Sweet corn phytoglycogen dendrimers as a lyoprotectant for dry-state protein storage.

Protein biotherapeutics typically require expensive cold-chain storage to maintain their fold and function. Packaging proteins in the dry state via lyophilization can reduce these cold-chain requirements. However, formulating proteins for lyophilization often requires extensive optimization of excipients that both maintain the protein folded state during freezing and drying (i.e., "cryoprotection" and "lyoprotection"), and form a cake to carry the dehydrated protein. Here we show that sweet corn phytoglycogens, which are glucose dendrimers, can act as both a protein lyoprotectant and a cake-forming agent. Phytoglycogen (PG) dendrimers from 16 different maize sources (PG1-16) were extracted via ethanol precipitation. PG size was generally consistent at ~70-100 nm for all variants, whereas the colloidal stability in water, protein contaminant level, and maximum density of cytocompatibility varied for PG1-16. 10 mg/mL PG1, 2, 9, 13, 15, and 16 maintained the activity of various proteins, including green fluorescent protein, lysozyme, ß-galactosidase, and horseradish peroxidase, over a broad range of concentrations, through multiple rounds of lyophilization. PG13 was identified as the lead excipient candidate as it demonstrated narrow dispersity, colloidal stability in phosphate-buffered saline, low protein contaminants, and cytocompatibility up to 10 mg/mL in NIH3T3 cell cultures. All dry protein-PG13 mixtures had a cake-like appearance and all frozen protein-PG13 mixtures had a Tg' of ~ -26°C. The lyoprotection and cake-forming properties of PG13 were density-dependent, requiring a minimum density of 5 mg/mL for maximum activity. Collectively these data establish PG dendrimers as a new class of excipient to formulate proteins in the dry state.

Preoperative Expectations of Women Undergoing Breast Reconstruction Surgery.

Background: The study investigated the expectations of patients undergoing immediate breast reconstruction after mastectomy, considering factors such as the cause for mastectomy (cancer versus prophylactic due BRCA1 or BRCA2 gene mutations), age, marital status, and education. Methods: The study had a cross-sectional design. Eligible patients at Oslo University Hospital received a link to the BREAST-Q Expectations questionnaire, which they filled out before surgery from 2019 to 2022. Results: One hundred forty-six patients completed the questionnaire (79.8% response rate). The mean age was 46.6 years, and the majority (95.1%) were undergoing reconstruction with implants. Most patients (86.9%) wanted to be involved in the decision-making. The highest expectation was for breast appearance and the lowest for sensation after surgery. Patients not diagnosed with cancer (n = 27) before surgery expected significantly more pain after surgery compared with patients diagnosed with cancer (P = 0.016). Patients 40 years or younger had higher expectation of pain after surgery than patients 41 years or older, 73.2 versus 54.2, P < 0.001, respectively. After 10 years, 26.7% of the patients expected that further reconstruction procedures might be necessary. Conclusions: Our study's results regarding patient's expectations with breast reconstruction, as assessed using the BREAST-Q Expectations module, align with previous research in terms of overall trends. However, our study provides a more nuanced understanding by exploring variations within different patient subgroups. These differences emphasize the need for personalized preoperative counseling and support to align patient's expectations with realistic outcomes.

Advancing insights into recurrent lumbar disc herniation: A comparative analysis of surgical approaches and a new classification.

Background: The management of recurrent lumbar disc herniation (rLDH) lacks a consensus. Consequently, the choice between repeat microdiscectomy (MD) without fusion, discectomy with fusion, or endoscopic discectomy without fusion typically hinges on the surgeon's expertise. This study conducts a comparative analysis of postoperative outcomes among these three techniques and proposes a straightforward classification system for rLDH aimed at optimizing management. Patients and Methods: We examined the patients treated for rLDH at our institution. Based on the presence of facet resection, Modic-2 changes, and segmental instability, they patients were categorized into three groups: Types I, II, and III rLDH managed by repeat MD without fusion, MD with transforaminal lumbar interbody fusion (TLIF) (MD + TLIF), and transforaminal endoscopic discectomy (TFED), respectively. Results: A total of 127 patients were included: 52 underwent MD + TLIF, 50 underwent MD alone, and 25 underwent TFED. Recurrence rates were 20%, 12%, and 0% for MD alone, TFED, and MD + TLIF, respectively. A facetectomy exceeding 75% correlated with an 84.6% recurrence risk, while segmental instability correlated with a 100% recurrence rate. Modic-2 changes were identified in 86.7% and 100% of patients experiencing recurrence following MD and TFED, respectively. TFED exhibited the lowest risk of durotomy (4%), the shortest operative time (70.80 ± 16.5), the least blood loss (33.60 ± 8.1), and the most favorable Visual Analog Scale score, and Oswestry Disability Index quality of life assessment at 2 years. No statistically significant differences were observed in these parameters between MD alone and MD + TLIF. Based on this analysis, a novel classification system for recurrent disc herniation was proposed. Conclusion: In young patients without segmental instability, prior facetectomy, and Modic-2 changes, TFED was available should take precedence over repeat MD alone. However, for patients with segmental instability, MD + TLIF is recommended. The suggested classification system has the potential to enhance patient selection and overall outcomes.

