Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage.

BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known. METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients' assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment. RESULTS: A total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and -0.013 (95% Bayesian credible interval, -0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration. CONCLUSIONS: Among patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.).

Neuropeptide substance P alters stem cell fate to aid wound healing and promote epidermal stratification through asymmetric stem cell divisions.

Loss of sensory innervation delays wound healing and administration of the neuropeptide substance P improves re-epithelialization. Keratinocyte hyperproliferation post-wounding may result from symmetric stem cell (SC) self-renewal, asymmetric SC self-renewal, committed progenitor divisions, or a combination of these. However, the effects of sensory denervation and of neuropeptides on SC proliferation are not known. Here we show that early after wounding both asymmetric and symmetric SC self-renewal increase, without significant committed progenitor (CP) activation. Decreased sensory innervation is associated with a decrease in both SC and CP proliferation. Based on previous work showing that substance P is decreased in capsaicin-treated mice and improves wound healing in normal skin, we examined the effects of substance P on SC and CP proliferation during wound healing. Substance P restored asymmetric SC proliferation in skin with decreased sensory innervation, both at baseline and following wounding. Epidermis with decreased sensory innervation was severely thinned. Consistent with this, substance P-induced asymmetric SC proliferation resulted in increased stratification in skin with both normal and decreased innervation. Lapatinib prevented the substance P-induced increase in asymmetric SC divisions in murine epidermis, as well as the increase in epidermal stratification, suggesting that asymmetric SC divisions are required for epidermal stratification.

Risk Factors for Peripheral Nerve Injury Following Revision Total Knee Arthroplasty in 132,960 Patients.

BACKGROUND: Peripheral nerve injury (PNI) following revision total knee arthroplasty (rTKA) is a potentially devastating injury for patients. This study assessed the frequency of and risk factors for postoperative PNI following rTKA. METHODS: Patients who underwent rTKA from 2003 to 2015 were identified using the National Inpatient Sample. Demographics, medical histories, surgical details, and complications were compared between patients who sustained a PNI and those who did not to identify risk factors for the development of PNI after rTKA. RESULTS: Overall, 132,960 patients who underwent rTKA were identified, and 737 (0.56%) sustained a postoperative PNI. After adjusting for confounders, patients with a history of a spine condition (adjusted odds ratio [aOR]: 1.7, 95%-confidence interval 1.2 to 2.4, P = .003) and postoperative anemia (aOR: 1.3, 95%-CI: 1.1 to 1.5, P = .004) had higher risk of PNI following rTKA. Intraoperative periprosthetic fracture (aOR: 1.3, 0.78 to 2.2, P = .308), rheumatoid arthritis (aOR: 1.0, 95%-CI: 0.68 to 1.6, P = .865), and history of knee dislocation (aOR: 1.1, 95%-CI: 0.85 to 1.5, P = .412), were not significantly associated with higher risk for PNI. CONCLUSIONS: This study found a 0.56% incidence of PNI following rTKA, and patients who had preexisting spine conditions or postoperative anemia were at an increased risk for this complication. Orthopedic surgeons may use the results of this study to appropriately counsel patients on the potential for a PNI following rTKA.

Is the Rise of Medicare Advantage Impacting the Fidelity of Traditional Medicare Claims Data? Implications for Reporting of Long-Term Total Hip Arthroplasty Survivorship.

BACKGROUND: Arthroplasty registries often use traditional Medicare (TM) claims data to report long-term total hip arthroplasty (THA) survivorship. The purpose of this study was to determine whether the large number of patients leaving TM for Medicare Advantage (MA) has compromised the fidelity of TM data. METHODS: We identified 10,962 THAs in 9,333 Medicare-eligible patients who underwent primary THA from 2000 to 2020 at a single institution. Insurance type was analyzed, and 83% of patients had TM at the time of THA. Survivorship free from any revision or reoperation was calculated for patients who have TM. The same survivorship end points were recalculated with censoring performed when a patient transitioned to an MA plan after their primary THA to model the impact of losing patients from the TM dataset. Differences in survivorship were compared. The mean follow-up was 7 years. RESULTS: From 2000 to 2020, there was a decrease in TM insurance (93 to 73%) and a corresponding increase in MA insurance (0 to 19%) among THA patients. Following THA, 23% of TM patients switched to MA. For patients who had TM at the time of surgery, 15-year survivorship free from any reoperation or revision was 90% and 93%, respectively. When censoring patients upon transition from TM to MA, survivorship free from any reoperation became significantly higher (92 versus 90% at 15 years; hazard ratio = 1.16, P = .033), and there was a trend toward higher survivorship free from any revision (95 versus 93% at 15 years; hazard ratio = 1.16, P = .074). CONCLUSIONS: Approximately 1 in 4 patients left TM for MA after primary THA, effectively making them lost to follow-up within TM datasets. The mass exodus of patients out of TM appears to have led to a slight overestimation of survivorship free from any reoperation and trended toward overestimating survivorship free from any revision. If MA continues to grow, efforts to obtain MA data will become even more important.

