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Viral infection leads to heterogeneous cellular outcomes ranging from refractory to abortive and fully productive states. Single cell transcriptomics enables a high resolution view of these distinct post-infection states. Here, we have interrogated the host-pathogen dynamics following reactivation of Epstein-Barr virus (EBV). While benign in most people, EBV is responsible for infectious mononucleosis, up to 2% of human cancers, and is a trigger for the development of multiple sclerosis. Following latency establishment in B cells, EBV reactivates and is shed in saliva to enable infection of new hosts. Beyond its importance for transmission, the lytic cycle is also implicated in EBV-associated oncogenesis. Conversely, induction of lytic reactivation in latent EBV-positive tumors presents a novel therapeutic opportunity. Therefore, defining the dynamics and heterogeneity of EBV lytic reactivation is a high priority to better understand pathogenesis and therapeutic potential. In this study, we applied single-cell techniques to analyze diverse fate trajectories during lytic reactivation in three B cell models. Consistent with prior work, we find that cell cycle and MYC expression correlate with cells refractory to lytic reactivation. We further found that lytic induction yields a continuum from abortive to complete reactivation. Abortive lytic cells upregulate NFκB and IRF3 pathway target genes, while cells that proceed through the full lytic cycle exhibit unexpected expression of genes associated with cellular reprogramming. Distinct subpopulations of lytic cells further displayed variable profiles for transcripts known to escape virus-mediated host shutoff. These data reveal previously unknown and promiscuous outcomes of lytic reactivation with broad implications for viral replication and EBV-associated oncogenesis. Author summary: Viral infections profoundly alter host cell biological programming in ways that potentiate disease. Epstein-Barr virus (EBV) is a particularly prevalent human pathogen associated with diverse cancers and several autoimmune disorders. EBV predominantly establishes latent infection in B cells and can promote B cell malignancies through functions of well-characterized latent oncoproteins. Aspects of the viral lytic cycle also clearly contribute to EBV-associated diseases, although pathologic roles of lytic reactivation are incompletely understood. Here we use single-cell techniques to examine cellular responses to EBV lytic reactivation in multiple B cell models. Consistent with prior studies, reactivation from latency is incomplete (abortive) in some cells and successful in others. Abortive and full lytic trajectories exhibit distinct biological responses that each may promote pathogenesis and reinforce bimodal latent-lytic control. Intriguingly, a portion on cells that proceed through the lytic cycle exhibits unexpected and striking expression of genes associated with cellular reprogramming, pluripotency, and self-renewal. Collectively, this study provides a valuable resource to understand diverse host-virus dynamics and fates during viral reactivation and identifies multiple modes of EBV lytic pathogenesis to investigate in future research. [ABSTRACT FROM AUTHOR]

Tetraallylsilane can undergo either a mono or double rearrangement when treated with iodine (I2). The extent of rearrangement depends on the equivalents of I2 used, where 1 equivalent gives high yields of mono-rearranged products and excess (e.g., 3 equivalents) causes double rearrangement to occur. This transformation can be applied to the synthesis of potentially valuable silicon-stereogenic organosilanes. [ABSTRACT FROM AUTHOR]

Based on the seminal publications of Paul Broca and Carl Wernicke who established that aphasic syndromes (disorders of the verbal–linguistic aspects of communication) were predominantly the result of focal left-hemisphere lesions, “language” is traditionally viewed as a lateralized function of the left hemisphere. This, in turn, has diminished and delayed the acceptance that the right hemisphere also has a vital role in language, specifically in modulating affective prosody, which is essential for communication competency and psychosocial well-being. Focal lesions of the right hemisphere may result in disorders of affective prosody (aprosodic syndromes) that are functionally and anatomically analogous to the aphasic syndromes that occur following focal left-hemisphere lesions. This paper will review the deductive research published over the last four decades that has elucidated the neurology of affective prosody which, in turn, has led to a more complete and nuanced understanding of the neurology of language, depression, emotions and memory. In addition, the paper will also present the serendipitous clinical observations (inductive research) and fortuitous inter-disciplinary collaborations that were crucial in guiding and developing the deductive research processes that culminated in the concept that primary emotions and related display behaviors are a lateralized function of the right hemisphere and social emotions, and related display behaviors are a lateralized function of the left hemisphere.

