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Abstract Background Leveraging Alzheimer’s disease (AD) imaging biomarkers and longitudinal cognitive data may allow us to establish evidence of cognitive resilience (CR) to AD pathology in-vivo. Here, we applied latent class mixture modeling, adjusting for sex, baseline age, and neuroimaging biomarkers of amyloid, tau and neurodegeneration, to a sample of cognitively unimpaired older adults to identify longitudinal trajectories of CR. Methods We identified 200 Harvard Aging Brain Study (HABS) participants (mean age = 71.89 years, SD = 9.41 years, 59% women) who were cognitively unimpaired at baseline with 2 or more timepoints of cognitive assessment following a single amyloid-PET, tau-PET and structural MRI. We examined latent class mixture models with longitudinal cognition as the dependent variable and time from baseline, baseline age, sex, neocortical Aβ, entorhinal tau, and adjusted hippocampal volume as independent variables. We then examined group differences in CR-related factors across the identified subgroups from a favored model. Finally, we applied our favored model to a dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI; n = 160, mean age = 73.9 years, SD = 7.6 years, 60% women). Results The favored model identified 3 latent subgroups, which we labelled as Normal (71% of HABS sample), Resilient (22.5%) and Declining (6.5%) subgroups. The Resilient subgroup exhibited higher baseline cognitive performance and a stable cognitive slope. They were differentiated from other groups by higher levels of verbal intelligence and past cognitive activity. In ADNI, this model identified a larger Normal subgroup (88.1%), a smaller Resilient subgroup (6.3%) and a Declining group (5.6%) with a lower cognitive baseline. Conclusion These findings demonstrate the value of data-driven approaches to identify longitudinal CR groups in preclinical AD. With such an approach, we identified a CR subgroup who reflected expected characteristics based on previous literature, higher levels of verbal intelligence and past cognitive activity.

Abstract Background Despite increasing evidence for the effectiveness of psychotherapy for Borderline Personality Disorder (BPD), estimates show that approximately half of those in treatment do not clinically improve or reach reliable change criteria. There are limited qualitative descriptions of treatment factors associated with non-response from the perspectives of those struggling to improve. Method Eighteen people (72.2% female, mean age 29.4 (SD = 8)) with experience of receiving psychotherapeutic treatment for BPD were interviewed to obtain their perspectives on hindering factors in treatment and what may be helpful to reduce non-response. The data in this qualitative study was analysed thematically. Results Four domains were created from the insights patients shared on non-response and what may be needed to mitigate it. The focus of Domain 1 was that therapy cannot be effective until two factors are in place. First, the patient needs sufficient safety and stability in their environment in order to face the challenges of therapy. Second, they need to be able to access therapy. Domain 2 described factors the patients themselves contribute. The themes in this domain were described as phases that need to be progressed through before therapy can be effective. These phases were ceasing denial that help is warranted and deserved, taking responsibility for behaviours that contribute to unwellness, and committing to the hard work that is required for change. Domain 3 described how the lack of a safe alliance and ruptures in the safety of the relationship with the therapist can contribute to non-response. Domain 4 was comprised of factors that patients identified as supportive of moving through the barriers to response. The first theme in this domain was prioritising the safety of the therapy relationship. The second theme was giving a clear diagnosis and taking a collaborative approach in sessions. The final theme described the importance of focusing on practical goals with the patient to create tangible life changes. Conclusion This study found that non-response is complex and multifaceted. First, it is clear that systems need to be in place to support access to adequate care and foster life stability. Second, considerable effort may be needed at the engagement phase of therapy to clarify expectations. Third, attention to specific interpersonal challenges between patients and therapists is an important focus. Finally, structured work to improve relationships and vocational outcomes is indicated.

BackgroundBorderline Personality Disorder (BPD) is a chronic, debilitating, and difficult to treat condition. BPD has recently been linked to steroid hormone dysregulation and medical conditions characterized by disturbed androgen metabolism. This study aimed to investigate cortisol and testosterone levels in BPD, and changes in hormones following psychological treatment.MethodsParticipants with BPD (n = 33) completed a 12-week Dialectical Behavior Therapy group program. Pre and post salivary testosterone and cortisol were analyzed. Baseline hormones in the BPD group were compared to age-and-sex matched controls (n = 33). Non-parametric tests were utilized to investigate group differences, pre-post treatment hormone and symptom changes, and associations between symptoms and hormone levels.ResultsParticipants with BPD had significantly higher testosterone levels than controls. Mean testosterone levels in females with BPD were double that of female controls. Testosterone and cortisol levels were related, and some BPD symptoms were associated with with hormone levels. BPD symptoms reduced significantly with treatment, however pre to post hormone levels did not change.ConclusionsThis study supports an association between BPD symptoms and neuroendocrine dysfunction at baseline, however we found no reduction in hormone dysfunction post treatment. Further research into relationships between stress signaling and neuroendocrine disturbances in BPD may inform aetiological and treatment models.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12618000477224. Registered on 3 April 2018.

About 40 trans-Neptunian binaries (TNBs) have fully determined orbits with about 10 others being solved except for breaking the mirror ambiguity. Despite decades of study, almost all TNBs have only ever been analyzed with a model that assumes perfect Keplerian motion (e.g., two point masses). In reality, all TNB systems are non-Keplerian due to nonspherical shapes, possible presence of undetected system components, and/or solar perturbations. In this work, we focus on identifying candidates for detectable non-Keplerian motion based on sample of 45 well-characterized binaries. We use MultiMoon , a non-Keplerian Bayesian inference tool, to analyze published relative astrometry allowing for nonspherical shapes of each TNB system’s primary. We first reproduce the results of previous Keplerian fitting efforts with MultiMoon , which serves as a comparison for the non-Keplerian fits and confirms that these fits are not biased by the assumption of a Keplerian orbit. We unambiguously detect non-Keplerian motion in eight TNB systems across a range of primary radii, mutual orbit separations, and system masses. As a proof of concept for non-Keplerian fitting, we perform detailed fits for (66652) Borasisi-Pabu, possibly revealing a J _2 ≈ 0.44, implying Borasisi (and/or Pabu) may be a contact binary or an unresolved compact binary. However, full confirmation of this result will require new observations. This work begins the next generation of TNB analyses that go beyond the point mass assumption to provide unique and valuable information on the physical properties of TNBs with implications for their formation and evolution.

Summary: Peripheral neuropathy, which can include axonal degeneration and/or demyelination, impacts adipose tissues with obesity, diabetes, and aging. However, the presence of demyelinating neuropathy had not yet been explored in adipose. Both demyelinating neuropathies and axonopathies implicate Schwann cells (SCs), a glial support cell that myelinates axons and contributes to nerve regeneration after injury. We performed a comprehensive assessment of SCs and myelination patterns of subcutaneous white adipose tissue (scWAT) nerves, and changes across altered energy balance states. We found that mouse scWAT contains both myelinated and unmyelinated nerves and is populated by SCs, including SCs that were associated with synaptic vesicle-containing nerve terminals. BTBR ob/ob mice, a model of diabetic peripheral neuropathy, exhibited small fiber demyelinating neuropathy and alterations in SC marker gene expression in adipose that were similar to obese human adipose. These data indicate that adipose SCs regulate the plasticity of tissue nerves and become dysregulated in diabetes.

