Search

Laboratories offering cell-free DNA often reserve the right to share prenatal genetic data for research or even commercial purposes, and obtain this permission on the patient consent form. Although it is known that nonpregnant patients are often reluctant to share their genetic data for research, pregnant patients' knowledge of, and opinions about, genetic data privacy are unknown.We investigated whether pregnant patients who had already undergone cell-free DNA screening were aware that genetic data derived from cell-free DNA may be shared for research. Furthermore, we examined whether pregnant patients exposed to video education about the Genetic Information Nondiscrimination Act-a federal law that mandates workplace and health insurance protections against genetic discrimination-were more willing to share cell-free DNA-related genetic data for research than pregnant patients who were unexposed.In this randomized controlled trial (ClinicalTrials.gov Identifier: NCT04420858), English-speaking patients with singleton pregnancies who underwent cell-free DNA and subsequently presented at 17 0/7 to 23 6/7 weeks of gestation for a detailed anatomy scan were randomized 1:1 to a control or intervention group. Both groups viewed an infographic about cell-free DNA. In addition, the intervention group viewed an educational video about the Genetic Information Nondiscrimination Act. The primary outcomes were knowledge about, and willingness to share, prenatal genetic data from cell-free DNA by commercial laboratories for nonclinical purposes, such as research. The secondary outcomes included knowledge about existing genetic privacy laws, knowledge about the potential for reidentification of anonymized genetic data, and acceptability of various use and sharing scenarios for prenatal genetic data. Eighty-one participants per group were required for 80% power to detect an increase in willingness to share data from 60% to 80% (α=0.05).A total of 747 pregnant patients were screened, and 213 patients were deemed eligible and approached for potential study participation. Of these patients, 163 (76.5%) consented and were randomized; one participant discontinued the intervention, and two participants were excluded from analysis after the intervention when it was discovered that they did not fulfill all eligibility criteria. Overall, 160 (75.1%) of those approached were included in the final analysis. Most patients in the control group (72 [90.0%]) and intervention (76 [97.4%]) group were either unsure about or incorrectly thought that cell-free DNA companies could not share prenatal genetic data for research. Participants in the intervention group were more likely to incorrectly believe that their prenatal genetic data would not be shared for nonclinical purposes than participants in the control group (28.8% in the control group vs 46.2% in the intervention; P=.03). However, video education did not increase participant willingness to share genetic data in multiple scenarios. Non-White participants were less willing than White participants to allow sharing of genetic data specifically for academic research (P.001).Most participants were unaware that their prenatal genetic data may be used for nonclinical purposes. Pregnant patients who were educated about the Genetic Information Nondiscrimination Act were not more willing to share genetic data than those who did not receive this education. Surprisingly, video education about the Genetic Information Nondiscrimination Act led patients to falsely believe that their data would not be shared for research, and participants who identified as racial minorities were less willing to share genetic data. New strategies are needed to improve pregnant patients' understanding of genetic privacy.

As induction of labor (IOL) becomes more common, hospitals must adjust to accommodate longer length of stays on labor and delivery. An alternative to reduce the length of time spent on labor and delivery during an IOL is to perform cervical ripening on an antepartum unit. However, this may affect patient satisfaction and knowledge about the birthing process. This study aimed to evaluate whether cervical ripening conducted in an antepartum unit, rather than on a labor and delivery unit, was associated with changes in patient satisfaction with birth experience and baseline knowledge about IOL. Additionally, the study aimed to understand how patients would prefer to receive education on the IOL process.This prospective observational study recruited English and Spanish-speaking patients at or after 39 weeks and 0 days gestation who were admitted for IOL. Consenting patients completed a preliminary survey containing sociodemographic and obstetric information as well as a previously validated survey on IOL knowledge on admission. Within 48 h of delivery, patients completed a follow-up survey including a validated birth satisfaction survey, the Birth Satisfaction Scale-Revised, and questions eliciting their preferred IOL education method. Data analyses compared patients who were admitted to antepartum for IOL to those admitted directly to labor and delivery. Multivariate analyses adjusted for sociodemographic and obstetric differences between the two groups. The primary outcomes were scores on the Birth Satisfaction Scale-Revised and on a test examining IOL knowledge. Secondary outcomes included preferred method of IOL education, obstetric outcomes, and neonatal outcomes.A total of 277 eligible patients were approached from October 2020 to March 2021. Of the 216 (78%) that consented, 159 (74%) completed the follow-up survey and were subsequently included in this analysis. Individuals admitted directly to antepartum (Unit of admission for IOL is not associated with satisfaction with birth experience but is associated with patient knowledge of IOL. This suggests that IOL may be initiated in less acute units than labor and delivery without altering birth experience and may potentially allow for increased patient knowledge. Additionally, IOL checklists or technology-based education may help to further increase patient knowledge about IOL.

Background Cancer patients experience increased risk of death from accident and suicide. Cognitive impairment induced by cancer-related inflammation and stress-related psychiatric symptoms may be underlying mechanisms. We therefore studied the association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of these outcomes. Methods Following a cohort of 388,443 cancer patients diagnosed between October 2005 and December 2014 in Sweden, we ascertained dispense of aspirin or non-aspirin NSAIDs from 3 months before cancer diagnosis onward and defined the on-medication period as from date of drug dispense until the prescribed dosage was consumed. Follow-up time outside medicated periods and time from unexposed patients were defined as off-medication periods. We used Cox models to estimate hazard ratios (HRs) of death due to suicide or accident, by comparing the on-medication periods with off-medication periods. Results In total, 29.7% of the cancer patients had low-dose aspirin dispensed and 29.1% had non-aspirin NSAIDs dispensed. Patients with aspirin use were more likely to be male than patients without aspirin use. Compared with off-medication periods, there was a 22% lower risk of accidental death (N = 651; HR 0.78, 95% confidence interval [CI]: 0.70 to 0.87) during on-medication periods with aspirin. The use of aspirin was not associated with risk of suicide (N = 59; HR 0.96, 95% CI: 0.66 to 1.39). No association was noted between use of non-aspirin NSAIDs and the risk of suicide (N = 13; HR 0.95, 95% CI: 0.42 to 2.18) or accidental death (N = 59; HR 0.92, 95% CI: 0.68 to 1.26). Conclusions Intake of low-dose aspirin after cancer diagnosis was associated with a lower risk of unnatural deaths among cancer patients.

OBJECTIVE We examined weight loss patterns and feeding practices of infants hospitalized for neonatal opioid withdrawal syndrome (NOWS) managed by the eat, sleep, console approach, which emphasizes nonpharmacologic treatment. Although feeding practices during hospitalization vary widely, weight loss patterns for infants managed under this approach have not yet been described. METHODS Of 744 infants with NOWS born from 2014 to 2019 at our institution, 330 met inclusion criteria (≥35 weeks’ gestation and no NICU transfer). We examined maximum weight loss and created weight loss percentile curves by delivery type using mixed effects quantile modeling with spline effect for hour of life; 95% confidence intervals (CI) were compared to published early weight loss nomograms. RESULTS In the cohort, the mean gestational age was 39.2 weeks, mean birth weight was 3.1 kg, and mean length of stay was 6.5 days; 94.6% did not require pharmacologic treatment. Median percent weight loss was significantly more compared to early weight loss nomograms for both vaginally-delivered infants at 48 hours (6.9% [95% CI: 5.8–8.5] vs 2.9%) and cesarean-delivered infants at 48 hours (6.5% [95% CI: 4.1–9.1] vs 3.7%) and 72 hours (7.2% [95%CI 4.7–9.9] vs 3.5%), all P < .001. Overall, 27.9% lost >10% birth weight. CONCLUSIONS We demonstrate weight loss patterns of infants with NOWS managed by the eat, sleep, console approach at a single center. Infants with NOWS lose significantly more weight than nonopioid exposed infants and are at increased risk of morbidity and health care use. Studies to address optimal feeding methods in these infants are warranted.

