Molecular bowls for inclusion complexation of toxic anticancer drug methotrexate.

We describe the preparation and study of novel cavitands, molecular bowls 16+ and 26+, as good binders of the anticancer drug methotrexate (MTX). Molecular bowls are comprised of a curved tribenzotriquinacene (TBTQ) core conjugated to three macrocyclic pyridinium units at the top. The cavitands are easily accessible via two synthetic steps from hexabromo-tribenzotriquinacene in 25% yield. As amphiphilic molecules, bowls 16+ and 26+ self-associate in water by the nucleation-to-aggregation pathway (NMR). The bowls are preorganized, having a semi-rigid framework comprising a fixed bottom with a wobbling pyridinium rim (VT NMR and MD). Further studies, both experimental (NMR) and computational (DFT and MCMM), suggested that a folded MTX occupies the cavity of bowls wherein it forms π-π, C-H-π, and ion pairing intermolecular contacts but also undergoes desolvation to give stable binary complexes (µM) in water. Moreover, a computational protocol is introduced to identify docking pose(s) of MTX inside molecular bowls from NMR shielding data. Both molecular bowls have shown in vitro biocompatibility with liver and kidney cell lines (MTS assay). As bowl 26+ is the strongest binder of MTX reported to date, we envision it as an excellent candidate for further studies on the way toward developing an antidote capable of removing MTX from overdosed cancer patients.

Connected communities: Perceived neighborhood social cohesion during adolescence and subsequent health and well-being in young adulthood-An outcome-wide longitudinal approach.

Does higher perceived neighborhood social cohesion in adolescence lead to better health and well-being 10-12 years later? We evaluated this question using data from a large, prospective, and nationally representative sample of US adolescents (Add Health; N = 10,963), and an outcome-wide approach. Across 38 outcomes, perceived neighborhood social cohesion was associated with some: mental health outcomes (i.e., depressive symptoms, suicidal ideation, perceived stress), psychological well-being outcomes (i.e., happiness, optimism), social outcomes (i.e., loneliness, romantic relationship quality, satisfaction with parenting), and civic/prosocial outcomes (i.e., volunteering). However, it was not associated with health behaviors nor physical health outcomes. These results were maintained after robust control for a wide range of potential confounders.

Gratitude and Mortality Among Older US Female Nurses.

Importance: Supporting healthy aging is a US public health priority, and gratitude is a potentially modifiable psychological factor that may enhance health and well-being in older adults. However, the association between gratitude and mortality has not been studied. Objective: To examine the association of gratitude with all-cause and cause-specific mortality in later life. Design, Setting, and Participants: This population-based prospective cohort study used data from self-reported questionnaires and medical records of 49 275 US older female registered nurses who participated in the Nurses' Health Study (2016 questionnaire wave to December 2019). Cox proportional hazards regression models estimated the hazard ratio (HR) of deaths by self-reported levels of gratitude at baseline. These models adjusted for baseline sociodemographic characteristics, social participation, physical health, lifestyle factors, cognitive function, and mental health. Data analysis was conducted from December 2022 to April 2024. Exposure: Gratitude was assessed with the 6-item Gratitude Questionnaire, a validated and widely used measure of one's tendency to experience grateful affect. Main Outcomes and Measures: Deaths were identified from the National Death Index, state statistics records, reports by next of kin, and the postal system. Causes of death were ascertained by physicians through reviewing death certificates and medical records. Results: Among the 49 275 participants (all female; mean [SD] age at baseline, 79 [6.16] years), 4608 incident deaths were identified over 151 496 person-years of follow-up. Greater gratitude at baseline was associated with a lower hazard of mortality in a monotonic fashion. For instance, the highest tertile of gratitude, compared with the lowest tertile, was associated with a lower hazard of all-cause deaths (HR, 0.91; 95% CI, 0.84-0.99) after adjusting for baseline sociodemographic characteristics, social participation, religious involvement, physical health, lifestyle factors, cognitive function, and mental health. When considering cause-specific deaths, death from cardiovascular disease was inversely associated with gratitude (HR, 0.85; 95% CI, 0.73-0.995). Conclusions and Relevance: This study provides the first empirical evidence suggesting that experiencing grateful affect is associated with increased longevity among older adults. The findings will need to be replicated in future studies with more representative samples.

Differential effects of deep brain stimulation on reinstatement of cocaine seeking in male and female rats.