Chimeric antigen receptor macrophages target and resorb amyloid plaques.

Substantial evidence suggests a role for immunotherapy in treating Alzheimer's disease (AD). While the precise pathophysiology of AD is incompletely understood, clinical trials of antibodies targeting aggregated forms of ß amyloid (Aß) have shown that reducing amyloid plaques can mitigate cognitive decline in patients with early-stage AD. Here, we describe what we believe to be a novel approach to target and degrade amyloid plaques by genetically engineering macrophages to express an Aß-targeting chimeric antigen receptor (CAR-Ms). When injected intrahippocampally, first-generation CAR-Ms have limited persistence and fail to significantly reduce plaque load, which led us to engineer next-generation CAR-Ms that secrete M-CSF and self-maintain without exogenous cytokines. Cytokine secreting "reinforced CAR-Ms" have greater survival in the brain niche and significantly reduce plaque load locally in vivo. These findings support CAR-Ms as a platform to rationally target, resorb, and degrade pathogenic material that accumulates with age, as exemplified by targeting Aß in AD.

Detection of caries around restorations on bitewings using deep learning.

OBJECTIVE: Secondary caries lesions adjacent to restorations, a leading cause of restoration failure, require accurate diagnostic methods to ensure an optimal treatment outcome. Traditional diagnostic strategies rely on visual inspection complemented by radiographs. Recent advancements in artificial intelligence (AI), particularly deep learning, provide potential improvements in caries detection. This study aimed to develop a convolutional neural network (CNN)-based algorithm for detecting primary caries and secondary caries around restorations using bitewings. METHODS: Clinical data from 7 general dental practices in the Netherlands, comprising 425 bitewings of 383 patients, were utilized. The study used the Mask-RCNN architecture, for instance, segmentation, supported by the Swin Transformer backbone. After data augmentation, model training was performed through a ten-fold cross-validation. The diagnostic accuracy of the algorithm was evaluated by calculating the area under the Free-Response Receiver Operating Characteristics curve, sensitivity, precision, and F1 scores. RESULTS: The model achieved areas under FROC curves of 0.806 and 0.804, and F1-scores of 0.689 and 0.719 for primary and secondary caries detection, respectively. CONCLUSION: An accurate CNN-based automated system was developed to detect primary and secondary caries lesions on bitewings, highlighting a significant advancement in automated caries diagnostics. CLINICAL SIGNIFICANCE: An accurate algorithm that integrates the detection of both primary and secondary caries will permit the development of automated systems to aid clinicians in their daily clinical practice.

Management of recurrent lumbar disc herniation: a comparative analysis of posterior lumbar interbody fusion and repeat discectomy.

Background: For recurrent lumbar disc herniation, many experts suggest a repeat discectomy without stabilization due to its minimal tissue manipulation, lower blood loss, shorter hospital stay, and lower cost, recent research on the role of instability in disc herniation has made fusion techniques popular among spinal surgeons. The authors compare the postoperative outcomes of posterior lumbar interbody fusion (PLIF) and repeat discectomy for same-level recurrent disc herniation. Methods: The patients included had previously undergone discectomy and presented with a same-level recurrent lumbar disc herniation. The patients were placed into two groups: 1) discectomy only, 2) PLIF based on the absence or presence of segmental instability. Preoperative and postoperative Oswestry disability index scores, duration of surgery, blood loss, duration of hospitalization, and complications were analyzed. Results: The repeat discectomy and fusion groups had 40 and 34 patients, respectively. The patients were followed up for 2.68 (1-4) years. There was no difference in the duration of hospitalization (3.73 vs. 3.29 days P=0.581) and operative time (101.25 vs. 108.82 mins, P=0.48). Repeat discectomy had lower intraoperative blood loss, 88.75 ml (50-150) versus 111.47 ml (30-250) in PLIF (P=0.289). PLIF had better ODI pain score 4.21 (0-10) versus 9.27 (0-20) (P-value of 0.018). Recurrence was 22.5% in repeat discectomy versus 0 in PLIF. Conclusion: PLIF and repeat discectomy for recurrent lumbar disc herniation have comparable intraoperative blood loss, duration of surgery, and hospital stay. PLIF is associated with lower durotomy rates and better long-term pain control than discectomy. This is due to recurrence and progression of degenerative process in discectomy patients, which are eliminated and slowed, respectively, by PLIF.

