Human neutrophil development and functionality are enabled in a humanized mouse model.

Mice with a functional human immune system serve as an invaluable tool to study the development and function of the human immune system in vivo. A major technological limitation of all current humanized mouse models is the lack of mature and functional human neutrophils in circulation and tissues. To overcome this, we generated a humanized mouse model named MISTRGGR, in which the mouse granulocyte colony-stimulating factor (G-CSF) was replaced with human G-CSF and the mouse G-CSF receptor gene was deleted in existing MISTRG mice. By targeting the G-CSF cytokine-receptor axis, we dramatically improved the reconstitution of mature circulating and tissue-infiltrating human neutrophils in MISTRGGR mice. Moreover, these functional human neutrophils in MISTRGGR are recruited upon inflammatory and infectious challenges and help reduce bacterial burden. MISTRGGR mice represent a unique mouse model that finally permits the study of human neutrophils in health and disease.

The Use of Frailty Scores for Screening the Surgical Risk Benefits: A Multidisciplinary Approach.

OBJECTIVE: Our study aims to examine the role of multi-disciplinary surgical pause committees (MDSPC) in perioperative planning to reduce adverse postoperative events and mortality rates. SUMMARY BACKGROUND DATA: Frail patients could benefit from preoperative MDSPCs when utilizing risk-benefit ratios for the proposed surgical plan. We examined whether MDSPCs improved clinical outcomes by developing individualized care plans and stratifying patients based on their level of frailty and ability to overcome external stressors. METHODS: We retrospectively collected patient information after MDSPC evaluation, at our medical center for 12 years since 2011. Patient's frailty risk assessment index (RAI) scores were calculated, and survival status was updated. MDSPCs plans were put into the following categories: proceed with the planned surgery (G1), proceed after medical optimization (G2), reduce invasiveness of surgery or anesthesia plan (G3), or adopt a non-surgical approach (G4). Chi-square and independent t-tests were used for categorical and numerical data, respectively. Survival analysis for 30-day (primary endpoint), one-year, and overall mortality rates used Kaplan-Meier. The alpha was set at 0.05. RESULTS: Clinical information was accessed from 12 women and 382 men. The average age was 71±11 years. 87.3% of planned surgical operations were stratified as ASA class III and IV. RAI scores were 36.4±9.6 (G1), similar to 37.4±10.8 (G2) but lower than 41.4±9.3 (G3) and 44.2±9.7 (G4) (P<0.001). Average survival duration was 35 months (G1), 35 months (G2), both significantly longer than 20 months (G3) and 18 months (G4) (P<0.001). CONCLUSION: Medical optimization improved overall survival and reduced death within 30 days and one year to be comparable to G1. Additionally, reducing the surgical invasiveness only improved survival advantage for six months, after which it was comparable to those in G4 with the worst outcome. RAI scoring is an excellent tool to predict the outcome of surgery, and it was used successfully in critically ill patients.

Impact of 18FFDG-PET/CT and Laparoscopy in Staging of Locally Advanced Gastric Cancer: A Cost Analysis in the Prospective Multicenter PLASTIC-Study.

BACKGROUND: Unnecessary D2-gastrectomy and associated costs can be prevented after detecting non-curable gastric cancer, but impact of staging on treatment costs is unclear. This study determined the cost impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) and staging laparoscopy (SL) in gastric cancer staging. MATERIALS AND METHODS: In this cost analysis, four staging strategies were modeled in a decision tree: (1) 18FFDG-PET/CT first, then SL, (2) SL only, (3) 18FFDG-PET/CT only, and (4) neither SL nor 18FFDG-PET/CT. Costs were assessed on the basis of the prospective PLASTIC-study, which evaluated adding 18FFDG-PET/CT and SL to staging advanced gastric cancer (cT3-4 and/or cN+) in 18 Dutch hospitals. The Dutch Healthcare Authority provided 18FFDG-PET/CT unit costs. SL unit costs were calculated bottom-up. Gastrectomy-associated costs were collected with hospital claim data until 30 days postoperatively. Uncertainty was assessed in a probabilistic sensitivity analysis (1000 iterations). RESULTS: 18FFDG-PET/CT costs were €1104 including biopsy/cytology. Bottom-up calculations totaled €1537 per SL. D2-gastrectomy costs were €19,308. Total costs per patient were €18,137 for strategy 1, €17,079 for strategy 2, and €19,805 for strategy 3. If all patients undergo gastrectomy, total costs were €18,959 per patient (strategy 4). Performing SL only reduced costs by €1880 per patient. Adding 18FFDG-PET/CT to SL increased costs by €1058 per patient; IQR €870-1253 in the sensitivity analysis. CONCLUSIONS: For advanced gastric cancer, performing SL resulted in substantial cost savings by reducing unnecessary gastrectomies. In contrast, routine 18FFDG-PET/CT increased costs without substantially reducing unnecessary gastrectomies, and is not recommended due to limited impact with major costs. TRIAL REGISTRATION: NCT03208621. This trial was registered prospectively on 30-06-2017.

