Discovering dominant tumor immune archetypes in a pan-cancer census.

Cancers display significant heterogeneity with respect to tissue of origin, driver mutations, and other features of the surrounding tissue. It is likely that individual tumors engage common patterns of the immune system-here "archetypes"-creating prototypical non-destructive tumor immune microenvironments (TMEs) and modulating tumor-targeting. To discover the dominant immune system archetypes, the University of California, San Francisco (UCSF) Immunoprofiler Initiative (IPI) processed 364 individual tumors across 12 cancer types using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained from cell sub-compartments uncovered dominant patterns of immune composition across cancers. These archetypes were profound insofar as they also differentiated tumors based upon unique immune and tumor gene-expression patterns. They also partitioned well-established classifications of tumor biology. The IPI resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune organization and provides a rational path forward to learn how to modulate these to improve therapy.

Neurorehabilitation for Adults with Brain and Spine Tumors.

Central nervous system (CNS) malignancies (i.e. brain and spine tumors) and their treatments can result in a multitude of neurologic deficits. Patients with CNS malignancies experience physical, cognitive, and psychosocial sequelae that can impact their mobility and quality of life. Neurorehabilitation can play a critical role in maintaining independence, preventing disability, and optimizing safety with activities of daily living. This review provides an overview of the neurorehabilitation approaches for patients with CNS malignancies, neurologic impairments frequently treated, and rehabilitation interventions in various health care settings. In addition, we will highlight rehabilitative outcomes between patients with nononcologic neurologic conditions compared to brain and spine tumors. Finally, we address medical challenges that may impact rehabilitation care in these medically complex cancer patients.

Demoralization and Quality of Life of Patients with Parkinson Disease.

INTRODUCTION: Demoralization is quite prevalent in patients with Parkinson disease (PD). Unrecognized or untreated, demoralization may progress, at times, to demands for euthanasia and the desire for suicide. Typically, patients with PD do not complain of being "demoralized"; rather, they report disruptions in the quality of their lives. Hence, early identification of disruptions in health-related quality of life (HRQoL) specifically associated with demoralization may prompt earlier recognition and treatment. Published data on such associations, however, could not be found. Alleviation of demoralization in PD is likely to improve treatment outcomes. OBJECTIVE: This research aimed at identifying the disruptions of HRQoL specifically associated with the demoralization of patients with PD. METHODS: Consecutive general hospital outpatients with PD (n = 95) were assessed for: demoralization, with the Diagnostic Criteria for Psychosomatic Research Demoralization Scale (DCPR-D) and the Demoralization Scale (DS); depression, with the Patient Health Questionnaire-9 (PHQ-9); HRQoL, with the Parkinson Disease Questionnaire-Short Form (PDQ-8); sociodemographic variables; medical comorbidities; PD severity; and types of treatment. RESULTS: The prevalence of demoralization was 19%. Regression analyses showed that demoralization was significantly more likely to be experienced by participants who had difficulty with mobility and felt embarrassed in public due to having PD. Demoralization explained HRQoL over and above depression. CONCLUSIONS: Stigma and perceived difficulty with mobility are associated with demoralization of PD patients, and they may signal the need for psychotherapeutic and behavioral interventions to prevent the progression to helplessness, hopelessness, demands for euthanasia, and desire for suicide.

Roll maneuvers are essential for active reorientation of Caenorhabditis elegans in 3D media.

Locomotion of the nematode Caenorhabditis elegans is a key observable used in investigations ranging from behavior to neuroscience to aging. However, while the natural environment of this model organism is 3D, quantitative investigations of its locomotion have been mostly limited to 2D motion. Here, we present a quantitative analysis of how the nematode reorients itself in 3D media. We identify a unique behavioral state of C. elegans-a roll maneuver-which is an essential component of 3D locomotion in burrowing and swimming. The rolls, associated with nonzero torsion of the nematode body, result in rotation of the plane of dorsoventral body undulations about the symmetry axis of the trajectory. When combined with planar turns in a new undulation plane, the rolls allow the nematode to reorient its body in any direction, thus enabling complete exploration of 3D space. The rolls observed in swimming are much faster than the ones in burrowing; we show that this difference stems from a purely hydrodynamic enhancement mechanism and not from a gait change or an increase in the body torsion. This result demonstrates that hydrodynamic viscous forces can enhance 3D reorientation in undulatory locomotion, in contrast to known hydrodynamic hindrance of both forward motion and planar turns.

