Vaccination during pregnancy and modulation of IgG response to pertussis vaccines in infants: The impact of different vaccine formulations.

The IgG response following infant diphtheria-tetanus-acellular pertussis (DTaP) immunization is influenced by the formulation of the infant and/or the adult vaccine (Tdap) given during pregnancy. DTaP vaccines containing either 3 (DTaP3) or 5 (DTaP5) pertussis antigens are commonly used. By conducting a secondary analysis of a large randomized controlled trial, we compared IgG levels against pertussis vaccine antigens in children of Td- and Tdap5-vaccinated mothers, after stratifying by infant vaccine formulation. After immunization with a primary series of DTaP5, but not DTaP3, IgG GMCs against pertussis antigens were significantly lower in infants of Tdap-immunized mothers compared with infants of Td-vaccinated mothers (pertussis toxin: GMC = 52.3[Tdap5] vs 83.5[Td], p < 0.001). Before and after the DTaP booster dose, IgG GMCs were similar in infants of Tdap- and Td-immunized mothers specifically when infants received the DTaP3 vaccine. The combination of the TdaP5 vaccine for mothers and the DTaP3 vaccine for children could attenuate Tdap-associated immunomodulation.

Informal coercion in inpatient mental healthcare: a scoping review protocol.

INTRODUCTION: Comprehending informal coercion, which encompasses a wide range of phenomena characterised by subtle and non-legalised pressures, can be complex. Its use is underestimated within the continuum of coercion in mental health, although its application may have a negative impact on the persons involved. A better understanding of informal coercion is crucial for improving mental healthcare and informing future research. This scoping review aims to explore the nature, extent and consequences of informal coercion in mental health hospitalisation to clarify this phenomenon, establish its boundaries more clearly and identify knowledge gaps. METHODS AND ANALYSIS: Following the methodological framework from the Joanna Briggs Institute, this scoping review will encompass 10 key steps. Literature searches will be conducted in electronic databases, including CINAHL, PubMed, MEDLINE, EMBASE, Web of Science, PsycINFO, and ProQuest Dissertation and Theses. Then, a search in grey literature sources (Open Grey, Grey Guide), psychiatric and mental health journals, government agencies and among the references of selected studies will be conducted. The research will include all literature focusing on informal coercion with inpatients aged 18 and above. Data will be extracted and analysed descriptively, mapping the available knowledge and identifying thematic patterns. The quality of included studies will be assessed using appropriate appraisal tools. An exploratory search was conducted in November 2023 and will be updated in December 2023 when the selection of relevant evidence will begin. ETHICS AND DISSEMINATION: Ethical approval is not required as this study involves the analysis of existing published literature. The findings will be disseminated through a peer-reviewed publication and presentations at relevant conferences. They will be shared with people living with mental disorders and professionals working in mental healthcare.

Heterologous expression of influenza haemagglutinin leads to early and transient activation of the unfolded protein response in Nicotiana benthamiana.

The unfolded protein response (UPR) allows cells to cope with endoplasmic reticulum (ER) stress induced by accumulation of misfolded proteins in the ER. Due to its sensitivity to Agrobacterium tumefaciens, the model plant Nicotiana benthamiana is widely employed for transient expression of recombinant proteins of biopharmaceutical interest, including antibodies and virus surface proteins used for vaccine production. As such, study of the plant UPR is of practical significance, since enforced expression of complex secreted proteins often results in ER stress. After 6 days of expression, we recently reported that influenza haemagglutinin H5 induces accumulation of UPR proteins. Since up-regulation of corresponding UPR genes was not detected at this time, accumulation of UPR proteins was hypothesized to be independent of transcriptional induction, or associated with early but transient UPR gene up-regulation. Using time course sampling, we here show that H5 expression does result in early and transient activation of the UPR, as inferred from unconventional splicing of NbbZIP60 transcripts and induction of UPR genes with varied functions. Transient nature of H5-induced UPR suggests that this response was sufficient to cope with ER stress provoked by expression of the secreted protein, as opposed to an antibody that triggered stronger and more sustained UPR activation. As up-regulation of defence genes responding to H5 expression was detected after the peak of UPR activation and correlated with high increase in H5 protein accumulation, we hypothesize that these immune responses, rather than the UPR, were responsible for onset of the necrotic symptoms on H5-expressing leaves.

