In mice, discrete odors can selectively promote the neurogenesis of sensory neuron subtypes that they stimulate.

In mammals, olfactory sensory neurons (OSNs) are born throughout life, presumably solely to replace neurons lost via turnover or injury. This assumption follows from the hypothesis that olfactory neurogenesis is strictly stochastic with respect to neuron subtype, as defined by the single odorant receptor allele that each neural precursor stochastically chooses out of hundreds of possibilities. This hypothesis is challenged by recent findings that the birthrates of a fraction of subtypes are selectively diminished by olfactory deprivation. These findings raise questions about how, and why, olfactory stimuli are required to promote the neurogenesis of some OSN subtypes, including whether the stimuli are generic (e.g., broadly activating odors or mechanical stimuli) or specific (e.g., discrete odorants). Based on RNA-seq and scRNA-seq analyses, we hypothesized that the neurogenic stimuli are specific odorants that selectively activate the same OSN subtypes whose birthrates are accelerated. In support of this, we have found, using subtype-specific OSN birthdating, that exposure to male and musk odors can accelerate the birthrates of responsive OSNs. Collectively, our findings reveal that certain odor experiences can selectively "amplify" specific OSN subtypes, and that persistent OSN neurogenesis may serve, in part, an adaptive function.

Congenital Cytomegalovirus-Associated Sensorineural Hearing Loss in Children: Identification Following Universal Newborn Hearing Screening, Effect of Antiviral Treatment, and Long-Term Hearing Outcomes.

OBJECTIVES: Congenital cytomegalovirus (cCMV) is the most common cause of nongenetic sensorineural hearing loss (SNHL) in children. We examined the longitudinal hearing outcomes of children with cCMV in relation to their newborn hearing screening findings, and their use of antiviral therapy. DESIGN: The study was based on a retrospective chart review using a database of pediatric patients (N = 445) seen at the University of Minnesota Lions clinic. Chart review identified infants with cCMV, and records were reviewed for information about universal newborn hearing screen (UNHS) results, the clinical course of SNHL, and the use of antiviral therapy. RESULTS: A total of 44 children were identified with cCMV. In this group, 33 (75%) had SNHL of varying degree and age at onset. Notably, 17 (39%) children passed UNHS bilaterally. Of those children, 6 (35%) ultimately acquired bilateral or unilateral SNHL, detected at a mean age of 20 months (median age, 12 months). Five out of 10 children (50%) that did not pass UNHS in one ear acquired late-onset hearing loss in the contralateral ear, identified at a mean age of 24 months (median age, 4 months). Eleven (25%) children passed UNHS bilaterally and continued to demonstrate normal hearing in both ears at their most recent follow-up visit at a mean age of 19 months (SD, 18 months). Of the 33 children with cCMV and SNHL, 18 (55%) received antiviral medication (ganciclovir and/or valganciclovir). While, on average, both treated and untreated ears experienced a progression of hearing loss over time, the group that received antiviral treatment experienced less overall hearing change compared with the untreated group (baseline-adjusted expected mean difference, -10.5 dB; 95% confidence interval, -28.1 to 7.2 dB). CONCLUSIONS: Among children with cCMV included in this study who passed UNHS in both ears, 35% demonstrated delayed-onset SNHL. Notably, of those children who referred unilaterally, 50% later demonstrated SNHL in the contralateral ear. These findings have implications for audiological monitoring, and potentially antiviral therapy, of children with cCMV. As implementation of universal cCMV screening moves forward, a key aspect of follow-up will be appropriate long-term audiologic monitoring.

A Wearable System for Continuous Monitoring and Assessment of Speech, Gait, and Cognitive Decline for Early Diagnosis of ADRD.

