The role of surgical tissue injury and intraoperative sympathetic activation in postoperative immunosuppression after breast-conserving surgery versus mastectomy: a prospective observational study.

BACKGROUND: Breast cancer is the second most common cause of death from cancer in women worldwide. Counterintuitively, large population-based retrospective trials report better survival after breast-conserving surgery (BCS) compared to mastectomy, corrected for tumour- and patient variables. More extensive surgical tissue injury and activation of the sympathetic nervous system by nociceptive stimuli are associated with immune suppression. We hypothesized that mastectomy causes a higher expression of plasma damage associated molecular patterns (DAMPs) and more intraoperative sympathetic activation which induce postoperative immune dysregulation. Immune suppression can lead to postoperative complications and affect tumour-free survival. METHODS: In this prospective observational study, plasma DAMPs (HMGB1, HSP70, S100A8/A9 and S100A12), intraoperative sympathetic activation (Nociception Level (NOL) index from 0 to 100), and postoperative immune function (plasma cytokine concentrations and ex vivo cytokine production capacity) were compared in patients undergoing elective BCS (n = 20) versus mastectomy (n = 20). RESULTS: Ex vivo cytokine production capacity of TNF, IL-6 and IL-1ß was nearly absent in both groups one hour after surgery. Levels appeared recovered on postoperative day 3 (POD3), with significantly higher ex vivo production capacity of IL-1ß after BCS (p = .041) compared to mastectomy. Plasma concentration of IL-6 was higher one hour after mastectomy (p = .045). Concentrations of plasma alarmins S100A8/A9 and S100A12 were significantly higher on POD3 after mastectomy (p = .003 and p = .041, respectively). Regression analysis showed a significantly lower percentage of NOL measurements ≤ 8 (absence of nociception) during mastectomy when corrected for norepinephrine equivalents (36% versus 45% respectively, p = .038). Percentage of NOL measurements ≤ 8 of all patients correlated with ex vivo cytokine production capacity of IL-1ß and TNF on POD3 (r = .408; p = .011 and r = .500; p = .001, respectively). CONCLUSIONS: This pilot study revealed substantial early postoperative immune suppression after BCS and mastectomy that appears to recover in the following days. Differences between BCS and mastectomy in release of DAMPs and intraoperative sympathetic activation could affect postoperative immune homeostasis and thereby contribute to the better survival reported after BCS in previous large population-based retrospective trials. These results endorse further exploration of (1) S100 alarmins as potential therapeutic targets in breast cancer surgery and (2) suppression of intraoperative sympathetic activation to substantiate the observed association with postoperative immune dysregulation.

Evaluating the Impact of Operative Team Familiarity on Cardiac Surgery Outcomes: A Retrospective Cohort Study of Medicare Beneficiaries.

OBJECTIVE: To associate surgeon-anesthesiologist team familiarity (TF) with cardiac surgery outcomes. BACKGROUND: TF, a measure of repeated team member collaborations, has been associated with improved operative efficiency; however, examination of its relationship to clinical outcomes has been limited. METHODS: This retrospective cohort study included Medicare beneficiaries undergoing coronary artery bypass grafting (CABG), surgical aortic valve replacement (SAVR), or both (CABG+SAVR) between January 1, 2017, and September 30, 2018. TF was defined as the number of shared procedures between the cardiac surgeon and anesthesiologist within 6 months of each operation. Primary outcomes were 30- and 90-day mortality, composite morbidity, and 30-day mortality or composite morbidity, assessed before and after risk adjustment using multivariable logistic regression. RESULTS: The cohort included 113,020 patients (84,397 CABG; 15,939 SAVR; 12,684 CABG+SAVR). Surgeon-anesthesiologist dyads in the highest [31631 patients, TF median (interquartile range)=8 (6, 11)] and lowest [44,307 patients, TF=0 (0, 1)] TF terciles were termed familiar and unfamiliar, respectively. The rates of observed outcomes were lower among familiar versus unfamiliar teams: 30-day mortality (2.8% vs 3.1%, P =0.001), 90-day mortality (4.2% vs 4.5%, P =0.023), composite morbidity (57.4% vs 60.6%, P <0.001), and 30-day mortality or composite morbidity (57.9% vs 61.1%, P <0.001). Familiar teams had lower overall risk-adjusted odds of 30-day mortality or composite morbidity [adjusted odds ratio (aOR) 0.894 (0.868, 0.922), P <0.001], and for SAVR significantly lower 30-day mortality [aOR 0.724 (0.547, 0.959), P =0.024], 90-day mortality [aOR 0.779 (0.620, 0.978), P =0.031], and 30-day mortality or composite morbidity [aOR 0.856 (0.791, 0.927), P <0.001]. CONCLUSIONS: Given its relationship with improved 30-day cardiac surgical outcomes, increasing TF should be considered among strategies to advance patient outcomes.