There are currently no FDA-approved treatments for cocaine use disorder. Recent preclinical and clinical studies showed that deep brain stimulation (DBS) in limbic regions reduced drug seeking behavior. Our previous work indicated that DBS of the nucleus accumbens shell attenuated reinstatement of cocaine seeking, a model of relapse, in male rats. The current experiments were designed to evaluate the effect of electrical DBS on cocaine reinstatement in female rats across the estrous cycle. Rats were allowed to self-administer cocaine and lever responding was subsequently extinguished. Cocaine seeking was reinstated by an acute injection of experimenter-delivered cocaine. The effect of nucleus accumbens shell DBS vs. sham stimulation on cocaine-primed reinstatement was evaluated in female and male rats using a within-subjects counterbalanced design. Consistent with previous work, accumbens shell DBS suppressed cocaine seeking in male rats. In sharp contrast, accumbens shell DBS had no effect on cocaine reinstatement in female rats evaluated in either the estrus or non-estrus phases. These results suggest that changes across the estrous cycle are not responsible for the differences in the effect of DBS on cocaine reinstatement between female and male rats.

Maritime Applications of Prolonged Casualty Care Sepsis on a Destroyer During Distributed Maritime Operations.

During distributed maritime operations, individual components of the naval force are more geographically dispersed. As the U.S. Navy further develops this concept, smaller vessels may be operating at a significant time and distance away from more advanced medical capabilities. Therefore, during both current and future contested Distributed Maritime Operations, Role 1 maritime caregivers such as Independent Duty Corpsman will have to manage patients for prolonged periods of time. This manuscript presents an innovative approach to teaching complex operational medicine concepts (including Prolonged Casualty Care [PCC]) to austere Role 1 maritime caregivers using a hypothetical scenario involving a patient with sepsis and septic shock. The scenario incorporates the Joint Trauma System PCC Clinical Practice Guidelines (CPG) and other standard references. The scenario includes a stem clinical vignette, expected clinical changes for the affected patient at specific time points (e.g., time 0, 1, 2, and 48h), and expected interventions based on the PCC CPG and available shipboard equipment. Epidemiology of sepsis in the deployed environment is also reviewed. This process also identifies opportunities to improve training, clinical skills sustainment, and standard shipboard medical supplies.

Association of Sociodemographic Factors With Overtriage, Undertriage, and Value of Care After Major Surgery.

Objective: To determine whether certain patients are vulnerable to errant triage decisions immediately after major surgery and whether there are unique sociodemographic phenotypes within overtriaged and undertriaged cohorts. Background: In a fair system, overtriage of low-acuity patients to intensive care units (ICUs) and undertriage of high-acuity patients to general wards would affect all sociodemographic subgroups equally. Methods: This multicenter, longitudinal cohort study of hospital admissions immediately after major surgery compared hospital mortality and value of care (risk-adjusted mortality/total costs) across 4 cohorts: overtriage (N = 660), risk-matched overtriage controls admitted to general wards (N = 3077), undertriage (N = 2335), and risk-matched undertriage controls admitted to ICUs (N = 4774). K-means clustering identified sociodemographic phenotypes within overtriage and undertriage cohorts. Results: Compared with controls, overtriaged admissions had a predominance of male patients (56.2% vs 43.1%, P < 0.001) and commercial insurance (6.4% vs 2.5%, P < 0.001); undertriaged admissions had a predominance of Black patients (28.4% vs 24.4%, P < 0.001) and greater socioeconomic deprivation. Overtriage was associated with increased total direct costs [$16.2K ($11.4K-$23.5K) vs $14.1K ($9.1K-$20.7K), P < 0.001] and low value of care; undertriage was associated with increased hospital mortality (1.5% vs 0.7%, P = 0.002) and hospice care (2.2% vs 0.6%, P < 0.001) and low value of care. Unique sociodemographic phenotypes within both overtriage and undertriage cohorts had similar outcomes and value of care, suggesting that triage decisions, rather than patient characteristics, drive outcomes and value of care. Conclusions: Postoperative triage decisions should ensure equality across sociodemographic groups by anchoring triage decisions to objective patient acuity assessments, circumventing cognitive shortcuts and mitigating bias.

Spatial molecular profiling of mixed invasive ductal-lobular breast cancers reveals heterogeneity in intrinsic molecular subtypes, oncogenic signatures, and mutations.

