Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura.

In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP.

Brain monoamine vesicular transport disease caused by homozygous SLC18A2 variants: A study in 42 affected individuals.

PURPOSE: Brain monoamine vesicular transport disease is an infantile-onset movement disorder that mimics cerebral palsy. In 2013, the homozygous SLC18A2 variant, p.Pro387Leu, was first reported as a cause of this rare disorder, and dopamine agonists were efficient for treating affected individuals from a single large family. To date, only 6 variants have been reported. In this study, we evaluated genotype-phenotype correlations in individuals with biallelic SLC18A2 variants. METHODS: A total of 42 affected individuals with homozygous SLC18A2 variant alleles were identified. We evaluated genotype-phenotype correlations and the missense variants in the affected individuals based on the structural modeling of rat VMAT2 encoded by Slc18a2, with cytoplasm- and lumen-facing conformations. A Caenorhabditis elegans model was created for functional studies. RESULTS: A total of 19 homozygous SLC18A2 variants, including 3 recurrent variants, were identified using exome sequencing. The affected individuals typically showed global developmental delay, hypotonia, dystonia, oculogyric crisis, and autonomic nervous system involvement (temperature dysregulation/sweating, hypersalivation, and gastrointestinal dysmotility). Among the 58 affected individuals described to date, 16 (28%) died before the age of 13 years. Of the 17 patients with p.Pro237His, 9 died, whereas all 14 patients with p.Pro387Leu survived. Although a dopamine agonist mildly improved the disease symptoms in 18 of 21 patients (86%), some affected individuals with p.Ile43Phe and p.Pro387Leu showed milder phenotypes and presented prolonged survival even without treatment. The C. elegans model showed behavioral abnormalities. CONCLUSION: These data expand the phenotypic and genotypic spectra of SLC18A2-related disorders.

Adolescents' Love Lives: Heterogeneity in Relationship Status Trajectories and Links with Affect.

Romantic experiences are more fluid and heterogeneous during middle adolescence than at any other life stage, but current understanding of this heterogeneity and flux is limited because of imprecise measurement. A sample of 531 adolescents (55% female; 28% non-Hispanic White; 32% Black; 27% Hispanic; 14% Other) recruited from an ongoing birth cohort study (Mean age = 16.7 years, SD = 0.358), was administered bi-weekly diaries over 52 weeks to prospectively record transitions in and out of romantic and sexual relationships and to assess links with positive affect (frequency of happiness) and negative affect (frequency of sadness). Relationship statuses considered included not only dating, but also liminal and asymmetrical statuses such as talking/flirting and crushes. Latent profile analyses revealed six relationship status trajectories, or love life profiles, based on the number of intra-year partners and on the extent of involvement in each of the relationship statuses. Approximately half of teens either were in stable dating relationships or uninvolved romantically during the year; however, half experienced variable levels of flux in their love lives. Relationship instability, not romantic involvement per se, was associated with higher levels of sadness and lower levels of happiness. Snapshots of teen romantic involvement based on one or two points in time obscure the extent of relationship heterogeneity and flux and how relationship status trajectories are associated with positive and negative affect.

Financial Toxicity and Its Association With Prostate and Colon Cancer Screening.