Molecular responses of agroinfiltrated Nicotiana benthamiana leaves expressing suppressor of silencing P19 and influenza virus-like particles.

The production of influenza vaccines in plants is achieved through transient expression of viral hemagglutinins (HAs), a process mediated by the bacterial vector Agrobacterium tumefaciens. HA proteins are then produced and matured through the secretory pathway of plant cells, before being trafficked to the plasma membrane where they induce formation of virus-like particles (VLPs). Production of VLPs unavoidably impacts plant cells, as do viral suppressors of RNA silencing (VSRs) that are co-expressed to increase recombinant protein yields. However, little information is available on host molecular responses to foreign protein expression. This work provides a comprehensive overview of molecular changes occurring in Nicotiana benthamiana leaf cells transiently expressing the VSR P19, or co-expressing P19 and an influenza HA. Our data identifies general responses to Agrobacterium-mediated expression of foreign proteins, including shutdown of chloroplast gene expression, activation of oxidative stress responses and reinforcement of the plant cell wall through lignification. Our results also indicate that P19 expression promotes salicylic acid (SA) signalling, a process dampened by co-expression of the HA protein. While reducing P19 level, HA expression also induces specific signatures, with effects on lipid metabolism, lipid distribution within membranes and oxylipin-related signalling. When producing VLPs, dampening of P19 responses thus likely results from lower expression of the VSR, crosstalk between SA and oxylipin pathways, or a combination of both outcomes. Consistent with the upregulation of oxidative stress responses, we finally show that reduction of oxidative stress damage through exogenous application of ascorbic acid improves plant biomass quality during production of VLPs.

Community treatment orders: A qualitative study of stakeholder perspectives.

INTRODUCTION: For people with a serious mental disorder, a community treatment order (CTO) is a legal response that requires them to undergo psychiatric treatment unwillingly under certain conditions. Qualitative studies have explored the perspectives of individuals involved in CTOs, including persons with lived experiences of a CTO, family members and mental health care providers, who are directly involved in these procedures. However, few studies have integrated their different perspectives. METHOD: This descriptive and qualitative study aimed to explore the experience associated with a CTO in hospital and community settings among individuals with a history of CTO, relatives, and mental health care providers. Using a participatory research approach, individual semi-structured interviews were conducted with 35 participants. The data were reviewed using content analysis. RESULTS: Three themes and seven sub-themes were identified: 1) differential positions as a function of meaning conferred to CTOs; 2) a risk management tool; and 3) coping strategies used to deal with CTOs. Overall, relatives' and mental health care providers' perspectives tended to be in opposition to those who went under a CTO. CONCLUSIONS: In a context of recovery-oriented care, more research is needed to reconcile the seemingly contradictory positions of individual with experiential knowledge and the legal leverage that deprives them of their fundamental right to autonomy.

Crisis plans in mental health: A scoping review.

Crisis situations are frequent among people with mental health disorders. Several interventions have been developed to act in prevention, including crisis plans recognized as particularly effective in reducing coercive measures. In the literature, several models of crisis plans are proposed with similar aims and contents. Based on the methodology proposed by the Joanna Briggs Institute, a scoping review was conducted to map the state of knowledge on crisis plans in adult mental health settings. The literature search conducted on six databases (CINAHL, PubMed, Medline, EMBASE, PsychINFO and Cochrane) yielded 2435 articles. Of these, 122 full-text articles were assessed for eligibility, and 78 met the inclusion criteria. Studies were critically appraised using the Joanna Briggs Institute appraisal tools, and data were extracted by two independent reviewers. Content analysis identified a typology of crisis plans: (1) the legal crisis plan and (2) the formal crisis plan. Five modalities were identified for its completion: the sections, the moment, the completion steps, the people involved and the training of key actors. Most identified outcomes are consistent with the main purpose of the intervention, which is crisis prevention. However, the most identified outcomes focused on the service user's recovery and indicated that crisis plans could provide an opportunity to operationalize recovery in mental healthcare, thus suggesting an evolution in the aim of the intervention. Future research should further focus on the modalities of crisis plans to guide the implementation in clinical practice.

[The Model of Prevention of Seclusion and Restraint Use in Mental Health: An Integrative Review]. / Le Modèle de prévention de l'utilisation des mesures de contrôle en santé mentale : une revue intégrative.

