Evaluation of a push-and-pull strategy using volatiles of host and non-host plants for the management of pear psyllids in organic farming.

Introduction: Pear decline (PD) is one of the most devastating diseases of Pyrus communis in Europe and North America. It is caused by the pathogen 'Candidatus Phytoplasma pyri' and transmitted by pear psyllids (Cacopsylla pyri, C. pyricola, and C. pyrisuga). Identifying attractant and repellent volatile organic compounds (VOCs) could improve the development of alternative plant protection measurements like push-pull or attract-and-kill strategies against pear psyllids. Our objective was to investigate which chemical cues of the host plant could influence the host-seeking behavior of pear psyllids, and if cedarwood (CWO) and cinnamon bark (CBO) essential oils could serve as repellents. Results and discussion: Based on the literature, the five most abundant VOCs from pear plants elicited EAG responses in both C. pyri and C. pyrisuga psyllid species. In Y-olfactometer trials, single compounds were not attractive to C. pyri. However, the main compound mixture was attractive to C. pyri and C. pyrisuga females. CWO and CBO were repellent against C. pyri, and when formulated into nanofibers (NF), both were repellent in olfactometer trials. However, CBO nanoformulation was ineffective in masking the odors of pear plants. In a field trial, attractive, repellent CWO and blank formulated NF were inserted in attractive green sticky traps. C. pyri captures in traps with CWO NF were statistically lower than in traps with the attractive mixture. Nevertheless, no statistical differences in the numbers of caught specimens were observed between CWO NF and those captured in green traps baited with blank NF. Transparent traps captured fewer psyllids than green ones. In a second field study with a completed different design (push-and-count design), dispensers filled with CBO were distributed within the plantation, and attractive green sticky traps were placed around the plantation. The numbers of trapped pear psyllids increased significantly in the border of the treated plantation, showing that psyllids were repelled by the EOs in the plantation. Although further field evaluation is needed to assess and improve their effectiveness, our results show that these aromatic compounds, repellent or attractive both in nanoformulations and marking pen dispensers, offer great potential as an environmentally sustainable alternative to currently applied methods for managing pear decline vectors.

ALYREF/THOC4 expression and cell growth modulation in retinoblastoma.

In this study, we tested the hypothesis that ALYREF/THOC4, a poor prognostic factor in different cancer types, has potential as a drug target and prognostic biomarker for retinoblastoma (RB). Immunostaining (IHC), Western blot, and RT-qPCR analyses detected overexpression of ALYREF in the RB cell lines Y79, RB143, WERI-RB1, and RB116. IHC analysis on RB tumor array showed that 11/14 of RB tumors were ALYREF+ to varying degrees, with eight tumors at maximum 3+ intensity. The IHC analysis also detected ALYREF+ cells in normal retina, mainly in the inner nuclear and ganglion cell layer, while some tumor-bearing human eyes were ALYREF+ in the optic nerve suggesting a role in optic invasion/tumor invasion. The expression of ALYREF within the tumor itself, in the optic nerve, as well as in adjacent "normal" retina, suggest that this pattern of expression may lead to ALYREF being a potentially useful prognostic indicator for RB, as it is for other tumors. siRNA knockdown of ALYREF resulted in a 40 % decrease in cell growth in both WERI-RB1 and Y79 cells (p<0.05) and this was associated with decreased expression of mRNAs for the cell proliferation markers Ki67 and PCNA (p<0.005). These results suggest a role for ALYREF in RB cell growth regulation and its potential as both a target and a biomarker for tumor growth inhibition by anti-cancer therapies.

Prediction of mortality among severely injured trauma patients A comparison between TRISS and machine learning-based predictive models.

