Uremic Pericarditis and Cardiac Tamponade Resolving With Intensive Hemodialysis.

We present an interesting and complex case of cardiac tamponade due to uremic pericarditis (UP), resolving with intensive hemodialysis (HD). HD should be considered as first line management for patients with UP and pericardial effusion. Intensification of HD should be considered based on clinical presentation and severity of presentation.

Perinatal loss of galactosylceramidase in both oligodendrocytes and microglia is crucial for the pathogenesis of Krabbe disease in mice.

Lysosomal galactosylceramidase (GALC) is expressed in all brain cells, including oligodendrocytes (OLs), microglia, and astrocytes, although the cell-specific function of GALC is largely unknown. Mutations in GALC cause Krabbe disease (KD), a fatal neurological lysosomal disorder that usually affects infants. To study how Galc ablation in each glial cell type contributes to Krabbe pathogenesis, we used conditional Galc-floxed mice. Here, we found that OL-specific Galc conditional knockout (CKO) in mice results in a phenotype that includes wasting, psychosine accumulation, and neuroinflammation. Microglia- or astrocyte-specific Galc deletion alone in mice did not show specific phenotypes. Interestingly, mice with CKO of Galc from both OLs and microglia have a more severe neuroinflammation with an increase in globoid cell accumulation than OL-specific CKO alone. Moreover, the enhanced phenotype occurred without additional accumulation of psychosine. Further studies revealed that Galc knockout (Galc-KO) microglia cocultured with Galc-KO OLs elicits globoid cell formation and the overexpression of osteopontin and monocyte chemoattractant protein-1, both proteins that are known to recruit immune cells and promote engulfment of debris and damaged cells. We conclude that OLs are the primary cells that initiate KD with an elevated psychosine level and microglia are required for the progression of neuroinflammation in a psychosine-independent manner.

Texas tobacco quitline knowledge, attitudes, and practices within healthcare agencies serving individuals with behavioral health needs: A multimethod study.

Patients with behavioral health conditions have disproportionately high tobacco use rates and face significant barriers to accessing evidence-based tobacco cessation services. Tobacco quitlines are an effective and accessible resource, yet they are often underutilized. We identify knowledge, practices, and attitudes towards the Texas Tobacco Quitline (TTQL) within behavioral healthcare settings in Texas. Quantitative and qualitative data were collected in 2021 as part of a statewide needs assessment in behavioral healthcare settings. Survey respondents (n = 125) represented 23 Federally Qualified Health Centers, 29 local mental health authorities (LMHAs), 12 substance use treatment programs in LMHAs, and 61 standalone substance use treatment centers (26 people participated in qualitative interviews). Over half of respondents indicated familiarity with the TTQL and believed that the TTQL was helpful for quitting. Qualitative findings reveal potential concerns about inconsistency of services, long wait time, and the format of the quitline. About half of respondents indicated that their center promoted patient referral to TTQL, and few indicated that their center had an electronic referral system with direct TTQL referral capacity. Interview respondents reported overall lack of systematic follow up with patients regarding their use of the TTQL services. Findings suggest the need for (1) increased TTQL service awareness among healthcare providers; (2) further investigation into any changes needed to better serve patients with behavioral health conditions who use tobacco; and (3) electronic health record integration supporting direct referrals and enhanced protocols to support patient follow up after TTQL referral.

Behavioral health care provider's beliefs, confidence, and knowledge in treating cigarette smoking in relation to their use of the 5A's intervention.