Real-world evidence of Pressure-Enabled Drug Delivery for trans-arterial chemoembolization and radioembolization among patients with hepatocellular carcinoma and liver metastases.

OBJECTIVES: Pressure-Enabled Drug Delivery (PEDD), a method using pressure to advance catheter-delivered drug distribution, can improve treatment for hepatocellular carcinoma (HCC) and liver metastases, but real-world evidence is limited. We compared baseline patient characteristics, clinical complexity, and post-procedure healthcare resource utilization (HRUs) and clinical complications for PEDD and non-PEDD procedures. METHODS: This study used a retrospective, longitudinal, cohort design of claims data from Clarivate's Real World Data Repository, which includes 98% of US payers with over 300 million unique patients from all US states. We identified patients with a trans-arterial chemoembolization (TACE) or trans-arterial radioembolization (TARE) from 1 January 2019 to 31 December 2022. Subsamples grouped patients with HCC receiving a TARE procedure at their first embolization and patients with metastatic colorectal cancer (CRC) that received a TARE procedure. We reported descriptive comparisons of our full sample of patients with HCC and liver metastases receiving PEDD versus non-PEDD procedures. We then conducted a matching-adjusted comparison of HRUs and clinical complications for PEDD and non-PEDD patients among our subsamples (HCC receiving a TARE procedure at their first embolization and patients with metastatic CRC that received a TARE procedure). Matching was based on baseline demographic and clinical characteristics using coarsened exact matching and propensity-score matching. HRUs included inpatient, outpatient, and emergency department visits. Clinical complications included ascites, cholecystitis, fatigue, gastric ulcer, gastritis, jaundice, LFT increase, lymphopenia, portal hypertension, and post-embolization syndrome. RESULTS: PEDD procedures were used on patients with worse baseline disease burdens: baseline Charlson comorbidity index (mean of 6.5 vs. 5.8), any prior clinical complication related to underlying disease (33.7 vs. 31.0%), and prior systemic therapy (22.1% vs. 16.2%). PEDD patients had a greater number of procedural codes indicative of technical complexity for TACE (PEDD mean = 226.3; non-PEDD mean = 134.5; p value <.01) and TARE (PEDD mean = 205.56; non-PEDD mean = 94.8; p value <0.01). Matching-adjusted analyses of patients with HCC and CRC demonstrated comparable HRU and clinical complications for PEDD and non-PEDD procedures post-index. CONCLUSION: Despite higher baseline disease burden and complexity, post-procedure HRU and clinical complications for PEDD patients were similar to non-PEDD patients. The complex baseline clinical profile may reflect selection of challenging cases for PEDD use. Future studies should validate the benefits observed with PEDD embolization in larger samples with greater statistical power.

Parental Stress, Infant Feeding and Well-being in Families Affected by Cleft Lip and/or Cleft Palate: The Impact of Early Follow-up.

OBJECTIVE: To document the impact of early follow-up by specialized cleft nurses (SCNs) provided to families affected by cleft lip and/or palate (CL/P) and the status of parental stress, infant feeding and well-being. DESIGN: Prospective inclusion of a control group, which only received standard care, followed by an intervention group that also received early SCN follow-up. SETTING: The cleft lip and palate team at Oslo University Hospital, Norway. PARTICIPANTS: Seventy families (69 mothers and 57 fathers) distributed into an intervention group (n = 32) and a control group (n = 38). INTERVENTION: SCNs provided a consultation at the maternity ward and a follow-up conversation by phone or face-to-face at scheduled times for six months. OUTCOME MEASURES: Parental Stress Index (PSI), Perceived Stress Scale (PSS-14), feeding questionnaire, survey of infant diets, weight percentiles. RESULTS: The mothers reported higher stress scores than the fathers, but in the control group only in the PSI parent domain at T2 and T3 (P = .007, P = .018). Infants in the intervention group used pacifiers less frequently than in the control group (55.2% vs. 81.1%, P = .023). Otherwise, no significant differences were found between the groups. Overall, the infants received less breast milk than norms. CONCLUSION: Contextual strategies for early follow-up of families affected by clefts need to be developed, with an emphasis on involving fathers and those parents reporting elevated stress and/or feeding difficulties. There is a need for diagnosis-specific guidelines about the use of pacifiers as well as collaboration between the health professionals involved to increase breastmilk feeding.

