Tonic prime-boost of STING signalling mediates Niemann-Pick disease type C.

The classic mode of STING activation is through binding the cyclic dinucleotide 2'3'-cyclic GMP-AMP (cGAMP), produced by the DNA sensor cyclic GMP-AMP synthase (cGAS), which is important for the innate immune response to microbial infection and autoimmune disease. Modes of STING activation that are independent of cGAS are much less well understood. Here, through a spatiotemporally resolved proximity labelling screen followed by quantitative proteomics, we identify the lysosomal membrane protein Niemann-Pick type C1 (NPC1) as a cofactor in the trafficking of STING. NPC1 interacts with STING and recruits it to the lysosome for degradation in both human and mouse cells. Notably, we find that knockout of Npc1 'primes' STING signalling by physically linking or 'tethering' STING to SREBP2 trafficking. Loss of NPC1 protein also 'boosts' STING signalling by blocking lysosomal degradation. Both priming and boosting of STING signalling are required for severe neurological disease in the Npc1-/- mouse. Genetic deletion of Sting1 (the gene that encodes STING) or Irf3, but not that of Cgas, significantly reduced the activation of microglia and relieved the loss of Purkinje neurons in the cerebellum of Npc1-/- mice, leading to improved motor function. Our study identifies a cGAS- and cGAMP-independent mode of STING activation that affects neuropathology and provides a therapeutic target for the treatment of Niemann-Pick disease type C.

Widespread monoclonal IgE antibody convergence to an immunodominant, proanaphylactic Ara h 2 epitope in peanut allergy.

BACKGROUND: Despite their central role in peanut allergy, human monoclonal IgE antibodies have eluded characterization. OBJECTIVE: We sought to define the sequences, affinities, clonality, and functional properties of human monoclonal IgE antibodies in peanut allergy. METHODS: We applied our single-cell RNA sequencing-based SEQ SIFTER discovery platform to samples from allergic individuals who varied by age, sex, ethnicity, and geographic location in order to understand commonalities in the human IgE response to peanut allergens. Select antibodies were then recombinantly expressed and characterized for their allergen and epitope specificity, affinity, and functional properties. RESULTS: We found striking convergent evolution of IgE monoclonal antibodies (mAbs) from several clonal families comprising both memory B cells and plasmablasts. These antibodies bound with subnanomolar affinity to the immunodominant peanut allergen Ara h 2, specifically a linear, repetitive motif. Further characterization of these mAbs revealed their ability to single-handedly cause affinity-dependent degranulation of human mast cells and systemic anaphylaxis on peanut allergen challenge in humanized mice. Finally, we demonstrated that these mAbs, reengineered as IgGs, inhibit significant, but variable, amounts of Ara h 2- and peanut-mediated degranulation of mast cells sensitized with allergic plasma. CONCLUSIONS: Convergent evolution of IgE mAbs in peanut allergy is a common phenomenon that can reveal immunodominant epitopes on major allergenic proteins. Understanding the functional properties of these molecules is key to developing therapeutics, such as competitive IgG inhibitors, that are able to stoichiometrically outcompete endogenous IgE for allergen and thereby prevent allergic cascade in cases of accidental allergen exposure.

Reproductive outcomes and reproductive health care utilization among male survivors of childhood cancer: A DCCSS-LATER study.

BACKGROUND: Treatment-related gonadal dysfunction leading to fertility problems is a frequently encountered late effect in childhood cancer survivors (CCSs). This study evaluated reproductive outcomes and reproductive health care utilization among male CCSs compared with male siblings. METHODS: A nationwide cohort study was conducted as part of the Dutch Childhood Cancer Survivor LATER study part 1, a questionnaire and linkage study. A questionnaire addressing reproductive outcomes and reproductive health care was completed by 1317 male CCSs and 407 male siblings. A total of 491 CCSs and 185 siblings had a previous or current desire for children and were included in this study. RESULTS: Fewer CCSs had biological children compared with siblings (65% vs. 88%; p < .001). The type of conception by men who fathered a child was comparable between CCSs and siblings (spontaneous conception of 90% of both groups; p = .86). The percentage of men who had consulted a reproductive specialist because of not siring a pregnancy was higher in CCSs compared with siblings (34% vs. 12%; p < .001). Following consultation, fewer CCSs underwent assisted reproductive techniques (ART) compared with siblings (41% vs. 77%; p = .001). After ART, fewer CCSs fathered a child compared with siblings (49% vs. 94%; p = .001). CONCLUSIONS: More male survivors consult a reproductive specialist, but fewer survivors undergo ART and father a child after ART compared with siblings. This insight is important for understanding potential problems faced by survivors regarding family planning and emphasizes the importance of collaboration between oncologists and reproductive specialists.

