Activation of the antiviral factor RNase L triggers translation of non-coding mRNA sequences.

Ribonuclease L (RNase L) is activated as part of the innate immune response and plays an important role in the clearance of viral infections. When activated, it endonucleolytically cleaves both viral and host RNAs, leading to a global reduction in protein synthesis. However, it remains unknown how widespread RNA decay, and consequent changes in the translatome, promote the elimination of viruses. To study how this altered transcriptome is translated, we assayed the global distribution of ribosomes in RNase L activated human cells with ribosome profiling. We found that RNase L activation leads to a substantial increase in the fraction of translating ribosomes in ORFs internal to coding sequences (iORFs) and ORFs within 5' and 3' UTRs (uORFs and dORFs). Translation of these alternative ORFs was dependent on RNase L's cleavage activity, suggesting that mRNA decay fragments are translated to produce short peptides that may be important for antiviral activity.

A Digital Music-Based Mindfulness Intervention ("healing attempt") for Race-Based Anxiety in Black Americans.

This study replicates and extends findings that "healing attempt"-a brief digital music-based mindfulness intervention-represents a feasible and potentially effective intervention for race-based anxiety in the Black community.

Superior Capsular Reconstruction: A Salvage Option for Massive Irreparable Rotator Cuff Tears with Pseudoparalysis or Subscapularis Insufficiency.

PURPOSE: We sought to examine superior capsular reconstruction (SCR) outcomes after minimum 2-year follow-up and determine risk factors that were predictive of outcomes. METHODS: Forty consecutive patients (mean age 57.3 years, 87.5% male) who underwent SCR for massive irreparable rotator cuff tears (RCT) met the inclusion criteria. Minimum 2-year follow-up was obtained for 32 patients (80% follow-up). Patient demographics and preoperative clinical findings were collected. Postoperative data, including complications, patient satisfaction, strength and range-of-motion (ROM), and patient-reported outcomes were collected. RESULTS: The Hamada score was ≤2 in 88% with average acromiohumeral interval distance of 6.8 mm. Preoperatively, 6 patients had external rotation lag (19%) and 6 had pseudoparalysis (19%). Intraoperative assessment of the subscapularis demonstrated true insufficiency in 38%. There was significant improvement in forward elevation (FE) (31° increase; P = .007) and strength in all planes (all P < .05). Patient-reported outcomes significantly improved (American Shoulder and Elbow Surgeon [ASES] 34-point increase; visual analog scale [VAS] 2.9-point decrease; single alpha-numeric evaluation [SANE] 48-point increase; all P < .05). Twenty-six patients (81%) were completely or somewhat satisfied with surgery. At time of final follow-up, 3/32 patients (9%) failed SCR and converted to reverse total shoulder arthroplasty. There were 4 (13%) reported complications (2 patients had postoperative falls; 1 patient had persistent severe pain; 1 had persistent stiffness). One patient was deceased. Patients with pseudoparalysis (n = 6) had significant improvement in post-operative FE (28 vs 154°; P < .0001) and SANE score (P = .016) with 66% patient satisfaction. However, outcome scores overall remained lower than SCR without pseudoparalysis. Regarding subscapularis insufficiency (n = 12), significant improvement was seen in postoperative FE (108 vs 158°; P = .019) and patient-reported outcome scores (P < .005). In patients converted from SCR to reverse total shoulder arthroplasty (n = 3), there were no distinguishing characteristics present. CONCLUSION: Superior capsular reconstruction is an effective salvage operation for massive irreparable RCT. Patients with pseudoparalysis or subscapularis insufficiency demonstrate significant postoperative improvement in FE and patient-reported outcomes. LEVEL OF EVIDENCE: IV, retrospective cohort.

Pectoralis muscle injuries in Major and Minor League Baseball.