Abstract Background Pregnancy is an important time for women’s mental health and marks the foundations of the emerging bond between mother and baby. This study aimed to investigate the role of pregnancy acceptability and intendedness in maternal mental health and bonding during pregnancy. Methods Data were collected from a community sample of 116 Australian pregnant women (M = 29.54, SD = 5.31) through a series of self-report questionnaires pertaining to mental health and antenatal bonding. Results Lower pregnancy acceptability was correlated with higher depression, anxiety and total distress, lower physical and environmental quality of life and lower antenatal bonding. Women who reported their pregnancy was intended reported higher physical quality of life than those who reported their pregnancy was unintended. The relationship between total distress and antenatal bonding was moderated by women’s degree of pregnancy acceptability (low versus high). For women with low acceptability, higher distress was associated with lower bonding, but there was no such association for women with high pregnancy acceptability. The moderation model examining associations between distress and pregnancy acceptability explained 15% of the variance in antenatal bonding scores. Conclusion Consideration of women’s appraisal of their pregnancy acceptability may provide a valuable framework for identifying individuals who may be at risk for mental health and bonding difficulties.

Historically, middle grade schools doled out the harshest and most exclusionary discipline to adolescent African American males. African American males were routed along school to prison pathways at rates higher than African American females and their peers from other racial backgrounds. National conversations about exclusionary discipline practices and the school-to-prison pipeline have focused primarily on African American males. More recently, however, African American girls experience exclusionary discipline practices and school-to-prison pathways at rates that, in some cases, exceed African American males. Consequently, national conversations can no longer be single-gendered. African American girls must also be central to dialogues on school discipline and the school-to-prison pipeline. This paper shines klieg lights on middle grade African American girls' subjection to exclusionary school discipline, school-to-prison pipelines, and negative and stereotypical perceptions. Lastly, this author draws from the literature and her experiences working with middle grade African American girls with multiple school suspensions. She concludes the discussion with culturally responsive recommendations for equitable school discipline practices.

Abstract Background Pathological narcissism is a severe mental health condition that includes disturbances in interpersonal functioning. Interpersonal difficulties by those affected include aggressive, domineering, cold and coercive behaviours which often result in strong negative reactions from others. We sought to examine the moment-to-moment patterns that emerge within close relationships between intimate partners and family members. Methods Participants (N = 15) were romantic partners (73.3%) and family members (26.6%) in a close and long-term relationship (+ 10 years) with an individual with pathological narcissism. Participants told verbatim relationship narratives involving five narrative interactions with their relative with pathological narcissism and five narrative interactions with others. Transcripts were coded using the using Core Conflictual Relationship Theme method. Participants also completed three versions of the Relationship Questionnaire, reporting on 1. their relationship style ‘in general’, 2. their relationship style ‘with their relative’ and 3. the relationship style of their relative. Results A total of 133 relationship episodes were analysed, comprising 783 components (wishes, responses of others and responses of self). While the identified wishes (e.g., for love, for support) were consistent between relative and non-relative narratives, there was significantly higher disharmony and lower harmony in narratives involving relatives with pathological narcissism. Described disharmony in these relationships involved the relative’s rejecting, subjugating and attacking behaviours, and participants rejecting and withdrawing behaviours. There was a prominent deactivation of participants attachment system when interacting with their relative with pathological narcissism, endorsing predominately dismissing relationship styles. Individuals with pathological narcissism were similarly rated as predominately dismissing. Conclusions Together, these results reflect the cycles of interpersonal dysfunction for individuals with pathological narcissism and their partners and family members. Treatment implications point to the risk of therapists withdrawing and dismissing a patient with high pathological narcissism in the countertransference. Strategies to monitor and manage these core relational themes in treatment remain a challenge.

Abstract Introduction Tenofovir alafenamide (TAF) is approved for paediatric use in fixed‐dose combination tablets, but efficacy and safety data in children are limited. We conducted a systematic review on the efficacy/effectiveness and safety of TAF in infants, children and adolescents living with HIV. Methods We searched MEDLINE, Embase, the Cochrane Library, clinical trial registries, reference lists and relevant conferences to identify literature published January 2009–March 2021. We included clinical trials and observational studies assessing the efficacy/effectiveness or safety of TAF through ≥6 months of treatment in participants aged 0–19 years. Results and discussion Overall 3626 abstracts and 371 full papers were screened. Four single‐arm, innovator‐funded trials (341 participants) and a pooled analysis of those trials were identified. All four trials included treatment‐experienced and virally suppressed children or adolescents. One trial also included treatment‐naïve adolescents with baseline viral load >1000 copies/ml. The risk of bias was rated as low in one study and unclear in the other three owing to missing data on study design (all conference presentations). At 48 weeks, 92% (46/50) of treatment‐naïve participants were virally suppressed (one trial). Among treatment‐experienced participants with viral load at 48 weeks, 214 of 224 participants were virally suppressed. Across the studies, one grade 3/4 adverse event was considered drug‐related (intermediate uveitis). There were three discontinuations for adverse events (grade 2 anxiety and insomnia, grade 1 iridocyclitis [drug‐related] and grade 1 pulmonary tuberculosis [unrelated to treatment]). One accidental death occurred across the four studies. In the pooled analysis of 223 participants, the median change in bone mineral density z‐score (height‐ and age‐adjusted) from baseline to 48 weeks was −0.12 (interquartile range [IQR] −0.46, 0.17) to 0.05 (IQR not reported) for spine, and −0.09 (IQR −0.33, 0.07) to 0.09 (IQR not reported) for total body less head. Weight‐for‐age z‐scores increased by 0.25 from baseline to 48 weeks. Conclusions Four single‐arm trials were identified in this systematic review, with initial evidence suggesting good viral suppression and no obvious safety concerns in children and adolescents on TAF‐containing regimens over 24–48 weeks. However, further comparative and longer‐term safety data are needed in children and adolescents, including on weight and metabolic changes.

This longitudinal cohort study aimed to determine whether circulating neurofilaments (NFs) can monitor response to molecular therapies in newborns with spinal muscular atrophy (SMA; NCT02831296). We applied a mixed-effect model to examine differences in serum NF levels among healthy control infants (n = 13), untreated SMA infants (n = 68), and SMA infants who received the genetic therapies nusinersen and/or onasemnogene abeparvovec (n = 22). Increased NF levels were inversely associated with SMN2 copy number. SMA infants treated with either nusinersen or onasemnogene abeparvovec achieved important motor milestones not observed in the untreated cohort. NF levels declined more rapidly in the nusinersen cohort as compared with the untreated cohort. Unexpectedly, those receiving onasemnogene abeparvovec monotherapy showed a significant rise in NF levels regardless of SMN2 copy number. In contrast, symptomatic SMA infants who received nusinersen, followed by onasemnogene abeparvovec within a short interval after, did not show an elevation in NF levels. While NF cannot be used as the single marker to predict outcomes, the elevated NF levels observed with onasemnogene abeparvovec and its absence in infants treated first with nusinersen may indicate a protective effect of co-therapy during a critical period of vulnerability to acute denervation.

