A Qualitative Investigation of the Experiences of Women with Perinatal Depression and Anxiety during the COVID-19 Pandemic.

OBJECTIVES: The COVID-19 pandemic has had significant impacts on maternal mental health. We explored the lived experiences of women with perinatal depression and anxiety to elucidate their perceptions of how the pandemic influenced their mental health and access to care. METHODS: We conducted a qualitative descriptive study using semi-structured interviews. From March to October 2021, purposive sampling was used to recruit a socio-demographically diverse sample of women with self-reported perinatal depression or anxiety who were pregnant or within one year postpartum between March 2020 and October 2021. Interviews were conducted remotely and thematically analyzed. RESULTS: Fourteen women were interviewed. Three major themes arose. Theme 1, Negative impacts of COVID-19 on symptoms of depression and anxiety, described how the pandemic magnified underlying symptoms of depression and anxiety, increased social isolation, generated anxiety due to fears of COVID-19 infection, and caused economic stress. In theme 2, Negative impacts of COVID-19 on access to and quality of health care, women described stressful and isolating delivery experiences, negative psychological impact of partners not being able to participate in their perinatal health care, interruptions and barriers to mental health treatment, and challenges in using telehealth services for mental health care. Theme 3, Positive impacts of COVID-19 on mental health, identified advantages of increased telehealth access and ability to work and study from home. CONCLUSIONS FOR PRACTICE: The COVID-19 pandemic negatively affected women with perinatal depression and anxiety by magnifying underlying symptoms, increasing stress and social isolation, and disrupting access to mental health care. Findings provide support for policies and interventions to prevent and address social isolation, as well as optimization of telehealth services to prevent and address gaps in perinatal mental health treatment.

CTCF Governs the Identity and Migration of MGE-Derived Cortical Interneurons.

The CCCTC-binding factor (CTCF) is a central regulator of chromatin topology recently linked to neurodevelopmental disorders such as intellectual disability, autism, and schizophrenia. The aim of this study was to identify novel roles of CTCF in the developing mouse brain. We provide evidence that CTCF is required for the expression of the LIM homeodomain factor LHX6 involved in fate determination of cortical interneurons (CINs) that originate in the medial ganglionic eminence (MGE). Conditional Ctcf ablation in the MGE of mice of either sex leads to delayed tangential migration, abnormal distribution of CIN in the neocortex, a marked reduction of CINs expressing parvalbumin and somatostatin (Sst), and an increased number of MGE-derived cells expressing Lhx8 and other markers of basal forebrain projection neurons. Likewise, Ctcf-null MGE cells transplanted into the cortex of wild-type hosts generate fewer Sst-expressing CINs and exhibit lamination defects that are efficiently rescued upon reexpression of LHX6. Collectively, these data indicate that CTCF regulates the dichotomy between Lhx6 and Lhx8 to achieve correct specification and migration of MGE-derived CINs.SIGNIFICANCE STATEMENT This work provides evidence that CCCTC-binding factor (CTCF) controls an early fate decision point in the generation of cortical interneurons mediated at least in part by Lhx6. Importantly, the abnormalities described could reflect early molecular and cellular events that contribute to human neurological disorders previously linked to CTCF, including schizophrenia, autism, and intellectual disability.

Pericytes as Inducers of Rapid, Matrix Metalloproteinase-9-Dependent Capillary Damage during Ischemia.