BACKGROUND: The term "financial toxicity" or "hardship" is a patient-reported outcome that results from the material costs of cancer care, the psychological impacts of these costs, and the coping strategies that patients use to deal with the strain that includes delaying or forgoing care. However, little is known about the impact of financial toxicity on cancer screening. We examined the effects of financial toxicity on the use of screening tests for prostate and colon cancer. We hypothesized that greater financial hardship would show an association with decreased prevalence of cancer screening. METHODS: This cross-sectional survey-based US study included men and women aged ≥50 years from the National Health Interview Survey database from January through December 2018. A financial hardship score (FHS) between 0 and 10 was formulated by summarizing the responses from 10 financial toxicity dichotomic questions (yes or no), with a higher score associated with greater financial hardship. Primary outcomes were self-reported occurrence of prostate-specific antigen (PSA) blood testing and colonoscopy for prostate and colon cancer screening, respectively. RESULTS: Overall, 13,439 individual responses were collected. A total of 9,277 (69.03%) people had undergone colonoscopies, and 3,455 (70.94%) men had a PSA test. White, married, working men were more likely to undergo PSA testing and colonoscopy. Individuals who had not had a PSA test or colonoscopy had higher mean FHSs than those who underwent these tests (0.70 and 0.79 vs 0.47 and 0.61, respectively; P≤.001 for both). Multivariable logistic regression models demonstrated that a higher FHS was associated with a decreased odds ratio for having a PSA test (0.916; 95% CI, 0.867-0.967; P=.002) and colonoscopy (0.969; 95% CI, 0.941-0.998; P=.039). CONCLUSIONS: Greater financial hardship is suggested to be associated with a decreased probability of having prostate and colon cancer screening. Healthcare professionals should be aware that financial toxicity can impact not only cancer treatment but also cancer screening.

Adolescents' Partner Search in the Digital Age: Correlates and Characteristics of Relationships Initiated Online.

Digital technology and social media platforms have transformed the ways adolescents communicate and cultivate romantic relationships, but few studies consider whether relationships initiated online are less salutary than those formed in person. A sample of 531 adolescents (Mean age = 16.7 years, SD = 0.358; 55% female) was recruited from an ongoing birth cohort study and administered bi-weekly diaries over a year to evaluate the circumstances associated with adolescents' romantic relationship formation and relationship quality. Two-thirds of respondents initiated one or more romantic relationships during the study, of which 15% were initiated online. Girls who did not fit in well at school and who had difficulty making friends were more likely to initiate romantic relationships online than their more sociable peers who fit in well at school; for boys, however, access to mobile devices increased the odds that romantic relationships were initiated online. The diaries captured considerable flux in the evolution of romantic relationships, but there was limited evidence that relationships initiated online involved greater risks, with the notable exception of greater age asymmetry.

The Social Significance of Interracial Cohabitation: Inferences Based on Fertility Behavior.

Interracial couples cohabit at higher rates than same-race couples, which is attributed to lower barriers to interracial cohabitation relative to intermarriage. This begs the question of whether the significance of cohabitation differs between interracial and same-race couples. Using data from the 2006-2017 National Survey of Family Growth, we assessed the meaning of interracial cohabitation by comparing the pregnancy risk, pregnancy intentions, and union transitions following a pregnancy among women in interracial and same-race cohabitations. The pregnancy and union transition behaviors of women in White-Black cohabitations resembled those of Black women in same-race cohabitations, suggesting that White-Black cohabitation serves as a substitute to marriage and reflecting barriers to the formation of White-Black intermarriages. The behaviors of women in White-Hispanic cohabitations fell between those of their same-race counterparts or resembled those of White women in same-race cohabitations. These findings suggest that White-Hispanic cohabitations take on a meaning between trial marriage and substitute to marriage and support views that Hispanics with White partners are a more assimilated group than Hispanics in same-race unions. Results for pregnancy intentions deviated from these patterns. Women in White-Black cohabitations were less likely than Black women in same-race cohabitations to have an unintended pregnancy, suggesting that White-Black cohabitations are considered marriage-like unions involving children. Women in White-Hispanic cohabitations were more likely than White and Hispanic women in same-race cohabitations to have an unintended pregnancy, reflecting possible concerns about social discrimination. These findings indicate heterogeneity in the significance of interracial cohabitation and continuing obstacles to interracial unions.

Racial and Ethnic Patterning of Low Birth Weight, Normal Birth Weight, and Macrosomia.