Mixed invasive ductal and lobular carcinoma (MDLC) is a rare histologic subtype of breast cancer displaying both E-cadherin positive ductal and E-cadherin negative lobular morphologies within the same tumor, posing challenges with regard to anticipated clinical management. It remains unclear whether these distinct morphologies also have distinct biology and risk of recurrence. Our spatially-resolved transcriptomic, genomic, and single-cell profiling revealed clinically significant differences between ductal and lobular tumor regions including distinct intrinsic subtype heterogeneity (e.g., MDLC with TNBC/basal ductal and ER+/luminal lobular regions), distinct enrichment of senescence/dormancy and oncogenic (ER and MYC) signatures, genetic and epigenetic CDH1 inactivation in lobular, but not ductal regions, and single-cell ductal and lobular sub-populations with unique oncogenic signatures further highlighting intra-regional heterogeneity. Altogether, we demonstrated that the intra-tumoral morphological/histological heterogeneity within MDLC is underpinned by intrinsic subtype and oncogenic heterogeneity which may result in prognostic uncertainty and therapeutic dilemma. Significance: MDLC displays both ductal and lobular tumor regions. Our multi-omic profiling approach revealed that these morphologically distinct tumor regions harbor distinct intrinsic subtypes and oncogenic features that may cause prognostic uncertainty and therapeutic dilemma. Thus histopathological/molecular profiling of individual tumor regions may guide clinical decision making and benefit patients with MDLC, particularly in the advanced setting where there is increased reliance on next generation sequencing.

High Rate of Concomitant Lumbo-Sacral Spine Pathology in the Setting of Hip Abductor Tendon Repair.

BACKGROUND: Hip abductor deficiency is a common cause of lateral hip pain in middle-aged patients. Identifying upstream muscle denervation originating in the lumbo-sacral spine could potentially impact the management of patients who have abductor deficiency. The purpose of this study was to estimate the prevalence of lumbo-sacral pathology (L4 to S1) in patients undergoing hip abductor tendon repair. METHODS: All cases of primary hip abductor repair performed at a tertiary care center between January 2010 and December 2021 were reviewed. Patients were classified into the following groups: A) confirmed L4 to S1 disease based on preoperative or perioperative L4 to S1 interventions (ie, surgery, epidural injections, and/or positive electromyography findings); B) radiographic evidence on lumbar spine magnetic resonance imaging demonstrating nerve compression at L4 to S1; and C) no evidence of L4 to S1 disease. RESULTS: There were 131 cases of primary hip abductor repair that were included. Over 80% of patients were women, who had a mean age of 64 years (range, 20 to 85). There were thirteen patients (9.9%) who underwent concomitant total hip arthroplasty (THA). Of the included patients, 29% (n = 38) were categorized into group A, 12% (n = 16) into group B, and 59% (n = 77) into group C. Patients who had L4 to S1 pathology were older than patients who did not have L4 to S1 pathology (67 versus 61 years, P = .004). Of the patients undergoing concomitant THA and hip abductor repair, 54% demonstrated evidence of lumbo-sacral spine pathology. CONCLUSIONS: Over 40% of patients undergoing isolated hip abductor tendon repair and >50% of patients undergoing concomitant hip abductor tendon repair and THA demonstrated evidence of L4 to S1 disease perioperatively. Patients demonstrating symptomatic hip abductor deficiency should be screened for concomitant lower lumbo-sacral spine pathology.

Patients Undergoing Reverse Total Shoulder Arthroplasty Have Less Pain and Require Fewer Opioid Pain Medications Compared to Anatomic Total Shoulder Arthroplasty in the Early Postoperative Period: A Retrospective Review.