Association between underweight status and chylothorax after esophagectomy for esophageal cancer: A propensity score-matched analysis.

Objective: To use a nationwide database of hospitalizations to investigate underweight status as a risk factor for postesophagectomy complications. Methods: We identified all patients who underwent esophagectomy with a diagnosis of esophageal cancer and known body mass index in the 2018-2020 Nationwide Readmissions Database. All hospital visits for esophagectomy and within 30 days of initial discharge were analyzed for postoperative complications, including chylothorax. Patients who were underweight were propensity score matched with patients who were not. Multivariable logistic regression was performed to identify complications that were significantly associated with underweight status. Results: There were 1877 patients with esophageal cancer meeting inclusion criteria. Following propensity score matching, 433 patients who were underweight were matched to 433 patients who were not. In the multivariable model of the matched sample, which adjusted for age, sex, Charlson Comorbidity Index, history of chemotherapy or radiation therapy, and preoperative surgical feeding access, patients who were underweight were estimated to have 2.06 times the odds for chylothorax (95% confidence interval [CI], 1.07-4.25, P = .035). Underweight status was also significantly associated with acute bleed (odds ratio [OR], 1.52; 95% CI, 1.12-2.05, P = .007), pneumothorax (OR, 2.33; 95% CI, 1.19-4.85; P = .017), pneumonia (OR, 2.30; 95% CI, 1.53-3.50, P < .001), and in-hospital mortality (OR, 2.42; 95% CI, 1.31-4.69, P = .006). Conclusions: Underweight status was found to be a risk factor for chylothorax after esophagectomy, which may have implications for perioperative care of esophageal cancer patients. Future studies should assess whether using feeding tubes or total parenteral nutrition preoperatively or thoracic duct ligation intraoperatively decreases risk of chylothorax among patients who were underweight.

The Lifespan of D. melanogaster Depends on the Function of the Gagr Gene, a Domesticated gag Gene of Drosophila LTR Retrotransposons.

(1) Background: The Gagr gene in Drosophila melanogaster's genome originated from the molecular domestication of retrotransposons and retroviruses' gag gene. In all Drosophila species, the Gagr protein homologs exhibit a conserved structure, indicative of a vital role. Previous studies have suggested a potential link between the Gagr gene function and stress responses. (2) Methods: We compared flies with Gagr gene knockdown in all tissues to control flies in physiological tests and RNA-sequencing experiments. (3) Results: Flies with the Gagr gene knockdown exhibited shorter lifespans compared to control flies. Transcriptome analysis revealed that Gagr knockdown flies showed elevated transcription levels of immune response genes. We used ammonium persulfate, a potent stress inducer, to elicit a stress response. In control flies, ammonium persulfate activated the Toll, JAK/STAT, and JNK/MAPK signaling pathways. In contrast, flies with the Gagr gene knockdown displayed reduced expression of stress response genes. Gene ontology enrichment analysis identified categories of genes upregulated under ammonium persulfate stress in control flies but not in Gagr knockdown flies. These genes are involved in developmental control, morphogenesis, and central nervous system function. (4) Conclusion: Our findings indicate the significance of the Gagr gene in maintaining immune response and homeostasis.

Prevalence and Predictors of Concomitant Meniscal and Ligamentous Injuries Associated With ACL Surgery: An Analysis of 20 Years of ACL Reconstruction at a Tertiary Care Children's Hospital.