Early detection of cognitive decline is essential to study mild cognitive impairment and Alzheimer's Disease in order to develop targeted interventions and prevent or stop the progression of dementia. This requires continuous and longitudinal assessment and tracking of the related physiological and behavioral changes during daily life. In this paper, we present a low cost and low power wearable system custom designed to track the trends in speech, gait, and cognitive stress while also considering the important human factor needs such as privacy and compliance. In the form factors of a wristband and waist-patch, this multimodal, multi-sensor system measures inertial signals, sound, heart rate, electrodermal activity and pulse transit time. A total power consumption of 2.6 mW without any duty cycling allows for more than 3 weeks of run time between charges when 1500 mAh batteries are used.Clinical Relevance- Much earlier detection of Alzheimer's disease and related dementias may be possible by continuous monitoring of physiological and behavioral state using application specific wearable sensors during the activities of daily life.

A histological protocol for quantifying the birthrates of specific subtypes of olfactory sensory neurons in mice.

Mammals typically have hundreds of distinct olfactory sensory neuron subtypes, each defined by expression of a specific odorant receptor gene, which undergo neurogenesis throughout life at rates that can depend on olfactory experience. Here, we present a protocol to quantify the birthrates of specific neuron subtypes via the simultaneous detection of corresponding receptor mRNAs and 5-ethynyl-2'-deoxyuridine. For preparation prior to beginning the protocol, we detail procedures for generating odorant receptor-specific riboprobes and experimental mouse olfactory epithelial tissue sections. For complete details on the use and execution of this protocol, please refer to van der Linden et al. (2020).1.

Third and Fourth Vaccine Doses Broaden and Prolong Immunity to SARS-CoV-2 in Adult Patients with Immune-Mediated Inflammatory Diseases.

Previous studies have reported impaired humoral responses after SARS-CoV-2 mRNA vaccination in patients with immune-mediated inflammatory diseases (IMIDs), particularly those treated with anti-TNF biologics. We previously reported that IMID patients diagnosed with inflammatory bowel disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, or rheumatoid arthritis exhibited greater waning of Ab and T cell responses than healthy control subjects after SARS-CoV-2 vaccine dose 2. Fewer data are available on the effects of third and fourth doses. This observational cohort study collected plasma and PBMCs from healthy control subjects and untreated or treated patients with IMIDs prevaccination and after one to four doses of SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273). SARS-CoV-2-specific Ab levels, neutralization, and T cell cytokine release were measured against wild-type and Omicron BA.1 and BA.5 variants of concern. Third vaccine doses substantially restored and prolonged Ab and T cell responses in patients with IMIDs and broadened responses against variants of concern. Fourth-dose effects were subtle but also prolonged Ab responses. However, patients with IMIDs treated with anti-TNF, especially patients with inflammatory bowel disease, exhibited lower Ab responses even after the fourth dose. Although T cell IFN-γ responses were maximal after one dose, IL-2 and IL-4 production increased with successive doses, and early production of these cytokines was predictive of neutralization responses at 3-4 mo postvaccination. Our study demonstrates that third and fourth doses of the SARS-CoV-2 mRNA vaccines sustain and broaden immune responses to SARS-CoV-2, supporting the recommendation for three- and four-dose vaccination regimens in patients with IMIDs.

"Weight of the World" and "I Want Them to Know": Skilled Nursing Facility Administrators' Perspectives on COVID-19 in Research Poems.

COVID-19 has had a drastic, long-lasting impact on skilled nursing facilities (SNFs), forcing communities to continuously adapt to rapidly changing guidelines, restrictions, and challenges. In spring 2020, we conducted a sequential mixed-methods study with administrators of SNFs in the Midwest to understand the experience of administrators, staff, and residents during the pandemic. We collected 60 surveys with open-ended items related to the impact of the pandemic on communities as a whole, staff, and residents. Survey findings informed supplemental interviews with six administrators working in diverse regions. Due to the affective nature of the data, we present the findings in two found poems, which emphasize the lyrical, emotional, and poignant aspects of the participant voices. The first poem, Weight of the World, captures the struggle to adapt during the transition into the pandemic and its negative impacts on the lives of residents and their families. The second, I Want Them to Know, describes the resiliency with which administrators and staff responded to adversity while maintaining motivation to continue the work in the midst of unprecedented challenges. The two poems offer contrasting or balancing narratives of struggle and survival during the pandemic era.

