Exploration of Rapid Automatized Naming and Standard Visual Tests in Prodromal Alzheimer Disease Detection.

BACKGROUND: Visual tests in Alzheimer disease (AD) have been examined over the last several decades to identify a sensitive and noninvasive marker of the disease. Rapid automatized naming (RAN) tasks have shown promise for detecting prodromal AD or mild cognitive impairment (MCI). The purpose of this investigation was to determine the capacity for new rapid image and number naming tests and other measures of visual pathway structure and function to distinguish individuals with MCI due to AD from those with normal aging and cognition. The relation of these tests to vision-specific quality of life scores was also examined in this pilot study. METHODS: Participants with MCI due to AD and controls from well-characterized NYU research and clinical cohorts performed high and low-contrast letter acuity (LCLA) testing, as well as RAN using the Mobile Universal Lexicon Evaluation System (MULES) and Staggered Uneven Number test, and vision-specific quality of life scales, including the 25-Item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement. Individuals also underwent optical coherence tomography scans to assess peripapillary retinal nerve fiber layer and ganglion cell/inner plexiform layer thicknesses. Hippocampal atrophy on brain MRI was also determined from the participants' Alzheimer disease research center or clinical data. RESULTS: Participants with MCI (n = 14) had worse binocular LCLA at 1.25% contrast compared with controls (P = 0.009) and longer (worse) MULES test times (P = 0.006) with more errors in naming images (P = 0.009) compared with controls (n = 16). These were the only significantly different visual tests between groups. MULES test times (area under the receiver operating characteristic curve [AUC] = 0.79), MULES errors (AUC = 0.78), and binocular 1.25% LCLA (AUC = 0.78) showed good diagnostic accuracy for distinguishing MCI from controls. A combination of the MULES score and 1.25% LCLA demonstrated the greatest capacity to distinguish (AUC = 0.87). These visual measures were better predictors of MCI vs control status than the presence of hippocampal atrophy on brain MRI in this cohort. A greater number of MULES test errors (rs = -0.50, P = 0.005) and worse 1.25% LCLA scores (rs = 0.39, P = 0.03) were associated with lower (worse) NEI-VFQ-25 scores. CONCLUSIONS: Rapid image naming (MULES) and LCLA are able to distinguish MCI due to AD from normal aging and reflect vision-specific quality of life. Larger studies will determine how these easily administered tests may identify patients at risk for AD and serve as measures in disease-modifying therapy clinical trials.

Diaper Need Is Associated with Pediatric Care Use: An Analysis of a Nationally Representative Sample of Parents of Young Children.

OBJECTIVE: To examine the possible association between diaper need, difficulty affording an adequate amount of diapers, and pediatric care visits for urinary tract infections and diaper dermatitis. STUDY DESIGN: This cross-sectional analysis using nationally representative survey data collected July-August 2017 using a web-based panel examined 981 parents of children between 0 and 3 years of age in the US (response rate, 94%). Survey weighting for differential probabilities of selection and nonresponse was used to estimate the prevalence of diaper need and to perform multivariable logistic regression of the association between parent reported diaper need and visits to the pediatrician for diaper rash or urinary tract infections within the past 12 months. RESULTS: An estimated 36% of parents endorsed diaper need. Both diaper need (aOR 2.37; 95% CI 1.69-3.31) and visiting organizations to receive diapers (aOR 2.14; 95% CI 1.43-3.21) were associated with diaper dermatitis visits. Similar associations were found for diaper need (aOR 2.63; 95% CI 1.54-4.49) and visiting organizations to receive diapers (aOR 4.50; 95% CI 2.63-7.70) for urinary tract infection visits. CONCLUSIONS: Diaper need is common and associated with increased pediatric care visits. These findings suggest pediatric provider and policy interventions decreasing diaper need could improve child health and reduce associated healthcare use.

Structural Barriers to Citizenship: A Mental Health Provider Perspective.

This study employed a citizenship measure to explore mental health providers' views of citizenship to support the societal participation of people with mental illnesses, with citizenship defined as a person's (or people's) strong connection to the 5Rs of rights, responsibilities, roles, resources and relationships and a sense of belonging that is validated by others. Providers identified key structural barriers to full citizenship for clients. Their comments reflect openness to citizenship as a framework for understanding their clients and the need for greater access to normative community life, but also skepticism regarding providers' and public mental health centers' abilities to incorporate citizenship approaches in current care models. Findings suggest there are challenges to implementing "citizenship-oriented care" in public mental health settings, but efforts to address these challenges can support the goal of "a life in the community."

