The Impact of Intimate Partner Violence on Homelessness and Returns to Housing: A Qualitative Analysis From the California Statewide Study of People Experiencing Homelessness.

Homelessness is a public health concern in California and throughout the United States. Intimate partner violence (IPV) is a risk factor for experiencing homelessness. Few studies have examined the interplay between IPV, homelessness, and housing. Qualitative methods can provide a greater understanding of the lived experience of IPV and homelessness to identify potential solutions. We purposefully sampled 104 adults who reported experiencing IPV in the California Statewide Study of People Experiencing Homelessness (CASPEH), a representative, mixed-methods study. We administered semi-structured interviews focusing on IPV and six other topic areas pertaining to homelessness from October 2021 to May 2022. We created and applied a codebook with a multidisciplinary team using a hybrid of deductive and inductive logic. Our analysis included all participants who discussed IPV and homelessness across the seven studies. We conducted a thematic analysis using an interpretivist approach and informed by grounded theory. We found that violence within a partnership was multidimensional (physical, sexual, emotional, and financial) and bidirectional. We identified six themes: (1) IPV precipitated and prolonged homelessness; (2) Need for housing, financial stability, and material resources influenced staying in abusive relationships; (3) Alcohol and illicit substance use exacerbated violence between partners; (4) Participants struggled to find resources in domestic violence (DV) shelters; (5) The healthcare system did not provide substantial support; and (6) discrimination and stigma influenced equitable access to housing and DV resources. Experiencing IPV contributed to homelessness and impeded returns to housing. Limitations in current IPV resources impede care. We propose equitable expansion of survivor-centered services that improve access to long-term subsidized housing, prevent IPV and homelessness with flexible funding options, and facilitate rapid exits from homelessness through trauma-informed, non-congregate shelter that transitions to permanent housing.

"We Remember the Pain": A qualitative study of intergenerational trauma among older adults experiencing homelessness in the HOPE HOME study.

Rates of homelessness among adults aged 50 and over are rising. Common strategies for exiting homelessness rely on social and family support. However, intergenerational trauma may disrupt these social support networks and contribute to homelessness. Understanding the impact of intergenerational trauma on living with family or friends may give insight into addressing homelessness among older adults. We purposefully sampled 46 adults who reported living with family or friends from the HOPE HOME study cohort (350 community-recruited adults, ≥ 50 years and experiencing homelessness in Oakland, California) and 19 family/friends who had hosted the participants in their living spaces. We conducted independent, semi-structured interviews and used grounded theory methodologies to analyze data. We identified four major themes from the interviews: (1) Intergenerational trauma was common and made it difficult to stay with family or friends; (2) Participants and hosts sought to protect future generations from intergenerational trauma; (3) Relationships endured despite intergenerational trauma; and (4) social structures exacerbated the impact of intergenerational trauma and played a significant role in perpetuating homelessness. Trauma-informed policies that confront the structures that propagate or exacerbate intergenerational trauma may mitigate their impact and facilitate housing for older adults.

Use of Patient-Reported Outcome Measures to Assess the Effectiveness of Hybrid Psychiatric Visits.

OBJECTIVE: Little empirical evidence exists to support the effectiveness of hybrid psychiatric care, defined as care delivered through a combination of telephone, videoconferencing, and in-person visits. The authors aimed to investigate the effectiveness of hybrid psychiatric care compared with outpatient waitlist groups, assessed with patient-reported outcome measures (PROMs). METHOD: Participants were recruited from an adult psychiatry clinic waitlist on which the most common primary diagnoses were unipolar depression, generalized anxiety disorder, and bipolar disorder. Patients (N=148) were randomly assigned to one of two waitlist groups that completed PROMs once or monthly before treatment initiation. PROMs were used to assess symptoms of depression (Patient Health Questionnaire-9 [PHQ-9]), anxiety (Generalized Anxiety Disorder-7 [GAD-7]), and daily psychological functioning (Brief Adjustment Scale-6 [BASE-6]). Patient measures were summarized descriptively with means, medians, and SDs and then compared by using the Kruskal-Wallis test; associated effect sizes were calculated. PROM scores for patients who received hybrid psychiatric treatment during a different period (N=272) were compared with scores of the waitlist groups. RESULTS: PROM assessments of patients who engaged in hybrid care indicated significant improvements in symptom severity compared with the waitlist groups, regardless of the number of PROMs completed while patients were on the waitlist. Between the hybrid care and waitlist groups, the effect size for the PHQ-9 score was moderate (d=0.66); effect sizes were small for the GAD-7 (d=0.46) and BASE-6 (d=0.45) scores. CONCLUSIONS: The findings indicate the clinical effectiveness of hybrid care and that PROMs can be used to assess this effectiveness.

