PPD improvement (OR = 5.10, 95%CI: 1.89-13.78), while 25% of the experimental group and 70% of remaining control group participants reported current MDD (p < 0.01). Statistically significant improvements in worry and the mother-infant relationship were also observed, decreases maintained at six months post-treatment. CONCLUSIONS: Public health nurses with little to no previous psychiatric training can be trained to deliver effective group CBT for PPD to improve depression, worry, and the mother-infant relationship. Task shifting PPD treatment with group CBT to public health nurses could improve treatment uptake and lead to better outcomes for mothers, families, and the healthcare system.(Trial Registration NCT03039530).

Naturalistic Study on the Effects of Electroconvulsive Therapy (ECT) on Depressive Symptoms.

OBJECTIVE: The effectiveness of ECT under naturalistic conditions has not been well-studied. The current study aimed to 1) characterize a naturalistic sample of ECT patients; and 2) examine the long-term outcomes of ECT on depressive symptoms (Beck Depression Inventory-II; BDI-II) and functional disability symptoms (WHO Disability Assessment Schedule 2.0) in this sample. METHODS: Participants were adults who received ECT for a major depressive episode at an ambulatory ECT clinic between September 2010 and November 2020. Clinical and cognitive assessments were completed at baseline (n = 100), mid-ECT (n = 94), 2-4 weeks post-ECT (n = 64), 6-months post-ECT (n = 34), and 12-months post-ECT (n = 19). RESULTS: At baseline, participants had severe levels of depressive symptoms (BDI-II: M = 41.0, SD = 9.4), and 62.9% screened positive for multiple psychiatric diagnoses on the MINI International Neuropsychiatric Interview. Depressive symptoms (F(4,49.1) = 49.92, P < 0.001) and disability symptoms (F(3,40.72) = 12.30, P < 0.001) improved significantly following ECT, and this was maintained at 12-months follow-up. Improvement in depressive symptoms trended towards significantly predicting reduction in disability symptoms from baseline to post-ECT, (F(1,56) = 3.67, P = 0.061). Although our clinical remission rate of 27% (BDI-II score ≤ 13 and ≥ 50% improvement) and overall response rate of 41.3% (≥50% improvement in BDI-II score) were lower than the rates reported in the extant RCT and community ECT literature, 36% of those treated with ECT were lost to follow-up and did not complete post-ECT rating scales. At baseline, remitters had significantly fewer psychiatric comorbidities, lower BDI-II scores, and lower disability symptoms than non-responders (P < 0.05). CONCLUSIONS: Participants were severely symptomatic and clinically complex. ECT was effective at reducing depressive symptoms and functional disability in this heterogeneous sample. Although a large amount of missing data may have distorted our calculated response/remission rates, it is also likely that clinical heterogeneity and severity contribute to lower-than-expected remission and response rates to ECT.

Peer-Delivered Cognitive-Behavioral Therapy for Postpartum Depression: A Randomized Controlled Trial.

Objective: To determine if a 9-week group cognitive-behavioral therapy (CBT) intervention delivered by women who have recovered from postpartum depression (peers) can effectively reduce symptoms of postpartum depression (PPD) and anxiety and improve social support and the mother-infant relationship.Methods: A sample of 73 mothers living in Ontario, Canada, were randomized into experimental and waitlist control groups between March 2018 and February 2020. Participants were ≥ 18 years of age, had an infant < 12 months old, were fluent in English, and scored ≥ 10 on the Edinburgh Postnatal Depression Scale. The experimental group completed the 9-week group CBT intervention immediately after study enrollment, while the control group did so after a 9-week waiting period. All outcomes were assessed at enrollment (n = 54) and 9 weeks later (n = 38). Outcomes were assessed in the experimental group at 6 months to assess treatment stability.Results: Peer-delivered group CBT for PPD led to clinically and statistically significant improvements in symptoms of depression (F1,47 = 22.52, P < .01) and anxiety (F1,45 = 20.56, P < .05) in the experimental group, and these improvements were stable at the 6-month follow-up. Perceptions of impaired mother-infant bonding (t15 = 3.72, P < .01) and rejection and pathological anger (t15 = 3.01, P < .01) also decreased at the 6-month follow-up in the experimental group.Conclusions: Peer-delivered group CBT for PPD effectively treats symptoms of PPD and anxiety and may lead to improvements in the mother-infant relationship. This intervention is an effective and potentially scalable means by which access to a treatment that meets the needs and wants of mothers with PPD can be increased.Trial Registration: ClinicalTrials.gov Identifier: NCT03285139.

A barbed end interference mechanism reveals how capping protein promotes nucleation in branched actin networks.

Heterodimeric capping protein (CP/CapZ) is an essential factor for the assembly of branched actin networks, which push against cellular membranes to drive a large variety of cellular processes. Aside from terminating filament growth, CP potentiates the nucleation of actin filaments by the Arp2/3 complex in branched actin networks through an unclear mechanism. Here, we combine structural biology with in vitro reconstitution to demonstrate that CP not only terminates filament elongation, but indirectly stimulates the activity of Arp2/3 activating nucleation promoting factors (NPFs) by preventing their association to filament barbed ends. Key to this function is one of CP's C-terminal "tentacle" extensions, which sterically masks the main interaction site of the terminal actin protomer. Deletion of the ß tentacle only modestly impairs capping. However, in the context of a growing branched actin network, its removal potently inhibits nucleation promoting factors by tethering them to capped filament ends. End tethering of NPFs prevents their loading with actin monomers required for activation of the Arp2/3 complex and thus strongly inhibits branched network assembly both in cells and reconstituted motility assays. Our results mechanistically explain how CP couples two opposed processes-capping and nucleation-in branched actin network assembly.