A Comparison of Respiratory Variables in a Wild Population of Ventilated and Nonventilated Black Kites (Milvus migrans govinda).

Black kites (Milvus migrans govinda) often become injured due to kite-string injuries obtained during the International Kite Flying Festival that takes place during the celebration of Uttarayan, in Ahmedabad, India. The purpose of this study was to compare respiratory variables in ventilated and nonventilated black kites, to facilitate an evidence-based decision on whether to ventilate injured birds. A total of 56 juvenile and adult black kites of unknown sex were anesthetized and divided into a ventilated group (VG) and a nonventilated group (NVG). The variables recorded were end tidal carbon dioxide (ETCO2), peripheral capillary oxygen saturation, heart rate, respiratory rate, and maintenance percentage of isoflurane (%ISO). The ETCO2 values were higher in the NVG compared to the VG (72.9 ± 19.8 mm Hg compared to 16.0 ± 5.6 mm Hg, P < .01). The %ISO required to maintain adequate depth of anesthesia was higher in NVG compared to VG (3.5% ± 0.5% compared to 2.2% ± 0.4%, P < .001). Peripheral capillary oxygen saturation was not statistically different between groups (NVG 96.3% ± 3.5% compared to the VG 96.0% ± 5.1%, P = .867). Ventilation under anesthesia appears to lower the ETCO2 and the %ISO flow rate used to maintain a surgical plane of anesthesia. These findings should provide information that will be helpful in the anesthetic management of black kites and may apply to other avian species as well.

A Qualitative Exploration of Mothers' Experiences Receiving Mental Health Services in a Supermarket Setting.

Objectives Innovative mental health care delivery models have been proposed as a method to address disparities in access and utilization. The aim of this study is to characterize patients' perspectives and experiences of participating in one such innovative delivery model, group cognitive behavioral therapy within a supermarket setting. Methods In this qualitative study, 16 mothers were interviewed to explore their experiences and perspectives of receiving group-based cognitive behavioral therapy in a supermarket setting, as part of their participation in an academic-community research collaborative whose mission is to address mental health needs within low-resourced communities. Data from semi-structured interviews were analyzed using inductive coding. Results Five themes related to receiving mental health services in a supermarket setting emerged from the data: (1) Participants reported a convergence of life stressors and their introduction to supermarket-based services; (2) Participants perceived the supermarket setting as convenient; (3) Participants perceived the supermarket setting as less stigmatizing; (4) Participants perceived services in the supermarket as an acceptable form of mental health treatment; and (5) Participants described the program staff as an influential component of their treatment experience. Conclusions Understanding patient experiences of various service delivery models is critical to improving access to treatment and addressing disparities in mental health service utilization and outcomes. This study supports the use of innovative delivery models to increase access to mental health services in low-resourced communities.

Long term at-home treatment with transcranial direct current stimulation (tDCS) improves symptoms of cerebellar ataxia: a case report.

BACKGROUND: Progressive cerebellar ataxia is a neurodegenerative disorder without effective treatment options that seriously hinders quality of life. Previously, transcranial direct current stimulation (tDCS) has been demonstrated to benefit cerebellar functions (including improved motor control, learning and emotional processing) in healthy individuals and patients with neurological disorders. While tDCS is an emerging therapy, multiple daily sessions are needed for optimal clinical benefit. This case study tests the symptomatic benefit of remotely supervised tDCS (RS-tDCS) for a patient with cerebellar ataxia. METHODS: We report a case of a 71-year-old female patient with progressive cerebellar ataxia, who presented with unsteady gait and balance impairment, treated with tDCS. tDCS was administered using our RS-tDCS protocol and was completed daily in the patient's home (Monday - Friday) with the help of a trained study technician. tDCS was paired with 20 min of simultaneous cognitive training, followed by 20 min of physical exercises directed by a physical therapist. Stimulation consisted of 20 min of 2.5 mA direct current targeting the cerebellum via an anodal electrode and a cathodal electrode placed over the right shoulder. The patient completed baseline and treatment end visits with neurological, cognitive, and motor (Lafayette Grooved Pegboard Test, 25 ft walk test and Timed Up and Go Test) assessments. RESULTS: The patient successfully completed sixty tDCS sessions, 59 of which were administered remotely at the patient's home with the use of real time supervision as enabled by video conferencing. Mild improvement was observed in the patient's gait with a 7% improvement in walking speed, which she completed without a walking-aid at treatment end, which was in stark contrast to her baseline assessment. Improvements were also achieved in manual dexterity, with an increase in pegboard scores bilaterally compared to baseline. CONCLUSIONS: Results from this case report suggest that consecutively administered tDCS treatments paired with cognitive and physical exercise hold promise for improving balance, gait, and manual dexterity in patients with progressive ataxia. Remotely supervised tDCS provides home access to enable the administration over an extended period. Further controlled study in a large group of those with cerebellar ataxia is needed to replicate these findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03049969 . Registered 10 February 2017- Retrospectively registered.