Abstract Introduction Globally about 1.7 million children were living with HIV in 2020. Two integrase strand transfer inhibitors, dolutegravir and raltegravir, are increasingly used in children. We conducted a systematic review to assess the effectiveness and safety of dolutegravir and raltegravir in children and adolescents living with HIV, aged 0–19 years. Methods Sources included MEDLINE, Embase, the Cochrane Library, clinical trial registries, abstracts from key conferences and reference list searching. Observational studies and clinical trials published January 2009–March 2021 were eligible. Outcomes included efficacy/effectiveness (CD4 counts and viral load) and/or safety outcomes (mortality, grade 3/4 adverse events and treatment discontinuation) through 6 months or more post‐treatment initiation. Risk of bias was assessed using previously published tools appropriate for the study design. Narrative syntheses were conducted. Results and discussion In total, 3626 abstracts and 371 papers were screened. Eleven studies, including 2330 children/adolescents, reported data on dolutegravir: one randomized controlled trial (RCT; low risk of bias), one single‐arm trial (unclear risk of bias) and nine cohort studies (three low risk of bias, two unclear risk and four high risk). Ten studies, including 649 children/adolescents receiving raltegravir, were identified: one RCT (low risk of bias), one single‐arm trial (low risk of bias) and eight cohort studies (four low risk of bias, three unclear risk and one high risk). Viral suppression levels in children/adolescents at 12 months were high (>70%) in most studies assessing dolutegravir (mostly second‐ or subsequent‐line, or mixed treatment lines), and varied from 42% (5/12) to 83% (44/53) at 12 months in studies assessing raltegravir (mostly second‐ or subsequent‐line). Across all studies assessing dolutegravir or raltegravir, grade 3/4 adverse events (clinical and/or laboratory) were reported in 0–50% of subjects, few resulted in discontinuation, few were drug related and no deaths were attributed to either drug. Conclusions These reassuring findings suggest that dolutegravir and raltegravir are effective and safe as preferred regimens in children and adolescents living with HIV. With the rollout of dolutegravir in paediatric populations already underway, it is critical that data are collected on safety and effectiveness in infants, children and adolescents, including on longer‐term outcomes, such as weight and metabolic changes.

Respiratory viruses such as influenza do not typically cause viremia; however, SARS-CoV-2 has been detected in the blood of COVID-19 patients with mild and severe symptoms. Detection of SARS-CoV-2 in blood raises questions about its role in pathogenesis as well as transfusion safety concerns. Blood donor reports of symptoms or a diagnosis of COVID-19 after donation (post-donation information, PDI) preceded or coincided with increased general population COVID-19 mortality. Plasma samples from 2,250 blood donors who reported possible COVID-19–related PDI were tested for the presence of SARS-CoV-2 RNA. Detection of RNAemia peaked at 9%–15% of PDI donors in late 2020 to early 2021 and fell to approximately 4% after implementation of widespread vaccination in the population. RNAemic donors were 1.2- to 1.4-fold more likely to report cough or shortness of breath and 1.8-fold more likely to report change in taste or smell compared with infected donors without detectable RNAemia. No infectious virus was detected in plasma from RNAemic donors; inoculation of permissive cell lines produced less than 0.7–7 plaque-forming units (PFU)/mL and in susceptible mice less than 100 PFU/mL in RNA-positive plasma based on limits of detection in these models. These findings suggest that blood transfusions are highly unlikely to transmit SARS-CoV-2 infection.

Case summary An 8-year-old domestic longhair cat was evaluated for a right ventral subcutaneous cervical mass. Serial bloodwork and contrast-enhanced cranial and thoracic CT initially lacked ethmoturbinate lysis and showed a progressive, vascularized, right ventral cervical mass involving local lymph nodes. The mass was removed surgically on two occasions. Histopathology and fungal culture were diagnostic for a recurring sclerosing fungal granuloma and pyogranulomatous and eosinophilic lymphadenitis, consistent with Aspergillus species. The cat was treated with oral itraconazole; however, owing to the owner’s non-compliance in administering the medication and disease progression, the cat was humanely euthanized 3 years after diagnosis. Relevance and novel information The development of a cervical subcutaneous fungal granuloma of Aspergillus species in a domestic longhair cat before obvious maxillary, orbital or ethmoturbinate lysis on initial diagnostics is rare and suggests an early onset of lymphatic or hematogenous spread from a suspected nidus of infection within the sinonasal cavity.

Abstract Background Chronic feelings of emptiness are significant in the lives of people with Borderline Personality Disorder (BPD). Feelings of emptiness have been linked to impulsivity, self-harm, suicidal behaviour and impaired psychosocial function. This study aimed to understand the experience of chronic emptiness, the cognitions, emotions and behaviours linked to emptiness, and clarify the differences between chronic emptiness and hopelessness, loneliness and depression. Methods This study interviewed people (n = 15) with BPD and used a template analysis qualitative approach to understand their experiences of chronic feelings of emptiness. Results Chronic feelings of emptiness were experienced as a feeling of disconnection from both self and others, and a sense of numbness and nothingness which was frequent and reduced functional capacity. Feelings of purposelessness and unfulfillment were closely associated with emptiness, and most participants experienced emptiness as distressing. Responses to feelings of emptiness varied, with participants largely engaging in either impulsive strategies to tolerate feelings of emptiness or distracting by using adaptive behaviours. Most participants distinguished chronic feelings of emptiness from loneliness, hopelessness, dissociation, and depression. Conclusions Feelings of chronic emptiness are an important and challenging symptom of BPD which require clinical intervention. Strengthening identity, sense of purpose and vocational and relationship functioning may reduce the intensity of emptiness.

Abstract Background Reducing substance use in youth is a global health priority. We compared two cohorts from the same 12-week residential substance use disorder (SUD) facility over a 10 year period: Cohort A (2008–2009) and Cohort B (2018–2020). The essential components of the program remained the same with the primary treatment being dialectical behaviour therapy (DBT) plus residential milieu. Methods Young people in the current Cohort B (N = 100) versus historical Cohort A (N = 102) had a similar ratio of males (74 vs. 70%) but were slightly older (mean 20.6 vs. 19.5 years). Linear mixed models were used to model outcome measures (global psychiatric symptoms, substance use severity, and quality of life) longitudinally up to 12 months later. Results Baseline to end-of-treatment comparisons showed that the current Cohort B had overall higher levels of global psychiatric symptoms (d = 0.70), but both groups reduced psychiatric symptoms (Cohort A: d = 1.05; Cohort B: d = 0.61), and had comparable increases in confidence to resist substance use (d = 0.95). Longitudinal data from the current Cohort B showed significant decreases in substance use severity from baseline to 6-month follow-up (d = 1.83), which were sustained at 12-month follow-up (d = 0.94), and increases in quality of life from baseline to end-of-treatment (d = 0.83). Conclusions We demonstrate how DBT plus milieu residential care for young people continues to show positive effects in a 10-year comparison. However, youth seeking treatment today compared to 10 years ago evidenced higher acuity of psychiatric symptoms reinforcing the importance of continuous improvement of psychological treatments. Trial registration Australian New Zealand Clinical Trials Registry: trial ID ACTRN12618000866202 , retrospectively registered on 22/05/2018, .

