Liver-specific mitochondrial amidoxime-reducing component 1 (Mtarc1) knockdown protects the liver from diet-induced MASH in multiple mouse models.

BACKGROUND: Human genetic studies have identified several mitochondrial amidoxime-reducing component 1 (MTARC1) variants as protective against metabolic dysfunction-associated steatotic liver disease. The MTARC1 variants are associated with decreased plasma lipids and liver enzymes and reduced liver-related mortality. However, the role of mARC1 in fatty liver disease is still unclear. METHODS: Given that mARC1 is mainly expressed in hepatocytes, we developed an N-acetylgalactosamine-conjugated mouse Mtarc1 siRNA, applying it in multiple in vivo models to investigate the role of mARC1 using multiomic techniques. RESULTS: In ob/ob mice, knockdown of Mtarc1 in mouse hepatocytes resulted in decreased serum liver enzymes, LDL-cholesterol, and liver triglycerides. Reduction of mARC1 also reduced liver weight, improved lipid profiles, and attenuated liver pathological changes in 2 diet-induced metabolic dysfunction-associated steatohepatitis mouse models. A comprehensive analysis of mARC1-deficient liver from a metabolic dysfunction-associated steatohepatitis mouse model by metabolomics, proteomics, and lipidomics showed that Mtarc1 knockdown partially restored metabolites and lipids altered by diet. CONCLUSIONS: Taken together, reducing mARC1 expression in hepatocytes protects against metabolic dysfunction-associated steatohepatitis in multiple murine models, suggesting a potential therapeutic approach for this chronic liver disease.

Statewide surveillance of Ixodes scapularis (Acari: Ixodidae) for the presence of the human pathogen Borrelia miyamotoi (Spirochaetales: Spirochaetaceae), a relapsing fever spirochete in Pennsylvania, USA, 2019-2020.

Borrelia miyamotoi disease is an emerging tick-borne human illness in the United States caused by Borrelia miyamotoi (Spirochaetales: Spirochaetaceae) bacterium. With Pennsylvania reporting thousands of tick-borne disease cases annually, determining the minimum infection rate (MIR) of B. miyamotoi in Ixodes scapularis (Say, Acari: Ixodidae) adults within Pennsylvania is of utmost importance. Active surveillance was performed from October 2019 to April 2020 to collect a minimum of 50 I. scapularis ticks from every county within Pennsylvania and then screened for B. miyamotoi via qPCR. Ticks were collected from all 67 counties with the majority of those being adult I. scapularis. Additional ticks collected were Dermacentor albipictus (Packard, Acari: Ixodidae), Haemaphysalis longicornis (Neumann, Acari: Ixodidae), and immature I. scapularis. Adult I. scapularis were pooled and tested for B. miyamotoi. MIR for positive B. miyamotoi pools and density of infected adult I. scapularis varied by county, with positive pools from 38 Pennsylvania counties. This is the first statewide evaluation of B. miyamotoi in Pennsylvania in questing adult I. scapularis. These prevalence and distribution data will aid health care practitioners within the state of Pennsylvania and the northeast United States to understand potential risk and bring awareness to the lesser known human Borrelia illness, Borrelia miyamotoi disease.

Running Habits and Injury Frequency Following COVID-19 Restrictions in Adolescent Long-Distance Runners.

PURPOSE: A decline in youth running was observed at the start of the COVID-19 pandemic. We investigated whether the resumption of organized running after social distancing restrictions changed running habits or injury frequency in adolescent runners. METHODS: Adolescents (age = 16.1 [2.1] y) who participated in long-distance running activities completed an online survey in the Spring and Fall of 2020. Participants self-reported average weekly running habits and whether they sustained an injury during the Fall 2020 season. Poisson regression models and 1-way analysis of variance compared running habits while Fisher exact test compared differences in frequencies of injuries during Fall 2020 among season statuses (full, delayed, and canceled). RESULTS: All runners, regardless of season status, increased weekly distance during Fall 2020. Only runners with a full Fall 2020 season ran more times per week and more high-intensity runs per week compared with their Spring 2020 running habits. There were no differences in running volume or running-related injury frequency among Fall 2020 season statuses. CONCLUSIONS: There were no significant differences in running-related injury (RRI) frequency among runners, regardless of season status, following the resumption of cross-country. Health care providers may need to prepare for runners to increase running volume and intensity following the resumption of organized team activities.