Development, validation of QuEChERS-based method for simultaneous determination of multiclass pesticide residue in milk, and evaluation of the matrix effect.

Extraction and quantification of pesticide residue from the milk matrix at or below the established maximum residue limit (MRL) is a challenging task for both analytical chemists and the regulatory institutions to take corrective actions for the human health and safety. The main aim of the study is to develop a simple rapid and less expensive QuEChERS extraction and cleanup method for simultaneous analysis of 41 multiclass pesticide residue in milk by gas chromatography-electron capture detector (GC-ECD), followed by confirmation of the residues with gas chromatography-mass spectrometer (GC-MS). Effect of sorbent type, temperature, spiking concentration, matrix effect (ME), measurement uncertainty (MU), inter- and intra-assay repeatability, reproducibility of recovery, and trueness of the results were investigated to validate the effectiveness of the method. Limit of determination (LOD) and limit of quantitation (LOQ) for all the analytes ranged within 0.001-0.02 and 0.002-0.05 µg mL-1, respectively. The % recovery of all the pesticides ranged between 91.38 and 117.56% with relative standard deviation (RSD) below 2.79%. The MU for all the analytes was ≤29% of respective LOQs, and except for few pesticides, the ME was largely negative. The method fulfilled all the SANTE guidelines and thus can be extended for routine analysis of multiclass pesticide residue in milk.

Immunotherapy for Prostate Cancer: Where Do We Go From Here?-PART 1: Prostate Cancer Vaccines.

Immunotherapies have emerged as a revolutionary modality for cancer treatment, and a variety of immune-based approaches are currently being investigated in the field of prostate cancer. Despite the 2010 approval of sipuleucel-T, subsequent progress in prostate cancer immunotherapy development has been limited by disappointing results with novel vaccination approaches and by prostate cancer's general resistance to immune checkpoint blockade. Nevertheless, there remains strong preclinical and clinical evidence to suggest that prostate cancer is a susceptible target for immune therapies. Innovative strategies for vaccine development, adoptive cell transfer, alleviation of immunosuppression in the tumor microenvironment, and combinatorial approaches using existing drugs and novel immune agents hold great promise for improving the treatment of prostate cancer. The first article in this two-part series will provide an overview of both past and present therapeutic vaccination strategies for the promotion of antitumor immunity against prostate cancer. Later, in Part 2, we will discuss novel areas of clinical development and identify the trends that may define the future of prostate cancer immunotherapy.

Immunotherapy for Prostate Cancer: Where Do We Go From Here?-PART 2: Checkpoint Inhibitors, Immunotherapy Combinations, Tumor Microenvironment Modulation, and Cellular Therapies.

Therapeutic approaches that harness the power of the immune system to eliminate cancer cells have produced a paradigm shift in the management of a variety of malignancies. Prostate cancer has been a particularly active area of investigation in cancer immunotherapy, with significant laboratory and clinical evidence suggesting that this disease can be a viable target for cytotoxic immune cells. In the first article of this series, we discussed the diverse vaccination approaches that have been employed to prime native antigen-specific responses against prostate cancer, highlighting successes such as sipuleucel-T, as well as the significant challenges that remain. Here we focus on alternative methods of harnessing both adaptive and innate antitumor immunity to target prostate cancer cells. Approaches that enhance the activation of T cells, modulation of the tumor microenvironment to abrogate its inherent immunosuppressive mechanisms, and engineering of antigen-specific antibody and cellular products to target tumor cells will be discussed. We will then look ahead to provide a perspective on how this growing collection of immunotherapeutic approaches may ultimately be combined to target prostate cancer from a variety of angles.

Upper pole urologist-obtained percutaneous renal access for PCNL is safe and efficacious.

