Factors associated with a history of treatment interruption among pregnant women living with HIV in Malawi: A cross-sectional study.

INTRODUCTION: Long-term care engagement of women on antiretroviral therapy (ART) is essential to effective HIV public health measures. We sought to explore factors associated with a history of HIV treatment interruption among pregnant women living with HIV presenting to an antenatal clinic in Lilongwe, Malawi. METHODS: We performed a cross-sectional study of pregnant women living with HIV who had a history of ART interruption presenting for antenatal care. Women were categorized as either retained in HIV treatment or reinitiating care after loss-to-follow up (LTFU). To understand factors associated with treatment interruption, we surveyed socio-demographic and partner relationship characteristics. Crude and adjusted prevalence ratios (aPR) for factors associated with ART interruption were estimated using modified Poisson regression with robust variance. We additionally present patients' reasons for ART interruption. RESULTS: We enrolled 541 pregnant women living with HIV (391 retained and 150 reinitiating). The median age was 30 years (interquartile range (IQR): 25-34). Factors associated with a history of LTFU were age <30 years (aPR 1.46; 95% CI: 1.33-1.63), less than a primary school education (aPR 1.25; CI: 1.08-1.46), initiation of ART during pregnancy or breastfeeding (aPR 1.49, CI: 1.37-1.65), nondisclosure of HIV serostatus to their partner (aPR 1.39, CI: 1.24-1.58), lack of awareness of partner's HIV status (aPR 1.41, CI: 1.27-1.60), and no contraception use at conception (aPR 1.60, CI 1.40-1.98). Access to care challenges were the most common reasons reported by women for treatment interruption (e.g., relocation, transport costs, or misplacing health documentation). CONCLUSIONS: Interventions that simplify the ART clinic transfer process, facilitate partner disclosure, and provide counseling about the importance of lifelong ART beyond pregnancy and breastfeeding should be further evaluated for improving retention in ART treatment of women living with HIV in Malawi.

Probable perinatal depression and social support among women enrolled in Malawi's Option B+ Program: A longitudinal analysis.

BACKGROUND: Malawi's PMTCT Option B+ program has expanded the reach of ART services among pregnant and breastfeeding women, but retention in lifelong HIV care remains challenging. Given that depression can undermine retention, it is important to understand how depression changes over the perinatal period, varies across treatment and retention groups, and could be buffered by social support. METHODS: Data are from an observational study conducted among women enrolled in Malawi's PMTCT Option B+ program. We used multilevel generalized linear models to estimate the odds of probable depression by time, treatment and retention group, and social support. Probable depression was assessed with the Edinburgh Postnatal Depression Scale and Patient Health Questionnaire-9. RESULTS: Of 468 women, 15% reported probable depression at antenatal enrollment and prevalence differed across newly diagnosed individuals, second line therapy users, and previous defaulters (18%, 21%, 5%, p = 0.001). Odds of probable perinatal depression decreased over time (OR per month: 0.87, 95% CI: 0.82-0.92) but were higher among those newly diagnosed (OR: 3.25, 95% CI: 1.59-6.65) and on second line therapy (OR: 3.39, 95% CI: 1.44-7.99) as compared to previous defaulters. Odds of probable postpartum depression were lower for participants with high social support (OR: 0.19, 95% CI: 0.09-0.39). LIMITATIONS: Lack of diagnostic psychiatric evaluation precludes actual diagnosis of depression. CONCLUSIONS: Probable depression varied across the perinatal period and across treatment and retention groups. Social support was protective for postpartum depression among all participants. Depression screening and provision of social support should be considered in PMTCT programs.

A 1-minute blood test detects decreased immune function and increased clinical risk in COVID-19 patients.