BACKGROUND: There is an increasing rate of procedures being performed for concomitant injuries during anterior cruciate ligament (ACL) surgery. Few studies have examined risk factors for these associated injuries in young patients. HYPOTHESIS: There are patient-related factors predictive of concomitant knee pathology that differ between age-based cohorts. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Natural language processing was used to extract clinical variables from available notes of patients undergoing ACL surgery between 2000 and 2020 at a single institution (5174 ACL surgeries; mean age, 17 ± 4 years; 53.1% female; accuracy, >98%). Patients were stratified to pediatric (5-13 years), adolescent (14-19 years), and young adult (20-35 years) cohorts. Logistic regression was used to determine predictors of concomitant injury to the menisci, medial collateral ligament (MCL), posterolateral corner (PLC), and posterior cruciate ligament (PCL). RESULTS: Between 2000 and 2020, 54% of pediatric, 71% of adolescent, and 70% of adult patients had ≥1 concomitant soft tissue injury. In children and adolescents, increased age was consistently predictive of sustaining a concomitant injury (P < .02). Female children had increased odds of concomitant medial meniscal injury, while female adults had decreased odds (P≤ .046). Adolescent and adult female patients had decreased odds of concomitant lateral meniscal injury (P≤ .027). Female children had increased odds of injury to the MCL (P = .015), whereas female children and adolescents had decreased odds of PCL injury (P≤ .044). Adolescents undergoing revision ACL surgery had increased odds of meniscal injury (P≤ .001) and decreased odds of concomitant MCL injury (P = .028). Increased body mass index (BMI) was associated with increased odds of concomitant medial meniscal injury in all cohorts (P≤ .041), lateral meniscal injury in adults (P = .045), and PLC injury in children (P = .016). Contact injuries were associated with increased odds of MCL injury in adolescents (P = .017) and PLC injury in adolescents and adults (P < .014). CONCLUSION: These findings support the hypothesis, as there were multiple factors that significantly affected the risk of concomitant injuries that differed between cohorts. Increased age, BMI, and contact injury history were generally associated with increased odds of sustaining a concomitant injury, whereas female sex and revision ACL surgery had mixed effects. Further studies are essential to investigate the sex-based differences in risk for concomitant injuries and to develop tailored treatment plans that minimize the risk of secondary ACL injury.

Mapping of multiple neurotransmitter receptor subtypes and distinct protein complexes to the connectome.

Neurons express various combinations of neurotransmitter receptor (NR) subunits and receive inputs from multiple neuron types expressing different neurotransmitters. Localizing NR subunits to specific synaptic inputs has been challenging. Here, we use epitope-tagged endogenous NR subunits, expansion light-sheet microscopy, and electron microscopy (EM) connectomics to molecularly characterize synapses in Drosophila. We show that in directionally selective motion-sensitive neurons, different multiple NRs elaborated a highly stereotyped molecular topography with NR localized to specific domains receiving cell-type-specific inputs. Developmental studies suggested that NRs or complexes of them with other membrane proteins determine patterns of synaptic inputs. In support of this model, we identify a transmembrane protein selectively associated with a subset of spatially restricted synapses and demonstrate its requirement for synapse formation through genetic analysis. We propose that mechanisms that regulate the precise spatial distribution of NRs provide a molecular cartography specifying the patterns of synaptic connections onto dendrites.

Ectropion. / Ektropion.

In ectropion, the eyelid margin - typically the lower eyelid - is turned outward. This condition is becoming increasingly common due to the ageing population. Ectropion is classified as either acquired or congenital, with the former being the most prevalent. Acquired ectropion is further divided into involutional, paralytic, mechanical and cicatricial subtypes. Involutional ectropion is the most common where there is no patient population bias. This clinical review provides an overview of ectropion.

Longer hospitalizations, more complications, and greater readmissions for patients with comorbid psychiatric disorders undergoing pulmonary lobectomy.