INTRODUCTION: Interventional radiologist may be hesitant to obtain upper pole access for percutaneous nephrolithotomy (PCNL) due to a higher complication rate. Renal access gained by urologists may achieve higher stone-free rates with similar complication rates. We evaluate our institution's contemporary results of percutaneous renal access in the upper pole for nephrolithotomy by urologists, which we believe both safe and efficacious. MATERIALS AND METHODS: This retrospective chart review included all PCNL's performed by fellowship-trained endourologists from 2003 to 2014 at a single institution. Inclusion criteria included patients in which renal access was obtained by the urologist via the upper pole for PCNL. Stone-free status was determined by either KUB or CT scan on POD #1. Patients without stones visible on KUB or less than 4 mm on CT were considered stone-free. RESULTS: A total of 144 patients obtained upper pole access for PCNL. There were a total of 53 (37%%) staghorn calculi, of which 35 (66%) were partial staghorn stones. Renal access was obtained above 11th rib in 12.5% (n = 18), between the 11th and 12th rib in 57.6% (n = 83), subcostal in 14.6% (n = 21) and undetermined in the rest. Complications were seen in 18 (12.5%) of patients. Hydropneumothorax requiring chest tube was seen in 8 (5.6%) patients. Postoperative imaging confirmed 93 (64.5%) patients stone-free, and 35 (24.3%) required a second look PCNL. CONCLUSIONS: Our experience with upper pole percutaneous renal access for nephrolithotomy has shown that it has an acceptable complication risk. It should be a part of an endourologist's armamentarium that operate on large burden, complex stones or ureteral pathology.

Football Equipment Removal Improves Chest Compression and Ventilation Efficacy.

OBJECTIVE: Airway access recommendations in potential catastrophic spine injury scenarios advocate for facemask removal, while keeping the helmet and shoulder pads in place for ensuing emergency transport. The anecdotal evidence to support these recommendations assumes that maintaining the helmet and shoulder pads assists inline cervical stabilization and that facial access guarantees adequate airway access. Our objective was to determine the effect of football equipment interference on performing chest compressions and delivering adequate ventilations on patient simulators. We hypothesized that conditions with more football equipment would decrease chest compression and ventilation efficacy. METHODS: Thirty-two certified athletic trainers were block randomized to participate in six different compression conditions and six different ventilation conditions using human patient simulators. Data for chest compression (mean compression depth, compression rate, percentage of correctly released compressions, and percentage of adequate compressions) and ventilation (total ventilations, mean ventilation volume, and percentage of ventilations delivering adequate volume) conditions were analyzed across all conditions. RESULTS: The fully equipped athlete resulted in the lowest mean compression depth (F5,154 = 22.82; P < 0.001; Effect Size = 0.98) and delivery of adequate compressions (F5,154 = 15.06; P < 0.001; Effect Size = 1.09) compared to all other conditions. Bag-valve mask conditions resulted in delivery of significantly higher mean ventilation volumes compared to all 1- or 2-person pocketmask conditions (F5,150 = 40.05; P < 0.001; Effect Size = 1.47). Two-responder ventilation scenarios resulted in delivery of a greater number of total ventilations (F5,153 = 3.99; P = 0.002; Effect Size = 0.26) and percentage of adequate ventilations (F5,150 = 5.44; P < 0.001; Effect Size = 0.89) compared to one-responder scenarios. Non-chinstrap conditions permitted greater ventilation volumes (F3,28 = 35.17; P < 0.001; Effect Size = 1.78) and a greater percentage of adequate volume (F3,28 = 4.85; P = 0.008; Effect Size = 1.12) compared to conditions with the chinstrap buckled or with the chinstrap in place but not buckled. CONCLUSIONS: Chest compression and ventilation delivery are compromised in equipment-intense conditions when compared to conditions whereby equipment was mostly or entirely removed. Emergency medical personnel should remove the helmet and shoulder pads from all football athletes who require cardiopulmonary resuscitation, while maintaining appropriate cervical spine stabilization when injury is suspected. Further research is needed to confirm our findings supporting full equipment removal for chest compression and ventilation delivery.