Upon infection with SARS-CoV-2, the virus that causes COVID-19, most people will develop no or mild symptoms. However, a small percentage of the population will become severely ill, and some will succumb to death. The clinical severity of COVID-19 has a close connection to the dysregulation of the patient's immune functions. We previously developed a simple, nanoparticle-enabled blood test that can determine the humoral immune status in animals. In this study, we applied this new test to analyze the immune function in relation to disease severity in COVID-19 patients. From the testing of 153 COVID-19 patient samples and 142 negative controls, we detected a drastic decrease of humoral immunity in COVID-19 patients who developed moderate to severe symptoms, but not in patients with no or mild symptoms. The new test may be potentially used to monitor the immunity change and predict the clinical risk of patients with COVID-19.

The Interpersonal Neurobiology of Intersubjectivity.

In 1975, Colwyn Trevarthen first presented his groundbreaking explorations into the early origins of human intersubjectivity. His influential model dictates that, during intimate and playful spontaneous face-to-face protoconversations, the emotions of both the 2-3-month-old infant and mother are nonverbally communicated, perceived, mutually regulated, and intersubjectively shared. This primordial basic interpersonal interaction is expressed in synchronized rhythmic-turn-taking transactions that promote the intercoordination and awareness of positive brain states in both. In this work, I offer an interpersonal neurobiological model of Trevarthen's intersubjective protoconversations as rapid, reciprocal, bidirectional visual-facial, auditory-prosodic, and tactile-gestural right brain-to-right brain implicit nonverbal communications between the psychobiologically attuned mother and the developing infant. These co-constructed positive emotional interactions facilitate the experience-dependent maturation of the infant's right brain, which is in an early critical period of growth. I then address the central role of interpersonal synchrony in intersubjectivity, expressed in a mutual alignment or coupling between the minds and bodies of the mother and infant in face-to-face protoconversations, as well as how these right brain-to-right brain emotional transmissions generate bioenergetic positively charged interbrain synchrony within the dyad. Following this, I offer recent brain laterality research on the essential functions of the right temporoparietal junction, a central node of the social brain, in face-to-face nonverbal communications. In the next section, I describe the ongoing development of the protoconversation over the 1st year and beyond, and the co-creation of a fundamental energy-dependent, growth-promoting social emotional matrix that facilitates the emergence of the highly adaptive human functions of mutual play and mutual love. In the final section, I discuss the clinical applications of this interpersonal neurobiological model of intersubjectivity, which has a long history in the psychotherapy literature. Toward that end, I offer very recent paradigm-shifting hyperscanning research that simultaneously measures both the patient and therapist during a psychotherapeutic interaction. Using the Trevarthen's two-person intersubjective model, this research demonstrates changes in both brains of the therapeutic dyad and the critical role of nonverbal communications in an emotionally-focused psychotherapy session. These studies specifically document interbrain synchronization between the right temporoparietal junction of the patient and the right temporoparietal junction of the clinician, a right brain-to-right brain nonverbal communication system in the co-constructed therapeutic alliance. Lastly, I discuss the relationship between the affect communicating functions of the intersubjective motivational system and the affect regulating functions of the attachment motivational system.

Constituents of buriti oil (Mauritia flexuosa L.) like inhibitors of the SARS-Coronavirus main peptidase: an investigation by docking and molecular dynamics.

Statistics show alarming numbers of infected and killed in the world, caused by the Covid-19 pandemic, which still doesn't have a specific treatment and effective in combating all efforts to seek treatments and medications against this disease. Natural products are of relevant interest in the search for new drugs. Thus, Buriti oil (Mauritia flexuosa L.) is a natural product extracted from the fruit of the palm and is quite common in the legal Amazon region, Brazil. In the present work, the anti-Covid-19 biological activity of some constituents of Buriti oil was investigated using in silico methods of Molecular Docking and Molecular Dynamics Simulations. The main results of Molecular Docking revealed favorable interaction energies in the formation of the 2GTB peptidase complex (main peptidase of SARS-CoV) with the 13-cis-ß-carotene ligands (ΔGbind = -10.23Kcal mol-1), 9-cis -ß-carotene (ΔGbind = -9.82Kcal mol-1), and α-carotene (ΔGbind = -8.34Kcal mol-1). Molecular Dynamics simulations demonstrated considerable interaction for these ligands with emphasis on α-carotene. Such theoretical results encourage and enable a direction for experimental studies in vitro and in vivo, essential in the development of new drugs with enzymatic inhibitory action for Covid-19.Communicated by Ramaswamy H. Sarma.