Exotic Dark Matter Search with the Majorana Demonstrator.

With excellent energy resolution and ultralow-level radiogenic backgrounds, the high-purity germanium detectors in the Majorana Demonstrator enable searches for several classes of exotic dark matter (DM) models. In this work, we report new experimental limits on keV-scale sterile neutrino DM via the transition magnetic moment from conversion to active neutrinos ν_{s}→ν_{a}. We report new limits on fermionic dark matter absorption (χ+A→ν+A) and sub-GeV DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), and new exclusion limits for bosonic dark matter (axionlike particles and dark photons). These searches utilize the (1-100)-keV low-energy region of a 37.5-kg y exposure collected by the Demonstrator between May 2016 and November 2019 using a set of ^{76}Ge-enriched detectors whose surface exposure time was carefully controlled, resulting in extremely low levels of cosmogenic activation.

A Practical Dosing Algorithm for Deep Neuromuscular Blockade during Total Intravenous Anesthesia: ROCURITHM.

BACKGROUND: The number of trials investigating the effects of deep neuromuscular blockade (NMB) on surgical conditions and patient outcomes is steadily increasing. Consensus on which surgical procedures benefit from deep NMB (a posttetanic count [PTC] of 1 to 2) and how to implement it has not been reached. The European Society of Anaesthesiology and Intensive Care does not advise routine application but recommends use of deep NMB to improve surgical conditions on indication. This study investigates the optimal dosing strategy to reach and maintain adequate deep NMB during total intravenous anesthesia. METHODS: Data from three trials investigating deep NMB during laparoscopic surgery with total intravenous anesthesia (n = 424) were pooled to analyze the required rocuronium dose, when to start continuous infusion, and how to adjust. The resulting algorithm was validated (n = 32) and compared to the success rate in ongoing studies in which the algorithm was not used (n = 180). RESULTS: The mean rocuronium dose based on actual bodyweight for PTC 1 to 2 was (mean ± SD) 1.0 ± 0.27 mg · kg-1 ·h-1 in the trials, in which mean duration of surgery was 116 min. An induction dose of 0.6 mg ·kg-1 led to a PTC of 1 to 5 in a quarter of patients after a mean of 11 min. The remaining patients were equally divided over too shallow (additional bolus and direct start of continuous infusion) or too deep; a 15-min wait after PTC of 0 for return of PTC to 1 or higher. Using the proposed algorithm, a mean 76% of all 5-min measurements throughout surgery were on target PTC 1 to 2 in the validation cohort. The algorithm performed significantly better than anesthesiology residents without the algorithm, even after a learning curve from 0 to 20 patients (42% on target, P ≤ 0.001, Cohen's d = 1.4 [95% CI, 0.9 to 1.8]) to 81 to 100 patients (61% on target, P ≤ 0.05, Cohen's d = 0.7 [95% CI, 0.1 to 1.2]). CONCLUSIONS: This study proposes a dosing algorithm for deep NMB with rocuronium in patients receiving total intravenous anesthesia.

Recovery and immune function after low pressure pneumoperitoneum during robot-assisted radical prostatectomy: a randomised controlled trial.

