Ancestral allele of DNA polymerase gamma modifies antiviral tolerance.

Mitochondria are critical modulators of antiviral tolerance through the release of mitochondrial RNA and DNA (mtDNA and mtRNA) fragments into the cytoplasm after infection, activating virus sensors and type-I interferon (IFN-I) response1-4. The relevance of these mechanisms for mitochondrial diseases remains understudied. Here we investigated mitochondrial recessive ataxia syndrome (MIRAS), which is caused by a common European founder mutation in DNA polymerase gamma (POLG1)5. Patients homozygous for the MIRAS variant p.W748S show exceptionally variable ages of onset and symptoms5, indicating that unknown modifying factors contribute to disease manifestation. We report that the mtDNA replicase POLG1 has a role in antiviral defence mechanisms to double-stranded DNA and positive-strand RNA virus infections (HSV-1, TBEV and SARS-CoV-2), and its p.W748S variant dampens innate immune responses. Our patient and knock-in mouse data show that p.W748S compromises mtDNA replisome stability, causing mtDNA depletion, aggravated by virus infection. Low mtDNA and mtRNA release into the cytoplasm and a slow IFN response in MIRAS offer viruses an early replicative advantage, leading to an augmented pro-inflammatory response, a subacute loss of GABAergic neurons and liver inflammation and necrosis. A population databank of around 300,000 Finnish individuals6 demonstrates enrichment of immunodeficient traits in carriers of the POLG1 p.W748S mutation. Our evidence suggests that POLG1 defects compromise antiviral tolerance, triggering epilepsy and liver disease. The finding has important implications for the mitochondrial disease spectrum, including epilepsy, ataxia and parkinsonism.

CCR2 and CCR5 co-inhibition modulates immunosuppressive myeloid milieu in glioma and synergizes with anti-PD-1 therapy.

Immunotherapy has revolutionized the treatment of cancers. Reinvigorating lymphocytes with checkpoint blockade has become a cornerstone of immunotherapy for multiple tumor types, but the treatment of glioblastoma has not yet shown clinical efficacy. A major hurdle to treat GBM with checkpoint blockade is the high degree of myeloid-mediated immunosuppression in brain tumors that limits CD8 T-cell activity. A potential strategy to improve anti-tumor efficacy against glioma is to use myeloid-modulating agents to target immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. We found that the co-inhibition of the chemokine receptors CCR2 and CCR5 in murine model of glioma improves the survival and synergizes robustly with anti-PD-1 therapy. Moreover, the treatment specifically reduced the infiltration of monocytic-MDSCs (M-MDSCs) into brain tumors and increased lymphocyte abundance and cytokine secretion by tumor-infiltrating CD8 T cells. The depletion of T-cell subsets and myeloid cells abrogated the effects of CCR2 and CCR5 blockade, indicating that while broad depletion of myeloid cells does not improve survival, specific reduction in the infiltration of immunosuppressive myeloid cells, such as M-MDSCs, can boost the anti-tumor immune response of lymphocytes. Our study highlights the potential of CCR2/CCR5 co-inhibition in reducing myeloid-mediated immunosuppression in GBM patients.

Antioxidant constituents from Ribes glaciale Wall.: bioassay targeted in-vitro and in-silico evaluation.

Bioassay targeted phyto-investigation of dried green walnut husk of Ribes glaciale Wall. yielded one new compound as ß-D-glucopyrano (4'→3)-ß-D-glucopyranose (1) and four known compounds namely scoparone (2), apigenin (3), ß-sitosterol (4) and ß-sitosterol-D-glucoside (5). The structure of new compound was elucidated with the help of 1D, 2D and HRESIMS analysis. The antioxidant activity of extract, fractions and pure were evaluated using 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric ion reducing antioxidant power (FRAP) assays that found in the following order: butanol fr. (BF) > chloroform fr. (CF) > ethylacetate fr. (EF) > Petroleum ether fr. (PF). To search for potent antioxidant agents in extract, the isolated compounds 1, 2, 3, 4 and 5 were docked on the enzyme human NADPH oxidase, lipoxygenase, cytochrome P450 and myeloperoxidase. The compound 1 was found a potent inhibitor of target enzyme revealing its high free radical scavenging potential.