Locally contextualizing understandings of depression, the EPDS, and PHQ-9 among a sample of postpartum women living with HIV in Malawi.

BACKGROUND: The Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire-9 (PHQ-9) are widely used depression screening tools, yet perceptions and understandings of their questions and of depression are not well defined in cross-cultural research. METHODS: 30 postpartum women living with HIV in Malawi were recruited from a cohort study and participated in in-depth cognitive interviews. Transcripts were evaluated following an inductive approach to identify common themes. RESULTS: Participants most frequently described looking sad or different than usual, self-isolation, 'thinking too much,' and anger as key symptoms of being depressed. HIV-associated stigma was commonly identified as a cause of depression. The EPDS and PHQ-9 were generally well understood but did not capture all the important symptoms of depression that women described. Participants sometimes requested clarification or rephrasing of certain EPDS and PHQ-9 questions when asked to explain the questions' meanings in their own words, and requested rephrasing more often for EPDS questions than PHQ-9 questions. Few women believed either tool was sufficient to detect depression. LIMITATIONS: Our results may not be generalizable, but are locally contextualized. Women suffering with depression may have been more or less likely to agree to the qualitative interview depending on their comfort level discussing any current depressive symptoms. CONCLUSIONS: Researchers and practitioners who use the EPDS and PHQ-9 should be aware of the tools' limitations in their context and population. New instruments may need to be developed or adaptations to existing tools made to improve accuracy of depression screening and diagnosis in different cultural contexts.

A One-Minute Blood Test to Monitor Immune Responses in COVID-19 Patients and Predict Clinical Risks of Developing Moderate to Severe Symptoms

Coronavirus disease 2019 (COVID-19) has brought enormous loss and interruption to human life and the global economy since the first outbreak reported in China between late 2019 to early 2020, and will likely remain a public health threat in the months and years to come. Upon infection with SARS-CoV-2, the virus that causes COVID-19, most people will develop no or mild symptoms, however, a small percentage of the population will become severely ill, require hospitalization, intensive care, and some succumb to death. The current knowledge of COVID-19 disease progression with worsening symptom complex implicates the critical importance of identifying patients with high clinical risk compared to those who would be at lower risk for disease control and patient management with better therapeutic output. Currently no clinical test is available that can predict risk factors and immune status change at different severity scales. The immune system plays a critical role in the defense against infectious diseases. Extensive research has found that COVID-19 patients with poor clinical outcomes differ significantly in their immune responses to the virus from those who exhibit milder symptoms. We previously developed a nanoparticle-enabled blood test that can detect the humoral immune status change in animals. In this study, we applied this new test to analyze the immune response in relation to disease severity in COVID-19 patients. From the testing of 153 COVID-19 patient samples and 142 negative controls, we detected statistically significant differences between COVID-19 patients with no or mild symptoms from those who developed moderate to severe symptoms. Mechanistic study suggests that these differences are associated with type 1 versus type 2 immune responses. We conclude that this new rapid test could potentially become a valuable clinical tool for COVID-19 patient risk stratification and management.

Uganda's experience in Ebola virus disease outbreak preparedness, 2018-2019.