OBJECTIVE: To compare the effectiveness of low intra-abdominal pressure (IAP) facilitated by deep neuromuscular block (NMB) to standard practice in improving the quality of recovery, preserving immune function, and enhancing parietal perfusion during robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: In this blinded, randomised controlled trial, 96 patients were randomised to the experimental group with low IAP (8 mmHg) facilitated by deep NMB (post-tetanic count 1-2) or the control group with standard IAP (14 mmHg) and moderate NMB (train-of-four 1-2). Recovery was measured using the 40-item Quality of Recovery questionnaire and 36-item Short-Form Health survey. Immune function was evaluated by plasma damage-associated molecular patterns, cytokines, and ex vivo lipopolysaccharide-stimulated cytokine production. Parietal peritoneum perfusion was measured by analysing the recordings of indocyanine-green injection. RESULTS: Quality of recovery was not superior in the experimental group (n = 46) compared to the control group (n = 50). All clinical outcomes, including pain scores, postoperative nausea and vomiting, and hospital stay were similar. There were no significant differences in postoperative plasma concentrations of damage-associated molecular patterns, cytokines, and ex vivo cytokine production capacity. The use of low IAP resulted in better parietal peritoneum perfusion. CONCLUSION: Despite better perfusion of the parietal peritoneum, low IAP facilitated by deep NMB did not improve the quality of recovery or preserve immune function compared to standard practice in patients undergoing RARP.

Five Year Results of Endovascular versus Medical Therapy in Acute Type B Aortic Intramural Haematoma: Meta-Analysis of Reconstructed Time to Event Data.

OBJECTIVE: To evaluate outcomes in the follow up of thoracic endovascular aortic repair (TEVAR) vs. medical therapy in patients with acute type B aortic intramural haematoma (IMH). DATA SOURCES: The following sources were searched for articles meeting the inclusion criteria and published by July 2023: PubMed/MEDLINE, EMBASE, CENTRAL/CCTR (Cochrane Controlled Trials Register). REVIEW METHODS: This systematic review with pooled meta-analysis of time to event data followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, and its protocol was registered on the public platform PROSPERO (CRD42023456222). The following were analysed: overall survival (all cause mortality), aortic related mortality, and restricted mean survival time. Certainty of evidence was evaluated through the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. RESULTS: Eight studies met the eligibility criteria, including 1 015 patients (440 in the TEVAR group and 575 in the medical therapy group). All studies were observational, and the pooled cohort had a median follow up of 5.1 years. Compared with patients who received medical therapy alone, those who underwent TEVAR had a statistically significantly lower risk of all cause death (HR 0.44, 95% CI 0.30 - 0.65; p < .001; GRADE certainty: low), lower risk of aortic related death (HR 0.04, 95% CI 0.01 - 0.31; p = .002; GRADE certainty: low) and lifetime gain (restricted mean survival time was overall 201 days longer with TEVAR; p < .001). CONCLUSION: Thoracic endovascular aortic repair may be associated with lower risk of all cause and aortic related death compared with medical therapy in patients with acute type B IMH; however, the underlying data are not strong enough to draw robust clinical conclusions. Randomised controlled trials with large sample sizes and longer follow up are warranted to elucidate this question.

Deep neuromuscular blockade in adults undergoing an abdominal laparoscopic procedure.

