Dissecting OGT's TPR domain to identify determinants of cellular function.

O-GlcNAc transferase (OGT) is an essential mammalian enzyme that glycosylates myriad intracellular proteins and cleaves the transcriptional coregulator Host Cell Factor 1 to regulate cell cycle processes. Via these catalytic activities as well as noncatalytic protein-protein interactions, OGT maintains cell homeostasis. OGT's tetratricopeptide repeat (TPR) domain is important in substrate recognition, but there is little information on how changing the TPR domain impacts its cellular functions. Here, we investigate how altering OGT's TPR domain impacts cell growth after the endogenous enzyme is deleted. We find that disrupting the TPR residues required for OGT dimerization leads to faster cell growth, whereas truncating the TPR domain slows cell growth. We also find that OGT requires eight of its 13 TPRs to sustain cell viability. OGT-8, like the nonviable shorter OGT variants, is mislocalized and has reduced Ser/Thr glycosylation activity; moreover, its interactions with most of wild-type OGT's binding partners are broadly attenuated. Therefore, although OGT's five N-terminal TPRs are not essential for cell viability, they are required for proper subcellular localization and for mediating many of OGT's protein-protein interactions. Because the viable OGT truncation variant we have identified preserves OGT's essential functions, it may facilitate their identification.

Top Ten Tips Palliative Care Clinicians Should Know About Providing Care for People With Disabilities.

Palliative care (PC) clinicians are well poised to help people with disabilities (PWD) live well in the context of serious illness. PC prioritizes person-centered care with a focus on function, autonomy, and quality of life. This approach aligns with principles of high-quality care for PWD. An understanding of the unique experiences and needs of PWD can advance the delivery of comprehensive, equitable PC for this population. In this article, we provide 10 tips to help PC clinicians develop an informed disability lens in their approach to care.

Hospital cost differences between open and endoscopic lumbar spine decompression surgery.

OBJECTIVE: In recent years, fully endoscopic decompression surgery for degenerative spine disease has become increasingly popular in the US. Although an endoscopic approach has demonstrated some benefits compared with open procedures in randomized controlled trials, the cost of advanced technologies remains contested. The authors evaluated the differences in costs and cost drivers between open and endoscopic decompression surgical procedures performed at a single institution. METHODS: Using associated Current Procedural Terminology codes, the authors identified all open and endoscopic decompression lumbar surgical procedures performed from January 1, 2016, through December 31, 2022. Preoperative comorbidities, surgical characteristics, and postoperative outcomes were captured. The costs of index surgery-related readmission for revision, washout, or other complications were included in the index surgery expenses. Associated in-hospital costs were collected; these were reported in comparative percentages with open surgical procedures as the baseline because of an institutional agreement. Univariate and multivariate analyses were performed. RESULTS: The retrospective search identified 633 open surgical procedures and 195 endoscopic surgical procedures for inclusion. The two patient cohorts were similar, with clinically nonrelevant but statistically significant differences in mean age (open 55.7 years vs endoscopic 59.4 years, p = 0.01) and mean American Society of Anesthesiologists physical status class (open 2.3 vs endoscopic 2.4, p = 0.03). Postoperatively, patients who underwent open surgical procedures had significantly longer mean hospital stays (open 1.4 days vs endoscopic 0.7, p < 0.01) and more perioperative complications (open 7.9% of patients vs endoscopic 3.1%, p = 0.02), and they required washout surgical procedures in some cases (open 1.3% vs endoscopic 0%, p = 0.12). The largest cost difference between open and endoscopic surgical procedures was the significantly greater cost of disposable supplies for endoscopic cases (10.1% vs 31.7% of the total cost of open procedures, p < 0.01), and open surgical procedures were generally less costly in total (100.0% vs 115.1%, p < 0.01). In multivariate linear regression, endoscopic surgery was independently associated with greater total costs (standardized beta 15.9%, p < 0.01), although length of hospital stay (standardized beta 34.0%) and readmissions (standardized beta 30.0%, p < 0.01) had larger effects on cost. CONCLUSIONS: The endoscopic approach was associated with greater total in-hospital costs compared with open procedures. The findings of further cost evaluations, including those of patient-reported outcomes, social cost, and capital costs per procedure type, need to be included in operational and clinical decisions.