Background Seclusion and restraint are still being used frequently in psychiatric and mental health care despite their known harmful effects. Many countries have the goal of reducing their use, leading to a number of research on prevention interventions. While many of these interventions have been shown to be effective, reducing restrictive practices depends on several factors. Conceptual models have been developed in relation to seclusion and restraint, but none have addressed their prevention specifically. Aim This article aims to propose The Model of prevention of seclusion and restraint use in mental health by carrying an integrative review on the subject. Methods An integrative review was conducted using Whittemore et Knafl's (2005) approach. Four databases (Pubmed, PsycINFO, EMBASE, CINAHL) were searched for publications between 2010 and 2020, in French or English. Search terms included seclusion, restraint, psychiatr*, mental health reduction and mental health prevent*. The search resulted in the inclusion of 138 articles. Data was analyzed using thematic analysis (Miles et coll., 2014) and categorized with Bronfenbrenner's (1979) ecological model. Results The six categories represented in the ecological model are described in terms of systems mutually involved in the prevention of seclusion and restraint use: the person (individual), the professionals and the physical environment (microsystem), the ward culture (mesosystem), organizational initiatives (exosystem), national policies and international organizations (macrosystem) and evolution of the discourse or resistance to change (chronosystem). Specific interventions are presented for each system, as well as their interactions. Conclusion The prevention of seclusion and restraint use in mental health is a shared responsibility between the systems involved, who must act as leaders and agents of change by implementing their specific activities. Preventing restrictive practices in mental health will be achieved by developing a shared responsibility and a shift towards a culture of partnership.

Factors associated with perceived coercion in adults receiving psychiatric care: a scoping review protocol.

INTRODUCTION: Coercion is inevitably linked to psychiatric and mental healthcare. Though many forms of coercion exist, perceived coercion appears to be a less studied form despite its marked prevalence and negative consequences. In the literature, several factors have been studied for their association with perceived coercion, but few literature reviews have focused on this precise subject. Gaining knowledge of the association between these factors and the degree of perceived coercion is essential to guide future research and develop informed interventions. The purpose of this review will be to identify, in the literature, factors associated with perceived coercion by adults receiving psychiatric care. METHODS AND ANALYSIS: A scoping review will be conducted by following the Joanna Briggs Institute methodology. A search with descriptors and keywords will be performed in the following databases: CINAHL, MEDLINE, PUBMED, EMBASE and PsycINFO. Then, a search for grey literature will be conducted, psychiatric and mental health journals will be searched, and reference lists will be examined to identify further pertinent literature. All literature on factors (human, health related, organisational, etc) and their association to perceived coercion by adults (18 and older) in inpatient, outpatient and community-based psychiatry will be included. A quality assessment of the literature included will be performed. The extracted data will be analysed with a method of content analysis. An exploratory search was conducted in September 2021 and will be updated in September 2022 once the evidence selection process is planned to begin. ETHICS AND DISSEMINATION: No ethics approval is required for this review. The results of this scoping review will be submitted to a scientific journal for publication, presented in conferences and shared with clinicians working in psychiatric and mental healthcare.

Assessment and care of individuals at risk of suicide in Emergency Department: The SecUrgence protocol.

Almost half (48,5%) of all individuals who die by suicide visited the Emergency Department (ED) in the year preceding their death by suicide and for almost a third (29,5%) of these individuals, the ED visit occurred within the month preceding their death by suicide. The ED is a key location for suicide prevention. The aim of this study was to develop and reach a consensus on the SecUrgence Protocol, a clinical protocol that intends to assess and provide care for individuals at risk of suicide that present themselves to the ED. This project was conducted in 3 stages: 1) Review of the literature, 2) Development of the list of the protocol statements by a first panel of experts, and 3) Validation, using the Delphi consensus method, on the final statements to include in the SecUrgence Protocol by a second panel of experts. Two rounds of the Delphi questionnaire were conducted until a final consensus of over 75% was reached. The SecUrgence Protocol is a first scientific step towards improving suicide prevention in the ED in Quebec as it was validated by a rigorous research process that included a consensus by all key stakeholders.

Solitary Confinement of Inmates Associated With Relapse Into Any Recidivism Including Violent Crime: A Systematic Review and Meta-Analysis.