BACKGROUND: Recovery after anatomic total shoulder arthroplasty (aTSA) and reverse total shoulder arthroplasty (rTSA) has many similarities; however, recently surgeons have suggested patients undergoing rTSA have a less difficult postoperative course with less pain compared with aTSA patients. Given the heightened awareness to postoperative pain control and opioid consumption, as well as the expanding indications for rTSA, we sought to determine the differences in pain and opioid consumption between aTSA and rTSA patients in a 12-week postoperative period. METHODS: A retrospective chart review was performed to identify all patients who underwent a primary aTSA or rTSA from January 2013 to April 2018 at a single institution. Patients with recorded visual analog scale (VAS) and American Shoulder and Elbow Surgeons (ASES) scores were included for analysis. Revision arthroplasties were excluded. VAS scores were recorded preoperatively and at standard 2-week, 6-week, and 12-week postoperative time points. P-values < 0.05 were considered statistically significant, except where Bonferroni corrections were applied. RESULTS: A total of 690 patients underwent TSA (278 aTSA, 412 rTSA). Preoperatively, aTSA and rTSA patient groups had similar VAS scores (6 vs 6, P = 0.38). Postoperatively, the aTSA group had a higher VAS at the 6-week visit, compared with rTSA patients (2.8 vs 2.2, P = 0.003). aTSA patients remained on opioids at a higher rate at the 2-week (62.4% vs 45.6%, P = < 0.001) time period. aTSA patients needed more opioid prescription refills before the 2-week (61.7% vs 45.5%, P = <0.001) and 6-week (40.4% vs 30.7%, P = 0.01) follow-up visits. CONCLUSIONS: Despite similar preoperative VAS and rates of preoperative opioid use, aTSA patients required more opioid medication refills and remained on opioids for a longer duration in the early postoperative period to achieve similar postoperative pain control as indicated by similar VAS. This study suggests that the recovery from rTSA is less difficult compared with aTSA as indicated by VAS and opioid consumption.

otb: an Automated HiC/HiFi Pipeline Assembles the Prosapia bicincta Genome.

The implementation of a new genomic assembly pipeline named only the best (otb) has effectively addressed various challenges associated with data management during the development and storage of genome assemblies. otb, which incorporates a comprehensive pipeline involving a setup layer, quality checks, templating, and the integration of Nextflow and Singularity. The primary objective of otb is to streamline the process of creating a HiFi/HiC genome, aiming to minimize the manual intervention required in the genome assembly process. The Two-lined spittlebug, (Prosapia bicincta, Hemiptera: Cercopidae), a true bug insect herbivore, serves as a practical test case for evaluating otb. The two-lined spittlebug is both a crucial agricultural pest and a genomically understudied insect belonging to the order Hemiptera. This insect is a significant threat to grasslands and pastures, leading to plant wilting and phytotoxemia when infested. Its presence in tropical and subtropical regions around the world poses a long-term threat to the composition of plant communities in grassland landscapes, impacting rangelands, and posing a substantial risk to cattle production.

Association of COVID-19 Vaccination With Changes in Smell and Taste.

Since the introduction of vaccines for severe acute respiratory syndrome coronavirus 2 in the United States, there has been significant vaccine hesitancy, in part due to fear of adverse effects. We sought to investigate the rates of smell and taste changes after COVID-19 vaccination compared to other common vaccines. Our study cohort included individuals identified by Current Procedural Terminology code in the TriNetX database receiving the COVID-19 first series, COVID-19 booster, influenza, tetanus, diphtheria, pertussis (TDAP), or pneumococcal vaccines between December 15, 2020, and August 15, 2023. After 1:1 propensity score matching, postvaccination incidence of disturbance of smell and taste was significantly less likely after COVID-19 first series vaccine compared to influenza (odds ratios, OR: 0.27 [95% confidence interval, CI: 0.20-0.36]), TDAP (OR: 0.35 [95% CI: 0.26-0.47]), and pneumococcal vaccines (OR: 0.17 [95% CI: 0.09-0.32]). Similarly, incidence of disturbance of smell and taste was significantly less likely after COVID-19 booster vaccine compared to the influenza (OR: 0.60 [95% CI: 0.48-0.76]), TDAP (OR: 0.63 [95% CI: 0.47-0.85]), and pneumococcal vaccines (OR: 0.44 [95% CI: 0.28-0.68]). This study builds upon the literature demonstrating the safety of COVID-19 vaccination.

Association between PM2.5 from a coal mine fire and FeNO concentration 7.5 years later.