Introduction: Evidence-based smoking cessation interventions are underused settings where behavioral health treatment is provided, contributing to smoking-related health disparities in this patient group. This study assessed the relationship of provider's beliefs about patients' smoking, perceptions of treatment capability, and knowledge of referral options and their use of the 5A's (Ask, Advise, Assess, Assist, and Arrange) intervention for smoking cessation. Methods: Surveys were collected from providers in healthcare settings in Texas where patients receive behavioral health care (N = 86; 9 federally qualified health centers, 16 Local Mental Health Authorities (LMHAs), 6 substance use treatment programs in LMHAs, and 55 stand-alone substance use treatment centers). Logistic regression analyses were used to assess the association between provider's beliefs about patients' concern and desire to quit smoking; perceptions of their confidence, skills, and effectiveness in treating smoking; their knowledge of referral options; and their use of the 5A's with patients who smoked. Results: Providers who believed that patients were concerned about smoking and wanted to quit; who perceived themselves as confident in providing cessation care, having the required skills, and being effective in providing advice; and/or who had greater referral knowledge were more likely to use the 5A's with patients who smoked than their (respective) provider counterparts (ps < 0.05). Conclusion: Provider-level constructs affect their 5A's provision for patients with behavioral health needs. Future work should train providers to correct misconceptions about patients' interest in quitting, bolster their confidence, and provide referral options to support tobacco provision efforts.

Impact of Delayed Cord Clamping on Red Blood Cell Transfusion and Related Outcomes in Very Low Birth Weight Infants.

OBJECTIVE: Delayed cord clamping (DCC) for 30 to 60 seconds after birth facilitates placental transfusion, increases blood volume, and decreases red blood cell (RBC) transfusion in preterm infants. Study objective was to determine (1) RBC transfusion burden over a 5-year period, (2) impact of DCC practice on RBC transfusions, and (3) association of RBC transfusion on outcomes in very low birthweight (VLBW) preterm infants. STUDY DESIGN: A retrospective medical chart review was performed in 787 VLBW infants between 2016 and 2020. Demographic factors, DCC status, number of RBC transfusions, and neonatal outcomes were determined in eligible infants. Adjusted association between DCC, RBC transfusion, and outcomes were determined using logistic and linear regression methods. RESULTS: Of the 538 eligible VLBW infants, 62% (N = 332) received RBC transfusions. Proportion receiving RBC transfusion were significantly higher for infants <1,000 g (N = 217, 65.4%) and gestational age (GA) <29 weeks (N = 256, 77.1%) than larger (1,001-1,250 g, N = 77, 23.2% and 1,251-1,500 g, N = 38, 11.4%) and older GA ≥ 29 weeks' infants (N = 76, 22.9%, p < 0.05). Of the 81/538 (15.1%) who received DCC, 48 (59.2%) received no RBC transfusion (p < 0.001). In multivariable logistic regression analysis, preterm infants with DCC were 55% less likely to receive RBC transfusions as compared with infants with no DCC. At any given GA, the number of RBC transfusions in preterm infants with DCC was 25% lower as compared with infants without DCC (p < 0.05). Transfusion was associated with 8-fold increased odds for bronchopulmonary dysplasia and 4-fold increased odds for medical and surgically treated patent ductus arteriosus compared with no transfusion. There was no significant association of transfusion with neonatal sepsis, laser treated retinopathy of prematurity, necrotizing enterocolitis, and intraventricular hemorrhage. CONCLUSION: DCC was significantly associated with reduced RBC transfusion, but fewer preterm infants received DCC. Further research is needed to explore the feasibility of providing neonatal resuscitation during DCC in preterm infants. KEY POINTS: · Delayed cord clamping significantly reduced the need for RBC transfusions.. · Fewer very preterm infants received DCC.. · Future research is needed to explore feasibility of neonatal resuscitation during DCC..

Lung Cancer Screening Eligibility and Referral Practices in Texas Organizations Serving People with Substance Use Disorders.

For people at elevated risk for lung cancer, lung cancer screening (LCS) reduces lung cancer mortality. People with non-nicotine substance use disorders (SUDs) have elevated rates of smoking compared with the general population, highlighting them as a priority population for LCS consideration. Although research has shown LCS is underutilized, there is little literature to inform whether organizations that serve individuals with SUDs have existing clinical protocols surrounding LCS. In the current study, we examine the LCS eligibility and referral practices among these organizations. We conducted a statewide needs assessment survey in 2021 to discern how tobacco use was being addressed at Texas organizations that provide treatment or services to individuals with SUDs. Respondents were asked to report on their center's LCS eligibility and referral practices. The analytic sample consists of 125 respondents who represented 23 federally qualified health centers, 29 global local mental health authorities (LMHAs), 12 substance use treatment programs in LMHAs, and 61 standalone substance use treatment centers. Very few respondents indicated that healthcare providers at their center made referrals to LCS for patients (8.8%); a few respondents indicated that their healthcare providers assessed patients' eligibility for LCS but did not make referrals (3.2%). Intervention and implementation efforts are needed in these and other SUD healthcare settings to bolster organizational capacity and ensure that patients are being navigated to lung cancer screening at multiple touch points across the care continuum.