Long-term outcomes of robotic versus video-assisted pulmonary lobectomy for non-small cell lung cancer: systematic review and meta-analysis of reconstructed patient data.

Background: Video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS) are two viable options in patients undergoing lobectomy for non-small cell lung cancer (NSCLC); however, the debate on which one is superior is unceasing. Methods: PubMed and Scopus databases were queried for studies including patients who underwent either VATS or RATS lobectomy. This meta-analysis is in accordance with the recommendations of the PRISMA statement. Individual patient data on overall survival (OS) and disease-free survival (DFS) were extracted from Kaplan-Meier curves. One- and two-stage survival analyses, and random-effects meta-analyses were conducted. Results: Ten studies met our eligibility criteria, incorporating 1,231 and 814 patients in the VATS and RATS groups, respectively. Patients who underwent VATS had similar OS compared with those who underwent RATS [hazard ratio (HR): 1.05, 95% confidence interval (CI): 0.88-1.27, P=0.538] during a weighted median follow-up of 51.7 months, and this was validated by the two-stage meta-analysis (HR: 1.27, 95% CI: 0.85-1.90, P=0.24, I2=68.50%). Regarding DFS, the two groups also displayed equivalent outcomes (HR: 1.07, 95% CI: 0.92-1.25, P=0.371) and this was once again validated by the two-stage meta-analysis (HR: 1.05, 95% CI: 0.85-1.30, P=0.67, I2=28.27%). Both RATS and VATS had similar postoperative complication rates, prolonged air leak, conversion to thoracotomy and operative times. RATS was found to be superior to VATS in terms of length of hospital stay and number of lymph nodes dissected. Conclusions: In patients undergoing lobectomy for NSCLC, VATS and RATS have equivalent overall and DFS at a median follow-up of 51.7 months.

Primary Total Shoulder Arthroplasty is Superior to Hemiarthroplasty for the Treatment of Glenohumeral Arthritis: Analysis of 5-year Outcomes in a Large Surgical Database.

Background: Total shoulder arthroplasty (TSA) is the preferred treatment for glenohumeral arthritis refractory to nonoperative measures. However, some surgeons have argued for a role for hemiarthroplasty (HA) in the setting of a smooth glenoid that articulates appropriately with the humeral head. The purpose of this study is to evaluate long-term revision rates and short-term postoperative complications in patients undergoing either HA or TSA for glenohumeral arthritis. Methods: A retrospective review of patients who underwent HA and TSA was conducted using a commercially available national database. Demographics, postoperative complications, risk factors, revision rates, and costs were analyzed using 2 sample t-tests, chi-squared tests, and multivariate logistic regressions. Results: Patients were stratified by operation: (1) HA (n = 1615) or 2) TSA (n = 7845). Patients undergoing primary TSA had higher rates of prior ipsilateral rotator cuff repair and corticosteroid injections. At 2 years, patients who underwent HA, 3.0% of patients had revision surgery, compared to 1.6% of patients who underwent TSA (P = .002); at 5 years, 3.7% of the HA cohort (P < .0001) had revision surgery, compared to 1.9% of patients who underwent TSA. Conclusions: Patients undergoing TSA or RTSA for glenohumeral arthritis had higher preoperative co-morbidities but had no difference in short-term complication rates with a lower risk of revision surgery at both 2-year and 5-year follow-up when compared to HA. Increasing age, female sex, hyperlipidemia, postoperative infection, shoulder instability, and thromboembolism all independently increased odds for revision shoulder arthroplasty for glenohumeral arthritis. Level of evidence Level: III.

Creating resistance to avian influenza infection through genome editing of the ANP32 gene family.