Effects of unilateral eye closure on middle ear muscle contractions.

Middle ear muscle contractions (MEMCs) are most commonly considered a response to high-level acoustic stimuli. However, MEMCs have also been observed in the absence of sound, either as a response to somatosensory stimulation or in concert with other motor activity. The relationship between MEMCs and non-acoustic sources is unclear. This study examined associations between measures of voluntary unilateral eye closure and impedance-based measures indicative of middle ear muscle activity while controlling for demographic and clinical factors in a large group of participants (N=190) with present clinical acoustic reflexes and no evidence of auditory dysfunction. Participants were instructed to voluntarily close the eye ipsilateral to the ear canal containing a detection probe at three levels of effort. Orbicularis oculi muscle activity was measured using surface electromyography. Middle ear muscle activity was inferred from changes in total energy reflected in the ear canal using a filtered (0.2 to 8 kHz) click train. Results revealed that middle ear muscle activity was positively associated with eye muscle activity. MEMC occurrence rates for eye closure observed in this study were generally higher than previously published rates for high-level brief acoustic stimuli in the same participant pool suggesting that motor activity may be a more reliable elicitor of MEMCs than acoustic stimuli. These results suggest motor activity can serve as a confounding factor for auditory exposure studies as well as complicate the interpretation of any impulsive noise damage risk criteria that assume MEMCs serve as a consistent, uniform protective factor. The mechanism linking eye and middle ear muscle activity is not understood and is an avenue for future research.

Analysis of Postpartum Uptake of Long-Acting Reversible Contraceptives Before and After Implementation of Medicaid Reimbursement Policy.

OBJECTIVES: The postpartum period is a time of high unmet contraception need. Providing long-acting reversible contraception (LARC), particularly in the immediate postpartum period, is one strategy to meet contraceptive needs. This practice may also prevent unintended and short interpregnancy interval pregnancies. In recent years, state Medicaid programs have implemented reimbursement policies for LARC use in the inpatient setting. The purpose of this study was to assess the uptake of inpatient postpartum LARCs at a large urban hospital with a sizable Medicaid population, before and after policy implementation. METHODS: Using billing records from January 2015 and December 2017, we extracted data on patient demographics and LARC uptake before Medicaid policy change (2015) and after policy change (2016 and 2017). Implant and intrauterine device insertions were classified as inpatient postpartum (0-7 days after birth), outpatient postpartum (1-8 weeks after) or interval (9+ weeks after). RESULTS: In the 3-year study period, 2091 LARC insertions occurred, of which 700 (33.5%) were inpatient postpartum, 429 (20.5%) outpatient postpartum, and 962 (46.0%) interval. After policy implementation, inpatient postpartum LARC insertions increased from 2.6 per 100 deliveries to 16.8 per 100 deliveries. Significant differences in uptake were seen in Black and Hispanic populations. The number of outpatient postpartum LARCs remained stable and tubal sterilizations decreased. CONCLUSIONS FOR PRACTICE: Implementation of reimbursement policies contributed to a sharp uptake of inpatient postpartum LARCs. Improved access to effective, reversible contraception could reduce the number of unplanned and short interpregnancy interval pregnancies, ultimately lowering rates of maternal morbidity and mortality.

Effect of Competition, Signal-to-Noise Ratio, Race, and Sex on Southern American English Dialect Talkers' Sentence Recognition.