Characterization of germinal center B and T cell responses yields critical insights into vaccine immunogenicity. Nonhuman primates are a key preclinical animal model for human vaccine development, allowing both lymph node (LN) and circulating immune responses to be longitudinally sampled for correlates of vaccine efficacy. However, patterns of vaccine Ag drainage via the lymphatics after i.m. immunization can be stochastic, driving uneven deposition between lymphoid sites and between individual LN within larger clusters. To improve the accurate isolation of Ag-exposed LN during biopsies and necropsies, we developed and validated a method for coformulating candidate vaccines with tattoo ink in both mice and pigtail macaques. This method allowed for direct visual identification of vaccine-draining LN and evaluation of relevant Ag-specific B and T cell responses by flow cytometry. This approach is a significant advancement in improving the assessment of vaccine-induced immunity in highly relevant nonhuman primate models.

To determine the relationship between maternal age and labor induction duration among nulliparous women.This retrospective cohort study included nulliparous women with non-anomalous, term, singleton pregnancies undergoing labor induction with intact membranes at a tertiary-care academic hospital from January 2015 to April 2017. Maternal age was stratified as follows:25 years, 25-29 years, 30-34 years, 35-39 years, and ≥ 40 years. The primary outcome was induction duration, defined as the time the first induction agent was administered to time of birth. Secondary outcomes were cesarean delivery, cesarean indication, hemorrhage, blood transfusion, peripartum infection, composite neonatal morbidity, and induction duration among the subset of women who ultimately underwent cesarean. The data were analyzed using chi-squared and Fisher exact tests. Multivariable regression was used to adjust for maternal race/ethnicity, maternal body mass index, gestational age at start of induction, and induction indication. Hazard ratios were used to calculate induction duration among women who underwent cesarean delivery, stratified by age and adjusted by the same variables.Among the 955 patients included, the median induction duration was 32.3 h (interquartile range (IQR) 20.4-41.0 h). Women 40 years and older had a slight increase in induction duration (adjusted odds ratio (aOR) 1.03, 95% confidence interval (CI) 1.01-1.05) and a seven-fold increased risk of induction lasting 60 h or longer (adjusted relative risk (aRR) 7.3, CI 1.8-29.9) when compared to those under 25 years of age; otherwise, there was no association between maternal age and labor induction duration. There was no association between age and cesarean delivery, cesarean indication, hemorrhage, transfusion, peripartum infection, or adverse neonatal outcomes. Furthermore, there was no association between maternal age and induction duration even among women who ultimately underwent cesarean.We found no association between maternal age and induction duration for women under 40 years of age. For women 40 years of age and older, these was an increased risk of labor induction lasting 60 h or longer. Despite this, we found no association between maternal age and cesarean delivery or other adverse maternal or fetal outcomes.

Hereditary angioedema (HAE) is a disease manifested by repeated episodes of localized submucosal or subcutaneous edematous episodes, potentially triggered by emotional stress, mechanical trauma, or intake of estrogens. We present our experience managing two parturients with HAE. Multidisciplinary care is essential for planning and executing the specialized care of these patients, and management included extensive planning among obstetric, anesthesiology, and allergy and immunology teams. Pregnancy has been shown to have a variable effect on triggering HAE episodes. First-line treatment includes C1 esterase inhibitor concentrate, which can also be used for prophylaxis in high-risk patients. Neuraxial analgesia is recommended to avoid general anesthesia and was established early in both individuals. Vaginal delivery was well tolerated without need for emergent treatment for angioedema symptoms.

We aimed to determine a safe zone of intraoperative fluid management associated with the lowest postoperative complication rates without increased acute kidney injury (AKi) risk for elective colorectal surgery patients. To date, standard practice within institutions, let alone national expectations related to fluid administration, are limited. This fact has perpetuated a quality gap. Elective colorectal surgeries between 2018 and 2020 were included. Unadjusted odds ratios (ORs) for postoperative ileus, prolonged LOS, and AKi were plotted against the rate of intraoperative RL infusion (mL/ kg/h) and total intraoperative volume. Binary logistic regression analysis, including fluid volumes as a confounder, was used to identify risk factors for postoperative complications. A total of 2900 patients were identified. Of them, 503 (17.3%) patients had ileus, 772 (26.6%) patients had prolonged LOS, and 240 (8.3%) patients had AKI. The intraoperative fluid resuscitation rate (mg/kg/h) was less impactful on postoperative ileus, LOS, and AKI than the total amount of intraoperative fluid. A total fluid administration range between 300 mL and 2.7 L was associated with the lowest complication rate. Total intraoperative RL ≥2.7 L was independently associated with a higher risk of ileus (adjusted OR 1.465; 95% confidence interval 1.154-1.858) and prolonged LOS (adjusted OR 1.300; 95% confidence interval 1.047-1.613), but not AKI. Intraoperative RL ≤300 mL was not associated with an increased risk of AKI. Total intraoperative RL ≥2.7 L was independently associated with postoperative ileus and prolonged LOS in elective colorectal surgery patients. A new potential standard for intraoperative fluids will require anesthesia case planning (complexity and duration) to ensure total fluid volume meets this new opportunity to improve care.

Shared bacteria between maternal breast milk and infant stool, infers that transfer of maternal breast milk microbiota through breastfeeding seeds the establishment of the infant gut microbiome. Whether combination antiretroviral therapy (cART) impacts the breast milk microbiota in women living with HIV is unknown. Since current standard of care for people living with HIV includes cART, it has been difficult to evaluate the impact of cART on the microbiome. Here, we performed a next-generation sequencing retrospective study from pre-ART era clinical trials in Nairobi, Kenya (between 2003-2006 before cART was standard of care) that tested the effects of ART regimens to prevent mother-to-child HIV transmission. Kenyan women living with HIV were randomized to receive either no ART during breastfeeding (

For breast cancer patients, the extent of regional lymph node (LN) metastasis influences the decision to remove all axillary LNs. Metastases are currently identified and classified with visual analysis of a few thin tissue sections with conventional histology that may underrepresent the extent of metastases.We sought to enable nondestructive three-dimensional (3D) pathology of human axillary LNs and to develop a practical workflow for LN staging with our method. We also sought to evaluate whether 3D pathology improves staging accuracy in comparison to two-dimensional (2D) histology.We developed a method to fluorescently stain and optically clear LN specimens for comprehensive imaging with multiresolution open-top light-sheet microscopy. We present an efficient imaging and data-processing workflow for rapid evaluation of HE-like datasets in 3D, with low-resolution screening to identify potential metastases followed by high-resolution localized imaging to confirm malignancy.We simulate LN staging with 3D and 2D pathology datasets from 10 metastatic nodes, showing that 2D pathology consistently underestimates metastasis size, including instances in which 3D pathology would lead to upstaging of the metastasis with important implications on clinical treatment.Our 3D pathology method may improve clinical management for breast cancer patients by improving staging accuracy of LN metastases.