Chickens genetically resistant to avian influenza could prevent future outbreaks. In chickens, influenza A virus (IAV) relies on host protein ANP32A. Here we use CRISPR/Cas9 to generate homozygous gene edited (GE) chickens containing two ANP32A amino acid substitutions that prevent viral polymerase interaction. After IAV challenge, 9/10 edited chickens remain uninfected. Challenge with a higher dose, however, led to breakthrough infections. Breakthrough IAV virus contained IAV polymerase gene mutations that conferred adaptation to the edited chicken ANP32A. Unexpectedly, this virus also replicated in chicken embryos edited to remove the entire ANP32A gene and instead co-opted alternative ANP32 protein family members, chicken ANP32B and ANP32E. Additional genome editing for removal of ANP32B and ANP32E eliminated all viral growth in chicken cells. Our data illustrate a first proof of concept step to generate IAV-resistant chickens and show that multiple genetic modifications will be required to curtail viral escape.

Correlates of poor clinical outcomes related to COVID-19 among older people with psychiatric illness - a mixed methods study.

OBJECTIVE: COVID-19 may lead to a range of clinical outcomes among older people with psychiatric and medical conditions. Evidence guiding management of future outbreaks among this vulnerable population in psychiatric hospital settings are sparse. In this study, we examined the correlates of poor clinical outcomes related to COVID-19 and explored the perspectives of COVID-19 survivors hospitalized in psychiatry settings. METHOD: The correlates of poor clinical outcomes related to COVID-19 were examined using a retrospective chart review of 81 older people hospitalized in psychiatry settings. Correlates of clinical outcomes related to COVID-19 were assessed by multiple logistic regression models. In addition, the perspectives of 10 COVID-19 survivors were explored by qualitative interviews. The qualitative data was subject to thematic analysis. RESULTS: Although 25.9% (n = 21) participants were asymptomatic, there was high COVID-19 related mortality (14.8%; n = 12). Vitamin-D deficiency, anticholinergic burden, and isolation policies within psychiatric wards were significantly (p < 0.05) related to COVID-19 related deaths. In qualitative interviews, participants emphasized the importance of strengthening local support networks and making vaccination centers more accessible. CONCLUSIONS: Reducing anticholinergic prescriptions and improving isolation policies may help to mitigate poor clinical outcomes. Future research investigating the impact of vitamin-D supplementation on COVID-19 related outcomes is warranted.

Outcomes Following Lung Transplant for COVID-19-Related Complications in the US.

Importance: The COVID-19 pandemic led to the use of lung transplant as a lifesaving therapy for patients with irreversible lung injury. Limited information is currently available regarding the outcomes associated with this treatment modality. Objective: To describe the outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis. Design, Setting, and Participants: In this cohort study, lung transplant recipient and donor characteristics and outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis were extracted from the US United Network for Organ Sharing database from March 2020 to August 2022 with a median (IQR) follow-up period of 186 (64-359) days in the acute respiratory distress syndrome group and 181 (40-350) days in the pulmonary fibrosis group. Overall survival was calculated using the Kaplan-Meier method. Cox proportional regression models were used to examine the association of certain variables with overall survival. Exposures: Lung transplant following COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis. Main Outcomes and Measures: Overall survival and graft failure rates. Results: Among 385 included patients undergoing lung transplant, 195 had COVID-19-related acute respiratory distress syndrome (142 male [72.8%]; median [IQR] age, 46 [38-54] years; median [IQR] allocation score, 88.3 [80.5-91.1]) and 190 had COVID-19-related pulmonary fibrosis (150 male [78.9%]; median [IQR] age, 54 [45-62]; median [IQR] allocation score, 78.5 [47.7-88.3]). There were 16 instances of acute rejection (8.7%) in the acute respiratory distress syndrome group and 15 (8.6%) in the pulmonary fibrosis group. The 1-, 6-, and 12- month overall survival rates were 0.99 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.91-0.98), and 0.88 (95% CI, 0.80-0.94) for the acute respiratory distress syndrome cohort and 0.96 (95% CI, 0.92-0.98), 0.92 (95% CI, 0.86-0.96), and 0.84 (95% CI, 0.74-0.90) for the pulmonary fibrosis cohort. Freedom from graft failure rates were 0.98 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.90-0.97), and 0.88 (95% CI, 0.79-0.93) in the 1-, 6-, and 12-month follow-up periods in the acute respiratory distress cohort and 0.96 (95% CI, 0.92-0.98), 0.93 (95% CI, 0.87-0.96), and 0.85 (95% CI, 0.74-0.91) in the pulmonary fibrosis cohort, respectively. Receiving a graft from a donor with a heavy and prolonged history of smoking was associated with worse overall survival in the acute respiratory distress syndrome cohort, whereas the characteristics associated with worse overall survival in the pulmonary fibrosis cohort included female recipient, male donor, and high recipient body mass index. Conclusions and Relevance: In this study, outcomes following lung transplant were similar in patients with irreversible respiratory failure due to COVID-19 and those with other pretransplant etiologies.