BACKGROUND AND HYPOTHESIS: Although shoulder and elbow injuries in professional baseball players have been thoroughly studied, little is known about the frequency and impact of pectoralis muscle injuries in this population. The purpose of this study was to use the official league injury surveillance system to describe pectoralis muscle injuries in professional baseball players in Major League Baseball (MLB) and Minor League Baseball (MiLB). Specifically, (1) player demographic characteristics, (2) return to play (RTP), (3) injury mechanism, (4) throwing- and batting-side dominance, and (5) injury rate per athlete exposure (AE) were characterized to guide future injury prevention strategies. METHODS: The MLB Health and Injury Tracking System database was used to compile all pectoralis muscle injuries in MLB and MiLB athletes in the 2011-2017 seasons. Injury-related data including diagnosis (tear or rupture vs. strain), player demographic characteristics, injury timing, need for surgical intervention, RTP, and mechanism of injury were recorded. Subanalyses of throwing- and batting-side dominance, as well as MLB vs. MiLB injury frequency, were performed. RESULTS: A total of 138 pectoralis muscle injuries (32 MLB and 106 MiLB injuries) were reported in the study period (5 tears or ruptures and 133 strains), with 5 of these being recurrent injuries. Operative intervention was performed in 4 athletes (2.9%). Of the 138 injuries, 116 (84.1%) resulted in missed days of play, with a mean time to RTP of 19.5 days. Starting pitchers sustained the greatest proportion of pectoralis injuries (48.1%), with pitching being the most common activity at the time of injury (45.9%). A majority of injuries (86.5%) were sustained during non-contact play. Overall, 87.5% of injuries occurred on the player's dominant throwing side and 81.3% occurred on the player's dominant batting side. There was no significant difference in the rate of pectoralis injuries in the MLB regular season (0.584 per 10,000 AEs) vs. the MiLB regular season (0.425 per 10,000 AEs) (P = .1018). CONCLUSION: Pectoralis muscle injuries are most frequently non-contact injuries, most commonly sustained by pitchers. An understanding of these injuries can guide athletic trainers and management in expectation management and decision making, in addition to directing future efforts at injury prevention.

Obesity and sex influence fatty infiltration of the rotator cuff: the Rotator Cuff Outcomes Workgroup (ROW) and Multicenter Orthopaedic Outcomes Network (MOON) cohorts.

BACKGROUND: Fatty infiltration (FI) is one of the most important prognostic factors for outcomes after rotator cuff surgery. Established risk factors include advancing age, larger tear size, and increased tear chronicity. A growing body of evidence suggests that sex and obesity are associated with FI; however, data are limited. METHODS: We recruited 2 well-characterized multicenter cohorts of patients with rotator cuff tears (Multicenter Orthopaedic Outcomes Network [MOON] cohort [n = 80] and Rotator Cuff Outcomes Workgroup [ROW] cohort [n = 158]). We used multivariable logistic regression to evaluate the relationship between body mass index (BMI) and the presence of FI while adjusting for the participant's age at magnetic resonance imaging, sex, and duration of shoulder symptoms, as well as the cross-sectional area of the tear. We analyzed the 2 cohorts separately and performed a meta-analysis to combine estimates. RESULTS: A total of 27 patients (33.8%) in the Multicenter Orthopaedic Outcomes Network (MOON) cohort and 57 patients (36.1%) in the Rotator Cuff Outcomes Workgroup (ROW) cohort had FI. When BMI < 25 kg/m2 was used as the reference category, being overweight was associated with a 2.37-fold (95% confidence interval [CI], 0.77-7.29) increased odds of FI and being obese was associated with a 3.28-fold (95% CI, 1.16-9.25) increased odds of FI. Women were 4.9 times (95% CI, 2.06-11.69) as likely to have FI as men. CONCLUSIONS: Among patients with rotator cuff tears, obese patients had a substantially higher likelihood of FI. Further research is needed to assess whether modifying BMI can alter FI in patients with rotator cuff tears. This may have significant clinical implications for presurgical surgical management of rotator cuff tears. Sex was also significantly associated with FI, with women having higher odds of FI than men. Higher odds of FI in female patients may also explain previously reported early suboptimal outcomes of rotator cuff surgery and higher pain levels in female patients as compared with male patients.