Both low birthweight (<2500 g; LBW) and macrosomia (>4000 g) are considered adverse birth outcomes and are associated with later poor health conditions, yet the social determinants of macrosomia are understudied. In this study, we explore patterning of LBW, normal birthweight, and macrosomia by race/ethnicity and nativity. We examined data from all live births between 1999 and 2014 in New Jersey with a non-missing, plausible value of birthweight (n = 1,609,516). We compared the risk for LBW and macrosomia among non-Hispanic White, non-Hispanic Black, Hispanic, and non-Hispanic Asian mothers, and between the US- and native-born. For Hispanics and Asians, we also examined differences by country of origin. The racial/ethnic patterns for macrosomia mirrored those of LBW, suggesting that the factors underlying LBW shift birthweight distributions. For example, non-Hispanic White mothers had the lowest risk for LBW and the highest risk for macrosomia. Nativity patterns differed by subgroup, however, with unique risks for macrosomia among some origin groups, such as foreign-born Cubans. The racial/ethnic and nativity patterns of macrosomia do not completely mirror those of LBW, suggesting some distinct social risk factors for macrosomia. Our findings raise questions about whether and how racial/ethnic and nativity patterning in both low and excess birthweight is retained in later conditions, such as childhood obesity.

Using Bi-Weekly Surveys to Portray Adolescent Partnership Dynamics: Lessons From a Mobile Diary Study.

Partnership formation is an important developmental task for adolescents, but cross-sectional and periodic longitudinal studies have lacked the measurement precision to portray partnership stability and flux and to capture the range of adolescent partnership experiences. This article assesses the promises and challenges of using bi-weekly mobile diaries administered over the course of a year to study adolescent partnership dynamics. Descriptive findings illustrate the potential of bi-weekly diaries for both capturing the longitudinal complexity and fluidity of adolescent partnerships as well as for reducing retrospection biases. Results also underscore several challenges, including those posed by missing data, and highlight several strategies for maximizing participant engagement and reliably tracing adolescent partnerships.

The Practicalities and Perils of Ambulatory Assessment's Promise: Introduction to a Special Section.

Ambulatory assessment (AA) offers one of the most exciting approaches for opening the dynamic "black box" of adolescents' daily lives. In this introduction, we spotlight AA's surprisingly restricted market share within adolescent scholarship. We describe thorny challenges these intense methods can pose when conducting adolescent research "in situ" and underscore that capturing quality AA data means placing adolescents' developmental stage at the forefront. The novel research reported in this special section speaks to these challenges and underscores the promise of AA for conducting developmentally salient science. The nine articles included in the section span multiple disciplines (Sociology, Psychology, Public Health) and reflect diverse viewpoints, approaches, and theories. All provide multiple novel best-practice strategies for conducting AA scholarship with adolescents.

Older Smokers' Beliefs About e-Cigarettes and Intent to Quit Conventional Cigarettes.

To explore associations between older smokers' attitudes and beliefs about electronic cigarettes (e-cigarettes) and tobacco use behavior, descriptive and correlational analysis of a cross-sectional survey of a random national sample of current smokers (age ≥45 years [considered "older" herein]) was performed. Of 498 older smokers, 75% wanted to quit smoking cigarettes and 60% had tried e-cigarettes. The 108 current e-cigarette users believed e-cigarettes help quit cigarettes (p < 0.001), are safer than cigarettes (p = 0.002), and are acceptable to friends (p = 0.010) and family (p = 0.007). Smokers not considering cessation believed friends and family think it is okay to smoke cigarettes (p < 0.001). Among older smokers: (a) most want to quit cigarettes; (b) e-cigarette use is increasing; (c) most believe e-cigarettes are healthier than cigarettes and effective for cessation; and (d) perceived social acceptability modifies tobacco use behavior by influencing initiation and maintenance of conventional cigarette and e-cigarette use. [Journal of Gerontological Nursing, 44(12), 17-24.].

Age at migration, family instability, and timing of sexual onset.

This study builds on and extends previous research on nativity variations in adolescent health and risk behavior by addressing three questions: (1) whether and how generational status and age at migration are associated with timing of sexual onset among U.S. adolescents; (2) whether and how family instability mediates associations between nativity and sexual debut; and (3) whether and how these associations vary by gender. We find that first- and second-generation immigrant youth initiate sexual activity later than native youth. Foreign-born youth who migrate after the start of adolescence exhibit the latest sexual onset; boys' sexual behavior is particularly sensitive to age at migration. Parental union stability is protective for first- and second-generation youth, especially boys; however, instability in co-residence with parents accelerates sexual debut for foreign-born girls, and dilutes protections from parental marital stability. Use of a non-English language at home delays sexual onset for immigrant girls, but not boys.