Significance As the recall of CD8+ T cell memory promotes rapid recovery in, for example, influenza, we investigated circulating SARS-CoV-2−specific CD8+ T cells from COVID-19 patients. For two HLA-A*02:01 SARS-CoV-2−specific CD8+ T cell epitopes, we found that, while ex vivo frequencies of responding T cells were approximately fivefold higher than for pre−COVID-19 samples, they were ∼10-fold lower than for influenza or EBV-specific memory CD8+ T cells. Additionally, SARS-CoV-2−specific CD8+ T cells recovered from convalescent COVID-19 patients had an atypically high prevalence of stem cell memory, central memory, and naïve phenotypes. Might this unexpectedly low prevalence of classical effector memory T cells be a negative consequence of the infectious process that could be avoided by prior priming with an appropriately constituted vaccine?, An improved understanding of human T cell-mediated immunity in COVID-19 is important for optimizing therapeutic and vaccine strategies. Experience with influenza shows that infection primes CD8+ T cell memory to peptides presented by common HLA types like HLA-A2, which enhances recovery and diminishes clinical severity upon reinfection. Stimulating peripheral blood mononuclear cells from COVID-19 convalescent patients with overlapping peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to the clonal expansion of SARS-CoV-2−specific CD8+ and CD4+ T cells in vitro, with CD4+ T cells being robust. We identified two HLA-A*02:01-restricted SARS-CoV-2-specfic CD8+ T cell epitopes, A2/S269–277 and A2/Orf1ab3183–3191. Using peptide−HLA tetramer enrichment, direct ex vivo assessment of A2/S269+CD8+ and A2/Orf1ab3183+CD8+ populations indicated that A2/S269+CD8+ T cells were detected at comparable frequencies (∼1.3 × 10−5) in acute and convalescent HLA-A*02:01+ patients. These frequencies were higher than those found in uninfected HLA-A*02:01+ donors (∼2.5 × 10−6), but low when compared to frequencies for influenza-specific (A2/M158) and Epstein–Barr virus (EBV)-specific (A2/BMLF1280) (∼1.38 × 10−4) populations. Phenotyping A2/S269+CD8+ T cells from COVID-19 convalescents ex vivo showed that A2/S269+CD8+ T cells were predominantly negative for CD38, HLA-DR, PD-1, and CD71 activation markers, although the majority of total CD8+ T cells expressed granzymes and/or perforin. Furthermore, the bias toward naïve, stem cell memory and central memory A2/S269+CD8+ T cells rather than effector memory populations suggests that SARS-CoV-2 infection may be compromising CD8+ T cell activation. Priming with appropriate vaccines may thus be beneficial for optimizing CD8+ T cell immunity in COVID-19.

Background Pathological forms of TAR DNA-binding protein 43 (TDP-43) are present in motor neurons of almost all amyotrophic lateral sclerosis (ALS) patients, and mutations in TDP-43 are also present in ALS. Loss and gain of TDP-43 functions are implicated in pathogenesis, but the mechanisms are unclear. While the RNA functions of TDP-43 have been widely investigated, its DNA binding roles remain unclear. However, recent studies have implicated a role for TDP-43 in the DNA damage response. Methods We used NSC-34 motor neuron-like cells and primary cortical neurons expressing wildtype TDP-43 or TDP-43 ALS associated mutants (A315T, Q331K), in which DNA damage was induced by etoposide or H2O2 treatment. We investigated the consequences of depletion of TDP-43 on DNA repair using small interfering RNAs. Specific non homologous end joining (NHEJ) reporters (EJ5GFP and EJ2GFP) and cells lacking DNA-dependent serine/threonine protein kinase (DNA-PK) were used to investigate the role of TDP-43 in DNA repair. To investigate the recruitment of TDP-43 to sites of DNA damage we used single molecule super-resolution microscopy and a co-immunoprecipitation assay. We also investigated DNA damage in an ALS transgenic mouse model, in which TDP-43 accumulates pathologically in the cytoplasm. We also examined fibroblasts derived from ALS patients bearing the TDP-43 M337V mutation for evidence of DNA damage. Results We demonstrate that wildtype TDP-43 is recruited to sites of DNA damage where it participates in classical NHEJ DNA repair. However, ALS-associated TDP-43 mutants lose this activity, which induces DNA damage. Furthermore, DNA damage is present in mice displaying TDP-43 pathology, implying an active role in neurodegeneration. Additionally, DNA damage triggers features typical of TDP-43 pathology; cytoplasmic mis-localisation and stress granule formation. Similarly, inhibition of NHEJ induces TDP-43 mis-localisation to the cytoplasm. Conclusions This study reveals that TDP-43 functions in DNA repair, but loss of this function triggers DNA damage and is associated with key pathological features of ALS.

Background and objectivesThoracic paravertebral blockade is often used as an anesthetic and/or analgesic technique for breast surgery. With ultrasound guidance, the rate of complications is speculated to be lower than when using landmark-based techniques. This investigation aimed to quantify the incidence of pleural puncture and pneumothorax following non-continuous ultrasound-guided thoracic paravertebral blockade for breast surgery.MethodsPatients who received thoracic paravertebral blockade for breast surgery were identified by retrospective query of our institution’s electronic database over a 5-year period. Data collected included patient demographics, level of block, type and volume of local anesthetic, occurrence of pleural puncture, occurrence of pneumothorax, evidence of local anesthetic toxicity, and patient vital signs. The incidence of block complications, including pleural puncture, pneumothorax, and local anesthetic toxicity, were ascertained.Results529 patients underwent 2163 thoracic paravertebral injections. Zero pleural punctures were identified during block performance; however, two patients were found to have a pneumothorax on postoperative chest X-ray (3.6 per 1000 surgeries, 95% CI 0.5 to 13.6; 0.9 per 1000 levels blocked, 95% CI 0.1 to 3.3). There were no cases of local anesthetic systemic toxicity or associated lipid emulsion therapy administration.ConclusionsPneumothorax following non-continuous ultrasound-guided thoracic paravertebral block using a parasagittal approach is an uncommon occurrence, with a similar rate to pneumothorax following breast surgery alone.

We sought to determine hemodynamic mechanisms of exercise intolerance in a group of patients with the HeartWare ventricular assist device (VAD) compared to a group of heart failure patients. Twenty VAD and 22 heart failure patients underwent symptom-limited active straight leg raising exercise during right heart catheterization with thermodilution (TD), and upright cycling cardiopulmonary stress testing with cardiac output measurement by inert gas rebreathing (IGR) method. The TD and IGR exercise cardiac indexes were higher in VAD compared with heart failure group (both P < 0.05), although there was only a borderline increase in peak exercise oxygen consumption (VO2) (P = 0.06). Baseline and exercise right heart catheterization pressures were not significantly different between the two groups. The only significant independent predictors of peak VO2 in the heart failure group were exercise heart rate and cardiac index (both P < 0.05). In contrast, for the VAD group only, resting pulmonary arterial wedge and pulmonary arterial mean pressures were independently related to peak VO2 (both P < 0.05). Thus, in heart failure, exercise cardiac index is an important limitation to exercise capacity, and VADs increase exercise cardiac index. However, in VAD patients, this only produces limited benefits as increased pulmonary and pulmonary wedge pressures limit increases in exercise capacity.

Fluctuations in mental and bodily states have both been shown to be associated with negative affective experience. Here we examined how momentary fluctuations in attentional and cardiac states combine to regulate the perception of positive social value. Faces varying in trustworthiness were presented during a go/no-go letter target discrimination task synchronized with systolic or diastolic cardiac phase. Go trials lead to an attentional boosting of perceived trust on high trust and ambiguous neutral faces, suggesting attention both boosted existing and generated positive social value. Cardiac phase during face presentation interacted with attentional boosting of trust, enhancing high trust faces specifically during relaxed diastolic cardiac states. Confidence judgments revealed that attentional trust boosting, and its cardiac modulation, did not reflect altered perceptual or response fluency. These results provide evidence for how moment-to moment fluctuations in top-down mental and bottom-up bodily inputs combine to enhance a priori and generate de novo positive social value.