BACKGROUND: Given the huge impact of trauma on hospital systems around the world, several attempts have been made to develop predictive models for the outcomes of trauma victims. The most used, and in many studies most accurate predictive model, is the "Trauma Score and Injury Severity Score" (TRISS). Although it has proven to be fairly accurate and is widely used, it has faced criticism for its inability to classify more complex cases. In this study, we aimed to develop machine learning models that better than TRISS could predict mortality among severely injured trauma patients, something that has not been studied using data from a nationwide register before. METHODS: Patient data was collected from the national trauma register in Sweden, SweTrau. The studied period was from the 1st of January 2015 to 31st of December 2019. After feature selection and multiple imputation of missing data three machine learning (ML) methods (Random Forest, eXtreme Gradient Boosting, and a Generalized Linear Model) were used to create predictive models. The ML models and TRISS were then tested on predictive ability for 30-day mortality. RESULTS: The ML models were well-calibrated and outperformed TRISS in all the tested measurements. Among the ML models, the eXtreme Gradient Boosting model performed best with an AUC of 0.91 (0.88-0.93). CONCLUSION: This study showed that all the developed ML-based prediction models were superior to TRISS for the prediction of trauma mortality.

Magnetically Steered Cell Therapy For Functional Restoration Of Intraocular Pressure Control In Open-Angle Glaucoma.

Trabecular meshwork (TM) cell therapy has been proposed as a next-generation treatment for elevated intraocular pressure (IOP) in glaucoma, the most common cause of irreversible blindness. Using a magnetic cell steering technique with excellent efficiency and tissue-specific targeting, we delivered two types of cells into a mouse model of glaucoma: either human adipose-derived mesenchymal stem cells (hAMSCs) or induced pluripotent cell derivatives (iPSC-TM cells). We observed a 4.5 [3.1, 6.0] mmHg or 27% reduction in intraocular pressure (IOP) for nine months after a single dose of only 1500 magnetically-steered hAMSCs, associated with restoration of function to the conventional outflow pathway, as judged by increased outflow facility and TM cellularity. iPSC-TM cells were also effective, but less so, showing only a 1.9 [0.4, 3.3] mmHg or 13% IOP reduction and increased risk of tumorigenicity. In both cases, injected cells remained detectable in the iridocorneal angle three weeks post-transplantation. Based on the locations of the delivered cells, the mechanism of IOP lowering is most likely paracrine signaling. We conclude that magnetically-steered hAMSC cell therapy has potential for long-term treatment of ocular hypertension in glaucoma. One Sentence Summary: A novel magnetic cell therapy provided effective intraocular pressure control in a mouse model of glaucoma, motivating future translational studies.

Retinoblastoma with MYCN Amplification Diagnosed from Cell-Free DNA in the Aqueous Humor.

Introduction: The objective of this study was to report the clinicopathologic features of three cases of MYCN-amplified retinoblastoma identified genetically by aqueous humor sampling. Methods: Whole-genome sequencing was performed using isolated cell-free DNA (cfDNA) from aqueous humor of 3 retinoblastoma patients. We analyzed genomic copy number and mutational alterations, histologic and pathologic features, and clinical data. Results: The most common genetic alteration identified in these three retinoblastoma cases was a focal MYCN amplification on 2p. All tumors showed an early age of diagnosis with a median of 9 months. The tumor histopathologic features included neovascularization and subretinal seeding in case 1, diffuse nature with choroidal and prelaminar optic nerve invasion in case 2, and complete vitreous seeding in case 3. Case 1 expressed RB protein and had no RB1 mutation, case 2 did not express RB protein and had an RB1 mutation, and case 3 did not express RB protein and likely had an epigenetic effect on RB expression. Conclusions: Our report shows 3 cases of unilateral retinoblastomas diagnosed in patients ranging from 4 months to 18 months old. Genomic analysis from AH cfDNA revealed MYCN amplification with intact RB protein staining in case 1 and lack of RB staining in cases 2 and 3. RB1 mutational analysis in the AH confirmed a pathogenic variant in case 2. Clinical pathology showed features requiring aggressive treatment, specifically enucleation. Importance: MYCN-amplified retinoblastomas demonstrate unique pathogenesis and aggressive behavior, regardless if MYCN is a primary or secondary driver of disease. Genomic analysis from aqueous humor may be useful when deciding to enucleate as opposed to treating conservatively. Focal MYCN amplification on 2p might be relevant for tumor growth in this subset of the retinoblastoma population in terms of targeted therapeutics.