Biomechanical Analysis of All-Inside, Arthroscopic Suture Repair Versus Extensor Retinaculum Capsulorrhaphy for Triangular Fibrocartilage Complex Tears With Instability.

PURPOSE: To assess ulnocarpal joint stability after treatment of a peripheral triangular fibrocartilage complex (TFCC) injury with all-inside arthroscopic suture repair (SR), extensor retinaculum capsulorrhaphy with the Herbert sling (HS), and a combination of both (SR+HS). METHODS: Twelve fresh-frozen, age-matched, upper-extremity specimens intact from the distal humerus were prepared. Nondestructive mechanical testing was performed to assess native ulnocarpal joint stability and load-displacement curves were recorded. A peripheral, ulnar-sided TFCC injury was created with arthroscopic assistance, and mechanical testing was performed. Each specimen was treated with SR or HS and testing was repeated. The 6 specimens treated with SR were then treated with HS (SR+HS), and testing was repeated. We used paired Student t tests for statistical analysis within cohorts. RESULTS: For all cohorts, there was an average increase in ulnar translation after the creation of a peripheral TFCC injury and an average decrease after repair. Herbert sling decreased translation by 21%, SR decreased translation by 12%, and SR+HS decreased translation by 26%. CONCLUSIONS: Suture repair plus HS and HS reduce ulnar translation the most after a peripheral TFCC injury, followed by SR alone. CLINICAL RELEVANCE: Ulnocarpal joint stability should be assessed clinically in patients with peripheral TFCC injury, and consideration should be made for using extensor capsulorrhaphy in isolation or as an adjunct to SR as a treatment option.

Functional outcomes of replantation following radiocarpal amputation.

PURPOSE: To assess the long-term functional and clinical outcomes of patients who have undergone replantation after radiocarpal amputation. METHODS: We performed a retrospective review of radiocarpal joint amputations at a level 1 trauma center over a 13-year period. Medical records of patients treated with replantation were queried for injury data, operative reports, complications, and clinical progress. Patients who met inclusion criteria were contacted for long-term follow-up. We measured total active motion of each digit, strength (grip and pinch), and 2-point discrimination. Functional outcomes were assessed with Disabilities of Arm, Shoulder, and Hand score, Mayo Wrist Score, Patient-Rated Wrist Evaluation, and Michigan Hand Questionnaire. Descriptive statistics were calculated, including frequencies for categorical variables and means and ranges for continuous variables. RESULTS: Six patients met the inclusion criteria. The mean age was 36 years (range, 26-50 y). Five patients were available at a mean follow-up of 3.9 years (range, 1.0-6.9 y). Compared with the contralateral uninjured extremity, total active motion of the hand was 38% (range, 26% to 59%) and grip strength was 9% (range, 0% to 18%). Neither tip nor key pinch was present. Mean 2-point discrimination was 10.6 mm (range, 8-12 mm). All mean outcome scores indicated moderate disability, including Disabilities of Arm, Shoulder, and Hand (76; range, 45-82), Mayo Wrist Score (23; range, 5-50), Patient-Rated Wrist Evaluation (86; range, 56-98), and Michigan Hand Questionnaire (27; range, 15-55). Two patients were able to return to work and 3 were permanently disabled. All patients were satisfied with the hand function. CONCLUSIONS: Successful replantation for a radiocarpal joint amputation is associated with major restriction of motion, decreased strength, and moderate disability on functional outcome assessments. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Early Use of 60 Hz Frequency Subthalamic Stimulation in Parkinson's Disease: A Case Series and Review.