The accelerated risk of cardiovascular disease (CVD) in Rheumatoid Arthritis (RA) requires further study of the underlying pathophysiology and determination of the at-risk RA phenotype. Our objectives were to describe the cardiac structure and function and arterial stiffness, and association with disease phenotype in patients with established) RA, in comparison to healthy controls, as measured by cardiovascular magnetic resonance imaging (CMR). 76 patients with established RA and no history of CVD/diabetes mellitus were assessed for RA and cardiovascular profile and underwent a non-contrast 3T-CMR, and compared to 26 healthy controls. A univariable analysis and multivariable linear regression model determined associations between baseline variables and CMR-measures. Ten-year cardiovascular risk scores were increased in RA compared with controls. Adjusting for age, sex and traditional cardiovascular risk factors, patients with RA had reduced left ventricular ejection fraction (mean difference − 2.86% (− 5.17, − 0.55) p = 0.016), reduced absolute values of mid systolic strain rate (p 2 (− 8.92, − 0.20), p = 0.041). CMR-measures predominantly associated with traditional cardiovascular risk factors; male sex and systolic blood pressure independently with increasing LVMI. Patients with established RA and no history of CVD have evidence of reduced LV systolic function and LVMI after adjustment for traditional cardiovascular risk factors; the latter suggesting cardiac pathology other than atherosclerosis in RA. Traditional cardiovascular risk factors, rather than RA disease phenotype, appear to be key determinants of subclinical CVD in RA potentially warranting more effective cardiovascular risk reduction programs.

Objective This study aimed to quantify the relative maternal and fetal risks and benefits of continuing labor induction. Study Design This retrospective cohort study included nulliparous women with nonanomalous, singleton, vertex, term pregnancies undergoing labor induction with intact membranes at a tertiary-care academic hospital from January 2015 to April 2017. The primary outcome was mode of delivery. Secondary outcomes included hemorrhage, transfusion, infection, and composite neonatal morbidity. The data were analyzed using chi-square and Fisher's exact tests. Multivariable regression was used to control for potential confounders. Results A total of 955 patients met the inclusion criteria. The median induction duration was 32.3 hours (interquartile range: 20.4–41 hours) and the vaginal delivery rate was 70.5% (n = 673). The chance of vaginal delivery at 12, 24, 36, 48, 60, and ≥60 hours was 76, 83, 77, 74, 72, and 48%, respectively. After controlling for confounders, there was a 20% decrease in chance of vaginal delivery with induction ≥ 24 hours compared with induction Conclusion In this cohort, the chance of vaginal delivery remained nearly 50% even when induction extended beyond 60 hours. Risks of hemorrhage and maternal infection rose modestly over time, but primarily in patients who underwent cesarean delivery. There was no difference in the risk of transfusion beyond 24 hours and no association between induction duration and neonatal morbidity. These findings may be useful when engaging patients in shared decision-making during labor induction.

The Movement Disorder Society criteria for progressive supranuclear palsy introduced the category 'probable 4-repeat (4R)-tauopathy' for joint clinical diagnosis of progressive supranuclear palsy and corticobasal degeneration.To validate the accuracy of these clinical criteria for 'probable 4R-tauopathy' to predict underlying 4R-tauopathy pathology.Diagnostic accuracy for 4R-tauopathies according to the established criteria was estimated retrospectively in autopsy-confirmed patients with progressive supranuclear palsy and corticobasal degeneration (grouped as 4R-tauopathies), and Parkinson's disease, multiple system atrophy, and frontotemporal lobar degeneration (grouped as non-4R-tauopathies).We identified 250 cases with progressive supranuclear palsy (N = 195) and corticobasal degeneration (N = 55) and with and non-4R-tauopathies (N = 161). Sensitivity and specificity of 'probable 4R-tauopathy' was 10% and 99% in the first year and 59% and 88% at final record.The new diagnostic category 'probable 4R-tauopathy' showed high specificity and may be suitable for the recruitment of patients with progressive supranuclear palsy and corticobasal degeneration into therapeutic trials targeting 4R-tauopathy. The low sensitivity underpins the need for diagnostic biomarkers. © 2019 International Parkinson and Movement Disorder Society.

Recent studies have established that memory B cells, largely thought to be circulatory in the blood, can take up long-term residency in inflamed tissues, analogous to widely described tissue-resident T cells. The dynamics of recruitment and retention of memory B cells to tissues and their immunological purpose remains unclear. Here, we characterized tissue-resident memory B cells (B RM ) that are stably maintained in the lungs of mice after pulmonary influenza infection. Influenza - specific B RM were localized within inducible bronchus-associated lymphoid tissues (iBALTs) and displayed transcriptional signatures distinct from classical memory B cells in the blood or spleen while showing partial overlap with memory B cells in lung-draining lymph nodes. We identified lung-resident markers, including elevated expression of CXCR3, CCR6, and CD69, on hemagglutinin (HA)– and nucleoprotein (NP)–specific lung B RM . We found that CCR6 facilitates increased recruitment and/or retention of B RM in lungs and differentiation into antibody-secreting cells upon recall. Although expression of CXCR3 and CCR6 was comparable in total and influenza-specific memory B cells isolated across tissues of human donors, CD69 expression was higher in memory B cells from lung and draining lymph nodes of human organ donors relative to splenic and PBMC-derived populations, indicating that mechanisms underpinning B RM localization may be evolutionarily conserved. Last, we demonstrate that human memory B cells in lungs are transcriptionally distinct to populations in lung-draining lymph nodes or PBMCs. These data suggest that B RM may constitute a discrete component of B cell immunity, positioned at the lung mucosa for rapid humoral response against respiratory viral infections.

OBJECTIVE: Antenatal depression (AD) is frequently cited as a risk factor for cesarean delivery (CD) with limited supporting data. STUDY DESIGN: We utilized 2016–2018 data from the Pregnancy Risk Assessment Monitoring System (PRAMS) survey for the state of Rhode Island. Nulliparous women who reported AD (n=242) were compared to women who did not (n=1,081). Maternal demographics, pregnancy and delivery characteristics were compared by AD status using population-weighted bivariable analyses and multivariable logistic regression. RESULTS: 17.7% reported AD, and 34% underwent CD. There was no difference in CD based on reported AD status (aOR 1.04; 95% CI 0.69, 1.56). However, there were significant differences between those reporting AD compared to those who did not: less education, more public insurance, use of Women, Infants and Children (WIC) benefits, tobacco use, and pre-gestational hypertension/diabetes. CONCLUSION: In this large, population-based, state representative sample, we found no difference in CD among recently delivered nulliparous women with and without AD.

OBJECTIVE The objective of this study was to assess the relevance of shunted hydrocephalus in regard to participation by young patients in physical education (PE) classes. Students diagnosed with this condition are very often restricted in PE classes owing to the lack of official and well-defined guidelines. However, the medical literature suggests that there is no relationship between the disease and risk of sport-related injuries. In this study, the authors intended to evaluate not only the accuracy of this statement, but also to explore the factors that delay or foreclose return to exercise. METHODS The analysis was conducted on patients aged < 18 years with a diagnosis of shunt-treated hydrocephalus who received follow-up for a minimum of 1 year. Collected medical data were examined for factors limiting participation in PE at school. Indicators of both sport-related injuries and conditions acceptable for return to exercise were gathered during follow-up visits. RESULTS In this study, 72.72% of patients attended sport activities in schools. The group based on return to PE class differed significantly in the occurrence of neurological deficits, as well as presence of comorbidities. In univariate analysis, the authors identified these parameters as risk factors limiting participation in PE. On the contrary, etiology of hydrocephalus, type of shunting device, number of shunt malfunctions, and presence of epilepsy did not significantly influence sport engagement. CONCLUSIONS This study shows that many patients with shunt-treated hydrocephalus can safely participate in PE. Presence of neurological deficits before and after neurosurgical treatment, as well as presence of comorbidities, are factors that negatively impact the possibility of a patient returning to physical activity. Sport-related injuries do occur, but at a low incidence.