Burden and seasonality of primary and secondary symptomatic common cold coronavirus infections in Nicaraguan children.

BACKGROUND: The current SARS-CoV-2 pandemic highlights the need for an increased understanding of coronavirus epidemiology. In a pediatric cohort in Nicaragua, we evaluate the seasonality and burden of common cold coronavirus (ccCoV) infection and evaluate likelihood of symptoms in reinfections. METHODS: Children presenting with symptoms of respiratory illness were tested for each of the four ccCoVs (NL63, 229E, OC43, and HKU1). Annual blood samples collected before ccCoV infection were tested for antibodies against each ccCoV. Seasonality was evaluated using wavelet and generalized additive model (GAM) analyses, and age-period effects were investigated using a Poisson model. We also evaluate the risk of symptom presentation between primary and secondary infections. RESULTS: In our cohort of 2576 children from 2011 to 2016, we observed 595 ccCoV infections and 107 cases of ccCoV-associated lower respiratory infection (LRI). The overall incidence rate was 61.1 per 1000 person years (95% confidence interval (CI): 56.3, 66.2). Children under two had the highest incidence of ccCoV infections and associated LRI. ccCoV incidence rapidly decreases until about age 6. Each ccCoV circulated throughout the year and demonstrated annual periodicity. Peaks of NL63 typically occurred 3 months before 229E peaks and 6 months after OC43 peaks. Approximately 69% of symptomatic ccCoV infections were secondary infections. There was slightly lower risk (rate ratio (RR): 0.90, 95% CI: 0.83, 0.97) of LRI between secondary and primary ccCoV infections among participants under the age of 5. CONCLUSIONS: ccCoV spreads annually among children with the greatest burden among ages 0-1. Reinfection is common; prior infection is associated with slight protection against LRI among the youngest children.

The Spectrum of Influenza in Children.

BACKGROUND: Children constitute an important component of the influenza burden and community transmission, but the frequency of asymptomatic infection and post-influenza sequelae at the community level is poorly understood. METHODS: Two community-based prospective cohort studies (2011-2020, 2017-2020) and 1 case-ascertained study (2012-2017) were conducted in Managua, Nicaragua. Non-immunocompromised children aged 0-14 years with ≥1 influenza infections, determined by polymerase chain reaction and hemagglutination inhibition assay, were included. RESULTS: A total of 1272 influenza infections occurred in the household-based portion of the study. Influenza infection was asymptomatic in 84 (6.6%) infections, and the asymptomatic fraction increased with age (1.7%, 3.5%, and 9.1% for ages 0-1, 2-4, and 5-14, respectively; P < .001). Of asymptomatic children, 43 (51.2%) shed virus, compared to 1099 (92.5%) symptomatic children (P < .001). Also, 2140 cases of influenza occurred in the primary care portion of the study. Sequelae of influenza were rare, with the most common being pneumonia (52, 2.4%) and acute otitis media (71, 3.3%). A/H1N1 had higher age-adjusted odds of acute otitis media (odds ratio [OR] 1.99, 95% confidence interval [CI]: 1.14-3.48; P = .015) and hospitalization (OR 3.73, 95% CI: 1.68-8.67; P = .002) than A/H3N2. B/Victoria had higher age-adjusted odds of pneumonia (OR 10.99, 95% CI: 1.34-90.28; P = .026) than B/Yamagata. CONCLUSIONS: Asymptomatic influenza infection is much less common in children than adults, although viral shedding still occurs in asymptomatic children. Post-influenza sequelae are rare in children in the community setting, and virus strain may be important in understanding the risk of sequelae.