BACKGROUND: Since the declaration of the 10th Ebola Virus Disease (EVD) outbreak in DRC on 1st Aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent EVD cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed EVD outbreak in the country. We describe Uganda's experience in EVD preparedness. RESULTS: On 4 August 2018, the Uganda Ministry of Health (MoH) activated the Public Health Emergency Operations Centre (PHEOC) and the National Task Force (NTF) for public health emergencies to plan, guide, and coordinate EVD preparedness in the country. The NTF selected an Incident Management Team (IMT), constituting a National Rapid Response Team (NRRT) that supported activation of the District Task Forces (DTFs) and District Rapid Response Teams (DRRTs) that jointly assessed levels of preparedness in 30 designated high-risk districts representing category 1 (20 districts) and category 2 (10 districts). The MoH, with technical guidance from the World Health Organisation (WHO), led EVD preparedness activities and worked together with other ministries and partner organisations to enhance community-based surveillance systems, develop and disseminate risk communication messages, engage communities, reinforce EVD screening and infection prevention measures at Points of Entry (PoEs) and in high-risk health facilities, construct and equip EVD isolation and treatment units, and establish coordination and procurement mechanisms. CONCLUSION: As of 31 May 2019, there was no confirmed case of EVD as Uganda has continued to make significant and verifiable progress in EVD preparedness. There is a need to sustain these efforts, not only in EVD preparedness but also across the entire spectrum of a multi-hazard framework. These efforts strengthen country capacity and compel the country to avail resources for preparedness and management of incidents at the source while effectively cutting costs of using a "fire-fighting" approach during public health emergencies.

Forging Connections in Group Psychotherapy Through Right Brain-to-Right Brain Emotional Communications. Part 1: Theoretical Models of Right Brain Therapeutic Action. Part 2: Clinical Case Analyses of Group Right Brain Regressive Enactments.

Part 1: Theoretical Models of Right Brain Therapeutic Action. The first part of this article on the central role of the right brain in group psychotherapy offers evidence-based theoretical models of therapeutic action cocreated by the group members and the group leader. It describes how recent advances in interpersonal neurobiology and neuropsychoanalysis allow for a deeper understanding of the underlying nonverbal right brain change mechanisms beneath the words in individual psychotherapy. It then expands this model to the group context, specifically focusing on the theoretical constructs of cohesion, attachment, transference-countertransference dynamics, and implicit affect regulation, all of which are right brain functions. Part 1 concludes with a discussion of the fundamental role of these right brain mechanisms in synchronized group regressions and reenactments of attachment trauma that allow for new beginnings in emotional and relational development. Part 2: Clinical Case Analyses of Group Right Brain Regressive Enactments. The second part of this article offers case examples and commentary on working with early dysregulated attachment histories and the affect blunting defense of dissociation. Clinical vignettes demonstrate how the group reenacts attachment dynamics in transient regressions into an earlier stage of preverbal development, outside of the domain of language. Such emotionally shared regressions of attachment trauma, rupture, and repair allow the group members and leader to companion each other into and out of enactments. In this manner, regulated reenactments of preverbal emotional experiences potentially allow the cohesive group to expand adaptive right brain capacities to regulate and communicate a broader range of affectively charged subjective self states, thereby cocreating new ways of being with others.

Xpert® MTB/RIF assay on formalin-fixed paraffin-embedded tissues in the diagnosis of extrapulmonary tuberculosis.

BACKGROUND: Diagnosis of extrapulmonary tuberculosis continues to be a challenge due to the complexity of the causative organism and the wide array of pathologic features seen in this infection. Xpert MTB/RIF can be used on fresh or frozen tissue specimens for diagnosis of tuberculosis with good results. However, there is little data on its use with formalin-fixed paraffin-embedded (FFPE) tissues. OBJECTIVES: The aim of this study was to demonstrate the potential utility of Xpert MTB/RIF and to compare its performance to Ziehl-Neelsen staining for the detection of Mycobacterium tuberculosis from FFPE tissues using histological features from haematoxylin and eosin staining as the gold standard. METHODS: Eighty randomly selected archival FFPE tissues exhibiting histological features of tuberculosis were included in the study. After deparaffinisation and lysis, all the tissue specimens were subjected to the Xpert® MTB/RIF assay. The outcome measures were proportions of positively identified cases by each test. RESULTS: Using histology as the gold standard, the sensitivity of Ziehl-Neelsen staining was 20.3% (95% confidence interval: 12% - 30.8%), and the sensitivity of the Xpert® MTB/RIF assay was 53.2% (95% confidence interval: 41.6% - 64.9%); the difference was statistically significant (p = 0.002). None of the cases tested positive for rifampicin resistance. CONCLUSION: With prior deparaffinisation and lysis, FFPE tissues are amenable to testing by Xpert® MTB/RIF assay. A validation study to determine the clinical utility, analytical optimisation and cost implications of this assay for FFPE tissues is recommended.