Intussusception With a Pathological Lead Point in a Two-Month-Old Infant.

Intussusception is one of the most common causes of acute intestinal obstruction in infancy and early childhood. Most cases of intussusception tend to occur in infancy, between the ages of four and six months. The causes can be split into two categories: non-pathologic and pathologic. Non-pathological causes include administration of the rotavirus vaccine, dehydration, and recent illness. Pathological causes can be attributed to Meckel's diverticulum (in 75% of cases), polyps (15%), and lymphoma or other tumors (3%). Intussusception rarely occurs in infants less than three months of age. If intussusception does occur in patients under three months of age, the cause is idiopathic in up to 75% of the cases. Additionally, myoglandular-type polyps are exceedingly rare and very rarely occur in patients under the age of 50. This case report discusses the diagnosis and treatment of intussusception in a two-month-old male patient who initially presented to the pediatric inpatient unit for dehydration secondary to a suspected viral illness, later developing colicky abdominal pain and bloody stools. He was found to have colo-colonic intussusception with a myoglandular-type polyp lead point. In discussing this case, the aim is to teach about intussusception and myoglandular-type polyps, as well as reveal a rarity in both etiologies for this age group.

Clinical and molecular characteristics of hemophilia A affected individuals and carriers: A 24 years experience from three centers.

Hemophilia A is a rare bleeding disorder with variable expressivity and allelic heterogeneity. Despite the advancement of prenatal diagnostics and molecular studies, the number of studies reviewing the reproductive choices of hemophilia A carriers and affected individuals remains limited. Through this retrospective review, we hope to gain a deeper understanding of hemophilia A-affected individuals' clinical and molecular characteristics, as well as the reproductive choices of the at-risk couples. A total of 122 individuals harboring likely causative F8 gene alterations from 64 apparently unrelated families attending three centers between 3/2000 and 3/2023 were included in this study. Their clinical and molecular findings as well as reproductive choices were gathered in a clinical setting and verified through the electronic medical record database of the public health system. Forty-seven affected males and 75 female heterozygous carriers were included in the analysis. Among 64 apparently unrelated families, 36 distinct pathogenic/likely pathogenic variants were identified, of which 30.6% (11/36) of variants were novel. While the majority of clinical findings and genotype-phenotype correlations appear to be in accordance with existing literature, female carriers who had no fertility intention were significantly more likely to have affected sons than those who had fertility intention (5/19 vs. 4/5; p = 0.047). Through this retrospective review, we summarized the clinical and molecular characteristics of 122 individuals harboring pathogenic/likely pathogenic F8 variants, as well as their fertility intentions and reproductive outcomes. Further studies are required to look into the considerations involved in reproductive decision-making.

Integrative multi-omics profiling in human decedents receiving pig heart xenografts.

In a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity. Longitudinal analyses indicated the presence of ischemia reperfusion injury, exacerbated by inadequate immunosuppression of T cells, consistent with previous findings of perioperative cardiac xenograft dysfunction in pig-to-nonhuman primate studies. Moreover, at 42 h after transplantation, substantial alterations in cellular metabolism and liver-damage pathways occurred, correlating with profound organ-wide physiological dysfunction. By contrast, relatively minor changes in RNA, protein, lipid and metabolism profiles were observed in decedent 2 (female) as compared to decedent 1. Overall, these multi-omics analyses delineate distinct responses to cardiac xenotransplantation in the two human decedents and reveal new insights into early molecular and immune responses after xenotransplantation. These findings may aid in the development of targeted therapeutic approaches to limit ischemia reperfusion injury-related phenotypes and improve outcomes.

Association Between Sleep Apnea Treatment and Health Care Resource Use in Patients With Atrial Fibrillation.