Structural Mechanisms of Nucleosome Recognition by Linker Histones.

Linker histones bind to the nucleosome and regulate the structure of chromatin and gene expression. Despite more than three decades of effort, the structural basis of nucleosome recognition by linker histones remains elusive. Here, we report the crystal structure of the globular domain of chicken linker histone H5 in complex with the nucleosome at 3.5 Å resolution, which is validated using nuclear magnetic resonance spectroscopy. The globular domain sits on the dyad of the nucleosome and interacts with both DNA linkers. Our structure integrates results from mutation analyses and previous cross-linking and fluorescence recovery after photobleach experiments, and it helps resolve the long debate on structural mechanisms of nucleosome recognition by linker histones. The on-dyad binding mode of the H5 globular domain is different from the recently reported off-dyad binding mode of Drosophila linker histone H1. We demonstrate that linker histones with different binding modes could fold chromatin to form distinct higher-order structures.

Implementation of Automated Pipeline for Resting-State fMRI Analysis with PACS Integration.

In recent years, the quantity and complexity of medical imaging acquisition and processing have increased tremendously. The explosion in volume and need for advanced imaging analysis have led to the creation of numerous software programs, which have begun to be incorporated into clinical practice for indications such as automated stroke assessment, brain tumor perfusion processing, and hippocampal volume analysis. Despite these advances, there remains a need for specialized, custom-built software for advanced algorithms and new areas of research that is not widely available or adequately integrated in these "out-of-the-box" solutions. The purpose of this paper is to describe the implementation of an image-processing pipeline that is versatile and simple to create, which allows for rapid prototyping of image analysis algorithms and subsequent testing in a clinical environment. This pipeline uses a combination of Orthanc server, custom MATLAB code, and publicly available FMRIB Software Library and RestNeuMap tools to automatically receive and analyze resting-state functional MRI data collected from a custom filter on the MR scanner output. The processed files are then sent directly to Picture Archiving and Communications System (PACS) without the need for user input. This initial experience can serve as a framework for those interested in simple implementation of an automated pipeline customized to clinical needs.

[Diagnostic values of conventional tumor markers and their combination with chest CT for patients with stageâ A lung cancer].

Objective: To investigate the diagnostic efficiency of conventional serum tumor markers and their combination with chest CT for stage ⅠA lung cancer. Methods: A total of 1 155 patients with stage ⅠA lung cancer and 200 patients with benign lung lesions (confirmed by surgery) treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to October 2020 were retrospectively enrolled in this study. Six conventional serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), squamous cell carcinoma associated antigen (SCCA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and gastrin-releasing peptide precursor (ProGRP)] and chest thin-slice CT were performed on all patients one month before surgery. Pathology was taken as the gold standard to analyze the difference of positivity rates of tumor markers between the lung cancer group and the benign group, the moderate/poor differentiation group and the well differentiation group, the adenocarcinoma group and the squamous cell carcinoma group, the lepidic and non-lepidic predominant adenocarcinoma groups, the solid nodule group and the subsolid nodule group based on thin-slice CT, and subgroups of ⅠA1 to ⅠA3 lung cancers. The diagnostic performance of tumor markers and tumor markers combined with chest CT was analyzed using the receiver operating characteristic curve. Results: The positivity rates of six serum tumor markers in the lung cancer group and the benign group were 2.32%-20.08% and 0-13.64%, respectively; only the SCCA positivity rate in the lung cancer group was higher than that in the benign group (10.81% and 0, P=0.022). There were no significant differences in the positivity rates of other serum tumor markers between the two groups (all P>0.05). The combined detection of six tumor markers showed that the positivity rate of the lung cancer group was higher than that of the benign group (40.93% and 18.18%, P=0.004), and the positivity rate of the adenocarcinoma group was lower than that of the squamous cell carcinoma group (35.66% and 47.41%, P=0.045). The positivity rates in the poorly differentiated group and moderately differentiated group were higher than that in the well differentiated group (46.48%, 43.75% and 22.73%, P=0.025). The positivity rate in the non-lepidic adenocarcinoma group was higher than that in lepidic adenocarcinoma group (39.51% and 21.74%, P=0.001). The positivity rate of subsolid nodules was lower than that of solid nodules (30.01% vs 58.71%, P=0.038), and the positivity rates of stageⅠA1, ⅠA2 and ⅠA3 lung cancers were 33.33%, 48.96% and 69.23%, respectively, showing an increasing trend (P=0.005). The sensitivity and specificity of the combined detection of six tumor markers in the diagnosis of stage ⅠA lung cancer were 74.00% and 56.30%, respectively, and the area under the curve (AUC) was 0.541. The sensitivity and specificity of the combined detection of six serum tumor markers with CT in the diagnosis of stage ⅠA lung cancer were 83.0% and 78.3%, respectively, and the AUC was 0.721. Conclusions: For stage ⅠA lung cancer, the positivity rates of commonly used clinical tumor markers are generally low. The combined detection of six markers can increase the positivity rate. The positivity rate of markers tends to be higher in poorly differentiated lung cancer, squamous cell carcinoma, or solid nodules. Tumor markers combined with thin-slice CT showed limited improvement in diagnostic efficiency for early lung cancer.