What do we know about children living with HIV-infected or AIDS-ill adults in Sub-Saharan Africa? A systematic review of the literature.

Millions of children in Sub-Saharan Africa live with adults, often parents, who are HIV-infected or ill due to AIDS. These children experience social, emotional, and health vulnerabilities that overlap with, but are not necessarily the same as, those of orphans or other vulnerable children. Despite their distinctive vulnerabilities, research aimed at understanding the situation of these children has been limited until very recently. This review summarizes the state of knowledge based on a systematic search of PubMed and Web of Science that identified 47 empirical research articles that examined either the population prevalence of children living with HIV-infected or AIDS-sick adults, or the consequences of adult HIV infection or AIDS illness for child well-being. This review confirms that this population of children is substantial in size, and that the vulnerabilities they experience are multi-faceted, spanning physical and emotional health and schooling. Mechanisms were examined empirically in only a small number of studies, but encompass poverty, transmission of opportunistic infections, care for unwell adults, adult distress, AIDS stigma, lack of social support, maternal breastfeeding issues, and vertical HIV transmission. Some evidence is provided that infants, adolescents, children with infected or ill mothers, and children living with severely ill adults are particularly vulnerable. Future research would benefit from more attention to causal inference and further characterization of processes and circumstances related to vulnerability and resilience. It would also benefit from further study of variation in observed associations between adult HIV/AIDS and child well-being based on characteristics such as age, sex, kinship, severity of illness, TB co-infection, disclosure, and serostatus awareness. Almost one-quarter of the studies reviewed did not investigate variation based on any of these factors. More nuanced understanding of the short- and long-term effects of adult HIV on children's needs and circumstances will be important to ongoing discussions about equity in policies and interventions.

An Update on MR Spectroscopy in Cancer Management: Advances in Instrumentation, Acquisition, and Analysis.

MR spectroscopy (MRS) is a noninvasive imaging method enabling chemical and molecular profiling of tissues in a localized, multiplexed, and nonionizing manner. As metabolic reprogramming is a hallmark of cancer, MRS provides valuable metabolic and molecular information for cancer diagnosis, prognosis, treatment monitoring, and patient management. This review provides an update on the use of MRS for clinical cancer management. The first section includes an overview of the principles of MRS, current methods, and conventional metabolites of interest. The remainder of the review is focused on three key areas: advances in instrumentation, specifically ultrahigh-field-strength MRI scanners and hybrid systems; emerging methods for acquisition, including deuterium imaging, hyperpolarized carbon 13 MRI and MRS, chemical exchange saturation transfer, diffusion-weighted MRS, MR fingerprinting, and fast acquisition; and analysis aided by artificial intelligence. The review concludes with future recommendations to facilitate routine use of MRS in cancer management. Keywords: MR Spectroscopy, Spectroscopic Imaging, Molecular Imaging in Oncology, Metabolic Reprogramming, Clinical Cancer Management © RSNA, 2024.

Associations between epicardial, visceral, and subcutaneous adipose tissue with diastolic function in men with and without HIV.