Abstract Background Borderline personality disorder (BPD) is a high prevalence and serious mental health disorder that has historically challenged the finite resources of health services. Despite empirical evidence supporting structured psychological therapy as the first line of treatment, there remains significant barriers in providing timely access to evidence-based treatment for this population. The primary aim of this study is to evaluate the effectiveness of providing a stepped-care structured psychological group treatment to individuals with BPD within local mental health services. The secondary aims of the study are to identify the variables that predict the need to step up or down in care and the effectiveness of treatment on psychosocial functioning. Methods Participants seeking treatment at two community mental health services will be invited to participate. Randomised controlled trial assignment will be to either (i) group skills treatment or (ii) treatment as usual. Group treatment will be offered via a stepped-care pathway with participants initially attending a 12-week group with the option of a subsequent 16-week group. The criteria for inclusion in continuing treatment includes meeting > 4 BPD diagnostic criteria or severity on GAF (< 65) at the completion of the 12-week group. Data will be collected at baseline and at five follow-up time points over a 12-month period. Discussion This pragmatic trial will provide valuable information regarding the effectiveness of a progressive stepped-care group treatment for individuals with BPD in the real-world setting of a community mental health service. It will further the current understanding of variables that predict treatment dose and duration. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12618000477224 . Registered on 3 April 2018

Peripheral nerves allow a bidirectional communication between brain and adipose tissues, and many studies have clearly demonstrated that a loss of the adipose nerve supply results in tissue dysfunction and metabolic dysregulation. Neuroimmune cells closely associate with nerves in many tissues, including subcutaneous white adipose tissue (scWAT). However, in scWAT, their functions beyond degrading norepinephrine in an obese state remain largely unexplored. We previously reported that a myeloid-lineage knockout (KO) of brain-derived neurotrophic factor (BDNF) resulted in decreased innervation of scWAT, accompanied by an inability to brown scWAT after cold stimulation, and increased adiposity after a high-fat diet. These data underscored that adipose tissue neuroimmune cells support the peripheral nerve supply to adipose and impact the tissue’s metabolic functions. We also reported that a subset of myeloid-lineage monocyte/macrophages (Ly6c+CCR2+Cx3cr1+) is recruited to scWAT in response to cold, a process known to increase neurite density in adipose and promote metabolically healthy processes. These cold-induced neuroimmune cells (CINCs) also expressed BDNF. Here we performed RNAseq on CINCs from cold-exposed and room temperature-housed mice, which revealed a striking and coordinated differential expression of numerous genes involved in neuronal function, including neurotrophin signaling and axonal guidance, further supporting that CINCs fulfill a nerve-supporting role in adipose. The increased expression of leukocyte transendothelial migration genes in cold-stimulated CINCs also confirms prior evidence that they are recruited to scWAT and are not tissue resident. We now provide whole-depot imaging of scWAT from LysM-BDNF KO mice, revealing a striking reduction of innervation across the depot fitting with their reduced energy expenditure phenotype. By contrast, Cx3cr1-BDNF KO mice (a macrophage subset of LysM+ cells) exhibited increased thermogenesis and energy expenditure, with compensatory increased food intake and no change in adiposity or body weight. While these KO mice also exhibit a significantly reduced innervation of scWAT, especially around the subiliac lymph node, they displayed an increase in small fiber sympathetic neurite branching, which may underlie their increased thermogenesis. We propose a homeostatic role of scWAT myeloid-lineage neuroimmune cells together in nerve maintenance and neuro-adipose regulation of energy expenditure.

Abstract Background Innervation of adipose tissue is essential for the proper function of this critical metabolic organ. Numerous surgical and chemical denervation studies have demonstrated how maintenance of brain-adipose communication through both sympathetic efferent and sensory afferent nerves helps regulate adipocyte size, cell number, lipolysis, and ‘browning’ of white adipose tissue. Neurotrophic factors are growth factors that promote neuron survival, regeneration, and plasticity, including neurite outgrowth and synapse formation. Peripheral immune cells have been shown to be a source of neurotrophic factors in humans and mice. Although a number of immune cells reside in the adipose stromal vascular fraction (SVF), it has remained unclear what roles they play in adipose innervation. We previously demonstrated that adipose SVF secretes brain derived neurotrophic factor (BDNF). Methods We now show that deletion of this neurotrophic factor from the myeloid lineage of immune cells led to a ‘genetic denervation’ of inguinal subcutaneous white adipose tissue (scWAT), thereby causing decreased energy expenditure, increased adipose mass, and a blunted UCP1 response to cold stimulation. Results We and others have previously shown that noradrenergic stimulation via cold exposure increases adipose innervation in the inguinal depot. Here we have identified a subset of myeloid cells that home to scWAT upon cold exposure and are Ly6C+ CCR2+ Cx3CR1+ monocytes/macrophages that express noradrenergic receptors and BDNF. This subset of myeloid lineage cells also clearly interacted with peripheral nerves in the scWAT and were therefore considered neuroimmune cells. Conclusions We propose that these myeloid lineage, cold induced neuroimmune cells (CINCs) are key players in maintaining adipose innervation as well as promoting adipose nerve remodeling under noradrenergic stimulation, such as cold exposure.

Objective: Increasing the mass and/or activity of brown adipose tissue (BAT) is one promising avenue for treating obesity and related metabolic conditions, given that BAT has a high potential for energy expenditure and is capable of improving glucose and lipid homeostasis. BAT occurs either in discrete “classical” depots, or interspersed in white adipose tissue (WAT), termed “inducible/recruitable” BAT, or ‘beige/brite’ adipocytes. We and others have demonstrated that bone morphogenetic protein 7 (BMP7) induces brown adipogenesis in committed and uncommitted progenitor cells, resulting in increased energy expenditure and reduced weight gain in mice. BMP7 is therefore a reliable growth factor to induce browning of WAT.Methods: In this study, we sought to deliver BMP7 specifically to subcutaneous (sc)WAT in order to induce tissue-resident progenitor cells to differentiate into energy-expending recruitable brown adipocytes, without off-target effects like bone formation, which can occur when BMPs are in the presence of bone progenitor cells (outside of WAT). BMP7 delivery directly to WAT may also promote tissue innervation, or directly activate mitochondrial activity in brown adipocytes, as we have demonstrated previously. We utilized silk protein in the form of an injectable hydrogel carrying BMP7. Silk scaffolds are useful for in vivo delivery of substances due to favorable material properties, including controlled release of therapeutic proteins in an active form, biocompatibility with minimal immunogenic response, and prior FDA approval for some medical materials. For this study, the silk was engineered to meet desirable release kinetics for BMP7 in order to mimic our prior in vitro brown adipocyte differentiation studies. Fluorescently-labeled silk hydrogel loaded with BMP7 was directly injected into WAT through the skin and monitored by non-invasive in vivo whole body imaging, including in UCP1-luciferase reporter mice, thereby enabling an approach that is translatable to humans.Results: Injection of the BMP7-loaded silk hydrogels into the subcutaneous WAT of mice resulted in “browning”, including the development of multilocular, uncoupling protein 1 (UCP1)-positive brown adipocytes, and an increase in whole-body energy expenditure and skin temperature. In diet-induced obese mice, BMP7-loaded silk delivery to subcutaneous WAT resulted in less weight gain, reduced circulating glucose and lower respiratory exchange ratio (RER).Conclusions: In summary, BMP7 delivery via silk scaffolds directly into scWAT is a novel translational approach to increase browning and energy expenditure, and represents a potential therapeutic avenue for delivering substances directly to adipose depots in pursuit of metabolic treatments.