Orthopedic Surgery Matched Applicants Are Publishing More: A Bibliometric Analysis of Research Output.

Introduction This study analyzed the number of peer-reviewed publications submitted by matriculants prior to applying for the orthopedic surgery residency. The graduating residency classes of 2023 and 2027 were included in the study to understand the trend of publications, to inform aspiring orthopedic surgeons. Methods The top, middle, and bottom 10 orthopedic surgery residency programs were identified on the Doximity online website. Matriculants were searched on PubMed and Google Scholar for publication contributions. Variables including number of publications, orthopedic publications, first-author authorship, and H-index were analyzed. A logistic regression model was created, and a t-test was conducted to statistically compare the 2027 and 2023 graduating classes. Results Matriculants of the 2023 match had higher numbers of publications, orthopedic surgery-specific publications, first authorships, and h-indices than the matriculants of the 2018 match. Conclusion The average number of publications has been observed to increase over four years, indicating an increase in competition to match into orthopedic surgery residency. Publishing in higher numbers may be a good indicator of an applicant's success in not only matching but also matching into a higher-tier program.

A Comprehensive Review of the Historical Description of Spine Surgery and Its Evolution.

Major strides in the advancement of spine surgery came about in the 21st century. However, the extensive history of spine surgery can be traced back to long before this time. A clear description of the journey from a primitive yet accurate understanding of the human musculoskeletal system to today's modern aspects of spinal techniques is lacking. A narrative literature review was conducted to elucidate where spine surgery began and the techniques used that evolved over time. This review was conducted using PubMed and Google Scholar. Search terms used included "history of spine surgery," "evolution of spine surgery," "origins of spine surgery," "history of laminectomy," "history of spinal fusion," "history of lumbar interbody fusion," "minimally invasive spine surgery," and "navigation in spine surgery." We highlight the evolution of the basic understanding of anatomy and non-surgical and surgical techniques, including bracing, laminectomy, discectomy, and spinal fusion. The current evolution and integration of minimally invasive techniques, lumbar interbody fusion techniques, robotics, navigation, and motion preservation are discussed, as these are the major areas of focus for technological advancement. This review presents an overarching synopsis of the events that chronicle the progress made in spine surgery since its conception. The review uniquely contributes to the growing body of literature on the expansion of spine surgery and highlights major events in its history.

Robotic-Assisted Versus Fluoroscopic-Guided Surgery on the Accuracy of Spine Pedicle Screw Placement: A Systematic Review and Meta-Analysis.

Spinal fusion is a common method by which surgeons decrease instability and deformity of the spinal segment targeted. Pedicle screws are vital tools in fusion surgeries and advancements in technology have introduced several modalities of screw placement. Our objective was to evaluate the accuracy of pedicle screw placement in robot-assisted (RA) versus fluoroscopic-guided (FG) techniques. The PubMed and Cochrane Library databases were systematically reviewed from January 2007 through to August 8, 2022, to identify relevant studies. The accuracy of pedicle screw placement was determined using the Gertzbein-Robbins (GR) classification system. Facet joint violation (FJV), total case radiation dosage, total case radiation time, total operating room (OR) time, and total case blood loss were collected. Twenty-one articles fulfilled the inclusion criteria. Successful screw accuracy (GR Grade A or B) was found to be 1.02 (95% confidence interval: 1.01 - 1.04) times more likely with the RA technique. In defining accuracy solely based on the GR Grade A criteria, screws placed with RA were 1.10 (95% confidence interval: 1.06 - 1.15) times more likely to be accurate. There was no significant difference between the two techniques with respect to blood loss (Hedges' g: 1.16, 95% confidence interval: -0.75 to 3.06) or case radiation time (Hedges' g: -0.34, 95% CI: -1.22 to 0.53). FG techniques were associated with shorter operating room times (Hedges' g: -1.03, 95% confidence interval: -1.76 to -0.31), and higher case radiation dosage (Hedges' g: 1.61, 95% confidence interval: 1.11 to 2.10). This review suggests that RA may slightly increase pedicle screw accuracy and decrease per-case radiation dosage compared to FG techniques. However, total operating times for RA cases are greater than those for FG cases.

