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Objective: To identify and evaluate montelukast deprescribing in outpatient specialty clinics. Methods: This was a single-center, retrospective, cross-sectional study conducted at an academic health system in the southern US including 21 specialty clinics. Subjects included adults ≥18 years with an active prescription for montelukast who attended at least one appointment in pulmonology, otolaryngology, or neurology outpatient specialty clinics between January 1, 2021 to December 31, 2022. Patients

Abstract Background Clinicians and public health professionals have allocated resources to curb opioid over-prescription and address psychological needs among patients with musculoskeletal pain. However, associations between psychological distress, risk of surgery, and opioid prescribing among those with hip pathologies remain unclear. Methods Using a retrospective cohort study design, we identified patients that were evaluated for hip pain from January 13, 2020 to October 27, 2021. Patients’ surgical histories and postoperative opioid prescriptions were extracted via chart review. Risk of hip surgery within one year of evaluation was analyzed using multivariable logistic regression. Multivariable linear regression was employed to predict average morphine milligram equivalents (MME) per day of opioid prescriptions within the first 30 days after surgery. Candidate predictors included age, gender, race, ethnicity, employment, insurance type, hip function and quality of life on the International Hip Outcome Tool (iHOT-12), and psychological distress phenotype using the OSPRO Yellow Flag (OSPRO-YF) Assessment Tool. Results Of the 672 patients, n = 350 (52.1%) underwent orthopaedic surgery for hip pain. In multivariable analysis, younger patients, those with TRICARE/other government insurance, and those with a high psychological distress phenotype had higher odds of surgery. After adding iHOT-12 scores, younger patients and lower iHOT-12 scores were associated with higher odds of surgery, while Black/African American patients had lower odds of surgery. In multivariable analysis of average MME, patients with periacetabular osteotomy (PAO) received opioid prescriptions with significantly higher average MME than those with other procedures, and surgery type was the only significant predictor. Post-hoc analysis excluding PAO found higher average MME for patients undergoing hip arthroscopy (compared to arthroplasty or other non-PAO procedures) and significantly lower average MME for patients with public insurance (Medicare/Medicaid) compared to those with private insurance. Among those only undergoing arthroscopy, older age and having public insurance were associated with opioid prescriptions with lower average MME. Neither iHOT-12 scores nor OSPRO-YF phenotype assignment were significant predictors of postoperative mean MME. Conclusions Psychological distress characteristics are modifiable targets for rehabilitation programs, but their use as prognostic factors for risk of orthopaedic surgery and opioid prescribing in patients with hip pain appears limited when considered alongside other commonly collected clinical information such as age, insurance, type of surgery pursued, and iHOT-12 scores.

Introduction: Articular cartilage injuries of the knee are a complex and challenging clinical pathology. Objectives: The purpose of this study was to establish consensus statements via a Delphi process on chondrocyte-based cartilage (CBC) approaches and scaffolds for cartilage injury. Methods: A consensus process on knee cartilage injuries utilizing a modified Delphi technique was conducted. Seventy-nine surgeons across 17 countries participated in these consensus statements. Ten questions were generated on chondrocyte-based approaches and scaffolds, with 3 rounds of questionnaires and final voting occurring. Consensus was defined as achieving 80% to 89% agreement, whereas strong consensus was defined as 90% to 99% agreement, and unanimous consensus was defined as 100% agreement with a proposed statement. Results: Of the 10 total questions and consensus statements on CBC repair developed from 3 rounds of voting, 1 question achieved unanimous consensus, 6 achieved strong consensus, 2 achieved consensus, and 1 did not achieve consensus. Conclusions: The statements that achieved strong or unanimous consensus were related to indication and relative indications for CBC repair, harvesting site for chondrocytes, differentiating healthy and unhealthy cartilage, sizing defects, minimizing complications, and orthobiologics utility. These consensus statements regarding chondrocyte-based approaches and scaffolds for cartilage injury will hopefully assist clinicians in the management of this challenging pathology.

Several comorbid conditions have been observed to be associated with an increased risk of poor outcomes following a diagnosis of COVID-19. The purpose of this investigation was to assess associations between Centers for Medicare and Medicaid Services (CMS) designated priority conditions and an inability to access care, treat ongoing conditions, and obtain prescription medications among Medicare beneficiaries in the United States during the COVID-19 pandemic. Nationally representative CMS Medicare Current Beneficiary Survey (MCBS) COVID-19 Supplement Public Use Files (PUF) were analyzed via bivariable, binomial generalized linear models across three time periods: (1) Summer 2020; (2) Fall 2020; and (3) Winter 2021. Across an estimated 55.3–57.4 million Medicare beneficiaries, approximately one-fifth reported an inability to access at least one type of care at the onset of the pandemic. Significantly worse odds of an ability to get care across various time periods was observed among several priority conditions including immune disorders, cancer, depression, osteoporosis, diabetes, arthritis, and numerous cardiovascular and pulmonary conditions. Among those reporting an inability to access care, approximately one-third involved treatment of an ongoing condition, and under one-tenth involved prescription medications. To identify modifiable risk factors and to develop active interventions, future work should continue to assess the complex associations between outcomes, access to care, comorbidities, evolving healthcare infrastructures, computerization, and various public health initiatives.