Male Sex, Western Ontario Shoulder Instability Index Score, and Sport as Predictors of Large Labral Tears of the Shoulder: A Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability Cohort Study.

PURPOSE: To identify factors predictive of a large labral tear at the time of shoulder instability surgery. METHODS: As part of the Multicenter Orthopaedic Outcomes Network (MOON) Shoulder Instability cohort, patients undergoing open or arthroscopic shoulder instability surgery for a labral tear were evaluated. Patients with >270° tears were defined as having large labral tears. To build a predictive logistic regression model for large tears, the Feasible Solutions Algorithm was used to add significant interaction effects. RESULTS: After applying exclusion criteria, 1235 patients were available for analysis. There were 222 females (18.0%) and 1013 males (82.0%) in the cohort, with an average age of 24.7 years (range 12 to 66). The prevalence of large tears was 4.6% (n = 57), with the average tear size being 141.9°. Males accounted for significantly more of the large tears seen in the cohort (94.7%, P = .01). Racquet sports (P = .01), swimming (P = .02), softball (P = .05), skiing (P = .04), and golf (P = .04) were all associated with large labral tears, as was a higher Western Ontario Shoulder Instability Index (WOSI; P = .01). Age, race, history of dislocation, and injury during sport were not associated with having a larger tear. Using our predictive logistic regression model for large tears, patients with a larger body mass index (BMI) who played contact sports were also more likely to have large tears (P = .007). CONCLUSIONS: Multiple factors were identified as being associated with large labral tears at the time of surgery, including male sex, preoperative WOSI score, and participation in certain sports including racquet sports, softball, skiing, swimming, and golf. LEVEL OF EVIDENCE: I, prognostic study.

Epidemiology of acromioclavicular joint injuries in professional baseball: analysis from the Major League Baseball Health and Injury Tracking System.

BACKGROUND: Shoulder injuries account for a large portion of all recorded injuries in professional baseball. Much is known about other shoulder pathologies in the overhead athlete, but the incidence and impact of acromioclavicular (AC) joint injuries in this population are unknown. We examined the epidemiology of AC joint injuries in Major League Baseball (MLB) and Minor League Baseball (MiLB) players and determined the impact on time missed. METHODS: The MLB Health and Injury Tracking System was used to compile records of all MLB and MiLB players from 2011 to 2017 with documented AC joint injuries. These injuries were classified as acute (sprain or separation) or chronic (AC joint arthritis or distal clavicular osteolysis), and associated data extracted included laterality, date of injury, player position, activity, mechanism of injury, length of return to play, and need for surgical intervention. RESULTS: A total of 312 AC joint injuries (183 in MiLB players and 129 in MLB players; range, 39-60 per year) were recorded: 201 acute (64.4%) and 111 chronic (35.6%). A total of 81% of acute and 59% of chronic injuries resulted in time missed, with a mean length of return to play of 21 days for both. Of the injuries in outfielders, 79.6% were acute (P < .0001), as were 66.3% of injuries in infielders (P = .004). Pitchers and catchers had more equal proportions of acute and chronic AC injuries (P > .05 for all). Acute AC injuries occurred most often while fielding (n = 100, 84.7%), running (n = 25, 80.6%), and hitting (n = 19, 61.3%), whereas chronic injuries tended to be more common while pitching (n = 26, 68.4%). Of contact injuries, 82.5% were acute (P < .0001), whereas 59.0% of noncontact injuries were chronic (P = .047). MLB players showed consistently higher regular-season rates of both acute and chronic AC injuries than MiLB players (P < .0001 for each). CONCLUSION: Acute AC joint injuries are contact injuries occurring most commonly among infielders and outfielders while fielding that result in 3 weeks missed before return to play, whereas chronic AC joint injuries occur more commonly in pitchers and catchers from noncontact repetitive overhead activity. Knowledge of these data can better guide expectation management in this elite population to better elucidate the prevalence of 2 common injury patterns in the AC joint.