IFI16 is an innate immune sensor for intracellular DNA.

The detection of intracellular microbial DNA is critical to appropriate innate immune responses; however, knowledge of how such DNA is sensed is limited. Here we identify IFI16, a PYHIN protein, as an intracellular DNA sensor that mediates the induction of interferon-ß (IFN-ß). IFI16 directly associated with IFN-ß-inducing viral DNA motifs. STING, a critical mediator of IFN-ß responses to DNA, was recruited to IFI16 after DNA stimulation. Lowering the expression of IFI16 or its mouse ortholog p204 by RNA-mediated interference inhibited gene induction and activation of the transcription factors IRF3 and NF-κB induced by DNA and herpes simplex virus type 1 (HSV-1). IFI16 (p204) is the first PYHIN protein to our knowledge shown to be involved in IFN-ß induction. Thus, the PYHIN proteins IFI16 and AIM2 form a new family of innate DNA sensors we call 'AIM2-like receptors' (ALRs).

Merkel cell carcinoma of unknown primary: Clinical presentation and outcomes.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy that usually occurs in the head/neck or extremities. However, there are reports of MCC developing in the lymph nodes or parotid gland without evidence of a primary cutaneous lesion. METHODS: We reviewed 415 patients with biopsy-proven MCC. Patients with MCC of unknown primary (n = 37, 9%, MCCUP) made up the study cohort. The primary endpoints of the study were rate of recurrence, disease-free survival, and overall survival. RESULTS: Patients with MCCUP presented with tumors in lymph nodes (n = 34) or parotid gland (n = 3). Nodal disease was most commonly detected in the inguinal/external iliac (n = 15) or axillary (n = 14) regions. The mean age at diagnosis was 70 years and 24% were female. Patients presented with distant metastases in 24.3% of cases. Patients with stage IIIA disease treated with regional lymph node dissection (RLND) had a lower risk of disease recurrence (hazard ratio 0.26, p = 0.046). Recurrence-free survival was 59.3% at 5 years. Disease-specific survival was 63.3% at 5 years. CONCLUSION: Patients with MCCUP have a high risk of recurrence and mortality. The optimal treatment for MCCUP has yet to be elucidated, although therapeutic RLND appears beneficial for these patients.

The catalytic subunit of the SWR1 remodeler is a histone chaperone for the H2A.Z-H2B dimer.

Histone variant H2A.Z-containing nucleosomes exist at most eukaryotic promoters and play important roles in gene transcription and genome stability. The multisubunit nucleosome-remodeling enzyme complex SWR1, conserved from yeast to mammals, catalyzes the ATP-dependent replacement of histone H2A in canonical nucleosomes with H2A.Z. How SWR1 catalyzes the replacement reaction is largely unknown. Here, we determined the crystal structure of the N-terminal region (599-627) of the catalytic subunit Swr1, termed Swr1-Z domain, in complex with the H2A.Z-H2B dimer at 1.78 Å resolution. The Swr1-Z domain forms a 310 helix and an irregular chain. A conserved LxxLF motif in the Swr1-Z 310 helix specifically recognizes the αC helix of H2A.Z. Our results show that the Swr1-Z domain can deliver the H2A.Z-H2B dimer to the DNA-(H3-H4)2 tetrasome to form the nucleosome by a histone chaperone mechanism.