In 2016, we undertook a nationally representative wind power perceptions survey of individuals living within 8 km of over 600 projects in the United States, generating 1705 telephone, web, and mail responses. We sought information on a variety of topics, including procedural fairness and its relationship to project attitude, the foci of the present analysis. We present a series of descriptive statistics and regression results, emphasizing those residents who were aware of their local project prior to construction. Sample weighting is employed to account for stratification and non-response. We find that a developer being open and transparent, a community being able to influence the outcome, and having a say in the planning process are all statistically significant predictors of a process perceived as being ‘fair,’ with an open and transparent developer having the largest effect. We also find developer transparency and ability to influence outcomes to have statistically significant relationships to a more positive attitude, with those findings holding when aesthetics, landscape, and wind turbine sound considerations are controlled for. The results indicate that jurisdictions might consider developing procedures, which ensure citizens are consulted and heard, and benchmarks or best practices for developer interaction with communities and citizens.

Otolaryngology surgical education continues to evolve where trainees increasingly use videos to learn technical skills. Trainees commonly use YouTube, but no study to date has evaluated the educational quality (EQ) of otologic surgical videos on YouTube. We aim to assess the EQ of cholesteatoma surgical videos. Cholesteatoma surgical videos were queried using YouTube search terms, assessed using LAParoscopic surgery Video Educational GuidelineS (LAP-VEGaS), a validated assessment tool for publication, and categorized into low (0-6), medium (7-12), and high (13-18) EQ groups. In total, 74 videos were identified (mean LAP-VEGaS score = 9.6 ± 4.0) and 44.6% had medium EQ. Videos commonly lacked graphic aids to highlight anatomy (71.6%) and postprocedural outcomes (68.9%). LAP-VEGaS scores were greater in videos originating from US surgeons compared to non-US surgeons (12.4 ± 3.4 vs 8.0 ± 3.5; P < .001). Our study highlights that otolaryngology trainees may experience difficulty finding high-EQ cholesteatoma surgery videos on YouTube. Areas for improved EQ content are discussed. Level of evidence : IV

Human B cells encompass functionally diverse lineages and phenotypic states that contribute to protective as well as pathogenic responses. Epstein-Barr virus (EBV) provides a unique lens for studying heterogeneous B cell responses, given its adaptation to manipulate intrinsic cell programming. EBV promotes the activation, proliferation, and eventual outgrowth of host B cells as immortalized lymphoblastoid cell lines (LCLs) in vitro, which provide a foundational model of viral latency and lymphomagenesis. Although cellular responses and outcomes of infection can vary significantly within populations, investigations that capture genome-wide perspectives of this variation at single-cell resolution are in nascent stages. We have recently used single-cell approaches to identify EBV-mediated B cell heterogeneity in de novo infection and within LCLs, underscoring the dynamic and complex qualities of latent infection rather than a singular, static infection state. Here, we expand upon these findings with functional characterizations of EBV-induced dynamic phenotypes that mimic B cell immune responses. We found that distinct subpopulations isolated from LCLs could completely reconstitute the full phenotypic spectrum of their parental lines. In conjunction with conserved patterns of cell state diversity identified within scRNA-seq data, these data support a model in which EBV continuously drives recurrent B cell entry, progression through, and egress from the Germinal Center (GC) reaction. This “perpetual GC” also generates tangent cell fate trajectories including terminal plasmablast differentiation, which constitutes a replicative cul-de-sac for EBV from which lytic reactivation provides escape. Furthermore, we found that both established EBV latency and de novo infection support the development of cells with features of atypical memory B cells, which have been broadly associated with autoimmune disorders. Treatment of LCLs with TLR7 agonist or IL-21 was sufficient to generate an increased frequency of IgD-/CD27-/CD23-/CD38+/CD138+ plasmablasts. Separately, de novo EBV infection led to the development of CXCR3+/CD11c+/FCRL4+ B cells within days, providing evidence for possible T cell-independent origins of a recently described EBV-associated neuroinvasive CXCR3+ B cell subset in patients with multiple sclerosis. Collectively, this work reveals unexpected virus-driven complexity across infected cell populations and highlights potential roles of EBV in mediating or priming foundational aspects of virus-associated immune cell dysfunction in disease.