BACKGROUND: Obstructive sleep apnea (OSA) contributes to the generation, recurrence, and perpetuation of atrial fibrillation, and it is associated with worse outcomes. Little is known about the economic impact of OSA therapy in atrial fibrillation. This retrospective cohort study assessed the impact of positive airway pressure (PAP) therapy adherence on health care resource use and costs in patients with OSA and atrial fibrillation. METHODS AND RESULTS: Insurance claims data for ≥1 year before sleep testing and 2 years after device setup were linked with objective PAP therapy use data. PAP adherence was defined from an extension of the US Medicare 90-day definition. Inverse probability of treatment weighting was used to create covariate-balanced PAP adherence groups to mitigate confounding. Of 5867 patients (32% women; mean age, 62.7 years), 41% were adherent, 38% were intermediate, and 21% were nonadherent. Mean±SD number of all-cause emergency department visits (0.61±1.21 versus 0.77±1.55 [P=0.023] versus 0.95±1.90 [P<0.001]), all-cause hospitalizations (0.19±0.69 versus 0.24±0.72 [P=0.002] versus 0.34±1.16 [P<0.001]), and cardiac-related hospitalizations (0.06±0.26 versus 0.09±0.41 [P=0.023] versus 0.10±0.44 [P=0.004]) were significantly lower in adherent versus intermediate and nonadherent patients, as were all-cause inpatient costs ($2200±$8054 versus $3274±$12 065 [P=0.002] versus $4483±$16 499 [P<0.001]). All-cause emergency department costs were significantly lower in adherent and intermediate versus nonadherent patients ($499±$1229 and $563±$1292 versus $691±$1652 [P<0.001 and P=0.002], respectively). CONCLUSIONS: These data suggest clinical and economic benefits of PAP therapy in patients with concomitant OSA and atrial fibrillation. This supports the value of diagnosing and managing OSA and highlights the need for strategies to enhance PAP adherence in this population.

Pregnancy dedifferentiates memory CD8+ T cells into hypofunctional cells with exhaustion-enriched programs.

Alloreactive memory, unlike naive, CD8+ T cells resist transplantation tolerance protocols and are a critical barrier to long-term graft acceptance in the clinic. We here show that semiallogeneic pregnancy successfully reprogrammed memory fetus/graft-specific CD8+ T cells (TFGS) toward hypofunction. Female C57BL/6 mice harboring memory CD8+ T cells generated by the rejection of BALB/c skin grafts and then mated with BALB/c males achieved rates of pregnancy comparable with naive controls. Postpartum CD8+ TFGS from skin-sensitized dams upregulated expression of T cell exhaustion (TEX) markers (Tox, Eomes, PD-1, TIGIT, and Lag3). Transcriptional analysis corroborated an enrichment of canonical TEX genes in postpartum memory TFGS and revealed a downregulation of a subset of memory-associated transcripts. Strikingly, pregnancy induced extensive epigenetic modifications of exhaustion- and memory-associated genes in memory TFGS, whereas minimal epigenetic modifications were observed in naive TFGS. Finally, postpartum memory TFGS durably expressed the exhaustion-enriched phenotype, and their susceptibility to transplantation tolerance was significantly restored compared with memory TFGS. These findings advance the concept of pregnancy as an epigenetic modulator inducing hypofunction in memory CD8+ T cells that has relevance not only for pregnancy and transplantation tolerance, but also for tumor immunity and chronic infections.

Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: A RECOVER trial report.

BACKGROUND: RECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention. OBJECTIVE: To describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine. METHODS: Medical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) versus not qualified (N = 228) for RECOVER, and among the qualified group as a function of exposure to INTs during the current major depressive episode (MDE). RESULTS: Unipolar MDD patients who qualified for RECOVER had marked TRD (median of 11.0 lifetime failed antidepressant treatments), severe disability (median WHODAS score of 50.0), and high rate of baseline suicidality (77% suicidal ideation, 40% previous suicide attempts). Overall, 71% had received at least one INT. Compared to the no INT group, INT recipients were younger and more severely depressed (QIDS-C, QIDS-SR), had greater suicidal ideation, earlier diagnosis of MDD, and failed more antidepressant medication trials. CONCLUSIONS: RECOVER-qualified unipolar patients had marked TRD and marked treatment resistance with most failing one or more prior INTs. Treatment with ≥1 INTs in the current MDE was associated with earlier age of MDD onset, more severe clinical presentation, and greater treatment resistance relative to patients without a history of INT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03887715.

Blood Pressure Variability is Better Associated with Acute Relative Hyperglycemia Than the Heart Rate Variability in Healthy Young Adults.