Feasibility and potential effectiveness of nurse-led video-coaching interventions for childhood, adolescent, and young adult cancer survivors: the REVIVER study.

BACKGROUND: Childhood, adolescent, and young adult (CAYA) cancer survivors, at risk for late effects, including cancer-related fatigue, cardiovascular issues, and psychosocial challenges, may benefit from interventions stimulating behaviour adjustments. Three nurse-led eHealth interventions (REVIVER) delivered via video calls and elaborating on person-centred care, cognitive behaviour therapy and/or motivational interviewing were developed. These interventions target: 1) fatigue management, 2) healthier lifestyle behaviours, and 3) self-efficacy and self-management. This study aimed to assess the feasibility and potential effectiveness of the REVIVER interventions for CAYA cancer survivors and healthcare professionals. METHODS: In a single-group mixed methods design, CAYA cancer survivors aged 16-54, more than five years post-treatment, were enrolled. Feasibility, assessed via Bowen's outcomes for feasibility studies, included acceptability, practicality, integration and implementation, demand and adherence. Qualitative data from semi-structured interviews and a focus group interview with survivors and healthcare professionals supplemented the evaluation. Paired sample t-tests assessed changes in self-reported quality of life, fatigue, lifestyle, self-management, and self-efficacy at baseline (T0), post-intervention (T1), and 6-month follow-up (T2). RESULTS: The interventions and video consults were generally acceptable, practical, and successfully integrated and implemented. Success factors included the nurse consultant (i.e., communication, approach, and attitude) and the personalised approach. Barriers included sustainability concerns, technical issues, and short intervention duration. Regarding demand, 71.4%, 65.4%, and 100% of eligible CAYA cancer survivors engaged in the fatigue (N = 15), lifestyle (N = 17) and empowerment (N = 3) intervention, respectively, with 5, 5 and 2 participants interviewed, correspondingly. Low interest (demand) in the empowerment intervention (N = 3) and dropout rates of one-third for both fatigue and empowerment interventions were noted (adherence). Improvements in quality of life, fatigue (fatigue intervention), lifestyle (lifestyle intervention), self-efficacy, and self-management were evident among survivors who completed the fatigue and lifestyle interventions, with medium and large effect sizes observed immediately after the intervention and six months post-intervention. CONCLUSIONS: Our study demonstrates the feasibility of nurse-led video coaching (REVIVER interventions) despite lower demand for the empowerment intervention and lower adherence to the fatigue and empowerment interventions. The medium and high effect sizes found for those who completed the interventions hold potential clinical significance for future studies investigating the effectiveness of the REVIVER interventions.

Division of labor within the DNA damage tolerance system reveals non-epistatic and clinically actionable targets for precision cancer medicine.

Crosslink repair depends on the Fanconi anemia pathway and translesion synthesis polymerases that replicate over unhooked crosslinks. Translesion synthesis is regulated via ubiquitination of PCNA, and independently via translesion synthesis polymerase REV1. The division of labor between PCNA-ubiquitination and REV1 in interstrand crosslink repair is unclear. Inhibition of either of these pathways has been proposed as a strategy to increase cytotoxicity of platinating agents in cancer treatment. Here, we defined the importance of PCNA-ubiquitination and REV1 for DNA in mammalian ICL repair. In mice, loss of PCNA-ubiquitination, but not REV1, resulted in germ cell defects and hypersensitivity to cisplatin. Loss of PCNA-ubiquitination, but not REV1 sensitized mammalian cancer cell lines to cisplatin. We identify polymerase Kappa as essential in tolerating DNA damage-induced lesions, in particular cisplatin lesions. Polk-deficient tumors were controlled by cisplatin treatment and it significantly delayed tumor outgrowth and increased overall survival of tumor bearing mice. Our results indicate that PCNA-ubiquitination and REV1 play distinct roles in DNA damage tolerance. Moreover, our results highlight POLK as a critical TLS polymerase in tolerating multiple genotoxic lesions, including cisplatin lesions. The relative frequent loss of Polk in cancers indicates an exploitable vulnerability for precision cancer medicine.

PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome: A case report and review of the literature.

PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome is a rare autoinflammatory disorder often arising in pediatric patients. We present a case of an 18-year-old female with a past medical history of growth failure, immunoglobulin A nephropathy, and inflammatory arthritis who presented to a pediatric dermatology clinic with findings of acne, psoriasiform dermatitis, and hidradenitis suppurativa, whose clinical, genetic, and laboratory findings were most consistent with PAMI syndrome. We conducted a literature review to better characterize this rare condition in the context of dermatologic findings. Recognition of the distinctive skin findings seen in PAMI syndrome can help distinguish it from other inflammatory disorders, enabling expedited diagnosis and treatment.

Keratoconus in Down syndrome: Prevalence, risk factors, severity and corneal tomographic characteristics.

BACKGROUND: This study investigated the prevalence, risk factors and severity of corneal tomographic features of keratoconus in Down syndrome (DS). Additionally, previous studies indicate anomalous corneal features in DS, without keratoconus, this study characterised corneal features in DS without keratoconus. METHODS: This prospective observational study included participants with DS ≥10 years old. Keratoconus diagnosis, risk factors and corneal tomographic characteristics were recorded. Participants underwent slit-lamp biomicroscopy, Scheimpflug corneal tomography, corneal topography and autorefraction. A diagnosis of keratoconus (DS-KC), suspect keratoconus (DS-SK) and non-keratoconus (DS-NK) was made based on expert review of scans by three fellowship trained anterior segment ophthalmologists. Corneal tomography parameters from one eye of each participant were analysed. RESULTS: Keratoconus affected 50 (26.3%) of 190 participants, diagnosed by corneal tomography, topography or slit-lamp signs. Corneal hydrops affected 14.0% of DS-KC participants. Eye rubbing was a significant risk factor for keratoconus (p = 0.036). 175 (92%) participants could undertake corneal tomography of which tomography assessment alone identified 47 (26.9%) DS-KC participants, 64 (36.6%) DS-SK participants and 64 (36.6%) DS-NK participants. Significant differences (p < 0.001) were identified when the DS-KC, DS-SK and DS-NK groups were compared in maximum keratometry and posterior elevation at the thinnest point respectively: median (interquartile range) 50.20 (10.30D), 47.60 (1.95D), 46.50 (2.40D); 24.0 (38.00 µm), 10.00 (13.75 µm), 8.00 (6.00 µm). The DS-SK and DS-NK cohorts had similar minimum pachymetry, however, had several significantly different parameters among which included greater maximum keratometry, posterior elevation at the thinnest point in the DS-SK group. CONCLUSIONS: Keratoconus is common in DS. Keratoconus screening with corneal tomography is recommended for early detection.

Women are expected to smile: Preliminary evidence for the role of gender in the neurophysiological processing of adult emotional faces in 3-year-old children.

Children form stereotyped expectations about the appropriateness of certain emotions for men versus women during the preschool years, based on cues from their social environments. Although ample research has examined the development of gender stereotypes in children, little is known about the neural responses that underlie the processing of gender-stereotyped emotions in children. Therefore, the current study examined whether 3-year-olds differ in the neural processing of emotional stimuli that violate gender stereotypes (i.e., male faces with fearful or happy expressions) or confirm gender stereotypes (i.e., female faces with fearful or happy expressions), and whether boys and girls differ in their neural processing of the violation and confirmation of gender stereotypes. Data from 72 3-year-olds (±6 months, 43% boy) were obtained from the YOUth Cohort Study. Electroencephalography data were obtained when children passively viewed male and female faces displaying neutral, happy, or fearful facial expressions. This study provided first indications that happy male faces elicited larger P1 amplitudes than happy female faces in preschool children, which might reflect increased attentional processing of stimuli that violate gender stereotypes. Moreover, there was preliminary evidence that girls had larger negative central (Nc) responses, associated with salience processing, toward female happy faces than male happy faces, whereas boys had larger Nc responses toward male happy faces than female happy faces. No gender differences were found in the processing of neutral and fearful facial expressions. Our results indicate that electroencephalography measurements can provide insights into preschoolers' gender-stereotype knowledge about emotions, potentially by looking at the early occipital and late fronto-central responses.

The Level of Political Astuteness in Nursing Leaders: A Baseline Assessment.