BackgroundAtazanavir/ritonavir is recommended as a preferred second-line antiretroviral regimen in children older than 3 months, alternatively to lopinavir/ritonavir. We performed a systematic review to assess safety and effectiveness of atazanavir use in children and adolescents.MethodsWe searched observational studies and clinical trials on Web of Science, Embase and Cochrane CENTRAL database between 2009/01/01 and 2020/10/01; as well as grey literature. We extracted safety (adverse events, grade 3 or 4 adverse events, treatment discontinuation) and effectiveness (CD4 cell counts and HIV viral load) outcomes. We estimated weighted summary pooled incidence with corresponding 95% confidence intervals.ResultsOut of the 1,085 records screened, we included five studies (one comparative cohort, three single phase 2-3 trial arms, one retrospective cohort) reporting 975 children and adolescents, of whom 56% (544) received atazanavir. Three studies reported all-cause treatment discontinuation rates, yielding a pooled incidence of 19% [15–22] at 12 months. The comparative cohort compared atazanavir to darunavir, with few grade 3–4 adverse events, except transient hyperbilirubinemia, occurring in half (92/188) of the atazanavir patients. No death occurred (two studies reporting). Four studies described increased CD4 cell counts and decreased HIV viral load at 6 or 12 months.ConclusionFew safety and effectiveness data were available for children and adolescents exposed to atazanavir. Transient grade 3–4 hyperbilirubinemia was the main adverse outcome reported. Immune and viral responses were descriptive. The use of atazanavir/ritonavir in children and adolescents needs further investigation, but remains a suitable option for a preferred second-line antiretroviral regimen.PROSPERO numberCRD42022309230

Summary: Here we provide a clearing-free protocol for processing intact, whole mount subcutaneous white adipose tissue (scWAT) for immunofluorescence as an alternative to current clearing-based approaches. We use a combination of Z-depth reduction and autofluorescence quenching techniques to fluorescently label, image, and quantify adipose tissue innervation effectively throughout intact mouse tissues without the need for optical clearing or light sheet microscopy. This protocol has been optimized and validated for adipose neurovascular labeling.For complete details on the use and execution of this protocol, please refer to Willows et al. (2021).

Abstract Background Peer support is a recovery oriented approach where consumers and carers are introduced to people with lived experience of the disorder who have recovered. Paid roles within health services for such consumer peer workers and carer peer workers (or ‘specialists’) are increasingly common. To date specific studies on such peer support for consumers with borderline personality disorder (BPD) and their carers has not been conducted. Methods This qualitative study used interviews to explore perceptions and models of peer support for BPD from the perspectives of 12 consumers, 12 carers, and 12 mental health professionals. Participant responses were analyzed using reflexive thematic analysis within a phenomenological methodology. Results All groups described how consumer peer workers may provide hope, connection, and validation to a consumer’s lived experience. Offering both traditional mental health treatment plus peer support, and giving consumers choice regarding a consumer peer worker was welcomed. Differences in opinion were found regarding the consumer peer worker’s role in relation to the mental health team, including whether consumer peer workers should access medical records. Perspectives differed regarding the consumer peer worker and carer peer worker positions, highlighting potential role confusion. Carers discussed the value of receiving support from carer peer workers and consumer peer workers. Mental health professionals described how consumer peer workers can experience workplace stigma and problems with boundary setting, and acknowledged a need for peer workers to be valued by having a duty of care and confidentiality code to follow and be offered supervision. Conclusions Two models of peer support for BPD emerged: an integrated model where consumer peer workers work within the mental health team, and a complementary model where consumer peer workers are separate from the mental health team. Based on these findings we provide recommendations for services to help support such peer work for consumers with BPD and their carers.

Abstract Background Despite effective treatments for personality disorders being developed, consumers and carers often report negative experiences of mental health services, including challenges accessing these treatments. Methods This qualitative study used separate focus groups to compare the unique perspectives of consumer and carers, and to investigate how to improve services for individuals with personality disorders. Reflexive thematic analysis was used to analyze the data. Results Both consumers and carers (N = 15) discussed the value of providing appropriate information to consumers when they are diagnosed with personality disorder. Consumers and carers described the importance of creating a safe environment for consumers when they present to the emergency department. Both groups discussed experiencing positive and negative treatment from mental health professionals, and suggested that professionals should be trained to understand personality disorder. Limited accessibility and quality of services, and offering peer support to consumers were also described by consumers and carers. Consumers and carers also had perspectives which were unique to their group. Consumers identified the importance of psychological treatment, having a strong therapeutic relationship with a mental health professional, and the benefit of long term psychotherapy with the same professional. Broadening the scope of psychotherapies including creative, animal-assisted, and physical therapies was recommended by consumers. Carers described the importance of assessing for personality disorder and intervening early. Involvement in the assessment, diagnosis, and intervention process was important to carers. The desire to be recognized and supported by mental health professionals was discussed by carers. Conclusions This research contributes to the concern that consumers with personality disorder and their carers experience stigma and low quality care within mental health services. In line with these findings, we recommend guidelines for health professionals who work with consumers with personality disorder.

Abstract Background Research into the personality trait of narcissism have advanced further understanding of the pathological concomitants of grandiosity, vulnerability and interpersonal antagonism. Recent research has established some of the interpersonal impacts on others from being in a close relationship with someone having such traits of pathological narcissism, but no qualitative studies exist. Individuals with pathological narcissism express many of their difficulties of identity and emotion regulation within the context of significant interpersonal relationships thus studying these impacts on others is warranted. Method We asked the relatives of people high in narcissistic traits (indexed by scoring above a cut-off on a narcissism screening measure) to describe their relationships (N = 436; current romantic partners [56.2%]; former romantic partners [19.7%]; family members [21.3%]). Participants were asked to describe their relative and their interactions with them. Verbatim responses were thematically analysed. Results Participants described ‘grandiosity’ in their relative: requiring admiration, showing arrogance, entitlement, envy, exploitativeness, grandiose fantasy, lack empathy, self-importance and interpersonal charm. Participants also described ‘vulnerability’ of the relative: contingent self-esteem, hypersensitivity and insecurity, affective instability, emptiness, rage, devaluation, hiding the self and victimhood. These grandiose and vulnerable characteristics were commonly reported together (69% of respondents). Participants also described perfectionistic (anankastic), vengeful (antisocial) and suspicious (paranoid) features. Instances of relatives childhood trauma, excessive religiosity and substance abuse were also described. Conclusions These findings lend support to the importance of assessing the whole dimension of the narcissistic personality, as well as associated personality patterns. On the findings reported here, the vulnerable aspect of pathological narcissism impacts others in an insidious way given the core deficits of feelings of emptiness and affective instability. These findings have clinical implications for diagnosis and treatment in that the initial spectrum of complaints may be misdiagnosed unless the complete picture is understood. Living with a person with pathological narcissism can be marked by experiencing a person who shows large fluctuations in affect, oscillating attitudes and contradictory needs.