BACKGROUND: Although numerous studies have examined regional and racial-ethnic labeling of talker identity, few have evaluated speech perception skills of listeners from the southern United States. PURPOSE: The objective of the study was to examine the effect of competition, signal-to-noise ratio (SNR), race, and sex on sentence recognition performance in talkers from the Southern American English dialect region. RESEARCH DESIGN: A four-factor mixed-measures design was used. STUDY SAMPLE: Forty-eight normal-hearing young African American and White adults participated. DATA COLLECTION AND ANALYSES: The Perceptually Robust English Sentence Test Open-set was used in quiet and in continuous and interrupted noise and multitalker babble at SNRs of -10, -5, 0, and 5 dB. RESULTS: Significant main effects of competition (p < 0.001) and SNR (p < 0.001) and a competition by SNR interaction were found (p < 0.001). Performance improved with increasing SNRs. Performance was also greater in the interrupted broadband noise at poorer SNRs, relative to the other competitors. Multitalker babble performance was significantly poorer than the continuous noise at the poorer SNRs. There was no effect of race or sex on performance in quiet or competition. CONCLUSIONS: Although African American English and White American English talkers living in the same geographic region demonstrate differences in speech production, their speech perception in noise does not appear to differ under the conditions examined in this study.

Poor Access to Opioid Addiction Care for Total Joint Arthroplasty Patients.

INTRODUCTION: The United States is experiencing an opioid epidemic, and orthopedists prescribe a large proportion of these drugs. Patients often become dependent on painkillers and face barriers to treatment. Given that many joint arthroplasty patients are enrolled in Medicare, we aimed to examine the ease of orthopedic patients with various insurance types to access addiction and pain specialists. METHODS: Using three web-based directories, we identified addiction specialists within a 5-mile radius of our hospital. We contacted these practices and inquired as to whether they treated addiction, types of insurance they accepted, and appointment availability. RESULTS: We identified 190 addiction and pain management specialists and were able to reach 134/190 (70.5%). Nine (6.7%) of the 134 reachable physicians accepted Medicare or Medicaid, which is nine (4.7%) of the 190 physicians initially located. The average wait time to an appointment was 4.2 days, and a significant difference in wait time existed across insurance types (p = 0.0284). DISCUSSION: Orthopedic patients face many barriers to receiving treatment for painkiller addiction. Wait time to see an addiction specialist also varied based on insurance type. Online directories may not be useful for certain patient populations to identify physicians. Orthopedic surgeons should partner with addiction and pain specialists to help alleviate the barriers that patients face.

Phlpp1 is associated with human intervertebral disc degeneration and its deficiency promotes healing after needle puncture injury in mice.

Back pain is a leading cause of global disability and is strongly associated with intervertebral disc (IVD) degeneration (IDD). Hallmarks of IDD include progressive cell loss and matrix degradation. The Akt signaling pathway regulates cellularity and matrix production in IVDs and its inactivation is known to contribute to a catabolic shift and increased cell loss via apoptosis. The PH domain leucine-rich repeat protein phosphatase (Phlpp1) directly regulates Akt signaling and therefore may play a role in regulating IDD, yet this has not been investigated. The aim of this study was to investigate if Phlpp1 has a role in Akt dysregulation during IDD. In human IVDs, Phlpp1 expression was positively correlated with IDD and the apoptosis marker cleaved Caspase-3, suggesting a key role of Phlpp1 in the progression of IDD. In mice, 3 days after IVD needle puncture injury, Phlpp1 knockout (KO) promoted Akt phosphorylation and cell proliferation, with less apoptosis. At 2 and 8 months after injury, Phlpp1 deficiency also had protective effects on IVD cellularity, matrix production, and collagen structure as measured with histological and immunohistochemical analyses. Specifically, Phlpp1-deletion resulted in enhanced nucleus pulposus matrix production and more chondrocytic cells at 2 months, and increased IVD height, nucleus pulposus cellularity, and extracellular matrix deposition 8 months after injury. In conclusion, Phlpp1 has a role in limiting cell survival and matrix degradation in IDD and research targeting its suppression could identify a potential therapeutic target for IDD.

The emergence and prevalence of hearing loss in children with homozygous sickle cell disease.