OBJECTIVE: To assess the baseline knowledge of nursing leaders regarding political advocacy and healthcare policy. BACKGROUND: Although there has been considerable attention to the need for nurses' involvement in health policy, there has not been a prior assessment of the political astuteness of nursing leaders. METHODS: Researchers analyzed self-reported data from 101 nursing leaders collected via electronic survey from American Organization for Nursing Leadership members. Descriptive, correlational analysis of data assessing political astuteness and background information was completed. RESULTS: Half of the nurse leader participants demonstrated slight political astuteness. Nurse executives, including those in chief nursing officer, chief nurse executive, and vice president positions, had higher levels of political astuteness than those in nurse director and manager positions. CONCLUSION: Nursing leaders have beginning levels of political astuteness. Formal education is recommended to increase the knowledge base of nurse leaders in the areas of understanding the political and legislative process and the skills needed to advocate regarding healthcare policy, thus increasing their level of political astuteness.

Facilitators of and Barriers to the Therapeutic Nurse-Patient Relationship: Perceptions From Psychiatric Mental Health Nurses.

BACKGROUND: The therapeutic relationship serves as a cornerstone in psychiatric mental health nursing practice, providing a basis for implementing various interventions. AIMS: This study aimed to explore the perspectives of psychiatric mental health nurses regarding factors that facilitate and impede the therapeutic nurse-patient relationship. METHODS: A descriptive study was conducted among psychiatric mental health nurses employed at two community psychiatric hospitals in the northeast area of the United States. A list of facilitators and barriers was developed based on an extensive literature review and subsequently validated by three experts in the field of psychiatric mental health nursing. Participants rated these factors on a 10-point scale. RESULTS: The study included 74 registered nurses from two psychiatric hospitals, yielding a 24% response rate. The highest-ranked facilitator was awareness that the relationship enables collaborative goal setting with patients. The most significant barrier was insufficient time due to administrative tasks. CONCLUSIONS: This study highlights the importance of understanding facilitators and barriers in the therapeutic nurse-patient relationship. Replicating the study nationally on a larger scale among psychiatric mental health nurses is recommended.

Desire for children among male survivors of childhood cancer: A DCCSS LATER study.

BACKGROUND: Knowledge of the desire for children among childhood cancer survivors (CCSs) is scarce. This study evaluated the desire for children in male CCSs in comparison with male siblings. METHODS: A nationwide cohort study was conducted as part of the Dutch Childhood Cancer Survivor Study LATER study: 1317 male CCSs and 407 male sibling controls completed a questionnaire addressing the desire for children. Logistic regression analyses were used to explore the independent association between survivorship status and the desire for children. Furthermore, additional analyses were performed to identify which cancer-related factors were associated with the desire for children in male CCSs. RESULTS: After adjustments for the age at assessment, the percentage of men who had a desire for children was significantly lower among CCSs compared with the siblings (74% vs. 82%; odds ratio [OR], 0.61; 95% CI, 0.46-0.82; p = .001). The association between survivorship status and the desire for children was attenuated after adjustments for marital status, level of education, and employment status (OR, 0.83; 95% CI, 0.61-1.14; p = .250). The percentage of men who had an unfulfilled desire for children remained significantly higher among CCSs compared with the siblings after adjustments for sociodemographic factors (25% vs. 7%; OR, 5.14; 95% CI, 2.48-10.64; p < .001). CONCLUSIONS: The majority of male CCSs have a desire for children. The likelihood of having to deal with an unfulfilled desire for children is 5 times higher among CCSs compared with their siblings. This insight is important for understanding the needs and experienced problems of CCSs regarding family planning and fertility issues.

Efficacy, safety, and tolerability of nivasorexant in adults with binge-eating disorder: A randomized, Phase II proof of concept trial.