Association analysis of indel variants and gene expression identifies MDM4 as a novel locus for skeletal muscle hypertrophy and power athlete status.

Insertions and deletions (indels) are the second most common type of variation in the human genome. However, limited data on their associations with exercise-related phenotypes have been documented. The aim of the present study was to examine the association between 18,370 indel variants and power athlete status, followed by additional studies in 357,246 individuals. In the discovery phase, the D allele of the MDM4 gene rs35493922 I/D polymorphism was over-represented in power athletes compared with control subjects (P = 7.8 × 10-9) and endurance athletes (P = 0.0012). These findings were replicated in independent cohorts, showing a higher D allele frequency in power athletes compared with control subjects (P = 0.016) and endurance athletes (P = 0.031). Furthermore, the D allele was positively associated (P = 0.0013) with greater fat-free mass in the UK Biobank. MDM4 encodes a protein that inhibits the activity of p53, which induces muscle fibre atrophy. Accordingly, we found that MDM4 expression was significantly higher in the vastus lateralis of power athletes compared with endurance athletes (P = 0.0009) and was positively correlated with the percentage of fast-twitch muscle fibres (P = 0.0062) and the relative area occupied by fast-twitch muscle fibres (P = 0.0086). The association between MDM4 gene expression and an increased proportion of fast-twitch muscle fibres was confirmed in two additional cohorts. Finally, we found that the MDM4 DD genotype was associated with increased MDM4 gene expression in vastus lateralis and greater cross-sectional area of fast-twitch muscle fibres. In conclusion, MDM4 is suggested to be a potential regulator of muscle fibre specification and size, with its indel variant being associated with power athlete status. HIGHLIGHTS: What is the central question of this study? Which indel variants are functional and associated with sport- and exercise-related traits? What is the main finding and its importance? Out of 18,370 tested indels, the MDM4 gene rs35493922 I/D polymorphism was found to be the functional variant (affecting gene expression) and the most significant, with the deletion allele showing associations with power athlete status, fat-free mass and cross-sectional area of fast-twitch muscle fibres. Furthermore, the expression of MDM4 was positively correlated with the percentage of fast-twitch muscle fibres and the relative area occupied by fast-twitch muscle fibres.

Exploring the relationship between caffeine metabolism-related CYP1A2 rs762551 polymorphism and team sport athlete status and training adaptations.

BACKGROUND: This study aimed to achieve a dual objective: to compare the frequencies of CYP1A2 rs762551 genotypes between team sport athletes and a control group, and to determine the association between the rs762551 polymorphism and changes in physical performance after a six-week training program among elite basketball players. METHODS: The study encompassed an analysis of 504 individuals, comprising 320 athletes and 184 controls. For the Turkish cohort, DNA was isolated using the buccal swab method, and genotyping was conducted using the KASP technique. Performance assessments included the Yo-Yo IR2 and 30 m sprint tests. For Russian participants, DNA samples were extracted from peripheral blood, a commercial kit was used for DNA extraction, and genotyping of the rs762551 polymorphism was conducted using DNA microarray. RESULT: Notably, a statistically significant linear decline in the prevalence of the CC genotype was observed with ascending levels of athletic achievement within team sports (sub-elite: 18.0%, elite: 8.2%, highly elite: 0%; p = 0.001). Additionally, the CA genotype was the most prevalent genotype in the highly elite group compared to controls (80.0% vs. 45.1%, p = 0.048). Furthermore, statistically significant improvements in Yo-Yo IR2 performance were noted exclusively among basketball players harboring the CA genotype (p = 0.048). CONCLUSIONS: The study's findings indicate that the rs762551 CC genotype is a disadvantage in elite team sports, whereas the CA genotype provides an advantage in basketball performance.