Severe Thrombocytopenia in Infective Endocarditis.

Thrombocytopenia can be seen in about 20-25% of patients with bacterial infective endocarditis (IE). Platelets have a major role in the pathogenesis of endocarditis, and they are also sensitive monitors of systemic host response to bacteremia. Thrombocytopenia on presentation of patients with IE identifies higher risk groups and carries higher mortality risk. The presence of thrombocytopenia is an independent prognosticator of poor outcomes in IE. We present a case of a 40-year-old male with the history of injection drug use who was diagnosed with IE and was found to have severe thrombocytopenia on admission was treated with intravenous antibiotics, which dramatically improved his platelet counts as well without any need for plasmapheresis or platelet transfusions.

Providers' Non-Cigarette Tobacco Use Intervention Practices in Relation to Beliefs about Patients, Prioritization of and Skills for Intervention, and Referral Knowledge in Texas Healthcare Centers Providing Care to Persons with Behavioral Health Needs.

Rates of non-cigarette (colloquially, other) tobacco use is elevated among adults with behavioral health conditions. Little is known about whether behavioral health providers are using brief interventions, including the evidence-based 5As (Ask, Advise, Assess, Assist, and Arrange) for other tobacco use, or what provider factors may be associated with use of these interventions. The current study redressed this gap. Overall, 86 providers in Texas (9 Federally Qualified Health Centers, 16 Local Mental Health Authorities (LMHAs) that provide a broad range of mental and behavioral health services, 6 substance use treatment programs in LMHAs, and 55 stand-alone substance use treatment programs) took a survey assessing their beliefs regarding (1) patients' concerns about other tobacco use; (2) their desire to quit; (3) importance of intervening on other tobacco use with cessation counseling; (4) perceived skills to intervene; (5) knowledge of referral options for treatment. Logistic regression analyses were conducted to determine the association between each factor and use of the 5As. Results showed that 70.9% of providers asked patients about other tobacco use status, 65.1% advised them to quit, 59.3% assessed quit interest, 54.7% assisted with a quit attempt, and 31.4% arranged a follow-up. Providers who believed patients were concerned about other tobacco use, recognized the importance of offering other tobacco use cessation counseling, believed they had the necessary skills to treat other tobacco use, and possessed knowledge of referral options, respectively, were more likely to deliver the 5As (ps < 0.05). Results add to a limited literature on provider intervention practices for other tobacco use in settings where behavioral health care is provided, highlighting the significance of provider beliefs, perceived skills, and referral knowledge to care delivery. Findings reveal opportunities to increase delivery of the 5As for other tobacco use to behavioral health patients and suggest provider factors that could be targeted to build this capacity.

Class III obesity is an independent risk factor for unsuccessful induction of labor.