OBJECTIVES: Many children with sickle cell disease (SCD) experience the effect of cochlear insult due to hemolytic anemia and vaso-occlusion that accompanies the disease. As a result, hearing sensitivity eventually decreases. The purpose of this study was to investigate the emergence of hearing loss and the prevalence of such in children with homozygous SCD. METHODS: A large pediatric database was utilized to gather audiometric outcomes in children with homozygous SCD. Children were identified by primary diagnosis ICD codes. Demographic and audiometric data was drawn to determine presence, type, degree, and laterality of hearing loss. Hearing loss was defined as an elevated audiometric threshold >15 dB HL for pure tone air conduction audiometry or >20 dB HL minimal response level for sound-field testing. RESULTS: One hundred and twenty-eight children were identified. The prevalence of hearing loss ranged from 28.8% to 50.8% depending on the calculation method (i.e., individual vs. ear specific prevalence and any elevated threshold vs. a three-frequency pure tone average). Conductive hearing loss and bilateral loss were most prevalent. The degree of hearing loss ranged from slight to profound. The mean age of identification of sensorineural hearing loss was 9.6 years. CONCLUSION: The prevalence of hearing loss in children with homozygous SCD is higher than in normal children. Regular hearing assessments of children with SCD is warranted and should be advocated in early infancy and as part of their ongoing care.

Racial Differences in Pelvic Organ Prolapse Symptoms Among Women Undergoing Pelvic Reconstructive Surgery for Prolapse.

OBJECTIVE: The aim of this study was to determine if there is a difference in Pelvic Floor Disability Index Questionnaire (PFDI-20) scores between black and white women seeking surgical management for pelvic organ prolapse (POP). METHODS: A retrospective cohort study of 232 women who underwent pelvic reconstructive surgery with apical suspension for POP was performed. Demographic and clinical data were collected. All women completed the PFDI-20 and had a Pelvic Organ Prolapse Quantification examination at the initial consultation. Appropriate statistical tests were used to compare black and white women. Multivariable regression models adjusting for demographic and clinical variables were developed to determine the independent relationship between race and POP symptoms. RESULTS: In our cohort, 174 (75%) were white and 58 (25%) were black. Compared with white women, black women had higher parity, body mass index, Charlson Comorbidity Index score, and anterior POP stage. White women had higher total PFDI-20 scores corresponding to higher scores on all symptom subscales. After controlling for potential confounders, white race and prior anti-incontinence surgery remained associated with higher total PFDI scores. Higher Urogenital Distress Inventory 6 scores were significantly associated with white race, prior anti-incontinence procedures, and increasing body mass index, whereas higher CRADI-8 scores were associated with prior anti-incontinence surgery and higher POP stages. CONCLUSIONS: White women appeared to have more overall symptom bother from prolapse, as well as urinary symptoms, as compared with black women, when assessed by validated questionnaire tools in a cohort of patients who underwent prolapse surgery. Further research is required to determine if racial differences in symptoms translate to differences in outcomes.

Retrospective Cohort Study on the Perioperative Risk Factors for Transient Voiding Dysfunction After Apical Prolapse Repair.