BACKGROUND: People with HIV (PWH) are at greater risk for diastolic dysfunction compared with persons without HIV (PWOH). An increase in visceral adipose tissue is common among PWH and greater visceral adipose tissue is associated with diastolic dysfunction among PWOH. We investigated associations of visceral adipose tissue, subcutaneous adipose tissue, and other fat depots with subclinical diastolic dysfunction among men with and without HIV (MWH and MWOH). DESIGN: Cross-sectional analysis of MWH and MWOH in the Multicenter AIDS Cohort Study (MACS). METHODS: Participants underwent echocardiography for diastolic dysfunction assessment and CT scanning including subcutaneous, visceral, epicardial, and liver adiposity measurements. Diastolic dysfunction was defined by characterizing heart function on antiretroviral therapy0 criteria. Odds for diastolic dysfunction with each measure of adiposity were estimated using multivariable logistic regression. RESULTS: Among 403 participants (median age 57, 55% white, median BMI 26 kg/m 2 ), 25% met criteria for diastolic dysfunction and 59% MWH (82% undetectable plasma HIV RNA). Greater epicardial adipose tissue area was associated with higher odds of diastolic dysfunction [odds ratio:1.54 per SD; 95%confidence interval (CI) 1.15-2.05] when adjusted for demographics, HIV serostatus, and cardiovascular risk factors. This association did not differ by HIV serostatus and persisted when excluding MWH who were not virally suppressed. Less subcutaneous adipose tissue was associated with higher odds of diastolic dysfunction. Other adipose depots were not associated with diastolic dysfunction. CONCLUSION: Greater epicardial adipose tissue and less subcutaneous adipose tissue were associated with diastolic dysfunction, regardless of HIV serostatus and viral suppression. Greater epicardial adipose tissue and less subcutaneous adipose tissue observed among PWH may contribute to risk for heart failure with preserved ejection fraction in this population.

Dimensions of Rural-to-Urban Migration and Premarital Pregnancy in Kenya.

Rural-to urban migration is increasingly common among youth and could affect sexual activities. We use life history calendar data collected in Kisumu, Kenya, to investigate how the timing and number of rural-to-urban moves are associated with premarital pregnancy. Among sexually experienced young women aged 18-24 (N=226), 39 percent have experienced a premarital pregnancy and 60 percent experienced a move in the last 10 years. Results of the event history analysis show that those who experienced one or two moves or whose most recent move occurred in the last seven to 12 months are at increased risk of premarital pregnancy compared to nonmovers. Those whose last move occurred at age 13 or younger were also at an elevated risk. Migration brings about specific needs for youth, including the need for sexual and reproductive health education and services, which should be made available and accessible to new urban residents.

Adolescent Partnership Quality and Emotional Health: Insights from an Intensive Longitudinal Study.

Prior research has documented an association between adolescents' romantic experiences and poor emotional health. However, lack of intensive longitudinal measurement and an emphasis on negative affect have limited understanding about the extent to which adolescent relationship quality influences the emotional health of adolescents in partnerships, including the potential benefits of high-quality partnerships. Previous research has also been limited in its ability to account for factors that select adolescents into lower or higher quality partnerships. Using biweekly intensive longitudinal data from the mDiary Study of Adolescent Relationships linked to six waves of birth cohort data from the Fragile Families and Child Wellbeing Study, this paper uses multilevel mixed-effects models to address three questions: (1) How are changes in partnership quality (defined as validation, frequency of disagreements, and global quality) associated with changes in both positive and negative affect; (2) Do observed associations persist net of factors that potentially select adolescents into lower or higher quality partnerships (e.g., childhood family experiences); and (3) Do associations between partnership quality and affect differ by gender? Results show that higher quality partnerships are associated with both decreases in negative affect and increases in positive affect. There were no significant gender differences on average. The study's findings highlight the importance of partnership quality as a key source of temporal variation in adolescents' emotional states.

Characteristics and Predictors of Late Right Heart Failure After Left Ventricular Assist Device Implantation.

Late right heart failure (LRHF) following left ventricular assist device (LVAD) implantation remains poorly characterized and challenging to predict. We performed a multicenter retrospective study of LRHF in 237 consecutive adult LVAD patients, in which LRHF was defined according to the 2020 Mechanical Circulatory Support Academic Research Consortium guidelines. Clinical and hemodynamic variables were assessed pre- and post-implant. Competing-risk regression and Kaplan-Meier survival analysis were used to assess outcomes. LRHF prediction was assessed using multivariable logistic and Cox proportional hazards regression. Among 237 LVAD patients, 45 (19%) developed LRHF at a median of 133 days post-LVAD. LRHF patients had more frequent heart failure hospitalizations ( p < 0.001) alongside other complications. LRHF patients did not experience reduced bridge-to-transplant rates but did suffer increased mortality (hazard ratio 1.95, 95% confidence interval [CI] 1.11-3.42; p = 0.02). Hemodynamically, LRHF patients demonstrated higher right atrial pressure, mean pulmonary arterial pressure, and pulmonary vascular resistance (PVR), but no difference in pulmonary arterial wedge pressure. History of early right heart failure, blood urea nitrogen (BUN) > 35 mg/dl at 1 month post-LVAD, and diuretic requirements at 1 month post-LVAD were each significant, independent predictors of LRHF in multivariable analysis. An LRHF prediction risk score incorporating these variables predicted LRHF with excellent discrimination (log-rank p < 0.0001). Overall, LRHF post-LVAD is more common than generally appreciated, with significant morbidity and mortality. Elevated PVR and precapillary pulmonary pressures may play a role. A risk score using early right heart failure, elevated BUN, and diuretic requirements 1 month post implant predicted the development of LRHF.