Recidivism among released inmates is associated with a substantial societal burden given the financial and medical consequences of victimization. Among incarcerated North Americans, approximately 7% are housed in solitary confinement (SC). Studies show SC can lead to psychological deterioration and dispute it can effectively reduce institutional misconduct or recidivism. This meta-analysis aims to clarify the impact of SC on postrelease recidivism, which we hypothesized would increase following SC. A meta-analysis was conducted using PubMed, PsycINFO, Web of Science, and Google Scholar databases from inception until December 2019. Studies on adult inmates in correctional settings were included if they met an operational definition of SC, measured recidivism, and included a comparison group in general inmate population. Random-effect models were used to assess the impact of SC on multiple types of recidivism. Of the 2,713 identified records, 12 met inclusion criteria (n = 194,078). A moderate association was found between SC and any recidivism (odds ratio [OR] = 1.67, 95% confidence interval [1.41, 1.97]), which persisted in controlled studies (OR = 1.41). This association was replicated across types of recidivism comprising violence (OR = 1.41), rearrests (OR = 1.37), and reincarceration (OR = 1.67). Moreover, a more recent exposure to SC increased recidivism risk (OR = 2.02), and a dose-response relationship was found between days in SC and recidivism. The overall database presented high heterogeneity but no publication bias. Findings show a small to moderate association between SC and future crime/violence. Considering the societal costs associated with antisocial behaviors following SC, mental health and psychosocial programming facilitating inmates' successful reentry into society should be implemented and rigorously evaluated in strong research design.

The therapeutic relationship in the context of involuntary treatment orders: The perspective of nurses and patients.

WHAT IS KNOWN ON THE SUBJECT?: Involuntary treatment orders are increasingly being used around the world to allow the treatment of individuals living with a mental illness deemed incapable of giving consent and who are actively refusing treatment. The use of involuntary treatment orders can impact the nurse-patient therapeutic relationship, which is essential to offer quality care and promote recovery. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: Nurses and patients do not agree on the possibility to develop a therapeutic relationship, with nurses believing they can build a bond with the patients despite the challenges imposed by the involuntary treatment order, and patients rejecting this possibility. Nurses caring for patients on involuntary treatment orders feel obligated to apply the conditions of this measure, even if it damages the relationship with their patients. This difficult aspect of their work leads them to question their role in relation to the management of involuntary treatment orders. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Nurses need to be aware of the reasons why patients on involuntary treatment orders do not believe in the possibility of building a therapeutic relationship. Nurses need to reflect on and express their concerns about the damaging effects that managing involuntary treatment orders conditions can have on the nurse-patient therapeutic relationship. ABSTRACT: Introduction Involuntary treatment orders (ITO) can impact the nurse-patient therapeutic relationship (TR) negatively. Despite the increasing use of ITOs around the world, few studies have explored their influence on the TR from the perspectives of nurses and patients. Aim To describe the TR in the context of ITOs as reported by nurses and individuals living with a mental illness. Method Secondary data analysis of qualitative interviews with nurses (n = 9) and patients (n = 6) was performed using content analysis. Results Participants described the TR as fundamentally embedded in a power imbalance amplified by the ITO, which was discussed through the conflicting roles of nurses, the legal constraints imposed on patients and nurses, the complex relation between the ITO and the TR, and the influence of mental healthcare settings' context. Discussion Nurses and patients' views were opposed, questioning the authenticity of the relationship. Implications for Practice Nurses should be aware of the patients' lack of faith in the TR to ensure that they are sensitive to patients' behaviours that may falsely suggest that a relationship is established. Further studies should explore ways to alleviate the burden of the management of ITOs on nurses and allow for a trusting relationship to be build.

Harnessing the functional diversity of plant cystatins to design inhibitor variants highly active against herbivorous arthropod digestive proteases.