Blood-brain barrier disruption (BBB) and release of toxic blood molecules into the brain contributes to neuronal injury during stroke and other cerebrovascular diseases. While pericytes are builders and custodians of the BBB in the normal brain, their impact on BBB integrity during ischemia remains unclear. We imaged pericyte-labeled transgenic mice with in vivo two-photon microscopy to examine the relationship between pericytes and blood plasma leakage during photothrombotic occlusion of cortical capillaries. Upon cessation of capillary flow, we observed that plasma leakage occurred with three times greater frequency in regions where pericyte somata adjoined the endothelium. Pericyte somata covered only 7% of the total capillary length in cortex, indicating that a disproportionate amount of leakage occurred from a small fraction of the capillary bed. Plasma leakage was preceded by rapid activation of matrix metalloproteinase (MMP) at pericyte somata, which was visualized at high resolution in vivo using a fluorescent probe for matrix metalloproteinase-2/9 activity, fluorescein isothiocyanate (FITC)-gelatin. Coinjection of an MMP-9 inhibitor, but not an MMP-2 inhibitor, reduced pericyte-associated FITC-gelatin fluorescence and plasma leakage. These results suggest that pericytes contribute to rapid and localized proteolytic degradation of the BBB during cerebral ischemia. SIGNIFICANCE STATEMENT: Pericytes are a key component of the neurovascular unit and are essential for normal BBB function. However, during acute ischemia, we find that pericytes are involved in creating rapid and heterogeneous BBB disruption in the capillary bed. The mechanism by which pericytes contribute to BBB damage warrants further investigation, as it may yield new therapeutic targets for acute stroke injury and other neurological diseases involving capillary flow impairment.

A murine toolbox for imaging the neurovascular unit.

The neurovascular unit (NVU) coordinates many essential functions in the brain including blood flow control, nutrient delivery, and maintenance of BBB integrity. These functions are the result of a cellular and molecular interplay that we are just beginning to understand. Cells of the NVU can now be investigated in the intact brain through the combined use of high-resolution in vivo imaging and non-invasive molecular tools to observe and manipulate cell function. Mouse lines that target transgene expression to cells of the NVU will be of great value in future work. However, a detailed evaluation of target cell specificity and expression pattern within the brain is required for many existing lines. The purpose of this review was to catalog mouse lines available to cerebrovascular biologists and to discuss their utility and limitations in future imaging studies.

Childhood Polyvictimization and Associated Health Outcomes: A Systematic Scoping Review.

Background: Polyvictimization, the experience of multiple types of victimization, is associated with detrimental health outcomes. Despite extensive research on the health consequences of polyvictimization, one challenge in understanding this literature lies in the varied operationalized definitions of polyvictimization and health outcomes. This scoping review provides the volume of the current literature on this topic, documents the varied constructs of polyvictimization and associated health outcomes, identifies knowledge gaps, and guides future research directions. Method: A systematic search of English-language original articles that presented quantitative associations of childhood polyvictimization and health outcomes was performed through six-database searches, a gray literature search, and citation mining from June 2020 to January 2021. The varied constructs of polyvictimization, health outcomes, and other study characteristics were extracted. Results: A total of 96 studies were included. Two ways of creating continuous variables (30.21%) and four ways of constructing categorical variables (72.92%) were identified for operationalizing polyvictimization. The majority of health outcomes were mental, behavioral, or social (96.88%), while slightly more than 10% of studies examined physical health (11.46%) or general health conditions (10.42%), respectively. More than half of studies used U.S. samples (56.25%). Conclusions: The varied constructs of polyvictimization suggests that there is a need to establish a valid polyvictimization construct that is consistently agreed upon in the research community. Findings summarize the specific health outcomes that can be targeted for further investigation and prevention efforts. Findings also suggest that the study of resilience and coping education for childhood polyvictims is sorely needed.

Child abuse-related homicides precipitated by caregiver use of harsh physical punishment.

BACKGROUND: Physical punishment (PP), which may involve the use of physical force, has been linked to negative effects in children and can escalate to abusive or harsh PP, resulting in injury or death. OBJECTIVE: To examine characteristics associated with fatal abuse involving caregiver use of harsh PP. METHODS: Data were from the National Violent Death Reporting System in 40 states, the District of Columbia, and Puerto Rico for years 2012-2018. Qualitative analysis was used to code textual material into categorial data, and logistic regression was used to examine associations between various characteristics and harsh PP. RESULTS: Approximately 4 % (n = 87) of the 2414 abuse-related homicides were known to have been precipitated by caregiver use of harsh PP. In adjusted models, homicides had greater odds of being harsh PP-related when incidents involved mothers' male companions (versus fathers), victims had a previous nonfatal injury (versus no previous nonfatal injury), and another adult participated in the fatal incident or had awareness of prior abuse/neglect (versus those without this characteristic). Two common precipitators of caregivers' use of harsh PP were: 1) child had a bathroom-related accident/soiled clothes (23.0 %; n = 20), and 2) child disobeyed a directive given by the perpetrator (17.2 %; n = 15). CONCLUSIONS: This study highlights characteristics associated with fatal abuse precipitated by caregiver use of harsh PP. Children were physically punished for developmentally normative behaviors. Ensuring caregivers are aware of and use effective parenting practices that focus on use of nonphysical discipline and promote healthy child development, may help decrease harsh PP and physical abuse-related homicides among children.