Translation and Adaptation of Cognistat in Hindi Language: For Computerized Evaluation of Cognitive Functioning.

OBJECTIVE: Cognitive assessment is a crucial element of the mental health screening process. However, there is a lack of culturally appropriate cognitive screening tools for the Hindi-speaking aging population in India. We aimed to translate and culturally tailor the English version of the computerized Cognistat test for the Hindi-speaking aging population. METHOD: The computer-based Cognistat Assessment System was culturally adapted for the North Indian Hindi-speaking population. Participants with mild cognitive impairment (MCI) (n = 30), depression (n = 30), and healthy control (n = 30) groups between the age range of 50 and 83 years were assessed using the translated version of the tool. The group differences were analyzed using analysis of variance, multivariate analysis of variance, Tukey's post hoc analysis for continuous variables, and Fisher's exact test for categorical variables. The correlation between the Cognistat domains was analyzed using Pearson's correlation, and test reliability was assessed using Cronbach's alpha. RESULTS: The MCI group had significantly lower scores as compared with the depression and control groups on orientation, language, repetition, and calculation domain tasks. For attention and construction tasks, the MCI group had lower scores than the control group. MCI group scores were significantly lower than the control group on naming domain. The Hindi version of the test was reliable for the Hindi-speaking aging population. CONCLUSIONS: Cognistat Hindi can be used by trained healthcare professionals with Hindi-speaking populations for culturally tailored primary evaluation of cognitive difficulties. Future research should focus on further validation and assessment of its properties.

Venous Anomalies Complicating Anterior Lumbar Interbody Fusion Exposures.

The effects of anomalous vasculature impeding optimal exposure to an anterior lumbar interbody fusion approach are limited in literature. We present five individual, unique cases of vascular anomalies in patients undergoing two-stage anterior-posterior lumbar interbody fusion. Cases 1, 2, 4, and 5 have yet to be described in literature in context of anterior lumbar interbody fusions. Case 3 presents anomalous vasculature that has only been described in two other case reports. Case 1 presents the right internal iliac vein originating from the left common iliac vein which was transected for L4-L5 vertebral disc exposure. Case 2 presents the left internal iliac vein originating from the right common iliac vein which required an oblique approach. Case 3 presents a duplicated inferior vena cava that was taken into account but did not interfere with the anterior retroperitoneal approach. Case 4 presents large osteophytes adhering to the left common iliac vein which limited safe dissection and mobilization. Case 5 presents the left internal iliac vein with a high takeoff spanning across the L5-S1 vertebral disc space and requiring transection. This case series highlights the need for preoperative imaging and a working detailed knowledge of anatomy to avoid damaging vasculature that can potentially lead to fatal consequences. The information given in this case series should inform both spine and vascular surgeons on proper preoperative planning. To maximize operative efficiency and safety, spine surgeons and vascular surgeons should collaborate to minimize surgical complications.

Lumbosacral Vertebral Osteomyelitis With Iliopsoas and Epidural Abscess Following Intravesical Bacillus Calmette-Guérin Therapy.