Liver-targeted polymeric prodrugs delivered subcutaneously improve tafenoquine therapeutic window for malaria radical cure.

Approximately 3.3 billion people live with the threat of Plasmodium vivax malaria. Infection can result in liver-localized hypnozoites, which when reactivated cause relapsing malaria. This work demonstrates that an enzyme-cleavable polymeric prodrug of tafenoquine addresses key requirements for a mass administration, eradication campaign: excellent subcutaneous bioavailability, complete parasite control after a single dose, improved therapeutic window compared to the parent oral drug, and low cost of goods sold (COGS) at less than $1.50 per dose. Liver targeting and subcutaneous dosing resulted in improved liver:plasma exposure profiles, with increased efficacy and reduced glucose 6-phosphate dehydrogenase-dependent hemotoxicity in validated preclinical models. A COGS and manufacturability analysis demonstrated global scalability, affordability, and the ability to redesign this fully synthetic polymeric prodrug specifically to increase global equity and access. Together, this polymer prodrug platform is a candidate for evaluation in human patients and shows potential for P. vivax eradication campaigns.

Reducing radiation exposure and costs: CT body scout views with an enhanced protocol versus conventional radiography after shunt surgery.

OBJECTIVE: Ventriculoperitoneal shunt implantation has become standard treatment for cerebrospinal fluid diversion, besides endoscopic third ventriculostomy for certain indications. Postoperative X-ray radiography series of skull, chest and abdomen combined with cranial CT are obtained routinely in many institutions to document the shunt position and valve settings in adult patients. Measures to reduce postoperative radiation exposure are needed, however, there is only limited experience with such efforts. Here, we aim to compare routine postoperative cranial CT plus conventional radiography series (retrospective arm) with cranial CT and body scout views only (prospective arm) concerning both diagnostic quality and radiation exposure. PATIENTS AND METHODS: After introduction of an enhanced CT imaging protocol, routine skull and abdomen radiography was no longer obtained after VP shunt surgery. The image studies of 25 patients with routine postoperative cranial CT and conventional radiography (retrospective arm of study) were then compared to 25 patients with postoperative cranial CT and CT body scout views (prospective arm of study). Patient demographics such as age, sex and primary diagnosis were collected. The image quality of conventional radiographic images and computed tomography scout views images were independently analyzed by one neurosurgeon and one neuroradiologist. RESULTS: There were no differences in quality assessments according to three different factors determined by two independent investigators for both groups. There was a statistically significant difference, however, between the conventional radiography series group and the CT body scout view imaging group with regard to radiation exposure. The effective dose estimation calculation yielded a difference of 0.05 mSv (two-tailed t-test, p = 0.044) in favor of CT body scout view imaging. Furthermore, the new enhanced protocol resulted in a reduction of cost and the use of human resources. CONCLUSION: CT body scout view imaging provides sufficient imaging quality to determine shunt positioning and valve settings. With regard to radiation exposure and costs, we suggest that conventional postoperative shunt series may be abandoned.

Ground penetrating radar observations of the contact between the western delta and the crater floor of Jezero crater, Mars.

The delta deposits in Jezero crater contain sedimentary records of potentially habitable conditions on Mars. NASA's Perseverance rover is exploring the Jezero western delta with a suite of instruments that include the RIMFAX ground penetrating radar, which provides continuous subsurface images that probe up to 20 meters below the rover. As Perseverance traversed across the contact between the Jezero crater floor and the delta, RIMFAX detected a distinct discontinuity in the subsurface layer structure. Below the contact boundary are older crater floor units exhibiting discontinuous inclined layering. Above the contact boundary are younger basal delta units exhibiting regular horizontal layering. At one location, there is a clear unconformity between the crater floor and delta layers, which implies that the crater floor experienced a period of erosion before the deposition of the overlying delta strata. The regularity and horizontality of the basal delta sediments observed in the radar cross sections indicate that they were deposited in a low-energy lake environment.