BACKGROUND AND AIM: There are few long-term studies of respiratory health effects of landscape fires, despite increasing frequency and intensity due to climate change. We investigated the association between exposure to coal mine fire PM2.5 and fractional exhaled nitric oxide (FeNO) concentration 7.5 years later. METHODS: Adult residents of Morwell, who were exposed to the 2014 Hazelwood mine fire over 6 weeks, and unexposed residents of Sale, participated in the Hazelwood Health Study Respiratory Stream in 2021, including measurements of FeNO concentration, a marker of eosinophilic airway inflammation. Individual exposure to coal mine fire PM2.5 was modelled and mapped to time-location diaries. The effect of exposure to PM2.5 on log-transformed FeNO in exhaled breath was investigated using multivariate linear regression models in the entire sample and stratified by potentially vulnerable subgroups. RESULTS: A total of 326 adults (mean age: 57 years) had FeNO measured. The median FeNO level (interquartile range [IQR]) was 17.5 [15.0] ppb, and individual daily exposure to coal mine fire PM2.5 was 7.2 [13.8] µg/m3. We did not identify evidence of association between coal mine fire PM2.5 exposure and FeNO in the general adult sample, nor in various potentially vulnerable subgroups. The point estimates were consistently close to zero in the total sample and subgroups. CONCLUSION: Despite previous short-term impacts on FeNO and respiratory health outcomes in the medium term, we found no evidence that PM2.5 from the Hazelwood coal mine fire was associated with any long-term impact on eosinophilic airway inflammation measured by FeNO levels.

The name's bond. parasocial bond: imagined interactions and state-level empathy.

Empathy, whether state or trait, is an individual's ability to adopt another's perspective, feel another's feelings, or identify with another's situation (Campbell & Babrow, 2004; Davis, 1983; Nezlek etal., 2007). Research reliably shows relationships between empathy and parasocial interactions (e.g. psychological engagements with fictional characters; Giles, 2002; Tsao, 1996; Zillmann, 1994). The current study sought to identify the relationship between the type of parasocial interactions and subsequent changes in state-level empathy via an experimental design. Results indicate state-level empathy changes are contingent upon valence (i.e. Favorite vs. Least Favorite) and status (i.e. Real vs. Parasocial) of the imagined interaction.

Androgen Deprivation Therapy and Outcomes After Radiation Therapy in Black Patients With Prostate Cancer.

Importance: Prostate cancer in Black men compared with White men may be more sensitive to radiation therapy resulting in better outcomes in equal-access settings. The outcomes of androgen-deprivation therapy (ADT) vs radiation therapy itself remains uncharacterized. Objectives: To quantify any outcome modification by receipt of ADT on the association between Black race and prostate cancer outcomes following radiation therapy. Design, Setting, and Participants: This was a retrospective, nationwide cohort study of Black and White patients treated in the US Veterans Healthcare system between 2000 and 2020 receiving definitive radiation for localized prostate cancer. Data were analyzed from January 2000 to December 2020. Exposure: Patient self-identified race and use of ADT defined as any gonadotrophin-releasing hormone agonist or antagonist prescription within 6 months of radiation. Main Outcomes and Measures: Biochemical recurrence (BCR) from time of completion of radiation therapy (prostate-specific antigen nadir plus 2 ng/mL) and development of metastatic disease or prostate cancer mortality (PCSM) from time of recurrence. Results: A total of 26 542 patients (8716 Black men with median [IQR] age of 64 [59-69] years and 17 826 White men with median [IQR] age of 67 [62-72] years) received definitive radiation therapy for nonmetastatic prostate cancer and had complete staging and follow-up data. A total of 5144 patients experienced BCR (3384 White and 1760 Black patients). The cumulative incidence of BCR at 10 years was not significantly different between Black and White men (1602 [22.14%] vs 3099 [20.13%], respectively) with multivariable hazard ratio (HR) of 1.03 (95% CI, 0.97-1.09; P = .33). In men receiving ADT, Black men had an HR for BCR of 0.90 (95% CI, 0.82-0.99; P = .03) compared with White men, and in men not receiving ADT, Black men had an HR of 1.13 (95% CI, 1.05-1.22; P = .002). Black race was associated with a decreased risk of developing metastatic disease (HR, 0.90; 95% CI, 0.82-0.98; P = .02) or PCSM (subdistribution HR, 0.72; 95% CI, 0.63-0.82; P < .001) from time of biochemical recurrence. Conclusions and Relevance: Black patients treated with radiation appear to specifically benefit from the addition of ADT with regard to biochemical control. Additionally, BCR in Black men results in a lower rate of metastatic disease and death from prostate cancer. Future analyses of radiosensitivity in Black men should evaluate for the possibility of outcome modification by ADT.

Effect of traditional roughage-based or limit-fed, high-energy diets on growth performance and digestion in newly received growing cattle and subsequent implications on feedlot growth performance and carcass characteristics.