BACKGROUND: Although obesity is a known risk factor for cesarean delivery, there is a paucity of data on the course of induction of labor in these patients. OBJECTIVE: With emerging data on the safety of 39-week inductions, we aimed to: (1) determine if Class III obesity, including morbid obesity, is an independent risk factor for nonachievement of complete dilation and vaginal delivery after induction of labor, (2) evaluate the characteristics of the induction of labor course and immediate complications, and (3) evaluate the number of induction agents necessary to be associated with vaginal deliveries. We hypothesized that as body mass index increased, it would take longer to achieve complete cervical dilation, more induction agents would be required, and there would be a higher rate of cesarean delivery. STUDY DESIGN: This was a retrospective cohort study of singleton gestations undergoing induction of labor from 2013 to 2020 at a single center. Study groups were defined as nonobese (body mass index <30 kg/m2), non-Class III obesity (body mass index of 30-39.9 kg/m2), and Class III obesity (body mass index ≥40 kg/m2). The primary outcome was achievement of complete cervical dilation. Secondary outcomes included time from start of induction to complete dilation, cesarean delivery rates, doses of misoprostol used, combination of induction agents used, and incidence of chorioamnionitis and postpartum hemorrhage. Univariate and multivariate logistic regression analyses were used to estimate risks. A secondary analysis was performed on nulliparous patients. RESULTS: A total of 3046 individuals met the inclusion criteria. As body mass index increased, the indications for induction were more likely to be maternal. Rate of achievement of complete dilation decreased with increasing body mass index (973 [88.5%] in the body mass index <30 group vs 455 [70.8%] in the body mass index ≥40 group; adjusted odds ratio, 0.3; 95% confidence interval, 0.2-0.4). The rate of cesarean delivery also increased (149 [13.5%] in the body mass index <30 group vs 207 [30.9%] in the body mass index ≥40 group; adjusted odds ratio, 3.2; 95% confidence interval, 2.5-4.2), as did the time to complete dilation (15.3 hours in the body mass index <30 group vs 18.8 hours in the body mass index ≥40 group; P<.001). Morbidly obese patients required higher doses and more types of induction agents. Misoprostol was used as the sole induction agent in 362 (35.1%) of patients in the body mass index <30 group vs 160 (25.4%) of patients in the body mass index ≥40 group (adjusted odds ratio, 0.6; 95% confidence interval, 0.5-0.8). In the body mass index ≥40 group, a greater number required a combination of misoprostol, mechanical ripening, and oxytocin for induction (147 [14.3%] in the body mass index <30 group vs 158 [25.0%] in the body mass index ≥40 group; adjusted odds ratio, 1.7; 95% confidence interval, 1.3-2.3). For nulliparous patients, the rate of cesarean delivery was significantly higher with increasing body mass index (118 [18.3%] in the body mass index <30 group and 157 [48.2%] in the body mass index ≥40 group; P<.001), with 5 more hours spent in labor (18.3 hours in the body mass index <30 group vs 23.3 hours in the body mass index ≥40 group; P<.001). Nulliparous patients were also more likely to require multiple induction agents (122 [20.3%] for body mass index <30 vs 108 [33.6%] for body mass index ≥40; P<.001). CONCLUSION: Class III obesity is an independent risk factor for nonachievement of complete dilation and vaginal delivery following induction of labor. Furthermore, inductions in these patients require more time and are more likely to require multiple agents.

Pediatric burden and seasonality of human metapneumovirus over 5 years in Managua, Nicaragua.

BACKGROUND: Human metapneumovirus (hMPV) is an important cause of pediatric respiratory infection. We leveraged the Nicaraguan Pediatric Influenza Cohort Study (NPICS) to assess the burden and seasonality of symptomatic hMPV infection in children. METHODS: NPICS is an ongoing prospective study of children in Managua, Nicaragua. We assessed children for hMPV infection via real-time reverse-transcription polymerase chain reaction (RT-PCR). We used classical additive decomposition analysis to assess the temporal trends, and generalized growth models (GGMs) were used to estimate effective reproduction numbers. RESULTS: From 2011 to 2016, there were 564 hMPV symptomatic infections, yielding an incidence rate of 5.74 cases per 100 person-years (95% CI 5.3, 6.2). Children experienced 3509 acute lower respiratory infections (ALRIs), of which 160 (4.6%) were associated with hMPV infection. Children under the age of one had 55% of all symptomatic hMPV infections (62/112) develop into hMPV-associated ALRIs and were five times as likely as children over one to have an hMPV-associated ALRI (rate ratio 5.5 95% CI 4.1, 7.4 p < 0.001). Additionally, symptomatic reinfection with hMPV was common. In total, 87 (15%) of all observed symptomatic infections were detected reinfections. The seasonality of symptomatic hMPV outbreaks varied considerably. From 2011 to 2016, four epidemic periods were observed, following a biennial seasonal pattern. The mean ascending phase of the epidemic periods were 7.7 weeks, with an overall mean estimated reproductive number of 1.2 (95% CI 1.1, 1.4). CONCLUSIONS: Symptomatic hMPV infection was associated with substantial burden among children in the first year of life. Timing and frequency of symptomatic hMPV incidence followed biennial patterns.

Tobacco Screening Practices and Perceived Barriers to Offering Tobacco Cessation Services among Texas Health Care Centers Providing Behavioral Health Treatment.