Abstract Background Individuals with borderline personality disorder (BPD) may experience additional challenges in their parenting role, including increased stress and lower self-efficacy and satisfaction. These difficulties have been shown to impact their children, and may be implicated in the potential intergenerational transmission of personality vulnerabilities. Methods Parental stress and competence variables were examined in a cross-sectional study of 284 parents (94.72% female, M = 37.37, SD = 8.04 years), of which 69 (24.30%) met caseness for BPD criteria. We completed a multivariate analysis of variance to test how parents with ‘high BPD features’ (meeting caseness for BPD) compared to those with ‘low BPD features’ on a range of parenting and mental health variables. Multivariate linear regression modelling was then utilised to explore whether these parenting variables were associated with personality and psychological wellbeing, recalled trauma history, orientation to attachment relationships and reflective capacity. Results Individuals high in BPD features experienced more stress and lower competence in their parenting role than those low in BPD features. These parents also reported more personality vulnerabilities, poorer psychological wellbeing, recalled more traumatic experiences in their childhood, were more likely to endorse insecure attachment styles and had poorer reflective capacity. In the regression model, parenting stress and competence was associated with personality traits, general psychological wellbeing, recalled trauma history, attachment style and reflective capacity variables. Parental reflective capacity had the strongest association with parenting stress, satisfaction, efficacy, the perception of having a difficult child and a difficult parent-child relationship, and psychological wellbeing had the greatest association with parenting distress. Conclusions Parents who were able to imaginatively enter the subjective world of the child and hold the child’s mind in mind with less certainty, reported reduced parenting stress and greater parenting satisfaction and efficacy. Helping to improve personality and mental health functioning, increasing parental reflective capacity and strengthening parent-child attachment relationships, may reduce parenting stress and increase parenting competence in individuals with BPD.

Borderline Personality Disorder (BPD) is often perceived to be a female-predominant disorder in both research and clinical contexts. Although there is growing recognition of possible sex differences, the current literature remains fragmented and inconclusive. This scoping review aimed to synthesize available research evidence on potential sex differences in BPD. PsycINFO, PubMed, Scopus and Web-of-Science were searched from January 1982 to July 2022 surrounding the key concepts of sex and BPD. Data searching and screening processes followed the Joanna Briggs Institute methodology involving two independent reviewers, and a third reviewer if necessary, and identified 118 papers. Data regarding BPD symptoms, comorbid disorders, developmental factors, biological markers, and treatment were extracted. Data was summarized using the vote counting method or narrative synthesis depending on the availability of literature. Males with BPD were more likely to present externalizing symptoms (e.g., aggressiveness) and comorbid disorders (e.g., substance use), while females with BPD were more likely to present internalizing symptoms (e.g., affective instability) and comorbid disorders (e.g., mood and eating disorders). This review also revealed that substantially more research attention has been given to overall sex differences in baseline BPD symptoms and comorbid disorders. In contrast, there is a dearth of sex-related research pertaining to treatment outcomes, developmental factors, and possible biological markers of BPD. The present scoping review synthesized current studies on sex differences in BPD, with males more likely to present with externalizing symptoms in contrast to females. However, how this might change the prognosis of the disorder or lead to modifications of treatment has not been investigated. Most studies were conducted on western populations, mainly North American (55%) or European (33%), and there is a need for future research to also take into consideration genetic, cultural, and environmental concomitants. As the biological construct of 'sex' was employed in the present review, future research could also investigate the social construct 'gender'. Longitudinal research designs are needed to understand any longer-term sex influence on the course of the disorder.

Summary: Little is known about the diversity and function of adipose tissue nerves, due in part to the inability to effectively visualize the tissue’s diverse nerve subtypes and the patterns of innervation across an intact depot. The tools to image and quantify adipose tissue innervation are currently limited. Here, we present a method of tissue processing that decreases tissue thickness in the z-axis while leaving cells intact for subsequent immunostaining. This was combined with autofluorescence quenching techniques to permit intact whole tissues to be mounted on slides and imaged by confocal microscopy, with a complementary means to perform whole tissue neurite density quantification after capture of tiled z-stack images. Additionally, we demonstrate how to visualize nerve terminals (the neuro-adipose nexus) in intact blocks of adipose tissue without z-depth reduction. We have included examples of data demonstrating nerve subtypes, neurovascular interactions, label-free imaging of collagen, and nerve bundle digital cross-sections.

Abstract Background Although there is growing evidence that stepped models of care are useful for providing appropriate, person centered care, there are very few studies applied to personality disorders. A brief, four session, psychological treatment intervention for personality disorder within a whole of service stepped care model was evaluated. The intervention stepped between acute emergency crisis mental health services and longer-term outpatient treatments. Methods Study 1 used service utilization data from 191 individuals referred to the brief intervention at a single community health site in a metropolitan health service. Proportions of individuals retained across the intervention and the referral pathways accessed following the intervention were examined. Study 2 examined 67 individuals referred to the brief intervention across 4 different sites in metropolitan health services. A range of measures of symptoms and quality of life were administered at the first and last session of the intervention. Effect sizes were calculated to examine mean changes across the course of the intervention. Results Study 1 found that 84.29% of individuals referred to the intervention attended at least 1 session, 60.21% attended 2 sessions or more and 41.89% attended 3 or more sessions. 13.61% of the sample required their care to be “stepped up” within the service, whereas 29.31% were referred to other treatment providers following referral to the intervention. Study 2 found a significant reduction in borderline personality disorder symptom severity and distress following the intervention, and an increase in quality of life. The largest reduction was found for suicidal ideation (d = 1.01). Conclusions Brief psychological intervention was a useful step between acute services and longer-term treatments in this stepped model of care for personality disorder. Suicide risk and symptom severity reduced and quality of life improved, with only a small proportion of individuals requiring ongoing support from the health service following the intervention.

Abstract Background The concept of recovery in borderline personality disorder (BPD) is not well defined. Whilst clinical approaches emphasise symptom reduction and functioning, consumers advocate for a holistic approach. The consumer perspective on recovery and comparisons of individuals at varying stages have been minimally explored. Method Fourteen narratives of a community sample of adult women with a self-reported diagnosis of BPD, were analysed using qualitative interpretative phenomenological analysis to understand recovery experiences. Individuals were at opposite ends of the recovery continuum (seven recovered and seven not recovered). Results Recovery in BPD occurred across three stages and involved four processes. Stages included; 1) being stuck, 2) diagnosis, and 3) improving experience. Processes included; 1) hope, 2) active engagement in the recovery journey, 3) engagement with treatment services, and 4) engaging in meaningful activities and relationships. Differences between individuals in the recovered and not recovered group were prevalent in the improving experience stage. Conclusion Recovery in BPD is a non-linear, ongoing process, facilitated by the interaction between stages and processes. Whilst clinical aspects are targets of specialist interventions, greater emphasis on fostering individual motivation, hope, engagement in relationships, activities, and treatment, may be required within clinical practice for a holistic recovery approach.