BACKGROUND: Laparoscopic surgery is the preferred option for many procedures. To properly perform laparoscopic surgery, it is essential that sudden movements and abdominal contractions in patients are prevented, as it limits the surgeon's view. There has been a growing interest in the potential beneficial effect of deep neuromuscular blockade (NMB) in laparoscopic surgery. Deep NMB improves the surgical field by preventing abdominal contractions, and it is thought to decrease postoperative pain. However, it is uncertain if deep NMB improves intraoperative safety and thereby improves clinical outcomes. OBJECTIVES: To evaluate the benefits and harms of deep neuromuscular blockade versus no, shallow, or moderate neuromuscular blockade during laparoscopic intra- or transperitoneal procedures in adults. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 31 July 2023. SELECTION CRITERIA: We included randomised clinical trials (irrespective of language, blinding, or publication status) in adults undergoing laparoscopic intra- or transperitoneal procedures comparing deep NMB to moderate, shallow, or no NMB. We excluded trials that did not report any of the primary or secondary outcomes of our review. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. all-cause mortality, 2. health-related quality of life, and 3. proportion of participants with serious adverse events. Our secondary outcomes were 4. proportion of participants with non-serious adverse events, 5. readmissions within three months, 6. short-term pain scores, 7. measurements of postoperative recovery, and 8. operating time. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 42 randomised clinical trials with 3898 participants. Most trials included participants undergoing intraperitoneal oncological resection surgery. We present the Peto fixed-effect model for most dichotomous outcomes as only sparse events were reported. Comparison 1: deep versus moderate NMB Thirty-eight trials compared deep versus moderate NMB. Deep NMB may have no effect on mortality, but the evidence is very uncertain (Peto odds ratio (OR) 7.22, 95% confidence interval (CI) 0.45 to 115.43; 12 trials, 1390 participants; very low-certainty evidence). Deep NMB likely results in little to no difference in health-related quality of life up to four days postoperative (mean difference (MD) 4.53 favouring deep NMB on the Quality of Recovery-40 score, 95% CI 0.96 to 8.09; 5 trials, 440 participants; moderate-certainty evidence; mean difference lower than the mean clinically important difference of 10 points). The evidence is very uncertain about the effect of deep NMB on intraoperatively serious adverse events (deep NMB 38/1150 versus moderate NMB 38/1076; Peto OR 0.95, 95% CI 0.59 to 1.52; 21 trials, 2231 participants; very low-certainty evidence), short-term serious adverse events (up to 60 days) (deep NMB 37/912 versus moderate NMB 42/852; Peto OR 0.90, 95% CI 0.56 to 1.42; 16 trials, 1764 participants; very low-certainty evidence), and short-term non-serious adverse events (Peto OR 0.94, 95% CI 0.65 to 1.35; 11 trials, 1232 participants; very low-certainty evidence). Deep NMB likely does not alter the duration of surgery (MD -0.51 minutes, 95% CI -3.35 to 2.32; 34 trials, 3143 participants; moderate-certainty evidence). The evidence is uncertain if deep NMB alters the length of hospital stay (MD -0.22 days, 95% CI -0.49 to 0.06; 19 trials, 2084 participants; low-certainty evidence) or pain scores one hour after surgery (MD -0.31 points on the numeric rating scale, 95% CI -0.59 to -0.03; 22 trials, 1823 participants; very low-certainty evidence; mean clinically important difference 1 point) and 24 hours after surgery (MD -0.60 points on the numeric rating scale, 95% CI -1.05 to -0.15; 16 trials, 1404 participants; very low-certainty evidence; mean clinically important difference 1 point). Comparison 2: deep versus shallow NMB Three trials compared deep versus shallow NMB. The trials did not report on mortality and health-related quality of life. The evidence is very uncertain about the effect of deep NMB compared to shallow NMB on the proportion of serious adverse events (RR 1.66, 95% CI 0.50 to 5.57; 2 trials, 158 participants; very low-certainty evidence). Comparison 3: deep versus no NMB One trial compared deep versus no NMB. There was no mortality in this trial, and health-related quality of life was not reported. The proportion of serious adverse events was 0/25 in the deep NMB group and 1/25 in the no NMB group. AUTHORS' CONCLUSIONS: There was insufficient evidence to draw conclusions about the effects of deep NMB compared to moderate NMB on all-cause mortality and serious adverse events. Deep NMB likely results in little to no difference in health-related quality of life and duration of surgery compared to moderate NMB, and it may have no effect on the length of hospital stay. Due to the very low-certainty evidence, we do not know what the effect is of deep NMB on non-serious adverse events, pain scores, or readmission rates. Randomised clinical trials with adequate reporting of all adverse events would reduce the current uncertainties. Due to the low number of identified trials and the very low certainty of evidence, we do not know what the effect of deep NMB on serious adverse events is compared to shallow NMB and no NMB. We found no trials evaluating mortality and health-related quality of life.

Perioperative outcomes of laparoscopic low anterior resection using ArtiSential® versus robotic approach in patients with rectal cancer: a propensity score matching analysis.