OBJECTIVE: To examine the influence of comorbid psychiatric disorders (PSYD) on postoperative outcomes in patients undergoing pulmonary lobectomy. METHODS: A retrospective analysis of the Healthcare Cost and Utilization Project Nationwide Readmissions Database from 2016 to 2018 was performed. Patients with lung cancer with and without psychiatric comorbidities who underwent pulmonary lobectomy were collated and analyzed (International Classification of Diseases, 10th Revision, Clinical Modification Mental, Behavioral and Neurodevelopmental disorders [F01-99]). The association of PSYD with complications, length of stay, and readmissions was assessed using a multivariable regression analysis. Additional subgroup analyses were performed. RESULTS: A total of 41,691 patients met inclusion criteria. Of these, 27.84% (11,605) of the patients had at least 1 PSYD. PSYD was associated with a significantly increased risk of postoperative complications (relative risk, 1.041; 95% CI, 1.015-1.068; P = .0018), pulmonary complications (relative risk, 1.125; 95% CI, 1.08-1.171; P < .0001), longer length of stay (PSYD mean, 6.79 days and non-PSYD mean, 5.68 days; P < .0001), higher 30-day readmission rate (9.2% vs 7.9%; P < .0001), and 90-day readmission rate (15.4% vs 12.9%; P < .007). Among patients with PSYD, those with cognitive disorders and psychotic disorders (eg, schizophrenia) appear to have the highest rates and risks of postoperative morbidity and in-hospital mortality. CONCLUSIONS: Patients with lung cancer with comorbid psychiatric disorders undergoing lobectomy experience worse postoperative outcomes with longer hospitalization, increased rates of overall and pulmonary complications, and greater readmissions suggesting potential opportunities for improved psychiatric care during the perioperative period.

Vaccine response after pneumococcal vaccination in allogeneic hematopoietic stem cell transplant recipients.

Current guidelines for vaccination in allogeneic hematopoietic stem cell transplant (HCT) recipients recommend initiation of pneumococcal vaccination series three to six months post-HCT, with most data supporting initiation at six months due to a more robust immune response. This single-center, retrospective, observational chart review aimed to evaluate the impact of initiating the pneumococcal vaccine series at three months post-HCT compared to six months post-HCT. The primary endpoints were defined as a percentage of patients with a serologic response of >1 and >1.3 µg/mL for over 50% of the defined serotypes. Outcomes showed no difference in immunologic response between the two groups.

A comparison between hyaluronic acid and other single ingredient eye drops for dry eye, a review.

Dry eye disease (DED) is a highly prevalent and debilitating condition. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan that has a long history as a safe and effective DED treatment. HA is frequently used as a comparator when assessing other topical DED treatments. This study aims to summarise and critically evaluate the literature describing all isolated active ingredients that have been directly compared with HA in the treatment of DED. A literature search was conducted in Embase using Ovid on the 24th of August 2021 and in PubMed including MEDLINE on the 20th of September 2021. Twenty-three studies met the inclusion criteria, 21 of which were randomised controlled trials. Seventeen different ingredients representing six treatment categories were compared with HA treatment. Most measures showed no significant difference between treatments, suggesting either equivalency of treatments or that studies were underpowered. Only two ingredients were represented in more than two studies; carboxymethyl cellulose treatment appears equivalent to HA treatment, while Diquafosol treatment appears superior to HA treatment. Drop-frequency varied from one to eight drops daily. No single study explained the choice of drop frequency. Nine studies used a HA concentration of 0.1% which may be below therapeutic levels. Nine studies reported using preserved formulations, six of them with differences in preservatives between the compared groups. Thirteen studies were financially linked to industry. No major complications were reported. Studies were not designed to find differences in treatment effects for different types or severities of DED. HA is a good comparator treatment when assessing other DED treatments, although consensus after decades of use is still lacking for best choice of concentration, molecular weight and drop tonicity. Well-designed studies are needed to determine an evidence-based standard for HA treatment to be used as comparator.

Association of perioperative plasma concentration of neurofilament light with delirium after cardiac surgery: a nested observational study.

BACKGROUND: Neurofilament light is a blood-based biomarker of neuroaxonal injury that can provide insight into perioperative brain vulnerability and injury. Prior studies have suggested that increased baseline and postoperative concentrations of neurofilament light are associated with delirium after noncardiac surgery, but results are inconsistent. Results have not been reported in cardiac surgery patients, who are among those at highest risk for delirium. We hypothesised that perioperative blood concentrations of neurofilament light (both baseline and change from baseline to postoperative day 1) are associated with delirium after cardiac surgery. METHODS: This study was nested in a trial of arterial blood pressure targeting during cardiopulmonary bypass using cerebral autoregulation metrics. Blood concentrations of neurofilament light were measured at baseline and on postoperative day 1. The primary outcome was postoperative delirium. Regression models were used to examine the associations between neurofilament light concentration and delirium and delirium severity, adjusting for age, sex, race, logistic European System for Cardiac Operative Risk Evaluation, bypass duration, and cognition. RESULTS: Delirium occurred in 44.6% of 175 patients. Baseline neurofilament light concentration was higher in delirious than in non-delirious patients (median 20.7 pg ml-1 [IQR 16.1-33.2] vs median 15.5 pg ml-1 [IQR 12.1-24.2], P<0.001). In adjusted models, greater baseline neurofilament light concentration was associated with delirium (odds ratio, 1.027; 95% confidence interval, 1.003-1.053; P=0.029) and delirium severity. From baseline to postoperative day 1, neurofilament light concentration increased by 42%, but there was no association with delirium. CONCLUSIONS: Baseline neurofilament light concentration, but not change from baseline to postoperative day 1, was associated with delirium after cardiac surgery.