Facilitating community connections among people with mental illnesses: Perspectives from grassroots community leaders.

We conducted focus groups comprising 20 grassroots community leaders to identify social and structural elements that affect community engagement among people with serious mental illnesses. Community leaders not affiliated with mental health systems have been mostly left out of the discussions about inclusion and engagement, even though they possess unique information about the places where they live and can be essential partners in making community connections. The findings from the focus groups point to elements that both facilitate and inhibit connections, as well as roles community mental health practitioners may take on, to engage with community leaders and people with mental illness to minimize barriers and foster connections in community settings. Additionally, the focus groups elucidated the interplay between the right to be a member of one's community and a community's responsibility to create a welcoming environment. The current study garnered information regarding the broader needs and implications of community connections, as well as some specific suggestions to enhance community engagement among people with serious mental illness. Hesitation and stigma around engaging individuals with mental illnesses were identified as barriers to inclusion. Further study about how community leaders and groups may be involved in facilitating meaningful community connections is recommended.

Reliability and Validity of a Newly Developed Measure of Citizenship Among Persons with Mental Illnesses.

Following development of a 46-item of measure citizenship, a framework for supporting the full membership in society of persons with mental illness, this study tested the measure's reliability and validity. 110 persons from a mental health center completed a questionnaire packet containing the citizenship measure and other measures to assess internal consistency and validity of the citizenship instrument. Correlation matrices were examined for associations between the citizenship instrument and other measures. Stepwise regression examines demographic factors, sense of community, and social capital as predictors of citizenship, recovery, and well-being. Analyses revealed that the measure is psychometrically sound. The measure captures subjective information about the degree to which individuals experience rights, sense of belonging, and other factors associated with community membership that have been previously difficult to assess. The measure establishes a platform for interventions to support the full participation in society of persons with mental illnesses.

SASH1 is a scaffold molecule in endothelial TLR4 signaling.

Recognition of microbial products by TLRs is critical for mediating innate immune responses to invading pathogens. In this study, we identify a novel scaffold protein in TLR4 signaling called SAM and SH3 domain containing protein 1 (SASH1). Sash1 is expressed across all microvascular beds and functions as a scaffold molecule to independently bind TRAF6, TAK1, IκB kinase α, and IκB kinase ß. This interaction fosters ubiquitination of TRAF6 and TAK1 and promotes LPS-induced NF-κB, JNK, and p38 activation, culminating in increased production of proinflammatory cytokines and increased LPS-induced endothelial migration. Our findings suggest that SASH1 acts to assemble a signaling complex downstream of TLR4 to activate early endothelial responses to receptor activation.

The Citizenship Project part II: impact of a citizenship intervention on clinical and community outcomes for persons with mental illness and criminal justice involvement.

This study assessed the effectiveness of an intervention based on a theoretical framework of citizenship on reducing psychiatric symptoms, alcohol use, and drug use, and increasing quality of life for persons with serious mental illness (SMI) and criminal justice involvement. One-hundred fourteen adults with SMI and a history of criminal justice involvement participated in a 2 × 3 longitudinal randomized controlled trial of a four-month citizenship intervention versus usual services. Linear mixed model analyses were used to assess the intervention's impact on quality of life, symptoms, and substance use. After controlling for baseline covariates, participants in the experimental condition reported significantly increased quality of life, greater satisfaction with and amount of activity, higher satisfaction with work, and reduced alcohol and drug use over time. However, individuals in the experimental condition also reported increased anxiety/depression and agitation at 6 months (but not 12 months) and significantly increased negative symptoms at 12 months. Findings suggest that community-oriented, citizenship interventions for persons with SMI and criminal justice histories may facilitate improved clinical and community outcomes in some domains, but some negative clinical findings suggest the need for post-intervention support for intervention participants. Implications for practice and future research are discussed.