COVID-19 memories young adults may share: exploring event properties and motivations for transmission.

The COVID-19 pandemic has left an enduring mark on human history. This study investigates the intergenerational transmission of COVID-19 memories through a unique approach involving 49 participants aged 18-30. Specifically, participants were prompted to share a COVID-19 memory they would choose to transmit to their future children. Furthermore, participants provided reasons for selecting that particular memory, utilising a memory functions scale and open-ended responses. Applying Transition Theory, we examined the transitional impact, event importance, previous rehearsal, and valence of reported memories. Results revealed that 88% of memories revolve around distinctive events inducing psychological and material changes. Perceived as significant, negative, and transitional, these memories are predominantly public in nature. Predictors of event importance include previous rehearsal and psychological change. Participants share memories primarily for directive purposes, intending to inform future generations. The results imply that transitions not only organise personal memories but may also direct and shape memories for public events.

Underdiagnosis of Borderline oxacillin-resistant Staphylococcus aureus (BORSA) - Case series.

Borderline oxacillin-resistant Staphylococcus aureus (BORSA) are mecA-negative strains with oxacillin minimum inhibitor concentration (MIC) close to the resistance breakpoint of ≥ 4µg/mL. Instead of producing penicillin-binding protein with low affinity to methicillin (oxacillin) mediated by mecA gene as in methicillin-resistant S. aureus (MRSA), BORSA strains are characterised by the hyperproduction of ß-lactamase enzymes, thus able to break down methicillin. Common laboratory methods to detect MRSA such as cefoxitin disk diffusion alone may fail to detect methicillin resistance due to BORSA. We report five cases of BORSA blood-stream infections in a university teaching hospital. All isolates were found to be susceptible to cefoxitin using disk diffusion, resistant to oxacillin using automated MIC method, and did not harbour mecA gene. All patients were suscessfully treated with anti-MRSA antibiotics, and removal of primary sources were done if identified. A more cost-effective method for screening and diagnosis of BORSA is needed in addition to cefoxitin disk diffusion test, in order to monitor the spread, and to enable routine detection and treatment of this pathogen.

Volumetric measurements of weak current-induced magnetic fields in the human brain at high resolution.

PURPOSE: Clinical use of transcranial electrical stimulation (TES) requires accurate knowledge of the injected current distribution in the brain. MR current density imaging (MRCDI) uses measurements of the TES-induced magnetic fields to provide this information. However, sufficient sensitivity and image quality in humans in vivo has only been documented for single-slice imaging. METHODS: A recently developed, optimally spoiled, acquisition-weighted, gradient echo-based 2D-MRCDI method has now been advanced for volume coverage with densely or sparsely distributed slices: The 3D rectilinear sampling (3D-DENSE) and simultaneous multislice acquisition (SMS-SPARSE) were optimized and verified by cable-loop experiments and tested with 1-mA TES experiments for two common electrode montages. RESULTS: Comparisons between the volumetric methods against the 2D-MRCDI showed that relatively long acquisition times of 3D-DENSE using a single slab with six slices hindered the expected sensitivity improvement in the current-induced field measurements but improved sensitivity by 61% in the Laplacian of the field, on which some MRCDI reconstruction methods rely. Also, SMS-SPARSE acquisition of three slices, with a factor 2 CAIPIRINHA (controlled aliasing in parallel imaging results in higher acceleration) acceleration, performed best against the 2D-MRCDI with sensitivity improvements for the ∆ B z , c $$ \Delta {B}_{z,c} $$ and Laplacian noise floors of 56% and 78% (baseline without current flow) as well as 43% and 55% (current injection into head). SMS-SPARSE reached a sensitivity of 67 pT for three distant slices at 2 × 2 × 3 mm3 resolution in 10 min of total scan time, and consistently improved image quality. CONCLUSION: Volumetric MRCDI measurements with high sensitivity and image quality are well suited to characterize the TES field distribution in the human brain.

Optimal medical management in patients undergoing peripheral vascular interventions for chronic limb-threatening ischemia is associated with improved outcomes.