Safety and efficacy of Option B+ ART in Malawi: few severe maternal toxicity events or infant HIV infections among pregnant women initiating tenofovir/lamivudine/efavirenz.

OBJECTIVES: Malawi's Option B+ universal antiretroviral therapy (ART) program for pregnant and breastfeeding women does not include routine laboratory monitoring. We report safety outcomes of pregnant women who initiated ART through Option B+. METHODS: We analysed 12-month data from an observational cohort study on Option B+ among women newly initiating tenofovir/lamivudine/efavirenz (TDF/3TC/EFV) at a government antenatal clinic in Lilongwe, Malawi. Proportions of women engaged in care, incidence of DAIDS grade ≥ 2 laboratory toxicity, grade ≥ 3 adverse events (AEs), viral suppression (<1000 copies/mL), birth outcomes and infant HIV infections are reported. RESULTS: At ART initiation, participants (n = 299) had a median age of 26 years (IQR 22-30), median CD4 count of 352 cells/µl (IQR 231-520) and 94% were in WHO Stage 1. We noted 76 incident DAIDS Grade ≥ 2 laboratory results among 58 women, most commonly elevated liver function tests (n = 30 events) and low haemoglobin (n = 27). No women had elevated creatinine. Clinical AEs (n = 45) were predominantly infectious diseases and Grade 3. Five participants (2%) discontinued TDF/3TC/EFV due to virologic failure (3) or toxicity (2). Twelve months after ART initiation, most women were engaged in care (89%) and had HIV RNA < 1000 copies/ml (90%). 8% of pregnancies resulted in preterm birth, 9% were low birthweight (<2500 g), and 2% resulted in infant HIV infection at 6 weeks post-delivery. CONCLUSION: Most women remained on ART and were virally suppressed 12 months after starting Option B+. Few infants contracted HIV perinatally. While some women experienced adverse laboratory events, clinical symptom monitoring is likely reasonable.

OBJECTIFS: Le programme de traitement antirétroviral (ART) universel Option B+ du Malawi pour les femmes enceintes et allaitantes n'inclut pas de suivi de routine en laboratoire. Nous rapportons les résultats en matière de sécurité des femmes enceintes qui ont commencé l'ART via l'Option B+. MÉTHODES: Nous avons analysé les données sur 12 mois d'une étude observationnelle de cohorte portant sur l'Option B+ chez des femmes initiant récemment le traitement par ténofovir/lamivudine/éfavirenz (TDF/3TC/EFV) dans une clinique prénatale du gouvernement à Lilongwe, au Malawi. Les proportions des femmes engagées dans les soins, l'incidence de DAIDS de stade ≥ 2 toxicités de laboratoire, de stade ≥ 3 événements indésirables (EI), la suppression virale (<1000 copies/mL), les résultats de naissance et l'infection infantile par le VIH sont rapportés. RÉSULTATS: A l'initiation de l'ART, les participantes (n = 299) avaient un âge médian de 26 ans (IQR 22-30), taux médian de CD4: 352 cellules/µL (IQR 231-520) et 94% étaient au stade 1 de l'OMS. Nous avons noté 76 incidents DAIDS de stade ≥ 2 résultats de laboratoire chez 58 femmes, le plus souvent, élévationdes tests de la fonction hépatique (n = 30 événements) et faible taux d'hémoglobine (n = 27). Aucune femme n'avait de créatinine élevée. Les EI cliniques (n = 45) étaient principalement des maladies infectieuses et le stade 3. Cinq participantes (2%) ont arrêté TDF/3TC/EFV en raison d'un échec virologique (n=3) ou d'une toxicité (n = 2). Douze mois après l'initiation de l'ART, la plupart des femmes suivaient des soins (89%) et avaient un ARN-VIH <1000 copies/ml (90%). 8% des grossesses ont abouti à une naissance prématurée, 9% avaient un faible poids à la naissance (<2500 g) et 2% ont résulté en une infection par le VIH chez le nourrisson à6 semaines après l'accouchement. CONCLUSION: La plupart des femmes sont restées sous ART et ont connu une suppression virale12 mois après le début de l'Option B+. Peu d'enfants ont contracté le VIH pendant la période périnatale. Bien que certaines femmes aient connu des effets adversesde laboratoire, la surveillance des symptômes cliniques est probablement raisonnable.