Protein engineering approaches have been proposed to improve the inhibitory properties of plant cystatins against herbivorous arthropod digestive proteases, generally involving the site-directed mutagenesis of functionally relevant amino acids or the selection of improved inhibitor variants by phage display approaches. Here, we propose a novel approach where the function-related structural elements of a cystatin are substituted by the corresponding elements of an alternative cystatin. Inhibitory assays were first performed with 20 representative plant cystatins and model Cys proteases, including arthropod proteases, to appreciate the extent of functional variability among the plant cystatin family. The most, and less, potent of these cystatins were then used as 'donors' of structural elements to create hybrids of tomato cystatin SlCYS8 used as a model 'recipient' inhibitor. In brief, inhibitory activities against Cys proteases strongly differed from one plant cystatin to another, with Ki (papain) values diverging by more than 30-fold and inhibitory rates against arthropod proteases varying by up to 50-fold depending on the enzymes assessed. In line with theoretical assumptions from docking models generated for different Cys protease-cystatin combinations, structural element substitutions had a strong impact on the activity of recipient cystatin SlCYS8, positive or negative depending on the basic inhibitory potency of the donor cystatin. Our data confirm the wide variety of cystatin inhibitory profiles among plant taxa. They also demonstrate the usefulness of these proteins as a pool of discrete structural elements for the design of cystatin variants with improved potency against herbivorous pest digestive Cys proteases.

STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer.

Bioenergetic perturbations driving neoplastic growth increase the production of reactive oxygen species (ROS), requiring a compensatory increase in ROS scavengers to limit oxidative stress. Intervention strategies that simultaneously induce energetic and oxidative stress therefore have therapeutic potential. Phenformin is a mitochondrial complex I inhibitor that induces bioenergetic stress. We now demonstrate that inflammatory mediators, including IFNγ and polyIC, potentiate the cytotoxicity of phenformin by inducing a parallel increase in oxidative stress through STAT1-dependent mechanisms. Indeed, STAT1 signaling downregulates NQO1, a key ROS scavenger, in many breast cancer models. Moreover, genetic ablation or pharmacological inhibition of NQO1 using ß-lapachone (an NQO1 bioactivatable drug) increases oxidative stress to selectively sensitize breast cancer models, including patient derived xenografts of HER2+ and triple negative disease, to the tumoricidal effects of phenformin. We provide evidence that therapies targeting ROS scavengers increase the anti-neoplastic efficacy of mitochondrial complex I inhibitors in breast cancer.

Coercion in psychiatric and mental health nursing: A conceptual analysis.

The use of coercion in psychiatric and mental health nursing is a major challenge, which can lead to negative consequences for nurses and patients, including rupture in the therapeutic relationship and risk of injury and trauma. The concept of coercion is complex to define and is used in different ways throughout the nursing literature. This concept is defined broadly, referring to both formal (seclusion, restraint, and forced hospitalization), informal (persuasion, threat, and inducement), and perceived coercion, without fully addressing its evolving conceptualizations and use in nursing practice. We conducted a concept analysis of coercion using Rodgers' evolutionary method to identify its antecedents, attributes, and associated consequences. We identified five main attributes of the concept: different forms of coercion; the contexts in which coercion is exercised; nurses' justification of its use; the ethical issues raised by the presence of coercion; and power dynamics. Our conceptual analysis shows the need for more nursing research in the field of coercion to achieve a better understanding of the power dynamics and ethical issues that arise in the presence of coercion.

Intégration des droits humains dans la pratique du personnel infirmier faisant usage de coercition en santé mentale : recension systématique des écrits et méta-ethnographie.

Introduction and background : The last decade has seen a steady and rising use of coercion in mental health care, as well as an increase in the number of forms it takes. The application of these measures frequently relies on the work of nurses, but few studies have analyzed the human rights issues raised by these practices.Aim : To produce a qualitative synthesis of how human rights are integrated into the practice of nurses who use coercion in mental health care.Methodology : A systematic review of qualitative scientific literature published between 2008 and 2018 was conducted and supplemented by a meta-ethnographic analysis.Results : The analysis of the forty-six selected studies revealed four distinct themes : coercion in mental health care as a socio-legal object, issues of recognition of human rights in mental health care, role conflict experienced by nurses, and the conceptualization of coercion as a necessary evil or a critical incident.Discussion and conclusion : Further research is needed to understand the specifics of the continuum of support and control that characterizes the coercive work of psychiatric nurses.

Online and Recovery-Oriented Support Groups Facilitated by Peer Support Workers in Times of COVID-19: Protocol for a Feasibility Pre-Post Study.