OBJECTIVE: Optimizing medical management and risk factor modification are underused strategies in patients with chronic limb-threatening ischemia (CLTI), despite evidence of improved outcomes. The Vascular Quality Initiative (VQI) registry is a tool to improve quality of vascular care. In this study, we used the VQI to evaluate trends in medical management in patients with CLTI undergoing peripheral vascular interventions (PVI), and the impact of changes in management on overall survival (OS), amputation-free survival (AFS), and limb salvage (LS). METHODS: Patients undergoing index PVI for CLTI between 2012 and 2016, with ≥24 months of follow-up were identified from the national VQI registry. Patient details including smoking status and medication use, OS, LS, and AFS were analyzed with linear-by-linear association, t test, and logistic regression. RESULTS: There were 12,370 PVI completed in 11,466 patients. There was a significant increase in infrapopliteal interventions (from 29.8% to 39.0%; P < .001) and PVI performed for tissue loss (from 59.1% to 66.5%; P < .001). The percentage of current smokers at time of PVI decreased (from 36.2% to 30.7%; P = .036). At discharge, statins were initiated in 25%, aspirin in 45%, and P2Y12 therapy in 58% of patients not receiving these medications before PVI. Over the course of follow-up, dual antiplatelet therapy (DAPT) (from 41.1% to 48.0%; P < .001), angiotensin-converting enzyme (ACE) inhibitor (from 46.2% to 51.3%; P < .001), and statin (from 70.4% to 77.5%; P < .001) use increased. Combined DAPT, ACE inhibitor and statin use increased from 33.6% to 39.6% (P ≤ .001). Significant improvement in 24-month OS and AFS was noted (OS, from 90.9% to 93.7% [P = .002]: AFS, from 81.2% to 83.1% [P = .046]), but not LS (from 89.6% to 89.0%; P = .83). Combined therapy with P2Y12 inhibitors, statins and ACE inhibitors was an independent predictor of improved OS (hazard ratio, 0.61; 95% confidence interval, 0.39-0.96; P = .034). DAPT was independent predictor of improved LS (hazard ratio, 0.83; 95% confidence interval, 0.79-0.87; P < .007). CONCLUSIONS: Antiplatelet, ACE inhibitor, and statin use increased over the study period and was associated with improved OS and AFS. LS trends did not change significantly over time, possibly owing to the inclusion of patients with a greater disease burden or inadequate medical management. Medical management, although improved, remained far from optimal and represents an area for continued development.

The effects of boron-supplemented diets on adipogenesis-related gene expressions, anti-inflammatory, and antioxidative response in high-fat fed rats.

The fatty liver syndrome caused by nutritional factors is a common cause of hepatic dysfunction globally. This research was designed to study the shielding effect of boron in rats fed a diet having high fat. Overall, 40 Wistar albino male rats were placed into one control and four treatment groups, that is, each having eight rats. Group I was provided with a standard rat diet while group II was only provided a high-fat diet for 60 days. Groups III, IV, and V were provided with 5, 10, and 20 mg/kg/day boron, respectively, by gastric gavage besides a high-fat diet for 60 days. Malondialdehyde was increased significantly in rats' blood and tissue because of high-fat diets. Glutathione was decreased significantly in blood and tissues because of a high-fat diet. Moreover, the activities of superoxide dismutase (SOD) and catalase (CAT) were decreased in the blood and tissues of the high-fat-fed rats. The genes expression for C-reactive protein, interleukin-1ß, leptin, and tumor necrosis factor-α were increased while gene expression for peroxisome proliferator-activated receptors was decreased in the liver of rats fed with a high-fat diet. Contrariwise, boron supplementation improves antioxidative response in terms of increased SOD and CAT activities, gene expression regulation, and improved anti-inflammatory activities. In a nutshell, boron has dose-dependent shielding antioxidative and tissue regenerative effects in rats.

Patterns and Persistence of Perioperative Plasma and Cerebrospinal Fluid Neuroinflammatory Protein Biomarkers After Elective Orthopedic Surgery Using SOMAscan.