Intravesical Bacillus Calmette-Guérin (BCG) therapy is the gold-standard adjuvant therapy for patients with superficial or non-muscle-invasive bladder cancer. BCG is a live attenuated strain of Mycobacterium bovis, which induces an antitumor environment, effectively fighting malignant uroepithelial cells through cytotoxic reactions. However, BCG therapy may stimulate local or disseminated infections. In rare cases, vertebral osteomyelitis may arise in the thoracolumbar spine, mostly affecting older males. This is a case of an 84-year-old male patient who developed L5-S1 osteomyelitis with associated epidural and iliopsoas abscess. Symptoms manifested as severe low back pain and bilateral lower extremity weakness. This paper aims to raise awareness of and educate spine surgeons in recognizing this uncommon complication by taking into context a history of BCG therapy.

Interventional Therapy and Surgical Management of Lumbar Disc Herniation in Spine Surgery: A Narrative Review.

Significant advancements in lumbar disc herniation (LDH) management have been made in interventional pain therapy, operative therapy, peri-operative management, and cost analysis of various procedures. The present review aims to provide a concise narrative of all these topics, current trends, and possible future directions in the management of LDH. Interventional pain management using intradiscal injections often serves as a minimally invasive non-surgical approach. Surgical modalities vary, including traditional open laminectomy, microdiscectomy, endoscopic discectomy, tubular discectomy, percutaneous laser disc decompression, and transforaminal foraminotomy. Prevention of infections during surgery is paramount and is often done via a single-dose preoperative antibiotic prophylaxis. Recurrence of LDH post-surgery is commonly observed and thus mitigative strategies for prevention have been proposed including the use of annular closure devices. Finally, all treatments are well-associated with clear as well as hidden costs to the health system and society as described by billing codes and loss of patients' quality-adjusted life-years. Our summary of recent literature regarding LDH may allow physicians to employ up-to-date evidence-based practice in clinical settings and can help drive future advancements in LDH management. Future longitudinal and comprehensive studies elucidating how each type of treatments fare against different types of herniations are warranted.

Need to rethink tDCS protocols for the treatment of alcohol use disorder: Insights from a randomized sham-controlled clinical trial among detoxified inpatients.

OBJECTIVES: Alcohol use disorder (AUD) is a chronic disorder with various health problems. Reduced functioning of the Dorsolateral Prefrontal Cortex (DLPFC) is associated with impaired regulation of alcohol-seeking behaviors and increased cravings in individuals with AUD. This study aimed to investigate whether 10 add-on sessions of tDCS, over the left DLPFC in detoxified inpatients with AUD could reduce cravings and increase abstinence rates at three months. METHODS: Detoxified inpatients with AUD were randomly assigned to either treatment as usual (TAU) plus ten sessions of active tDCS over left DLPFC, or TAU plus ten sessions of sham tDCS treatment twice daily for five consecutive days. RESULTS: The results from the generalized linear mixed model (GLMM) revealed that time had a significant effect on OCDS scores, but neither treatment nor interaction between these two factors had a significant effect on OCDS scores The Chi-square test in the intention- to- treat analysis did not show a significant difference in complete abstinence rates between the active treatment group and the sham treatment group. CONCLUSIONS: we found that adding ten sessions of active tDCS over left DLPFC tDCS to the treatment as usual for AUD did not result in improved abstinence rates or reduced craving.

Development and Validation of the AIIMS Facial Toolbox for Emotion Recognition.

Background: Emotional facial expression database, used in emotion regulation studies, is a special set of pictures with high social and biological relevance. We present the AIIMS Facial Toolbox for Emotion Recognition (AFTER) database. It consists of pictures of 15 adult professional artists displaying seven facial expressions-neutral, happiness, anger, sadness, disgust, fear, and surprise. Methods: This cross-sectional study enrolled 15 volunteer students from a professional drama college in India (six males and nine females; mean age = 26.2 ± 1.93 years). They were instructed to pose with different emotional expressions in high and low intensity. A total of 240 pictures were captured in a brightly lit room against a common, light background. Each picture was validated independently by 19 mental health professionals and two professional teachers of dramatic art. Apart from recognition of emotional quality, ratings were done for each emotion on a 5-point Likert scale with respect to three dimensions-intensity, clarity, and genuineness. Results are discussed in terms of mean scores on all four parameters. Results: The percentage hit rate for all the emotions, after exclusion of contempt, was 84.3%, with the mean kappa for emotional expression being 0.68. Mean scores on intensity, clarity, and genuineness of the emotions depicted in the pictures were high. Conclusions: The database would be useful in the Indian context for researching facial emotion recognition. It has been validated among a group of experts and was found to have high inter-rater reliability.