Computational studies on the mechanism of the gold(I)-catalysed rearrangement of cyclopropenes.

Density functional theory calculations have been employed to investigate the mechanism of gold(I)-catalysed rearrangements of cyclopropenes. Product formation is controlled by the initial ring-opening step which results in the formation of a gold-stabilised carbocation/gold carbene intermediate. With 3-phenylcyclopropene-3-methylcarboxylate, the preferred intermediate allows cyclisation via nucleophilic attack of the carbonyl group and hence butenolide formation. Further calculations on simple model systems show that substituent effects can be rationalised by the charge distribution in the ring-opening transition state and, in particular, a loss of negative charge at what becomes the ß-position of the intermediate. With 1-C(3)H(3)R cyclopropenes (R = Me, vinyl, Ph), ring-opening therefore places the substituent at the ß-position.

Differences Between Sexual and Nonsexual Homicides of Women in the United States: Findings From the National Violent Death Reporting System.

Sexual homicide (SH) is the most severe outcome of sexual violence and disproportionately affects women. While SH is rare (<1% in the U.S.) and gravely understudied, it is among the most violent, feared, and well publicized forms of murder. Thus, examining predictors is pertinent to identifying targets for prevention and response efforts. Secondary analysis of 2015-2018 National Violent Death Reporting System data on 6461 female homicide victims age 20-64 was conducted to determine if SH represents a unique killing characterized by specific offender, victim, and incident profiles. Law enforcement and coroner/medical examiner narratives were reviewed to identify cases with sexual elements (N=324). Logistic regression estimated odds ratios with 95% confidence intervals. Findings highlight important differences between SH and non-SH. SH victims were more likely to be single (AOR=1.7,p=.006), have a substance abuse problem (AOR=1.4,p=.04), or engaged in prostitution (AOR=10.4,p<.001). SH suspects were more likely to be male (AOR=2.5,p=.04), use an illicit substance in the preceding hours (AOR=1.6,p=.03), or had recent contact with police (AOR=1.6,p=.01). SH was more likely to occur in a hotel/motel (AOR=3.0,p=.002), by asphyxiation (AOR =13.38,p<.001), be perpetrated against an acquaintance (AOR=1.64,p=.007), or be precipitated by another serious crime (AOR=2.1,p<.001). Findings advance our understanding of SH victim, suspect, and incident profiles, which can help to better inform police/investigative practices and crime prevention strategies/interventions as well as to improve how SH cases are managed in correctional programs for offenders who have the opportunity for release back into society.

Associations Among Age of First Experience of Violence, Type of Victimization, Polyvictimization, and Mental Distress in Nigerian Females.

This study explored associations of age of first victimization, sexual violence (SV), physical violence (PV), polyvictimization, and mental distress among females in Nigeria (n = 1,766, 13-24 years old) using the nationally representative 2014 Nigeria Violence Against Children Survey. Multinomial logistic regressions were performed. Nigerian females reporting SV victimization and polyvictimization were more likely to experience higher mental distress. The older the female was at the time of PV victimization, the greater the risk for mental distress. Violence is prevalent in Nigeria and its impact on youth's health is severe. However, evidence-based and data-driven policies and programs can reduce and prevent violence.

Osteopathic Physician Mortality in the Influenza Pandemic of 1918-1920.

The influenza outbreak that occurred during 1918-1920 was a defining moment in the history of the world and osteopathic medicine. Despite the tremendous loss of human life, osteopathic physicians also observed greater success in the treatment of patients with the disease, in contrast with their allopathic counterparts. Osteopathic physicians also succumbed to the deadly influenza effects while treating patients. A list of osteopathic physicians who died of influenza or related complications during the pandemic, obtained from osteopathic journals from that time, is provided, along with the historical context of the pandemic.