BACKGROUND: The neuroinflammatory response to surgery can be characterized by peripheral acute plasma protein changes in blood, but corresponding, persisting alterations in cerebrospinal fluid (CSF) proteins remain mostly unknown. Using the SOMAscan assay, we define acute and longer-term proteome changes associated with surgery in plasma and CSF. We hypothesized that biological pathways identified by these proteins would be in the categories of neuroinflammation and neuronal function and define neuroinflammatory proteome changes associated with surgery in older patients. METHODS: SOMAscan analyzed 1305 proteins in blood plasma (n = 14) and CSF (n = 15) samples from older patients enrolled in the Role of Inflammation after Surgery for Elders (RISE) study undergoing elective hip and knee replacement surgery with spinal anesthesia. Systems biology analysis identified biological pathways enriched among the surgery-associated differentially expressed proteins in plasma and CSF. RESULTS: Comparison of postoperative day 1 (POD1) to preoperative (PREOP) plasma protein levels identified 343 proteins with postsurgical changes ( P < .05; absolute value of the fold change [|FC|] > 1.2). Comparing postoperative 1-month (PO1MO) plasma and CSF with PREOP identified 67 proteins in plasma and 79 proteins in CSF with altered levels ( P < .05; |FC| > 1.2). In plasma, 21 proteins, primarily linked to immune response and inflammation, were similarly changed at POD1 and PO1MO. Comparison of plasma to CSF at PO1MO identified 8 shared proteins. Comparison of plasma at POD1 to CSF at PO1MO identified a larger number, 15 proteins in common, most of which are regulated by interleukin-6 (IL-6) or transforming growth factor beta-1 (TGFB1) and linked to the inflammatory response. Of the 79 CSF PO1MO-specific proteins, many are involved in neuronal function and neuroinflammation. CONCLUSIONS: SOMAscan can characterize both short- and long-term surgery-induced protein alterations in plasma and CSF. Acute plasma protein changes at POD1 parallel changes in PO1MO CSF and suggest 15 potential biomarkers for longer-term neuroinflammation that warrant further investigation.

Post-streptococcal scleredema an unusual rare mimicker of scleroderma: a case report.

cleredema of Buschke is a rare pathological disorder of connective tissue, which is characterized by a woody, diffuse induration of the skin, most often in the upper extremities. We report an extremely rare complication of post-streptococcal infection in a six-year-old male complaining of gradually progressing, painless skin thickening and tightness which was preceded by a one-month history of fever, cough, and tonsillitis. By reporting this case, we hope to contribute to the creation of a database for future research aimed at better understanding the incidence, pathophysiology, and management of this extremely rare complication.

P2Y12 inhibitor monotherapy is associated with superior outcomes as compared with aspirin monotherapy in chronic limb-threatening ischemia.

OBJECTIVE: Antiplatelet therapy is recommended in patients with peripheral arterial disease to reduce cardiovascular risk and improve outcomes. However, issues including the drug of choice and use of dual antiplatelet therapy (DAPT) vs monotherapy remain unclear. This study aims to compare the impact of aspirin (ASA) monotherapy, P2Y12 monotherapy, and DAPT on limb salvage (LS), amputation-free survival (AFS), and overall survival (OS) in patients undergoing lower extremity peripheral endovascular intervention (PVI) for chronic limb-threatening ischemia (CLTI). METHODS: The Vascular Quality Initiative PVI registry was used to identify index procedures completed for CLTI between March 1, 2010 and September 30, 2017. Patients were categorized by antiplatelet use at the time of last follow-up. Patients not on antiplatelet therapy were compared with ASA, P2Y12 monotherapy, and DAPT. Propensity score-matched samples were created for direct ASA vs P2Y12 and P2Y12 vs DAPT comparisons; veracity was confirmed by χ2 and Hosmer-Lemeshow tests. Kaplan-Meier and Cox regression were performed for OS, AFS, and LS. RESULTS: A total of 12,433 index PVI were completed for CLTI in 11,503 subjects in the pre-matched sample. Antiplatelet use at follow-up was: 12% none, 31% ASA, 14% P2Y12, and 43% DAPT. Median follow-up was 1389 days. P2Y12 monotherapy was associated with improved outcomes as compared with ASA monotherapy, OS (87.8% vs 85.5%l P = .026; Cox hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.68-0.98; P = .03), AFS (79.6% vs 74.8%; P < .001; Cox HR, 0.75; 95% CI, 0.65-0.86; P < .001) and LS (89.5% vs 86.8%; P = .013; Cox HR, 0.74; 95% CI, 0.60-0.91; P = .004). P2Y12 monotherapy and DAPT had comparable OS (87.8% vs 88.9%; P = .62; Cox HR, 0.94; 95% CI, 0.77-1.14; P = .50), AFS (79.6% vs 81.5%; P = .33; Cox HR, 0.92; 95% CI, 0.78-1.07; P = .28), and LS (91.7% vs 89.4; P = .03; Cox HR, 0.80; 95% CI, 0.64-1.00; P = .06). CONCLUSIONS: P2Y12 monotherapy was associated with superior OS, AFS, and LS as compared with ASA monotherapy, and comparable OS, LS, and AFS with DAPT in patients undergoing PVI for CLTI. P2Y12 monotherapy may be considered over ASA monotherapy and DAPT in patients with CLTI, especially in patients with high bleeding risk.