Somatic symptoms in schizophrenia: Association with socio-demographic and clinical characteristics, disability and quality of life.

Background and Aims: There is lack of research on somatic symptoms in schizophrenia. We aimed at finding prevalence and types of somatic symptoms in patients with schizophrenia and assessed their association with socio-demographic and clinical characteristics. Methods: We assessed somatic symptoms using Patient Health Questionnaire-15 (PHQ-15) in 93 patients with schizophrenia diagnosed on ICD10-DCR. Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms, WHO Disability Assessment Schedule 2.0, WHO Quality of Life (BREF) Hindi version and Liverpool University Neuroleptic Side-Effect Rating Scale were used to assess psychopathology, disability, quality of life and side effects. Results: Significant somatic symptoms (n ≥5 on PHQ-15) were present in 62 (67.7%) patients with schizophrenia. Forty three (69.4%) had mild (n = 5-9 on PHQ-15), 17 (27.4%) had moderate (n = 10-14 on PHQ-15), and only 2 (3.2%) had severe (n = ≥15 on PHQ -15) somatic symptoms. Mean somatic symptoms score on PHQ-15 was 7.28 (± 3.83); 96.8% reported feeling tired, 76.3% had constipation or diarrhoea, 67.7% trouble in sleeping, 61.3% nausea or indigestion, 52.7% back pain and 51.6% headache. Patients with somatic symptoms were older in age, had longer duration of illness and treatment, and had more negative symptoms. They had higher disability and poor quality of life especially in physical domain. Conclusion: Somatic symptoms are common in patients with schizophrenia and are associated with chronicity, refractoriness and negative symptoms, significant disability and poor quality of life. Thus during routine clinical practice, somatic symptoms should be assessed and managed in these patients.

Comparative evaluation of isoflurane and desflurane for postoperative cognitive decline in elderly patients: A prospective observational pilot study.

BACKGROUND: Approximately 16%-62% of patients undergoing non cardiac surgeries develop postoperative cognitive dysfunction. We compared the incidence of postoperative cognitive dysfunction in older adults aged 60-80 years who underwent open abdominal surgeries under general anaesthesia using isoflurane or desflurane and correlated it with the serum concentration of interleukin 1, interleukin 6, tumour necrosis factor alpha, amyloid ß and S100 on postoperative day 3. METHOD: Forty American Association of Anesthesiologists Physical Classification I or II patients were included after acquiring institutional ethics committee approval, registering in the Clinical Trials Registry - India, and informed written consent. They underwent open abdominal surgery under general anaesthesia and epidurals between 2017 and 2019. Patients with substance abuse or any disorder affecting cognition were excluded. Postoperative cognitive dysfunction was assessed by Stroop test, Wisconsin Card Sorting Test, Trail making test - B, Porteus Maze test, PGI memory scale, mini-mental state examination, and Bender Gestalt test the day before surgery and on the third postoperative day along with blood samples. RESULTS: Thirty-seven percent of the patients developed postoperative cognitive dysfunction. The risk was similar to isoflurane in comparison with desflurane (risk ratio: 0.65, 95% confidence interval: 0.30, 1.40). A significant percentage increase in reaction time for Porteus Maze test and Trail making test - B was noted with isoflurane (6.69 (4.20-8.94) and 8.01 (2.08-12.5), respectively) in comparison with desflurane group (13.01 (9.09-17.33), p = 0.003 and 11.62 (7.5-17.5), p = 0.017, respectively). CONCLUSION: Isoflurane and desflurane had a similar impact on the elderly for developing postoperative cognitive dysfunction and no correlation with any of the biomarkers used in the study on postoperative day 3.