Lithium oxide: a quantum-corrected and classical Monte Carlo study.

Extensive Monte Carlo simulations of lithium oxide, Li2O, an important material for fusion applications over a wide range of temperatures have been performed. In the low temperature range 1-500 K, quantum path-integral corrections to the enthalpy and unit cell size were determined. We show that classical Monte Carlo underestimates both these quantities and the difference between unit cell parameters with and without quantum corrections is large enough that such corrections should be included in any comparison between theory and experiment. Over the range 300-1000 K, the formation energies of Schottky and Frenkel defects are calculated and compared with those from direct free energy minimisation in the quasiharmonic approximation, which also includes quantum corrections; the Monte Carlo results highlight the onset of failure of the quasiharmonic approximation even at modest temperatures and suggest only a small variation of the defect enthalpies with temperature. Several possible diffusion mechanisms are identified. While an interstitialcy mechanism activates at around 900-1000 K, lithium vacancy migration dominates from 500 K. The estimated migration energy of the Li-vacancy jump (0.28 eV) agrees very well with the most recent NMR study. At temperatures above 1000 K, the superionic phase transition and subsequent melting are simulated and there is good agreement with available experimental data. Our simulations predict a rapid rise in the heat capacity and the thermal expansion coefficient which continues up to the melting point which leaves two interesting questions for future experimental studies: (i) whether above the superionic transition the heat capacity and the thermal expansion coefficient in antifluorite Li2O rise up to the melting point, as in our simulations, or fall, as observed in several fluorites, and (ii) the subsequent change in the heat capacity during melting.

Probable antenatal depression at antiretroviral initiation and postpartum viral suppression and engagement in care.

OBJECTIVE: To estimate the association of probable antenatal depression with postpartum HIV care engagement among pregnant women in Malawi. DESIGN: We conducted a prospective cohort study of 299 women who were initiating antiretroviral therapy (ART) through Option B+ at a government antenatal clinic in Malawi. METHODS: Probable antenatal depression was assessed on the day of ART initiation with the validated Chichewa version of the Edinburgh Postnatal Depression Scale (EPDS). We estimated crude and adjusted risk differences (RD, aRD) of visit attendance and prevalence differences (PD, aPD) of viral suppression through 12 months post-ART initiation comparing women with versus without probable antenatal depression. RESULTS: One in 10 women had probable antenatal depression. Most women were engaged in care through 12 months post-ART initiation: 85% attended all scheduled ART visits, and 81% were in care and virally suppressed. Women with and without probable antenatal depression had a comparable probability of attending all scheduled visits (RD: -0.02; 95% CI -0.16 to 0.12; aRD: -0.04; 95% CI -0.18 to 0.10), and of viral suppression (PD: -0.02; 95% CI -0.17 to 0.13; aPD: -0.01; 95% CI -0.17 to 0.15) in crude and adjusted analyses. CONCLUSION: Probable antenatal depression was not associated with engagement in HIV care through 12 months post-ART initiation. In a population with high HIV care engagement, antenatal depression may not impair HIV-related outcomes.