Design, synthesis and validation of a new Crimped Head-Piece for DNA-Encoded libraries generation.

Codification of DNA Encoded Libraries (DELs) is critical for successful ligand identification of molecules that bind a protein of interest (POI). There are different encoding strategies that permit, for instance, the customization of a DEL for testing single or dual pharmacophores (single strand DNA) or for producing and screening large diversity libraries of small molecules (double strand DNA). Both approaches challenges, either from the synthetic and encoding point of view, or from the selection methodology to be utilized for the screening. The Head-Piece contains the DNA sequence that is attached to a chemical compound, allowing the encoding of each molecule with a unique DNA tag. Designing the Head-Piece for a DNA-encoded library involves careful consideration of several key aspects including DNA barcode identity, sequence length and attachment chemistry. Here we describe a double stranded DNA versatile Head-Piece that can be used for the generation of single or dual pharmacophore libraries, but also shows other advanced DEL functionalities, stability and enlarged encoding capacity.

Subthalamic Nucleus Deep Brain Stimulation Restores Motor and Sensorimotor Cortical Neuronal Oscillatory Activity in the Free-Moving 6-Hydroxydopamine Lesion Rat Parkinson Model.

OBJECTIVES: Enhanced beta oscillations in cortical-basal ganglia (BG) thalamic circuitries have been linked to clinical symptoms of Parkinson's disease. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces beta band activity in BG regions, whereas little is known about activity in cortical regions. In this study, we investigated the effect of STN DBS on the spectral power of oscillatory activity in the motor cortex (MCtx) and sensorimotor cortex (SMCtx) by recording via an electrocorticogram (ECoG) array in free-moving 6-hydroxydopamine (6-OHDA) lesioned rats and sham-lesioned controls. MATERIALS AND METHODS: Male Sprague-Dawley rats (250-350 g) were injected either with 6-OHDA or with saline in the right medial forebrain bundle, under general anesthesia. A stimulation electrode was then implanted in the ipsilateral STN, and an ECoG array was placed subdurally above the MCtx and SMCtx areas. Six days after the second surgery, the free-moving rats were individually recorded in three conditions: 1) basal activity, 2) during STN DBS, and 3) directly after STN DBS. RESULTS: In 6-OHDA-lesioned rats (N = 8), the relative power of theta band activity was reduced, whereas activity of broad-range beta band (12-30 Hz) along with two different subbeta bands, that is, low (12-30 Hz) and high (20-30 Hz) beta band and gamma band, was higher in MCtx and SMCtx than in sham-lesioned controls (N = 7). This was, to some extent, reverted toward control level by STN DBS during and after stimulation. No major differences were found between contacts of the electrode grid or between MCtx and SMCtx. CONCLUSION: Loss of nigrostriatal dopamine leads to abnormal oscillatory activity in both MCtx and SMCtx, which is compensated by STN stimulation, suggesting that parkinsonism-related oscillations in the cortex and BG are linked through their anatomic connections.

Unusual conjunctival melanocytic proliferations. Report of five cases and review of the literature.

Indeterminate melanocytic proliferations of the conjunctiva have both benign and malignant features that previously made these lesions nearly impossible to categorize in existing classification schemes. With the evolution of immunohistochemistry and molecular genetics, however, subclassifications have emerged that allow for a more tailored diagnosis and management. These conjunctival melanocytic proliferations include deep penetrating nevus, granular cell nevus, and nevoid melanoma. There remains a small subset of conjunctival melanocytic proliferations that defy precise characterization as nevi, primary acquired melanosis, or melanomas despite currently available ancillary diagnostic modalities and remain indeterminate. We highlight these unusual types of nevi and melanomas, with an update on their morphologic, immunohistochemical, and molecular genetic characteristics.

Does Temporary Externalization of Electrodes After Deep Brain Stimulation Surgery Result in a Higher Risk of Infection?