BACKGROUND: In times of pandemics, social distancing, isolation, and quarantine have precipitated depression, anxiety, and substance misuse. Scientific literature suggests that patients living with mental health problems or illnesses (MHPIs) who interact with peer support workers (PSWs) experience not only the empathy and connectedness that comes from similar life experiences but also feel hope in the possibility of recovery. So far, it is the effect of mental health teams or programs with PSWs that has been evaluated. OBJECTIVE: This paper presents the protocol for a web-based intervention facilitated by PSWs. The five principal research questions are whether this intervention will have an impact in terms of (Q1) personal-civic recovery and (Q2) clinical recovery, (Q3) how these recovery potentials can be impacted by the COVID-19 pandemic, (Q4) how the lived experience of persons in recovery can be mobilized to cope with such a situation, and (Q5) how sex and gender considerations can be taken into account for the pairing of PSWs with service users beyond considerations based solely on psychiatric diagnoses or specific MHPIs. This will help us assess the impact of PSWs in this setting. METHODS: PSWs will lead a typical informal peer support group within the larger context of online peer support groups, focusing on personal-civic recovery. They will be scripted with a fixed, predetermined duration (a series of 10 weekly 90-minute online workshops). There will be 2 experimental subgroups-patients diagnosed with (1) psychotic disorders (n=10) and (2) anxiety or mood disorders (n=10)-compared to a control group (n=10). Random assignment to the intervention and control arms will be conducted using a 2:1 ratio. Several instruments will be used to assess clinical recovery (eg, the Recovery Assessment Scale, the Citizenship Measure questionnaire). The COVID-19 Stress Scales will be used to assess effects in terms of clinical recovery and stress- or anxiety-related responses to COVID-19. Changes will be compared between groups from baseline to endpoint in the intervention and control groups using the Student paired sample t test. RESULTS: This pilot study was funded in March 2020. The protocol was approved on June 16, 2020, by the Research Ethics Committees of the Montreal Mental Health University Institute. Recruitment took place during the months of July and August, and results are expected in December 2020. CONCLUSIONS: Study results will provide reliable evidence on the effectiveness of a web-based intervention provided by PSWs. The investigators, alongside key decision makers and patient partners, will ensure knowledge translation throughout, and our massive open online course (MOOC), The Fundamentals of Recovery, will be updated with the evidence and new knowledge generated by this feasibility study. TRIAL REGISTRATION: ClinicalTrials.gov NCT04445324; https://clinicaltrials.gov/ct2/show/NCT04445324. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/22500.

Shedding Light on "the Hole": A Systematic Review and Meta-Analysis on Adverse Psychological Effects and Mortality Following Solitary Confinement in Correctional Settings.

OBJECTIVES: To systematically review and meta-analyze the psychological effects and mortality rate in inmates having been exposed to solitary confinement in correctional settings. METHODS: PubMed, PsycINFO, Web of Science, and Google Scholar were searched using keywords describing solitary confinement in combination with keywords for psychological or mortality outcomes. Eligible case-control studies for the systematic review met an operational definition for solitary confinement and evaluated outcomes after exposure to such confinement. Studies presenting statistical data which allowed to compute standardized mean differences for symptom scales or odds ratio for mortality were further meta-analyzed using random-effects models. RESULTS: Systematic review identified 13 studies for inclusion, with a total sample of 382,440 inmates (23% having been exposed to solitary confinement). Higher quality evidence showed solitary confinement was associated with an increase in adverse psychological effects, self-harm, and mortality, especially by suicide. Meta-analysis of five studies (n = 4,517) showed a standardized mean difference of 0.45 for general psychological symptomatology, which increased to 0.51 upon outlier exclusion. Small to moderate significant effects were observed for mood, psychotic, and hostility symptoms specifically. In addition, meta-analysis of two mortality studies (n = 243,050) showed a trend for a moderate effect for mortality by any or unnatural causes (i.e., suicide, homicide, overdose, and accidents). CONCLUSIONS: Analyses showed that solitary confinement is associated with the psychological deterioration of inmates. This effect appears to be beyond that of general incarceration or presence of prior mental illness. Thus, solitary confinement may pose significant harm for inmates. Still, further studies are required to show that exposure to SC can increase risk of post-release death. Finally, add-on treatments and alternatives to solitary confinement that could alleviate the associated psychological harm are discussed.

Three Copies of Four Interferon Receptor Genes Underlie a Mild Type I Interferonopathy in Down Syndrome.