OBJECTIVE: This Phase II, placebo-controlled, double-blind study investigated the efficacy, safety, and tolerability of nivasorexant in the treatment of adults with moderate to severe binge-eating disorder (BED). METHODS: Adults meeting the DSM-5 BED criteria were randomized 1:1 to placebo or nivasorexant (100 mg b.i.d.). The primary endpoint was the change from baseline to Week 12 in the number of binge eating (BE) days per week. Exploratory efficacy endpoints included cessation of BE in the last 4 weeks of treatment; and change from baseline to Week 12 in the number of BE episodes/week, the clinician global impression (CGI) of change, the Yale-Brown Obsessive-Compulsive Scale modified for BE, and the Hamilton rating scale for depression (HAMD-17). Key safety outcomes included treatment-emergent adverse events (TEAEs) and adverse events of special interest (i.e., somnolence and fatigue). RESULTS: Sixty-eight participants were randomized to each treatment arm. The change from baseline to Week 12 in the number of BE days/week was the same for placebo (least squares mean [LSM]: -2.93) and nivasorexant (LSM: -2.93), with no difference between the treatment groups (LSM difference = .000 [95% confidence interval (CI): -.69, .69], p = .9992). Furthermore, no differences between treatment groups were observed in the exploratory efficacy endpoints. Nivasorexant was well tolerated; the overall incidence of TEAEs was balanced between treatment groups, and the frequency of somnolence and fatigue in the nivasorexant group were similar to placebo. DISCUSSION: In this proof-of-concept study, 100 mg b.i.d. nivasorexant did not improve BE in adults with moderate to severe BED. PUBLIC SIGNIFICANCE: The results of this Phase II study indicate that nivasorexant was well tolerated in adults with BED, but did not improve binge eating behavior over placebo. Further research is needed to improve our understanding of the role of the orexin-1 receptor in BED.

Associations between parental dispositional attributions, dismissing and coaching reactions to children's emotions, and children's problem behaviour moderated by child gender.

This study examined whether parents' attribution of their child's emotions (internalizing, externalizing) to dispositional causes is associated with children's problem behaviour (internalizing, externalizing). The mediating roles of parents' emotion-dismissing and -coaching reactions and the moderating role of child's gender was also examined. Participants were 241 US parents with a child (43% girls) between the ages of 5 and 7. Parents were presented with vignettes in which a gender-neutral child displayed internalizing and externalizing emotions and were asked to imagine their own child in the vignettes. Subsequently, parents indicated whether they attributed the child's emotion to dispositional causes and the likelihood of reacting in an emotion-dismissing and -coaching way in each situation. Child problem behaviour was measured using the CBCL. Results show that parental dispositional attributions were associated with child internalizing and externalizing problems, and this association was consistently mediated by emotion-dismissing reactions. The association between parental dispositional attributions and emotion-dismissing, as well as its indirect effect on child internalizing problems, was stronger for boys than for girls, whereas the indirect effect via emotion-coaching was stronger for girls than for boys. Thus, the parental attribution process seems to be different for boys and girls.

Individual and Work-Related Characteristics Associated with COVID-19 Vaccination Status among Ohio Nurses.

Uptake of the COVID-19 vaccine by nurses lags behind that of other health care professionals with minimal empirical evidence to understand this phenomenon. In this secondary analysis, we examined nurses' individual and work-related characteristics and their association with COVID-19 vaccination status. Alumni of three Ohio nursing colleges and members of a professional organization were invited to complete questionnaires from June through August 2021. Logistic regression models were used to evaluate associations between nurse characteristics and vaccination status. Among 844 respondents, 754 (80.30%) had received at least one dose of the vaccine. Older age, having a bachelor's degree or higher, and working in critical care were associated with vaccination. Providing direct care for COVID-19 patients in the last 7 days and a higher perception of one's work being affected by COVID-19 were significantly associated with being vaccinated, whereas prior COVID-19 infection was inversely associated with vaccination status. Our findings suggest that COVID-19 vaccine uptake among nurses is influenced by a host of factors related to virus knowledge, beliefs, and risk perceptions. Awareness of these factors can aid the development of interventions to increase nurses' acceptance of vaccines.

Eating Disorders: Identification and Management in General Medical and Psychiatric Settings.

OBJECTIVE: Eating disorders (EDs) are serious, complex illnesses with both behavioral and physical health features. EDs have high rates of medical and psychiatric morbidity, and a 6% mortality rate, the highest of any mental illness. Early detection of EDs offers the best opportunity for recovery; yet, estimates are that as few as one in 10 individuals with an ED receive treatment. The purpose of this article is to provide an ED identification and management overview for inpatient nurse clinicians in general psychiatric and medical settings, helping to facilitate timely recognition and care. METHOD: An overview of ED diagnostic criteria and two evidence-based ED tools are introduced for consideration. RESULTS: Opportunities to identify and help manage an ED are numerous. Most individuals with an ED make several health care visits in either medical or psychiatric settings without ever being screened for an ED. General ED screening and assessment tool familiarization can facilitate a treatment trajectory for these patients, improve overall quality of life, and may potentially result in a life-saving intervention for this often-deadly cluster of medical and psychiatric disorders. CONCLUSION: Screening and assessment in general clinical settings, identifying patients with undiagnosed EDs, beginning basic treatment plans, and referrals for appropriate follow-up care, have the potential to reduce ED recidivism and related health care costs. Simultaneously, and most important, long-term outcomes for patients with EDs may improve.