Evolving Expectations of the Orthopedic Team Physician: Managing the Sidelines and Landmines.

ABSTRACT: The role of orthopedic team physicians has evolved greatly over the past decade having been influenced by advances in sports science and performance, new surgical and biologic technologies, social media, medicolegal liability, marketing, and sexual misconduct cases by some team physicians. The great variety of events and sports that are covered from high school and collegiate to the Olympic and professional levels requires a myriad of skills outside of the traditional medical training curriculum. In the current climate of increasing media scrutiny from a 24-h news cycle it is imperative for orthopedic team physicians, whether operative or nonoperative, to continually adapt to the needs and expectations of athletes who also are patients. This is especially true in the wake of the COVID-19 pandemic. Orthopedic team physicians' responsibilities continue to evolve ensuring their relevance and necessity on the sidelines and in the training room as well as in the operative suite.

Monocytes Are the Predominant Cell Type Associated with Listeria monocytogenes in the Gut, but They Do Not Serve as an Intracellular Growth Niche.

After foodborne transmission of the facultative intracellular bacterial pathogen Listeria monocytogenes, most of the bacterial burden in the gut is extracellular. However, we previously demonstrated that intracellular replication in an as yet unidentified cell type was essential for dissemination and systemic spread of L. monocytogenes In this article, we show that the vast majority of cell-associated L. monocytogenes in the gut were adhered to Ly6Chi monocytes, a cell type that inefficiently internalized L. monocytogenes With bone marrow-derived in vitro cultures, high multiplicity of infection or the use of opsonized bacteria enhanced uptake of L. monocytogenes in CD64- monocytes, but very few bacteria reached the cell cytosol. Surprisingly, monocytes that had upregulated CD64 expression in transition toward becoming macrophages fully supported intracellular growth of L. monocytogenes In contrast, inflammatory monocytes that had increased CD64 expression in the bone marrow of BALB/c/By/J mice prior to L. monocytogenes exposure in the gut did not support L. monocytogenes growth. Thus, contrary to the perception that L. monocytogenes can infect virtually all cell types, neither naive nor inflammatory Ly6Chi monocytes served as a productive intracellular growth niche for L. monocytogenes. These results have broad implications for innate immune recognition of L. monocytogenes in the gut and highlight the need for additional studies on the interaction of extracellular, adherent L. monocytogenes with the unique subsets of myeloid-derived inflammatory cells that infiltrate sites of infection.

Listeria monocytogenes Replicate in Bone Marrow-Derived CD11c+ Cells but Not in Dendritic Cells Isolated from the Murine Gastrointestinal Tract.

Recent fate-mapping studies and gene-expression profiles suggest that commonly used protocols to generate bone marrow-derived cultured dendritic cells yield a heterogeneous mixture, including some CD11chi cells that may not have a bona fide counterpart in vivo. In this study, we provide further evidence of the discordance between ex vivo-isolated and in vitro-cultured CD11c+ cells by analyzing an additional phenotype, the ability to support cytosolic growth of the facultative intracellular bacterial pathogen Listeria monocytogenes Two days after foodborne infection of mice with GFP-expressing L. monocytogenes, a small percentage of CD103neg and CD103+ conventional dendritic cells (cDC) in the intestinal lamina propria and mesenteric lymph nodes were GFP+ However, in vitro infection of the same subsets of cells harvested from naive mice resulted in inefficient invasion by the bacteria (<0.1% of the inoculum). The few intracellular bacteria detected survived for only a few hours. In contrast, cultured CD103negCD11c+ cells induced by GM-CSF readily supported exponential growth of L. monocytogenes Flt3 ligand-induced cultures yielded CD103+CD11c+ cells that more closely resembled cDC, with only a modest level of L. monocytogenes replication. For both culture protocols, the longer the cells were maintained in vitro, the more readily they supported intracellular growth. The results of this study suggest that cDC are not a niche for intracellular growth of L. monocytogenes during intestinal infection of mice.