Purpose: To identify common pain-related psychological factors among patients seeking care for athletic hip pain, as well as characterize psychological distress phenotypes and compare hip-specific quality-of-life measures across those phenotypes. Methods: A total of 721 patients were recruited from hip preservation clinics. The Optimal Screening for Prediction of Referral and Outcome–Yellow Flag Assessment Tool (OSPRO-YF) was used to identify the presence or absence of 11 different pain-associated psychological distress characteristics (yellow flags), while the International Hip Outcome Tool–12 (iHOT-12) was used to assess hip-related quality of life. Latent class analysis identified patient subgroups (phenotypes) based on naturally occurring combinations of distress characteristics. An analysis of variance was used to compare demographics, number of yellow flags, and iHOT-12 scores across phenotypes. Results: The median (interquartile range) number of yellow flags was 6 (3-9), with 13.5% of the sample reporting 11 yellow flags. Latent class analysis (L2 = 543.3, classification errors = 0.082) resulted in 4 phenotypes: high distress (n = 299, 41.5%), low distress (n = 172, 23.9%), low self-efficacy and acceptance (n = 74, 10.3%), and negative pain coping (n = 276, 24.4%). Significant differences in mean yellow flags existed between all phenotypes except low self-efficacy and negative pain coping. There were no differences in demographics between phenotypes. The high distress class had the lowest mean iHOT-12 score (mean [SD], 23.5 [17.6]), with significant differences found between each phenotypic class. Conclusions: There was a high prevalence of pain-associated psychological distress in patients presenting to tertiary hip arthroscopy clinics with hip pain. Furthermore, hip quality-of-life outcome scores were uniformly lower in patients with higher levels of psychological distress. Level of Evidence: Level III, retrospective cohort study.

Abstract Gametic isolation is thought to play an important role in the evolution of reproductive isolation in broadcast‐spawning marine invertebrates. However, it is unclear whether gametic isolation commonly evolves early in the speciation process or only accumulates after other reproductive barriers are already in place. It is also unknown whether gametic isolation is an effective barrier to introgression following speciation. Here, we used whole‐genome sequencing data and multiple complementary phylogenomic approaches to test whether the well‐documented gametic incompatibilities among the strongylocentrotid sea urchins have limited introgression. We quantified phylogenetic discordance, inferred reticulate phylogenetic networks, and applied the Δ statistic using gene tree topologies reconstructed from multiple sequence alignments of protein‐coding single‐copy orthologs. In addition, we conducted ABBA–BABA tests on genome‐wide single nucleotide variants and reconstructed a phylogeny of mitochondrial genomes. Our results revealed strong mito‐nuclear discordance and considerable nonrandom gene tree discordance that cannot be explained by incomplete lineage sorting alone. Eight of the nine species examined demonstrated a history of introgression with at least one other species or ancestral lineage, indicating that introgression was common during the diversification of the strongylocentrotid urchins. There was strong support for introgression between four extant species pairs (Strongylocentrotus pallidus ⇔ S. droebachiensis, S. intermedius ⇔ S. pallidus, S. purpuratus ⇔ S. fragilis, and Mesocentrotus franciscanus ⇔ Pseudocentrotus depressus) and additional evidence for introgression on internal branches of the phylogeny. Our results suggest that the existing gametic incompatibilities among the strongylocentrotid urchin species have not been a complete barrier to hybridization and introgression following speciation. Their continued divergence in the face of widespread introgression indicates that other reproductive isolating barriers likely exist and may have been more critical in establishing reproductive isolation early in speciation.

Summary: Pancreatic ductal adenocarcinoma (PDA) orchestrates a suppressive tumor microenvironment that fosters immunotherapy resistance. Tumor-associated macrophages (TAMs) are the principal immune cell infiltrating PDA and are heterogeneous. Here, by employing macrophage fate-mapping approaches and single-cell RNA sequencing, we show that monocytes give rise to most macrophage subsets in PDA. Tumor-specific CD4, but not CD8, T cells promote monocyte differentiation into MHCIIhi anti-tumor macrophages. By conditional major histocompatibility complex (MHC) class II deletion on monocyte-derived macrophages, we show that tumor antigen presentation is required for instructing monocyte differentiation into anti-tumor macrophages, promoting Th1 cells, abrogating Treg cells, and mitigating CD8 T cell exhaustion. Non-redundant IFNγ and CD40 promote MHCIIhi anti-tumor macrophages. Intratumoral monocytes adopt a pro-tumor fate indistinguishable from that of tissue-resident macrophages following loss of macrophage MHC class II or tumor-specific CD4 T cells. Thus, tumor antigen presentation by macrophages to CD4 T cells dictates TAM fate and is a major determinant of macrophage heterogeneity in cancer.

Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer in the United States following basal cell carcinoma. The majority are successfully cured by surgical excision or Mohs microsurgery. A subset of cSCCs are more aggressive and likely to recur locally, spread to regional lymph nodes or even distantly, and can even result in death. High-risk features of cSCC including perineural invasion of nerve >0.1 mm in diameter and invasion beyond the subcutaneous fat are not routinely reported by Mohs microsurgery. Facial cSCC commonly involves branches of the facial nerve (VII) or trigeminal nerve (V). Clinical symptoms associated with cranial nerve VII and V involvement include pain, paresthesia of the face and tongue, facial paralysis. Assessment of nerve involvement by magnetic resonance imaging (MRI) is the most optimal imaging modality. Here, we present a case where Mohs microsurgery was performed on a facial cSCC 1.5 years prior to the development of facial paresis. We aim to highlight the interesting perineural path resulting in facial paralysis and associated symptomatology, the importance of MRI, and to remind clinicians of important high-risk features of cSCC.

Introduction: English proficiency and race are both independently known to affect surgical access and quality, but relatively little is known about the impact of race and limited English proficiency (LEP) on admission for emergency surgery from the emergency department (ED). Our objective was to examine the influence of race and English proficiency on admission for emergency surgery from the ED. Methods: We conducted a retrospective observational cohort study from January 1–December 31, 2019 at a large, quaternary-care urban, academic medical center with a 66-bed ED Level I trauma and burn center. We included ED patients of all self-reported races reporting a preferred language other than English and requiring an interpreter or declaring English as their preferred language (control group). A multivariable logistic regression was fit to assess the association of LEP status, race, age, gender, method of arrival to the ED, insurance status, and the interaction between LEP status and race with admission for surgery from the ED. Results: A total of 85,899 patients (48.1% female) were included in this analysis, of whom 3,179 (3.7%) were admitted for emergent surgery. Regardless of LEP status, patients identifying as Black (odds ratio [OR] 0.456, 95% CI 0.388–0.533; P

Background: Concomitant cartilage injury is commonly associated with patellofemoral instability. While nonoperative treatment remains the gold standard for first time dislocators, there has been an increased trend toward addressing patellar instability when symptomatic cartilage disease is present. Indications: A healthy active 29-year-old woman >2 years of patellar instability and pain symptoms in the right knee. Imaging revealed tibial tubercle to trochlear groove (TT-TG) distance of 19.8 mm, and a Caton Deschamps Ratio of 1.54. Initial staging arthroscopy demonstrated a near full thickness cartilage defect of the lateral patellar facet measuring 2x2 cm. Technique Description: In the index procedure, a staging diagnostic arthroscopy is performed to evaluate the extent of the cartilage defect. Given the size of the lesion, a matrix-induced autologous chondrocyte implantation (MACI) biopsy is performed for later implantation. At the second stage procedure, a midline approach to the patella and tibial tubercle is performed. A 45° osteotomy is initiated with a cutting jig. The osteotomy is detached distally to allow for both anteromedialization and distalization to offload the cartilage defect and improve patellar articulation. The lateral patellar facet cartilage defect is prepared, and a combination of fibrin sealant and digital pressure is used to implant the pre-shaped MACI transplant. The osteotomy is then secured with 2 bicortical screws. A semitendinosus allograft is secured to the upper half of the medial border of the patellar and secured to its anatomometric point on the femur to reconstruct the medial patellofemoral ligament (MPFL). Results: Patient successfully returned to running and is currently working on return to other sports with no anterior knee pain or instability. Recent studies have demonstrated overall good clinical outcomes following MACI for patellofemoral lesions. Addressing underlying bony deformity and offloading patellofemoral cartilage lesions with tibial tubercle osteotomy in combination with MPFL reconstruction has improved patellar stability and good patient satisfaction. Discussion/Conclusion: Combined tibial tubercle osteotomy, MPFL reconstruction, and MACI in a comprehensive approach can successfully address symptomatic patellofemoral cartilage disease in the setting of patellar instability with underlying bony abnormalities.

Supervised personal training is most effective in improving the health effects of exercise in older adults. Yet, low frequency (60 min, 1–3 sessions/week) of trainer contact limits influence on behavior change outside sessions. Strategies to extend the effect of trainer contact outside of supervision and that integrate meaningful and intelligent two-way communication to provide complex and interactive problem solving may motivate older adults to “move more and sit less” and sustain positive behaviors to further improve health. This paper describes the experimental protocol of a 16-week pilot RCT (N = 46) that tests the impact of supplementing supervised exercise (i.e., control) with a technology-based behavior-aware text-based virtual “Companion” that integrates a human-in-the-loop approach with wirelessly transmitted sensor-based activity measurement to deliver behavior change strategies using socially engaging, contextually salient, and tailored text message conversations in near-real-time. Primary outcomes are total-daily and patterns of habitual physical behaviors after 16 and 24 weeks. Exploratory analyses aim to understand Companion’s longitudinal behavior effects, its user engagement and relationship to behavior, and changes in cardiometabolic and cognitive outcomes. Our findings may allow the development of a more scalable hybrid AI Companion to impact the ever-growing public health epidemic of sedentariness contributing to poor health outcomes, reduced quality of life, and early death.