Utp22p acts in concert with Utp8p to channel aminoacyl-tRNA from the nucleolus to the nuclear tRNA export receptor Los1p but not Msn5p.

Utp8p is an essential nucleolar protein that channels aminoacyl-tRNAs from aminoacyl-tRNA synthetases in the nucleolus to the nuclear tRNA export receptors located in the nucleoplasm and nuclear pore complex in Saccharomyces cerevisiae. Utp8p is also part of the U3 snoRNA-associated protein complex involved in 18S rRNA biogenesis in the nucleolus. We report that Utp22p, which is another member of the U3 snoRNA-associated protein complex, is also an intranuclear component of the nuclear tRNA export machinery. Depletion of Utp22p results in nuclear retention of mature tRNAs derived from intron-containing and intronless precursors. Moreover, Utp22p copurifies with the nuclear tRNA export receptor Los1p, the aminoacyl-tRNA synthetase Tys1p and Utp8p, but not with the RanGTPase Gsp1p and the nuclear tRNA export receptor Msn5p. Utp22p interacts directly with Utp8p and Los1p in a tRNA-independent manner in vitro. Utp22p also interacts directly with Tys1p, but this binding is stimulated when Tys1p is bound to tRNA. However, Utp22p, unlike Utp8p, does not bind tRNA saturably. These data suggest that Utp22p recruits Utp8p to aminoacyl-tRNA synthetases in the nucleolus to collect aminoacyl-tRNA and then accompanies the Utp8p-tRNA complex to deliver the aminoacyl-tRNAs to Los1p but not Msn5p. It is possible that Nrap/Nol6, the mammalian orthologue of Utp22p, plays a role in channelling aminoacyl-tRNA to the nuclear tRNA export receptor exportin-t.

Asymbiotic in vitro seed germination, in vitro seedling development, and ex vitro acclimatization of Spiranthes.

Premise: Reproducible seed propagation and production protocols were developed for Spiranthes and related taxa to facilitate ex situ conservation practices. Methods and Results: Spiranthes seeds were scarified for 3- and 10-min intervals in 10% sodium hypochlorite solution, then cultured on three seed germination media. After germination, seedlings were given one of the three photoperiod treatments, and then planted in one of four greenhouse substrates. Seed germination ranged from 0% to 90% and occurred on all three media only after the 3-min scarification. Seedlings in the 24/0-h light/dark and 16/8-h light/dark photoperiods on P723 medium had significantly higher fresh weight than those in the dark treatment group. Ex vitro survival ranged from 55% to 95% across substrates. Conclusions: Results show that Spiranthes seeds are damaged by extended chemical scarification, are adaptable to a variety of culture media, and require light for optimal development. Further experimentation showed that the propagation protocols described here can be applied broadly within the genus.

Centralizing neurofibromatosis experimental tool knowledge with the NF Research Tools Database.

Experimental tools and resources, such as animal models, cell lines, antibodies, genetic reagents and biobanks, are key ingredients in biomedical research. Investigators face multiple challenges when trying to understand the availability, applicability and accessibility of these tools. A major challenge is keeping up with current information about the numerous tools available for a particular research problem. A variety of disease-agnostic projects such as the Mouse Genome Informatics database and the Resource Identification Initiative curate a number of types of research tools. Here, we describe our efforts to build upon these resources to develop a disease-specific research tool resource for the neurofibromatosis (NF) research community. This resource, the NF Research Tools Database, is an open-access database that enables the exploration and discovery of information about NF type 1-relevant animal models, cell lines, antibodies, genetic reagents and biobanks. Users can search and explore tools, obtain detailed information about each tool as well as read and contribute their observations about the performance, reliability and characteristics of tools in the database. NF researchers will be able to use the NF Research Tools Database to promote, discover, share, reuse and characterize research tools, with the goal of advancing NF research. Database URL: https://tools.nf.synapse.org/.