The impact of frailty on postoperative complications in geriatric patients undergoing multi-level lumbar fusion surgery.

STUDY DESIGN: Retrospective Cohort Study. PURPOSE: This study evaluates the impact of patient frailty status on postoperative complications in those undergoing multi-level lumbar fusion surgery. METHODS: The Nationwide Readmission Database (NRD) was retrospectively queried between 2016 and 2017 for patients receiving multi-level lumbar fusion surgery. Demographics, frailty status, and relevant complications were queried at index admission and readmission intervals. Primary outcome measures included perioperative complications and 30-, 90-, and 180-day complication and readmission rates. Perioperative complications of interest were infection, urinary tract infection (UTI), and posthemorrhagic anemia. Secondary outcome measures included inpatient length of stay (LOS), adjusted all-payer costs, and discharge disposition. Nearest-neighbor propensity score matching for demographics was implemented to identify non-frail patients with similar diagnoses and procedures. Subgroup analysis of minimally invasive surgery (MIS) versus open surgery within frail and non-frail cohorts was conducted to evaluate differences in surgical and medical complication rates. The analysis used nonparametric Mann-Whitney U testing and odds ratios. RESULTS: Frail patients encountered higher rates perioperative complications including posthemorrhagic anemia (OR: 1.73, 95%CI 1.50-2.00, p < 0.0001), infection (OR: 2.94, 95%CI 2.04-4.36, p < 0.0001), UTI (OR: 2.57, 95%CI 2.04-3.26, p < 0.0001), and higher rates of non-routine discharge (OR: 2.07, 95%CI 1.80-2.38, p < 0.0001). Frail patients had significantly greater LOS and total all-payer inpatient costs compared to non-frail patients (p < 0.0001). Frailty was associated with significantly higher rates of 90- (OR: 1.43, 95%CI 1.18-1.74, p = 0.0003) and 180-day (OR: 1.28, 95%CI 1.03-1.60, p = 0.02) readmissions along with higher rates of wound dehiscence (OR: 2.21, 95%CI 1.17-4.44, p = 0.02) at 90 days. Subgroup analysis revealed that frail patients were at significantly higher risk for surgical complications with open surgery (16%) compared to MIS (0%, p < 0.0001). No significant differences were found between surgical approaches with respect to medical complications in both cohorts, nor surgical complications in non-frail patients. CONCLUSIONS: Frailty was associated with higher odds of all perioperative complications, LOS, and all-payer costs following multi-level lumbar fusion. Frail patients had significantly higher rates of 90 and 180-day readmission and higher rates of wound disruption at 90-days. On subgroup analysis, MIS was associated with significantly reduced rates of surgical complications specifically in frail patients. Our results suggest frailty status to be an important predictor of perioperative complications and long-term readmissions in geriatric patients receiving multi-level lumbar fusions. Frail patients should undergo surgery utilizing minimally invasive techniques to minimize risk of surgical complications. Future studies should explore the utility of implementing frailty in risk stratification assessments for patients undergoing spine surgery.

Identifying risks factors in thoracolumbar anterior fusion surgery through predictive analytics in a nationally representative inpatient sample.

PURPOSE: Anterior thoracolumbar (TL) surgical approaches provide more direct trajectories compared to posterior approaches. Proper patient selection is key in identifying populations that may benefit from anterior TL fusion. Here, we utilize predictive analytics to identify risk factors in anterior TL fusion in patients with trauma and deformity. METHODS: In this retrospective cohort study of patients receiving anterior TL fusion (between and including T12/L1), population-based regression models were developed to identify risk factors using the National Readmission Database 2016-2017. Readmissions were analyzed at 30- and 90-day intervals. Risk factors included hypertension, obesity, malnutrition, smoking, alcohol use, long-term opioid use, and frailty. Multivariate regression models were developed to determine the influence of each risk factor on complication rates. RESULTS: A total of 265 and 375 patients were identified for the scoliosis and burst fracture cohorts, respectively. In patients with scoliosis, alcohol use was found to increase the length of stay (LOS) (p = 0.00061) and all-payer inpatient cost following surgery (p = 0.014), and frailty was found to increase the inpatient LOS (p = 0.0045). In patients with burst fractures, malnutrition was found to increase the LOS (p < 0.0001) and all-payer cost (p < 0.0001), obesity was found to increase the all-payer cost (p = 0.012), and frailty was found to increase the all-payer cost (p = 0.031) and LOS (p < 0.0001). DISCUSSION: Patient-specific risk factors in anterior TL fusion surgery significantly influence complication rates. An understanding of relevant risk factors before surgery may facilitate preoperative patient selection and postoperative patient triage and risk categorization.