Background Posthemorrhagic hydrocephalus of prematurity (PHHP) is a result of intraventricular hemorrhage (IVH). IVH occurs in 6 to 23% of the preterms in countries with advanced medical health care. Most of these patients will eventually require the use of ventriculoperitoneal shunt (VPS). The purpose of this study is to assess the risk factors of VPS implantation in patients with PHHP who have been treated with ventricular catheter with subcutaneous reservoir (VCSR). Methods The retrospective study was conducted evaluating 35 premature patients who suffered from severe IVH. Their mean gestational age was 28 weeks. The assessment included antenatal factors such as gestational age, birth weight, and intrauterine and perinatal infection. Postparturient period factors such as the IVH grade, time between diagnosis, and VCSR implantation and body weight on VCSR implantation were also considered in the study. Postprocedural complications, such as bacterial cerebrospinal fluid (CSF) infection, sepsis, and skin lesions, were evaluated. Data were calculated with R program, version 4.04. Results From among 35 evaluated patients, 23 (65.71%) required a VPS. Median of birth weight was 1,190 g. Infections were observed in 11 (31.43%) cases. Mean time between IVH diagnosis and VCSR implantation was 2.6 weeks. Postprocedural complications occurred in 19 (54.29%) patients. None of the evaluated factors has proven its statistical significance (p > 0.05) for being a potential risk factor for VPS implantation. Conclusion External factors seem to not affect the necessity of VPS implantation in patients after the severe IVH. Ostensibly, there seems to be no difference between the grades III and the IV of Papile's IVH scale regarding VPS implantation necessity.

Iron deficiency anemia (IDA) is common during pregnancy and associated with adverse maternal and neonatal outcomes. Treatment with iron supplementation is recommended during pregnancy, but the optimal delivery route is unclear. Oral iron risks has high risk of gastrointestinal side effects and low absorption. Intravenous iron is infused directly but is expensive. The American College of Obstetricians and Gynecologists currently recommends oral iron to treat IDA in pregnancy with intravenous iron reserved as second-line therapy, if needed. This approach is associated with persistent anemia, increasing the risk of peripartum blood transfusion. We aim to provide data on optimal route of iron repletion for IDA in pregnancy.In IVIDA2, a double-blind, placebo controlled, multicenter randomized trial in the United States, 746 pregnant people with moderate-to-severe IDA (hemoglobin10 g/dL and ferritin30 ng/mL) at 24-28 weeks' gestation will be randomized 1:1 to either a single 1000 mg dose of intravenous ferric derisomaltose and oral placebo (1-3 times daily) or a single placebo infusion with 1-3 times daily 325 mg ferrous sulfate (65 mg elemental iron) tablet. The primary outcome is peripartum blood transfusion (blood transfusion from delivery to 7 days postpartum). Secondary outcomes include adverse medication reactions, maternal and neonatal hematologic indices, and offspring neurodevelopment.A central ethical review board-Advarra-granted ethical approval (Pro00060930). Participating centers-WomenInfants Hospital of Rhode Island, University of Michigan Medical Center, Washington University School of Ethics and dissemination: A central ethical review board-Advarra-granted ethical approval (Pro00060930). Participating centers-WomenInfants Hospital of Rhode Island, University of Michigan Medical Center, Washington University School of.

OBJECTIVE Iron-deficiency anemia (IDA) can have serious consequences for mothers and babies. Iron supplementation is recommended, but the administration route is controversial. We sought to conduct a randomized controlled trial (RCT) testing the effectiveness and safety of intravenous (IV) iron compared with oral iron on perinatal outcomes in pregnant women with IDA. STUDY DESIGN This open-label RCT randomized patients with IDA (hemoglobin [hgb]

Purpose Cancer-related cognitive impairment (CRCI) is a recognised adverse consequence of cancer and its treatment. This study assessed the feasibility of collecting longitudinal data on cognition in patients with newly diagnosed, aggressive lymphoma undergoing standard therapy with curative intent via self-report, neuropsychological assessment, peripheral markers of inflammation, and neuroimaging. An exploration and description of patterns of cancer-related cognitive impairment over the course of treatment and recovery was also undertaken and will be reported separately. Methods Eligible participants completed repeated measures of cognition including self-report and neuropsychological assessment, and correlates of cognition including blood cell–based inflammatory markers, and neuroimaging at three pre-specified timepoints, time 1 (T1) — pre-treatment (treatment naïve), time 2 (T2) — mid-treatment, and time 3 (T3) — 6 to 8 weeks post-completion of treatment. Results 30/33 eligible patients (91%, 95% CI: 76%, 97%) were recruited over 10 months. The recruitment rate was 3 patients/month (95% CI: 2.0, 4.3 patients/month). Reasons for declining included feeling overwhelmed and rapid treatment commencement. Mean age was 57 years (SD = 17 years) and 16/30 (53%) were male. Most patients (20/30, 67%) had diffuse large B cell lymphoma or Hodgkin lymphoma (4/30, 13%). The neuroimaging sub-study was optional, 11/30 participants (37%) were eligible to take part, and all agreed. The remaining 19 participants were ineligible as their diagnostic PET/CT scan was completed prior. Retention and compliance with all assessments were 89 to 100% at all timepoints. Only one participant was withdrawn due to disease progression. Conclusions Findings from this study including excellent recruitment, retention, and compliance rates demonstrate it is feasible to longitudinally assess cognition in people with newly diagnosed aggressive lymphoma during their initial treatment and recovery to inform the development of future research to improve patient experiences and cognitive outcomes. Trial registration. Australian New Zealand Clinical Trials Registry ACTRN12619001649101.

INTRODUCTION: Prescription opioids are frequently used for pain management in pregnancy. Studies examining perinatal complications in mothers who received prescription opioids during pregnancy are still limited. OBJECTIVES: The aim of this study was to assess the association of prescription opioid use and maternal pregnancy and obstetric complications. METHODS: This retrospective cohort study with the Rhode Island (RI) Medicaid claims data linked to vital statistics throughout 2008–2015 included pregnant women aged 12–55 years with one or multiple live births. Women were excluded if they had cancer, opioid use disorder, or opioid dispensing prior to but not during pregnancy. Main outcomes included adverse pregnancy and obstetric complications. Marginal Structural Cox Models with time-varying exposure and covariates were applied to control for baseline and time-varying covariates. Analyses were conducted for outcomes that occurred 1 week after opioid exposure (primary) or within the same week as exposure (secondary). Sensitivity studies were conducted to assess the effects of different doses and individual opioids. RESULTS: Of 9823 eligible mothers, 545 (5.5%) filled one or more prescription opioid during pregnancy. Compared with those unexposed, no significant risk was observed in primary analyses, while in secondary analyses opioid-exposed mothers were associated with an increased risk of cesarean antepartum depression (HR 3.19; 95% CI 1.22–8.33), and cardiac events (HR 9.44; 95% CI 1.19–74.83). In sensitivity analyses, results are more prominent in high dose exposure and are consistent for individual opioids. CONCLUSIONS: Prescription opioid use during pregnancy is associated with an increased risk of maternal complications.