Mild pericyte deficiency is associated with aberrant brain microvascular flow in aged PDGFRß+/- mice.

The receptor tyrosine kinase PDGFRß is essential for pericyte migration to the endothelium. In mice lacking one allele of PDGFRß (PDGFRß+/-), previous reports have described an age-dependent loss of pericytes in the brain, leading to cerebrovascular dysfunction and subsequent neurodegeneration reminiscent of that seen in Alzheimer's disease and vascular dementia. We examined 12-20-month-old PDGFRß+/- mice to better understand how pericyte loss affects brain microvascular structure and perfusion in vivo. We observed a mild reduction of cortical pericyte number in PDGFRß+/- mice (27% fewer cell bodies) compared to controls, but no decrease in pericyte coverage of the endothelium. This mild degree of pericyte loss caused no discernable change in cortical microvascular density, length, basal diameter or reactivity to hypercapnia. Yet, it was associated with an increase in basal blood cell velocity, primarily in pre-capillary arterioles. Taken together, our results suggest that mild pericyte loss can lead to aberrant cerebral blood flow despite a lack of apparent effect on microvascular structure and reactivity.

An analysis of unplanned return to the operating room following deceased donor kidney transplantation.

INTRODUCTION: This study was undertaken to characterize unplanned return to the OR following kidney transplantation(KT). METHODS: All patients undergoing KT at a single center from 1/2015 through 11/2017 were evaluated. The primary endpoint was unplanned return to the OR within 90 days. Perioperative and one year patient and graft outcomes were also determined. RESULTS: Of 190 patients, 14(7.4%) of patients had unplanned reoperation. The most common individual indications were bleeding from biopsy sites(n = 2), poor vascular flow on postop ultrasound(n = 4), and perforated diverticulitis(n = 2). Forty Three percent of all reoperations were unrelated to the technical conduct of the transplant operation. Reoperated patients had significantly worse survival at one year(78.6% vs. 96.6%), although graft function in survivors was similar to those who did not return to the OR. CONCLUSION: Reoperation following KT is frequently unrelated to the technical conduct of the transplant procedure, thus it may not be useful as a quality metric.

Imaginary Companions, Inner Speech, and Auditory Verbal Hallucinations: What Are the Relations?

Interacting with imaginary companions (ICs) is now considered a natural part of childhood for many children, and has been associated with a range of positive developmental outcomes. Recent research has explored how the phenomenon of ICs in childhood and adulthood relates to the more unusual experience of hearing voices (or auditory verbal hallucinations, AVH). Specifically, parallels have been drawn between the varied phenomenology of the two kinds of experience, including the issues of quasi-perceptual vividness and autonomy/control. One line of research has explored how ICs might arise through the internalization of linguistically mediated social exchanges to form dialogic inner speech. We present data from two studies on the relation between ICs in childhood and adulthood and the experience of inner speech. In the first, a large community sample of adults (N = 1,472) completed online the new Varieties of Inner Speech - Revised (VISQ-R) questionnaire (Alderson-Day et al., 2018) on the phenomenology of inner speech, in addition to providing data on ICs and AVH. The results showed differences in inner speech phenomenology in individuals with a history of ICs, with higher scores on the Dialogic, Evaluative, and Other Voices subscales of the VISQ-R. In the second study, a smaller community sample of adults (N = 48) completed an auditory signal detection task as well as providing data on ICs and AVH. In addition to scoring higher on AVH proneness, individuals with a history of ICs showed reduced sensitivity to detecting speech in white noise as well as a bias toward detecting it. The latter finding mirrored a pattern previously found in both clinical and nonclinical individuals with AVH. These findings are consistent with the view that ICs represent a hallucination-like experience in childhood and adulthood which shows meaningful developmental relations with the experience of inner speech.

Tropheryma Whipplei Endocarditis: Case Report and Literature Review.