Psychological Distress During Pregnancy and the Development of Pregnancy-Induced Hypertension: A Prospective Study.

OBJECTIVE: Pregnancy-induced hypertension (PIH) is associated with serious complications in both the mother and the unborn child. We examined the possible association between trajectories of maternal psychological distress symptoms and PIH separately in primiparous and multiparous women. METHODS: Pregnancy-specific negative affect (P-NA) and depressive symptoms were assessed prospectively at each trimester using the Tilburg Pregnancy Distress Scale pregnancy negative affect subscale (P-NA) and the Edinburgh Depression Scale (EDS). Data on PIH were collected from medical records. Growth mixture modeling analysis was used to identify trajectories of P-NA and EDS. The independent role of P-NA and EDS symptom trajectories on developing PIH was examined using multivariate logistic regression models. RESULTS: One hundred (7.6%) women developed PIH and were compared with 1219 women without hypertension or other complications during pregnancy. Three P-NA trajectories were identified: low stable (reference group; 90%), decreasing (5.2%), and increasing (4.8%). The latter two classes showed persistently and significantly higher P-NA symptoms during pregnancy compared with the reference group. In multiparous women, high P-NA scores (belonging to classes 2 and 3) were related to PIH (odds ratio [OR] = 6.91, 95% confidence interval [CI] = 2.26-21.2), independent of body mass index (OR = 1.17, 95% CI = 1.06-1.27) and previous PIH (OR = 14.82, 95% CI = 6.01-32.7). No associations between P-NA and PIH were found in primiparous women. EDS trajectories were not related to PIH in both primiparous and multiparous women. CONCLUSIONS: In multiparous women, persistently high levels of P-NA symptoms but not depressive symptoms were independently associated with development of PIH.

The changing impact of cytomegalovirus among hematopoietic cell transplant recipients during the past decade: A single institutional cohort study.

BACKGROUND: With advancements in allogeneic hematopoietic cell transplantation (alloHCT), the need for cytomegalovirus (CMV) surveillance persists. METHODS: We present a retrospective analysis on the impact of CMV with preemptive therapy in 1065 alloHCT patients with donor and/or recipient CMV seropositivity from 2009 to 2019. RESULTS: Fifty-one percent developed clinically significant CMV infection (CMV-CSI); 6.5% had CMV disease. In multivariate analysis stratified by serostatus and preparative regimen, the use of anti-thymocyte globulin (hazard ratios 2.97, 95% confidence interval 2.00-4.42, p < .001) was associated with development of CMV-CSI. Median length of stay for index hospitalization was longer in patients with CMV-CSI (27 vs. 25 days, respectively; p = .002), as were rates (32.9% vs. 17.7%; p < .001) and duration (9 d vs. 6 d; p < .001) of rehospitalization, and median total inpatient days (28 d vs. 26 d; p < .001). Patients with CMV-CSI had higher rates of neutropenia (47% vs. 20%; p < .001) and transfusion support (packed red blood cell, median 5 vs. 3; p < .001; platelets, median 3 vs. 3; p < .001). CONCLUSION: Preemptive therapy does not negate the impact of CMV-CSI on peri-engraftment toxicity and healthcare utilization. This cohort represents a large single center study on the impact of CMV in the preletermovir era and serves as a real-world comparator for assessing the impact of future prophylaxis.

Characterizing spatiotemporal variability in airborne heavy metal concentration: Changes after 18 Years in Baltimore, MD.