Impact of diagnosis and type of sacroiliac joint fusion on postoperative complications.

PURPOSE: Two main surgical approaches are available for fusing the sacroiliac joint (SIJ): an open or minimally invasive (MIS) approach. The purpose of this study was to analyze the associated total hospital charges and postoperative complications of the MIS and open approach. METHODS: Using the 2016 and 2017 National Readmission Database, we conducted a retrospective cohort analysis of 2521 patients who received a SIJ fusion with an open (N = 1990) or MIS (N = 531) approach for diagnosed sacrum pain, sacroiliitis, sacral instability, or spondylosis. Each cohort was analyzed for postoperative complications. RESULTS: We identified 604 patients diagnosed with sacrum pain, 1142 with sacroiliitis, 315 with spondylosis, and 288 with sacral instability. Patients who received the open approach for sacrum pain had significantly higher rates of novel post-procedural pain (p = 0.045) and novel lumbar pathology (p = 0.015) within 30 days. On 30-day follow-up, patients with sacroiliitis treated with open SIJ fusion had significantly higher rates of novel postprocedural pain compared to those treated with MIS fusion (p = 0.045). Patients who received the open approach for spondylosis resulted in significantly higher rates of non-elective readmission within 30 days compared to the MIS approach (p < 0.0001). In addition, the open technique for spondylosis resulted in significantly higher rates of non-elective readmissions for infection within 30 days (p = 0.014). On 30-day follow-up, patients with sacral instability treated with open SIJ fusion had significantly higher rates of UTI (p = 0.045). CONCLUSION: Our study suggests that there exist unique postoperative complications that arise after SIJ fusion specific to preoperative diagnosis and surgical approach.

Ultraefficient thermophotovoltaic power conversion by band-edge spectral filtering.

Thermophotovoltaic power conversion utilizes thermal radiation from a local heat source to generate electricity in a photovoltaic cell. It was shown in recent years that the addition of a highly reflective rear mirror to a solar cell maximizes the extraction of luminescence. This, in turn, boosts the voltage, enabling the creation of record-breaking solar efficiency. Now we report that the rear mirror can be used to create thermophotovoltaic systems with unprecedented high thermophotovoltaic efficiency. This mirror reflects low-energy infrared photons back into the heat source, recovering their energy. Therefore, the rear mirror serves a dual function; boosting the voltage and reusing infrared thermal photons. This allows the possibility of a practical >50% efficient thermophotovoltaic system. Based on this reflective rear mirror concept, we report a thermophotovoltaic efficiency of 29.1 ± 0.4% at an emitter temperature of 1,207 °C.

Midterm Survivorship of Robotic-Assisted Lateral Unicompartmental Knee Arthroplasty.

BACKGROUND: Lateral unicompartmental knee arthroplasty (UKA) is a popular alternative to total knee arthroplasty (TKA) for patients with isolated lateral compartment osteoarthritis. Few studies have investigated outcomes following robotic-assisted lateral UKA. The purpose of this study is to evaluate mid-term survivorship and patient-reported outcomes of robotic-assisted lateral UKA. METHODS: A retrospective case series was conducted on all robotic-assisted lateral UKAs performed by a single surgeon between 2013 and 2019. Patient demographics, surgical variables, and Kozinn and Scott criteria were collected. Implant survivorship was estimated using the Kaplan-Meier method with all-cause reoperation and conversion to TKA as endpoints. Participating patients were assessed for patient satisfaction and the Forgotten Joint Score-12. Correlations between patient demographics and patient outcome scores were investigated. RESULTS: In total, 120 lateral UKAs were identified, 84 of which met inclusion criteria, with a mean follow-up of 4.0 years (range 2.0-7.0). Five-year survivorship was 92.9% (95% confidence interval [CI] 84.5-96.7) with all-cause reoperation as the endpoint, and 100% (95% CI 95.0-100) with conversion to TKA as the endpoint. One patient was converted to TKA after the 5-year mark, resulting in a 6-year survival for conversion to TKA of 88.9% (95% CI 44.9-98.5). Average Forgotten Joint Score-12 score was 82.7/100, and patient satisfaction 4.7/5. Mean coronal plane correction was 2.5° ± 1.9° toward the mechanical axis. Neither final postoperative alignment nor failure to meet classic Kozinn and Scott criteria for UKA resulted in differences in patient-reported outcomes. CONCLUSION: The current study demonstrates high mid-term survivorship and excellent patient-reported outcomes with robotic-assisted lateral UKA. Robotic-assisted lateral UKA is a viable treatment option for isolated lateral compartment arthritis even in patients who do not meet classic indications.