Effect of Online 1-Day Cognitive Behavioral Therapy-Based Workshops Plus Usual Care vs Usual Care Alone for Postpartum Depression: A Randomized Clinical Trial.

Importance: Postpartum depression (PPD) affects as many as 20% of mothers, yet just 1 in 10 of these women receives evidence-based treatment. The COVID-19 pandemic has increased PPD risk, reduced treatment access, and shifted preferences toward virtual care. Objective: To determine whether an online 1-day cognitive behavioral therapy (CBT)-based workshop added to treatment as usual improves PPD, anxiety, social support, mother-infant relationship quality, and infant temperament more than treatment as usual alone. Design, Setting, and Participants: This randomized clinical trial included 403 women with PPD who were recruited across Ontario, Canada, during the COVID-19 pandemic (April 20 to October 4, 2020). Women with Edinburgh Postnatal Depression Scale (EPDS) scores of at least 10 who were 18 years or older and had an infant younger than 12 months were eligible. Interventions: Women were randomly assigned to receive a live, interactive online 1-day CBT-based workshop delivered by a registered psychotherapist, psychiatrist, or clinical psychology graduate student in addition to treatment as usual (n = 202) or to receive treatment as usual and wait-listed to receive the workshop 12 weeks later (n = 201). Main Outcomes and Measures: The primary outcome was change in PPD (EPDS scores) in experimental and wait list control groups 12 weeks after baseline. Secondary outcomes included maternal anxiety (7-item Generalized Anxiety Disorder Questionnaire [GAD-7]), social support (Social Provisions Scale), quality of the mother-infant relationship (Postpartum Bonding Questionnaire), and infant temperament (Infant Behavior Questionnaire-Revised Very Short Form). Results: Participants all identified as women with a mean (SD) age of 31.8 (4.4) years. The workshop led to significant mean (SD) reductions in EPDS scores (from 16.47 [4.41] to 11.65 [4.83]; B = -4.82; P < .001) and was associated with a higher odds of exhibiting a clinically significant decrease in EPDS scores (odds ratio, 4.15; 95% CI, 2.66-6.46). The mean (SD) GAD-7 scores decreased from 12.41 (5.12) to 7.97 (5.54) after the workshop (B = -4.44; 95% CI, -5.47 to -3.38; P < .001) and participants were more likely to experience a clinically significant change (odds ratio, 3.09; 95% CI, 1.99-4.81). Mothers also reported improvements in bonding (B = -3.22; 95% CI, -4.72 to -1.71; P < .001), infant-focused anxiety (B = -1.64; 95% CI, -2.25 to 1.00; P < .001), social support (B = 3.31; 95% CI, 1.04 to 5.57; P < .001), and positive affectivity/surgency in infants (B = 0.31; 95% CI, 0.05 to 0.56; P < .001). Conclusions and Relevance: In this randomized clinical trial, an online 1-day CBT-based workshop for PPD provides an effective, brief option for mothers, reducing PPD and anxiety as well as improving social support, the mother-infant relationship, and positive affectivity/surgency in offspring. Trial Registration: ClinicalTrials.gov Identifier: NCT04485000.

Cryo-EM Resolves Molecular Recognition Of An Optojasp Photoswitch Bound To Actin Filaments In Both Switch States.

Actin is essential for key processes in all eukaryotic cells. Cellpermeable optojasps provide spatiotemporal control of the actin cytoskeleton, confining toxicity and potentially rendering F-actin druggable by photopharmacology. Here, we report cryo electron microscopy (cryo-EM) structures of both isomeric states of one optojasp bound to actin filaments. The high-resolution structures reveal for the first time the pronounced effects of photoswitching a functionalized azobenzene. By characterizing the optojasp binding site and identifying conformational changes within F-actin that depend on the optojasp isomeric state, we refine determinants for the design of functional F-actin photoswitches.

A Predictive Model for Estimating Risk of Harm and Aggression in Inpatient Mental Health Clinics.

Serious mental illness is a major risk factor for aggression and violence. The present study aimed to develop and test an algorithm to predict inpatient aggressions that involve a risk of harm to self or others. This work is based on a retrospective study aimed to investigate the prediction of risk of harm and aggressions at St. Joseph's Healthcare Hamilton, between 2016 and 2017. An analysis of the risk factors most strongly associated with harmful incidents is, followed by the description of the process involved in the development of a predictive model which estimates the risk of harm. The efficiency of the model developed is finally evaluated, showing an overall accuracy of 75%: the specificity to identify episodes considered not at risk of harm is equal to 91.85%, whereas the sensitivity to identify episodes considered harmful is equal to 28.57%. The model proposed can be seen as a seminal project towards the development of a more comprehensive, precise and effective tool capable to predict the risk of harm in the inpatient setting.