Activation of T cells requires a rapid surge in cellular protein synthesis. However, the role of translation initiation in the early induction of specific genes remains unclear. Here, we show human translation initiation factor eIF3 interacts with select immune system related mRNAs including those encoding the T cell receptor (TCR) subunits TCRA and TCRB. Binding of eIF3 to the TCRA and TCRB mRNA 3’-untranslated regions (3’-UTRs) depends on CD28 coreceptor signaling and regulates a burst in TCR translation required for robust T cell activation. Use of the TCRA or TCRB 3’-UTRs to control expression of an anti-CD19 chimeric antigen receptor (CAR) improves the ability of CAR-T cells to kill tumor cells in vitro. These results identify a new mechanism of eIF3-mediated translation control that can aid T cell engineering for immunotherapy applications.

A 71 year old male presented to the emergency room for evaluation of acute erythema, edema and pain of the penis and scrotum. There was initial concern for Fournier's gangrene, however labs were unremarkable and vital signs were stable. He did not improve with antibiotics. Biopsy results showed neutrophil infiltration consistent with Sweet's Syndrome. He was started on corticosteroids and discharged home in stable condition. In a hemodynamically stable patient not responding to antibiotic therapy, close observation is prudent until the tissue biopsy results.

Seeding rate in hard red spring wheat (HRSW; Triticum aestivum L.) production impacts input cost and grain yield. Predicting the optimal seeding rate (OSR) for HRSW cultivars can eliminate the need for costly seeding rate research and growers using OSRs can maximize yield and seeding efficiency. Data were compiled from seeding rate studies conducted in 32 environments in the Northern Plains United States to determine the OSR of HRSW cultivars grown in diverse environments. Twelve cultivars with diverse genetic and phenotypic characteristics were evaluated at five seeding rates in 2013–2015, and nine cultivars were evaluated in 2017–2018. OSR varied among cultivar within environments. Cultivar x environment interactions were explored with the objective of developing a decision support system (DSS) to aid growers in determining the OSR for the cultivar they select, and for the environment in which it is sown. A 10-fold repeated cross-validation of the seeding rate data was used to fit 10 decision tree models and the most robust model was selected based on minimizing the value for model variance. The final decision tree model for predicting OSR of HRSW cultivars in diverse environments was considered the most reliable as bias was minimized by pruning methods, and model variance was acceptable for OSR predictions (RMSE = 1.24). Findings from this model were used to develop the grower DSS for determining OSR dependent on cultivar straw strength (as a measure of lodging resistance), tillering capacity, and yield of the environment. Recommendations for OSR ranged from 3.1 to 4.5 million seeds ha–1. Growers can benefit from using this DSS by sowing at OSR relative to their average yields; especially when seeding new HRSW cultivars.

Mucosal surfaces in the gastrointestinal tract are continually exposed to native, commensal antigens and susceptible to foreign, infectious antigens. Immunoglobulin A (IgA) provides dual humoral responses that create a symbiotic environment for the resident gut microbiota and prevent the invasion of enteric pathogens. This review features recent immunological and microbial studies that elucidate the underlying IgA and microbiota-dependent mechanisms for mutualism at physiological conditions. IgA derailment and concurrent microbiota instability in pathological diseases are also discussed in detail. Highlights of this review underscore that the source of IgA and its structural form can dictate microbiota reactivity to sustain a diverse niche where both host and bacteria benefit. Other important studies emphasize IgA insufficiency can result in the bloom of opportunistic pathogens that encroach the intestinal epithelia and disseminate into circulation. The continual growth of knowledge in these subjects can lead to the development of therapeutics targeting IgA and/or the microbiota to treat life threatening diseases.

Abstract Background Comparative genomics studies investigating the signals of positive selection among groups of closely related species are still rare and limited in taxonomic breadth. Such studies show great promise in advancing our knowledge about the proportion and the identity of genes experiencing diversifying selection. However, methodological challenges have led to high levels of false positives in past studies. Here, we use the well-annotated genome of the purple sea urchin, Strongylocentrotus purpuratus, as a reference to investigate the signals of positive selection at 6520 single-copy orthologs from nine sea urchin species belonging to the family Strongylocentrotidae paying careful attention to minimizing false positives. Results We identified 1008 (15.5%) candidate positive selection genes (PSGs). Tests for positive selection along the nine terminal branches of the phylogeny identified 824 genes that showed lineage-specific adaptive diversification (1.67% of branch-sites tests performed). Positively selected codons were not enriched at exon borders or near regions containing missing data, suggesting a limited contribution of false positives caused by alignment or annotation errors. Alignments were validated at 10 loci with re-sequencing using Sanger methods. No differences were observed in the rates of synonymous substitution (d S), GC content, and codon bias between the candidate PSGs and those not showing positive selection. However, the candidate PSGs had 68% higher rates of nonsynonymous substitution (d N) and 33% lower levels of heterozygosity, consistent with selective sweeps and opposite to that expected by a relaxation of selective constraint. Although positive selection was identified at reproductive proteins and innate immunity genes, the strongest signals of adaptive diversification were observed at extracellular matrix proteins, cell adhesion molecules, membrane receptors, and ion channels. Many candidate PSGs have been widely implicated as targets of pathogen binding, inactivation, mimicry, or exploitation in other groups (notably mammals). Conclusions Our study confirmed the widespread action of positive selection across sea urchin genomes and allowed us to reject the possibility that annotation and alignment errors (including paralogs) were responsible for creating false signals of adaptive molecular divergence. The candidate PSGs identified in our study represent promising targets for future research into the selective agents responsible for their adaptive diversification and their contribution to speciation.