BACKGROUND: Total mesorectal excision using conventional straight fixed devices may be technically difficult because of the narrow and concave pelvis. Several laparoscopic articulating tools have been introduced as an alternative to robotic systems. The aim of this study was to compare perioperative outcomes between laparoscopic low anterior resection using ArtiSential® and robot-assisted surgery for rectal cancer. METHODS: This retrospective study included 682 patients who underwent laparoscopic or robotic low anterior resection  for rectal cancer from September 2018 to December 2021. Among them, 82 underwent laparoscopic surgery using ArtiSential® (group A) and 201 underwent robotic surgery (group B). A total of 73 [group A; 66.37 ± 11.62; group B 65.79 ± 11.34] patients were selected for each group using a propensity score matching analysis. RESULTS: There was no significant difference in the baseline characteristics between group A and B. Mean operative time was longer in group B than A (163.5 ± 61.9 vs 250.1 ± 77.6 min, p < 0.001). Mean length of hospital stay was not significantly different between the two groups (6.2 ± 4.7 vs 6.7 ± 6.1 days, p = 0.617). Postoperative complications, reoperation, and readmission within 30 days after surgery were similar between the two groups. Pathological findings revealed that the circumferential resection margins were above 10 mm in both groups (11.00 ± 7.47 vs 10.17 ± 6.25 mm, p = 0.960). At least 12 lymph nodes were sufficiently harvested, with no significant difference in the number harvested between the groups (20.5 ± 9.9 vs 19.7 ± 7.3, p = 0.753). CONCLUSIONS: Laparoscopic low anterior resection using ArtiSential® can achieve acceptable clinical and oncologic outcomes. ArtiSential®, a multi-joint and articulating device, may serve a feasible alternative approach to robotic surgery in rectal cancer.

Buccal Mesenchymal Stromal Cells as a Source of Osseointegration of Titanium Implants.

We studied the interaction of human buccal mesenchymal stem cells (MSCs) and osteoblasts differentiated from them with the surface of titanium samples. MSCs were isolated by enzymatic method from buccal fat pads. The obtained cell culture was presented by MSCs, which was confirmed by flow cytometry and differentiation into adipocytes and osteoblasts. Culturing of buccal MSCs on titanium samples was accompanied by an increase in the number of cells for 15 days and the formation of a developed network of F-actin fibers in the cells. The viability of buccal MSCs decreased by 8 days, but was restored by 15 days. Culturing of osteoblasts obtained as a result of buccal MSC differentiation on the surface of titanium samples was accompanied by a decrease in their viability and proliferation. Thus, MSCs from buccal fat pads can be used to coat implants to improve osseointegration during bone reconstruction in craniofacial surgery and dentistry. To improve the integration of osteoblasts, modification of the surface of titanium samples is required.

Enhancing research culture in academia: a spotlight on early career researchers.

This editorial highlights common challenges faced by early career researchers (ECRs) who play a crucial role in our research community. We propose that enhancing the experiences of ECRs will yield benefits to the entire scientific community and we give practical suggestions on how such improvements may be achieved.

Spectrally encoded dual-mode interferometry with orthogonal scanning.

Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technique. Here, we present a method to integrate optical coherence tomography (OCT) and SECM for complementary imaging by adding orthogonal scanning to the SECM configuration. The co-registration of SECM and OCT is automatic, as all system components are shared in the same order, eliminating the need for additional optical alignment. The proposed multimode imaging system is compact and cost-effective while providing the benefits of imaging aiming and guidance. Furthermore, speckle noise can be suppressed by averaging the speckles generated by shifting the spectral-encoded field in the direction of dispersion. Using a near infrared (NIR) card and a biological sample, we demonstrated the capability of the proposed system by showing SECM imaging at depths of interest guided by the OCT in real time and speckle noise reduction. Interfaced multimodal imaging of SECM and OCT was implemented at a speed of approximately 7 frames/s using fast-switching technology and GPU processing.

Spiral-phase-objective for a compact spiral-phase-contrast microscopy.