BACKGROUND: Deranged cardiovascular autonomic functions are well-reported complications of diabetes mellitus, where chronic hyperglycemia is an important factor. The role of acute relative hyperglycemia on cardiovascular autonomic functions, particularly on blood pressure variability in healthy subjects, has been rarely explored. Therefore, this study aimed to examine the effect of acute relative hyperglycemia on cardiovascular autonomic functions in healthy young adults. METHODS: Beat-to-beat blood pressure and electrocardiogram were recorded to assess the heart rate variability and blood pressure variability in 42 young, healthy subjects during fasting and relative hyperglycemic states. Recorded cardiovascular parameters were analyzed in time and frequency domains. Correlations among analyzed parameters of cardiovascular autonomic variabilities were explored during fasting and relative hyperglycemic state. RESULTS: A few of the systolic, mean, and diastolic blood-pressure-variability parameters were significantly altered during acute relative hyperglycemia when compared to the fasting state. However, no significant changes were observed in any of the heart-rate-variability parameters. Also, novel significant correlations were found among many of the parameters of cardiovascular autonomic variabilities during fasting and relative hyperglycemic states. CONCLUSIONS: The blood pressure variability is affected significantly during acute relative hyperglycemia in healthy young adults; however, the heart rate variability does not show such changes. Also, many blood pressure variability parameters show significant correlations with heart rate variability and baroreflex sensitivity. It may be hypothesized that although the variabilities in heart rate and blood pressure assess cardiovascular autonomic functions, blood pressure variability is a better indicator of cardiovascular autonomic effects of acute relative hyperglycemia.

Cell-free DNA from nail clippings as source of normal control for genomic studies in hematologic malignancies.

Comprehensive genomic sequencing is becoming a critical component in the assessment of hematologic malignancies, with broad implications for patient management. In this context, unequivocally discriminating somatic from germline events is challenging but greatly facilitated by matched analysis of tumor:normal pairs. In contrast to solid tumors, conventional sources of normal control (peripheral blood, buccal swabs, saliva) could be highly involved by the neoplastic process, rendering them unsuitable. In this work we describe our real-world experience using cell free DNA (cfDNA) isolated from nail clippings as an alternate source of normal control, through the dedicated review of 2,610 tumor:nail pairs comprehensively sequenced by MSK-IMPACT-heme. Overall, we find nail cfDNA is a robust source of germline control for paired genomic studies. In a subset of patients, nail DNA may have tumor DNA contamination, reflecting unique attributes of the hematologic disease and transplant history. Contamination is generally low level, but significantly more common among patients with myeloid neoplasms (20.5%; 304/1482) compared to lymphoid diseases (5.4%; 61/1128) and particularly enriched in myeloproliferative neoplasms with marked myelofibrosis. When identified in patients with lymphoid and plasma-cell neoplasms, mutations commonly reflected a myeloid profile and correlated with a concurrent/evolving clonal myeloid neoplasm. For nails collected after allogeneic stem-cell transplantation, donor DNA was identified in 22% (11/50). In this cohort, an association with recent history of graft-vs-host disease was identified. These findings should be considered as a potential limitation for the use of nail as normal control but could also provide important diagnostic information regarding the disease process.

Early stage black pepper leaf disease prediction based on transfer learning using ConvNets.

Plants get exposed to diseases, insects and fungus. This causes heavy damages to crop resulting in various leaves diseases. Leaf diseases can be diagnosed at an early stage with the aid of a smart computer vision system and timely disease prevention can be targeted. Black pepper is a medicinal plant that is extensively used in Ayurvedic medicine because of its therapeutic properties. The proposed work represents an intelligent transfer learning technique through state-of-the-art deep learning implementation using convolutional neural network to predict the presence of prominent diseases in black pepper leaves. The ImageNet dataset available online is used for training deep neural network. Later, this trained network is utilized for the prediction of the newly developed black pepper leaf image dataset. The developed data set consist of real time leaf images, which are candidly taken from the fields and annotated under supervision of an expert. The leaf diseases considered are anthracnose, slow wilt, early stage phytophthora, phytophthora and yellowing. The hyperparameters chosen for tuning in to deep learning models are initial learning rates, optimization algorithm, image batches, epochs, validation and training data, etc. The accuracy obtained with 0.001 learning rate ranges from 99.1 to 99.7% for the Inception V3, GoogleNet, SqueezeNet and Resnet18 models. Proposed Resnet18 model outperforms all model with 99.67% accuracy. The resulting validation accuracy obtained using these models is high and the validation loss is low. This work represents improvement in agriculture and a cutting edge deep neural network method for early stage leaf disease identification and prediction. This is an approach using a deep learning network to predict early stage black pepper leaf diseases.

Advancing mouse models for transplantation research.