This paper is a preliminary analysis of an internet-based questionnaire on dialect attitudes and perceptions conducted in Slovene-speaking areas in Austrian and Slovene Carinthia. The survey largely confirmed expectations. Large majorities on both sides of the border claimed to use and value the local dialect. Lower percentages in Austrian Carinthia claimed proficiency in the local dialect and that the youth of Austrian Carinthia primarily spoke the local dialect. Overall a relatively large percentage of respondents from Carinthia claimed the local dialect was dying, 35% in Slovene Carinthia and 75% in Austrian Carinthia. Respondents claimed that the local dialect is being replaced by the colloquial standard language or, on the Austrian side of the border, by German. It appears likely that the local dialects in Carinthia are being leveled toward the standard language rather than toward the regional dialect. These are not positive indicators for dialect maintenance, especially in Austrian Carinthia.

A major challenge in HIV vaccine development is the identification of immunogens able to elicit broadly neutralizing antibodies (bNAbs). While remarkable progress has been made in the isolation and characterization of bNAbs, the epitopes they recognize appear to be poorly immunogenic. Thus, none of the candidate vaccines developed to date has induced satisfactory levels of neutralizing antibodies to the HIV envelope protein (Env). One approach to the problem of poor immunogenicity is to build vaccines based on envelope (env) genes retrieved from rare individuals termed elite neutralizers (ENs) who at one time possessed specific sequences that stimulated the formation of bNAbs. Env proteins selected from these individuals could possess uncommon, yet to be defined, structural features that enhance the immunogenicity of epitopes recognized by bNAbs. Here we describe the recovery of envs from an EN that developed unusually broad and potent bNAbs. As longitudinal specimens were not available, we combined plasma and provirus sequences acquired from a single time-point to infer a phylogenetic tree. Combining ancestral reconstruction data with virus neutralization data allowed us to sift through the myriad of virus quasi-species that evolved in this individual to identify envelope sequences from the nodes that appeared to define the transition from neutralization sensitive envs to the neutralization resistant envs that occur in EN plasma. Synthetic genes from these nodes were functional in infectivity assays and sensitive to neutralization by bNAbs, and may provide a novel source of immunogens for HIV vaccine development.

In the military, explosive blasts are a significant cause of mild traumatic brain injuries (mTBIs). The symptoms associated with blast mTBIs causes significant economic burdens and a diminished quality of life for many service members. At present, the distinction of the injury mechanism (blast versus non-blast) may not influence TBI diagnosis. However, using noninvasive imaging, this study reveals significant distinctions between the blast and non-blast TBI mechanisms. A cortical whole-brain thickness analysis was performed using structural high-resolution T1-weighted MRI to identify the effects of blasts in persistent mTBI (pmTBI) subjects. A total of 41 blast pmTBI subjects were individually age- and gender-matched to 41 non-blast pmTBI subjects. Using FreeSurfer, cortical thickness was quantified for the blast group, relative to the non-blast group. Cortical thinning was identified within the blast mTBI group, in two clusters bilaterally. In the left hemisphere, the cluster overlapped with the lateral orbitofrontal, rostral middle frontal, medial orbitofrontal, superior frontal, rostral anterior cingulate and frontal pole cortices (p

O crítico e historiador de arte Grant H. Kester tem se dedicado à pesquisa das práticas de arte socialmente engajada, da cultura visual de movimentos de reforma norte-americanos e das relações entre o político e a teoria estética. Entre os anos de 1990 e 1996 ele foi o editor de artes visuais e de media-art do periódico Afterimage. Grant H. Kester tem uma asta produção de ensaios e de livros, sendo os mais recentes Conversation Pieces: Community + Communication in Modern Art (University of California Press, 2004) e The One and the Many: Contemporary Collaborative Art in a Global Context (Duke University Press, 2011). Em 2006 Grant H. Kester foi convidado a visitar Dublin, Irlanda, pelo projeto City Arts para realizar uma conferência sobre suas pesquisas recentes. Alguns dias mais tarde, em 11/6/2006, ele foi entrevistado por Tim Stott para o periódico Circa.

The subscapularis is the strongest rotator cuff muscle in the shoulder. Until recently, most surgical repairs were performed through an open approach. Furthermore, the reporting of arthroscopic repair techniques and outcomes is fairly limited. This is likely due to the difficulty involved in all-arthroscopic repairs and the relative rarity of this injury compared with injuries of the other rotator cuff tendons. Arthroscopic subscapularis repair can be challenging, even for an expert surgeon, and attempting a double-row repair adds further complexity. Given these issues, this article provides techniques to allow for successful arthroscopic double-row subscapularis repair and avoid potential complications. The key features of an arthroscopic double-row repair include portal placement, surgical technique, and tips to avoid potential pitfalls, all of which are discussed.