BACKGROUND: Deep brain stimulation (DBS) is effective in treating the segmental symptoms of Parkinson's disease (PD) as well as axial symptoms that are levodopa responsive. PD patients on chronic DBS who develop axial symptoms and gait disturbances several years later oftentimes are refractory to high frequency stimulation (HFS). Several studies report benefit produced by low frequency subthalamic nucleus (STN) stimulation in such patients, though the sustainability of the effects has been mixed. OBJECTIVE: To report the clinical outcomes of a series of patients with Parkinson's disease and levodopa responsive axial and gait disturbances who were switched to 60 Hz stimulation within one year of their DBS surgery. METHODS: A retrospective review of 5 patients, whose severe pre-DBS, levodopa responsive gait disorders worsened on HFS STN-DBS and were subsequently switched to 60 Hz stimulation within 1 year of their surgery. RESULTS: The median age of this cohort was 66 years with median disease duration of 14 years. Four of 5 patients' experienced acute worsening of their axial and gait UPDRS III scores on HFS. All patients' gait disorder improved with 60 Hz along with amelioration of their segmental symptoms and reduction of their levodopa induced dyskinesia. The median time on HFS prior to switching to 60 Hz was two months. Stimulation through the ventral contacts was utilized in all patients with relatively modest changes achieved in levodopa equivalent daily dose. CONCLUSION: This case series demonstrates the clinical efficacy of utilizing low frequency (60 Hz) STN stimulation early in the DBS programming course in more advanced PD patients with levodopa responsive gait disturbance and freezing of gait. Activation of a broader stimulation field likely contributed to both axial and segmental symptom improvement while possibly aiding in the reduction of dyskinesia.

Selenium as an electron acceptor during the catalytic mechanism of thioredoxin reductase.

Mammalian thioredoxin reductase (TR) is a pyridine nucleotide disulfide oxidoreductase that uses the rare amino acid selenocysteine (Sec) in place of the more commonly used amino acid cysteine (Cys) in the redox-active tetrapeptide Gly-Cys-Sec-Gly motif to catalyze thiol/disulfide exchange reactions. Sec can accelerate the rate of these exchange reactions (i) by being a better nucleophile than Cys, (ii) by being a better electrophile than Cys, (iii) by being a better leaving group than Cys, or (iv) by using a combination of all three of these factors, being more chemically reactive than Cys. The role of the selenolate as a nucleophile in the reaction mechanism was recently demonstrated by creating a mutant of human thioredoxin reductase-1 in which the Cys497-Sec498 dyad of the C-terminal redox center was mutated to either a Ser497-Cys498 dyad or a Cys497-Ser498 dyad. Both mutant enzymes were incubated with human thioredoxin (Trx) to determine which mutant formed a mixed disulfide bond complex. Only the mutant containing the Ser497-Cys498 dyad formed a complex, and this structure has been determined by X-ray crystallography [Fritz-Wolf, K., Kehr, S., Stumpf, M., Rahlfs, S., and Becker, K. (2011) Crystal structure of the human thioredoxin reductase-thioredoxin complex. Nat. Commun. 2, 383]. This experimental observation most likely means that the selenolate is the nucleophile initially attacking the disulfide bond of Trx because a complex resulted only when Cys was present in the second position of the dyad. As a nucleophile, the selenolate of Sec helps to accelerate the rate of this exchange reaction relative to Cys in the Sec → Cys mutant enzyme. Another thiol/disulfide exchange reaction that occurs in the enzymatic cycle of the enzyme is the transfer of electrons from the thiolate of the interchange Cys residue of the N-terminal redox center to the eight-membered selenosulfide ring of the C-terminal redox center. The selenium atom of the selenosulfide could accelerate this exchange reaction by being a good leaving group (attack at the sulfur atom) or by being a good electrophile (attack at the selenium atom). Here we provide strong evidence that the selenium atom is attacked in this exchange step. This was shown by creating a mutant enzyme containing a Gly-Gly-Seccoo- motif that had 0.5% of the activity of the wild-type enzyme. This mutant lacks the adjacent, resolving Cys residue, which acts by attacking the mixed selenosulfide bond that occurs between the enzyme and substrate. A similar result was obtained when Sec was replaced with homocysteine. These results highlight the role of selenium as an electron acceptor in the catalytic mechanism of thioredoxin reductase as well as its established role as a donor of an electron to the substrate.

Safety and feasibility of concomitant surgery during holmium laser enucleation of the prostate (HoLEP).