Abstract Objectives Stapedotomy is performed to address conductive hearing deficits. While hearing thresholds reliably improve at low frequencies (LF), conductive outcomes at high frequencies (HF) are less reliable and have not been well described. Herein, we evaluate post‐operative HF air‐bone gap (ABG) changes and measure HF air conduction (AC) thresholds changes as a function of frequency. Methods Retrospective review of patients who underwent primary stapedotomy with incus wire piston prosthesis between January 2016 and May 2020. Pre‐ and postoperative audiograms were evaluated. LF ABG was calculated as the mean ABG of thresholds at 250, 500, and 1000 Hz. HF ABG was calculated at 4 kHz. Results Forty‐six cases met criteria. Mean age at surgery was 54.0 ± 11.7 years. The LF mean preoperative ABG was 36.9 ± 11.0 dB and postoperatively this significantly reduced to 9.35 ± 6.76 dB, (P

OBJECTIVES:. Timely regulation of oxygen (Fio2) is essential to prevent hyperoxemia or episodic hypoxemia. Exposure to excessive Fio2 is often noted early after onset of mechanical ventilation. In this pilot study, we examined the feasibility, safety, and efficacy of a clinical trial to prioritize Fio2 titration with electronic alerts to respiratory therapists. STUDY DESIGN:. Open-labeled, randomized control pilot trial. SETTING:. Medical ICU. SUBJECTS:. Adults requiring mechanical ventilation. INTERVENTIONS:. Protocolized oxygen titration was initiated one hour after initiation of mechanical ventilation. When Spo2 exceeded 92% while on Fio2 ≥ 0.5, an electronic alert to respiratory therapists was triggered at 30-minute intervals. In the control arm, respiratory therapists titrated Fio2 by standard physician’s orders. MEASUREMENTS AND MAIN RESULTS:. The primary end point was to determine if early Fio2 titration based on automated alerts was feasible in terms of reducing hyperoxemia. Secondary analyses included the number and frequency of alerts, mechanical ventilation duration, and ICU length of stay. Among 135 randomized patients, 72 were assigned to the intervention arm and 63 to the control arm. A total 877 alerts were sent. Exposure to hyperoxemia was significantly reduced in the intervention group by a median of 7.5 hours (13.7 [interquartile range (IQR), 2.9–31.1] vs 21.2 [IQR, 10.9–64.4]; p < 0.0004). Maximal Fio2 titration during the first quartile resulted in significant reduction in mechanical ventilation duration and ICU stay. Minor hypoxemic events (Spo2 < 88%) represented 12% of alerts, 9% were transient and responded to a single Fio2 increase, whereas 3% of alerts were associated with recurrent transient hypoxemia. CONCLUSIONS:. Our pilot study indicates that early Fio2 titration driven by automated alerts is feasible in the ICU, as reflected by a statistically significant reduction of hyperoxemia exposure, limited consequential hypoxemia, and reduced ICU resource utilization. The encouraging results of this pilot study need to be validated in a larger ICU cohort.