Tobacco use, and thus tobacco-related morbidity, is elevated amongst patients with behavioral health treatment needs. Consequently, it is important that centers providing health care to this group mandate providers' use of tobacco screenings to inform the need for tobacco use disorder intervention. This study examined the prevalence of mandated tobacco screenings in 80 centers providing health care to Texans with behavioral health needs, examined key factors that could enhance screening conduct, and delineated providers' perceived barriers to tobacco use intervention provision. The results indicated that 80% of surveyed centers mandated tobacco use screenings; those that did were significantly more likely than those that did not to have a hard stop for tobacco use status in health records and were marginally more likely to make training on tobacco screening available to providers. The most widespread barriers to tobacco use disorder care provision were relative perceived importance of competing diagnoses, lack of community resources to refer patients, perceived lack of time, lack of provider knowledge or confidence, and belief that patients do not comply with cessation treatment. Overall, the results suggest that there are opportunities for centers providing care to Texans with behavioral health needs to bolster their tobacco screening and intervention capacity to better address tobacco-related health disparities in this group. Health care centers can support their providers to intervene in tobacco use by mandating screenings, streamlining clinical workflows with hard stops in patient records, and educating providers about the importance of treating tobacco with brief evidence-based intervention strategies while providing accurate information about patients' interest in quitting and providers' potential impacts on a successful quit attempt.

Birth cohort relative to an influenza A virus's antigenic cluster introduction drives patterns of children's antibody titers.

An individual's antibody titers to influenza A strains are a result of the complicated interplay between infection history, cross-reactivity, immune waning, and other factors. It has been challenging to disentangle how population-level patterns of humoral immunity change as a function of age, calendar year, and birth cohort from cross-sectional data alone. We analyzed 1,589 longitudinal sera samples from 260 children across three studies in Nicaragua, 2006-16. Hemagglutination inhibition (HAI) titers were determined against four H3N2 strains, one H1N1 strain, and two H1N1pdm strains. We assessed temporal patterns of HAI titers using an age-period-cohort modeling framework. We found that titers against a given virus depended on calendar year of serum collection and birth cohort but not on age. Titer cohort patterns were better described by participants' ages relative to year of likely introduction of the virus's antigenic cluster than by age relative to year of strain introduction or by year of birth. These cohort effects may be driven by a decreasing likelihood of early-life infection after cluster introduction and by more broadly reactive antibodies at a young age. H3N2 and H1N1 viruses had qualitatively distinct cohort patterns, with cohort patterns of titers to specific H3N2 strains reaching their peak in children born 3 years prior to that virus's antigenic cluster introduction and with titers to H1N1 and H1N1pdm strains peaking for children born 1-2 years prior to cluster introduction but not being dramatically lower for older children. Ultimately, specific patterns of strain circulation and antigenic cluster introduction may drive population-level antibody titer patterns in children.

Oxytocin signaling is necessary for synaptic maturation of adult-born neurons.

Neural circuit plasticity and sensory response dynamics depend on forming new synaptic connections. Despite recent advances toward understanding the consequences of circuit plasticity, the mechanisms driving circuit plasticity are unknown. Adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and circuit integration. We and others have shown that efficient adult-born neuron circuit integration hinges on presynaptic activity in the form of diverse signaling peptides. Here, we demonstrate a novel oxytocin-dependent mechanism of adult-born neuron synaptic maturation and circuit integration. We reveal spatial and temporal enrichment of oxytocin receptor expression within adult-born neurons in the murine olfactory bulb, with oxytocin receptor expression peaking during activity-dependent integration. Using viral labeling, confocal microscopy, and cell type-specific RNA-seq, we demonstrate that oxytocin receptor signaling promotes synaptic maturation of newly integrating adult-born neurons by regulating their morphological development and expression of mature synaptic AMPARs and other structural proteins.

Smoking Intervention Practices in Texas Healthcare Centers with Sexual and Gender Minority Patients.