We describe a young man who initially presented with stroke and febrile illness. He was eventually diagnosed with Tropheryma whipplei endocarditis. This is a very rare condition and to the best of our knowledge, this is the first documented case of T. whipplei endocarditis in Australia and New Zealand regions. This report aims to increase awareness of clinicians of this very rare but potentially treatable condition. It is reasonable to exclude T. whipplei endocarditis when dealing with high-risk patients who are suspected for "culture-negative" endocarditis.

The role of FDG-PET in detecting rejection after liver transplantation.

BACKGROUND: The activation and increased metabolic activity of T cells in acute cellular rejection could allow fluoro-2-deoxyglucose positron emission tomography to be utilized for detection of acute cellular rejection. The objective of this study was to evaluate the effectiveness of fluoro-2-deoxyglucose positron emission tomography in detecting acute cellular rejection in the clinical setting. METHODS: Fluoro-2-deoxyglucose positron emission tomography studies were performed on 88 orthotopic liver transplant patients at 7 and 17 days postoperatively (first positron emission tomography and second positron emission tomography, respectively). Additional studies were performed if patients had suspicion of rejection and at resolution of rejection (third positron emission tomography and fourth positron emission tomography, respectively). A circular region of interest was placed over the liver for semiquantitative evaluation of fluoro-2-deoxyglucose positron emission tomography images by means of standard uptake values. RESULTS: Eighteen of 88 patients in our study (20.5%) had histologically proven acute cellular rejection during a 16 ± 11 day follow-up. There was no significant difference between the standard uptake values of first positron emission tomography among non-rejecters versus rejecters (2.05 ±0.46 non-rejecters versus 1.82 ± 0.40 rejecters, P = .127). Within the rejection cohort, the standard uptake values from the third positron emission tomography (rejection) were higher compared to the first positron emission tomography (baseline) (2.41 ± 0.48 third positron emission tomography versus 1.82 ± 0.41 first positron emission tomography, P < .001). CONCLUSION: Increased signal on fluoro-2-deoxyglucose positron emission tomography over baseline is associated with acute cellular rejection in liver transplant recipients. Additional prospective validation studies are essential to define the role of fluoro-2-deoxyglucose positron emission tomography scan as an early marker for acute cellular rejection.

Treatment of aspergillosis in an immunocompetent patient: a multidisciplinary approach.

CASE STUDY: P.J. was a 69-year-old woman who was referred to a large cancer center for an evaluation of brain and lung masses presumed to be cancerous lesions. During the three months before the referral, P.J. had experienced a gradual 40 lb weight loss, shortness of breath with exertion, chest pain, lip tremor, edema and progressive weakening of lower extremities, overall fatigue, and increasing balance and gait disturbances. Her diagnostic workup revealed aspergillosis in her lungs and brain. This case study reports the process of differentiating between cancer and fungal disease, antifungal treatment modalities used, and the multidisciplinary management approach used in the care of P.J.

Replacement or exclusion of the B-branch bacteriopheophytin in the purple bacterial reaction centre: the H(B) cofactor is not required for assembly or core function of the Rhodobacter sphaeroides complex.

All of the membrane-embedded cofactors of the purple bacterial reaction centre have well-defined functional or structural roles, with the exception of the bacteriopheophytin (H(B)) located approximately half-way across the membrane on the so-called inactive- or B-branch of cofactors. Sequence alignments indicate that this bacteriochlorin cofactor is a conserved feature of purple bacterial reaction centres, and a pheophytin is also found at this position in the Photosystem-II reaction centre. Possible structural or functional consequences of replacing the H(B) bacteriopheophytin by bacteriochlorophyll were investigated in the Rhodobacter sphaeroides reaction centre through mutagenesis of residue Leu L185 to His (LL185H). Results from absorbance spectroscopy indicated that the LL185H mutant assembled with a bacteriochlorophyll at the H(B) position, but this did not affect the capacity of the reaction centre to support photosynthetic growth, or change the kinetics of charge separation along the A-branch of cofactors. It was also found that mutation of residue Ala M149 to Trp (AM149W) caused the reaction centre to assemble without an H(B) bacteriochlorin, demonstrating that this cofactor is not required for correct assembly of the reaction centre. The absence of a cofactor at this position did not affect the capacity of the reaction centre to support photosynthetic growth, or the kinetics of A-branch electron transfer. A combination of X-ray crystallography and FTIR difference spectroscopy confirmed that the H(B) cofactor was absent in the AM149W mutant, and that this had not produced any significant disturbance of the adjacent ubiquinol reductase (Q(B)) site. The data are discussed with respect to possible functional roles of the H(B) bacteriopheophytin, and we conclude that the reason(s) for conservation of a bacteriopheophytin cofactor at this position in purple bacterial reaction centres are likely to be different from those underlying conservation of a pheophytin at the analogous position in Photosystem-II.