OBJECTIVES: Deep brain stimulation (DBS) is a well-established surgical therapy for movement disorders that comprises implantation of stimulation electrodes and a pacemaker. These procedures can be performed separately, leaving the possibility of externalizing the electrodes for local field potential recording or testing multiple targets for therapeutic efficacy. It is still debated whether the temporary externalization of DBS electrodes leads to an increased risk of infection. We therefore aimed to assess the risk of infection during and after lead externalization in DBS surgery. MATERIALS AND METHODS: In this retrospective study, we analyzed a consecutive series of 624 DBS surgeries, including 266 instances with temporary externalization of DBS electrodes for a mean of 6.1 days. Patients were available for follow-up of at least one year, except in 15 instances. In 14 patients with negative test stimulation, electrodes were removed. All kinds of infections related to implantation of the neurostimulation system were accounted for. RESULTS: Overall, infections occurred in 22 of 624 surgeries (3.5%). Without externalization of electrodes, infections were noted after 7 of 358 surgeries (2.0%), whereas with externalization, 15 of 252 infections were found (6.0%). This difference was significant (p = 0.01), but it did not reach statistical significance when comparing groups within different diagnoses. The rate of infection with externalized electrodes was highest in psychiatric disorders (9.1%), followed by Parkinson's disease (7.3%), pain (5.7%), and dystonia (5.5%). The duration of the externalization of the DBS electrodes was comparable in patients who developed an infection (6.1 ± 3.1 days) with duration in those who did not (6.0 ± 3.5 days). CONCLUSIONS: Although infection rates were relatively low in our study, there was a slightly higher infection rate when DBS electrodes were externalized. On the basis of our results, the indication for electrode externalization should be carefully considered, and patients should be informed about the possibility of a higher infection risk when externalization of DBS electrodes is planned.

Microsurgical posterior fossa re-exploration for recurrent trigeminal neuralgia after previous microvascular decompression: common grounds-scarring, deformation, and the "piston effect".

OBJECTIVE: Microvascular decompression (MVD) is a well-accepted treatment modality for trigeminal neuralgia (TN) with high initial success rates. The causes for recurrence of TN after previously successful MVD have not been fully clarified, and its treatment is still a matter of debate. Here, we present the surgical findings and the clinical outcome of patients with recurrent TN after MVD who underwent posterior fossa re-exploration. METHODS: Microsurgical posterior fossa re-exploration was performed in 26 patients with recurrent TN (mean age 59.1 years) who underwent MVD over a period of 10 years. The trigeminal nerve was exposed, and possible factors for recurrent TN were identified. Arachnoid scars and Teflon granulomas were dissected meticulously without manipulating the trigeminal nerve. Outcome of posterior fossa re-exploration was graded according to the Barrow Neurological Institute (BNI) pain intensity score. Follow-up was analyzed postoperatively at 3, 12, and 24 months and at the latest available time point for long-term outcome. RESULTS: The mean duration of recurrent TN after the first MVD was 20 months. Pain relief was achieved in all patients with recurrent TN on the first postoperative day. Intraoperative findings were as follows: arachnoid scar tissue in 22/26 (84.6%) patients, arterial compression in 1/26 (3.8%), venous contact in 8/26 (30.8%), Teflon granuloma in 14/26 (53.8%), compression by an electrode in Meckel's cave used for treatment of neuropathic pain in 1/26 (3.8%), evidence of pulsations transmitted to the trigeminal nerve through the Teflon inserted previously/scar tissue ("piston effect") in 15/26 (57.7%), and combination of findings in 18/26 (69.2%). At long-term follow-up (mean 79.5 months; range, 29-184 months), 21/26 (80.8%) patients had favorable outcome (BNI I-IIIa). New hypaesthesia secondary to microsurgical posterior fossa re-exploration occurred in 5/26 (19.2%) patients. CONCLUSIONS: Posterior fossa re-exploration avoiding manipulation to the trigeminal nerve, such as pinching or combing, may be a useful treatment option for recurrent TN after previously successful MVD providing pain relief in the majority of patients with a low rate of new hypaesthesia.

Long non-coding RNA APDC plays important regulatory roles in metabolism of bone and adipose tissues.