INTRODUCTION: This study investigates the impact of changes in local industry, urban development, and proximity to suspected emission sources on airborne metal concentration in Baltimore, Maryland between 2001 and 2019 with particular focus on the urban industrial community of Curtis Bay in South Baltimore. METHODS: Integrated PM2.5 and PM10 Harvard Impactors were set up at six locations in the Baltimore City metropolitan area in weeklong sampling sessions from January-July 2019 to assess variation in airborne metal concentration by proximity to suspected metal emission sources. PM2.5 and PM10 were collected on Teflo filters and analyzed for a panel of 12 metals and metalloids (As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Sb, and Zn) using inductively coupled plasma mass spectrometry. The findings were compared against airborne metal concentrations reported by the Baltimore Supersite in 2001 and 2003 to assess changes over the 18-year period. RESULTS: PM2.5 concentrations reported from this study ranged from 3.27 µg/m3 to 36.0 µg/m3 and PM10 concentrations ranged from 9.00 µg/m3 to 30.1 µg/m3 across all sampling sites. Metal concentrations ranged from 1.4 times (Cd) to 4.8 times (Cr) higher in PM10 compared to PM2.5. Compared to the study reference site, median PM2.5 concentrations of Co and Fe were roughly 1.8 times and 2.1 times higher, respectively, at near-road sampling sites indicating significant variability in airborne metal concentration by proximity to local traffic emissions. PM2.5 and PM10 Sb concentrations were 3.4 times and 6.7 times higher at a near incinerator site compared to the reference, consistent with existing evidence of Sb sourcing from municipal incinerators in Baltimore City. Decreases in Cr (-40%), Ni (-73%), Pb (-55%), and Zn (-36%) concentrations were observed over the 18-year period while concentrations of Cu, Fe, and Mn were not statistically significantly different. CONCLUSION: Declines in airborne Cr, Ni, Pb, and Zn concentration since 2001 appear to coincide with industrial decline highlighting the success of remediation and redevelopment efforts. Remaining spatial variability is related to vehicular traffic and proximity to a municipal incinerator which should be focal areas for future intervention to reduce metal exposure disparities in Baltimore City.

Sexual Double Standards: Contributions of Sexual Socialization by Parents, Peers, and the Media.

(Hetero)sexual double standards (SDS) entail that different sexual behaviors are appropriate for men and women. There is large variation in whether people endorse SDS in their expectations about the sexual behavior of women and men (i.e., SDS-norms). To explain these individual differences, we examined associations between SDS-norms of Dutch adolescents (aged 16-20 years, N = 566) and what parents, peers, and the media teach adolescents about appropriate sexual behavior of boys and girls (i.e., SDS-socialization). Adolescents completed an online survey at school. Regarding SDS-socialization, more traditional SDS-norms conveyed by the media and peers, but not of parents, and less perceived sexual activity of female peers, were associated with more traditional SDS-norms. Only for boys, exposure to sexy girls/women on social media and sexual music videos of female artists were associated with more traditional SDS-norms. Thus, SDS-socialization by peers and the media and opposite gender models (for boys) are important in light of adolescents' SDS-norms.

Preoperative Calcium and Parathyroid Hormone Values Are Poor Predictors of Gland Volume and Multigland Disease in Primary Hyperparathyroidism: A Review of 2000 Consecutive Patients.

OBJECTIVE: Calcium and parathyroid hormone (PTH) values are believed to have a linear relationship in patients with primary hyperparathyroidism and correlate with parathyroid gland size, with higher values predicting single-gland disease. In this modern series, these preoperative values were correlated with operative findings to determine their utility in predicting the gland involvement at parathyroid exploration. METHODS: Two thousand consecutive patients who underwent initial surgery for sporadic primary hyperparathyroidism from 2000 to 2014 were reviewed. All patients underwent a 4-gland exploration. Relationships between preoperative calcium and PTH values with the total gland volume of each patient were examined and stratified using the number of involved glands: single adenoma (SA), double adenoma (DA), and hyperplasia (H). RESULTS: There were 1274 (64%) SA, 359 (18%) DA, and 367 (18%) H cases. There was a poor correlation between preoperative calcium and PTH values (R = 0.37) and both poorly correlated with the total gland volume (R < 0.40). Similarly, subgroup analysis using the number of involved glands showed poor correlation. The mean total gland volume was similar among all subgroups (SA = 1.28 cm3, DA = 1.43 cm3, and H = 1.27 cm3; P = .52), implying that individual glands were smaller in multigland disease. SA was found in 271 (53%) of patients with calcium levels of ≤10.5 mg/dL and 122 (78%) with levels of ≥12 mg/dL (P < .001). CONCLUSION: This is the largest series correlating preoperative calcium and PTH values with operative findings of gland size and number of diseased glands. Although a lower calcium value predicts somewhat more multigland disease, the overall poor correlation should make the parathyroid surgeon aware that gland size and multigland disease cannot be predicted by preoperative laboratory testing.