Down syndrome (DS) is characterized by the occurrence of three copies of human chromosome 21 (HSA21). HSA21 contains a cluster of four interferon receptor (IFN-R) genes: IFNAR1, IFNAR2, IFNGR2, and IL10RB. DS patients often develop mucocutaneous infections and autoimmune diseases, mimicking patients with heterozygous gain-of-function (GOF) STAT1 mutations, which enhance cellular responses to three types of interferon (IFN). A gene dosage effect at these four loci may contribute to the infectious and autoimmune manifestations observed in individuals with DS. We report high levels of IFN-αR1, IFN-αR2, and IFN-γR2 expression on the surface of monocytes and EBV-transformed-B (EBV-B) cells from studying 45 DS patients. Total and phosphorylated STAT1 (STAT1 and pSTAT1) levels were constitutively high in unstimulated and IFN-α- and IFN-γ-stimulated monocytes from DS patients but lower than those in patients with GOF STAT1 mutations. Following stimulation with IFN-α or -γ, but not with IL-6 or IL-21, pSTAT1 and IFN-γ activation factor (GAF) DNA-binding activities were significantly higher in the EBV-B cells of DS patients than in controls. These responses resemble the dysregulated responses observed in patients with STAT1 GOF mutations. Concentrations of plasma type I IFNs were high in 12% of the DS patients tested (1.8% in the healthy controls). Levels of type I IFNs, IFN-Rs, and STAT1 were similar in DS patients with and without recurrent skin infections. We performed a genome-wide transcriptomic analysis based on principal component analysis and interferon modules on circulating monocytes. We found that DS monocytes had levels of both IFN-α- and IFN-γ-inducible ISGs intermediate to those of monocytes from healthy controls and from patients with GOF STAT1 mutations. Unlike patients with GOF STAT1 mutations, patients with DS had normal circulating Th17 counts and a high proportion of terminally differentiated CD8+ T cells with low levels of STAT1 expression. We conclude a mild interferonopathy in Down syndrome leads to an incomplete penetrance at both cellular and clinical level, which is not correlate with recurrent skin bacterial or fungal infections. The constitutive upregulation of type I and type II IFN-R, at least in monocytes of DS patients, may contribute to the autoimmune diseases observed in these individuals.

Is mental illness associated with placement into solitary confinement in correctional settings? A systematic review and meta-analysis.

The aim of this meta-analysis was to examine the association between any mental health problem and the risk of being placed into solitary confinement in correctional settings. PubMed, PsycINFO, Web of Science and Google Scholar were searched from each database's inception date to November 2019. All publications assessing both mental health problems and placement into solitary confinement in a sample of adult inmates in correctional settings were included. The meta-analysis was performed using random-effects models. Heterogeneity among study point estimates was assessed with Q statistics and quantified with I2 index. Publication bias was assessed with funnel plots. Guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed throughout. After screening 2777 potential studies, 11 studies were included amounting to a total of 163 414 inmates. Included studies comprised of a mix of mental disorders rather than a specific diagnosis per se. The odds ratio (OR) from the pooled studies was 1.62 (confidence interval (CI) = 1.21-2.15). The observed relationship remained unchanged regardless of the removal of outliers (OR = 1.63, CI = 1.47-1.80) and regardless of the adjustment of confounders (OR = 1.58, CI = 1.32-1.88). The present study shows a moderate association between any mental health problem and placement into solitary confinement within a considerable sample of inmates. As more individuals suffering from mental illness enter the correctional system, it is essential that correction officials create new safe interventions to manage these inmates and offer them proper mental health care to limit the use of solitary confinement, which may have deleterious effects.

Cystatin Activity-Based Protease Profiling to Select Protease Inhibitors Useful in Plant Protection.

Protease inhibitors of the cystatin protein superfamily show potential in plant protection for the control of herbivorous pests. Here, we describe a cystatin activity-based profiling procedure for the selection of potent cystatin candidates, using single functional variants of tomato cystatin SlCYS8 and digestive Cys proteases of the herbivore insect Colorado potato beetle as a case study. The procedure involves the capture of target Cys proteases with biotinylated versions of the cystatins, followed by the identification and quantitation of captured proteases by mass spectrometry. An example is given to illustrate usefulness of the approach as an alternative to current procedures for recombinant inhibitor selection based on in vitro assays with synthetic peptide substrates. A second example is given showing its usefulness as a tool to compare the affinity spectra of inhibitor variants toward different subsets of target protease complements.