Comparison of indoor (refrigerated) versus outdoor winter storage of commercial honey bee, Apis mellifera (Hymenoptera: Apidae), colonies in the Western United States.

Honey bees (Apis mellifera L.) are critical to the pollination of many important crops in the United States, and one crop that demands large numbers of colonies early each year is almonds. To provide adequate numbers of colonies for almond pollination, many beekeepers move colonies of bees to high-density holding yards in California in late fall, where the bees can fly and forage, but little natural pollen and nectar is available. In recent years, high colony losses have occurred in some operations following this management strategy, and alternative approaches, including indoor storage of colonies, have become more commonly used. The current study evaluated colonies kept indoors (refrigerated and/or controlled atmosphere) for the winter compared with those kept outdoors in either Washington or California. Colonies were evaluated for strength (frames of bees), brood area, lipid composition of worker bees, colony weight and survival, parasitic mites (Varroa mites, tracheal mites), and pathogens (Nosema spp.). No differences were found in colony weight, survival, parasitic mite levels, or pathogen prevalence among the treatments. Colonies stored indoors and outdoors in WA had significantly more frames of bees and less brood present after the storage period than colonies stored outdoors in CA. Lipid composition of honey bees stored indoors was significantly higher than colonies stored outdoors in WA or CA. The implications of these findings for overall colony health and improved pollination activity are discussed.

Communication of Positive Lung Cancer Screening Findings and Receipt of Recommended Follow-up Care.

This cohort study evaluates associations of communication methods and content of positive lung cancer screening findings with receipt of recommended follow-up care.

An Immunologic and Biomechanical Comparison of Polyether Ether Ketone-Zeolite and Polyether Ether Ketone Interbody Fusion Devices.

STUDY DESIGN: A laboratory study comparing polyether ether ketone (PEEK)-zeolite and PEEK spinal implants in an ovine model. OBJECTIVE: This study challenges a conventional spinal implant material, PEEK, to PEEK-zeolite using a nonplated cervical ovine model. SUMMARY OF BACKGROUND DATA: Although widely used for spinal implants due to its material properties, PEEK is hydrophobic, resulting in poor osseointegration, and elicits a mild nonspecific foreign body response. Zeolites are negatively charged aluminosilicate materials that are hypothesized to reduce this pro-inflammatory response when used as a compounding material with PEEK. MATERIALS AND METHODS: Fourteen skeletally mature sheep were, each, implanted with one PEEK-zeolite interbody device and one PEEK interbody device. Both devices were packed with autograft and allograft material and randomly assigned to one of 2 cervical disc levels. The study involved 2 survival time points (12 and 26 weeks) and biomechanical, radiographic, and immunologic endpoints. One sheep expired from complications not related to the device or procedure. A biomechanical evaluation was based on measures of segmental flexibility, using 6 degrees of freedom pneumatic spine tester. Radiographic evaluation was performed using microcomputed tomography scans in a blinded manner by 3 physicians. Levels of the pro-inflammatory cytokines, interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha at the implant, were quantified using immunohistochemistry. RESULTS: PEEK-zeolite and PEEK exhibited an equivalent range of motion in flexion extension, lateral bending, and axial torsion. A motion was significantly reduced for implanted devices at both time points as compared with native segments. Radiographic assessments of fusion and bone formation were similar for both devices. PEEK-zeolite exhibited lower levels of IL-1ß ( P = 0.0003) and IL-6 ( P = 0.03). CONCLUSION: PEEK-zeolite interbody fusion devices provide initial fixation substantially equivalent to PEEK implants but exhibit a reduced pro-inflammatory response. PEEK-zeolite devices may reduce the chronic inflammation and fibrosis previously observed with PEEK devices.