RNA-Protein Interactome at the Hepatitis E Virus Internal Ribosome Entry Site.

Multiple processes exist in a cell to ensure continuous production of essential proteins either through cap-dependent or cap-independent translation processes. Viruses depend on the host translation machinery for viral protein synthesis. Therefore, viruses have evolved clever strategies to use the host translation machinery. Earlier studies have shown that genotype 1 hepatitis E virus (g1-HEV) uses both cap-dependent and cap-independent translation machineries for its translation and proliferation. Cap-independent translation in g1-HEV is driven by an 87-nucleotide-long RNA element that acts as a noncanonical, internal ribosome entry site-like (IRESl) element. Here, we have identified the RNA-protein interactome of the HEV IRESl element and characterized the functional significance of some of its components. Our study identifies the association of HEV IRESl with several host ribosomal proteins, demonstrates indispensable roles of ribosomal protein RPL5 and DHX9 (RNA helicase A) in mediating HEV IRESl activity, and establishes the latter as a bona fide internal translation initiation site. IMPORTANCE Protein synthesis is a fundamental process for survival and proliferation of all living organisms. The majority of cellular proteins are produced through cap-dependent translation. Cells also use a variety of cap-independent translation processes to synthesize essential proteins during stress. Viruses depend on the host cell translation machinery to synthesize their own proteins. Hepatitis E virus (HEV) is a major cause of hepatitis worldwide and has a capped positive-strand RNA genome. Viral nonstructural and structural proteins are synthesized through a cap-dependent translation process. An earlier study from our laboratory reported the presence of a fourth open reading frame (ORF) in genotype 1 HEV, which produces the ORF4 protein using a cap-independent internal ribosome entry site-like (IRESl) element. In the current study, we identified the host proteins that associate with the HEV-IRESl RNA and generated the RNA-protein interactome. Through a variety of experimental approaches, our data prove that HEV-IRESl is a bona fide internal translation initiation site.

Functional near-infrared spectroscopy guided mapping of frontal cortex, a novel modality for assessing emergence delirium in children: A prospective observational study.

INTRODUCTION: Despite an 18%-30% prevalence, there is no consensus regarding pathogenesis of emergence delirium after anesthesia in children. Functional near-infrared spectroscopy (fNIRS) is an optical neuroimaging modality that relies on blood oxygen level-dependent response, translating to a mean increase in oxyhemoglobin and a decrease in deoxyhemoglobin. We aimed to correlate the emergence delirium in the postoperative period with the changes in the frontal cortex utilizing fNIRS reading primarily and also with blood glucose, serum electrolytes, and preoperative anxiety scores. METHODS: A total of 145 ASA I and II children aged 2-5 years, undergoing ocular examination under anesthesia, were recruited by recording the modified Yale Preoperative Anxiety Score after acquiring the Institute Ethics Committee approval and written informed parental consent. Induction and maintenance were done with O2, N2O, and Sevoflurane. The emergence delirium was assessed using the PAED score in the postoperative period. The frontal cortex fNIRS recordings were taken throughout anesthesia. RESULTS: A total of 59 children (40.7%) had emergence delirium. The ED+ group had a significant activation left superior frontal cortex (t = 2.26E+00; p = .02) and right middle frontal cortex (t = 2.27E+00; p = .02) during induction, significant depression in the left middle frontal (t = -2.22E+00; p = .02), left superior frontal and bilateral medial (t = -3.01E+00; p = .003), right superior frontal and bilateral medial (t = -2.44E+00; p = .015), bilateral medial and superior (t = -3.03E+00; p = .003), and right middle frontal cortex (t = -2.90E+00; p = .004) during the combined phase of maintenance, and significant activation in cortical activity in the left superior frontal cortex (t = 2.01E+00; p = .0047) during the emergence in comparison with the ED- group. CONCLUSION: There is significant difference in the change in oxyhemoglobin concentration during induction, maintenance, and emergence in specific frontal brain regions between children with and without emergence delirium.