Abstract Background There is a strong interest in the concept of developmental origins of health and disease and their influence on various factors “from cradle to grave”. Despite the increasing appreciation of this lifelong legacy across the human life course, many gaps remain in the scientific understanding of mechanisms influencing these formative phases. Cross-generational susceptibility to health problems is emerging as a focus of research in the context of birth cohort studies. The primary aim of the Illawarra Born study is to make scientific discoveries associated with improving health and wellbeing across the lifespan, with a particular focus on preventable chronic diseases, especially mental health. This birth cohort study will follow and collect data from three cohorts representing different stages across the lifespan: infants, adults (parents) and older adults (grandparents). The multi-generational, cross-sectional and longitudinal design of this birth cohort study supports a focus on the contributions of genetics, environment and lifestyle on health and wellbeing. The feasibility of conducting a multi-generational longitudinal birth cohort project was conducted through a small pilot study. Methods/design The purpose of this paper is to report on the feasibility and acceptability of the research protocol for a collaborative cross-generation health study in the community and test recruitment and outcome measures for the main study. This feasibility study included pregnant women who were intending to give birth in the Illawarra-Shoalhaven region in Eastern Australia. The area includes a large, regional referral hospital, with capacity to treat specialist and complex cases. Pregnant women were asked to participate in five data collection waves beginning at 22 weeks gestation and ending with a 6-month post-partum appointment. Recruitment was then extended, via the pregnant women, to also include fathers and maternal grandmothers. Discussion This feasibility study focused on the perinatal period and collected data across three multi-disciplinary domains including mental health, diet, exposures to toxins and the role of these in maternal and infant outcomes. Forty-one families participated in extensive data collection from 22 weeks gestation to 6-months post-partum. Factors impacting on viability and feasibility including recruitment solutions provide the basis for a large-scale study.

[This corrects the article DOI: 10.1371/journal.pone.0206033.].

BackgroundBorderline Personality Disorder (BPD) is a prevalent and serious mental health condition. People can experience recovery or remission after receiving psychotherapy for BPD; however, it is estimated that about 45% of people in well conducted treatment trials do not respond adequately to current psychological treatments.AimTo further advance psychotherapies for BPD by identifying the factors that contribute to the problem of non-response.Method184 consecutive participants with BPD in community treatment were naturalistically followed up over 12 months and measures of personality and social functioning were examined. Logistic regressions were used to determine which baseline factors were associated with the likelihood of being a non-responder after 12 months of psychotherapy. After 12 months, 48.4% of participants were classed as non-responders due to a lack of reduction in BPD symptoms according to the Reliable Change Index (RCI) method.ResultsAt baseline intake, patients who endorsed an adult preoccupied attachment relationship style and increased anger were more likely to be a non-responder regarding BPD symptoms at 12 months. In addition, those with preoccupied attachment patterns in their adult relationships were more likely to be non-responders regarding general psychological distress at follow up. Higher baseline levels of paranoia and endorsement of a dismissive adult relationship style was associated with being a non-responder in regard to global functioning.ConclusionsConsistent with previous research, almost half of the sample did not achieve reliable change at 12-month follow up. A relationship style characterised by preoccupied insecurity and high anger seemed to be particularly challenging in being able to benefit from psychotherapy. This style may have affected both relationships outside, but also inside therapy, complicating treatment engagement and alliance with the therapist. Early identification and modification of treatment based on challenges from these relationship styles may be one way to improve psychotherapy outcomes for BPD.

BACKGROUND:Chronic feelings of emptiness is an under-researched symptom of borderline personality disorder (BPD), despite indications it may be central to the conceptualisation, course, and outcome of BPD treatment. This systematic review aimed to provide a comprehensive overview of chronic feelings of emptiness in BPD, identify key findings, and clarify differences between chronic feelings of emptiness and related constructs like depression, hopelessness, and loneliness. METHOD:A PRISMA guided systematic search of the literature identified empirical studies with a focus on BPD or BPD symptoms that discussed chronic feelings of emptiness or a related construct. RESULTS:Ninety-nine studies met criteria for inclusion in the review. Key findings identified there were significant difficulties in defining and measuring chronic emptiness. However, based on the studies reviewed, chronic emptiness is a sense of disconnection from both self and others. When experienced at frequent and severe levels, it is associated with low remission for people with BPD. Emptiness as a construct can be separated from hopelessness, loneliness and intolerance of aloneness, however more research is needed to explicitly investigate these experiences. Chronic emptiness may be related to depressive experiences unique to people with BPD, and was associated with self-harm, suicidality, and lower social and vocational function. CONCLUSIONS AND IMPLICATIONS:We conclude that understanding chronic feelings of emptiness is central to the experience of people with BPD and treatment focusing on connecting with self and others may help alleviate a sense of emptiness. Further research is required to provide a better understanding of the nature of chronic emptiness in BPD in order to develop ways to quantify the experience and target treatment. Systematic review registration number: CRD42018075602.

The widespread accessibility and use of the internet provides numerous opportunities for women to independently seek out pregnancy-related information and social and emotional support during the antenatal period. Given the heightened psychological vulnerability of the pregnancy period there is a critical need to examine digital media use within the context of the feelings that women have about themselves and towards their fetus. The current study examined the relationship between digital media use during pregnancy, psychological wellbeing and their maternal-fetal attachment using an online survey. Forty-eight pregnant women completed a self-report questionnaire on their reasons for using digital media, and standardised measures of self-criticism, negative affect, social quality of life (QOL), and maternal-fetal attachment. The mean age of participants was 29.4 years (SD = 5.26), with a mean of 24.3 weeks gestation (SD = 9.95). Information seeking, emotional support and social support were highly endorsed reasons for digital media use (85.42%, 66.67%, 62.5% respectively). However, digital media use was positively correlated with negative affect (p = .003) and self-criticism (p < .001). Digital media use was also negatively correlated with QOL (p = .007). There was no evidence of a relationship between digital media use and maternal-fetal attachment (p = .330). Digital environments may be an important social context within which a pregnant woman develops her own maternal identity and knowledge. There are a number of benefits and limitations of this medium for providing information and support for women during pregnancy. Enhancing the opportunities to promote pregnant women's wellbeing in this context is an important avenue for further research and practice.

Abstract Background The school environment offers an ideal opportunity for early identification and intervention for youth with self-harm and complex mental health issues, such as borderline personality disorder (BPD). Yet, class teachers often report minimal knowledge, feeling ill-equipped to respond, and experience high levels of stress when exposed to such challenges. Research is required to understand how training and development activities led by school counsellors may enhance teacher attitudes, confidence and knowledge of self-harm and complex mental health issues, such as BPD. We aimed to explore the extent that a whole of school initiative might enhance capacity for early identification and intervention. Method 18 secondary schools implemented a manualised program, Project Air Strategy for Schools. N = 400 class teachers (71.3% female, mean age 42 years) across city and rural locations were evaluated before and after program implementation on attitudes, knowledge and skills. Results Providing class teachers with additional training on complex mental health issues and associated behaviours such as self-harm was well received. Participants reported post-program improvements in their optimism (d = .35), confidence (d = .63), knowledge (d = .73) and skills (d = 0.67) in working with young people with complex mental health issues, such as BPD. Conclusions Providing school counsellor led structured approaches, to help class teachers identify and respond to youth in distress, closed identified gaps. Results indicated improvements in class teachers’ knowledge and attitudes towards self-harm and BPD. The intervention also improved the capacity of schools to plan and implement strategies to reduce the impact of mental health problems on the young person and their peers. A stay-at-school psychological care approach was fostered by enhancing partnerships between class teachers and school counsellors.