Massive rotator cuff tears pose significant clinical and surgical challenges for orthopaedic surgeons and increased morbidity to the patient. Left untreated, this pathology can lead to inability to perform daily activities, weakness, pain, and eventual cuff tear arthropathy. Several treatment options exist for irreparable cuff tears, such as reverse shoulder arthroplasty and tendon transfers. However, there exists significant concern for high complication rates and unpredictable clinical outcomes following such treatments. Superior capsular reconstruction (SCR) represents a viable alternative in treating irreparable cuff tears, providing biomechanical stability and improving pain related to this pathology by reducing superior humeral instability and subacromial impingement. Over-the-top repair of the native rotator cuff tendons with incorporation of the SCR allograft may provide surgeons the opportunity to perform a robust repair in situations where arthroplasty or other more invasive procedures were once the only options. The authors present a surgical technique with associated pearls and pitfalls for their preferred procedure of SCR with incorporation of the native rotator cuff in transosseous equivalent double-row repair for the treatment of massive, irreparable rotator cuff tears.

Anterior cruciate ligament (ACL) reconstruction with a bone–patellar tendon–bone autograft yields good clinical outcomes. Despite appropriate clinical outcomes, the most common complaint after reconstruction with a bone–patellar tendon–bone autograft is anterior knee pain at the donor graft sites. Synthetic bone grafts, such as beta-tricalcium phosphate (β-TCP), have been previously used to fill the bony defect in fractures as well as removal of bony tumors, and have shown positive utility in improving anterior knee pain after ACL reconstruction. In this Technical Note, we describe the technique of placing a β-TCP graft in the donor graft site after bone–patellar tendon–bone ACL reconstruction. After standard arthroscopic ACL reconstruction, the β-TCP is appropriately sized with an osteotome and sagital saw before being placed into the patellar and tibial donor sites. A 0-Vicryl suture is used to suture the periosteum to secure the β-TCP graft at the donor sites. This described technique allows for appropriate sizing and secure placement of the graft to maximize bone regeneration at the donor site.

Massive rotator cuff tears, as classified by size or tendon involvement, are challenging to repair due to scarring, retraction of the tendons, and difficult visualization. Left untreated, these injuries can lead to fatty infiltration and reduced acromiohumeral distance that precludes future repair. The high rate of failure in these patients often impedes an anatomical repair. However, advanced mobilization techniques of the supraspinatus help facilitate a reduction of an otherwise irreparable tear. By performing this repair, more costly procedures may be avoided, such as a superior capsular reconstruction and reverse total shoulder arthroplasty. This Technical Note presents our preferred technique of an all-arthroscopic, medialized repair with double interval slides for the treatment of a massive rotator cuff tear.

Analgesic trials frequently fail to demonstrate efficacy of drugs known to be efficacious. Poor pain reporting accuracy is a possible source for this low essay-sensitivity. We report the effects of Accurate-Pain-Reporting-Training (APRT) on the placebo response in a trial of Pregabalin for painful-diabetic-neuropathy. The study was a two-stage randomized, double-blind trial: In Stage-1 (Training) subjects were randomized to APRT or No-Training. The APRT participants received feedback on the accuracy of their pain reports in response to mechanical stimuli, measured by R-square score. In Stage-2 (Evaluation) all subjects entered a placebo-controlled, cross-over trial. Primary (24-h average pain intensity) and secondary (current, 24-h worst, and 24-h walking pain intensity) outcome measures were reported. Fifty-one participants completed the study. APRT patients (n = 28) demonstrated significant (p = 0.036) increases in R-square scores. The APRT group demonstrated significantly (p = 0.018) lower placebo response (0.29 ± 1.21 vs. 1.48 ± 2.21, mean difference ± SD = -1.19±1.73). No relationships were found between the R-square scores and changes in pain intensity in the treatment arm. In summary, our training successfully increased pain reporting accuracy and resulted in a diminished placebo response. Theoretical and practical implications are discussed.

Seeding rate for maximum grain yield can differ for diverse hard red spring wheat (HRSW) (Triticum aestivum L.) cultivars and is derived from a yield response curve to seeding rates. Six groups of HRSW cultivars with combinations of Rht-B, Rht-D, and Ppd-D genes were planted at five seeding rates in 21 environments during 2013−2015 throughout Minnesota and eastern North Dakota, USA. Seeding rates ranged from 1.59 to 5.55 million seeds ha−1 and planting timings were optimal and delayed dates. An analysis of covariance predictive model with 13 predetermined training environments was built for yield and tillering, and validated with eight predetermined environments. Optimal seeding rates from the yield model were not predictive for yield, with latitude of the environment negatively skewing the predictions from observed values. A second yield model fit to only the six lowest-yielding environments (−1) was more predictive (R2 = 0.44), and revealed yield response to seeding rate was influenced by cultivar traits for photoperiod response (Ppd-D gene) and plant stature (semi-dwarfing gene Rht-D). The tillering model was also predictive for the validation environments, with a R2 of 0.71. Using regression predictions for yield and tillering from training and validation datasets with HRSW genetic and geographic predictors shows promise to help recommend seeding rates for future environments.