Need for Routine Preoperative Insertion of Indwelling Urinary Catheter Prior to Endovascular Repair of Abdominal Aortic Aneurysm.

BACKGROUND: Evaluate outcomes following urinary catheter (UC) versus no urinary catheter (NUC) insertion in elective endovascular repair (EVAR) of abdominal aortic aneurysm (AAA). METHODS: Retrospective record review of all elective EVAR at a university affiliated medical center over a 5-year period. Statistical analysis included Chi Sq, Independent Student t Test. RESULTS: Six surgeons performed 272 elective EVAR. Three surgeons preferred selective insertion of indwelling UC, such that 86 (32%) EVAR were completed without indwelling urinary catheters (NUC). Differences between NUC versus UC included; male: (86% vs. 70%; P = 0.004), CAD: (45% vs. 33%; p = 0.046), conscious sedation: (36% vs. 8%; P < 0.001), bilateral percutaneous EVAR (PEVAR): (100% vs. 90%; P = 0.01), within ProglideTM IFU guidelines (87% vs 75%; P = .05), major adverse operative event (MAOE): (3.5% vs. 10%; P = 0.05) and mean operative time (185 ± 73 vs. 140 ± 37; P < 0.001). Intra-operative catheterization was never required among NUC. Postoperative adverse urinary events (AUE) were more common among UC (11.4% vs. 8.1%; P = 0.41); with longer times to straight catheterization/reinsertion (1575 ± 987 vs, 522 ± 269 min; P = 0.015) and lower likelihood of eligibility for same day discharge (SDD); (41% vs. 59%; P = 0.008). Ineligibility for SDD was due to AUE in 18% of UC patients. CONCLUSION: Selective preoperative UC insertion should be considered for EVAR, with particular consideration to no preoperative catheterization in men meeting Proglide IFU. Adverse urinary events occurred less frequently among NUC and were identified/ treated earlier. Moreover, AUEs were the most common reason for potential SDD ineligibility among UC patients. Selective policies may facilitate SDD.

On the reconstruction of magnetic resonance current density images of the human brain: Pitfalls and perspectives.

Magnetic resonance current density imaging (MRCDI) of the human brain aims to reconstruct the current density distribution caused by transcranial electric stimulation from MR-based measurements of the current-induced magnetic fields. So far, the MRCDI data acquisition achieves only a low signal-to-noise ratio, does not provide a full volume coverage and lacks data from the scalp and skull regions. In addition, it is only sensitive to the component of the current-induced magnetic field parallel to the scanner field. The reconstruction problem thus involves coping with noisy and incomplete data, which makes it mathematically challenging. Most existing reconstruction methods have been validated using simulation studies and measurements in phantoms with simplified geometries. Only one reconstruction method, the projected current density algorithm, has been applied to human in-vivo data so far, however resulting in blurred current density estimates even when applied to noise-free simulated data. We analyze the underlying causes for the limited performance of the projected current density algorithm when applied to human brain data. In addition, we compare it with an approach that relies on the optimization of the conductivities of a small number of tissue compartments of anatomically detailed head models reconstructed from structural MR data. Both for simulated ground truth data and human in-vivo MRCDI data, our results indicate that the estimation of current densities benefits more from using a personalized volume conductor model than from applying the projected current density algorithm. In particular, we introduce a hierarchical statistical testing approach as a principled way to test and compare the quality of reconstructed current density images that accounts for the limited signal-to-noise ratio of the human in-vivo MRCDI data and the fact that the ground truth of the current density is unknown for measured data. Our results indicate that the statistical testing approach constitutes a valuable framework for the further development of accurate volume conductor models of the head. Our findings also highlight the importance of tailoring the reconstruction approaches to the quality and specific properties of the available data.