Management Patterns and Outcomes After Traumatic Brain Injury With Associated Blunt Cerebrovascular Injury.

BACKGROUND AND OBJECTIVES: Although blunt cerebrovascular injuries (BCVIs) are relatively common in patients with traumatic brain injuries (TBIs), uncertainty remains regarding optimal management strategies to prevent neurological complications, morbidity, and mortality. Our objectives were to characterize common care patterns; assess the prevalence of adverse outcomes, including stroke, functional deficits, and death, by BCVI grade; and evaluate therapeutic approaches to treatment in patients with BCVI and TBI. METHODS: Patients with TBI and BCVI treated at our Level I trauma center from January 2016 to December 2020 were identified. Presenting characteristics, treatment, and outcomes were captured for univariate and multivariate analyses. RESULTS: Of 323 patients with BCVI, 145 had Biffl grade I, 91 had grade II, 49 had grade III, and 38 had grade IV injuries. Lower-grade BCVIs were more frequently managed with low-dose (81 mg) aspirin ( P < .01), although all grades were predominantly treated with high-dose (150-600 mg) aspirin ( P = .10). Patients with low-grade BCVIs had significantly fewer complications ( P < .01) and strokes ( P < .01). Most strokes occurred in the acute time frame (<24 hours), including 10/11 (90.9%) grade IV-related strokes. Higher BCVI grade portended elevated risk of stroke (grade II odds ratio [OR] 5.3, grade III OR 12.2, and grade IV OR 19.6 compared with grade I; all P < .05). The use of low- or high-dose aspirin was protective against mortality (both OR 0.1, P < .05). CONCLUSION: In patients with TBI, BCVIs impart greater risk for stroke and other associated morbidities as their severity increases. It may prove difficult to mitigate high-grade BCVI-related stroke, considering most events occur in the acute window. The paucity of late time frame strokes suggest that current management strategies do help mitigate risks.

Impact of premorbid oral anticoagulant use on survival in patients with traumatic intracranial hemorrhage.

OBJECTIVE: Although oral anticoagulant use has been implicated in worse outcomes for patients with a traumatic brain injury (TBI), prior studies have mostly examined the use of vitamin K antagonists (VKAs). In an era of increasing use of direct oral anticoagulants (DOACs) in lieu of VKAs, the authors compared the survival outcomes of TBI patients on different types of premorbid anticoagulation medications with those of patients not on anticoagulation. METHODS: The authors retrospectively reviewed the records of 1186 adult patients who presented at a level I trauma center with an intracranial hemorrhage after blunt trauma between 2016 and 2022. Patient demographics; comorbidities; and pre-, peri-, and postinjury characteristics were compared based on premorbid anticoagulation use. Multivariable Cox proportional hazards regression modeling of mortality was performed to adjust for risk factors that met a significance threshold of p < 0.1 on bivariate analysis. RESULTS: Of 1186 patients with a traumatic intracranial hemorrhage, 49 (4.1%) were taking DOACs and 53 (4.5%) used VKAs at the time of injury. Patients using oral anticoagulants were more likely to be older (p < 0.001), to have a higher Charlson Comorbidity Index (p < 0.001), and to present with a higher Glasgow Coma Scale (GCS) score (p < 0.001) and lower Injury Severity Score (ISS; p < 0.001) than those on no anticoagulation. Patients using VKAs were more likely to undergo reversal than patients using DOACs (53% vs 31%, p < 0.001). Cox proportional hazards regression demonstrated significantly increased hazard ratios (HRs) for VKA use (HR 2.204, p = 0.003) and DOAC use (HR 1.973, p = 0.007). Increasing age (HR 1.040, p < 0.001), ISS (HR 1.017, p = 0.01), and Marshall score (HR 1.186, p < 0.001) were associated with an increased risk of death. A higher GCS score on admission was associated with a decreased risk of death (HR 0.912, p < 0.001). CONCLUSIONS: Patients with a traumatic intracranial injury who were on oral anticoagulant therapy before injury demonstrated higher mortality rates than patients who were not on oral anticoagulation after adjusting for age, comorbid conditions, and injury presentation.