Comparison of thrombotic and clinical outcomes in SARS-CoV-2-pneumonia versus other viral pneumonia in an urban academic medical center.

BACKGROUND: Infection with viral pneumonia (PNA) is known to offset the coagulation cascade. Recent studies assessing novel SARS-CoV-2 infection observed a high frequency of systemic thrombotic events resulting in ambiguity if severity of infection or specific viral strain drive thrombosis and worsen clinical outcomes. Furthermore, limited data exists addressing SARS-CoV-2 in underrepresented patient populations. OBJECTIVES: Assess clinical outcomes events and death in patients diagnosed with SARS-CoV-2 pneumonia compared to patients with other types of viral pneumonia. METHODS: Retrospective cohort study evaluated electronic medical records in adult patients admitted to University of Illinois Hospital and Health Sciences System (UIHHSS) with primary diagnosis of SARS-CoV-2 PNA or other viral (H1N1 or H3N2) PNA between 10/01/2017 and 09/01/2020. Primary composite outcome was the following event incidence rates: death, ICU admission, infection, thrombotic complications, mechanical ventilation, renal replacement therapy, and major bleeding. RESULTS: Of 257 patient records, 199 and 58 patients had SARS-CoV-2 PNA and other viral PNA, respectively. There was no difference in primary composite outcome. Thrombotic events (n = 6, 3%) occurred solely in SARS-CoV-2 PNA patients in the ICU. A significantly higher incidence of renal replacement therapy (8.5% vs 0%, p=0.016) and mortality (15.6% vs 3.4%, p=0.048) occurred in the SARS-CoV-2 PNA group. Multivariable logistic regression analysis revealed age, presence of SARS-CoV-2, and ICU admission, aOR 1.07, 11.37, and 41.95 respectively, was significantly associated with mortality risk during hospitalization; race and ethnicity were not. CONCLUSION: Low overall incidence of thrombotic events occurred only in the SARS-CoV-2 PNA group. SARS-CoV-2 PNA may lead to higher incidence of clinical events than those observed in H3N2/H1N1 viral pneumonia, and that race/ethnicity does not drive mortality outcomes.

What Is Digital Parenting? A Systematic Review of Past Measurement and Blueprint for the Future.

Concerns about parenting adolescents are not new, but the rapid diffusion of digital technologies has heightened anxieties over digital parenting. Findings are decidedly mixed regarding the impact of digital technologies on adolescent well-being, and parents are left to navigate their concerns without an empirically based road map. A missing link for understanding the state of the science is a clear characterization of how digital parenting is measured, including an evaluation of which areas demand an outsized share of scientific attention and which have been overlooked. To address this gap, we undertook two interdisciplinary systematic reviews of the digital-parenting literature and characterized measurement across (a) quantitative surveys (n = 145 studies) and (b) qualitative focus groups, interviews, codesign studies, and user studies (n = 49). We describe previously popular areas of survey measurement that are of decreasing relevance to parenting of digital spaces (e.g., co-use, hovering). We likewise highlight areas that have been overlooked, including consideration of positive uses of digital technologies, acknowledgment of bidirectional influence, and attention to heterogeneity among families and to extraparental social ecologies of support and monitoring. We provide recommendations for the future of digital-parenting research and propose a more comprehensive approach to measuring how modern adolescents are parented.