Parenteral lipid emulsions induce unique ileal fatty acid and metabolomic profiles but do not increase the risk of necrotizing enterocolitis in preterm pigs.

Necrotizing enterocolitis (NEC) is a manifestation of maladaptive intestinal responses in preterm infants centrally medicated by unattenuated inflammation. Early in the postnatal period, preterm infants develop a deficit in arachidonic and docosahexaenoic acid, both potent regulators of inflammation. We hypothesized that the fatty acid composition of parenteral lipid emulsions uniquely induces blood and intestinal fatty acid profiles which, in turn, modifies the risk of NEC development. Forty-two preterm pigs were randomized to receive one of three lipid emulsions containing 100% soybean oil (SO), 15% fish oil (MO15), or 100% fish oil (FO100) with enteral feedings over an 8-day protocol. Blood and distal ileum tissue were collected for fatty acid analysis. The distal ileum underwent histologic, proteomic, and metabolomic analyses. Eight pigs [3/14 SO (21%), 3/14 MO15 (21%), and 2/14 FO100 (14%)] developed NEC. No differences in NEC risk were evident between groups despite differences in induced fatty acid profiles in blood and ileal tissue. Metabolomic analysis of NEC versus no NEC tissue revealed differences in tryptophan metabolism and arachidonic acid-containing glycerophospholipids. Proteomic analysis demonstrated no differences by lipid group; however, 15 proteins differentiated NEC versus no NEC in the domains of tissue injury, glucose uptake, and chemokine signaling. Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles; however, these profiles are not linked to a difference in NEC development. Metabolomic and proteomic analyses of NEC versus no NEC intestinal tissue provide mechanistic insights into the pathogenesis of NEC in preterm infants.NEW & NOTEWORTHY Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles; however, these profiles are not linked to a difference in NEC risk in preterm pigs. Metabolomic and proteomic analyses provide mechanistic insights into NEC pathogenesis. Compared with healthy ileal tissue, metabolites in tryptophan metabolism and arachidonic acid-containing glycerophospholipids are increased in NEC tissue. Proteomic analysis differentiates NEC versus no NEC in the domains of tissue injury, glucose uptake, and chemokine signaling.

Identification of Plasma Proteome Signatures Associated With Surgery Using SOMAscan.

OBJECTIVES: To characterize the proteomic signature of surgery in older adults and association with postoperative outcomes. SUMMARY OF BACKGROUND DATA: Circulating plasma proteins can reflect the physiological response to and clinical outcomes after surgery. METHODS: Blood plasma from older adults undergoing elective surgery was analyzed for 1305 proteins using SOMAscan. Surgery-associated proteins underwent Ingenuity Pathways Analysis. Selected surgery-associated proteins were independently validated using Luminex or enzyme-linked immunosorbent assay methods. Generalized linear models estimated correlations with postoperative outcomes. RESULTS: Plasma from a subcohort (n = 36) of the Successful Aging after Elective Surgery (SAGES) study was used for SOMAscan. Systems biology analysis of 110 proteins with Benjamini-Hochberg (BH) corrected P value ≤0.01 and an absolute foldchange (|FC|) ≥1.5 between postoperative day 2 (POD2) and preoperative (PREOP) identified functional pathways with major effects on pro-inflammatory proteins. Chitinase-3-like protein 1 (CHI3L1), C-reactive protein (CRP), and interleukin-6 (IL-6) were independently validated in separate validation cohorts from SAGES (n = 150 for CRP, IL-6; n = 126 for CHI3L1). Foldchange CHI3L1 and IL-6 were associated with increased postoperative complications [relative risk (RR) 1.50, 95% confidence interval (95% CI) 1.21-1.85 and RR 1.63, 95% CI 1.18-2.26, respectively], length of stay (RR 1.35, 95% CI 0.77-1.92 and RR 0.98, 95% CI 0.52-1.45), and risk of discharge to postacute facility (RR 1.15, 95% CI 1.04-1.26 and RR 1.11, 95% CI 1.04-1.18); POD2 and PREOP CRP difference was associated with discharge to postacute facility (RR 1.14, 95% CI 1.04-1.25). CONCLUSION: SOMAscan can identify novel and clinically relevant surgery-induced protein changes. Ultimately, proteomics may provide insights about pathways by which surgical stress contributes to postoperative outcomes.

Sensitivity and resolution improvement for in vivo magnetic resonance current-density imaging of the human brain.