The long noncoding RNA (lncR) ANRIL in the human genome is an established genetic risk factor for atherosclerosis, periodontitis, diabetes, and cancer. However, the regulatory role of lncR-ANRIL in bone and adipose tissue metabolism remains unclear. To elucidate the function of lncRNA ANRIL in a mouse model, we investigated its ortholog, AK148321 (referred to as lncR-APDC), located on chr4 of the mouse genome, which is hypothesized to have similar biological functions to ANRIL. We initially revealed that lncR-APDC in mouse bone marrow cells (BMSCs) and lncR-ANRIL in human osteoblasts (hFOBs) are both increased during early osteogenesis. Subsequently, we examined the osteogenesis, adipogenesis, osteoclastogenesis function with lncR-APDC deletion/overexpression cell models. In vivo, we compared the phenotypic differences in bone and adipose tissue between APDC-KO and wild-type mice. Our findings demonstrated that lncR-APDC deficiency impaired osteogenesis while promoting adipogenesis and osteoclastogenesis. Conversely, the overexpression of lncR-APDC stimulated osteogenesis, but impaired adipogenesis and osteoclastogenesis. Furthermore, KDM6B was downregulated with lncR-APDC deficiency and upregulated with overexpression. Through binding-site analysis, we identified miR-99a as a potential target of lncR-APDC. The results suggest that lncR-APDC exerts its osteogenic function via miR-99a/KDM6B/Hox pathways. Additionally, osteoclasto-osteogenic imbalance was mediated by lncR-APDC through MAPK/p38 and TLR4/MyD88 activation. These findings highlight the pivotal role of lncR-APDC as a key regulator in bone and fat tissue metabolism. It shows potential therapeutic for addressing imbalances in osteogenesis, adipogenesis, and osteoclastogenesis.

Microelectrode recording and hemorrhage in functional neurosurgery: a comparative analysis in a consecutive series of 645 procedures.

OBJECTIVE: Functional stereotactic neurosurgery including deep brain stimulation (DBS) and radiofrequency lesioning is well established and widely used for treatment of movement disorders and various other neurological and psychiatric diseases. Although functional stereotactic neurosurgery procedures are considered relatively safe, intracranial hemorrhage resulting in permanent neurological deficits may occur in 1%-3% of patients. Microelectrode recording (MER) has been recognized as a valuable tool for refining the final target in functional stereotactic neurosurgery. Moreover, MER provides insight into the underlying neurophysiological pathomechanisms of movement disorders and other diseases. Nevertheless, there is an ongoing controversy on whether MER increases the risk for hemorrhage. The authors aimed to compare the risk of hemorrhage in functional stereotactic neurosurgical procedures with regard to the use of MER. METHODS: The authors performed a comparative analysis on a consecutive series of 645 functional neurosurgery procedures, including 624 DBS surgeries and 21 radiofrequency lesionings, to evaluate whether the use of MER would increase the risk for hemorrhage. MER was performed in 396 procedures, while no MER was used in 249 cases. The MER technique involved the use of a guiding cannula and a single trajectory when feasible. Postoperative CT scans were obtained within 24 hours after surgery in all patients and screened for the presence of hemorrhage. RESULTS: Twenty-one intracranial hemorrhages were detected on the postoperative CT scans (3.2%). Of the 21 intracranial hemorrhages, 14 were asymptomatic and 7 were symptomatic. Symptoms were transient except in 1 case. There was no statistically significant correlation between hemorrhage and the use of MER at any site (subdural, ventricle, trajectory, target, whether asymptomatic or symptomatic). There were 4 cases of symptomatic hemorrhage in the MER group (1%) and 3 cases in those without MER (1.2%). CONCLUSIONS: Intraoperative MER did not increase the overall risk of hemorrhage in the authors' experience using primarily a single MER trajectory and a guiding cannula.

A Glutaraldehyde-Free Crosslinking Method for the Treatment of Collagen-Based Biomaterials for Clinical Application.