Factors Influencing Surgeon's Choice of Procedure for Anterior Shoulder Instability: A Multicenter Prospective Cohort Study.

PURPOSE: To investigate preoperative factors associated with selection of surgical treatment for anterior shoulder instability. METHODS: Patient demographics, initial physical examinations, and patient-oriented outcome questionnaires were collected prospectively from 26 shoulder surgeons at 10 sites. Symptom duration, number of dislocations, sport, history of prior stabilization procedure, Hill-Sachs/glenoid bone loss, pain level, and failure of conservative treatment were recorded. Statistical analysis was performed with Fisher's exact test and logistic regression analysis. RESULTS: A total of 564 patients who underwent surgical treatment for anterior shoulder instability from November 2012 to June 2017 were enrolled. Of these, 426 shoulders underwent arthroscopic stabilization alone, 38 underwent arthroscopic stabilization with remplissage, 28 underwent open Bankart repair, and 72 underwent a Latarjet procedure. Predictors for undergoing Latarjet (P < .003) were symptom duration (75% had symptoms for >1 year), number of dislocations (47% had >5 dislocations), revision surgery (69%), Hill-Sachs lesion size (45% had a lesion between 11% and 20% of the humeral head), and glenoid bone loss (75% of Latarjet patients had 11% to 30% loss). Predictors for undergoing open Bankart repair (P < .001) were number of dislocations (32% had >5 dislocations), revision surgeries (54%), and glenoid bone loss (11% of open Bankart patients had 11% to 20% loss). History of prior shoulder surgery was the only significant predictor of open versus arthroscopic Bankart procedure. Prediction models showed athletes involved in high-risk sports were 2.61 times more likely to have a Latarjet (P < .01). CONCLUSIONS: Indications for the Latarjet were: humeral and glenoid bone loss, duration of symptoms, number of dislocations, and revision stabilizations. Athletes involved in high-risk sports were more likely to undergo the Latarjet procedure, even if other predictive factors were not present. The open Bankart procedure was the least common procedure performed, with a history of prior shoulder surgery being the only predictor for use when treating recurrent instability. LEVEL OF EVIDENCE: Level II, prospective prognostic cohort investigation.

A prospective evaluation of predictors of pain after arthroscopic rotator cuff repair: psychosocial factors have a stronger association than structural factors.

HYPOTHESIS: We evaluated the correlation of preoperative factors with pain after arthroscopic rotator cuff repair (ARCR). We hypothesized that nonstructural factors, including metrics of psychological well-being and preoperative narcotic use, would correlate with higher pain levels postoperatively and that structural factors, such as tear size, would not be predictive. METHODS: Ninety-three patients were prospectively enrolled and evenly distributed by tear size. Patient sex, age, occupation, smoking status, tear mechanism, tear characteristics on magnetic resonance imaging, visual analog scale (VAS) pain scores, narcotic usage, range of motion (ROM) by goniometry, and functional and psychological assessments through the American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form, Simple Shoulder Test, Western Ontario Rotator Cuff Index (WORC), and RAND 36-item Short Form Survey questionnaires were obtained preoperatively. VAS scores and ROM were collected postoperatively at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year. The ASES, SST, WORC, and RAND 36-item Short Form Survey questionnaires were repeated 1 year postoperatively. RESULTS: The patients (54% men) were a mean age of 56.4 years. There were 68% traumatic tears, 11% smokers, and 13% used narcotics preoperatively. ROM, VAS, ASES, and WORC scores improved significantly from the preoperative to 1-year postoperative assessment. Correlating with increased pain scores at 1 year were preoperative narcotic use, higher preoperative VAS, and lower scores on the WORC index and emotion sections. CONCLUSION: Our data show that the factors most predictive of persistent pain after ARCR are psychosocial characteristics, including poor performance on validated measures of emotional well-being. Demographic and tear-specific structural factors did not correlate with postoperative pain scores.