How to transform urban institutional green spaces into Ancillary Botanic Gardens to expand informal botanical learning opportunities in cities.

Since many cities lack botanical gardens, we introduced the concept of Ancillary Botanic Gardens (ABG), which builds on the premise that organizations can expand informal botanical learning by adding a secondary function to their institutional green spaces. This study guides the application of the ABG concept in various spatial and functional contexts by offering practical and interpretive tools to organizations who are less used to working with nature but are interested in mitigating urban residents' detachment from nature. Online maps of 220 botanic gardens were reviewed to define types of plant collections and produce an exhaustive list of physical botanic garden elements. The collected information was developed into an ABG field checklist that was tested on three case studies in Lebanon and then used to develop guidelines for ABG establishment. The guidelines and checklist are meant to empower and guide organizations interested in establishing an ABG.

Effect of Polysulfide Speciation on Mg Anode Passivation in Mg-S Batteries.

Mg-S batteries are a promising next-generation system for beyond conventional Li-ion chemistry. The Mg-S architecture pairs a Mg metal anode with an inexpensive, high-capacity S8 cathode. However, S8-based cathodes exhibit the "polysulfide shuttle" effect, wherein soluble partially reduced Sx2- species generated at the cathode diffuse to and react with the anode. While dissolved polysulfides may undergo reactions to form Li+-permeable layers in Li-S systems, the interfaces on Mg anodes are passivating. In this work, we probe the reactivity of various Mg polysulfide solutions at the Mg anode interface. Mg polysulfide solutions are prepared without any chelating agents to closely mimic conditions in a Mg-S cell. The polysulfides are synthesized by reacting Mg metal and S8 in electrolyte, and the speciation is controlled by varying the Mg:S precursor ratio. S-poor precursor ratios produce magnesium polysulfide solutions with a higher proportion of short-chain polysulfides that react at the Mg anode faster than the longer-chain analogues. Anode passivation can be slowed by shifting the polysulfide equilibria toward longer-chain polysulfides through addition of S8.

Using Frailty Measures to Predict Functional Outcomes and Mortality After Type II Odontoid Fracture in Elderly Patients: A Retrospective Cohort Study.

STUDY DESIGN: Single-center retrospective cohort study. OBJECTIVES: Type II odontoid fractures occur disproportionately among elderly populations and cause significant morbidity and mortality. It is a matter of debate whether these injuries are best managed surgically or conservatively. Our goal was to identify how treatment modalities and patient characteristics correlated with functional outcome and mortality. METHODS: We identified adult patients (>60 years) with traumatic type II odontoid fractures. We used multivariate regression controlling for patient demographics, Glasgow Coma Scale (GCS) score, Charlson Comorbidity Index (CCI), modified Rankin Scale (mRS) score, modified Frailty Index (mFI-5 and mFI-11), fracture displacement, and conservative vs operative treatment. RESULTS: Of the 59 patients (mean age 77.9 years), 24 underwent surgical intervention and 35 underwent conservative management. Operatively managed patients were younger (73.4 vs 80.6 years, P < .001) and had higher degree of fracture displacement (3.5 vs 1.0 mm, P = .002) than conservatively managed patients but no other differences in baseline characteristics. Twenty-four patients (40.7%) died within the study period (median time to death: 376 days). There were no differences between treatment groups in functional outcomes (mRS or Frankel Grade) or mortality (33.3% in operative group vs 45.7%, P = .34). There was a statistically significant correlation between higher presentation mRS score and subsequent mortality on multivariate analysis (OR = 2.06, 95% CI 1.04-4.10, P = .039), whereas surgical intervention, age, GCS score, CCI, mFI-5, mFI-11, sex, and fracture displacement were not significantly correlated. CONCLUSIONS: Mortality after type II odontoid fractures in elderly patients is common. mRS score at presentation may help predict mortality more accurately than other patient factors.

Analyzing risk factors for treatment failure in fracture-related infection.

