Influenza viruses remain a severe threat to human health, causing up to 650,000 deaths annually
. 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 developed
. Antibodies against the hemagglutinin stalk confer protection in animal studies
. 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 infection
. 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 vaccines
. 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.
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.
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.
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.
Despite activity as single agent cancer therapies, Rapamycin (rapa) and its rapalogs may have their greatest effects when combined with other therapeutic modalities. In addition to direct antitumor ...activity, rapalogs reverse multiple tumor-intrinsic immune evasion mechanisms. These should facilitate tumor-specific T cell activity, but since rapa directly inhibits effector T cells, this potential immune enhancement is lost. We hypothesized that if T cells were rendered resistant to rapa they could capitalize on its downregulation of tumor immune evasion. We therefore modified T cells with a rapa-resistant mutant of mTor, mTorRR, and directed them to B lymphomas by coexpressing a chimeric antigen receptor (CAR) for CD19 (CAR.CD19-28ζ). T cells expressing transgenic mTorRR from a piggyBac transposon maintain mTor signaling, proliferate in the presence of rapa and retain their cytotoxic function and ability to secrete interferon-γ (IFNγ) after stimulation, effector functions that were inhibited by rapa in control T cells. In combination, rapa and rapa-resistant-CAR.CD19-28ζ-expressing T cells produced greater antitumor activity against Burkitt's lymphoma and pre-B ALL cell lines in vitro than CAR.CD19-28ζ T cells or rapa alone. In conclusion, the combination of rapa and rapa-resistant, CAR.CD19-28ζ-expressing T cells may provide a novel therapy for the treatment of B cell malignancies and other cancers.
•Patients with behavioral health conditions (BHCs) have high tobacco use rates.•Tobacco quitlines provide accessible evidence-based cessation services.•Quitlines (e.g., Texas Tobacco Quitline (TTQL)) ...are underutilized.•Results identify barriers/facilitators to TTQL use in BHC treatment settings.•Interventions are needed to increase referrals to and use of the TTQL.
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.
•Cigarette smoking is elevated among individuals with behavioral healthcare needs.•There are notable gaps in cessation care provision in behavioral care settings.•Behavioral health providers do not ...consistently use the 5As intervention.•Provider-level constructs affect use of the 5As to treat cigarette smoking.•Training efforts are needed to support intervention and reduce health disparities.
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.
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.
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).
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.
Haemophilus influenzae is an important cause of respiratory infections, including acute otitis media, sinusitis, and chronic bronchitis, which are preceded by asymptomatic H. influenzae colonization ...of the human pharynx. The aim of this study was to describe the dynamics of pharyngeal colonization by H. influenzae and an intimately related species, Haemophilus haemolyticus, in healthy adults. Throat specimens from four healthy adult carriers were screened for Haemophilus species; 860 isolates were identified as H. influenzae or H. haemolyticus based on the porphyrin test and on dependence on hemin and NAD for growth. Based on tests for hemolysis, for the presence of the 7F3 epitope of the P6 protein, and for the presence of iga in 412 of the isolates, 346 (84%) were H. influenzae, 47 (11%) were H. haemolyticus, 18 (4%) were nonhemolytic H. haemolyticus, and 1 was a variant strain. Carriers A and B were predominantly colonized with nontypeable H. influenzae, carrier C predominantly with b⁻ H. influenzae mutants, and carrier D with H. haemolyticus. A total of 358 H. influenzae and H. haemolyticus isolates were genotyped by pulsed-field gel electrophoresis (PFGE) following SmaI or EagI digestion of their DNA, and the carriers displayed the following: carrier A had 11 unique PFGE genotypes, carrier B had 15, carrier C had 7, and carrier D had 10. Thus, adult H. influenzae and H. haemolyticus carriers are colonized with multiple unique genotypes, the colonizing strains exhibit genetic diversity, and we observed day-to-day and week-to-week variability of the genotypes. These results appear to reflect both evolutionary processes that occur among H. influenzae isolates during asymptomatic pharyngeal carriage and sample-to-sample collection bias from a large, variable population of colonizing bacteria.
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