Tissue factor targeting peptide enhances nanoparticle binding and delivery of a synthetic specialized pro-resolving lipid mediator to injured arteries.

Background: Specialized pro-resolving lipid mediators (SPM) such as resolvin D1 (RvD1) attenuate inflammation and exhibit vasculo-protective properties. Methods: We investigated poly-lactic-co-glycolic acid (PLGA)-based nanoparticles (NP), containing a peptide targeted to tissue factor (TF) for delivery of 17R-RvD1 and a synthetic analog 17-R/S-benzo-RvD1 (benzo-RvD1) using in vitro and in vivo models of acute vascular injury. NPs were characterized in vitro by size, drug loading, drug release, TF binding, and vascular smooth muscle cell migration assays. NPs were also characterized in a rat model of carotid angioplasty. Results: PLGA NPs based on a 75/25 lactic to glycolic acid ratio demonstrated optimal loading (507.3 pg 17R-RvD1/mg NP; P = ns) and release of RvD1 (153.1 pg 17R-RvD1/mg NP; P < .05). NPs incorporating the targeting peptide adhered to immobilized TF with greater avidity than NPs with scrambled peptide (50 nM: 41.6 ± 0.52 vs 32.66 ± 0.34; 100 nM: 35.67 ± 0.95 vs 23.5 ± 0.39; P < .05). NPs loaded with 17R-RvD1 resulted in a trend toward blunted vascular smooth muscle cell migration in a scratch assay. In a rat model of carotid angioplasty, 16-fold more NPs were present after treatment with TF-targeted NPs compared with scrambled NPs (P < .01), with a corresponding trend toward higher tissue levels of 17R-RvD1 (P = .06). Benzo-RvD1 was also detectable in arteries treated with targeted NP delivery and accumulated at 10 times higher levels than NP loaded with 17R-RvD1. There was a trend toward decreased CD45 immunostaining in vessels treated with NP containing benzo-RvD1 (0.76 ± 0.38 cells/mm2 vs 122.1 ± 22.26 cells/mm2; P = .06). There were no significant differences in early arterial inflammatory and cytokine gene expression by reverse transcription-polymerase chain reaction. Conclusions: TF-targeting peptides enhanced NP-mediated delivery of SPM to injured artery. TF-targeted delivery of SPMs may be a promising therapeutic approach to attenuate the vascular injury response.

Stress Induced Activation of LTR Retrotransposons in the Drosophila melanogaster Genome.

Background: Retrotransposons with long terminal repeats (LTR retrotransposons) are widespread in all groups of eukaryotes and are often both the cause of new mutations and the source of new sequences. Apart from their high activity in generative and differentiation-stage tissues, LTR retrotransposons also become more active in response to different stressors. The precise causes of LTR retrotransposons' activation in response to stress, however, have not yet been thoroughly investigated. Methods: We used RT-PCR to investigate the transcriptional profile of LTR retrotransposons and piRNA clusters in response to oxidative and chronic heat stresses. We used Oxford Nanopore sequencing to investigate the genomic environment of new insertions of the retrotransposons. We used bioinformatics methods to find the stress-induced transcription factor binding sites in LTR retrotransposons. Results: We studied the transposition activity and transcription level of LTR retrotransposons in response to oxidative and chronic heat stress and assessed the contribution of various factors that can affect the increase in their expression under stress conditions: the state of the piRNA-interference system, the influence of the genomic environment on individual copies, and the presence of the stress-induced transcription factor binding sites in retrotransposon sequences. Conclusions: The main reason for the activation of LTR retrotransposons under stress conditions is the presence of transcription factor binding sites in their regulatory sequences, which are triggered in response to stress and are necessary for tissue regeneration processes. Stress-induced transposable element activation can function as a trigger mechanism, triggering multiple signal pathways and resulting in a polyvariant cell response.