INTRODUCTION: Fracture-related infection (FRI) represents a challenging clinical scenario. Limited evidence exists regarding treatment failure after initial management of FRI. The objective of our investigation was to determine incidence and risk factors for treatment failure in FRI. MATERIALS AND METHODS: We conducted a retrospective review of patients treated for FRI between 2011 and 2015 at three level 1 trauma centers. One hundred and thirty-four patients treated for FRI were identified. Demographic and clinical variables were extracted from the medical record. Treatment failure was defined as the need for repeat debridement or surgical revision seven or more days after the presumed final procedure for infection treatment. Univariate comparisons were conducted between patients who experienced treatment failure and those who did not. Multivariable logistic regression was conducted to identify independent associations with treatment failure. RESULTS: Of the 134 FRI patients, 51 (38.1%) experienced treatment failure. Patients who failed were more likely to have had an open injury (31% versus 17%; p = 0.05), to have undergone implant removal (p = 0.03), and additional index I&D procedures (3.3 versus 1.6; p < 0.001). Most culture results identified a single organism (62%), while 15% were culture negative. Treatment failure was more common in culture-negative infections (p = 0.08). Methicillin-resistant Staphylococcus aureus (MRSA) was the most common organism associated with treatment failure (29%; p = 0.08). Multivariate regression demonstrated a statistically significant association between treatment failure and two or more irrigation and debridement (I&D) procedures (OR 13.22, 95% CI 4.77-36.62, p < 0.001) and culture-negative infection (OR 4.74, 95% CI 1.26-17.83, p = 0.02). CONCLUSIONS: The rate of treatment failure following FRI continues to be high. Important risk factors associated with treatment failure include open fracture, implant removal, and multiple I&D procedures. While MRSA remains common, culture-negative infection represents a novel risk factor for failure, suggesting aggressive treatment of clinically diagnosed cases remains critical even without positive culture data. LEVEL OF EVIDENCE: Retrospective cohort study; Level III.

Reasons for Visits to the Dermatologist Stratified by Race.

OBJECTIVES: The aim of this study was to examine, from the patient's perspective, the most common reasons for seeking medical attention for skin disease and how this varies among different races. METHODS: We conducted a cross-sectional analysis on the National Ambulatory Medical Care Survey between 2007 and 2018, the most recent years available. The frequency of each reason for visits was determined using the survey procedures of SAS version 9.4. RESULTS: Among White patients, skin cancer screening (8.2%) was the most common reason for visits followed by skin lesions (7.8%) and discoloration/abnormal pigmentation (7.4%). Among Blacks/African Americans, acne (9.2%), progress visit (8.2%), and skin rash (7.0%) were the top reasons for visits. Acne (12%), skin rash (7.5%), and discoloration/abnormal pigmentation (7.3%) were the most common reasons for patient visits in the "other" race category. CONCLUSIONS: Reasons for visits to the dermatologist vary with race. White patients appear to be aware of their increased risk of skin cancer, visiting frequently for skin cancer screenings and skin lesions, whereas Blacks/African Americans are more affected by conditions associated with chronic pruritus. To train dermatologists and nondermatologists to provide equitable care for cutaneous conditions to all races and skin types, especially for those groups experiencing barriers to receiving dermatologic care, it is important that we characterize the reasons why patients visit the dermatologist.

The State of Palliative Care Education in United States Physical Medicine and Rehabilitation Residency Programs: Heterogeneity and Opportunity for Growth.

ABSTRACT: Physical medicine and rehabilitation physicians routinely care for patients with serious illness and injury who could benefit from an integrated palliative care approach due to the propensity for high or complex symptom burden. Despite this, it has been unknown whether and how physical medicine and rehabilitation residency programs are equipping residents with a foundational palliative care skillset. We report national survey results characterizing the current status of palliative care education within US physical medicine and rehabilitation residency programs. Programs vary widely in the type and amount of palliative care education provided, with nearly a third of responding programs reporting no palliative care education at all. These findings suggest the need for nationally unifying palliative care education standards for physical medicine and rehabilitation residency programs to ensure that all physical medicine and rehabilitation residents have the opportunity to develop a robust palliative lens that can be applied across rehabilitation practice settings. An articulated set of standards could both facilitate achievement of palliative care-specific objectives and support achievement of foundational physical medicine and rehabilitation residency program objectives.