PURPOSE: To determine the feasibility and outcomes associated with performing simultaneous surgical procedures during holmium laser enucleation of the prostate (HoLEP) in patients with benign prostatic hyperplasia and concomitant urologic conditions. METHODS: A retrospective review of patients that underwent a HoLEP was performed. Patients undergoing a concomitant procedure at the time of HoLEP were selected and stratified based on complexity of the secondary procedure (simple, intermediate, and complex) and matched based on age and prostate volume to patients undergoing only a HoLEP. Baseline characteristics, preoperative, operative, and postoperative outcomes were collected. RESULTS: A total of 372 HoLEPs were performed. Thirty-eight (10.2 %) patients underwent concomitant procedures at the time of HoLEP. Compared to the simple and intermediate secondary surgical procedures, the matched control group that underwent a HoLEP alone did not demonstrate statistically significant differences in the preoperative, operative, or postoperative outcomes. Patients with a complex secondary surgical procedure at the time of HoLEP had statistically significant differences in operative time (221 vs. 65 min, p = 0.007), estimated blood loss (92 vs. 33 mL, p = 0.012), catheter time (8.5 vs. 1 day, p = 0.041), and length of hospitalization (2 vs. 1 day, p = 0.032) compared to the control group. CONCLUSIONS: Obstructive voiding symptoms secondary to BPH are common in older patients and may coincide with other concomitant lower urinary tract pathology that may require surgical intervention. Rather than staging surgical interventions, it appears that definitive treatment for BPH with HoLEP is safe and efficacious in those patients that also require secondary procedures.

Peri-procedural povidone-iodine rectal preparation reduces microorganism counts and infectious complications following ultrasound-guided needle biopsy of the prostate.

PURPOSE: The purpose of the study was to evaluate whether a peri-procedural povidone-iodine rectal preparation (PIRP) prior to transrectal ultrasound-guided prostate needle biopsy (TRUS PNB) can reduce microorganism colony counts and infectious complications. METHODS: Our institutional TRUS PNB database was reviewed to identify infectious post-biopsy complications (defined as fever >38.5 °C with positive culture). The last 570 biopsy patients were divided into those administered only preoperative oral and/or parenteral antibiotics (n = 456; chronologically cohorts A-D) versus men receiving peri-procedural PIRP in conjunction with standard preoperative antibiotics (n = 114; cohort E). Rectal cultures were obtained in the PIRP cohort to quantify changes in microorganism colony counts. RESULTS: Mean baseline PSA for patients was 11.6 ng/ml, 63 % were undergoing an initial biopsy, and 17 % had documented use of antibiotic therapy within the previous 6 months. A reduction in infectious complications was observed when comparing the conventional antibiotic (cohorts A-D) versus PIRP (cohort E) group (1.8 vs. 0 %), with the largest magnitude of decline occurring in the concurrent contemporary cohorts (cohort D-5.3 % vs. cohort E-0 %, p = 0.03). Rectal cultures obtained in 92 men before and after PIRP administration noted a 97 % reduction in microorganism colonies (2.1 × 10(5) vs. 6.3 × 10(3) CFU/ml, p < 0.001). No adverse reactions to the PIRP were reported by patients 7 days post-biopsy. CONCLUSIONS: Peri-procedural PIRP decreased microorganism colony counts and effectively reduced infectious complications following TRUS PNB. This safe, cheap, and simple strategy may be a reasonable alternative to systemic or targeted antibiotic therapy to reduce post-biopsy infections.

Pericardial Decompression Syndrome: A Comprehensive Review of a Controversial Entity.

Pericardial decompression syndrome is an ambiguous clinical entity which has generated controversy regarding its existence. Following pericardial decompression, patients experienced clinical deterioration ranging in complications from pulmonary edema to death that could not be attributed to any other distinct clinical pathology. Multiple theories have suggested the pathophysiology behind pericardial decompression syndrome is related to preload-afterload mismatch following pericardial decompression, coronary microvascular ischemia, and stress from high adrenergic state. Our review aims to describe this syndrome by analyzing demographics, etiology of pericardial effusion, method of drainage, volume of pericardial fluid removed, time to decompensation, and clinical outcomes. A systematic review of MEDLINE/PubMed and Google Scholar literature databases were queried for case reports, case series, review articles, and abstracts published in English journals between 1983 and December 2022. Each author's interpretation of echocardiographic and/or pulmonary arterial catheterization data provided in the case reports was used to characterize ventricular dysfunction. Based on our inclusion criteria, 72 cases of pericardial decompression syndrome were included in our review. Our results showed that phenotypic heterogeneity was present based on echocardiographic findings of right/left or biventricular failure with similar proportions in each type of ventricular dysfunction. Time to decompensation was similar between immediate, subacute, and acute cases with presentation varying between hypoxic respiratory failure and shock. This review article highlights theories behind the pathophysiology, clinical outcomes, and therapeutic options in this high mortality condition.