OBJECTIVES: The primary aim was to compare the incidence of transient voiding dysfunction (TVD) between vaginal uterosacral ligament suspension, sacrospinous ligament fixation, and robotic sacrocolpopexy. Secondarily, we identified risk factors for TVD and associated postoperative complications. METHODS: This was a retrospective cohort study of women who underwent apical repair at 1 institution. Data were collected from electronic medical records and were presented as means (SD) or numbers (percent) as appropriate. Univariate and multivariate analyses were performed to identify risk factors for TVD and its associated postoperative complications. RESULTS: Three hundred sixty women were included in analysis. Two hundred nineteen (60.8%) passed their voiding trial and 141 (39.2%) experienced TVD. The TVD group demonstrated a higher age, age-adjusted Charlson Comorbidity Index score, and preoperative postvoid residual (all P < 0.05). Univariate analysis demonstrated higher rates of TVD in the vaginal uterosacral ligament suspension and sacrospinous ligament fixation groups compared with the robotic sacrocolpopexy group (P = 0.012). Transient voiding dysfunction occurred more frequently with a concomitant anti-incontinence procedure, anterior repair, and/or posterior repair (all P < 0.05). In multivariate analysis, only an anti-incontinence procedure and concomitant anterior repair were independently associated with a risk of TVD (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.37-3.62, and OR, 2.20; CI, 1.14-4.27, respectively). Transient voiding dysfunction was associated with a culture-proven urinary tract infection within 6 weeks (OR, 3.2; CI, 1.3-8.55). CONCLUSIONS: There was no difference in TVD between types of apical repair. Concomitant anti-incontinence procedure and anterior repair were associated with TVD. Women with TVD have an increased risk of postoperative urinary tract infections.

Epstein-Barr Virus Latent Membrane Protein 1 Regulates Host B Cell MicroRNA-155 and Its Target FOXO3a via PI3K p110α Activation.

Epstein-Barr Virus (EBV) is associated with potentially fatal lymphoproliferations such as post-transplant lymphoproliferative disorder (PTLD), a serious complication of transplantation. The viral mechanisms underlying the development and maintenance of EBV+ B cell lymphomas remain elusive but represent attractive therapeutic targets. EBV modulates the expression of host microRNAs (miRs), non-coding RNAs that regulate gene expression, to promote survival of EBV+ B cell lymphomas. Here, we examined how the primary oncogene of EBV, latent membrane protein 1 (LMP1), regulates host miRs using an established model of inducible LMP1 signaling. LMP1 derived from the B95.8 lab strain or PTLD induced expression of the oncogene miR-155. However, PTLD variant LMP1 lost the ability to upregulate the tumor suppressor miR-193. Small molecule inhibitors (SMI) of p38 MAPK, NF-κB, and PI3K p110α inhibited upregulation of miR-155 by B95.8 LMP1; no individual SMI significantly reduced upregulation of miR-155 by PTLD variant LMP1. miR-155 was significantly elevated in EBV+ B cell lymphoma cell lines and associated exosomes and inversely correlated with expression of the miR-155 target FOXO3a in cell lines. Finally, LMP1 reduced expression of FOXO3a, which was rescued by a PI3K p110α SMI. Our data indicate that tumor variant LMP1 differentially regulates host B cell miR expression, suggesting viral genotype as an important consideration for the treatment of EBV+ B cell lymphomas. Notably, we demonstrate a novel mechanism in which LMP1 supports the regulation of miR-155 and its target FOXO3a in B cells through activation of PI3K p110α. This mechanism expands on the previously established mechanisms by which LMP1 regulates miR-155 and FOXO3a and may represent both rational therapeutic targets and biomarkers for EBV+ B cell lymphomas.

Paper Analytic Device to Detect the Presence of Four Chemotherapy Drugs.

A paper analytic device, the chemoPAD, was developed and validated to visually detect methotrexate, doxorubicin, cisplatin, and oxaliplatin at concentrations commonly found in injectable dosage forms. By testing residual solution after patient treatment, the chemoPAD can be used to monitor drug quality without restriction of patient access to medication. The chemoPAD is produced by wax printing on Ahlstrom paper to create separate reaction areas and deposits small amounts of chemicals to create color changes in response to different active pharmaceutical ingredients (APIs). This creates a unique color bar code to identify each medication. Internal validation studies show that the chemoPAD has excellent sensitivity and specificity to differentiate between samples of 100% and 0% API, which is the distinction relevant to the majority of reported falsified chemotherapy cases. The platinum-containing drugs, cisplatin and oxaliplatin, can be detected semiquantitatively. The cards can be read either visually by comparison with a standard image or by using computer image analysis. Dosage forms were collected from the Ethiopian health care system and analyzed with the chemoPAD followed by high-performance liquid chromatography. A substandard sample was discovered and reported to the Ethiopian Food Medicine and Healthcare Administration and Control Authority.