MicroRNAs (miRNAs, miRs) regulate cell fate decisions by post-transcriptionally tuning networks of mRNA targets. We used miRNA-directed pathway discovery to reveal a regulatory circuit that influences Ig class switch recombination (CSR). We developed a system to deplete mature, activated B cells of miRNAs, and performed a rescue screen that identified the miR-221/222 family as a positive regulator of CSR. Endogenous miR-221/222 regulated B cell CSR to IgE and IgG1 in vitro, and miR-221/222–deficient mice exhibited defective IgE production in allergic airway challenge and polyclonal B cell activation models in vivo. We combined comparative Ago2-HITS-CLIP and gene expression analyses to identify mRNAs bound and regulated by miR-221/222 in primary B cells. Interrogation of these putative direct targets uncovered functionally relevant downstream genes. Genetic depletion or pharmacological inhibition of Foxp1 and Arid1a confirmed their roles as key modulators of CSR to IgE and IgG1.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease commonly treated with riluzole, a small molecule that may act via modulation of glutamatergic neurotransmission. However, riluzole only modestly extends lifespan for people living with ALS, and its precise mechanisms of action remain unclear. Most ALS cases are characterised by accumulation of cytoplasmic TAR DNA binding protein of 43 kDa (TDP-43), and understanding the effects of riluzole in models that closely recapitulate TDP-43 pathology may provide insights for development of improved therapeutics. We therefore investigated the effects of riluzole in female transgenic mice that inducibly express nuclear localisation sequence (NLS)-deficient human TDP-43 in neurons (NEFH-tTA/tetO-hTDP-43ΔNLS, 'rNLS8', mice). Riluzole treatment from the first day of hTDP-43ΔNLS expression did not alter disease onset, weight loss or performance on multiple motor behavioural tasks. Riluzole treatment also did not alter TDP-43 protein levels, solubility or phosphorylation. Although we identified a significant decrease in GluA2 and GluA3 proteins in the cortex of rNLS8 mice, riluzole did not ameliorate this disease-associated molecular phenotype. Likewise, riluzole did not alter the disease-associated atrophy of hindlimb muscle in rNLS8 mice. Finally, riluzole treatment beginning after disease onset in rNLS8 mice similarly had no effect on progression of late-stage disease or animal survival. Together, we demonstrate specific glutamatergic receptor alterations and muscle fibre-type changes reminiscent of ALS in female rNLS8 mice, but riluzole had no effect on these or any other disease phenotypes. Future targeting of pathways related to accumulation of TDP-43 pathology may be needed to develop better treatments for ALS.

Introduction: The rapid development of coronavirus disease 2019 (COVID-19) into a pandemic required people to quickly acquire, evaluate, and apply novel complex health-related information about the virus and transmission risks. This study examined the potentially unique and synergistic roles of individual differences in neurocognition and health literacy in the early uptake and use of COVID-19 public health information.Method: Data were collected between April 23 and 21 May 2020, a period during which 42 out of 50 states were under a stay-at-home order. Participants were 217 healthy adults who completed a telephone-based battery that included standard tests of neurocognition, health literacy, verbal IQ, personality, and anxiety. Participants also completed measures of COVID-19 information-seeking skills, knowledge, prevention intentions, and prevention behaviors.Results: A series of hierarchical multiple regressions with data-driven covariates showed that neurocognition (viz, episodic verbal memory and executive functions) was independently related to COVID-19 knowledge (e.g. symptoms, risks) at a medium effect size, but not to information-seeking skills, prevention intentions, or prevention behaviors. Health literacy was independently related to all measured aspects of COVID-19 health information and did not interact with neurocognition in any COVID-19 health domain.Conclusions: Individual differences in neurocognition and health literacy played independent and meaningful roles in the initial acquisition of knowledge related to COVID-19, which is a novel human health condition. Future studies might examine whether neurocognitive supports (e.g. spaced retrieval practice, elaboration) can improve COVID-19-related knowledge and health behaviors in vulnerable populations.

Background To identify the association between inpatient postpartum opioid consumption, race, and amount of opioids prescribed at discharge after vaginal or cesarean delivery. Methods A total of 416 women who were prescribed an oral opioid following vaginal or cesarean delivery at a single tertiary academic institution between July 2018 and October 2018 were identified. Women with postoperative wound complications, third and fourth degree lacerations, cesarean hysterectomy, or a history of opioid abuse were excluded. The primary outcome was the number of oxycodone 5 mg tablets prescribed at discharge, stratified by race and mode of delivery. Only “Black” and “White” women were included in analyses due to low absolute numbers of other identities. Black women were compared to white women using multivariable logistic regression. Multiple sensitivity analyses were performed. Results The median number of oxycodone tablets consumed during hospitalization following cesarean delivery was seven (IQR: 2.5–12 tablets) and following vaginal delivery was one (IQR: 0–3). White women were more likely to be older at delivery regardless of route (median 32 vs. 30 years for cesarean delivery, and 29 vs. 27 years for vaginal delivery; p p = 0.02). White women were also significantly more likely to have private insurance and to experience perineal lacerations following vaginal delivery. The number of inpatient opioid tablets consumed, as well as the number prescribed at discharge, were not statistically different between Black and White women, regardless of mode of delivery. These findings persisted in sensitivity analyses. Conclusion At our large, academic hospital the number of tablets prescribed at discharge had no association with patient race or inpatient usage regardless of mode of delivery.

ObjectiveSince the first report of CHCHD10 gene mutations in amyotrophiclateral sclerosis (ALS)/frontotemporaldementia (FTD) patients, genetic variation in CHCHD10 has been inconsistently linked to disease. A pathological assessment of the CHCHD10 protein in patient neuronal tissue also remains to be reported. We sought to characterise the genetic and pathological contribution of CHCHD10 to ALS/FTD in Australia.MethodsWhole-exome and whole-genome sequencing data from 81 familial and 635 sporadic ALS, and 108 sporadic FTD cases, were assessed for genetic variation in CHCHD10. CHCHD10 protein expression was characterised by immunohistochemistry, immunofluorescence and western blotting in control, ALS and/or FTD postmortem tissues and further in a transgenic mouse model of TAR DNA-binding protein 43 (TDP-43) pathology.ResultsNo causal, novel or disease-associated variants in CHCHD10 were identified in Australian ALS and/or FTD patients. In human brain and spinal cord tissues, CHCHD10 was specifically expressed in neurons. A significant decrease in CHCHD10 protein level was observed in ALS patient spinal cord and FTD patient frontal cortex. In a TDP-43 mouse model with a regulatable nuclear localisation signal (rNLS TDP-43 mouse), CHCHD10 protein levels were unaltered at disease onset and early in disease, but were significantly decreased in cortex in mid-stage disease.ConclusionsGenetic variation in CHCHD10 is not a common cause of ALS/FTD in Australia. However, we showed that in humans, CHCHD10 may play a neuron-specific role and a loss of CHCHD10 function may be linked to ALS and/or FTD. Our data from the rNLS TDP-43 transgenic mice suggest that a decrease in CHCHD10 levels is a late event in aberrant TDP-43-induced ALS/FTD pathogenesis.