Microvascular basis for growth of small infarcts following occlusion of single penetrating arterioles in mouse cortex.

Small cerebral infarcts, i.e. microinfarcts, are common in the aging brain and linked to vascular cognitive impairment. However, little is known about the acute growth of these minute lesions and their effect on blood flow in surrounding tissues. We modeled microinfarcts in the mouse cortex by inducing photothrombotic clots in single penetrating arterioles. The resultant hemodynamic changes in tissues surrounding the occluded vessel were then studied using in vivo two-photon microscopy. We were able to generate a spectrum of infarct volumes by occluding arterioles that carried a range of blood fluxes. Those resulting from occlusion of high-flux penetrating arterioles (flux of 2 nL/s or higher) exhibited a radial outgrowth that encompassed unusually large tissue volumes. The gradual expansion of these infarcts was propagated by an evolving insufficiency in capillary flow that encroached on territories of neighboring penetrating arterioles, leading to the stagnation and recruitment of their perfusion domains into the final infarct volume. Our results suggest that local collapse of microvascular function contributes to tissue damage incurred by single penetrating arteriole occlusions in mice, and that a similar mechanism may add to pathophysiology induced by microinfarcts of the human brain.

Granulicatella adiacens subacute bacterial endocarditis as the underlying cause of type II mixed cryoglobulinaemia.

A 57-year-old man with type II mixed cryoglobulinaemia presented to the emergency department with a history of worsening lethargy, malaise and non-drenching night sweats in a relapsing-remitting pattern. He was diagnosed with type II mixed cryoglobulinaemia 7 months ago following episodes of fever, night sweats, lethargy and malaise associated with a non-blanching, purpuric, raised erythematous rash that responded partially to immunosuppressive therapy and short courses of oral antibiotics. A single blood culture then yielded Granulicatella adiacens which was reported as a possible contaminant and therefore, not pursued. Despite numerous other investigations, the underlying cause of his type II cryoglobulinaemia remained undetermined. On his current presentation, the physical examination revealed signs of infective endocarditis. Two further blood cultures grew G. adiacens. The diagnosis of infective endocarditis was established on a transoesophageal echocardiography, and the subsequent antibiotic and surgical therapy resulted in complete remission of his type II mixed cryoglobulinaemia.

Pericyte structure and distribution in the cerebral cortex revealed by high-resolution imaging of transgenic mice.

Pericytes are essential for normal brain function, but many aspects of their physiology remain enigmatic due to a lack of tools to genetically target this cell population. Here, we characterize brain pericytes using two existing Cre-recombinase driver mouse lines that can serve distinct purposes in cerebrovascular research. One line expresses an inducible version of Cre under the NG2 proteoglycan promoter, which provides the sparse labeling necessary to define the morphology of single cells. These mice reveal structural differences between pericytes adjacent to arterioles versus those broadly distributed in the capillary bed that may underlie differential roles in control of vessel caliber. A second line expresses Cre constitutively under the platelet-derived growth factor receptor ß promoter and provides continuous, highly specific and near-complete labeling of pericytes and myocytes along the entire cerebrovasculature. This line provides a three-dimensional view of pericyte distribution along the cortical angioarchitecture following optical clearing of brain tissue. In combination with recent reporter lines for expression of optogenetic actuators and activity-sensitive probes, these mice may be key tools for studying pericyte biology in the intact brain.