The objective was to determine the effects of ad libitum-fed roughage-based diets or limit-fed high-energy diets on growth performance, behavior, health, and digestion in newly received growing cattle and subsequent implications on feedlot growth performance and carcass characteristics. In experiment 1, 409 crossbred heifers (initial body weight [BW] = 279 ±â€…24 kg) in 32 pens were used in a randomized block design. Heifers were fed one of two dietary treatments: a total mixed ration with 0.99 Mcal net energy for gain (NEg)/kg dry matter (DM) fed ad libitum (0.99AL) or 1.32 Mcal NEg/kg DM limit-fed at 85% of intake of heifers fed 0.99AL (1.32LF85%). Both diets contained 40% DM as a branded wet corn gluten feed. In experiment 2, 370 crossbred heifers (initial BW = 225 ±â€…20 kg) were used in a randomized block design and were fed a diet formulated to contain 0.99 Mcal of NEg/kg DM for ad libitum intake or a diet formulated to contain 1.32 Mcal of NEg/kg DM and fed at 2.2% of BW daily (DM basis; 1.32LF2.2). For experiments 1 and 2, treatment integrity was maintained through the finishing phase where cattle were fed a common diet. Cattle were sorted by BW into heavy and light groups prior to finishing, with light cattle fed longer than heavy cattle to reach similar harvest BW. In experiment 3, eight ruminally cannulated heifers (average BW = 305 ±â€…23 kg) were used in a 2-period cross-over design and fed treatments from experiment 1 to assess digestibility and ruminal fermentation characteristics. Gain:feed was 47% and 35% greater (P < 0.01) in experiments 1 and 2, respectively, for limit-fed heifers compared with 0.99AL heifers. Rumination time was greater (P < 0.01) for 0.99AL compared with limit-fed treatments in experiments 1 and 2. Activity was greater (P < 0.01) for 1.32LF2.2 than for 0.99AL in experiment 2. In experiment 1, more (P = 0.03) carcasses from light-sort heifers than carcasses from heavy-sort heifers had livers with large, active abscesses. In experiment 2, finishing phase morbidity was greater (P < 0.01) for 1.32LF2.2 than for 0.99AL. Light-sort groups had fewer (P < 0.01) edible livers than heavy-sort groups, suggesting that greater number of days on feed may increase the risk of liver abscess prevalence and condemnation. In experiment 3, apparent total-tract DM and organic matter digestibilities were greater (P < 0.01) for 1.32LF85% than for 0.99AL. Overall, dietary treatments during the growing phase had little carryover effect on feedlot growth performance, carcass characteristics, or liver abscesses prevalence at harvest.

Quadriceps Tendon Anterior Cruciate Ligament Reconstruction in Skeletally Immature Patients: 3-Year Clinical and Patient-Reported Outcomes.

BACKGROUND: The rate of anterior cruciate ligament (ACL) rupture in active, skeletally immature patients is increasing. Although hamstring tendon autograft (HTA) was previously deemed the gold standard, recent studies have shown HTA to have a high failure rate in this high-risk population of young competitive athletes, and quadriceps tendon autograft (QTA) has yielded excellent preliminary outcomes in some studies examining this population. PURPOSE: To evaluate 3-year clinical and patient-reported functional outcomes of primary ACL reconstruction (ACLR) with soft tissue QTA in skeletally immature patients. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Skeletally immature patients who underwent ACLR with a full-thickness soft tissue QTA were included. Preoperative patient and surgical data were collected. The ACLR technique was selected predicated upon skeletal age and included all-epiphyseal and complete transphyseal techniques. Patients were followed for a minimum of 2 years with successive clinical visits or were contacted via telephone. Patients who did not have minimum 2-year follow-up after 3 contact attempts via telephone were excluded. Information regarding return to sports (RTS) and concomitant or subsequent surgical procedures was collected. Pediatric International Knee Documentation Committee (Pedi-IKDC), Hospital for Special Surgery Functional Activity Brief Scale (HSS Pedi-FABS), and Single Assessment Numeric Evaluation (SANE) scores were collected. RESULTS: Of 85 adolescent patients aged 11.1 to 17.6 years (mean age, 14.1 ± 1.2 years), 2 patients were determined to be lost to follow-up after 3 failed contact attempts. Of the patients included in this study (N = 83), 26 patients (31%) underwent all-epiphyseal and 57 patients (69%) underwent complete transphyseal ACLR. Additionally, 48 patients (58%) underwent concomitant lateral extra-articular tenodesis using the iliotibial band with a modified Lemaire technique. The mean follow-up time was 3.7 ± 1.2 years (range, 2-7 years). Twenty (24%) patients had subsequent surgical procedures, of which 3 (4%) were due to graft failures. At a mean 3-year follow-up, the mean Pedi-IKDC, HSS Pedi-FABS, and SANE scores were 90, 23, and 94 respectively; the RTS rate was 100%; and the rate of RTS at the previous level of performance was 93%. CONCLUSION: Use of a soft tissue QTA for ALCR in a high-risk skeletally immature population of athletes resulted in excellent postoperative outcomes with low rates of graft failure and high return to sport rates.