Harnessing the power of botanical gardens: Evaluating the costs and resources needed for exceptional plant conservation.

Premise: The effective ex situ conservation of exceptional plants, whether in living collections or cryo-collections, requires more resources than the conservation of other species. Because of their expertise with rare plants, botanical gardens are well positioned to lead this effort, but a well-developed strategy requires a clear understanding of the resources needed. Methods: Grant funding was obtained from the Institute of Museum and Library Services to support a three-year project on cryobanking, and to provide smaller grants to 10 other botanical gardens for one-year projects on either (1) seed behavior studies or (2) the development of protocols for in vitro propagation or cryopreservation. Results: Nine of the partner gardens worked on 19 species (one was unable to continue due to the COVID-19 pandemic), while the larger project focused on 14 species. A point system was developed for tasks accomplished, and the average costs per point of the larger and smaller projects were similar. Labor accounted for half the costs. Projects focused on species in the Asteraceae and Orchidaceae had lower costs per point than other species. Discussion: Both large and small projects can contribute to a strategy for exceptional plant conservation for similar costs. Prioritizing species with lower costs could help advance the field while allowing time for work on more difficult species to develop.

Viral time capsule: a global photo-elicitation study of child and adolescent mental health professionals during COVID-19.

OBJECTIVE: To examine, through photo-elicitation, the personal and professional impact of the COVID-19 pandemic on mental health professionals working with children and adolescents around the globe. METHODS: We invited the submission of images collected about the pandemic between May and August 2020. We encouraged participants to yoke personal reflections or voice memos to their images. Using snowball sampling, we began with two invitations, including one to the graduates of a mentorship program continuously hosted since 2004 by the International Association of Child and Adolescent Psychiatry and Allied Professions (IACAPAP). We analyzed de-identified images and anonymized transcripts through iterative coding using thematic analysis informed by rich picture analysis and aided by NVivo software. RESULTS: We collected submissions from child and adolescent mental health professionals (n = 134) working in 54 countries spread across the five continents. We identified four overarching domains with component themes that revealed both the commonality and the uniqueness of the pandemic experience around the globe: (1) Place (adjusting to emptiness and stillness; shifting timeframes; blending of spaces); (2) Person (disruption to life rhythms; emotional toll; positives of the pandemic); (3) Profession (changing practices; outreach efforts; guild pride-and guilt); and (4) Purpose (from pandemic to syndemic; from lamenting to embracing; planning toward a better tomorrow). CONCLUSIONS: Photo-elicitation provided a disarming and efficient means to learn about individual, regional, and global similarities and differences regarding the professionals charged with addressing the mental health needs of children and adolescents around the globe. These findings may help inform practice changes in post-pandemic times.

Meta-analysis of HIV-1 vaccine elicited mucosal antibodies in humans.

We studied mucosal immune responses in six HIV-1 vaccine trials investigating different envelope (Env)-containing immunogens. Regimens were classified into four categories: DNA/vector, DNA/vector plus protein, protein alone, and vector alone. We measured HIV-1-specific IgG and IgA in secretions from cervical (n = 111) and rectal swabs (n = 154), saliva (n = 141), and seminal plasma (n = 124) and compared to corresponding blood levels. Protein-containing regimens had up to 100% response rates and the highest Env-specific IgG response rates. DNA/vector groups elicited mucosal Env-specific IgG response rates of up to 67% that varied across specimen types. Little to no mucosal IgA responses were observed. Overall, gp41- and gp140-specific antibodies dominated gp120 mucosal responses. In one trial, prior vaccination with a protein-containing immunogen maintained durability of cervical and rectal IgG for up to 17 years. Mucosal IgG responses were boosted after revaccination. These findings highlight a role for protein immunization in eliciting HIV-1-specific mucosal antibodies and the ability of HIV-1 vaccines to elicit durable HIV-1-specific mucosal IgG.

Videoconferencing-Based Telemental Health: Important Questions for the COVID-19 Era From Clinical and Patient-Centered Perspectives.