An Exploration of Sulfur Redox in Lithium Battery Cathodes.

Secondary Li-ion batteries have enabled a world of portable electronics and electrification of personal and commercial transportation. However, the charge storage capacity of conventional intercalation cathodes is reaching the theoretical limit set by the stoichiometry of Li in the fully lithiated structure. Increasing the Li:transition metal ratio and consequently involving structural anions in the charge compensation, a mechanism termed anion redox, is a viable method to improve storage capacities. Although anion redox has recently become the front-runner as a next-generation storage mechanism, the concept has been around for quite some time. In this perspective, we explore the contribution of anions in charge compensation mechanisms ranging from intercalation to conversion and the hybrid mechanisms between. We focus our attention on the redox of S because the voltage required to reach S redox lies within the electrolyte stability window, which removes the convoluting factors caused by the side reactions that plague the oxides. We highlight examples of S redox in cathode materials exhibiting varying degrees of anion involvement with a particular focus on the structural effects. We call attention to those with intermediate anion contribution to redox and the hybrid intercalation- and conversion-type structural mechanism at play that takes advantage of the positives of both mechanistic types to increase storage capacity while maintaining good reversibility. The hybrid mechanisms often invoke the formation of persulfides, and so a survey of binary and ternary materials containing persulfide moieties is presented to provide context for materials that show thermodynamically stable persulfide moieties.

Pituitary Apoplexy Precipitated by Systemic Chemotherapy.

Pituitary apoplexy often occurs in patients with previously undiagnosed pituitary adenomas and no predisposing factors. Among patients with precipitating events, there are very few cases of pituitary apoplexy occurring in the setting of systemic chemotherapy treatment. A 31-year-old man with newly diagnosed metastatic testicular cancer developed headaches, nausea, and a right-sided visual field deficit one week after initiation of bleomycin, etoposide, and cisplatin chemotherapy. Computed tomography and magnetic resonance imaging revealed hemorrhage within a pituitary macroadenoma consistent with pituitary apoplexy, and he underwent urgent transnasal resection. We also review the four prior cases of pituitary apoplexy temporally associated with the administration of systemic chemotherapy.

Why Do Patients in the United States Seek Care from Dermatologists?

INTRODUCTION: While the diagnoses made at visits to the dermatologist are well characterized, the reasons patients visit the dermatologists are not well described. Understanding why patients present to dermatologists could be helpful in identifying patients' unmet needs and developing outreach programs to improve patients' access to care. The purpose of this study is to characterize the reasons why US patients sought medical attention from dermatologists. METHODS: We evaluated the National Ambulatory Medical Care Survey (NAMCS) between 2007 and 2018, the most recent years available, to characterize the most common reasons patients visit the dermatologist. RESULTS: Sixty-four thousand records were identified in the NAMCS estimating 1.55 billion visits to the dermatologist in the US during the study period. The most common reasons for visits were skin examination (7.8%), skin lesion (7.5%), and discoloration/abnormal pigmentation (7.3%). For patients ≤ 18 years, the most common reasons for visits were acne (28%), warts (7.7%), and skin rash (6.4%). For patients 19-65 years and ≥ 66 years, skin examinations (7.7%) and skin lesions (10%) were the most common reasons for visits to dermatologists, respectively. CONCLUSION: By identifying the most common reasons for visits to the dermatologist, we can improve our understanding of a patient's needs and appropriate health outreach resources to improve patients' access to care.

Skin conditions affect 1.9 billion people globally. While we understand the most common diagnoses made at a dermatology visit, the reasons why patients visit the dermatologist have not been evaluated. We utilized an annual survey conducted by the Centers for Disease Control and Prevention (CDC), the National Ambulatory Medical Care Survey (NAMCS), to identify the most common reasons patients visited the dermatologist between the years 2007 and 2018, the most recent years of the survey available. The most common reasons for visits were skin examination, skin lesion, and discoloration/abnormal pigmentation. For patients ≤ 18 years, the most common reasons for visits were acne, warts, and skin rash. For patients 19­65 years and ≥ 66 years, skin examinations and skin lesions were the most common reasons for visits to dermatologists, respectively. By identifying the most common reasons for visit to the dermatologist, we can better understand a patient's needs and improve a patient's ability to access care for skin conditions.