2013 Neer Award: predictors of failure of nonoperative treatment of chronic, symptomatic, full-thickness rotator cuff tears.

BACKGROUND: The purpose of this study is to help define the indications for rotator cuff repair by identifying predictors of failure of nonoperative treatment. METHODS: A prospective, multicenter, cohort study design was used. All patients with full-thickness rotator cuff tears on magnetic resonance imaging were offered participation. Baseline data from this cohort were used to examine risk factors for failing a standard rehabilitation protocol. Patients who underwent surgery were defined as failing nonoperative treatment. A Cox proportional hazards model was fit to determinethe baseline factors that predicted failure. The dependent variable was time to surgery. The independent variables were tear severity and baseline patient factors: age, activity level, body mass index, sex, Single Assessment Numeric Evaluation score, visual analog scale score for pain, education, handedness, comorbidities, duration of symptoms, strength, employment, smoking status, and patient expectations. RESULTS: Of the 433 subjects in this study, 87 underwent surgery with 93% follow-up at 1 year and 88% follow-up at 2 years. The median age was 62 years, and 49% were female patients. Multivariate modeling, adjusted for the covariates listed previously, identified patient expectations regarding physical therapy (P < .0001) as the strongest predictor of surgery. Higher activity level (P = .011) and not smoking (P = .023) were also significant predictors of surgery. CONCLUSION: A patient's decision to undergo surgery is influenced more by low expectations regarding the effectiveness of physical therapy than by patient symptoms or anatomic features of the rotator cuff tear. As such, patient symptoms and anatomic features of the chronic rotator cuff tear may not be the best features to use when deciding on surgical intervention.

Intracellular Listeria monocytogenes comprises a minimal but vital fraction of the intestinal burden following foodborne infection.

Listeria monocytogenes is a highly adaptive bacterium that replicates as a free-living saprophyte in the environment as well as a facultative intracellular pathogen that causes invasive foodborne infections. The intracellular life cycle of L. monocytogenes is considered to be its primary virulence determinant during mammalian infection; however, the proportion of L. monocytogenes that is intracellular in vivo has not been studied extensively. In this report, we demonstrate that the majority of wild-type (strain EGDe) and mouse-adapted (InlA(m)-expressing) L. monocytogenes recovered from the mesenteric lymph nodes (MLN) was extracellular within the first few days after foodborne infection. In addition, significantly lower burdens of L. monocytogenes were recovered from the colon, spleen, and liver of gentamicin-treated mice than of control mice. This led us to investigate whether intracellular replication of L. monocytogenes was essential during the intestinal phase of infection. We found that lipoate protein ligase-deficient L. monocytogenes (ΔlplA1) mutants, which display impaired intracellular growth, were able to colonize the colon but did not persist efficiently and had a significant defect in spreading to the MLN, spleen, and liver. Together, these data indicate that the majority of the L. monocytogenes burden in the gastrointestinal tract is extracellular, but the small proportion of intracellular L. monocytogenes is essential for dissemination to the MLN and systemic organs.

The alveolate translation initiation factor 4E family reveals a custom toolkit for translational control in core dinoflagellates.