The ideal analgesic modality for total shoulder arthroplasty (TSA) remains controversial. We hypothesized that a multimodal analgesic pathway incorporating continuous interscalene blockade (ISB) provides better analgesic efficacy than both single-injection ISB and local infiltration analgesia.This single-center, parallel, unblinded, randomized clinical trial evaluated 129 adults undergoing primary TSA. Patients were allocated to single-injection ISB, continuous ISB, or local infiltration analgesia. The primary outcome was the Overall Benefit of Analgesia Score (range, 0 [best] to 28 [worst]) on postoperative day 1. Additional outcomes included pain scores, opioid consumption, quality of life, and postoperative complications in the first 24 hours, at 3 months, and at 1 year.We analyzed 125 patients (42 with single-injection ISB, 41 with continuous ISB, and 42 with local infiltration analgesia). The Overall Benefit of Analgesia Score was significantly improved in the continuous group (median [25th percentile, 75th percentile], 0 [0, 2]) compared with the single-injection group (2 [1, 4]; P = .002) and local infiltration analgesia group (3 [2, 4]; P.001). Pain scores were significantly lower in the continuous group compared with the local infiltration analgesia group (P.001 for all time points) and after 12 hours from ward arrival compared with the single-injection group (median [25th percentile, 75th percentile], 1.0 [0.0, 2.8] vs. 2.5 [0.0, 4.0]; P = .016). After postanesthesia recovery discharge, opioid consumption (oral morphine equivalents) was significantly lower in the continuous group (median [25th percentile, 75th percentile], 7.5 mg [0.0, 25.0 mg]) than in the local infiltration analgesia group (30 mg [15.0, 52.5 mg]; P.001) and single-injection group (17.6 mg [7.5, 45.5 mg]; P = .010). No differences were found across groups for complications, 3-month outcomes, and 1-year outcomes.Continuous ISB provides superior analgesia compared with single-injection ISB and local infiltration analgesia in the first 24 hours after TSA.

Background Transverse abdominis plane (TAP) block is considered an effective alternative to neuraxial analgesia for abdominal surgery. However, limited evidence supports its use over traditional analgesic modalities in colorectal surgery. This study compared the analgesic efficacy of liposomal bupivacaine TAP block with intrathecal (IT) opioid administration in a multicentre RCT. Methods Patients undergoing elective small bowel or colorectal resection were randomized to receive TAP block or a single injection of IT analgesia with hydromorphone. Patients were assessed at 4, 8, 16, 24 and 48 h after surgery. Primary outcomes were mean pain scores and morphine milligram equivalents (MMEs) administered within 48 h after surgery. Secondary outcomes included duration of hospital stay, incidence of postoperative ileus and use of intravenous patient-controlled analgesia. Results In total, 209 patients were recruited and 200 completed the trial (TAP 102, IT 98). The TAP group had a 1·6-point greater mean pain score than the IT group at 4 h after surgery, and this difference lasted for 16 h after operation. The TAP group received more MMEs within the first 24 h after surgery than the IT group (median difference in MMEs 10·0, 95 per cent c.i. 3·0 to 20·5). There were no differences in MME use at 24 and 48 h, or with respect to secondary outcomes. Conclusion IT opioid administration provided better immediate postoperative pain control than TAP block. Both modalities resulted in low pain scores in patients undergoing elective colorectal surgery and should be considered in multimodal postoperative analgesic plans. Registration number: NCT02356198 ( http://www.clinicaltrials.gov).

The Speech Intelligibility Index includes a series of frequency importance functions for calculating the estimated intelligibility of speech under various conditions. Until recently, techniques to derive frequency importance required averaging data over a group of listeners, thus hindering the ability to observe individual differences due to factors such as hearing loss. In the current study, the “random combination strategy” [Bosen and Chatterjee (2016). J. Acoust. Soc. Am. 140, 3718–3727] was used to derive frequency importance functions for individual hearing-impaired listeners, and normal-hearing participants for comparison. Functions were measured by filtering sentences to contain only random subsets of frequency bands on each trial, and regressing speech recognition against the presence or absence of bands across trials. Results show that the contribution of each band to speech recognition was inversely proportional to audiometric threshold in that frequency region, likely due to reduced audibility, even though stimuli were shaped to compensate for each individual's hearing loss. The results presented in this paper demonstrate that this method is sensitive to factors that alter the shape of frequency importance functions within individuals with hearing loss, which could be used to characterize the impact of audibility or other factors related to suprathreshold deficits or hearing aid processing strategies.

The present vaccine against influenza virus has the inevitable risk of antigenic discordance between the vaccine and the circulating strains, which diminishes vaccine efficacy. This necessitates new approaches that provide broader protection against influenza. Here we designed a vaccine using the hypervariable receptor-binding domain (RBD) of viral hemagglutinin displayed on a nanoparticle (np) able to elicit antibody responses that neutralize H1N1 influenza viruses spanning over 90 years. Co-display of RBDs from multiple strains across time, so that the adjacent RBDs are heterotypic, provides an avidity advantage to cross-reactive B cells. Immunization with the mosaic RBD–np elicited broader antibody responses than those induced by an admixture of nanoparticles encompassing the same set of RBDs as separate homotypic arrays. Furthermore, we identified a broadly neutralizing monoclonal antibody in a mouse immunized with mosaic RBD–np. The mosaic antigen array signifies a unique approach that subverts monotypic immunodominance and allows otherwise subdominant cross-reactive B cell responses to emerge. Antigenic variation of influenza A viruses necessitates the annual reformulation of vaccines. Kanekiyo et al. develop a mosaic nanoparticle vaccine against influenza virus that is able to elicit neutralizing antibodies that span nearly 100 years of variation of influenza A virus.

To assess the effect of intravenous versus oral iron on hematologic indices and clinical outcomes for iron-deficiency anemia (IDA) in pregnancy. Searches in Ovid Medline, Embase, SCOPUS, Cochrane Database, and ClinicalTrials.gov identified randomized-controlled trials comparing intravenous to oral iron for treating IDA in pregnancy. Primary outcomes were maternal hematologic indices at delivery. Secondary outcomes were blood transfusion, cesarean delivery, neonatal outcomes, and medication reactions. Of 15,637 studies, 20 randomized trials met inclusion criteria and were analyzed. Mean hemoglobin at delivery (9 studies: WMD 0.66 g/dL (95% confidence Interval 0.31 –1.02 g/dL)) was significantly higher after intravenous iron therapy. Intravenous iron was associated with higher birthweight (8 studies: WMD 58.25 g (95% CI: 5.57–110.94 g)) but no significant differences in blood transfusion, cesarean delivery, or neonatal hemoglobin. There were fewer medication reactions with intravenous iron (21 studies: RR 0.34% (95% CI: 0.20–0.57)). Intravenous iron therapy is associated with higher maternal hemoglobin at delivery with no difference in blood transfusion and fewer mild medication reactions.

Influenza B viruses (IBV) drive a significant proportion of influenza-related hospitalisations yet are understudied compared to influenza A. Current vaccines target the head of the viral hemagglutinin (HA) which undergoes rapid mutation, significantly reducing vaccine effectiveness. Improved vaccines to control IBV are needed. Here we developed novel IBV HA probes to interrogate humoral responses to IBV in humans. A significant proportion of IBV HA-specific B cells recognise both B/Victoria/2/87-like and B/Yamagata/16/88-like lineages in a distinct pattern of cross-reactivity. Monoclonal antibodies (mAbs) were reconstituted from IBV HA-specific B cells, including mAbs providing broad protection in murine models of lethal IBV infection. Protection was mediated by neutralising antibodies targeting the receptor binding domain, or via Fc-mediated functions of non-neutralising antibodies binding alternative epitopes including the IBV HA stem. This work defines antigenic cross-recognition between IBV lineages and provides guidance for the rational design of improved IBV vaccines for broad and durable protection., Immune recognition of Influenza B virus (IBV) is poorly understood. Here, Liu et al. use flow cytometry to characterize IBV-specific memory B cell responses following seasonal vaccination and show that elicited cross-reactive antibodies can protect against infection, providing a platform for vaccine design.