Spiral-phase-contrast imaging, which utilizes a spiral phase optical element, has proven to be effective in enhancing various aspects of imaging, such as edge contrast and shadow imaging. Typically, the implementation of spiral-phase-contrast imaging requires the formation of a Fourier plane through a 4f optical configuration in addition to an existing optical microscope. In this study, we present what we believe to be a novel single spiral-phase-objective, integrating a spiral phase plate, which can be easily and simply applied to a standard microscope, such as a conventional objective. Using a new hybrid design approach that combines ray-tracing and field-tracing simulations, we theoretically realized a well-defined and high-quality vortex beam through the spiral-phase-objective. The spiral-phase-objective was designed to have conditions that are practically manufacturable while providing predictable performance. To evaluate its capabilities, we utilized the designed spiral-phase-objective to investigate isotropic spiral phase contrast and anisotropic shadow imaging through field-tracing simulations, and explored the variation of edge contrast caused by changes in the thickness of the imaging object.

Final Result of the Majorana Demonstrator's Search for Neutrinoless Double-ß Decay in

The Majorana Demonstrator searched for neutrinoless double-ß decay (0νßß) of ^{76}Ge using modular arrays of high-purity Ge detectors operated in vacuum cryostats in a low-background shield. The arrays operated with up to 40.4 kg of detectors (27.2 kg enriched to ∼88% in ^{76}Ge). From these measurements, the Demonstrator has accumulated 64.5 kg yr of enriched active exposure. With a world-leading energy resolution of 2.52 keV FWHM at the 2039 keV Q_{ßß} (0.12%), we set a half-life limit of 0νßß in ^{76}Ge at T_{1/2}>8.3×10^{25} yr (90% C.L.). This provides a range of upper limits on m_{ßß} of (113-269) meV (90% C.L.), depending on the choice of nuclear matrix elements.

Constraints on the Decay of

^{180m}Ta is a rare nuclear isomer whose decay has never been observed. Its remarkably long lifetime surpasses the half-lives of all other known ß and electron capture decays due to the large K-spin differences and small energy differences between the isomeric and lower-energy states. Detecting its decay presents a significant experimental challenge but could shed light on neutrino-induced nucleosynthesis mechanisms, the nature of dark matter, and K-spin violation. For this study, we repurposed the Majorana Demonstrator, an experimental search for the neutrinoless double-beta decay of ^{76}Ge using an array of high-purity germanium detectors, to search for the decay of ^{180m}Ta. More than 17 kg, the largest amount of tantalum metal ever used for such a search, was installed within the ultralow-background detector array. In this Letter, we present results from the first year of Ta data taking and provide an updated limit for the ^{180m}Ta half-life on the different decay channels. With new limits up to 1.5×10^{19} yr, we improved existing limits by 1-2 orders of magnitude which are the most sensitive searches for a single ß and electron capture decay ever achieved. Over all channels, the decay can be excluded for T_{1/2}<0.29×10^{18} yr.

Erratum: Search for Spontaneous Radiation from Wave Function Collapse in the Majorana Demonstrator [Phys. Rev. Lett. 129, 080401 (2022)].

This corrects the article DOI: 10.1103/PhysRevLett.129.080401.

Fenfluramine treatment is associated with improvement in everyday executive function in preschool-aged children (<5 years) with Dravet syndrome: A critical period for early neurodevelopment.