Introduction: There are many luting cements coming to market which claim to be adhesive, but there is no clinical protocol currently for testing these claims. There is a standardized protocol for testing direct restorations bonded to dentin and it is used extensively. Case Report: We describe a clinical procedure for restoring a non-carious cervical lesion (NCCL) with a ceramic inlay using Computer-Aided Design and Computer-Aided Manufacturing (CAD-CAM) technology and an adhesive resin cement.The procedure was straightforward and the result was good at one month. Discussion: NCCL′s can be restored with CAD-CAM technology in one appointment. This technique can be used to clinically test adhesion of luting cements to dentin, similarly to the current standard for direct restorations.

Information overload of the anesthesiologist through technological advances have threatened the safety of patients under anesthesia in the operating room (OR). Traditional monitoring and alarm systems provide independent, spatially distributed indices of patient physiological state. This creates the potential to distract caregivers from direct patient care tasks. To address this situation, a novel reactive agent decision support system with graphical human machine interface was developed. The system integrates the disparate data sources available in the operating room, passes the data though a decision matrix comprising a deterministic physiologic rule base established through medical research. Patient care is improved by effecting change to the care environment by displaying risk factors and alerts as an intuitive color coded animation. The system presents a unified, contextually appropriate snapshot of the patient state including current and potential risk factors, and alerts of critical patient events to the operating room team without requiring any user intervention. To validate the efficacy of the system, a retrospective analysis focusing on the hypotension rules were performed. Results show that even with vigilant and highly trained clinicians, deviations from ideal patient care exist and it is here that the proposed system may allow more standardized and improved patient care and potentially outcomes.

Mutations in the human LMNA gene cause muscular dystrophy by mechanisms that are incompletely understood. The LMNA gene encodes A-type lamins, intermediate filaments that form a network underlying the inner nuclear membrane, providing structural support for the nucleus and organizing the genome. To better understand the pathogenesis caused by mutant lamins, we performed a structural and functional analysis on LMNA missense mutations identified in muscular dystrophy patients. These mutations perturb the tertiary structure of the conserved A-type lamin Ig-fold domain. To identify the effects of these structural perturbations on lamin function, we modeled these mutations in Drosophila Lamin C and expressed the mutant lamins in muscle. We found that the structural perturbations had minimal dominant effects on nuclear stiffness, suggesting that the muscle pathology was not accompanied by major structural disruption of the peripheral nuclear lamina. However, subtle alterations in the lamina network and subnuclear reorganization of lamins remain possible. Affected muscles had cytoplasmic aggregation of lamins and additional nuclear envelope proteins. Transcription profiling revealed upregulation of many Nrf2 target genes. Nrf2 is normally sequestered in the cytoplasm by Keap-1. Under oxidative stress Nrf2 dissociates from Keap-1, translocates into the nucleus, and activates gene expression. Unexpectedly, biochemical analyses revealed high levels of reducing agents, indicative of reductive stress. The accumulation of cytoplasmic lamin aggregates correlated with elevated levels of the autophagy adaptor p62/SQSTM1, which also binds Keap-1, abrogating Nrf2 cytoplasmic sequestration, allowing Nrf2 nuclear translocation and target gene activation. Elevated p62/SQSTM1 and nuclear enrichment of Nrf2 were identified in muscle biopsies from the corresponding muscular dystrophy patients, validating the disease relevance of our Drosophila model. Thus, novel connections were made between mutant lamins and the Nrf2 signaling pathway, suggesting new avenues of therapeutic intervention that include regulation of protein folding and metabolism, as well as maintenance of redox homoeostasis.

To evaluate the magnitude and impact of diabetic foot ulcers (DFUs) in emergency department (ED) settings from 2006-2010 in the United States (US).This cross-sectional study utilized Agency for Healthcare Research and Quality (AHRQ) Healthcare Cost and Utilization Project (HCUP) National Emergency Department Sample (NEDS) discharge records of ED cases among persons ≥18 years with any-listed diagnosis of DFUs. Multivariable analyses were conducted for clinical outcomes of patient disposition from the ED and economic outcomes of charges and lengths of stay based upon patient demographic and socioeconomic factors, hospital characteristics, and comorbid disease states.Overall, 1,019,861 cases of diabetic foot complications presented to EDs in the US from 2006-2010, comprising 1.9% of the 54.2 million total diabetes cases. The mean patient age was 62.5 years and 59.4% were men. The national bill was $1.9 billion per year in the ED and $8.78 billion per year (US$ 2014) including inpatient charges among the 81.2% of cases that were admitted. Clinical outcomes included mortality in 2.0%, sepsis in 9.6% of cases and amputation in 10.5% (major-minor amputation ratio of 0.46). Multivariable analyses found that those residing in non-urban locations were associated with +51.3%, +14.9%, and +41.4% higher odds of major amputation, minor amputation, and inpatient death, respectively (p

The purpose of this study was to quantify the excess return in shareholder security prices following initial announcements of successful horizontal pharmaceutical mergers which occurred between 1985 and 1996. An event study methodology was used to study a sample of26 fim1s involved in 14 mergers wherein transaction costs exceeded $500 million. Overall, results of the study were consistent with prior research, indicating that target-firm shareholders received a majority oft he short-term merger-related wealth effects in comparison to those received by bidder- firm shareholders.