Diffuse microglial responses and persistent EEG changes correlate with poor neurological outcome in a model of subarachnoid hemorrhage.

The mechanism by which subarachnoid hemorrhage (SAH) leads to chronic neurologic deficits is unclear. One possibility is that blood activates microglia to drive inflammation that leads to synaptic loss and impaired brain function. Using the endovascular perforation model of SAH in rats, we investigated short-term effects on microglia together with long-term effects on EEG and neurologic function for up to 3 months. Within the first week, microglia were increased both at the site of injury and diffusely across the cortex (2.5-fold increase in SAH compared to controls, p = 0.012). Concomitantly, EEGs from SAH animals showed focal increases in slow wave activity and diffuse reduction in fast activity. When expressed as a fast-slow spectral ratio, there were significant interactions between group and time (p < 0.001) with less ipsilateral recovery over time. EEG changes were most pronounced during the first week and correlated with neurobehavioral impairment. In vitro, the blood product hemin was sufficient to increase microglia phagocytosis nearly six-fold (p = 0.032). Immunomodulatory treatment with fingolimod after SAH reduced microglia, improved neurological function, and increased survival. These findings, which parallel many of the EEG changes seen in patients, suggest that targeting neuroinflammation could reduce long-term neurologic dysfunction following SAH.

Risk Factors for Atraumatic Medial Patellar Facet Lesions.

Background: Medial patellar facet lesions have been well-described in the setting of patellar instability. However, relatively little is known about risk factors for atraumatic medial patellar facet lesions. Purpose/Hypothesis: To identify clinical and radiographic risk factors for medial patellar facet lesions in patients without a history of trauma or patellar instability. It was hypothesized that a posterior tibial tubercle relative to the trochlear groove would be a risk factor for atraumatic medial patellar facet lesions. Study Design: Case-control study; Level of evidence, 3. Methods: A total of 37 patients with atraumatic medial patellar facet lesions were matched by age, sex, and body mass index with 37 control patients without a history of patellofemoral dysplasia. Demographic and imaging characteristics were compared between groups. Plain radiography was used to evaluate Wiberg type, and magnetic resonance imaging was used to calculate Caton-Deschamps index, tibial tubercle-trochlear groove distance, trochlear facet asymmetry ratio, patellotrochlear index, sulcus depth, patellar bisect ratio, and tibial tubercle height. Statistically significant variables from univariate analysis were used as inputs to the multivariate regression model to assess independent risk factors. Results: There were no differences between groups with respect to Wiberg type, Caton-Deschamps index, tibial tubercle-trochlear groove distance, sulcus depth, or patellotrochlear index (P > .05 for all). The medial facet lesion group had a larger medial trochlear facet (trochlear facet asymmetry ratio, 0.72 ± 0.11 vs 0.60 ± 0.09; P < .001), a more medial-lying patella in the trochlear groove (patellar bisect ratio, 0.57 ± 0.06 vs 0.55 ± 0.07; P = .035), and a more posterior tibial tubercle relative to the trochlear groove (tibial tubercle height, -3.13 ± 5.21 vs -0.23 ± 5.93 mm; P = .030) compared with the control group. Multivariate regression analysis identified trochlear facet asymmetry and tibial tubercle height as independent risk factors for medial patellar facet lesions (relative risk = 97.3 [95% CI, 14.9-635.1], P < .001 and relative risk = 0.95 [95% CI, 0.92-0.98], P = .004, respectively). Conclusion: A relatively larger medial trochlear facet and a more posterior tibial tubercle relative to the trochlear groove were found to be risk factors for medial patellar facet lesions in patients without a history of trauma or patellar instability.