OBJECTIVE: To evaluate whether fenfluramine (FFA) is associated with improvement in everyday executive function (EF)-self-regulation-in preschool-aged children with Dravet syndrome (DS). METHODS: Children with DS received placebo or FFA in one of two phase III studies (first study: placebo, FFA 0.2 mg/kg/day, or FFA 0.7 mg/kg/day added to stiripentol-free standard-of-care regimens; second study: placebo or FFA 0.4 mg/kg/day added to stiripentol-inclusive regimens). Everyday EF was evaluated at baseline and Week 14-15 for children aged 2-4 years with parent ratings on the Behavior Rating Inventory of Executive Function®-Preschool (BRIEF®-P); raw scores were transformed to T-scores and summarized in Inhibitory Self-Control Index (ISCI), Flexibility Index (FI), Emergent Metacognition Index (EMI), and Global Executive Composite (GEC). Clinically meaningful improvement and worsening were defined using RCI ≥ 90% and RCI ≥ 80% certainty, respectively. The associations between placebo vs FFA combined (0.2, 0.4, and 0.7 mg/kg/day) or individual treatment groups and the likelihood of clinically meaningful change in BRIEF®-P indexes/composite T-scores were evaluated using Somers'd; pairwise comparisons were calculated by 2-sided Fisher's Exact tests (p ≤ 0.05) and Cramér's V. RESULTS: Data were analyzed for 61 evaluable children of median age 3 years (placebo, n = 22; FFA 0.2 mg/kg/day, n = 15; 0.4 mg/kg/day [with stiripentol], n = 10; 0.7 mg/kg/day, n = 14 [total FFA, n = 39]). Elevated or problematic T-scores (T ≥ 65) were reported in 55% to 86% of patients at baseline for ISCI, EMI, and GEC, and in ∼33% for FI. Seventeen of the 61 children (28%) showed reliable, clinically meaningful improvement (RCI ≥ 90% certainty) in at least one BRIEF®-P index/composite, including a majority of the children in the FFA 0.7 mg/kg/day group (9/14, 64%). Only 53% of these children (9/17) also experienced clinically meaningful reduction (≥50%) in monthly convulsive seizure frequency, including 6/14 patients in the FFA 0.7 mg/kg/day group. Overall, there were positive associations between the four individual treatment groups and the likelihood of reliable, clinically meaningful improvement in all BRIEF®-P indexes/composite (ISCI, p = 0.001; FI, p = 0.005; EMI, p = 0.040; GEC, p = 0.002). The FFA 0.7 mg/kg/day group showed a greater likelihood of reliable, clinically meaningful improvement than placebo in ISCI (50% vs 5%; p = 0.003), FI (36% vs 0%; p = 0.005), and GEC (36% vs 0%; p = 0.005). For EMI, the FFA 0.7 mg/kg/day group showed a greater likelihood of reliable, clinically meaningful improvement than the FFA 0.2 mg/kg/day group (29% vs 0%; p = 0.040), but did not meet the significance threshold compared with placebo (29% vs 5%; p = 0.064). There were no significant associations between treatment and the likelihood of reliable, clinically meaningful worsening (p > 0.05). SIGNIFICANCE: In this preschool-aged DS population with high baseline everyday EF impairment, FFA treatment for 14-15 weeks was associated with dose-dependent, clinically meaningful improvements in regulating behavior, emotion, cognition, and overall everyday EF. These clinically meaningful improvements in everyday EF were not entirely due to seizure frequency reduction, suggesting that FFA may have direct effects on everyday EF during the early formative years of neurodevelopment.

Biochar Production and Demineralization Characteristics of Food Waste for Fuel Conversion.

The pyrolysis of food waste has high economic potential and produces several value-added products, such as gas, bio-oil, and biochar. In South Korea, biochar production from food waste is prohibited, because dioxins are generated during combustion caused by the chloride ions arising from the high salt content. This study is the first to examine the water quality and the applicability of food waste-based biochar as solid refuse fuel (SRF) based on a demineralization process. The calorific value increased after demineralization due to the removal of ionic substances and the high carbon content. The chloride ion removal rate after demineralization increased with the increasing pyrolysis temperature. A proximate analysis of biochar indicated that the volatile matter decreased, while ash and fixed carbon increased, with increasing pyrolysis temperature. At 300 °C pyrolysis temperature, all domestic bio-SRF standards were met. The organic matter concentration in water decreased with increasing carbonization temperature, and the concentrations of soluble harmful substances, such as volatile organic compounds (VOCs), were within the standards or non-detectable. These results suggest that biochar can be efficiently generated from food waste while meeting the emission standards for chloride ions, dissolved VOCs, ash, and carbon.

Studying the Proliferative Activity of Human Corneal Stromal Cell Populations.

The proliferative activity of populations of stromal cells (fibroblasts) obtained from human corneal lenticles under conditions of their differentiation into keratocytes was studied. It was shown that during differentiation, the number of dividing fibroblasts and the frequency of divisions, and motor activity of these cells (speed of movement along the cell trajectory and the length of the trajectory) sharply decreased. These findings indicate a decrease in the proliferative activity of fibroblasts under conditions of their differentiation and transformation into keratocytes. A period of 17 days is sufficient for differentiation of corneal fibroblasts into keratocytes.