Mammalian ANP32A and ANP32B Proteins Drive Differential Polymerase Adaptations in Avian Influenza Virus.

ANP32 proteins, which act as influenza polymerase cofactors, vary between birds and mammals. In mammals, ANP32A and ANP32B have been reported to serve essential but redundant roles to support influenza polymerase activity. The well-known mammalian adaptation PB2-E627K enables influenza polymerase to use mammalian ANP32 proteins. However, some mammalian-adapted influenza viruses do not harbor this substitution. Here, we show that alternative PB2 adaptations, Q591R and D701N, also allow influenza polymerase to use mammalian ANP32 proteins, whereas other PB2 mutations, G158E, T271A, and D740N, increase polymerase activity in the presence of avian ANP32 proteins as well. Furthermore, PB2-E627K strongly favors use of mammalian ANP32B proteins, whereas D701N shows no such bias. Accordingly, PB2-E627K adaptation emerges in species with strong pro-viral ANP32B proteins, such as humans and mice, while D701N is more commonly seen in isolates from swine, dogs, and horses, where ANP32A proteins are the preferred cofactor. Using an experimental evolution approach, we show that the passage of viruses containing avian polymerases in human cells drove acquisition of PB2-E627K, but not in the absence of ANP32B. Finally, we show that the strong pro-viral support of ANP32B for PB2-E627K maps to the low-complexity acidic region (LCAR) tail of ANP32B. IMPORTANCE Influenza viruses naturally reside in wild aquatic birds. However, the high mutation rate of influenza viruses allows them to rapidly and frequently adapt to new hosts, including mammals. Viruses that succeed in these zoonotic jumps pose a pandemic threat whereby the virus adapts sufficiently to efficiently transmit human-to-human. The influenza virus polymerase is central to viral replication and restriction of polymerase activity is a major barrier to species jumps. ANP32 proteins are essential for influenza polymerase activity. In this study, we describe how avian influenza viruses can adapt in several different ways to use mammalian ANP32 proteins. We further show that differences between mammalian ANP32 proteins can select different adaptive changes and are responsible for some of the typical mutations that arise in mammalian-adapted influenza polymerases. These different adaptive mutations may determine the relative zoonotic potential of influenza viruses and thus help assess their pandemic risk.

Cancer-related Fatigue in Lung Cancer: A Research Agenda: An Official American Thoracic Society Research Statement.

Background: Fatigue is the most common symptom among cancer survivors. Cancer-related fatigue (CRF) may occur at any point in the cancer care continuum. Multiple factors contribute to CRF development and severity, including cancer type, treatments, presence of other symptoms, comorbidities, and medication side effects. Clinically, increasing physical activity, enhancing sleep quality, and recognizing sleep disorders are integral to managing CRF. Unfortunately, CRF is infrequently recognized, evaluated, or treated in lung cancer survivors despite more frequent and severe symptoms than in other cancers. Therefore, increased awareness and understanding of CRF are needed to improve health-related quality of life in lung cancer survivors. Objectives: 1) To identify and prioritize knowledge and research gaps and 2) to develop and prioritize research questions to evaluate mechanistic, diagnostic, and therapeutic approaches to CRF among lung cancer survivors. Methods: We convened a multidisciplinary panel to review the available literature on CRF, focusing on the impacts of physical activity, rehabilitation, and sleep disturbances in lung cancer. We used a three-round modified Delphi process to prioritize research questions. Results: This statement identifies knowledge gaps in the 1) detection and diagnostic evaluation of CRF in lung cancer survivors; 2) timing, goals, and implementation of physical activity and rehabilitation; and 3) evaluation and treatment of sleep disturbances and disorders to reduce CRF. Finally, we present the panel's initial 32 research questions and seven final prioritized questions. Conclusions: This statement offers a prioritized research agenda to 1) advance clinical and research efforts and 2) increase awareness of CRF in lung cancer survivors.