Transcriptome analysis of genes potentially associated with white and black plumage formation in Chinese indigenous ducks (Anas platyrhynchos).

1. Plumage colour is an important recognisable characteristic of duck (Anas platyrhynchos), but the colouration mechanisms remain largely unknown. To elucidate the molecular mechanisms underlying the formation of black and white plumage, the following study applied RNA sequencing (RNA-Seq) to catalogue the global gene expression profiles in the duck feather bulbs of black and white colours.2. Black feather bulbs were collected from Putian Black ducks (B-PTB) and black Longsheng Jade-green ducks (B-LS), while white feather bulbs were collected from Putian White ducks (W-PTW), Putian Black ducks (W-PTB) and Longsheng Jade-green ducks (W-LS). Sixteen cDNA libraries were constructed and sequenced for transcriptional analysis. Three comparison groups were employed to analyse differentially expressed genes (DEGs), including W-PTB versus B-PTB, W-PTW versus B-PTB and W-LS versus B-LS.3. The results showed 180 DEGs between W-PTB and B-PTB, 303 DEGs between W-PTW and B-PTB, and 108 DEGs between W-LS and B-LS. Further analysis showed that 18 DEGs were directly involved in the pigmentation process and melanogenesis signalling pathway. Additionally, the distribution of DEGs varied amongst groups whereby ASIP appeared only in the W-LS versus B-LS group, GNAI1 and ZEB2 appeared only in the W-PTW versus B-PTB group, and KITLG, EDN3 and FZD4 appeared only in W-PTB versus B-PTB.4. The findings suggested that the mechanism of feather albinism may differ between duck breeds. This study provided new information for discovering genes that are important for feather pigmentation and helps elucidate molecular mechanisms involved in black and white plumage in ducks.

Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor.

Recognition of DNA by the innate immune system is central to antiviral and antibacterial defenses, as well as an important contributor to autoimmune diseases involving self DNA. AIM2 (absent in melanoma 2) and IFI16 (interferon-inducible protein 16) have been identified as DNA receptors that induce inflammasome formation and interferon production, respectively. Here we present the crystal structures of their HIN domains in complex with double-stranded (ds) DNA. Non-sequence-specific DNA recognition is accomplished through electrostatic attraction between the positively charged HIN domain residues and the dsDNA sugar-phosphate backbone. An intramolecular complex of the AIM2 Pyrin and HIN domains in an autoinhibited state is liberated by DNA binding, which may facilitate the assembly of inflammasomes along the DNA staircase. These findings provide mechanistic insights into dsDNA as the activation trigger and oligomerization platform for the assembly of large innate signaling complexes such as the inflammasomes.

The cGAS-STING pathway for DNA sensing.

The nucleotidyl transferase cGAS, its second-messenger product cGAMP, and the cGAMP sensor STING form the basic mechanism of DNA sensing in the cytoplasm of mammalian cells. Several new reports now uncover key structural features associated with DNA recognition by cGAS and the catalytic mechanisms of cGAMP generation. Concurrent studies also reveal unique phosphodiester linkages in endogenous cGAMP that distinguish it from microbial cGAMP and other cyclic dinucleotides. Together, these studies provide a new perspective on DNA recognition in the innate immune system.

The influence of frailty on postoperative complications in geriatric patients receiving single-level lumbar fusion surgery.