Right Here Right Now (RHRN) pilot study: testing a method of near-real-time data collection on the social determinants of health.

BACKGROUND: Informing policy and practice with up-to-date evidence on the social determinants of health is an ongoing challenge. One limitation of traditional approaches is the time-lag between identification of a policy or practice need and availability of results. The Right Here Right Now (RHRN) study piloted a near-real-time data-collection process to investigate whether this gap could be bridged. METHODS: A website was developed to facilitate the issue of questions, data capture and presentation of findings. Respondents were recruited using two distinct methods - a clustered random probability sample, and a quota sample from street stalls. Weekly four-part questions were issued by email, Short Messaging Service (SMS or text) or post. Quantitative data were descriptively summarised, qualitative data thematically analysed, and a summary report circulated two weeks after each question was issued. The pilot spanned 26 weeks. RESULTS: It proved possible to recruit and retain a panel of respondents providing quantitative and qualitative data on a range of issues. The samples were subject to similar recruitment and response biases as more traditional data-collection approaches. Participants valued the potential to influence change, and stakeholders were enthusiastic about the findings generated, despite reservations about the lack of sample representativeness. Stakeholders acknowledged that decision-making processes are not flexible enough to respond to weekly evidence. CONCLUSION: RHRN produced a process for collecting near-real-time data for policy-relevant topics, although obtaining and maintaining representative samples was problematic. Adaptations were identified to inform a more sustainable model of near-real-time data collection and dissemination in the future.

A Case Study of Health-Related Support Processes in 2 Happy, Gay Couples.

The purpose of this case study was to explore 2, early-relationship, same-sex couples on the strategies used to support their partner's engagement in health promoting behaviors. A semistructured interview protocol was used to conduct 120-minute interviews with each couple and analyzed using grounded theory methods. Five organizing categories emerged during the analysis, resulting in a conceptual process model of health-related support in same-sex relationships. These categories, provided a snapshot of how processes interact with each other; they were context, relationship dynamics, health support processes, couple adaptation, and balancing physical/relational health. Couples described the balancing of relational and physical health as an ongoing, important theme in the success of health support. Implications for both health prevention and intervention are discussed.

Comprehensive Metaproteomic Analyses of Urine in the Presence and Absence of Neutrophil-Associated Inflammation in the Urinary Tract.

Inflammation in the urinary tract results in a urinary proteome characterized by a high dynamic range of protein concentrations and high variability in protein content. This proteome encompasses plasma proteins not resorbed by renal tubular uptake, renal secretion products, proteins of immune cells and erythrocytes derived from trans-urothelial migration and vascular leakage, respectively, and exfoliating urothelial and squamous epithelial cells. We examined how such proteins partition into soluble urine (SU) and urinary pellet (UP) fractions by analyzing 33 urine specimens 12 of which were associated with a urinary tract infection (UTI). Using mass spectrometry-based metaproteomic approaches, we identified 5,327 non-redundant human proteins, 2,638 and 4,379 of which were associated with SU and UP fractions, respectively, and 1,206 non-redundant protein orthology groups derived from pathogenic and commensal organisms of the urogenital tract. Differences between the SU and UP proteomes were influenced by local inflammation, supported by respective comparisons with 12 healthy control urine proteomes. Clustering analyses showed that SU and UP fractions had proteomic signatures discerning UTIs, vascular injury, and epithelial cell exfoliation from the control group to varying degrees. Cases of UTI revealed clusters of proteins produced by activated neutrophils. Network analysis supported the central role of neutrophil effector proteins in the defense against invading pathogens associated with subsequent coagulation and wound repair processes. Our study expands the existing knowledge of the urinary proteome under perturbed conditions, and should be useful as reference dataset in the search of biomarkers.