Rationale: Sarcoidosis is a granulomatous disorder of unclear cause notable for abnormal elevation of blood and tissue ACE1 (angiotensin converting enzyme 1) levels and activity. ACE1 regulates the renin-angiotensin-aldosterone system (RAAS), the terminal product of which is aldosterone, which selectively engages mineralocorticoid receptors to promote inflammation. Objectives: We sought to determine whether the RAAS promotes sarcoidosis granuloma formation and related inflammatory responses. Methods: Using an established ex vivo model, we first determined whether aldosterone was produced by sarcoidosis granulomas and verified the presence of CYP11B2, the enzyme required for its production. We then evaluated the effects of selective inhibitors of ACE1 (captopril), angiotensin type 1 receptor (losartan), and mineralocorticoid receptors (spironolactone, eplerenone) on granuloma formation, reflected by computer image analysis–generated granuloma area, and selected cytokines incriminated in sarcoidosis pathogenesis. Measurements and Main Results: Aldosterone was spontaneously produced by sarcoidosis peripheral blood mononuclear cells, and both intra- and extracellular levels steadily increased during granuloma formation. In parallel, peripheral blood mononuclear cells were shown to express more CYP11B2 during granuloma formation. Significant inhibition of sarcoidosis granulomas and related cytokines (TNFα, IL-1β, IFNγ, IL-10) was observed in response to pretreatments with captopril, losartan, spironolactone, or eplerenone, comparable to that of prednisone. Conclusions: The RAAS is intact in sarcoidosis granulomas and contributes significantly to early granuloma formation and to related inflammatory mediator responses, with important implications for clinical management. [ABSTRACT FROM AUTHOR]

Abstract Rationale Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures. Objective To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis). Methods Transcriptomic profiles of immune-related gene from micro-dissected sarcoidosis granulomas within lung and mediastinal lymph node tissues and compared to infectious granulomas from paraffin-embedded blocks. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways. Results Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers (STAB1, HBEGF, and NOTCH4), excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, NPR1 and CXCL2. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level. Conclusion These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.

Abstract Objectives Conventional reporting of postoperative hearing outcomes utilizes a pure‐tone averaged air‐bone gap (ABG) that is biased toward low frequencies. Consequently, a high‐frequency ABG after otologic surgery may go unnoticed. In this study, we evaluate changes in low‐ and high‐frequency ABG following ossiculoplasty. Study design Retrospective review. Subjects and setting Consecutive series of patients who underwent ossiculoplasty at a single tertiary care center. Patients with pre‐ and postoperative audiograms were included. Methods Low‐frequency ABG was calculated as the mean ABG at 250, 500, and 1000 Hz. High‐frequency ABG was calculated at 4 kHz. Pre‐ and postoperative ABGs were compared. Results Thirty‐seven consecutive patients were included. Mean age at surgery was 38 years (range, 7‐77 years). Reconstruction materials included: cartilage (N = 4), hydroxyapatite cement (N = 5), and partial or total ossicular replacement prostheses (N = 20 and N = 8, respectively). Postoperatively, the mean low‐frequency ABG improved by 11.9 ± 15.1 dB (P

Abstract Objective In cases of a severe to profound sensorineural hearing loss following head injury, the cochlear implant (CI) is the primary option for auditory rehabilitation. Few studies, however, have investigated long‐term CI outcomes in patients following head trauma, including those without temporal bone fracture (TBF). Herein, the aim of this study is to examine CI outcomes following cases of head injury with and without TBF. Methods Audiometric outcomes of patients who received a CI due to a head injury resulting in severe to profound hearing loss at two tertiary care hospitals were analyzed. Patients were divided into those who received a CI in a fractured temporal bone (group A, n = 11 patients corresponding to 15 ears) and those who received a CI in a non‐fractured temporal bone (group B, n = 8 patients corresponding to nine ears). Primary outcomes included duration of deafness prior to CI and postoperative consonant‐nucleus‐constant whole word (CNC) scores. Results Nineteen patients (84% male), corresponding to 24 CIs, were identified. Fifteen CI were performed on ears with TBF (group A), and nine CI were performed on ears without TBF (group B). No patients had an enlarged vestibular aqueduct (EVA). The mean duration of deafness was 5.7 and 11.3 years in group A and group B, respectively. The mean duration of CI follow‐up (CI experience) was 6.5 years in group A and 2.1 years in group B. The overall mean postoperative CNC score for all subjects was 68.6% (±21.2%, n = 19 with CNC testing). There was no difference in CNC score between group A and group B (69.8% and 66% respectively, P = .639). Conclusion The study is among the largest series examining long‐term outcomes of CI after head injury. CI is an effective method for auditory rehabilitation in patients after head injury. Level of evidence IV.