PURPOSE: This study evaluates the influence of patient frailty status on postoperative complications in those receiving single-level lumbar fusion surgery. METHODS: The nationwide readmission database was retrospectively queried between 2016 and 2017 for all patients receiving single-level lumbar fusion surgery. Readmissions were analyzed at 30, 90, and 180 days from primary discharge. Demographics, frailty status, and relevant complications were queried at index admission and all readmission intervals. Complications of interest included infection, urinary tract infection (UTI), posthemorrhagic anemia, inpatient length of stay (LOS), and adjusted all-payer costs. Nearest-neighbor propensity score matching for demographics was implemented to identify non-frail control patients with similar diagnoses and procedures. The analysis used nonparametric Mann-Whitney U testing and odds ratios. RESULTS: Comparing propensity-matched cohorts revealed significantly greater LOS and total all-payer inpatient costs in frail patients than non-frail patients with comparable demographics and comorbidities (p < 0.0001 for both). Furthermore, frail patients encountered higher rates of UTI (OR: 3.97, 95%CI: 3.21-4.95, p < 0.0001), infection (OR: 6.87, 95%CI: 4.55-10.86, p < 0.0001), and posthemorrhagic anemia (OR: 1.94, 95%CI: 1.71-2.19, p < 0.0001) immediately following surgery. Frail patients had significantly higher rates of 30-day (OR: 1.24, 95%CI: 1.02-1.51, p = 0.035), 90-day (OR: 1.38, 95%CI: 1.17-1.63, p < 0.001), and 180-day (OR: 1.55, 95%CI: 1.30-1.85, p < 0.0001) readmissions. Lastly, frail patients had higher rates of infection at 30-day (OR: 1.61, 95%CI: 1.05-2.46, p = 0.027) and 90-day (OR: 1.51, 95%CI: 1.07-2.16, p = 0.020) readmission intervals. CONCLUSIONS: Patient frailty status may serve as an important predictor of postoperative outcomes in patients receiving single-level lumbar fusion surgery.

The Efficacy of Platelet-Rich Plasma for Improving Pain and Function in Lateral Epicondylitis: A Systematic Review and Meta-analysis with Risk-of-Bias Assessment.

PURPOSE: To assess the efficacy of platelet-rich plasma (PRP) for lateral epicondylitis and evaluate its impact on pain and functional outcomes. METHODS: This study followed Preferred Reporting Items and Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search was conducted in September 2019 and repeated in April 2020 using electronic databases PubMed, MEDLINE, and the Cochrane Library. Baseline and 3-, 6-, and 12-month data were extracted for visual analog scale (VAS), Disabilities of the Arm, Shoulder, and Hand (DASH), and modified Mayo Clinic performance index for the elbow (MAYO) scores. Only level 1 studies with patients who had not undergone surgery were included. Outcomes data, study design, demographic variables, PRP formulation, and comparator treatments were recorded. Statistical analyses of pooled weighted mean differences (WMDs) were performed and compared with estimated minimal clinically important difference (MCID) values. The Coleman Methodology Score (CMS) was used to assess methodological quality, and the Cochrane risk-of-bias assessment was performed. RESULTS: This review included 16 level I studies, 9 of which (581 total patients, 281 receiving single injections of PRP) were quantitatively analyzed. The average age was 41.5 years, 56.8% of patients were female, and mean follow-up was 7.5 months. The mean CMS was 78.94 ± 12.74 (range 59 to 97), and 5 of 16 studies were at low risk for bias. Patients who received PRP had significantly improved VAS scores at 3 months (WMD -0.85; 95% confidence interval [CI] -1.03, -0.66; P < .01) and 6 months (WMD -0.74; 95% CI -0.98, -0.50; P < .01) compared with those who received autologous whole blood, though MAYO scores were statistically equivalent. Comparing PRP to corticosteroids, VAS and DASH scores were not significantly different at 3 months, although PRP was superior at 6 months for VAS (WMD -1.70; 95% CI -2.65, -0.75; P < .01) and DASH (WMD -6.23; 95% CI -10.78, -1.69; P < .01). Most differences in VAS and DASH scores exceeded the 5% absolute difference estimate for their respective MCIDs but fell short of the 10% estimate. CONCLUSION: Considering the small number of comparable studies, lack of quantification of specific PRP content, considerable heterogeneity between randomized control trials, and most effect sizes being equivocal within the framework of 2 estimated MCID values, the authors can neither scientifically support nor discourage the usage of PRP for lateral epicondylitis despite finding statistically significant improvements in pain and functional outcomes. LEVEL OF EVIDENCE: I, prognostic.