BACKGROUND: Dinoflagellates are eukaryotes with unusual cell biology and appear to rely on translational rather than transcriptional control of gene expression. The eukaryotic translation initiation factor 4E (eIF4E) plays an important role in regulating gene expression because eIF4E binding to the mRNA cap is a control point for translation. eIF4E is part of an extended, eukaryote-specific family with different members having specific functions, based on studies of model organisms. Dinoflagellate eIF4E diversity could provide a mechanism for dinoflagellates to regulate gene expression in a post-transcriptional manner. Accordingly, eIF4E family members from eleven core dinoflagellate transcriptomes were surveyed to determine the diversity and phylogeny of the eIF4E family in dinoflagellates and related lineages including apicomplexans, ciliates and heterokonts. RESULTS: The survey uncovered eight to fifteen (on average eleven) different eIF4E family members in each core dinoflagellate species. The eIF4E family members from heterokonts and dinoflagellates segregated into three clades, suggesting at least three eIF4E cognates were present in their common ancestor. However, these three clades are distinct from the three previously described eIF4E classes, reflecting diverse approaches to a central eukaryotic function. Heterokonts contain four clades, ciliates two and apicomplexans only a single recognizable eIF4E clade. In the core dinoflagellates, the three clades were further divided into nine sub-clades based on the phylogenetic analysis and species representation. Six of the sub-clades included at least one member from all eleven core dinoflagellate species, suggesting duplication in their shared ancestor. Conservation within sub-clades varied, suggesting different selection pressures. CONCLUSIONS: Phylogenetic analysis of eIF4E in core dinoflagellates revealed complex layering of duplication and conservation when compared to other eukaryotes. Our results suggest that the diverse eIF4E family in core dinoflagellates may provide a toolkit to enable selective translation as a strategy for controlling gene expression in these enigmatic eukaryotes.

InlA promotes dissemination of Listeria monocytogenes to the mesenteric lymph nodes during food borne infection of mice.

Intestinal Listeria monocytogenes infection is not efficient in mice and this has been attributed to a low affinity interaction between the bacterial surface protein InlA and E-cadherin on murine intestinal epithelial cells. Previous studies using either transgenic mice expressing human E-cadherin or mouse-adapted L. monocytogenes expressing a modified InlA protein (InlA(m)) with high affinity for murine E-cadherin showed increased efficiency of intragastric infection. However, the large inocula used in these studies disseminated to the spleen and liver rapidly, resulting in a lethal systemic infection that made it difficult to define the natural course of intestinal infection. We describe here a novel mouse model of oral listeriosis that closely mimics all phases of human disease: (1) ingestion of contaminated food, (2) a distinct period of time during which L. monocytogenes colonize only the intestines, (3) varying degrees of systemic spread in susceptible vs. resistant mice, and (4) late stage spread to the brain. Using this natural feeding model, we showed that the type of food, the time of day when feeding occurred, and mouse gender each affected susceptibility to L. monocytogenes infection. Co-infection studies using L. monocytogenes strains that expressed either a high affinity ligand for E-cadherin (InlA(m)), a low affinity ligand (wild type InlA from Lm EGDe), or no InlA (ΔinlA) showed that InlA was not required to establish intestinal infection in mice. However, expression of InlA(m) significantly increased bacterial persistence in the underlying lamina propria and greatly enhanced dissemination to the mesenteric lymph nodes. Thus, these studies revealed a previously uncharacterized role for InlA in facilitating systemic spread via the lymphatic system after invasion of the gut mucosa.

The duration of symptoms does not correlate with rotator cuff tear severity or other patient-related features: a cross-sectional study of patients with atraumatic, full-thickness rotator cuff tears.

HYPOTHESIS: The purpose of this cross-sectional study is to determine whether the duration of symptoms influences the features seen in patients with atraumatic, full-thickness rotator cuff tears. Our hypothesis is that an increasing duration of symptoms will correlate with more advanced findings of rotator cuff tear severity on magnetic resonance imaging, worse shoulder outcome scores, more pain, decreased range of motion, and less strength. METHODS: We enrolled 450 patients with full-thickness rotator cuff tears in a prospective cohort study to assess the effectiveness of nonoperative treatment and factors predictive of success. The duration of patient symptoms was divided into 4 groups: 3 months or less, 4 to 6 months, 7 to 12 months, and greater than 12 months. Data collected at patient entry into the study included (1) demographic data, (2) history and physical examination data, (3) radiographic imaging data, and (4) validated patient-reported measures of shoulder status. Statistical analysis included a univariate analysis with the Kruskal-Wallis test and Pearson test to identify statistically significant differences in these features for different durations of symptoms. RESULTS: A longer duration of symptoms does not correlate with more severe rotator cuff disease. The duration of symptoms was not related to weakness, limited range of motion, tear size, fatty atrophy, or validated patient-reported outcome measures. CONCLUSIONS: There is only a weak relationship between the duration of symptoms and features associated with rotator cuff disease.