[Control of hormonal rhinitis symptoms in patients with hypothyrosis: pathogenetic and clinical aspects]. / Kontrol' simptomov khronicheskogo rinita u patsientov s gipotireozom: patogeneticheskie i klinicheskie aspekty.

BACKGROUND: One of the poorly studied sections of the pathology of ENT organs is chronic rhinitis in patients with hypothyroidism, the pathogenesis of which has not been fully understood, the diagnosis causes significant difficulties, and there are no recommendations for treatment. Despite receiving replacement therapy with levothyroxine, the symptoms of rhinitis persist. OBJECTIVE: To study the effectiveness of the use of intranasal glucocorticosteroids in patients with chronic rhinitis and hypothyroidism. MATERIAL AND METHODS: Patients with chronic rhinitis and hypothyroidism used mometasone nasal spray 100 mcg 1 time per day for a course of treatment of 2 months (n=60). To assess the symptoms of rhinitis, a visual analog scale (0-10 points), endoscopic examination of ENT organs, anterior active rhinomanometry were used. Evaluation of mucociliary transport was used a saccharin test. The concentration of transforming growth factor (TGF-ß1) in nasal secretion and blood serum was studied by ELISA (Enzyme-Linked Immunosorbent Assay), the number of metabolites of NO - nitrites+nitrates (NOx) was recorded by colorimetric method. RESULTS: The use of mometasone nasal spray in patients with hypothyroidism helped to reduce complaints on a visual-analog scale (difficulty in nasal breathing, rhinorrhea) and improve nasal breathing according to anterior active rhinomanometry. The concentrations of TGF-ß1 and NOx in nasal secretions before mometasone treatment were higher than after treatment, which probably indicates the contribution of these substances to the formation of edematous hypertrophic changes from the nose in patients with hypothyroidism.

Quality of Recovery and Innate Immune Homeostasis in Patients Undergoing Low-pressure Versus Standard-pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery (RECOVER): A Randomized Controlled Trial.

OBJECTIVE: To study the effects of intra-abdominal pressure on the quality of recovery and innate cytokine production capacity after laparoscopic colorectal surgery within the enhanced recovery after surgery program. BACKGROUND: There is increasing evidence for the safety and advantages of low-pressure pneumoperitoneum facilitated by deep neuromuscular blockade (NMB). Nonetheless, there is a weak understanding of the relationship between clinical outcomes, surgical injury, postoperative immune dysfunction, and infectious complications. METHODS: Randomized controlled trial of 178 patients treated at standard-pressure pneumoperitoneum (12 mm Hg) with moderate NMB (train-of-four 1-2) or low pressure (8 mm Hg) facilitated by deep NMB (posttetanic count 1-2). The primary outcome was the quality of recovery (Quality of Recovery 40 questionnaire) on a postoperative day 1 (POD1). The primary outcome of the immune substudy (n=100) was ex vivo tumor necrosis factor α production capacity upon endotoxin stimulation on POD1. RESULTS: Quality of Recovery 40 score on POD1 was significantly higher at 167 versus 159 [mean difference (MD): 8.3 points; 95% confidence interval (CI): 2.5, 14.1; P =0.005] and the decline in cytokine production capacity was significantly less for tumor necrosis factor α and interleukin-6 (MD: -172 pg/mL; 95% CI: -316, -27; P =0.021 and MD: -1282 pg/mL; 95% CI: -2505, -59; P =0.040, respectively) for patients operated at low pressure. Low pressure was associated with reduced surgical site hypoxia and inflammation markers and circulating damage-associated molecular patterns, with a less impaired early postoperative ex vivo cytokine production capacity. At low pressure, patients reported lower acute pain scores and developed significantly less 30-day infectious complications. CONCLUSIONS: Low intra-abdominal pressure during laparoscopic colorectal surgery is safe, improves the postoperative quality of recovery and preserves innate immune homeostasis, and forms a valuable addition to future enhanced recovery after surgery programs.