Objectives: This study evaluated the use of evidence-based practices (EBPs) for smoking cessation in centers providing behavioral healthcare for patient populations that included some proportion of sexual and gender minorities (SGMs). Methods: Healthcare providers from 75 healthcare centers across Texas serving SGMs with behavioral health needs participated in a survey assessing their center's tobacco control policies and practices. Results: Nearly half (N = 36) of participating centers had a comprehensive tobacco-free workplace policy, 30.67% employed ≥1 tobacco treatment specialist, 73.91% employed ≥1 prescriber, 80.82% mandated screening for patient tobacco use at intake, and 57.53% provided a template for tobacco use assessments. Overall, 70.67% of providers asked patients about smoking status, 69.33% advised patients to quit, 64.00% assessed patients' interest in quitting, 58.67% assisted patients with quit attempts, and 36.00% arranged follow-up. Providers' ability to tailor interventions for special populations like SGMs ranged from very low/0 to very high/10 (M = 4.63 ± 2.59). Conclusions: There are opportunities to improve policy implementation, standardization and usage of evidence-based interventions, and intervention tailoring within settings providing care to SGM patients in Texas to better address their tobacco use inequities.

Symptoms, Infection Duration, and Hemagglutinin Inhibition Antibody Response in Influenza A Infections.

BACKGROUND: Many influenza studies assume that symptomatic and asymptomatic cases have equivalent antibody responses. METHODS: This study examines the relationship between influenza symptoms and serological response. Influenza-positive index cases and household members in Managua, Nicaragua, during 2012-2017 were categorized by symptom status. RESULTS: Antibody response was assessed using hemagglutination inhibition assays (HAI). Among 510 cases, 74.5% had ≥4-fold increase in HAI antibodies, and 75.3% had febrile illness. In a logistic regression model, febrile cases had 2.17 times higher odds of a ≥4-fold titer rise compared to asymptomatic cases (95% confidence interval, 1.02-4.64). CONCLUSIONS: Studies relying on serological assays may not generalize to asymptomatic infections.

Target specific functions of EPL interneurons in olfactory circuits.

Inhibitory interneurons are integral to sensory processing, yet revealing their cell type-specific roles in sensory circuits remains an ongoing focus. To Investigate the mouse olfactory system, we selectively remove GABAergic transmission from a subset of olfactory bulb interneurons, EPL interneurons (EPL-INs), and assay odor responses from their downstream synaptic partners - tufted cells and mitral cells. Using a combination of in vivo electrophysiological and imaging analyses, we find that inactivating this single node of inhibition leads to differential effects in magnitude, reliability, tuning width, and temporal dynamics between the two principal neurons. Furthermore, tufted and not mitral cell responses to odor mixtures become more linearly predictable without EPL-IN inhibition. Our data suggest that olfactory bulb interneurons, through exerting distinct inhibitory functions onto their different synaptic partners, play a significant role in the processing of odor information.

Novel correlates of protection against pandemic H1N1 influenza A virus infection.

Influenza viruses remain a severe threat to human health, causing up to 650,000 deaths annually1,2. Seasonal influenza virus vaccines can prevent infection, but are rendered ineffective by antigenic drift. To provide improved protection from infection, novel influenza virus vaccines that target the conserved epitopes of influenza viruses, specifically those in the hemagglutinin stalk and neuraminidase, are currently being developed3. Antibodies against the hemagglutinin stalk confer protection in animal studies4-6. However, no data exist on natural infections in humans, and these antibodies do not show activity in the hemagglutination inhibition assay, the hemagglutination inhibition titer being the current correlate of protection against influenza virus infection7-9. While previous studies have investigated the protective effect of cellular immune responses and neuraminidase-inhibiting antibodies, additional serological correlates of protection from infection could aid the development of broadly protective or universal influenza virus vaccines10-13. To address this gap, we performed a household transmission study to identify alternative correlates of protection from infection and disease in naturally exposed individuals. Using this study, we determined 50% protective titers and levels for hemagglutination inhibition, full-length hemagglutinin, neuraminidase and hemagglutinin stalk-specific antibodies. Further, we found that hemagglutinin stalk antibodies independently correlated with protection from influenza virus infection.