Within the context of clinical and other scientific research, a substantial need exists for an accurate determination of the point estimate in a lognormal mean model, given that highly skewed data are often present. As such, logarithmic transformations are often advocated to achieve the assumptions of parametric statistical inference. Despite this, existing approaches that utilize only a sample’s mean and variance may not necessarily yield the most efficient estimator. The current investigation developed and tested an improved efficient point estimator for a lognormal mean by capturing more complete information via the sample’s coefficient of variation. Results of an empirical simulation study across varying sample sizes and population standard deviations indicated relative improvements in efficiency of up to 129.47 percent compared to the usual maximum likelihood estimator and up to 21.33 absolute percentage points above the efficient estimator presented by Shen and colleagues (2006). The relative efficiency of the proposed estimator increased particularly as a function of decreasing sample size and increasing population standard deviation.

Research suggests theatre arts participation benefits student's academic and nonacademic outcomes. The purpose of this literature review was to identify the extent to which a relationship exists between participation in theatre arts and student outcomes for students K-12. Fourteen articles met the inclusion criteria. Results found theatre arts programs were positively related to self-beliefs, provide positive outcome experiences, foster student development, increase interpersonal and social skills, and expand theatre arts skills. The results indicate the importance of the creative process in theatre arts, which includes play production, theatre devising and theatre workshops and classes. The evidence from these findings suggest that students may benefit from the experiences of participation in a theatre arts program through the creative process and increase student outcomes through social and emotional development, enhancing self-beliefs, and increasing theatre arts skills. This informs current practice in implantation of a theatre arts program, which could include play production, theatre devising and theatre classes and workshops.

The antibiotic teixobactin is a promising drug candidate against drug-resistant pathogens, such as MRSA and VRE, but forms insoluble gels that may limit intravenous administration. O-Acyl isopeptide prodrug analogues of teixobactin circumvent the problem of gel formation while retaining antibiotic activity. The teixobactin prodrug analogues contain ester linkages between Ile6 and Ser7, Ile2 and Ser3, or between both Ile6 and Ser7 and Ile2 and Ser3. Upon exposure to physiological pH, the prodrug analogues undergo clean conversion to the corresponding amides, with half-lives between 13 and 115 min. Prodrug analogues containing lysine, arginine, or leucine at position 10 exhibit good antibiotic activity against a variety of Gram-positive bacteria while exhibiting little or no cytotoxicity or hemolytic activity. Because O-acyl isopeptide prodrug analogues of teixobactin exhibit clean conversion to the corresponding teixobactin analogues with reduced propensity to form gels, it is anticipated that teixobactin prodrugs will be superior to teixobactin as drug candidates.

PurposeTo evaluate the ability of patients to return to work following anteromedialization (AMZ) tibial tubercle osteotomy (TTO) due to isolated patellofemoral osteoarthritis or pain.MethodsConsecutive patients undergoing AMZ TTO were reviewed retrospectively at a minimum of 1 year postoperatively. Patients completed a subjective work questionnaire, a visual analog scale for pain, as well as a Kujala questionnaire and satisfaction questionnaire.ResultsFifty-seven patients (61 knees; average age: 32.7 ± 9.6 years) were contacted at an average follow-up of 4.86 ± 2.84 years postoperatively. The preoperative Kujala score improved from 55.7 ± 17.8 to 84.6 ± 15.8 at final follow-up (P < 0.001). Thirty-seven patients (64.9%) were employed within 3 years prior to surgery and 34 patients (91.9%) were able to return to work by 2.8 ± 2.6 months postoperatively. However, only 27 patients (73.0%) of patients were able to return to the same level of occupational intensity. Patients who held sedentary, light-, medium-, or high-intensity occupations were able to return to work at a rate of 100.0%, 93.8%, 77.8%, and 100.0% by 2.2 months, 3.0 months, 3.1 months, and 4.0 months, postoperatively. No patients underwent revision TTO or conversion to arthroplasty by the time of final follow-up.ConclusionIn patients with focal patellofemoral osteoarthritis or pain, AMZ TTO provides a high rate of return to work (91.9%) by 2.8 ± 2.6 months postoperatively. Patients with higher intensity occupations may take longer to return to work than those with less physically demanding occupations.Level of evidenceIII.

Activation of T cells requires a rapid surge in cellular protein synthesis. However, the role of translation initiation in the early induction of specific genes remains unclear. Here, we show human translation initiation factor eIF3 interacts with select immune system related mRNAs including those encoding the T cell receptor (TCR) subunits TCRA and TCRB. Binding of eIF3 to the TCRA and TCRB mRNA 3'-untranslated regions (3'-UTRs) depends on CD28 coreceptor signaling and regulates a burst in TCR translation required for robust T cell activation. Use of the TCRA or TCRB 3'-UTRs to control expression of an anti-CD19 chimeric antigen receptor (CAR) improves the ability of CAR-T cells to kill tumor cells in vitro. These results identify a new mechanism of eIF3-mediated translation control that can aid T cell engineering for immunotherapy applications.