Biological bioprostheses such as grafts, patches, and heart valves are often derived from biological tissue like the pericardium. These bioprostheses can be of xenogenic, allogeneic, or autologous origin. Irrespective of their origin, all types are pre-treated via crosslinking to render the tissue non-antigenic and mechanically strong or to minimize degradation. The most widely used crosslinking agent is glutaraldehyde. However, glutaraldehyde-treated tissue is prone to calcification, inflammatory degradation, and mechanical injury, and it is incapable of matrix regeneration, leading to structural degeneration over time. In this work, we are investigating an alternative crosslinking method for an intraoperative application. The treated tissue's crosslinking degree was evaluated by differential scanning calorimetry. To confirm the findings, a collagenase assay was conducted. Uniaxial tensile testing was used to assess the tissue's mechanical properties. To support the findings, the treated tissue was visualized using two-photon microscopy. Additionally, fourier transform infrared spectroscopy was performed to study the overall protein secondary structure. Finally, a crosslinking procedure was identified for intraoperative processing. The samples showed a significant increase in thermal and enzymatic stability after treatment compared to the control, with a difference of up to 22.2 °C and 100%, respectively. Also, the tissue showed similar biomechanics to glutaraldehyde-treated tissue, showing greater extensibility, a higher failure strain, and a lower ultimate tensile strength than the control. The significant difference in the structure band ratio after treatment is proof of the introduction of additional crosslinks compared to the untreated control with regard to differences in the amide-I region. The microscopic images support these findings, showing an alteration of the fiber orientation after treatment. For collagen-based biomaterials, such as pericardial tissue, the novel phenolic crosslinking agent proved to be an equivalent alternative to glutaraldehyde regarding tissue characteristics. Although long-term studies must be performed to investigate superiority in terms of longevity and calcification, our novel crosslinking agent can be applied in concentrations of 1.5% or 2.0% for the treatment of biomaterials.

Surgery with locking plate or hemiarthroplasty versus nonoperative treatment of 3-4-part proximal humerus fractures in older patients (NITEP): An open-label randomized trial.

BACKGROUND: Proximal humerus fractures (PHFs) are common fractures, especially in older female patients. These fractures are commonly treated surgically, but the consensus on the best treatment is still lacking. METHODS AND FINDINGS: The primary aim of this multicenter, randomized 3-arm superiority, open-label trial was to assess the results of nonoperative treatment and operative treatment either with locking plate (LP) or hemiarthroplasty (HA) of 3- and 4-part PHF with the primary outcome of Disabilities of the Arm, Shoulder, and Hand (DASH) at 2-year follow-up. Between February 2011 and December 2019, 160 patients 60 years and older with 3- and 4-part PHFs were randomly assigned in 1:1:1 fashion in block size of 10 to undergo nonoperative treatment (control) or operative intervention with LP or HA. In total, 54 patients were assigned to the nonoperative group, 52 to the LP group, and 54 to the HA group. Five patients assigned to the LP group were reassigned to the HA group perioperatively due to high comminution, and all of these patients had 4-part fractures. In the intention-to-treat analysis, there were 42 patients in the nonoperative group, 44 in the LP group, and 37 in the HA group. The outcome assessors were blinded to the study group. The mean DASH score at 2-year follow-up was 30.4 (standard error (SE) 3.25), 31.4 (SE 3.11), and 26.6 (SE 3.23) points for the nonoperative, LP, and HA groups, respectively. At 2 years, the between-group differences were 1.07 points (95% CI [-9.5,11.7]; p = 0.97) between nonoperative and LP, 3.78 points (95% CI [-7.0,14.6]; p = 0.69) between nonoperative and HA, and 4.84 points (95% CI [-5.7,15.4]; p = 0.53) between LP and HA. No significant differences in primary or secondary outcomes were seen in stratified age groups (60 to 70 years and 71 years and over). At 2 years, we found 30 complications (3/52, 5.8% in nonoperative; 22/49, 45% in LP; and 5/49, 10% in HA group, p = 0.0004) and 16 severe pain-related adverse events. There was a revision rate of 22% in the LP group. The limitation of the trial was that the recruitment period was longer than expected due to a high number of exclusions after the assessment of eligibility and a larger exclusion rate than anticipated toward the end of the trial. Therefore, the trial was ended prematurely. CONCLUSIONS: In this study, no benefit was observed between operative treatment with LP or HA and nonoperative treatment in displaced 3- and 4-part PHFs in patients aged 60 years and older. Further, we observed a high rate of complications related to operative treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT01246167.