US Prison Policies on Organ Donation for Individuals Who Are Incarcerated.

This cross-sectional study collects data on US prison policies concerning organ donation by incarcerated individuals.

Transthoracic fundoplication using the Belsey Mark IV technique versus Nissen fundoplication: A systematic review and meta-analysis.

BACKGROUND: Nissen fundoplication is considered the cornerstone surgical treatment for hiatal hernia repair. Belsey Mark IV (BMIV) transthoracic fundoplication is an alternative approach that is rarely utilized in today's minimally invasive era. This study aims to summarize the safety and efficacy of BMIV and to compare it with Nissen fundoplication. METHODS: We searched MEDLINE, Scopus, and Cochrane Library databases for single arm and comparative studies published by March 31st, 2022, according to PRISMA statement. Inverse-variance weights were used to estimate the proportion of patients experiencing the studied outcome and random-effects meta-analyses were performed. RESULTS: 17 studies were identified, incorporating 2136 and 638 patients that underwent Belsey Mark IV or Nissen fundoplication, respectively. A total of 13.8% (95% CI: 9.6-18.6) of the patients that underwent fundoplication with the BMIV technique had non-resolution of their symptoms and 3.5% (95% CI: 2.0-5.4) required a reoperation. Overall, 14.8% (95% CI: 9.5-20.1) of the BMIV arm patients experienced post-operative complications, 5.0% (95% CI: 2.0-9.0) experienced chronic postoperative pain and 6.9% (95% CI: 3.1-11.9) had a hernia recurrence. No statistically significant difference was observed between Belsey Mark IV and Nissen fundoplication in terms of post-interventional non-resolution of symptoms (odds ratio [OR]: 1.49 [95% Confidence Interval (95%CI):0.6-4.0]; p = 0.42), post-operative complications (OR:0.83, 95%CI: 0.5-1.5, p = 0.54) and in-hospital mortality (OR:0.69, 95%CI: 0.13-3.80, p = 0.67). Belsey Mark IV arm had significantly lower reoperation rates compared to Nissen arm (OR:0.28, 95%CI: 0.1-0.7, p = 0.01). CONCLUSIONS: BMIV fundoplication is a safe and effective but technically challenging. The BMIV technique may offer benefits to patients compared to the laparoscopic Nissen fundoplication. These benefits, however, are challenged by the increased morbidity of a thoracotomy.

Outpatient hospital utilization after single event multi-level surgery in children with cerebral palsy.

PURPOSE: This study aimed to examine outpatient hospital utilization (number of specialties seen and number of visits to each specialty) in the year after single event multi-level surgery (SEMLS) in children with cerebral palsy (CP), and to determine if utilization differs across the medical center in the year after compared to the year before SEMLS. METHODS: This retrospective cross-sectional study used electronic medical record data of outpatient hospital utilization in children with CP who underwent SEMLS. RESULTS: Thirty children with CP (Gross Motor Function Classification System Levels I-V, mean age of 9.9 years) were included. In the year after surgery, a significant difference (p = 0.001) was found for the number of specialties seen, with non-ambulatory children seeing more specialties than ambulatory children. No statistically significant difference was found between the number of outpatient visits to each specialty in the year after SEMLS. Compared to the year before SEMLS, fewer therapy visits occurred in the year after SEMLS (p < 0.001) but significantly more visits to orthopaedics (p = 0.001) and radiology (p = 0.001). CONCLUSION: Children with CP had fewer therapy visits but more orthopaedic and radiology visits the year after SEMLS. Nearly half of the children were non-ambulatory. Examination of care needs in children with CP undergoing SEMLS is justified with consideration of ambulatory status, surgical burden, and post-operative immobilization.