Abstract Background The initial presentation of sepsis in the emergency department (ED) is difficult to distinguish from other acute illnesses based upon similar clinical presentations. A new blood parameter, a measurement of increased monocyte volume distribution width (MDW), may be used in combination with other clinical parameters to improve early sepsis detection. We sought to determine if MDW, when combined with other available clinical parameters at the time of ED presentation, improves the early detection of sepsis. Methods A retrospective analysis of prospectively collected clinical data available during the initial ED encounter of 2158 adult patients who were enrolled from emergency departments of three major academic centers, of which 385 fulfilled Sepsis-2 criteria, and 243 fulfilled Sepsis-3 criteria within 12 h of admission. Sepsis probabilities were determined based on MDW values, alone or in combination with components of systemic inflammatory response syndrome (SIRS) or quick sepsis-related organ failure assessment (qSOFA) score obtained during the initial patient presentation (i.e., within 2 h of ED admission). Results Abnormal MDW (> 20.0) consistently increased sepsis probability, and normal MDW consistently reduced sepsis probability when used in combination with SIRS criteria (tachycardia, tachypnea, abnormal white blood count, or body temperature) or qSOFA criteria (tachypnea, altered mental status, but not hypotension). Overall, and regardless of other SIRS or qSOFA variables, MDW > 20.0 (vs. MDW ≤ 20.0) at the time of the initial ED encounter was associated with an approximately 6-fold increase in the odds of Sepsis-2, and an approximately 4-fold increase in the odds of Sepsis-3. Conclusions MDW improves the early detection of sepsis during the initial ED encounter and is complementary to SIRS and qSOFA parameters that are currently used for this purpose. This study supports the incorporation of MDW with other readily available clinical parameters during the initial ED encounter for the early detection of sepsis. Trial registration ClinicalTrials.gov, NCT03145428 . First posted May 9, 2017. The first subjects were enrolled June 19, 2017, and the study completion date was January 26, 2018.

Abstract Objective While cochlear ossification is a common sequalae of meningitic labyrinthitis, less is known about the effects of meningitis on peripheral vestibular end organs. Herein, we investigate histopathologic changes in the peripheral vestibular system and cochlea in patients with a history of meningitic labyrinthitis. Methods Temporal bone (TB) specimens from patients with a history of meningitis were evaluated and compared to age‐matched controls. Specimens were evaluated by light microscopy and assessed for qualitative changes, including the presence of vestibular and/or cochlear endolymphatic hydrops, presence and location of inflammatory cells, new bone formation, and labyrinthitis ossificans; and quantitative changes, including Scarpa's ganglion neuron (ScGN) and spiral ganglion neuron (SGN) counts. Results Fifteen TB from 10 individuals met inclusion and exclusion criteria. Presence of inflammatory cells and fibrous tissue was found in 5 TB. Of these, evidence of labyrinthitis ossificans was found in 2 TB. In the peripheral vestibular system, mild to severe degeneration of the vestibular membranous labyrinth was identified in 60% of cases (n = 9 TBs). There was a 21.2% decrease (range, 3%‐64%) in the mean total count of ScGN in patients with meningitis, compared to age‐matched controls. In the cochlea, there was a 45% decrease (range, 25.3%‐80.9%) in the mean total count of SGN compared to age‐matched controls (n = 14 TBs). Conclusions Otopathologic analysis of TB from patients with a history of meningitic labyrinthitis demonstrated distinct peripheral vestibular changes. Future research may help to delineate potential mechanisms for the observed otopathologic changes following meningitis. Level of Evidence N/A