Central Retinal Artery Occlusion: Visual Outcomes from a Large Northern California Cohort.

PURPOSE: To assess visual acuity (VA) outcomes in a large cohort of patients diagnosed with nonarteritic central retinal artery occlusion (CRAO), and to ascertain whether time from symptom onset to presentation, presenting VA, or conservative treatment delivery (anterior chamber paracentesis, ocular massage, intraocular pressure lowering drugs, hyperventilation, or some combination of those) impacted ultimate VA outcomes. DESIGN: Retrospective cohort study. SUBJECTS: The study included 794 patients who presented with CRAO between 2011 and 2020. Within this cohort, 484 individuals presented within 30 days of symptom onset and had comprehensive documentation regarding the details of their presentation, management, and follow-up ≥ 90 days postdiagnosis. METHODS: Retrospective chart review was conducted for all patients with a diagnosis of CRAO initially identified via International Classification of Diseases coding, followed by confirmation of diagnosis by 2 retina specialists. Cases of arteritic CRAO were excluded. MAIN OUTCOME MEASURES: Visual acuity recovery, defined as improvement from ≤ 20/200 or worse at presentation to ≥ 20/100 ≥ 90 days after diagnosis. RESULTS: Of the 794 identified patients, 712 (89.7%) presented with VA of ≤ 20/200. Similarly, 447 (92.4%) of the 484-patient subset that presented within 30 days and had comprehensive documentation presented with VA ≤ 20/200. Of the 441 of those patients with documented follow-up, 380 (86.2%) remained at that level. Of the 244 patients who presented within 4.5 hours of symptom onset, 227 (93%) presented ≤ 20/200 and 201 (92.6%) of the 217 of those with follow-up data did not improve beyond that threshold. There was no significant difference (P < 0.05) in final VA between patients presenting before versus after 4.5 hours from time of vision loss. There was also no significant difference (P < 0.05) in VA outcomes between patients who did or did not receive conservative treatment. CONCLUSIONS: This large retrospective study further highlights the poor visual prognosis for patients with CRAO. Earlier time to presentation did not seem to impact final VA outcome, nor did conservative treatment efforts. Efficacious evidence-based treatment options are needed for this patient population. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Comprehensive characterization of protease inhibiting gene family, cis-regulatory elements, and protein interaction network in linseed and their expression upon bud fly infestation.

Linseed, also known as flax is an important oilseed crop with many potential uses in paint, textile, food and pharmaceutical industries. Susceptibility to bud fly (Dasyneura lini Barnes) infestation is a serious biotic concern leading to severe yield penalty in linseed. Protease inhibitors (PIs) are potential candidates that activate during the insect-pest attack and modulate the resistance. In the present study, we explored the PI candidates in the linseed genome and a total of 100 LuPI genes were identified and grouped into five distinct subgroups. The analysis of cis-acting elements revealed that almost all LuPI promoters contain several regulatory elementary related to growth and development, hormonal regulation and stress responses. Across the subfamilies of PIs, the specific domains are consistently found conserved in all protein sequences. The tissue-specific in-silico expression pattern via RNA-seq revealed that all the genes were regulated during different stress. The expression through qRT-PCR of 15 genes revealed the significant up-regulation of LuPI-24, LuPI-40, LuPI-49, LuPI-53, and LuPI-63 upon bud fly infestation in resistant genotype EC0099001 and resistant check variety Neela. This study establishes a foundation resource for comprehending the structural, functional, and evolutionary dimensions of protease inhibitors in linseed.