Mouse models have been instrumental in understanding mechanisms of transplant rejection and tolerance, but cross-study reproducibility and translation of experimental findings into effective clinical therapies are issues of concern. The Mouse Models in Transplantation symposium gathered scientists and physician-scientists involved in basic and clinical research in transplantation to discuss the strengths and limitations of mouse transplant models and strategies to enhance their utility. Participants recognized that increased procedure standardization, including the use of prespecified, defined endpoints, and statistical power analyses, would benefit the field. They also discussed the generation of new models that incorporate environmental and genetic variables affecting clinical outcomes as potentially important. If implemented, these strategies are expected to improve the reproducibility of mouse studies and increase their translation to clinical trials and, ideally, new Food and Drug Administration-approved drugs.

Low-affinity CD8+ T cells provide interclonal help to high-affinity CD8+ T cells to augment alloimmunity.

Following solid organ transplantation, small precursor populations of polyclonal CD8+ T cells specific for any graft-expressed antigen preferentially expand their high-affinity clones. This phenomenon, termed "avidity maturation," results in a larger population of CD8+ T cells with increased sensitivity to alloantigen, posing a greater risk for graft rejection. Using a mouse model of minor-mismatched skin transplantation, coupled with the tracking of 2 skin graft-reactive CD8+ T cell receptor-transgenic tracer populations with high and low affinity for the same peptide-major histocompatibility complex, we explored the conventional paradigm that CD8+ T cell avidity maturation occurs through T cell receptor affinity-based competition for cognate antigen. Our data revealed "interclonal CD8-CD8 help," whereby lower/intermediate affinity clones help drive the preferential expansion of their higher affinity counterparts in an interleukin-2/CD25-dependent manner. Consequently, the CD8-helped high-affinity clones exhibit greater expansion and develop augmented effector functions in the presence of their low-affinity counterparts, correlating with more severe graft damage. Finally, interclonal CD8-CD8 help was suppressed by costimulation blockade treatment. Thus, high-affinity CD8+ T cells can leverage help from low-affinity CD8+ T cells of identical specificity to promote graft rejection. Suppressing provision of interclonal CD8-CD8 help may be important to improve transplant outcomes.

A multi-cohort genome-wide association study in African ancestry individuals reveals risk loci for primary open-angle glaucoma.

Primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African ancestry. We conducted a genome-wide association study (GWAS) for POAG in 11,275 individuals of African ancestry (6,003 cases; 5,272 controls). We detected 46 risk loci associated with POAG at genome-wide significance. Replication and post-GWAS analyses, including functionally informed fine-mapping, multiple trait co-localization, and in silico validation, implicated two previously undescribed variants (rs1666698 mapping to DBF4P2; rs34957764 mapping to ROCK1P1) and one previously associated variant (rs11824032 mapping to ARHGEF12) as likely causal. For individuals of African ancestry, a polygenic risk score (PRS) for POAG from our mega-analysis (African ancestry individuals) outperformed a PRS from summary statistics of a much larger GWAS derived from European ancestry individuals. This study quantifies the genetic architecture similarities and differences between African and non-African ancestry populations for this blinding disease.

Reference ranges for third-trimester maternal cardiovascular function parameters measured in normotensive pregnant women using a non-invasive cardiac output monitor: A study based on data from the prospective PEACH cohort study.

OBJECTIVE: We defined reference ranges for maternal cardiac output, systemic vascular resistance, and stroke volume measured in the third trimester of pregnancy using the Ultrasound Cardiac Output Monitor 1A. DESIGN: Based on data from the prospective PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension) cohort study. SETTING: Rigshospitalet and Hvidovre Hospital, Denmark. SAMPLE: Normotensive pregnant women aged 18-45 years with singleton pregnancies, enrolled in the PEACH study in 2016-2018. METHODS: We modelled cardiac output, systemic vascular resistance and stroke volume as a function of gestational age using multilevel linear models with fractional polynomials. MAIN OUTCOME MEASURES: Unconditional and conditional reference ranges for cardiovascular parameters measured in gestational weeks 28-40. RESULTS: Our study cohort included 405 healthy pregnant women who contributed 1210 cardiovascular function measurements for analysis. Maximum cardiac output and stroke volume values were measured in gestational weeks 30-32 and decreased over the third trimester, whereas systemic vascular resistance increased during the same period. We created reference ranges for eight combinations of maternal height, age and parity. We also created a simple calculator to allow for implementation of the reference ranges in clinical practice. CONCLUSIONS: Our reference ranges allow the use of a bedside ultrasound device to non-invasively assess cardiac function in pregnancy and identify women at risk of complications. The unconditional ranges allow clinicians to evaluate isolated measurements and identify women needing follow-up. The conditional ranges incorporate information from previous measurements and improve monitoring over time.