Abstract Objective The term “labyrinthine concussion” has evolved to mean audiovestibular dysfunction in the absence of a temporal bone fracture (TBF). Despite a multitude of case descriptions of labyrinthine concussion, the precise pathophysiology remains poorly understood. Herein, we explore the historical otopathologic underpinnings of the diagnosis of labyrinthine concussion with a focus on the auditory pathway during the late 19th to the mid‐20th centuries and conclude with a discussion of its contemporary relevance. Methods and Data Sources A review of primary and secondary medical sources written in English, German, and French on otopathology labyrinthine concussion studies from the late‐19th to the mid‐20th centuries. Results Around the turn of the 20th century, otopathologists identified histologic changes in the temporal bones of individuals that sustained head injury without TBFs. Based on these otopathologic findings in humans, early experiments investigating the pathophysiology of labyrinthine concussion were performed in animals through either the delivery of blows to the head or direct introduction of a pressure wave into the labyrinthine fluid. Collectively, otopathologists hypothesized that predominant mechanisms for labyrinthine concussion included inner ear hemorrhage, cochleovestibular nerve traction injury, direct damage from a labyrinthine fluid pressure wave, or vasomotor dysfunction. Conclusion Historical study shows a variety of inner ear pathologies potentially responsible for auditory dysfunction following head injury. Understanding the history and otopathology of labyrinthine concussion may help clinicians focus on new pathways toward novel research and improved patient care.

OBJECTIVES:. Increased monocyte distribution width (MDW) has recently been shown to be a reliable indicator of early sepsis detection. This study therefore sought to determine if inflammasome activation can be linked to monocyte size changes in sepsis. DESIGN:. An in vitro sepsis model using bacterial endotoxin (lipopolysaccharide [LPS]) to study the effect of inflammasome activation on monocyte cell size distribution by microscopy and MDW measurements using a standard clinical hematology analyzer. SETTING:. University research laboratory. SUBJECTS:. Healthy adult volunteers and cultured human monocyte cells in wild-type state and after clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 knockout of key inflammasome components (apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, gasdermin-D). INTERVENTIONS:. In vitro treatment of specimens with bacterial LPS. MEASUREMENTS AND MAIN RESULTS:. Wild-type THP1 cells demonstrated a significant increase in cell area (207 μm2 [159–400 μm2] vs 160 μm2 [134–198 μm2]; p < 0.001) and distribution width (198 vs 55 μm2; p < 0.0001) by microscopy following treatment with LPS. Increased MDW correlated with inflammasome activation as demonstrated by release of interleukin (IL)-1β and with the presence of large distended pyroptotic cells by microscopy. All of these effects were blocked in the inflammasome knockout cells. Whole blood samples treated similarly also demonstrated IL-1β release and increased MDW (median 24.7 U [22.2–27.2 U] vs 16.3 U [15.1–17.6 U]; p = 0.008) as measured using the Beckman-Coulter Unicel DxH900 analyzer. When peripheral blood mononuclear cells were isolated prior to treatment with LPS, microscopy confirmed the presence of large pyroptotic cells correlating to IL-1β release in the human subject samples as well. CONCLUSIONS:. The increased MDW seen in patients with sepsis can be reproduced in an in vitro sepsis model and blocked using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 technology to inactivate the inflammasome. These findings suggest that pyroptotic cellular swelling underlies changes in MDW in septic patients and connect MDW to early events in the inflammatory cascade of sepsis.

When people talk about their values they refer to what is meaningful to them. Although meaning is associated with life satisfaction, previous studies report inconsistent results regarding the association of values and well-being. A cross-sectional study (N = 276) addresses the research question, do values influence experiences of meaning and subjective evaluations of life satisfaction? To assess whether providing a definition of “meaningful” is necessary when employing meaning measures, we assigned participants to condition where some provided their definition and others read a definition of “meaningful”. All participants described a recent meaningful experience; they characterized it with sources of meaning; they read descriptions of 10 values and assessed the degree those were relevant to their experience; and they completed meaning and life satisfaction measures. Findings, which were unaffected by reading a definition of “meaningful”, indicated that the most common source of meaning (Family) was associated positively with the value of Tradition and negatively with the value of Universalism. Latent Profile Analysis identified three profiles denoting participants’ level of value orientation, which explained interindividual differences in average levels of meaning and life satisfaction variables. Participants who associated their meaningful experience with the 10 universal values at a high level scored higher in the meaning and life satisfaction measures than those who associated their experience to the 10 universal values at a low level. The present work advances knowledge regarding the relationship between meaning, values and life satisfaction and validates previous studies reporting on meaning as a marker of well-being.