PURPOSE: Magnetic resonance current-density imaging (MRCDI) combines MRI with low-intensity transcranial electrical stimulation (TES; 1-2 mA) to map current flow in the brain. However, usage of MRCDI is still hampered by low measurement sensitivity and image quality. METHODS: Recently, a multigradient-echo-based MRCDI approach has been introduced that presently has the best-documented efficiency. This MRCDI approach has now been advanced in three directions and has been validated by phantom and in vivo experiments. First, the importance of optimum spoiling for brain imaging was verified. Second, the sensitivity and spatial resolution were improved by using acquisition weighting. Third, navigators were added as a quality control measure for tracking physiological noise. Combining these advancements, the optimized MRCDI method was tested by using 1 mA TES for two different injection profiles. RESULTS: For a session duration of 4:20 min, the new MRCDI method was able to detect TES-induced magnetic fields at a sensitivity level of 84 picotesla, representing a twofold efficiency increase against our original method. A comparison between measurements and simulations based on personalized head models showed a consistent increase in the coefficient of determination of ΔR2 = 0.12 for the current-induced magnetic fields and ΔR2 = 0.22 for the current flow reconstructions. Interestingly, some of the simulations still clearly deviated from the measurements despite the strongly improved measurement quality. This highlights the utility of MRCDI to improve head models for TES simulations. CONCLUSION: The achieved sensitivity improvement is an important step from proof-of-concept studies toward a broader application of MRCDI in clinical and basic neuroscience research.

The reliability and success of peritoneal dialysis during the COVID-19 pandemic.

We evaluated the symptoms, changes in laboratory findings during the novel coronavirus disease (COVID-19) pandemic, and the effect of depression in patients with peritoneal dialysis (PD). This is an observational and cross-sectional study. All patients were asked to fill the clinical assessment form and Beck depression and anxiety inventory. Also, the last two laboratory evaluations during this period were examined. A total of 123 patients performing PD were included. None of the patients were diagnosed with COVID-19. In the total study population, parathyroid hormone (PTH), serum albumin, phosphorus and ferritin levels significantly elevated at the end of 97 ± 31 days. PTH and phosphorus levels remained stable in remote monitoring automated PD (RM-APD) group (p = 0.4 and p = 0.5), they tended to increase in continuous ambulatory PD group and significantly increased in automated PD group (p = 0.09 and p = 0.01 for PTH and p = 0.06 and p = 0.001 for phosphorus, respectively). Moderate to severe depression was associated with dyspnoea, weight gain more than 5 kg, fatigue, palpitation and increased anxiety. PD is a reliable and successful form of dialysis and can be safely administered even if hospital access is restricted. Also, RM-APD may be a better choice because of providing more stable bone-mineral metabolism. Moreover, evaluating depression and anxiety is essential for the accurate clinical assessment.

Enhanced rates of detection and treatment of depression and anxiety disorders among adult patients with epilepsy using automated EMR-based screening.

OBJECTIVE: Depression and anxiety disorders are common among patients with epilepsy (PWE). These comorbidities have been shown to influence prognosis and may have a greater impact on quality of life than seizure control. Despite guideline recommendations and expert consensus to regularly screen for and treat both conditions, there is evidence that they are underdiagnosed and undertreated. Our goal was to test a novel screening method to determine if it would increase the rate of detecting and treating depression and anxiety disorders among PWE. METHOD: The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the Brief Epilepsy Anxiety Survey Instrument (brEASI) were selected as validated screening instruments for depression and anxiety disorders, respectively. They were sent via an electronic medical record-linked patient portal to all patients of four epileptologists 48 h prior to their clinic appointment. We evaluated whether this increased the rate of detecting and treating depression and anxiety disorders relative to a historical control group. RESULTS: A total of 563 patients were included of whom 351 were sent the screening instruments. 62.7% of patients completed the screening instruments of whom 47.7% screened positive for either depression only (16.4%), anxiety disorders only (5.5%) or both (25.9%); a statistically significant increase relative to the control group. There was also a significantly increased proportion of patients for whom treatment was initiated for depression (p < 0.01), anxiety disorders (p < 0.01), or both (p < 0.01). CONCLUSIONS: We identified an easily applicable and efficient means of enhancing detection and treatment rates for depression and anxiety disorders among PWE in a busy clinic setting.