Race and ethnicity moderate the associations between lifetime psilocybin use and past year hypertension.

Background: Hypertension is a major source of morbidity and mortality worldwide, particularly for racial and ethnic minorities who face higher rates of hypertension and worse health-related outcomes. Recent research has reported on protective associations between classic psychedelics and hypertension; however, there is a need to explore how race and ethnicity may moderate such associations. Methods: We used data from the National Survey on Drug Use and Health (2005-2014) to assess whether race and ethnicity moderate the associations between classic psychedelic use - specifically psilocybin - and past year hypertension. Results: Hispanic identity moderated the associations between psilocybin use and past year hypertension. Furthermore, individuals who used psilocybin and identified as Non-Hispanic White had reduced odds of hypertension (aOR: 0.83); however, these associations were not observed for any other racial or ethnic groups in our study for individuals who used psilocybin. Conclusion: Overall, our results demonstrate that the associations between psychedelics and hypertension may vary by race and ethnicity. Longitudinal studies and clinical trials can further advance this research and determine whether such differences exist in causal contexts. Project registration: https://osf.io/xsz2p/?view_only=0bf7b56749034c18abb2a3f8d3d4bc0b.

The Relationship Between Changes in Mindfulness and Subsequent Changes in Well-Being Following Psychedelic Use: Prospective Cohort Study.

This study demonstrates that changes in mindfulness predict subsequent changes in well-being in a data set including individuals who recently engaged in psychedelic use.

The Predictors of Surgery for Symptomatic, Atraumatic Full-Thickness Rotator Cuff Tears Change Over Time: Ten-Year Outcomes of the MOON Shoulder Prospective Cohort.

BACKGROUND: A prospective cohort study was conducted to assess the predictors of failure of nonoperative treatment, defined as the patient undergoing surgery for symptomatic, atraumatic full-thickness rotator cuff tears. We present the 10-year follow-up data of this population to determine if predictors for surgery change over time, and secondarily we report the outcomes of the cohort. METHODS: At the time of enrollment, demographic, symptom, rotator cuff anatomy, and patient-reported outcome data were collected in patients with symptomatic, atraumatic full-thickness rotator cuff tears. Patients underwent a standard physical therapy protocol for 6 to 12 weeks. Patient data were then collected at 1, 2, 5, 7, and 10 years. Failure of nonoperative treatment was defined as the patient electing to undergo surgery. RESULTS: Of the 452 patients in the original cohort, 20 patients (5%) withdrew from the study, 37 (9%) died before 10 years, and 40 (9%) were otherwise lost to follow-up. A total of 115 patients (27.0%) underwent a surgical procedure at some point during the 10-year follow-up period. Of these patients, 56.5% underwent surgery within 6 months of enrollment and 43.5%, between 6 months and 10 years. Low patient expectations regarding the efficacy of physical therapy were found to be a predictor of early surgery. Workers' Compensation status and activity level were more important predictors of later surgery. Patient-reported outcome measures all improved following physical therapy. For patients who did not undergo a surgical procedure, patient-reported outcome measures did not decline over the 10-year follow-up period. CONCLUSIONS: Low patient expectations regarding the efficacy of physical therapy were found to be a predictor of early surgery, whereas Workers' Compensation status and activity level were predictors of later surgery. Physical therapy was successful in >70% of patients with symptomatic, atraumatic full-thickness rotator cuff tears at 10 years. Outcome measures improved with physical therapy and did not decline over the 10-year follow-up period. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.