Occupational Health Survey of Cosmetologists in Minnesota.

Cosmetologists face a variety of occupational health and safety challenges. To gather information on respiratory issues related to work as a cosmetologist, licensed cosmetologists were invited by e-mail to participate in a short online survey. The survey collected demographic data, work history, respiratory symptoms, product usage, and health and safety training. Results revealed that while 57% of cosmetologists reported having received training on customer or consumer safety, only 10.5% had received training on worker health such as work-related asthma and/or breathing issues. Respiratory symptoms were reported by 46% of respondents. Length of employment and the use of glues or adhesives were associated with a diagnosis of asthma.

ALL OUR SONS: THE DEVELOPMENTAL NEUROBIOLOGY AND NEUROENDOCRINOLOGY OF BOYS AT RISK.

Why are boys at risk? To address this question, I use the perspective of regulation theory to offer a model of the deeper psychoneurobiological mechanisms that underlie the vulnerability of the developing male. The central thesis of this work dictates that significant gender differences are seen between male and female social and emotional functions in the earliest stages of development, and that these result from not only differences in sex hormones and social experiences but also in rates of male and female brain maturation, specifically in the early developing right brain. I present interdisciplinary research which indicates that the stress-regulating circuits of the male brain mature more slowly than those of the female in the prenatal, perinatal, and postnatal critical periods, and that this differential structural maturation is reflected in normal gender differences in right-brain attachment functions. Due to this maturational delay, developing males also are more vulnerable over a longer period of time to stressors in the social environment (attachment trauma) and toxins in the physical environment (endocrine disruptors) that negatively impact right-brain development. In terms of differences in gender-related psychopathology, I describe the early developmental neuroendocrinological and neurobiological mechanisms that are involved in the increased vulnerability of males to autism, early onset schizophrenia, attention deficit hyperactivity disorder, and conduct disorders as well as the epigenetic mechanisms that can account for the recent widespread increase of these disorders in U.S. culture. I also offer a clinical formulation of early assessments of boys at risk, discuss the impact of early childcare on male psychopathogenesis, and end with a neurobiological model of optimal adult male socioemotional functions.

fMRI functional connectivity of the periaqueductal gray in PTSD and its dissociative subtype.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with hyperarousal and active fight or flight defensive responses. By contrast, the dissociative subtype of PTSD, characterized by depersonalization and derealization symptoms, is frequently accompanied by additional passive or submissive defensive responses associated with autonomic blunting. Here, the periaqueductal gray (PAG) plays a central role in defensive responses, where the dorsolateral (DL-PAG) and ventrolateral PAG (VL-PAG) are thought to mediate active and passive defensive responses, respectively. METHODS: We examined PAG subregion (dorsolateral and ventrolateral) resting-state functional connectivity in three groups: PTSD patients without the dissociative subtype (n = 60); PTSD patients with the dissociative subtype (n = 37); and healthy controls (n = 40) using a seed-based approach via PickAtlas and SPM12. RESULTS: All PTSD patients showed extensive DL- and VL-PAG functional connectivity at rest with areas associated with emotional reactivity and defensive action as compared to controls (n = 40). Although all PTSD patients demonstrated DL-PAG functional connectivity with areas associated with initiation of active coping strategies and hyperarousal (e.g., dorsal anterior cingulate; anterior insula), only dissociative PTSD patients exhibited greater VL-PAG functional connectivity with brain regions linked to passive coping strategies and increased levels of depersonalization (e.g., temporoparietal junction; rolandic operculum). CONCLUSIONS: These findings suggest greater defensive posturing in PTSD patients even at rest and demonstrate that those with the dissociative subtype show unique patterns of PAG functional connectivity when compared to those without the subtype. Taken together, these findings represent an important first step toward identifying neural and behavioral targets for therapeutic interventions that address defensive strategies in trauma-related disorders.