The COVID-19 pandemic has intensified the search for digital approaches in mental health treatment, particularly due to patients and clinicians practicing social distancing. This has resulted in the dramatic growth of videoconferencing-based telemental health (V-TMH) services. It is critical for behavioral health providers and those in the mental health field to understand the implications of V-TMH expansion on the stakeholders who use such services, such as patients and clinicians, to provide the service that addresses both patient and clinical needs. Several key questions arise as a result, such as the following: (1) in what ways does V-TMH affect the practice of psychotherapy (ie, clinical needs), (2) to what extent are ethical and patient-centered concerns warranted in terms of V-TMH services (ie, patient needs), and (3) how do factors related to user experience affect treatment dynamics for both the patient and therapist (ie, patient and clinical needs)? We discuss how behavioral health providers can consider the future delivery of mental health care services based on these questions, which pose strong implications for technological innovation, the adaptation of treatments to new technologies, and training professionals in the delivery of V-TMH services and other digital health interventions.

Testing the Family Stress Model among Black Women Receiving Temporary Assistance for Needy Families (TANF).

Black female primary caregivers who receive Temporary Assistance for Needy Families (TANF) are burdened not only by economic pressure but also by a disproportionate prevalence of psychological disorders. This is particularly pernicious given that poverty and maternal mental health impact child outcomes and may decrease the economic mobility of families. Consequently, it is imperative to understand the mechanisms that explain the association between economic pressure and child outcomes. The current study addressed this gap by testing an application of the Family Stress Model (FSM), which describes how economic pressure results in parental psychological distress, particularly depression, and in turn impacts parenting quality and child outcomes. Additionally, social support was assessed as a potential culturally-salient protective factor within the model. Four hundred sixteen Black female primary caregivers who receive TANF were administered a series of measures assessing mental health and family wellbeing. Structural equation modeling was utilized to test a single model that incorporated all hypotheses. Maternal depression and quality of parenting serially mediated the relationship between economic pressure and school performance. The relationship between economic pressure and adverse child outcomes, however, was mediated only by maternal depression. Social support did not significantly moderate the relationship between economic pressure and maternal depression; however, it did demonstrate a significant direct effect on maternal depression. The current study corroborates the application of FSM to another population. Further, it demonstrates the importance of interventions that target maternal mental health, parenting, social support, and family economic mobility as well as system-level policy interventions to address poverty.

The association of α4ß7 expression with HIV acquisition and disease progression in people who inject drugs and men who have sex with men: Case control studies.

BACKGROUND: α4ß7 is a gut-homing integrin heterodimer that can act as a non-essential binding molecule for HIV. A previous study in heterosexual African women found that individuals with higher proportions of α4ß7 expressing CD4+ T cells were more likely to become infected with HIV, as well as present with faster disease progression. It is unknown if this phenomenon is also observed in men who have sex with men (MSM) or people who inject drugs (PWID). METHODS: MSM and transgender women who seroconverted as part of the HVTN 505 HIV vaccine trial and PWID who seroconverted during the ALIVE cohort study were selected as cases and matched to HIV-uninfected controls from the same studies (1:1 and 1:3, respectively). Pre-seroconversion PBMC samples from cases and controls in both studies were examined by flow cytometry to measure levels of α4ß7 expression on CD4+ T cells. Multivariable conditional logistic regression was used to compare α4ß7 expression levels between cases and controls. A Kaplan-Meier curve was used to examine the association of α4ß7 expression pre-seroconversion with HIV disease progression. FINDINGS: In MSM and transgender women (n = 103 cases, 103 controls), there was no statistically significant difference in the levels of α4ß7 expression on CD4+ T cells between cases and controls (adjusted odds ratio [adjOR] =1.10, 95% confidence interval [CI]=0.94,1.29; p = 0.246). Interestingly, in PWID (n = 49 cases, 143 controls), cases had significantly lower levels of α4ß7 expression compared to their matched controls (adjOR = 0.80, 95% CI = 0.68, 0.93; p = 0.004). Among HIV-positive PWID (n = 47), there was no significant association in HIV disease progression in individuals above or below the median level of α4ß7 expression (log-rank p = 0.84). INTERPRETATION: In contrast to findings in heterosexual women, higher α4ß7 expression does not predict HIV acquisition or disease progression in PWID or MSM. FUNDING: This study was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. The study was also supported by extramural grants from NIAID T32AI102623 (E.U.P.), and UM1AI069470.