Mg Anode Passivation Caused by the Reaction of Dissolved Sulfur in Mg-S Batteries.

As Li-ion battery optimization approaches theoretical limits, interest has grown in designing next-generation batteries from low-cost earth-abundant materials. Mg-S batteries are promising candidates, exhibiting widespread abundance of elemental precursors and a relatively large theoretical energy density albeit at lower cell voltage. However, Mg-S batteries exhibit poor reversibility, in part due to interactions between dissolved polysulfides and the Mg anode. Herein, we employ electrochemical experiments using Ag2S quasi-reference electrodes to probe the interactions between Mg anodes and dissolved polysulfides. We show that Mg2+ reduction (charging) is impeded in the presence of polysulfides, while Mg metal oxidation (discharging) remains facile. Large reduction overpotentials arise due to the formation of a passivation layer on the anode surface, likely composed primarily of MgS. The passivation layer is removed under oxidative conditions but quickly reforms during reduction. We discover that dissolved S8 influences the rate of MgS formation by shifting the polysulfide disproportionation equilibria. Shorter-chain polysulfides react more readily than longer-chain polysulfides at the Mg electrode, and thus, film formation is mediated by the electrochemical generation of shorter-chain polysulfide species.

Protein Substrates Engage the Lumen of O-GlcNAc Transferase's Tetratricopeptide Repeat Domain in Different Ways.

Glycosylation of nuclear and cytoplasmic proteins is an essential post-translational modification in mammals. O-GlcNAc transferase (OGT), the sole enzyme responsible for this modification, glycosylates more than 1000 unique nuclear and cytoplasmic substrates. How OGT selects its substrates is a fundamental question that must be answered to understand OGT's unusual biology. OGT contains a long tetratricopeptide repeat (TPR) domain that has been implicated in substrate selection, but there is almost no information about how changes to this domain affect glycosylation of individual substrates. By profiling O-GlcNAc in cell extracts and probing glycosylation of purified substrates, we show here that ladders of asparagines and aspartates that extend the full length of OGT's TPR lumen control substrate glycosylation. Different substrates are sensitive to changes in different regions of OGT's TPR lumen. We also found that substrates with glycosylation sites close to the C-terminus bypass lumenal binding. Our findings demonstrate that substrates can engage OGT in a variety of different ways for glycosylation.

Developmentally anomalous cerebellar encephalocele arising within the cerebellopontine angle and extending into the adjacent skull base in a pediatric patient.

Lesions of the cerebellopontine angle (CPA) in young children are rare, with the most common being arachnoid cysts and epidermoid inclusion cysts. The authors report a case of an encephalocele containing heterotopic cerebellar tissue arising from the right middle cerebellar peduncle and filling the right internal acoustic canal in a 2-year-old female patient. Her initial presentation included a focal left 6th nerve palsy. Magnetic resonance imaging was suggestive of a high-grade tumor of the right CPA. The lesion was removed via a retrosigmoid approach, and histopathologic analysis revealed heterotopic atrophic cerebellar tissue. This report is the first description of a heterotopic cerebellar encephalocele within the CPA and temporal skull base of a pediatric patient.

Extending the Depth and Breadth of Physiatry Care: Five Strategies for Residents to Develop a Foundation in Hospice and Palliative Medicine.

ABSTRACT: Hospice and palliative medicine is one of seven accredited fellowship subspecialties available to graduates of physical medicine and rehabilitation residency programs. Hospice and palliative medicine and physical medicine and rehabilitation share many of the same principles and practices, and physical medicine and rehabilitation residency training can be excellent preparation for hospice and palliative medicine fellowship. However, unlike the other six physical medicine and rehabilitation subspecialties, there is currently no requirement for hospice and palliative medicine training during physical medicine and rehabilitation residency. As a result, physical medicine and rehabilitation residents may encounter limited hospice and palliative medicine exposure or education, and lack explicit opportunities to develop the basic set of palliative care symptom management and communication tools that can be applied across the spectrum of physiatry care. Here, we provide five strategies that residents can use within their own programs to develop knowledge and experience in hospice and palliative medicine.