Changes in brain resting-state functional connectivity (rsFC) were investigated using a longitudinal design by following a 2-month focused attention meditation (FAM) practice and analyzing their association with FAM practice time. Ten novice meditators were recruited from a university meditation course. Participants were scanned with a resting-state fMRI sequence with multi-echo EPI acquisition at baseline and at the 2-month follow-up. Total FAM practice time was calculated from the daily log of the participants. We observed significantly increased rsFC between the posterior cingulate cortex (PCC) and dorsal attention network (DAN), the right middle temporal (RMT) region and default mode network (DMN), the left and right superior parietal lobules (LSPL/RSPL) and DMN, and the LSPL/RSPL and DAN. Furthermore, the rsFC between the LSPL and medial prefrontal cortex was significantly associated with the FAM practice time. These results demonstrate increased connectivity within the DAN, between the DMN and DAN, and between the DMN and visual cortex. These findings demonstrate that FAM can enhance the brain connection among and within brain networks, especially DMN and DAN, indicating potential effect of FAM on fast switching between mind wandering and focused attention and maintaining attention once in the attentive state.

Background: Low-income women are less likely to breastfeed than high-income women. Technology-based interventions demonstrate promise in decreasing health disparities. We assessed whether increased use of breastfeeding smartphone applications (apps) impacts breastfeeding rates for low-income women. Materials and Methods: This is a secondary analysis of a randomized control trial (RCT), including nulliparous, low-income women. Women were randomized to one of two novel apps: control app containing digital breastfeeding handouts and BreastFeeding Friend (BFF), an interactive app containing on-demand breastfeeding educational and video content. App usage was securely tracked. The highest quartile of BFF and control app users were combined and compared to the lowest quartile of app users. The primary outcome was breastfeeding initiation. Secondary outcomes included breastfeeding outcomes and resource preferences through 6 months. Results: In the RCT, BFF and control app median uses were 15 (interquartile range [IQR] 4–24) and 9 (IQR 5–19) (p = 0.1), respectively. Breastfeeding initiation did not differ with app usage (84.1% in highest quartile versus 78.2% for lowest quartile; p = 0.5). Rates of sustained and exclusive breastfeeding through 6 months were similar between groups. Among both groups, smartphone apps were the most preferred breastfeeding resource at 6 weeks. Low quartile users also preferred alternative online breastfeeding resources: >50% of all users preferred technology-based breastfeeding resources. Conclusions: Increased usage of breastfeeding apps did not improve breastfeeding rates among low-income women. However, technology-based resources were the most preferred breastfeeding resource after hospital discharge, indicating ongoing development of technology-based interventions has potential to increase breastfeeding in this high-needs population. clinicaltrials.gov (NCT03167073).

Breastfeeding is available to nearly all women and has well-established short-term and long-term health benefits for mothers and infants. However, rates of breastfeeding initiation and continuation vary significantly according to sociodemographic factors, particularly in the United States. Mobile health (mHealth) interventions such as web-based/online education or smartphone applications have showed promise in increasing breastfeeding initiation and supporting breastfeeding continuation, and the importance of such mHealth-based breastfeeding support has increased significantly during the ongoing COVID-19 pandemic. This expert commentary reviews prior studies on mHealth in breastfeeding and highlights areas for future research on this topic.

Key Points Question Is there an association between prenatal prescription opioid exposure and the risk of major and minor congenital malformations? Findings In this cohort study of 12 424 pregnancies, 891 women were dispensed prescription opioids during pregnancy. Opioid exposure in trimester 1 was not associated with major birth defects, but women dispensed opioids in trimester 3 had higher risks of offspring with minor birth defects in the musculoskeletal system. Meaning The study findings suggest a higher risk of minor congenital malformations in the musculoskeletal system that is associated with prenatal prescription opioid exposure in the third trimester; this risk appears to be dose-dependent., Importance The rapid increase of opioid-related overdoses and deaths has become a public health concern in the US. Use of prescription opioids in pregnant women has increased; results from teratogenicity studies remain controversial. Objective To evaluate the association between maternal prescription opioid use (excluding opioid use disorders) during pregnancy and the incidence of congenital malformations. Design, Setting, and Participants This retrospective population-based cohort study evaluated linked Rhode Island Medicaid claims and vital statistics data of live births from January 1, 2008, to December 31, 2016. Data analysis was conducted from May 1, 2019, to May 31, 2020. Women who had a live birth during the study period, but no cancer or opioid use disorder, were followed up from 3 months before pregnancy to the end of pregnancy. Exposures Data on the mother’s prescription opioid exposure were obtained through pharmacy claims and exposure was defined as dispensing of at least 1 prescription opioid during the first, second, or third trimester. Main Outcomes and Measures The primary outcome was overall major or minor congenital malformations, defined as 1 or more major or minor congenital malformation. Secondary outcomes were defined as 10 specific categories of congenital malformations classified by organ systems using International Classification of Diseases diagnosis codes. Results Of 12 424 included pregnancies, 891 mothers (7.2%) received prescription opioids during pregnancy and 3153 infants (25.4%) were diagnosed with major or minor congenital malformations. Comparing prescription opioid exposure vs nonexposure, no excess risk was observed for major birth defects in infants with opioid exposure in trimester 1 (adjusted relative risk [aRR], 1.40; 95% CI, 0.84-2.34), and higher risks were found for overall minor birth defects in trimester 3 (aRR, 1.26; 95% CI, 1.04-1.53) and minor birth defects in the musculoskeletal system in trimester 2 (aRR, 1.50; 95% CI, 1.10-2.03) and trimester 3 (aRR, 1.65; 95% CI, 1.23-2.22). Significant dose responses in selected minor malformations and effects of specific opioids were also identified. Hydrocodone in trimester 2 (aRR, 3.01; 95% CI, 1.80-5.03) and oxycodone in trimester 3 (aRR, 2.43; 95% CI, 1.37-4.02) were associated with plagiocephaly, polydactyly, and other specified congenital deformities of the hip. Conclusions and Relevance The findings of this study suggest a higher risk of minor congenital malformations associated with use of prenatal prescription opioids in trimester 3, which seems to be dose-dependent. Further investigation is needed to establish causality and explore the physiologic plausibility of the association., This cohort study examines the incidence of major and minor congenital malformations in infants born to women who receive opioids for medical indications during pregnancy.

Background There is a great need to identify biomarkers that can accurately identify patients who will obtain the most clinical benefit from immune checkpoint inhibitor (ICI) therapy. While high intratumoral B cell gene expression correlated with an ICI response in melanoma, whether it adds predictive value in other cancers is unknown. Objective To examine the relationship between B cell gene signature (BCGS) expression and overall survival (OS) following ICI treatment. Design, setting, and participants A total of 348 patients with advanced urothelial carcinoma from the IMvigor 210 phase 2 clinical trial of atezolizumab and 406 patients with muscle-invasive bladder cancer from The Cancer Genome Atlas (TCGA) were included. Outcome measurements and statistical analysis We analyzed tumor RNA sequencing data of included patients to examine the relationships between a BCGS and clinical outcomes. Results and limitations Tumors with high levels of B cell and CD8+ T cell gene signatures (BCGS/CD8TGS or B8T high/high) were associated with the longest OS of all B8T groups. Moreover, the B8T cell signature stratified patients whose tumors had a high tumor mutational burden or high programmed death ligand 1 (PD-L1) into subsets with differential OS outcomes. Whereas the B8T high/high tumors were associated with the best clinical outcomes in ICI-treated men, they were not associated with better OS in women. Conversely, women with B8T high/high tumors had the best clinical outcomes in non–ICI-treated muscle-invasive bladder cancer. Conclusions These data suggest that the B8T signature can enhance OS stratification in patients with advanced urothelial carcinoma who are treated with ICI therapy and that sex-specific differences in the tumor immune microenvironment may drive disparate outcomes. Patient summary We examined whether the presence of two immune cell gene signatures within tumor samples impact survival in patients with bladder cancer. High levels of both of these signatures (B cells and CD8+ T cells) associate with superior survival in patients who receive immune therapy.