Return to play after rotator cuff tear in National Football League athletes.

Background: Rotator cuff tears are rare injuries in National Football League (NFL) athletes and there are limited data to help guide players and team physicians. The purpose of this study was to assess return to play (RTP) rates, performance levels, and career length following a rotator cuff tear during their playing career. Methods: Using publicly available data, we identified players who sustained a rotator cuff tear between 2000 and 2019. Demographic information, treatment (operative vs. nonoperative), RTP rate, preinjury and postinjury performance score, position, and career length were entered into the analysis. Results: Twenty-nine athletes with a mean age of 27.4 years (±3.1) at the time of injury were included in this study. Forty-eight percent were offensive and 52% defensive players. 79.3% (23/29) were able to RTP at the same professional level for an average of 2.8 ± 3.4 years. The average time to RTP after injury was 198.4 ± 125.3 days. The average age of players who RTP was 26.7 ± 2.5 years compared to those who did not (30.3 ± 3.7, P = .02). Similarly, the preinjury NFL career length was 4.0 ± 2.2 in players who RTP compared to those who did not (7.5 ± 2.7, P = .01). Most injuries (82.2%) were treated surgically; however, there was no significant difference (P > .05) in RTP rates, performance score, or career longevity between operative and nonoperative cohorts. Conclusion: Overall RTP rates for NFL athletes following a rotator cuff injury are promising with approximately 80% returning at the same performance level regardless of treatment type. Older, veteran players particularly those over the age of 30 were significantly less likely to RTP and should be counseled accordingly.

Inflammation and Fibrosis in Orbital Inflammatory Disease: A Histopathologic Analysis.

PURPOSE: The purpose of this study was to compare the histopathologic inflammation and fibrosis of orbital adipose tissue in orbital inflammatory disease (OID) specimens. METHODS: In this retrospective cohort study, inflammation, and fibrosis in orbital adipose tissue from patients with thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis, nonspecific orbital inflammation (NSOI), and healthy controls were scored by 2 masked ocular pathologists. Both categories were scored on a scale of 0 to 3 with scoring criteria based on the percentage of specimens containing inflammation or fibrosis, respectively. Tissue specimens were collected from oculoplastic surgeons at 8 international centers representing 4 countries. Seventy-four specimens were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 24 with NSOI, and 12 healthy controls. RESULTS: The mean inflammation and fibrosis scores for healthy controls were 0.0 and 1.1, respectively. Orbital inflammatory disease groups' inflammation (I) and fibrosis (F) scores, formatted [I, F] with respective p -values when compared to controls, were: TAO [0.2, 1.4] ( p = 1, 1), GPA [1.9, 2.6] ( p = 0.003, 0.009), sarcoidosis [2.4, 1.9] ( p = 0.001, 0.023), and NSOI [1.3, 1.8] ( p ≤ 0.001, 0.018). Sarcoidosis had the highest mean inflammation score. The pairwise analysis demonstrated that sarcoidosis had a significantly higher mean inflammation score than NSOI ( p = 0.036) and TAO ( p < 0.0001), but no difference when compared to GPA. GPA had the highest mean fibrosis score, with pairwise analysis demonstrating a significantly higher mean fibrosis score than TAO ( p = 0.048). CONCLUSIONS: Mean inflammation and fibrosis scores in TAO orbital adipose tissue samples did not differ from healthy controls. In contrast, the more "intense" inflammatory diseases such as GPA, sarcoidosis, and NSOI did demonstrate higher histopathologic inflammation and fibrosis. This has implications in prognosis, therapeutic selection, and response monitoring in orbital inflammatory disease.