Computational study on 2D three-phase lag bioheat model during cryosurgery using RBF meshfree method.

Biological tissue has a multidimensional and non-homogeneous inner structure by nature. The temperature distribution and freezing front locations in biological tissue are crucial to optimizing the damage to tissue during cryosurgery. There is a need for a good mathematical model and effective simulation techniques to predict the effectiveness of the therapy. The present study concerns the numerical study of phase change phenomena during cryosurgery using the three-phase lag (TPL) bioheat model in arbitrary soft tissue domains, i.e., circular (Γ1), ameba-like (Γ2), and multiconnected (Γ3). We employ the effective heat capacity formulation to solve the nonlinear governing equation. The Gaussian radial basis function and Crank-Nicolson finite difference approximation are applied for spatial and time derivatives, respectively. Using the present algorithm, we study the impact of phase lag (τv) due to thermal displacement involved in the TPL model on phase change interface position and thermal distribution in all three domains. The obtained results may be beneficial in the field of oncology.

Modified frailty index independently predicts morbidity in patients undergoing 3-column osteotomy.

PURPOSE: Adult Spinal Deformity (ASD) includes a spectrum of spinal conditions that can be associated with significant pain and loss of function. While 3-column osteotomies have been the procedures of choice for ASD patients, there is also a substantial risk for complications. The prognostic value of the modified 5-item frailty index (mFI-5) for these procedures has not yet been studied. The goal of this study is to evaluate the association of mFI-5 with 30-day morbidity, readmission, and reoperation following a 3-column osteotomy. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried to identify patients undergoing 3-Column Osteotomy procedures from 2011-2019. Multivariate modeling was utilized to assess mFI-5 and other demographic, comorbidity, laboratory, and perioperative variables as independent predictors of morbidity, readmission, and reoperation. RESULTS: N = 971. Multivariate analysis revealed that mFI-5 = 1 (OR = 1.62, p = 0.015) and mFI-5 ≥ 2 (OR = 2.17, p = 0.004) were significant independent predictors of morbidity. mFI-5 ≥ 2 was a significant independent predictor of readmission (OR = 2.16, p = 0.022) while mFI-5 = 1 was not a significant predictor of readmission (p = 0.053). Frailty did not predict reoperation. CONCLUSION: Frailty as defined by mFI-5 strongly and independently predicted increased odds of postoperative morbidity for patients undergoing 3-column osteotomy as surgical intervention for ASD. Only mFI-5 ≥ 2 was a significant independent predictor of readmission, while frailty did not predict reoperation. Other variables independently predicted increased and decreased odds of postoperative morbidity, readmission, and reoperation. LEVEL OF EVIDENCE: III.

Ablation of Adar1 in myeloid cells imprints a global antiviral state in the lung and heightens early immunity against SARS-CoV-2.

Under normal homeostatic conditions, self-double-stranded RNA (self-dsRNA) is modified by adenosine deaminase acting on RNA 1 (ADAR1) to prevent the induction of a type I interferon-mediated inflammatory cascade. Antigen-presenting cells (APCs) sense pathogen-associated molecular patterns, such as dsRNA, to activate the immune response. The impact of ADAR1 on the function of APCs and the consequences to immunity are poorly understood. Here, we show that ADAR1 deletion in CD11c+ APCs leads to (1) a skewed myeloid cell compartment enriched in inflammatory cDC2-like cells, (2) enhanced numbers of activated tissue resident memory T cells in the lung, and (3) the imprinting of a broad antiviral transcriptional signature across both immune and non-immune cells. The resulting changes can be partially reversed by blocking IFNAR1 signaling and promote early resistance against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our study provides insight into the consequences of self-dsRNA sensing in APCs on the immune system.