Abstract To acquire 3-D tracking data on juvenile salmonids, Juvenile Salmon Acoustic Telemetry System (JSATS) cabled hydrophone arrays were deployed in the forebays of two dams on the Snake River and at a mid-reach reservoir between the dams. The depth distributions of fish were estimated by statistical analyses performed on large 3-D tracking data sets from ~33,500 individual acoustic tagged yearling and subyearling Chinook salmon and juvenile steelhead at the two dams in 2012 and subyearling Chinook salmon at the two dams and the mid-reach reservoir in 2013. This research investigated the correlation between vertical migration behavior and passage routes. The depth distributions of fish within the forebays of the dams were significantly different from fish passing the mid-reach reservoir. Fish residing deeper in the forebay tended to pass the dam using deeper powerhouse routes. This difference in depth distributions indicated that the depth distribution of fish at the mid-reach reservoir was not related to behaviors of fish passing through certain routes of the adjacent dams. For fish that were detected deeper than 17.5 m in the forebays, the probability of powerhouse passage (i.e., turbine) increased significantly. Another important finding was the variation in depth distributions during dam passage associated with the diel period, especially the crepuscular periods.

Abstract Background Few data are available to guide biological sample collection around the time of birth for large-scale birth cohorts. We are designing a large UK birth cohort to investigate the role of infection and the developing immune system in determining future health and disease. We undertook a pilot to develop methodology for the main study, gain practical experience of collecting samples, and understand the acceptability of sample collection to women in late pregnancy. Methods Between February–July 2014, we piloted the feasibility and acceptability of collecting maternal stool, baby stool and cord blood samples from participants recruited at prolonged pregnancy and planned pre-labour caesarean section clinics at University College London Hospital. Participating women were asked to complete acceptability questionnaires. Results Overall, 265 women were approached and 171 (65%) participated, with ≥1 sample collected from 113 women or their baby (66%). Women had a mean age of 34 years, were primarily of white ethnicity (130/166, 78%), and half were nulliparous (86/169, 51%). Women undergoing planned pre-labour caesarean section were more likely than those who delivered vaginally to provide ≥1 sample (98% vs 54%), but less likely to provide maternal stool (10% vs 43%). Pre-sample questionnaires were completed by 110/171 women (64%). Most women reported feeling comfortable with samples being collected from their baby (

BackgroundAn emerging body of literature suggests there is a relationship between a pregnant woman's psychological wellbeing and the development of maternal-fetal attachment (MFA) and early postpartum bonding. The nature of this relationship is not well understood because of the limited theoretical framework surrounding the construct of MFA and variations in study methods and data collection points. In this systematic review, we synthesize the published literature to determine the nature of the relationship from the antenatal to early postnatal period and to provide recommendations for future research and clinical practice.MethodUsing the preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach, four electronic databases were searched for peer-reviewed empirical studies, published in English. Articles were considered for inclusion if data was collected on at least one domain of maternal wellbeing/mental health and MFA during pregnancy or MFA during pregnancy and the mother-infant relationship during the early postpartum period (up to 12 weeks). No date parameters were applied to the search strategy. The review was registered with PROPSERO (registration number: CRD42018096174).Results25 studies examining maternal mental health and MFA/postpartum bonding were selected for inclusion in this review. Key findings identified from the review were: a need to validate existing mental health measures or develop new measures specific for use in antenatal populations; inconsistencies in data collection points throughout pregnancy and postpartum; a lack of consensus about the construct of MFA and the way it is assessed; and a continued focus on postpartum outcomes.ConclusionScientific gaps remain in our understanding of the relationship between maternal mental health and both MFA and postpartum bonding which limit our theoretical understanding of the MFA construct. Recommendations for future research are to employ prospective longitudinal designs that span the full pregnancy and postpartum period, and for consistency in the terminology and methodology used when considering MFA. A re-focus of research attention on the theory behind MFA will allow a richer and more holistic account of the emerging relationship between mother and baby.

The difficulty in obtaining as well as maintaining weight loss, together with the impairment of metabolic control in conditions like diabetes and cardiovascular disease, may represent pathological situations of inadequate neural communication between the brain and peripheral organs and tissues. Innervation of adipose tissues by peripheral nerves provides a means of communication between the master metabolic regulator in the brain (chiefly the hypothalamus), and energy-expending and energy-storing cells in the body (primarily adipocytes). Although chemical and surgical denervation studies have clearly demonstrated how crucial adipose tissue neural innervation is for maintaining proper metabolic health, we have uncovered that adipose tissue becomes neuropathic (ie: reduction in neurites) in various conditions of metabolic dysregulation. Here, utilizing both human and mouse adipose tissues, we present evidence of adipose tissue neuropathy, or loss of proper innervation, under pathophysiological conditions such as obesity, diabetes, and aging, all of which are concomitant with insult to the adipose organ as well as metabolic dysfunction. Neuropathy is indicated by loss of nerve fiber protein expression, reduction in synaptic markers, and lower neurotrophic factor expression in adipose tissue. Aging-related adipose neuropathy particularly results in loss of innervation around the tissue vasculature, which cannot be reversed by exercise. Together with indications of neuropathy in muscle and bone, these findings underscore that peripheral neuropathy is not restricted to classic tissues like the skin of distal extremities, and that loss of innervation to adipose may trigger or exacerbate metabolic diseases. In addition, we have demonstrated stimulation of adipose tissue neural plasticity with cold exposure, which may ameliorate adipose neuropathy and be a potential therapeutic option to re-innervate adipose and restore metabolic health.

Background/objectivesMaladaptive parenting (including childhood maltreatment, abuse and neglect) has been implicated in the scientific literature exploring the aetiology of personality disorder, particularly borderline personality disorder (BPD). Our primary objective was to summarise the evidence on the relationship between parenting and personality disorder, assisting clinical decision-makers to translate this research into clinical policy and practice.MethodsWe conducted an overview of systematic reviews that assessed individuals with personality disorder pathology for experiences of maladaptive parenting, compared to psychiatric or healthy comparisons/controls, and the impact on psychopathological and relational outcomes. Systematic literature searches were conducted in Scopus, Web of Science, MEDLINE, PsycINFO, and by hand in August 2018. Methodological quality was assessed using the CASP systematic review checklist, and results were qualitatively synthesised. A pre-determined protocol was registered in Prospective Register of Systematic Reviews (PROSPERO 2019:CRD42018096177).ResultsOf the 312 identified records, 293 abstracts were screened, 36 full-text articles were retrieved and eight systematic reviews met pre-determined criteria for qualitative synthesises. The majority of studies reported outcomes related to BPD (n = 7), and study design, methodology and quality varied. Within the eight systematic reviews there were 211 primary studies, of which 140 (66.35%) met eligibility criteria for inclusion in this overview. Eligible primary studies reported on 121,895 adult, child/adolescent and parent-offspring participants, with most studies focused on borderline personality pathology (n = 100, 71.43%). Study design and methodology also varied for these studies. Overall, five systematic reviews overwhelming found that maladaptive parenting was a psychosocial risk factor for the development of borderline personality pathology, and three studies found that borderline personality pathology was associated with maladaptive parenting, and negative offspring and parenting-offspring outcomes.ConclusionsIn light of these findings, we recommend greater emphasis on parenting in clinical practice and the development of parenting interventions for individuals with personality disorder. However, our understanding is limited by the heterogeneity and varying quality of the evidence, and as such, future research utilising more rigorous research methodology is needed.